The inalienable right to life possessed by every human being is present from the moment of initial formation, and all human beings shall be entitled to the equal protection of persons under the law.
The Personhood Debates
Debate 8: In Vitro Fertilization Part 2
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After the previous debate between Bill Fortenberry of the Personhood Initiative and Atlee Breland of Parents Against Personhood, Bill made several attempts to elicit further responses from Atlee. He finally posted a challenge to the Parents Against Personhood wall on facebook, and the following conversation ensued:
Bill
I'm still waiting for Atlee to uphold her promise to finish the conversation linked below:
http://www.personhoodinitiative.com/debate-2.html
Atlee
Said conversation is over 2000 words and counting. It's a BIG topic, involving a lot of research and writing to really do it comprehensive justice. I've been working on it in between higher-priority tasks related to the new site, to say nothing of my family, my career, and the holidays.
And actually, I have a question for you, Bill, which is directly relevant to this topic. Considering that the process of fertilization takes about 24 hours from the time that sperm penetrates the zona pellucida of the egg for the DNA to completely combine, exactly when during that process do you consider personhood to begin?
Do you believe that personhood begins at the moment the sperm enters the oocyte's cytoplasm, at any particular point during the DNA fusion, when the merge is complete and a polar body is extruded, or from when the zygote completes its first mitosis?
Rebecca Kiessling strongly implied during the MC Law Symposium that she considered personhood to begin as soon as the sperm entered the egg, although her grasp of the biology seemed to be rather shaky. You frequently reference the "moment of fertilization", as does most personhood legislation, so I want to be sure I understand exactly what you mean by that.
Bill
Fertilization is actually a single moment rather than a process. There is a process leading up to that moment and a process which commences from that moment, but fertilization itself is the singular event of sperm-egg membrane fusion. Here is an article detailing the process leading up to that single moment of fertilization: http://www.biolreprod.org/content/68/1/1.full, and here is another describing part of the process which begins at that moment: http://dev.biologists.org/content/124/1/233.full.pdf.
In regards to our previous conversation, I must say that I find your explanation troubling. It seems as if you are admitting that you initiated a nation wide campaign against personhood before taking time to ensure that your campaign was scientifically sound. Your entire campaign seems to be predicated on a single assumption which I have demonstrated to be false. Your admission that answering this challenge takes a lower priority than the new website seems to indicate that you are more concerned with the popularity of your campaign than with the truth. I fear that you are letting pride and ambition cloud your judgement, but I hope that you will allay my fears by returning to our discussion soon.
Atlee
Taking the second part of this first: this is neither true nor correct. Prior to the start of the initiative 26 campaign, I was familiar enough with the basic position of the ASRM on egg freezing to know that medicine consider oocyte cryopreservation to be an experimental treatment with lower success rates.
That's scientifically sound, but not sufficient in the level of detail required for an explanation of this caliber, and a refutation of the numerous incorrect points you have attempted to make about IVF and oocyte cryopreservation. I have a master's degree and the associated experience in writing papers, and they inevitably involve a good deal of research even when one has substantial background knowledge. It's not because that background knowledge is incorrect -- it's because authoritatively building a comprehensive argument for someone without that background knowledge takes time and research.
In any case, anyone who cites studies about elective single embryo transfer to support personhood, or who attempts to dictate medical policy based on case studies which involve a dozen people, has very little standing to attempt to criticize someone else's scientific knowledge.
Furthermore, my priorities are not a question of popularity. It's a question of responsibilities. I have responsibilities to a lot of people, including some specific commitments and deadlines which have required work on the new website. Those take a higher priority, as they should, over an Internet debate on a non-time-sensitive subject.
Whining that you're being ignored is unseemly, particularly on an issue which I have previously stated is of some importance. I'm not just writing about oocyte preservation because I've promised you that I would, but also because I need to be able to address this subject in the context of upcoming campaigns.
Bill
That's very interesting and especially so since the ASRM website contains this statement on oocyte cryopreservation:
"ASRM holds the position that oocyte cryopreservation is 'experimental' due to the limited number of established pregnancies and deliveries from cryopreserved oocytes (2008). However, as of 2010, the number of comparative studies of oocyte cryopreservation published in peer-reviewed journals that demonstrate “there is adequate scientific evidence of safety and efficacy” has exploded. A number of ART programs are offering oocyte cryopreservation as an alternative to embryo cryopreservation to their patients and strongly feel the 'experimental' designation should be removed from this procedure."
And this statement about single embryo transfer:
"ASRM’s Practice Committee recommends: increased use of Single Embryo Transfer (SET) in IVF cycles."
I find your comment regarding studies of only a dozen cases to be interesting as well. If I remember correctly, a great deal of my proof consisted of quotes from the studies that you presented rather than my own. I also seem to recall that one of those studies catalogued over 900 successful cases. That's a far cry from the dozen that you are referring to.
As for your priorities, you are certainly free to choose to focus on whatever you like. I just think that your readers should be skeptical of your position until you find the time to prove your foundational tenet.
Atlee
That's not a position statement. That's a description of the topic of debate at an interactive panel at the ASRM meeting last October (http://www.asrm.org/events/detail.aspx?id=7676), and does not represent the official ASRM position in any way, shape, or form. As is noted in the first sentence, ASRM still holds that oocyte cryopreservation is highly observational.
Seriously, do you not even know the difference between an event description and an official position statement, or are you just throwing anything out there which you think is possibly relevant?
And for the last time, do you still not understand how ESET is completely irrelevant to the discussion at hand? The problem with personhood and IVF success rates isn't that it would prevent you from TRANSFERRING one -- in fact, it would require you to transfer more than one, if you have more than one surviving embryo. The problem is that attempting to FERTILIZE no more than two usually leaves you with zero embryos. ESET simply doesn't apply, because the problem happens at the embryo creation level rather than the transfer level. You cannot do ESET when you have zero embryos, so the comparable success rates (which, I will note, are for a specific group of women, not for the IVF population as a whole) simply don't even apply.
Honestly, I've explained this difference to you already. The fact that you're still talking about ESET (whose effectiveness I have never once disputed) shows either that you're fond of straw men, or that you're lacking the most basic grasp of the process.
I'm specifically referring to the following quote about vitrification from your article: '"Recently, however, several studies have reported better post-thaw oocyte survival, fertilization, and pregnancy rates." The second statement is supported by the citation of two independent studies.'
The two studies referred to as footnotes 27 and 28 of the ASRM opinion state, which you claim demonstrate better rates, respectively involve 12 and 15 patients. The full text of both studies is freely available online at http://humrep.oxfordjournals.org/content/17/12/3149.long and http://humrep.oxfordjournals.org/content/18/6/1250.long.
27 patients are hardly authoritative support for your assertion that oocyte preservation approaches the success rates of fresh IVF. (Indeed, if you actually read those papers, you will note that one has a 66% miscarriage rate, which is far higher than that of fresh IVF.)
As for the other six (actually, seven) studies under discussion, none of them show anything close to comparable results to fresh IVF, because that's not what's under discussion in that specific section. The narrow context of that paragraph is the comparative effectiveness of different techniques, which does not imply that they stack up favorably to current IVF results.
In fact, Fabbri 2000 (a study of slow-freezing method, not the newer vitrification method) supports my contention that fertilization rates are notably lower -- 57% in that study, versus 70% or higher for ICSI with fresh oocytes, with a thaw loss of 46%. The study involved 96 patients. There was great variability in the success rate of the different techniques studied, which underscores that this is still a truly experimental procedure. Pregnancy rates were not reported, so we can draw no conclusions.
Eroglu 2002 shows a 34-47% loss of eggs due to freezing; fertilization was not attempted, so it tells us nothing about fertilization or pregnancy rates. Sahananthan 1988 I haven't been able to get, but given the age of the paper, it's not to be expected that their results are anything but abysmal; nor did this study actually attempt to fertilize eggs. Trad 1998 likewise did not attempt to fertilize. Stachecki 2000 involves mouse oocytes.
Porcu 1997, a case report of a single patient, shows a 66% loss due to freezing, a 50% fertilization rate, and a 50% cleavage rate; from 12 eggs, they got 1 embryo, a rate far lower than would be expected for fresh IVF. Polak de Fried 1998 is likewise a single-patient case report, with a 70% loss due to freezing, a 66% fertilization rate.
So, to summarize those studies, we have: two single-patient case reports, one mouse study, three studies where fertilization wasn't even attempted, and one 96-patient study which shows lower success rates than fresh IVF, a high rate of oocyte loss in the freezing process, and the lack of well-established protocols for lab techniques. To the best of our knowledge, they involve two (2) actual pregnancies.
Exactly how do these seven studies demonstrate the success of oocyte cryopreservation compared to fresh IVF? In my opinion, they all reinforce the experimental nature and relatively poor success rates of oocyte cryopreservation.
Finally, the reference to over 900 successful cases is a population study which involved every child born through oocyte cryopreservation worldwide in the last two decades. Given that current estimates place the number of IVF children born at approximately 4 million, it reinforces that we are talking about an experimental procedure which shows future promise but is a long way from being ready for prime time.
Bill
Let me begin by thanking you for continuing the discussion. As I stated in our previous conversation, it is a pleasure to discuss this topic with someone who has actually done some research in this field.
Now, you are correct in pointing out that the quote I provided was from an ASRM event description. I never claimed otherwise. I did not provide the quote to say that ASRM has changed their position, but rather to demonstrate that their position on this topic has been challenged by those within their own ranks. A study by Noyes et al. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842870/) demonstrates that the 2008 paper which you presented in our previous discussion and which forms the foundation for ASRM's position is both outdated and amazingly narrow in its consideration of oocyte cryopreservation. The ASRM report made no mention of the work reported by Kuwayama et al. in 2005, Borini et al. in 2004, Setti et al. in 2006 or Cobo et al. in 2007 all of which demonstrated significant achievements in oocyte cryopreservation, and as the ASRM event statement admits, the number of studies disagreeing with their conclusion has increased dramatically in the three years since their report. As David Albertini wrote in the most recent issue of the Journal of Assisted Reproduction and Genetics, "The time is right to proceed full speed with adoption of oocyte cryopreservation." (http://www.springerlink.com/content/054n584x156rlw55/fulltext.html)
In regards to your comments on single embryo transfer, let me point out that the combination of this policy with oocyte cryopreservation would allow doctors to thaw and fertilize oocytes one at a time. This may lengthen the process slightly, but with multiple studies demonstrating a greater than 50% pregnancy rate from oocyte cryopreservation methods, the likelihood of having to repeat the process more than twice is very low. Furthermore, a 2009 study demonstrated that embryo cryopreservation can be successfully completed subsequent to oocyte cryopreservation (http://www.ncbi.nlm.nih.gov/pubmed/18692830). This provides doctors with an acceptable option for the rare cases in which the woman is unavailable at the time that the embryo is to be transferred. While neither single embryo transfer nor oocyte cryopreservation represent in themselves a full solution to the conflict between personhood and IVF, the two combined together solve that conflict very well.
By the way, the study of the 936 children born from oocyte cryopreservation bore the title of: "Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies." After studying every reported birth from this method of IVF, the authors were able to demonstrate that oocyte cryopreservation is safer for the child than the current methods of embryo cryopreservation. The fact that this study ranged over a period of two decades is significant in that it thus includes children born from oocyte cryopreservation prior to the current levels of success achieved by that method. In spite of this, the authors still only found 12 cases of birth defects.
Atlee
Do you think that the ASRM isn't aware of those studies? Or did you consider that there are excellent reasons why scientists don't consider those studies to be adequate proof of the reliability and efficacy of this method?
Kuwayama involved 67 patients, who were much younger than the average IVF patient, and transfer practices contrary to ASRM recommendations. Cobo had a population of 30 patients, and more importantly, used donor eggs rather than the eggs of patients with known infertility impairment. Borrini has 68 patients, with a pregnancy rate of just 25%.
Levi-Setti is a larger study, but it shows a pregnancy rate of just 12%, with a really high miscarriage rate of 33%. In fact, I'm very confused about why you cite this as "significant achievment", when the authors themselves note that "Our implantation rate (5.7%) after thawing is impressively lower than our implantation rate after the transfer of fresh embryos (23.2%)."
The Noyes paper is a review and an editorial, not a clinical study, and the studies she cites for efficacy are all likewise very small -- her own clinical studies have involved a total of 46 patients. No doubt you're aware that she runs an infertility clinic which offers an elective egg freezing program, so her interests are not purely academic.
And now we arrive at why I asked you precisely when you consider that fertilization begins. According to your own definition of personhood, every last one of these studies, and in fact all oocyte preservation that's currently being practiced, constitutes embryonic research, most of which has shown that it's harmful to the embryos.
Given that you believe that each egg becomes a legal person at the instant when the sperm is deposited into the cytoplasm via the ICSI needle, I'm surprised, to say the least, that you support the use of oocyte preservation. The overall body of evidence indicates that oocyte preservation offers each individual embryo a reduced chance of survival compared to what it would have if it were fertilized and transferred fresh, because it is less likely to cleave and continue to develop.
While this is unquestionably improving, the fact is that the larger studies performed to date show negative results compared to standard IVF. The only studies which show anything close to equivalent performance involve a scant handful of patients, far too few to reach true statistical significance, or be viewed as solid evidence on which to base clinical practice.
As the Albertini editorial comment you link notes, "With either slow freeze or vitrification, the normalization of protocol has yet to achieve something even remotely reproducible. Visits to IVF clinics around the world over the past 5 years reinforces suspicions regarding the absence of uniformity and variability in protocols." That means that there's still no standard agreement on the various details of the freezing process, and individual clinics are fumbling their way along with no consensus on which methods will ultimately produce a 40% pregnancy rate, and which ones will produce a 5% rate.
Consider if we were talking about a new form of cancer treatment compared to standard chemotherapy, with identical statistics as cryopreserved vs fresh embryos. Would you think it ethical for a hospital to tell a parent that the new treatment was a perfectly reasonable choice for their newborn, or offer it when standard chemotherapy is an available option? Of course you wouldn't. Nor would any review board permit such an experimental practice, with overall worse results and only limited non-significant positive results compared to an existing treatment, to be conducted on newborn infants (or a person of any other age).
No, oocytes don't have moral agency or rights under personhood, and the process of freezing and thawing the oocytes themselves doesn't raise an ethical question. However, isn't it wrong to deliberately take an action which the evidence indicates will result in an increased likelihood of loss of the embryo which will be created from those eggs?
As with embryo freezing, there's no offsetting benefit to the embryo which justifies the risks of being created from a previously-frozen oocyte. It's purely done for the benefit of the mother, and I think we've very firmly established that you don't consider even a grave threat to the mother's life to justify even incidental death to embryos.
Given your general views, and the experimental nature of the research, I think it's philosophically inconsistent of you to support oocyte cryopreservation at this juncture.
Bill
Before we proceed any further in our discussion of the scientific literature, I think that it would be very helpful for you to provide a brief outline of the criteria that a report must meet before you will consider it as evidence in favor of oocyte cryopreservation.
In response to your ethical argument, let me point out that we are not discussing whether in vitro fertilization itself or any given method thereof is ethical but rather if any of these would be deemed illegal under a personhood amendment. In a strict legal sense, neither method of in vitro fertilization would be illegal under that amendment. The only two things currently legal that would then be made illegal would be the intentional harming of an unborn child or the causing of such harm through criminal negligence.
Oocyte cryopreservation is recommended primarily as a support element for single embryo transfer. Relying on this method would allow doctors to extract multiple oocytes to be used for later cycles without having to freeze living embryos. This combination of oocyte cryopreservation and single embryo fertilization would eliminate the step in the standard IVF process which could be condemned under the personhood amendment - the destruction of embryos which are not used by the donor.
The other embryonic deaths that you have described are all naturally occurring and occur in spite of the doctor's efforts to the contrary. A doctor who has taken every reasonable precaution against the death of his patient is generally not prosecuted if that patient happens to die while under his care. A personhood amendment would simply place embryonic deaths in the same legal category as any other death that occurs under a doctor's care. Therefore, naturally occurring embryonic deaths would not be litigable under a personhood amendment.
By the way, I would be more than willing to discuss the ethics of our positions if you would care to provide a statement of your own ethical beliefs in regards to the beginning of life and the destruction of human embryos.
Atlee
You keep failing to understand that single embryo transfer is completely irrelevant. Under personhood, it's legal to transfer two or more embryos if desired and appropriate for the patient's particular situation. There's no requirement to do anything except transfer all of the embryos which are created.
As I've told you, what, five times now, studies of single-embryo transfer have nothing to do with the issue at hand, which is how to operate under fertilization limits which, if applied to current IVF practice, will leave most women with no embryos at all. The topic of debate here is fertilization, which happens several days prior to the point of single-embryo transfer. I suggest you stick to the topic at hand.
Bill
Perhaps I have not been as clear as I thought. Please allow me to repeat my position in an effort to generate more clarity. The IVF process which I am proposing would proceed as follows:
1) Harvesting of oocytes
2) Fertilization of a single oocyte
3) Freezing of extra oocytes
4) Observation of single embryo while waiting for it to develop
5) Transfer of single embryo into womb
6) Observation of mother to determine pregnancy status
7) Thawing and fertilization of a single oocyte to repeat steps 4 - 6 if they are not successful
(Those willing to give birth to multiples would be permitted to fertilize as many oocytes per cycle as they are willing carry to full term.)
As far as I can tell, this process would enable the practice of in vitro fertilization to continue under a personhood amendment.
Atlee
Okay, study criteria. For a drug or technique to pass out of the realm of the experimental, it has to meet the criteria of scale and reproducibility.
Results have to be reproducible by other researchers -- that is, doctors in other clinics achieve similar results by following identical techniques. As the Albertini commentary you cite approvingly above notes, "the normalization of protocol has yet to achieve something even remotely reproducible". In practical terms, what that means is that everyone's doing their own thing, and nobody's sorted out which methods truly are superior. There isn't even real consensus whether slow freezing truly is better than vitrification, and Albertini also states that there is a "spectrum of technicalities awaiting resolution that are not commonly evidenced (or popular) in public presentations".
Secondly, trials must be large enough to demonstrate statistical significance, which is usually defined as a p-value of <0.05 in comparison to current practice. If you're working with a group of 20 patients, any one patient's outcome will change your numbers by 5%. If you see a 10% difference in 20 patients, you might repeat the study in a different group of 20 patients and find that due to random chance, two patients have had different results and flipped your numbers 10% the other way.
You simply can't make any solid conclusions one way or another about such a small group of results, where random chance plays such a heavy role. If your results are relatively good, you might decide to repeat your experiment in a larger group. However, your initial trials aren't proof until you've done those larger studies and established that your initial results weren't just a statistical blip.
Think about how many times you've heard a news story about a promising new drug for some condition or another, that subsequently vanishes without a trace. That's what happens here -- the small initial trial shows a good result because of random chance, but larger followup studies don't demonstrate the same success, and the new drug is ultimately not proved superior to existing treatments. Or think about flipping a coin, where you might have a run of "luck" with a short period of very positive results. Keep playing long enough, though, and your results will inevitably move back down to 50-50. (The technical term is regression to the mean.)
It takes hundreds of subjects in each arm of a study to get good statistical significance. In testing drugs, Phase 2 studies usually involve 100-300 patients, and Phase 3 studies involve more than 300-3000 patients. For a drug to be approved for public usage by the FDA, it has to have at least two successful Phase 3 studies.
So when you cite a study like, say, Grifo/Noyes 2010, it really doesn't mean much of anything except that there's reason to perform larger studies. If that one had had three patients flip the other way, which can happen for all sorts of random reasons which have nothing to do with the intervention being studied, it would've showed worse pregnancy rates than controls.
(For the record, please note that while I am not a medical researcher, I do have some formal training and professional experience in probability theory, statistics, and data mining.)
Oh, and you also want to be careful about relying too heavily on meta-analyses, which are attempts to approximate a single larger study by combining the results of several smaller studies.
The reason for this also should be fairly intuitive: if I have three studies that show a 60% result, and three that show a 40% result, you can't add them up to get a 50% result that indicates that my proposed intervention is just as good as the existing strategy. It shows that I need to do more studies so that I can sort out whether it really is significantly better or significantly worse than the existing one, and why the outcomes of the trials were so different.
Meta-analyses have their place, but they're no substitute for looking at the results of the individual studies they examine.
Back to ESET: the question at hand is the efficacy of steps 1-3. Steps 4-6 are irrelevant to the question of continuing under personhood, because they do not differ from current clinical practice.
I will also note at this point that your scheme places a massive physical and financial burden on patients; my best estimate is that each attempt at oocyte thawing would cost $5-7K above and beyond the $10-15K from the initial fresh attempt. Of course cost is not the only consideration, but we must acknowledge that it is significant and will push IVF well beyond many patients' means -- or push them into clinics in other states.
Other points here: you want to make sure that you're not looking at studies which involve donor eggs, for obvious reasons. A lot of the freezing studies are donor-egg studies, and the results obviously don't apply to a standard infertile population.
When you're looking at Italian studies, you also have to keep in mind that they're mostly transferring three embryos at a time on both fresh and frozen cycles. That increases their overall pregnancy rates, but isn't compliant with ASRM recommendations for most patients because of the risk of multiples.
Seriously, there are reasons why ASRM isn't ready to declare this ready for prime time -- and NOBODY is advocating that it should replace current practices. If you suggested that to an embryologist, they'd laugh at the preposterousness of it. It's not because they're not aware of the research, either. It's because they understand the issues involved much better than you or I do, and they know that there's really very little solid data just yet.
As of 2009, over half of the clinics in the US which reported their data on egg freezing either haven't thawed a single egg or haven't achieved a live birth, and just 8 clinics reported more than 10 babies. http://www.nature.com/news/2011/110823/full/476382a.html That, more than anything else, argues that this is still a highly experimental procedure in the US.
Finally, back to the ethics of it: it's criminal negligence to subject a person to a treatment which you have good reason to believe is substantially more likely than standard practice to cause their death, especially when there is no benefit to that individual from such treatment.
For example, suppose we develop a new cancer treatment for children. There's some very thin evidence suggesting it's just as effective as existing treatment, but there's more evidence suggesting that it's less effective, and that it is more likely to cause the child to die from an unrelated cause than current practices. There's no benefit to the child from receiving the new treatment.
It would absolutely be considered medical neglect, as well as a violation of medical ethics, for the child to be subjected to the new treatment instead of the old. The doctor would not be protected, either, because he could have averted the death by providing the superior treatment. (Consider the case of doctors who get sued or charged with wrongful death for failing to perform C-sections in the face of known risk factors, which happens all the time.)
These same arguments all apply to freezing embryos, and other personhood advocates have found them to be unpersuasive in that context. These are "natural" deaths rather than deliberate ones, but the risk to the embryo is judged too high, and could be averted with fresh transfer instead.
Finally, the ethical argument does make a difference here. Doctors aren't allowed to provide unethical treatment, even if it's technically not illegal. They still wouldn't be able to treat patients under such a scenario.
Bill
Thank you for listing the above criteria. I'm sure that it will save us both a great deal of frustration. I have found two, independent studies which meet your criteria with the exception that the first is an Italian study and the second was a study of donor oocytes. Both were reproducible clinical studies demonstrating that there is no statistically significant difference between the results obtained by using cryopreserved oocytes versus fresh oocytes.
In regards to your comment on Italian studies, let me point out that you are mistaken in your understanding of the legal restrictions on IVF in that nation. The Italians were never required to transfer three embryos at a time. They were simply required to transfer every embryo that survived to that point of the procedure. (That requirement was partially lifted in 2009 by the way.) Therefore, they seldom attempted to fertilize more than three oocytes at a time and they had the potential for transferring up to three embryos at a time.
The transfer of up to three embryos at a time does increase the risk of multiples, but it does not have any real effect on the rate of pregnancy per oocyte. It is reasonable to conclude that the Italian study would have had similar results if each embryo had been implanted individually rather than in groups of up to three. If all other variables remained the same, then the embryos which implanted and survived to the 12th week of gestation would most likely have done so regardless of whether they were transferred individually or in small groups.
Furthermore, the restriction against selective transfer does not in any way affect the results presented in table III of the Italian study.
I can see where you are coming from in regards to studies of donor oocytes, but if nothing else, we should at least be able to agree that the second of these studies demonstrates the efficacy of oocyte cryopreservation for healthy oocytes. Having established that, we can then look back to the Italian study and see that it arrived at the same conclusion without relying on donor oocytes.
Here are the links for the two studies:
1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794665/?tool=pubmed
2) http://humrep.oxfordjournals.org/content/25/9/2239.long
Atlee
Check your data. The oocyte cryopreservation arm of Rienzi 2009 involved 40 patients. What's more, as the authors themselves note, this is the first clinical trial demonstrating results in a population of infertile patients, rather than donor egg patients. "Further studies, performed on a larger scale, are however needed to confirm clinical outcomes of vitrified oocytes and the safety of the technique."
I've never claimed that the Italian law required transfer of three embryos. What I've claimed is that common practice in the Italian studies is to transfer three embryos whenever possible, which you can easily verify for yourself by observing that the average number of embryos per transfer is well above 2, even in younger populations.
And yes, I'm aware that the Italian law was declared unconstitutional in 2009.
You may find this study of interest: http://humrep.oxfordjournals.org/content/early/2010/12/08/humrep.deq342.full.pdf . Following the lifting of the restrictions, the authors note that a statistically significantly higher percentage of cycles made it to the point of embryo transfer (meaning that the law left many patients with no embryos at all, exactly as I have contended all along). The overall pregnancy rate improvement following repeal reaches statistical significance.
And no, we can't extrapolate anything about oocyte cryopreservation in an infertile population from donor egg studies. The very criteria that make women eligible to donate eggs (that is, proven egg quality by way of a pregnancy) are precisely what infertile couples lack. Egg quality is a key issue in the success of oocyte cryopreservation.
Rienzi 2009 notes that "The origin of the oocytes involved is, in fact, clearly a determining factor in the results, with an obvious advantage of young donors compared with older infertile women". In support, she cites Kim 2009 (http://www.ncbi.nlm.nih.gov/pubmed/19217099), which shows pretty sub-optimal results for the same technique in leftover oocytes from infertile patients.
Bill
You are correct to point out the statement by Rienzi et al. that "Further studies, performed on a larger scale, are however needed to confirm clinical outcomes of vitrified oocytes and the safety of the technique." In fact, that statement provided sufficient motivation for the same group to publish the results of a larger study just six months later which confirmed their initial findings. The group stated in that study that "high cumulative ongoing pregnancy rates were achieved in a standard infertility program with transfers of embryos derived from fresh and subsequently vitrified oocytes." They also concluded that "The overall efficiency justifies the application of this strategy in routine infertility work."
You can see the results of this larger study at this link:
http://humrep.oxfordjournals.org/content/25/5/1199.full
Atlee
Yes, this meets the criteria I suggested for a Phase 2 study, and I will certainly agree that this individual study showed good results. However, it also shows something very important: the diagnoses of the patients included in this study are remarkably different in some key ways from the larger population of infertility patients.
Compare the patient diagnoses to the CDC's report of diagnoses among patients seeking IVF in 2008 (http://cdc.gov/art/ART2008/sect2_fig16-26.htm#f20), and the difference should be very obvious. Specifically, over 60% of patients in this study had either male factor or tubal infertility, whereas 26% of general infertility patients have either diagnosis. Only 4 individual cases had ovulatory issues, whereas almost 18% of the general infertility population has these diagnoses in isolation. The combined infertility rate (patients with multiple diagnoses) was also very low compared to the US rate, which means there's a further disparity for ovulatory issues.
This is very, very important, because the effectiveness of oocyte cryopreservation is directly related to egg quality and ovulatory issues. Tubal infertility and male factor infertility don't impact egg quality, and patients with these diagnoses are much likelier to get pregnant by IVF than the general population in fresh IVF. Furthermore, it is to be expected that they will have better results from oocyte cryopreservation, as their eggs are expected to be healthier than the general lot of IVF patients, and thus are somewhat more comparable to donor eggs.
This isn't necessarily a fault of the individual clinic, which considered all of their patient population for inclusion. Rather, it is a problem of self-selection in the Italian IVF population. Patients with difficult diagnoses independently choose, or are counseled, to pursue IVF tourism in countries with looser regulations -- and they do so, in huge numbers. (http://www.ivf.net/ivf/restrictive-fertility-law-forces-italian-patients-abroad-o2409.html, http://www.eshre.eu/01/MyDocuments/Shenfield_et_al_2010_Cross_border_reproductive_care_in_six_European_countries.pdf) Italy does approximately 40,000 cycles a year, which means that 10% of all Italian infertility patients seek treatment in just the 27 clinics observed here. Some clinics in neighboring countries now do more than 50%
of their cycles on Italian patients -- and those studies don't include IVF tourism in Asia or India, either.
Bottom line, when you stack the deck with patients who are predisposed to get good results from your intervention, you should expect to get good results from your intervention. It doesn't show that the results of your intervention are universally applicable.
That's why you do larger studies in several hundred patients, and in multiple locations, so that you can weed out external factors like deliberate or unintentional patient selection before you conclude that your new treatment really works in the larger patient pool.
Bill
I think that we've achieved a significant level of agreement here. Let's take a moment to review the discussion to this point and note several points with which we both concur.
1) We both agree with the ASRM that "as of 2010, the number of comparative studies of oocyte cryopreservation published in peer-reviewed journals that demonstrate 'there is adequate scientific evidence of safety and efficacy' has exploded."
2) We seem to agree that oocyte cryopreservation is a valid procedure for donor oocytes.
3) We agree that the efficacy of oocyte preservation has been demonstrated for all categories of infertility except that of ovulatory dysfunction.
We have therefore come to an agreement on the efficacy of my proposed treatment method for cases of fertility preservation as well as for 93.3% of all infertility cases. Your opposition to the personhood amendment therefore rests primarily on your claim that the validity of oocyte cryopreservation has not been demonstrated for 6.7% of the couples seeking fertility treatment. Let me point out that you make this claim in direct opposition to the statement made by Ubaldi et al. that "According to the Cox regression analysis, infertility factors ... did not influence the ongoing pregnancy rates." Nevertheless, let's assume that your claim is valid and that 6.7% of those seeking fertility treatment do not yet know if the methodology that I outlined will enable them to give birth to a child. What implications would this claim have in light of the personhood debate?
According to one of your own articles, the negative effect that a personhood amendment might have on IVF is that it could end the practice of freezing embryos and limit the number of eggs fertilized to the number of embryos that the patient is willing to transfer in a single cycle. You claimed that "these two restrictions would end physicians’ ability to perform IVF." (http://parentsagainstms26.com/start-here/ivf-overview/) This discussion, however, has revealed a different picture.
First, you have yourself admitted that the passage of a similar law in Italy did not end the practice of in vitro fertilization in that nation. In fact, you claim that the 27 clinics in that nation perform about 40,000 IVF cycles per year. Therefore your claim that a personhood amendment would end all IVF treatment is historically inaccurate.
Second, you have agreed that oocyte cryopreservation is an effective alternative to embryo cryopreservation for women who have healthy oocytes. This would allow the majority of women seeking IVF treatment to do so without freezing any embryos. Therefore your claim that a restriction on embryo freezing would end all IVF treatment is scientifically inaccurate as well.
A personhood amendment would definitely have an effect on IVF, but it most certainly would not have the extreme effect of ending the process altogether as you claim. At most, it would delay the availability of IVF treatment for a small percentage of women until further studies have been able to demonstrate the efficacy of oocyte cryopreservation for those suffering from ovulatory dysfunction.
Having established the flaws of your scientific claims, let me now address the ethical component of this discussion. This is where I believe that our real disagreement lies, and it is your ethical view of human embryos that I believe forms the real foundation of your opposition to the personhood amendment.
In an article for the Religious Dispatches magazine, you stated that you do not "believe that embryos are fully equivalent to people." (http://www.religiondispatches.org/archive/sexandgender/5249/of_personhood_and_the_pill%3A_what%E2%80%99s_at_stake/) I have yet to read any proof that you may have for this belief, but it is obvious that your views of personhood and IVF flow directly from this ethical foundation. Personhood advocates, on the other hand, have an entirely different foundation upon which we build our case. We believe that the moral equivalence between an embryo and a two-year old child is firmly established by the Bible, the law, judicial precedent and scientific inquiry. I am fairly certain that you have read my Personhood Booklet and that you are aware of the evidence supporting that belief. You have yet to address any of the claims made in that booklet, and I challenge you to do so as well as to present evidence to support your belief to the contrary.
This has been a very interesting discussion, and I thank you for participating. I have thoroughly enjoyed presenting your readers with the scientific evidence that debunks your claim regarding personhood and IVF. The crux of the argument, however, is not the effect that a personhood amendment would have on IVF, but whether or not the human embryo has an unalienable right to life. If the embryo does have a right to life, then a personhood amendment designed to protect that right is fully justified regardless of the cost. ("...That to secure these rights, Governments are instituted among Men...") If the embryo does not have a right to life, then the entire foundation of the personhood movement will crumble.
And so I ask you to meet the above challenge. To support your position on personhood and IVF, can you provide evidence to prove your own ethical position and disprove mine?
Atlee
We concur on none of the above. Let's start with #1: we don't both agree with ASRM, because that's not what ASRM says. That's a description of an interactive panel debate which was held at an ASRM meeting. It was written by the doctors hosting the panel, not by the ASRM, and does not in any way, shape, or form represent the ASRM's official position on the matter.
This has already been explained to you. For you to continue to represent it as an ASRM position, simply because they allowed such a debate to be held, is a deliberate falsehood. It even contradicts your own acknowledgment from your December 16 post that you "did not provide the quote to say that ASRM has changed their position, but rather to demonstrate that their position on this topic has been challenged by those within their own ranks".
ASRM continues to hold the position that oocyte cryopreservation is experimental, and that it needs to be subjected to much larger studies than have yet been performed before being offered without the guidance of an IRB, let alone universally substituted for existing IVF practices.
There's a Commandment against telling lies. I previously assumed it was ignorance, but if you're going to keep repeating it, I must conclude it's deliberate dishonesty.
2) and 3) Did you completely fail to listen to anything I said about how these studies are still too small and too few in number to conclusively demonstrate anything on their own? You need multiple studies of this size, performed at different clinics, to reach something that could be considered scientific consensus. You need them to reach true statistical significance, which I don't think a single one of the studies you've linked does.
It's literally laughable that you talk about the validity of Cox regression testing over the 29 pregnancies in the Ubaldi preservation arm -- just look at how wide those confidence levels are. Anyone with any statistics background at all will correctly note that this is clinically meaningless, and that the p-values indicate that it's perfectly possible to arrive at such a distribution by random chance alone, in such a tiny population.
Once again, you're showing why this truly IS an experimental technology. The very studies on which you're placing all your reliance are too underpowered to provide adequate statistical significance to regard any of their conclusions as scientifically reliable or equivalent to existing procedures. That's the definition of Type II statistical error, and it indicates nothing other than that more studies need to be done.
That's why people who actually understand statistics and research continue to regard this as an experimental area of interest, not as a replacement for existing procedures.
Additionally, check your numbers for ovulatory dysfunction, because you have those totally wrong. As I posted, 18% of the US infertility patient population has ovulatory problems in isolation, and a far larger percentage have ovulatory issues in combination with some other diagnosis such as male factor or endometriosis.
As I have already explained once to you, this is a flaw of the Ubaldi study, as well as all the other Italian studies, and it's a key reason why these can't be taken as predictive of wider clinical experience in the general infertility population.
Finally, in saying that IVF can continue because Italy does 40,000 cycles per year, you're ignoring several very important things about Italy.
1) the cost of undergoing IVF is trivial compared to the US, and is largely covered by insurance. Patients can afford to do a few cycles with a low probability of success, because those cycles cost them hundreds of dollars rather than tens of thousands. When those fail, they move on to clinics in other countries, where they can actually have reasonable odds of success.It's the same reason that US patients do multiple IUI cycles: the success rate is low, but it's relatively cheap. You never know when you might get lucky, and that keeps the clinics in business.
2) We know that the Italian legal restrictions already force a significant percentage of all Italian infertility patients to seek treatment in a foreign country. Over 10% seek treatment in a handful of other European countries, not including all those who travel to Asia, America, or non-reporting European clinics.
3) The Italian doctors inflate their pregnancy rates by medical practices which violate ASRM standards. They consequently saw a tenfold increase in their triplet rate. (Similar practices in Germany have resulted in a shockingly high selective reduction rate. ) They have more triplet births than any other European country, and account for 20% of all European IVF triplets. (http://humrep.oxfordjournals.org/content/suppl/2010/06/22/deq124.DC1/deq124supp.pdf)
4) Italy currently has the lowest overall pregnancy rate of any European country except Turkey. Their overall rate is just 12%, compared to 35% in the US.
When you dramatically reduce success rates, impose potentially frightening legal liabilities, and triple the already high costs of IVF, how many IVF clinics do you think you're going to have left? Given the very different medical and legal realities in America, US physicians won't be able to keep their clinics open and continue treating patients. This opinion is unanimous among all infertility organizations, including the ASRM and RESOLVE.
Bill
Ah, but we are in agreement. You see, I have not claimed that the ASRM has changed their official position. I have simply pointed out that they recognize the large number of scientific papers which take the opposite position. You have now come to admit that statement to be true.
Think back to our first conversation on this topic. Do you remember what you said about oocyte cryopreservation? You stated that:
1) There are only a few clinics who had had limited success with this method of IVF.
2) There is no research on the effectiveness of oocyte cryopreservation for couples with infertility issues.
3) Only two studies have demonstrated success rates comparable to existing IVF, and
4) The largest studies still demonstrate vastly lower implantation rates.
Over the course of the current discussion, however, we have addressed the contents of eight independent studies of oocyte cryopreservation which have demonstrated success rates comparable not just to embryo cryopreservation but to the "gold standard" of fresh IVF transfers. Each of these studies has also included citations of additional studies achieving similar results. Furthermore, you revealed your knowledge of additional studies when you attempted to preemptively reject them. In particular, you made reference to meta-analyses, donor egg studies and studies performed in Italy. In order to preemptively exclude studies in these three categories, you had to at least suspect that there actually were studies in these categories that disagree with the official position of the ASRM.
In fact, simply typing "oocyte cryopreservation" into the PubMed search engine will return 870 articles published since 2008, 53 of which include the exact phrase in their title. Here are some examples of articles that can be found via this search:
Cao et al. 2009 "Comparison of survival and embryonic development in human oocytes cryopreserved by slow-freezing and vitrification."
- Study of 605 oocytes demonstrating statistically significant difference between slow freezing and vitrification in the categories of oocyte survival rate, cleavage rate, percentage of high-quality embryos, percentage of blastocyst development and oocyte abnormalities. Vitrification was superior to slow freezing in every category.
http://www.ncbi.nlm.nih.gov/pubmed/18930218
Smith et al. 2010 "Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing or vitrification."
- Study revealing a much higher pregnancy rate with vitrification over slow freezing.
http://www.ncbi.nlm.nih.gov/pubmed/20171613
Belva et al. 2008 "Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles"
- Study showing significantly higher rate of major malformations in children born from cryopreserved embryos fertilized via ICSI. (According to Noyes et al. 2009, oocyte cryopreservation does not share this risk, and is therefore a safer procedure.)
http://humrep.oxfordjournals.org/content/23/10/2227.full
Virant-Klun et al. 2011 "Slow oocyte freezing and thawing in couples with no sperm or an insufficient number of sperm on the day of in vitro fertilization"
- Study of 22 couples utilizing slow freezing of oocytes with no statistically significant difference in pregnancy rates compared to fresh oocytes.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042381/?tool=pmcentrez
Hodes-Wertz et al. 2011 "Retrospective analysis of outcomes following transfer of previously cryopreserved oocytes, pronuclear zygotes and supernumerary blastocysts"
- Study of 200 cryopreservation cycles including oocyte, pronuclear zygote and day-5 blastocyst cycles. When compared to 400 fresh embryo cycles, the oocyte group showed similar rates of implantation, pregnancy and live birth.
http://www.rbmojournal.com/article/S1472-6483%2811%2900176-3/abstract
Noyes et al. 2010 "Oocyte cryopreservation outcomes including pre-cryo and post-thaw meiotic spindle evaluation following slow cooling and vitrification of human oocytes."
- Study of 32 women seeking oocyte cryopreservation for infertility treatment and achieving a live birth rate of 56%.
http://www.fertstert.org/article/S0015-0282%2810%2900079-8/abstract
As reported in "Oocyte cryopreservation: a feasible fertility preservation option for reproductive age cancer survivors" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941585/?tool=pmcentrez#CR6
Oktay et al. 2006 "Efficiency of oocyte cryopreservation: a meta-analysis."
- Study showing no statistically significant difference in pregnancies and live births from vitrified oocytes as compared to fresh oocytes.
http://www.ncbi.nlm.nih.gov/pubmed/16818031
Kuwayama and Leibo 2008 "Efficiency of the cryotop method to cryopreserve human oocytes; analysis of in vitro and in vivo results at eleven IVF clinics."
- Study of 360 patients achieving live birth following oocyte cryopreservation.
http://www.fertstert.org/article/S0015-0282%2808%2902428-X/abstract
Yoon et al. 2007 "Survival rate of human oocytes and pregnancy outcome after vitrification using slush nitrogen in assisted reproductive technologies."
- Study showing a 43.3% pregnancy rate from 30 cycles using vitrified oocytes.
http://www.ncbi.nlm.nih.gov/pubmed/17350007
Antinori et al. 2007 "Cryotop vitrification of human oocytes results in high survival rate and healthy deliveries."
- Study demonstrating a 32.5% pregnancy rate out of 330 vitrified oocytes from infertile couples
http://www.ncbi.nlm.nih.gov/pubmed/17207335
Garcia et al. 2011 "Efficacy of oocyte vitrification combined with blastocyst stage transfer in an egg donation program."
- Study of 1098 oocytes of which 312 were vitrified prior to fertilization with a pregnancy rate of 61.8%
http://www.ncbi.nlm.nih.gov/pubmed/21303777
Grifo and Noyes 2010 "Delivery rate using cryopreserved oocytes is comparable to conventional in vitro fertilization using fresh oocytes: potential fertility preservation for female cancer patients."
- Study of 22 infertile women who submitted oocytes for cryopreservation resulting in an ongoing pregnancy/life birth rate of 57%.
http://www.ncbi.nlm.nih.gov/pubmed/19439285
Fadini et al. 2009 "Human oocyte cryopreservation: comparison between slow and ultrarapid methods."
- Study of 285 vitrified oocytes which revealed a pregnancy rate of 18.2%.
http://www.ncbi.nlm.nih.gov/pubmed/19712551
Cobo et al. 2008 "Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method."
- Study of vitrified oocytes from 30 donors which produced an ongoing pregnancy rate of 47.8%.
http://www.ncbi.nlm.nih.gov/pubmed/17889865
Surely you must have read each of these as well as many other such articles prior to launching your campaign against personhood, and so it must be that we agree on the vastness of the scientific research which stands in opposition to the official position of the ASRM.
Similarly, we have also reached an agreement on point number two: "that oocyte cryopreservation is a valid procedure for donor oocytes."
You stated that you would accept the results of a study which contained reproducible results for a patient group large enough to establish statistical significance. I provided such a study in the form of a 2010 article by Cobo et al. published in the journal, Human Reproduction (http://humrep.oxfordjournals.org/content/25/9/2239.long). That article described the results of a "randomized, prospective, triple-blind, single-centre, parallel-group controlled-clinical trial, including 600 recipients," and it "confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme."
In response to this study, you said that "no, we can't extrapolate anything about oocyte cryopreservation in an infertile population from donor egg studies. The very criteria that make women eligible to donate eggs (that is, proven egg quality by way of a pregnancy) are precisely what infertile couples lack. Egg quality is a key issue in the success of oocyte cryopreservation." You have neither challenged nor questioned the primary claim of the article - that it confirms the efficacy of oocyte cryopreservation for donor oocytes.
In regards to our third point of agreement, it is significant to note that your disagreement to my claim of agreement consists of only two parts. First, you deny that any of the studies which I presented achieved true statistical significance. Second, you disputed the figure of 6.7% for women seeking infertility treatments for ovulatory problems. I will answer these arguments individually.
In response to your first argument, let me remind you that I presented three separate studies which corresponded to each of the three phases that you suggested in your list of criteria. You described phases 2 and 3 as: "Phase 2 studies usually involve 100-300 patients, and Phase 3 studies involve more than 300-3000 patients." This of course implies that phase 1 studies involve less than 100 patients. The Rienzi et al. study from 2009 was a phase 1 study. In regards to the 2009 study by Ubaldi et al., you said: "Yes, this meets the criteria I suggested for a Phase 2 study, and I will certainly agree that this individual study showed good results." The study from Cobo et al. in 2010 rounded out the criteria by qualifying as a phase 3 study. All three of these studies presented statistically significant results demonstrating the efficacy of oocyte cryopreservation for at least all categories of infertility except that of ovulatory dysfunction.
Your dispute over the 6.7% figure is very interesting. You claim that the CDC report you presented gives an 18% figure for couples seeking infertility treatment as a result of ovulatory problems. Since that report lists ovulatory dysfunction as representing just 6.7% and diminished ovarian reserve as representing 11%, I can only assume that you derived your 18% figure from adding these two. There is, however, a very important difference between ovulatory dysfunction and diminished ovarian reserve.
That same CDC report defines the first category as referring to those women whose "ovaries are not producing eggs normally," and the second as referring to those women for whom "the ability of the ovary to produce eggs is reduced." This distinction of definitions seems to indicate that the first category involves egg quality while the second refers only to egg quantity. Surely you must realize that a diminished quantity of healthy eggs would not have any statistical effect on the success of an IVF program utilizing oocyte cryopreservation. There is therefore no reason to remove the category of diminished ovarian reserve from the list of those for which oocyte cryopreservation has been proven to be effective.
Nevertheless, even if we accept your figure of 18%, that would still leave 82% of infertility cases for which the efficacy of oocyte cryopreservation has been proven. This fact alone fully disproves your claim that a personhood amendment would put an end to all IVF treatments. When we add to this the historical fact that similar legal restrictions did not end all IVF treatments in Italy, the fallacy of your position becomes irrefutable. We both know that IVF can still be completed under a legal restriction against the intentional killing of human embryos because we both know that this was successfully accomplished in Italy.
Atlee
The Nature report I linked earlier supports my position: only 8 clinics in the US have had more than 10 live births from oocyte cryopreservation. Over half the clinics which offer it have never had a live birth at all. I think it's fair to call 8 clinics a "handful", out of several hundred clinics in the US.
As for the ovulatory numbers, the reason I'm combining the CDC stats is because Ubaldi did likewise. They don't break ovulatory dysfunction out from diminished ovarian reserve, but lump it all together as "ovulatory". This isn unsurprisingly, given that they literally have only 4 patients meeting those criteria. Still, if we're going to compare apples to apples, we have to combine the patient populations.
Yes, it's ludicrous to make any judgments about 4 cases. That's precisely MY point: you want to modify treatment for over 26,000 American women per year, based on the results of four (4) Italian women. Can there be any better argument for the experimentality of this procedure -- that even your shining exemplar of a study involves numbers of patients which can be counted on one hand.
Re the ASRM: no, the ASRM does not say that. Not even the first part of that statement can be interpreted to reflect the ASRM's acknowledgment of anything. Are you STILL failing to understand that the statement in question was most likely written by the doctors hosting their panel? They don't have scientific committees sign off on debate session descriptions.
Once again, the very height of intellectual dishonesty for you to even attempt to reference this. You should be ashamed of yourself for attempting to imply that the ASRM agrees with you on oocyte cryopreservation's applicability to the general infertility population.
Since you want to talk about Italy and point to it as a shining example: would you like to explain why Italy's overall pregnancy rates are the lowest in Europe, except for Turkey? If oocyte preservation is such a great answer, why does Italy have an overall success rate which is 1/3 of the US overall rate -- and that pregnancy rate is only as high as it is because of practices which would not be permitted by personhood legislation like that proposed by Personhood Mississippi? Would you like to talk about how Italy's laws have driven literally thousands of patients to seek treatment in other countries?
See, that's what happens when you translate individual studies into entire populations: reversion to the mean. That's why you study it in large groups before even proposing it as a reasonable alternative, much less replacing the current standard of care.
Also, let's clarify something very important: if you want to throw around the 870 results for "oocyte cryopreservation" on Pubmed, I think it's only fair to clarify that the vast majority of these aren't human studies. On just the first page of that same search, we have hard corals, goats, mice, cats, and cows, plus several editorial-type articles which don't actually constitute clinical trials.
Seriously, it's nothing short of ridiculous to try to make a study of freeze-dried cow sperm as supportive of human oocyte cryopreservation, just because that study contains the words "oocyte" and "cryopreservation".
You keep throwing around the same handful of studies -- several of the ones listed in your bibliography salad have already been cited elsewhere in this discussion.
Re the birth defect rates, do you know the minimum sample size required to determine equivalence in the birth defect rate across a population of 150,000 cycles? You need 4,000 patients just to tell you whether the confidence interval is 0.5-2. In plain English, that means you'd have to look at at least 4000 patients' results to know whether oocyte cryopreservation is no more than twice as likely to produce congenital anomalies as standard IVF. A sample size of 936 patients can only identify that the birth defects are less than 3.75 times as likely to occur. That is, 936 patients can't even tell you whether birth defects are 3x as likely or half as likely following oocyte cryopreservation versus fresh IVF. It is, quite simply, vastly underpowered to draw any such conclusions as that the two rates are equal. You would need to study four times as many oocyte cryopreservation births to know that for sure -- only you can't, because there haven't been anywhere near that many births.
Once again, this highlights the difficulty of making conclusions based on the success rates of a few dozen patients. Even the largest studies we've discussed fall far, far below the threshold for true statistical significance. That's why we shouldn't base treatment standards for an entire country's worth of IVF patients off of those very preliminary standards.
Finally, I notice you still haven't addressed my contention that the experimental nature of oocyte cryopreservation represents an ethical and legal violation which would not be permissible under personhood.
Let's say that I am a Mississippi IVF clinic which has never performed oocyte cryopreservation. Personhood-style IVF legislation passes, and to try and keep my practice open, I decide to start attempting to preserve oocytes. I buy a VitMaster freezer and Cryotop kits, and start trying it out on my patients. The first round, I get a 10% successful fertilization rate, compared to my normal 70%. That is, 60% of my study population has died, who would have survived if I had performed standard fresh-ICSI. I try again, and get results similar to Levi-Setti 2006: a 12% pregnancy rate, compared to my usual 35% rate, and a 33% miscarrage of that 12% rather than the usual 20%.
Can you identify for me another situation where it would be scientifically and legally acceptable to cause this kind of death rate in human beings, when the usage of a known treatment would have prevented it without offering any disadvantages to the people being studied? Would it be in any way acceptable to perform such experimental treatment on newborns, if only 10% of them survived to age 5 versus 70% with a standard method? Can you explain how performing an equivalent study on newborn human beings would NOT be considered the very height of criminal neglect?
We routinely charge mothers for manslaughter when they engage in practices like drug abuse which raise their miscarriage rate by 20%, let alone by 300%. In fact, you have already stipulated that embryo cryopreservation ought not to be allowed under personhood, because up to 50% of the embryos involved don't survive the process, and this fits the legal definition of manslaughter. By that definition, oocyte cryopreservation would be equally impermissible.
Under personhood, oocyte cryopreservation is research involving live human beings, because all cryopreserved eggs become legal persons the moment that the ICSI micropipette is withdrawn. Subjecting them to cryopreservation beforehand is ethically no different than subjecting embryos to cryopreservation -- it's a procedure which materially threatens a person's basic rights.
You have previously concluded that even unintended death of embryo is not justifiable under personhood, even for so important a case as protecting the mother's life and fertility. If surgical removal of an ectopic pregnancy is not permissible, how much less permissible must it be to perform life-threatening experimentation on human beings, for no greater reason than the continuation of IVF?
It is thoroughly morally inconsistent for you to support oocyte cryopreservation.
Bill
Your ethical argument is flawed for three reasons.
First, you are mistaken in concluding that oocyte cryopreservation is research involving live human beings. Oocyte cryopreservation involves the freezing of unfertilized eggs. I am not aware of a single personhood proposal that attempts to grant constitutional protection to oocytes. If I ever become aware of such legislation, then I will publicly oppose it. Under a personhood amendment, the right to life begins at fertilization not at ovulation.
Second, I have not "previously concluded that even unintended death of embryo is not justifiable under personhood." What I have stated was that: "A doctor who has taken every reasonable precaution against the death of his patient is generally not prosecuted if that patient happens to die while under his care. A personhood amendment would simply place embryonic deaths in the same legal category as any other death that occurs under a doctor's care." I have also explained that I am not opposed to embryo cryopreservation. I stated very clearly that the "combination of oocyte cryopreservation and single embryo fertilization would eliminate the step in the standard IVF process which could be condemned under the personhood amendment - the destruction of embryos which are not used by the donor." Therefore, a correct statement of the ethics of my position would be that I oppose the intentional killing of living human beings except as permitted by the Giver of life in the Bible.
Third, you are mistaken in your understanding of manslaughter. The Code of Alabama states that:
"A person commits the crime of manslaughter if:
(1) He recklessly causes the death of another person, or
(2) He causes the death of another person under circumstances that would constitute murder under Section 13A-6-2; except, that he causes the death due to a sudden heat of passion caused by provocation recognized by law, and before a reasonable time for the passion to cool and for reason to reassert itself."
[Code of Alabama - §13A-6-3]
Most states have a similar definition, and under a personhood amendment, anyone recklessly causing the death of a human embryo could be charged with manslaughter. However, there is a very important clause in Alabama law which takes precedent over this definition. That clause states:
"Mistake, or unintentional error on the part of a licensed physician or other licensed health care provider or his or her employee or agent or any person acting on behalf of the patient shall not subject the licensed physician or other licensed health care provider or person acting on behalf of the patient to any criminal liability under this section."
[Code of Alabama - §13A-6-1]
In other words, a doctor who has taken every reasonable precaution against the death of his patient cannot be prosecuted in the state of Alabama if that patient happens to die while under his care. A personhood amendment would cause this clause to apply equally to the actions of fertility doctors toward the embryos under their care. Therefore, the scenarios which you describe would not result in criminal charges unless it could be demonstrated that the doctor intended to cause the death of human embryos.
Atlee
Freezing isn't a mistake or an unintentional error. It's a deliberate action which is known to subject an embryo, or an egg, to a higher rate of death than an un-frozen one, even when performed correctly in accordance with medical standards.
It is NOT taking every reasonable precaution against the death of the patient. If you want to take every reasonable precaution, you would only work from fresh eggs, in accordance with currently-accepted medical standards, and would require that the resulting embryos be transferred fresh.
This is exactly the same logic you've already conceded as prohibiting embryo cryopreservation: it causes the death of people. Intention isn't a necessary component of manslaughter.
Legally speaking, the ASRM's opinion carries much more weight here than your (mis)interpretations of these studies. Physicians are protected when they act according to the professional consensus, which would be the ASRM opinion. Until and unless the ASRM issues a statement judging oocyte cryopreservation to be equivalent to fresh IVF for all patients -- not just a reasonable option for certain patients who are willing to accept the risk of embryonic death -- physicians won't be legally protected from charges of using un-proven experimental treatments which put human life at risk.
Here I'm referencing the new language of the 2012 Arkansas and Colorado initiatives: any procedures which "cause the death of a person" are prohibited. There's no requirement that said death be intentional or even direct, as long as they demonstrably cause death. A procedure, or an individual action of a doctor, which causes embryos to die at higher rates would certainly qualify. It doesn't matter whether that procedure is performed pre- or post-fertilization, if it raises the risk of post-fertilization death.
And it doesn't matter whether YOU are personally opposed to embryo cryopreservation. It's a matter of public record that most official voices of the personhood movement consider it to be incompatible with personhood, and have publicly argued or against it.
For example, Les Riley of Personhood Mississippi is currently advocating the passage of legislation identical to Georgia's failed SB-169 from 2009, which explicitly prohibits embryo cryopreservation.
Insofar as any of you are authorities on how personhood ought to be interpreted in practice, it's reasonable to suppose that the courts and the legislature will interpret it as prohibiting embryo cryopreservation.
For the record, Mississippi has a similar code protecting physicians from legal liability for unintentional errors, and it was universally agreed by the Yes On 26 campaign that embryo cryopreservation would nonetheless be prohibited.
(The chief proponent of this stance was an OB-GYN, who might reasonably be assumed to understand how that statute would protect his profession.)
As for the question of the 870 studies, you've fallen victim to the black swan fallacy. I don't need to read all 870 of them if I can readily observe that a substantial number don't involve either oocyte cryopreservation or human clinical trials.
Had you actually read them before advocating your position -- and as the person arguing for a change to the existing procedure, it's far more incumbent on you to do so than it is for me to argue for the status quo -- you would see the same thing. Clearly, therefore, you either have not bothered to actually read the contents of your own search results, or you are happy to try to promote a statistic which you know to be false.
FYI, limiting the Pubmed query to human oocyte cryopreservation with a publication date within the last 3 years knocks the number down to 371 citations. Again, a quick scan of the first few pages is perfectly sufficient to demonstrate that many of them don't actually relate to the practice oocyte cryopreservation, but simply happen to contain both words.
For example, the results contain a study of sperm cryopreservation which mentions that even damaged sperm are still capable of fertilizing oocytes. Surely we can both agree that this is not a study which has any application to the question of oocyte cryopreservation. Another study is a mouse oocyte cryopreservation which mentions the difficulties of translating the results to humans.
Limiting the results to the exact phrase "oocyte cryopreservation", with a publication date of the last three years and a limit of humans-only, knocks it down to 76 citations, the vast majority of which aren't clinical trials. Even those search criteria still include a study on zebrafish, and one on rhesus monkeys. Most of the rest mention oocyte preservation only as a last-ditch option for cancer patients, not an equivalent for IVF.
That's why we keep going around about the same few papers: that's all there are. You keep trying to suggest otherwise, but that's just not what the evidence shows.
As further evidence of your cherry-picking, and in the context of Italy, let's discuss how the Italian National Register confirms poor results from vitrification: http://www.ncbi.nlm.nih.gov/pubmed/20797902. With almost 8700 vitrified oocyte cycles, that is a far larger study than anything we've yet discussed, and is a population analysis rather than a clinical sampling. That means it doesn't just extrapolate results from a sampling of a relatively small group of patients, but actually looks at what happens in real life when the technique is applied to the general patient population.
What happens isn't good at all, in comparison to fresh IVF. The pregnancy rate was about half that following fresh transfer -- and that is true statistical significance, p<0.001, over a large number of cycles. Embryos from vitrified oocytes were about half as likely to implant, again with p < 0.001, and were also significantly less likely to develop into good embryos following fertilization.
This has to be regarded as a more authoritative data source than anything you've yet cited, both because of its size and because it's a population analysis (which is more reliable than a randomized trial).
Then there's http://www.ncbi.nlm.nih.gov/pubmed/20047739, Borini et al from Fert Stert 2010, "Multicenter observational study on slow-cooling oocyte cryopreservation: clinical outcome." This was a multi-center report involving 931 thaw cycles at multiple clinics. Among the findings were that successful fertilization, implantation, and pregnancy rates were all significantly reduced in comparison to fresh cycles. It also notes that success rates differed among clinics, implying that the good results of a few are not widely reproducible.
I'm also given to understand that a meta-analysis will soon be published about elective egg freezing at American clinics -- see http://www.sart.org/news/article.aspx?id=7336. Obviously, I haven't read the actual paper since it hasn't been published, but the results listed in the abstract are pretty dismal in comparison to current CDC statistics.
Even for the 291 vitrified oocytes, the analysis only shows an implantation rate of 18.8% in patients under age 30, compared to an overall implantation rate of 34% in all IVF patients under 35. In other words, the study found an embryo is about half as likely to implant after vitrification, even in a younger and more favorable group of patients. The slow-freezing results are even worse, with no better than a 10% implantation rate.
Obviously, we'd both have to read the study itself and look at the raw data, as well as the component studies, and consider the previously mentioned issues with meta-analyses. However, it has to be considered as adding weight to the argument that oocyte cryopreservation is an inferior technique to fresh fertilization.
Re Nature, the credentials of the writer are absolutely irrelevant, since we're interested in the facts being reported. We can cite Rudick 2009 if you prefer: http://www.fertstert.org/article/S0015-0282(10)00800-9/abstract . We see that 337 live births have been reported, but we also see a couple other interesting things, such as that a majority of these programs only offer cryopreservation only to younger women, thus stacking the deck by excluding the age groups which constitute 40% of the US IVF population (non-donor). Furthermore, we find that most of these patients aren't actually diagnosed with infertility, but women who are electively preserving their eggs.
Furthermore, it's not in dispute that 75 of the responding 143 clinics have never had a live birth, and 11 more have achieved only 1 live birth. Only 8 clinics have achieved more than 80 live births. Arithmetic therefore tells us that the remaining 56 clinics have achieved somewhere between 2-9 live births, and that they collectively account for no more than 246 live births apiece (assuming arguendo that the most successful clinics had only 10 live births apiece). That leaves us with a maximum average of about 5 live births per moderately-successful clinic, total, over a period of however many years they've been offering cryopreservation.
To bring home the scale of what we're talking about, most IVF clinics see at least 5 live births every MONTH. We are still discussing a tiny, tiny number of patients. 337 live births is ridiculously small, compared to the 46,000 live births per year from ART.
What's more, we can safely assume that the reporting clinics represent most if not all of the US clinics offering cryopreservation. If you assume that the non-reporting clinics offer cryopreservation and achieve similar results, you would arrive at birth rates more than twice as high as the documented number of live births in the world as a whole as of the publication date. It's a pretty safe bet that the non-reporting clinics do not have large and successful cryopreservation programs.
As for the other link, Boldt is a literature review, not a clinical trial, and offers no new data beyond the studies we've already discussed. It may safely be categorized with other literature reviews such as Saragusty 2011 (http://www.reproduction-online.org/content/141/1/1.full), which note that the overall state of the literature indicates that cryopreservation shows overall results inferior to fresh transfer.
We could keep going: http://www.placentajournal.org/article/S0143-4004(08)00239-7/fulltext?refissn=1472-6483&refuid=S1472-6483%2810%2900785-6, showing an implantation rate of just 8% over 233 transfers in 2007, and a notably poorer pregnancy rate. (Which study, by the way, notes that its own sample of achieved pregnancies is still too small to compare to other ART techniques).
Even Nicole Noyes, whom you have repeatedly attempted to cite in support of cryopreservation, suggests only that it's an option for "appropriate patients", that "comprehensive informed consent" is necessary to inform them of the lower overall rates, and that it should only be offered once individual clinics have "established their own efficacy in the procedure".
I'm not sure how you'd do that last without experimentation on live human oocytes, knowing that you're probably going to screw it up and cause many of them to die in the process. We don't permit doctors to just go practicing new potentially life-threatening techniques on live patients without institutional oversight and formal training. If I'm a heart surgeon, I can't just decide to start offering heart transplants to my patients. I have to go do a fellowship in transplantation first, so that I can reasonably claim to have received the appropriate training to preserve my patients' life and health. If I didn't get that training, I wouldn't be protected under that medical-liability exception you reference above, since I'm working outside my experience, education, and normal scope of practice.
Since we've established that oocyte cryopreservation directly impacts the welfare of what would legally be considered live human beings, it's only reasonable to assume that doctors would be required to complete fellowships in oocyte cryopreservation, or demonstrate comparable clinical experience, before being able to perform it in their own clinics.
There are currently no such fellowship programs in existence, let alone adequate fellowships to train the thousands of US reproductive endocrinologists within a reasonable period of time.
For clarification: when I say that you've conceded that even the unintentional death of an embryo is unjustifiable, I'm referring to your position on ectopic pregnancies.
Many authorities believe that tubal removal surgery is permissible because the purpose is to treat the ruptured tube, and the death of the embryo is an unfortunate and unintended side effect. By arguing that these patients should instead be forced to rupture, you are agreeing that even a serious threat to maternal life is not justification for procedures which have the double effect of embryonic demise, and whose primary purpose is to treat the mother.
If even a direct threat to maternal life and physical health can't justify unintentional risk to the embryo, how much less can we justify risks which are designed only to reduce the risk of multiple birth, or preserve access to IVF?
Re sample sizes, you're using the wrong formula. The one you mention gives you the way to calculate the minimum number of patients required to extrapolate to a population of 150,000 -- which, I might add, also highlights that none of the studies you've presented come anywhere near the requisite sample size.
However, once you actually get the results of your 384 patients, you will then calculate a confidence interval. What I'm pointing out is that the confidence intervals under discussion here are very large, due to the small sample sizes, so you can't go comparing the observed means directly between two studies. You have to expand the sample size so that the confidence intervals don't overlap.
Italy and triplet rates: you're assuming that Italian women don't get selective reduction done elsewhere. This is undoubtedly false.
Also, I've already provided very solid sources to show that 10% of Italian patients seek treatment in just the few European countries under discussion. 4173 Italian couples sought out-of-country treatment in the 27 European clinics studied in 2005, according to the ESHRE's survey -- an increase from 1006 in 2003. It's not "supposedly" anything.
Finally for the night, because it's very late, oocyte cryopreservation DOES involve research on live human beings. Isn't that what you're saying is created the instant that the ICSI needle is withdrawn? You can freeze and thaw them all you like, but the minute you try to fertilize them, personhood means you're dealing with a live human being. Any difference in outcome from that point on (fertilization rates, implantation rates, etc) is affecting the survival rates of live human beings.
Let's say we conduct genetic experiments on oocytes, and identify a chromosome which is necessary for an embryo to develop past 8 cells. We somehow remove that chromosome from our oocytes. They fertilize as normal, becoming people, and every single one of them promptly dies 3 days later as expected. Have we performed research on live human beings? Of course we have, and we've knowingly caused them all to die, even though we didn't do anything to the embryos themselves.
In fact, all of the emergency contraception and hormonal birth control opposition opposition hinges on just this logic. Indirect damage to an embryo, the creation of a hostile environment where it is less likely to survive, is just as bad as directly destroying the embryo, and is therefore the equivalent of any other form of abortion. You've already stated that you agree with this position on hormonal birth control and feel that it is incompatible with personhood
If it's unacceptable to create a sub-standard home for an embryo which indirectly lowers its survival rates without ever directly touching the embryo itself, how can it be acceptable to modify the embryo's precursor components in a way which is much more provably hostile? After all, the evidence for harmful effects of oocyte cryopreservation is much more extensive than that of the abortifacient effect of birth control.
And I'm frankly shocked that you don't oppose embryo cryopreservation, either. You do realize that this process directly destroys up to 50% of the embryos involved, and damages others to the point where they are unable to implant?
How in the world can you justify opposing birth control pills and IUDs as "intentional killing" but consider freezing to be perfectly allowable? This defies logic in a way that I am at a loss to understand.
Bill
You seem to be somewhat confused about my position. First, you claim that I have already conceded that a personhood amendment would prohibit embryo cryopreservation. Then you claim that it doesn't matter if I am not personally opposed to embryo cryopreservation. Then you explain that you are extrapolating my supposed opposition to embryo cryopreservation from my position on ectopic pregnancies. Then you attempt to extrapolate my supposed opposition from a statement that I made in regards to oral contraceptives. And finally, you say that you are shocked that I do not oppose embryo cryopreservation. Perhaps it would help if you focus on the exact wording of the law rather than these wild speculations on the consistency of my morals.
As I have already explained, a doctor in the state of Alabama (and several other states as well) cannot be prosecuted for manslaughter over the death of his patient unless it can be demonstrated that the death was caused intentionally. There is no legal requirement that a doctor always utilize the methods that other doctors think are the best for a given situation. There is no requirement that a doctor conform to the dictates of the ASRM, and there is no restriction against the use of experimental treatments. The key element in medical manslaughter cases in either of our states is that of intent.
This is a very, very important legal distinction to keep in mind. My statements regarding the legality of various actions under a personhood amendment would make much more sense if you consider each of them in light of this explanation. Under a personhood amendment, it would be illegal for a doctor to take any action toward a human child with the intent of killing that child regardless of the child's stage of development. Neither oocyte cryopreservation nor embryo cryopreservation are initiated with the intent of killing a human child. Therefore, no doctor can be prosecuted for manslaughter in the event that a human child dies after being frozen. The only action associated with IVF which would be prosecutable under a personhood amendment is the intentional destruction of those embryos which are not used by the patient seeking infertility treatment.
This is also true of the proposed 2012 personhood amendment in Colorado. You quoted that amendment as stating that "any procedures which 'cause the death of a person' are prohibited. Contrary to your quote, however, the actual text of that amendment states that "the intentional killing of any innocent person is prohibited." (http://personhoodcolorado.com/) Thus, the Colorado amendment agrees with my claim that no doctor would be prosecuted for the death of an embryo under his care unless it can be demonstrated that he caused that death intentionally.
You also completely misrepresented Georgia's SB-169 by claiming that it "explicitly prohibits embryo cryopreservation." First of all, this bill was not a personhood bill but rather, as it was entitled, a bill for the "Ethical Treatment of Human Embryos." The text of that bill states that: "The creation of an in vitro human embryo shall be solely for the purposes of initiating a human pregnancy by means of transfer to the uterus of a human female for the treatment of human infertility or cryopreservation for such treatment in the future." (http://www1.legis.ga.gov/legis/2009_10/fulltext/sb169.htm) This bill does not explicitly prohibit embryo cryopreservation, rather it explicitly permits embryo cryopreservation.
Your misrepresentation of the Georgia bill and the Colorado amendment as well as your misunderstanding of the Alabama statute admits to only two possibilities. Either you have never read either of the first two and were ignorant of the third until I quoted it in this discussion, or you are intentionally attempting to convey a false impression of these documents. In either case, your credibility on matters of legal importance has been seriously compromised. Since your argument against personhood is a legal argument, this series of errors undermines the very foundation of your position.
Your errors in other areas follow a similar pattern. For example, your insistence that I am just repeating the same few studies over and over again indicates that either you have not read any of the studies which I have referenced in order to know that I am not repetitively listing them or you have read them and you are lying about their content. I would prefer to believe the former of the two, but even that is a serious mark against your character. Similarly, I would prefer to believe that you are simply ignorant of the recent advancements of the Italian oocyte cryopreservation studies rather than that you are intentionally presenting results that were obtained several years prior to those advancements as evidence against their efficacy. I would also like to believe that you just don't know the difference between slow freezing and vitrification and that this is why you keep referencing slow freezing studies as evidence against vitrification. Perhaps these beliefs are true. After all, you are directly relying on an absence of knowledge to argue that Italian women "get selective reduction done elsewhere." It might be best if you would take some time to study this issue more thoroughly and reconsider the validity of your position.
By the way, using the formula p +/- 1.96 x √((p(1-p))/n) yields a confidence interval of .0095 for a sample of 936 out of a population of 150,000 with 98.7% responding in the affirmative and only 1.3% responding in the negative.
Atlee
Honestly, it's not my job to teach you basic statistics, or to help you understand what those formulas actually mean.
Your formula tells you that your mean is WITHIN the confidence interval of 95%. That's the whole point of including the 1.96 standard-deviation coeffiicent in the equation. If we repeated the experiment 100 times, 95% of the time, our observed result would fall within 1.96 standard deviations of the mean.
As I have already explained to you twice, you need to calculate the endpoints of the confidence interval, and then determine whether that interval overlaps either the incidence rate of a population, or the confidence interval of the statistic to which you're attempting to compare it.
Do that, and you will see that you need a much larger sample size to arrive at non-overlapping confidence intervals, and therefore to have certainty that your observed outcome is statistically proven superior.
I must, however, acknowledge that I actually made an error in the math, because I did the calculation for the wrong one of Belva's groups. As it happens, I significantly UNDERESTIMATED the necessary sample size. You need 13,150 patients in each study to be able to compare the two, not 4150.
Belva's fresh ICSI group involves 3073 patients, with a birth defect percentage of 1.7%. The confidence interval, with a population of 150,000, is +/- 0.45, meaning that the "real" number is somewhere between 1.25-2.15%. As you can see, the 1.3% result from Noyes 2012 (CI +/- 0.72, 0.58-2.02%) also falls within this range. Therefore, we cannot say that 1.3% is "better" than 1.7%. (And it doesn't matter that it's at the low end of the CI, either.)
In order to make the confidence levels non-overlapping, each study would have to involve 13,150 patients. That would give us a CI of 1.49-1.94% on Belva's fresh ICSI results, and 1.09-1.48% on Noyes' cryo results. Then, and only then, we would be able to say with statistical certainty that the two studies differed, and that oocyte cryopreservation resulted in fewer birth defects than fresh ICSI.
Of course, it's certainly possible to imagine a study involving 13,150 fresh ICSI cycles, because many thousands of babies are born every year following ICSI. However, it is not possible to know the results of 13,150 oocyte cryopreservation births, because that is roughly an order of magnitude larger than the number of such births known to exist.
Bottom line, it is ABSOLUTELY unproven that oocyte cryopreservation shows a superior or even comparable rate of birth defects. If you repeated Noyes on another 936 patients, and Belva on another 3073 patients, you might arrive at a fresh rate of 1.3% and an OC rate of 1.95%.
The only thing we can conclude from Noyes is that oocyte cryopreservation is associated with something less than 2x as many birth defects as fresh ICSI. Of course, over a population of 150,000 cycles a year, that could mean that a switch to oocyte cryopreservation could cause up to an additional 1,155 babies with birth defects.
(I'd say that the arithmetic is left as an exercise for the reader, but since you like to question my math, it's the upper bound of the one CI vs the lower bound of the other, 150000*0.0202 - 150000*0.0125 = 1155.)
I hope this little exercise clarifies for you just how very unreliable the conclusions of ANY of these studies are, and that you're beginning to get a feel for the numbers required to draw truly valid statistical conclusions.
As for my misrepresentation of the Colorado language, please note that I mentioned the *Arkansas* and Colorado initiatives. You can review for yourself the text of the Arkansas initiative at http://www.katv.com/story/16420533/personhood-arkansas-wants-anti-abortion-measure-on-ballot , and clearly note that it refers to "causing the death". I await your apology for calling me a liar.
Furthermore, only the first line of the Colorado initiative refers to "intentional" killing. The lines prohibiting the usage of birth control and IVF practices only mention "killing" a person.
To extrapolate what is meant by this, we can look at the Colorado amendment writers' position on emergency contraception and IUDs. Clearly their intent is to prohibit both forms of contraception. Both have been specifically addressed by previous statements from Personhood USA and Personhood Colorado. As Gualberto Garcia Jones (co-drafter of the amendment) has said in reference to the new language that "It's not that we changed our position. We're just putting it in the language." (http://www.christianpost.com/news/new-colo-personhood-amendment-features-new-improved-language-62627/) I assume you are likewise opposed to both, since you mention being opposed even to oral contraception on your website.
Neither IUDs or emergency contraception are used with the same degree of deliberation as would be involved in discarding a frozen embryo. Women and doctors use them with the INTENTION of preventing fertilization, and the implantation-prevention is a secondary effect.
Therefore, if CO 46 is to prohibit so-called abortifacient contraceptives, we must assume that the mere foreknowledge of a possible embryo-destructive side effect is enough to violate the prohibition against "birth control which kills a person". We may then infer likewise that the knowledge of a much more certain embryo-destructive side effect is enough to violate the prohibition against ART practices which "kill a person".
In a legal context, "intention" has a special meaning. It doesn't require definitive proof that the defendant deliberately set out with the exclusive goal of killing someone else. It only requires that a reasonable person would know that a given action presents a non-trivial possibility of causing serious injury or death to another person, and that the defendant could choose not to take the action.
For example, drunk driving is considered intentional killing, and is prosecutable as a lesser degree of homicide. (Here in MS it's "depraved heart murder", while other places call it "voluntary manslaughter" or "negligent homicide" or the like.) A drunk driver doesn't leave the bar with the deliberate goal of killing someone else in a car accident, but everyone knows that DUI can kill, and he has the ability not to decide to drive. Therefore, if he should be involved in a fatal wreck, he will be charged with manslaughter.
Likewise, a woman and her doctor should reasonably know that using an IUD does sometimes cause the post-fertilization loss of an embryo. She has the simple option of choosing not to use an IUD. Therefore, it would be likewise considered an intentional and reckless act.
It's not first-degree murder as we usually think of it, but it is most definitely "intentional killing" in the eyes of the law, and would thus violate personhood.
Similarly, a doctor who performed a procedure on a newborn infant which had a known 50% death rate, and which offered no benefits to that infant, and which was not medically necessary for that infant, would be charged with lesser homicide in about 10 seconds flat. Can you even pretend that this doctor would be protected by the Alabama medical statute? Of course you can't, nor should he be.
This, BTW, is exactly how Dr. Conrad Murray was convicted for Michale Jackson's death.
You're referring to the wrong version of the ETEA. The version to which I'm referring is that located at http://personhood.net/index.php?option=com_content&view=article&id=235&Itemid=609 . This is the specific version previously cited by Les Riley in Facebook postings as "model legislation".
It was drafted by the Bioethics Defense Fund, and as you can read for yourself at http://www.bdfund.org/octomom-abuses, the drafters are quite clear that it was intended explicitly to stop embryo cryopreservation.
I await your apology for calling me a liar. I have not misrepresented or misunderstood either the Georgia or the Arkansas/Colorado legislation.
As for your position, you conceded that embryo cryopreservation would be prohibited in the first conversation we had about it, where we discussed it in the context of single-embryo transfer. I will note that this was subsequently backed up by the Yes On 26 campaign's "medical talking points", where it was explicitly noted in no uncertain terms: http://yeson26.net/media/4818/amdt26_discussion_points.pdf .
Mississippi has an identical statute to protect physicians from criminal liability. However, clearly Personhood Mississippi, which cited that same law in other contexts and was therefore aware of its existence, did not believe that the statute in question would permit physicians to continue embryo cryopreservation.
If you think they're incorrect, you are by all means free to take it up with them and have that argument amongst yourselves. However, I will take them at their word when they tell me what they intend for their law to do, and what they feel it will be able to do.
It's not inconsistent to believe that the law would prohibit cryopreservation, while still thinking that cryopreservation ought to be legal. One is a moral judgment, and the other is a legal judgment. Therefore, I don't think it illogical of you to believe that cryopreservation should be permitted while acknowledging that it won't be.
What I do think is illogical are your statements that a secondary effect of a contraceptive which occasionally causes embryo loss is abortifacient and impermissible, and that even a direct and immediate threat to maternal life doesn't justify the known double effect of embryonic death, but that it would be morally and legally acceptable for a physician to perform an action with a much higher risk than contraceptive usage, for a much less urgent reason than ectopic pregnancy.
Do you care to explain how you can "advocate for a ban on any form of birth control which can be proven to cause the deaths of innocent children", yet support a practice which much more provably causes the "deaths of innocent children"? When my doctor is banned from prescribing me birth control pills which have maybe a 5% chance of killing an embryo, how can he possibly be then be allowed to freeze embryos and destroy 50% of them?
You simply cannot have it both ways. Either that statute protects physicians' ability to prescribe possibly-abortifacient birth control, or it prohibits them from freezing embryos.
As for re-citing the same handful of studies, you've cited Cobo 2008 at least twice in this discussion already. You keep citing Nicole Noyes and Grifo as though these are different clinical trials rather than different presentations of the same dataset, when I have previously noted that Noyes has performed only 46 cycles at her clinic. My goodness, you cite Noyes twice in that same post, and follow it up with Hodes-Wertz, which is yet another presentation of those same NYU patients!
You've approvingly cited studies like Fadini 2009, which shows a pregnancy rate about half that currently found in the US even with vitrification. You cite a meta-analysis, Otkay 2006, and claim it proves the superiority of vitrification, when it explicitly says that it did not include vitrification due to there only having been ten (10) babies worldwide born from vitrification as of that publication date. You further claim it shows no significant differences, when the authors themselves find "significantly lower rates" with frozen vs fresh eggs (in fact, the pregnancy rate was 1/3 that of fresh).
You keep including donor studies. You make erroneous statistical judgments based on ridiculously small numbers -- roughly half of the studies you've cited as "demonstrating" something include less than 30 cycles. You cite Cao, which didn't actually transfer any of the created embryos and thus has nothing to tell us about pregnancy rates. You've stated in the IVF article on your site that your claims are "supported" by six additional studies which turn out to be nothing of the sort. You've implied that I'm lying when I note that you rest your claims on studies of a dozen people, when you have in fact done just that in the article on your site.
You've grossly misrepresented the number of studies on oocyte cryopreservation, and failed to acknowledge that less than 10% of them are actually referring to human oocyte cryopreservation, and still fewer are clinical trials (rather than literature reviews or editorials). You've completely failed to acknowledge any of the studies that I have cited which contradict your point.
You claim I am citing studies on slow freezing rather than vitrification, when I specifically cite the Italian National Register study, Scaravelli 2010, which specifically includes vitrification. You criticize me for citing slow freezing studies, when you've been perfectly happy to do so yourself. You've ignored the fact that a bare handful of US clinics have achieved even very modest successes.
You claim I'm ignorant of the "success" of the newer methods, or that I'm lying, when the fact is that you've cited only one vitrification study of even quasi-respectable size involving infertility patients with their own eggs, Ubaldi 2010. I have discussed at length the issues there, starting with the fact that it is still quite small, and that it involves demographics and practices very different from the US population. (Extra credit pop quiz: what is the 95% CI on the warmed pregnancy rate) The study itself acknowledges that it is the largest of its kind, and its results have not been duplicated at other clinics. Obviously, therefore, we cannot form any universal judgments based on it alone, and must rely on the body of previous evidence.
And yet somehow *I'm* the one who's misrepresenting the body of scientific knowledge? Truly, it beggars belief that you think there's adequate evidence to abolish the current standard of medical care and replace it based on such thin evidence.
"There is no legal requirement that a doctor always utilize the methods that other doctors think are the best for a given situation. There is no requirement that a doctor conform to the dictates of the ASRM, and there is no restriction against the use of experimental treatments."
This is absolutely, fundamentally, untrue. Doctors in Alabama, as elsewhere, are still required to conform to accepted standards of medical practice. The physician-liability statute only accounts for mistake or unintentional error, and does not except the physician from the responsibility to follow the standards of care.
The standard of care is formed by the medical consensus. When a physican uses a treatment which is classified as "experimental", and which is not overseen by an institutional review board, he opens himself up to liability (civil, if not necessarily criminal) for any negative outcomes. If I hang out my shingle and start offering oocyte cryopreservation with no formal training, experience, or institutional review, you can then sue me into oblivion if I screw up and destroy your eggs or embryos. You probably can't have me arrested -- note the distinction between this kind of unintentional error and the deliberate choice to freeze embryos -- but I'm certainly not protected.
Furthermore, if a doctor has any intention whatsoever of collecting data that he might possibly someday choose to publish, or even discuss at an academic conference, federal regulations REQUIRE him to have IRB oversight.
Finally, there's the issue of medical malpractice insurance policies, which often restrict doctors from offering experimental or less-successful techniques. Consider the exhaustively documented issue of VBACs, where both doctors and hospitals are often forbidden by their insurance companies from offering them to their patients. This is a civil issue rather than a criminal one, but it's just as real when it comes to determining whether a given doctor will be able to continue practicing.
Bill
You are once again mistaken in regards to the legal effect that a personhood amendment would have on IVF.
The Arkansas language does not state that "any procedures which 'cause the death of a person' are prohibited." Instead, it states that "This Amendment shall have no effect on in vitro fertilization or other methods of assisted reproduction that do not cause the death of a person." It is not legally plausible to conclude that this statement constitutes a ban on embryo cryopreservation. This clause does not make any statement at all about what effect the amendment would have on in vitro fertilization methods that result in the death of an embryo. It just states that it will have no effect on those that do not. The effect on those treatments that do result in death is explained in the previous section of the amendment which states that "the word 'person' shall apply to all human beings, including the unborn." Therefore, the Arkansas amendment would require the same proof of intent for charges of manslaughter or homicide of embryos as is currently required in other cases involving the death of a patient.
Similarly, there is no prohibition against embryo cryopreservation in the Colorado amendment. The line which you are referring to (2,b) states that "only in vitro fertilization and assisted reproduction that kills a person shall be affected by this section." This line does not state how those particular processes will be affected; it just says that the effect of the amendment would apply. To discover the effect of the amendment, we have to read the line (2) which states that effect: "Effect. The intentional killing of any innocent person is prohibited." That's it. There is no other effect of the Colorado amendment. It does not ban embryo cryopreservation or any other IVF method that may result in natural or incidental embryonic deaths. It only prohibits intentional killing.
The same is true of Georgia's Ethical Treatment of Embryos Act. Even the introductory form of that bill which you cited states very clearly that "The in vitro human embryo shall not be intentionally destroyed." There is no prohibition against unintended death, nor is there a prohibition against embryo cryopreservation. In fact, this bill specifically recognizes the existence of "legal rights and duties regarding the disposition of in vitro human embryos that were not transferred due to either of the fertility patient's death, divorce, abandonment, or dispute over the custody of the in vitro human embryo," and cryopreservation is not excluded as an option in such cases.
Your claim that the authors of this bill explicitly intended for it to stop embryo cryopreservation is not founded on a statement by the Bioethics Defense Fund but rather on a single comment by pro-life blogger Jill Stanek. To the best of my knowledge, Mrs. Stanek is not directly affiliated with the Bioethics Defense Fund, nor was she involved in drafting the Georgia bill in any way. Her comment that Georgia's SB169 would end embryo cryopreservation was simply in error.
In each of these cases, the importance of intention is abundantly evident, but you seem to have an improper understanding of what is meant by the legal term of "intent." I have not been able to find your definition in any legal dictionary, and your example of a homicide caused by a drunk driver does not apply because the unintended homicide was the natural result of the criminal act of driving under the influence of alcohol which was initiated intentionally. Thus, the homicide though not specifically intended falls under the general intent of the crime of driving under the influence. The key difference between this situation and that of deaths resulting from embryo or oocyte cryopreservation is that these deaths do not come about as the natural result of some other criminal act. These deaths occur in the absence of any criminal intent of any sort at all, and in fact, occur in spite of strong intention to prevent these deaths.
In contrast to your definition, Black's Law Dictionary defines intent as a "state of mind in which a person seeks to accomplish a given result through a course of action," and Morissette v. United States presents an excellent case study of this concept. Morissette was convicted for taking government property that he had thought was abandoned. On appeal to the Supreme Court, his conviction was overturned on the grounds that although he did take government property with full knowledge of his actions, he did so without any intent to commit a crime. In the process of presenting their decision, the Court deliberated upon the necessity of proving criminal intent in all cases involving serious crimes. You can read the full text of their decision at: http://laws.findlaw.com/us/342/246.html.
The decision of the Court in Morissette has been instrumental in several other decisions including Vacco v. Quill in which the Court upheld New York’s prohibition against assisted suicide. In Vacco, the Court stated that the intent of the doctor is the key difference between the legally permissible action of administering pain killers that may hasten the death of a patient and the illegal action of administering a lethal dose of medication in order to kill a patient. (http://laws.findlaw.com/us/000/95-1858.html) Likewise, the Court stated in Gonzales v. Carhart that the federal ban against partial birth abortion "contains scienter requirements concerning all the actions involved in the prohibited abortion ... If either intent is absent, no crime has occurred. This follows from the general principle that where scienter is required no crime is committed absent the requisite state of mind." (http://laws.findlaw.com/us/000/05-380.html) All of these cases support the conclusion that under a personhood amendment, no doctor would be prosecuted for the death of an embryo in his care unless it could be demonstrated that he intentionally caused that death.
I find it very interesting that you are comparing the results of the Noyes study with only the fresh ICSI group from Belva's study. I have never claimed that oocyte cryopreservation produces better results than the use of fresh oocytes, nor was this the claim put forth in the Noyes paper. Her claim, rather, was that there is not a statistically significant difference between these two groups. The claim that you should be trying to disprove is my statement that oocyte cryopreservation is safer than ICSI with subsequent embryo cryopreservation. In other words, you should be looking for some way to prove that the 6.4% malformation rate reported by Belva is not significantly higher than the 1.3% reported by Noyes.
In regards to your comments on the studies that I have cited...
I have made reference to two separate articles by Cobo et al. The first was an article entitled "Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method." I made two references to this article: one to point out that it was not mentioned in the ASRM position statement and another to include it in a sampling of articles on cryopreservation. The other article by Cobo et al. which I have referenced was a 2010 article entitled, "Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial," and I listed it as an example of a study meeting your phase three requirements.
I have mentioned six different articles which were co-authored by Nicole Noyes. The first was actually presented by you as evidence to support your position before I pointed out that it provides far more support for my position. The second was presented as direct opposition to the ASRM position paper that you presented. The other four were included in a sampling of articles on cryopreservation.
I made no claim in regards to those four other than that they exist, however, your claim that these studies are all from the same dataset is not correct and neither is your claim that I presented them as such. If you would be so kind to read through that list again, you would notice that I specifically linked the two listed as "Noyes et al." since the results of one were reported again in the other. However, the latter of those two also reported results for an additional 50 cryopreservation cycles. Similarly, the article listed as "Griffo et al." also differs enough from the other Noyes articles to warrant its reading as well, and it was included in the list for that reason. The Hodes-Wertz article, on the other hand, directly refutes your comments. That article reported the results of 200 cryopreservation cycles which, of course, we know includes the cycles reported in previous Noyes papers because we are told so right in the abstract of the Hodes-Wertz article. This article, however, includes the results of several additional cycles that were not reported in the other studies, and it decisively refutes your claim "that Noyes has performed only 46 cycles at her clinic."
You are mistaken to state that I approvingly cited the Fadini study. I neither approved of nor dismissed the Fadini study. I simply listed it in a sampling of articles on cryopreservation.
You are correct in pointing out my erroneous explanation for the Oktay analysis. I'm not sure what happened there, but I suspect that it was a copy and paste error. This analysis was also listed solely as part of a sampling of articles on oocyte cryopreservation.
I've already explained why I include donor studies, and the correct application of the Ubaldi study to this discussion.
Cao was cited simply as a sampling of articles on oocyte cryopreservation.
The "IVF article" on my site is not an article at all but rather a copy of our previous discussion on this topic. It does not state that my claims are supported by six additional studies. It states that the ASRM position paper cites six studies which support the ASRM's claim that "Numerous studies have also reported improved oocyte survival."
Neither does that "article" rest my claims on studies of a dozen people. I simply pointed out that the ASRM claimed that "several studies have reported better post-thaw oocyte survival, fertilization, and pregnancy rates," and I mentioned that they supported that statement by citing two independent studies. If you think that those two studies should not have been cited in support of that statement, then perhaps you should write to the ASRM and tell them so.
By the way, the Scaravelli paper that was published in 2010 only analyzed data from 2005-2007, a time period which precedes many of the advances made in oocyte cryopreservation in general and vitrification in particular over the past 4 years.
And last but not least, let me point out that I have never accused you of lying. I stated that as a possibility, but I also was very clear in stating that I would prefer to believe that your errors were the result of ignorance. Thus, I presented two possible explanations - one which requirs proof of intent (lying) and one which does not (ignorance). In the absence of any evidence for malicious intent, I would have had no grounds for accusing you of lying, and so I refrained from making that accusation. Once again, it is evident that the issue of intent plays as significant a role in my ethical system as it does in the American legal system.
Atlee
"The Arkansas language does not state that "any procedures which 'cause the death of a person' are prohibited." Instead, it states that "This Amendment shall have no effect on in vitro fertilization or other methods of assisted reproduction that do not cause the death of a person." It is not legally plausible to conclude that this statement constitutes a ban on embryo cryopreservation. "
Actually, that's exactly what it says. It says that "no innocent person shall be denied the right to life", and then goes on to make a specific exception for things which do not 'cause the death of a person'. If it did not prohibit birth control and IVF procedures which DO cause the death of a person, there would be no need to except the ones which do NOT.
But don't take my word for it -- ask the Arkansas attorney general, who has concluded that both birth control and IVF procedures which can potentially 'cause the death of a person' would be affected.
You are similarly incorrect about Jill Stanek and the Bioethics Defense Fund. I'm not citing Jill -- rather, the BDF is citing her directly in their press release, which they would not do if they did not agree with her statement.
I'm not sure why you're arguing this, anyway. It's crystal clear that personhood advocates intend for their measures to prohibit the cryopreservation of embryos. We know this because they have said as much, in no uncertain terms, on multiple occasions. For example, the Yes On 26 campaign published literature which explicitly said that freezing would be prohibited under Initiative 26. Do you dispute that Yes On 26 said so?
As for the question of intent with cryopreservation, it is exactly the same logic as that applying to birth control pills and IUDs.
Using birth control is not a criminal act in and of itself, and isn't done with any malicious intent. However, you yourself have said that birth control methods must be considered abortifacient if they present even a small likelihood of causing embryonic death as a side effect, and that they would be therefore prohibited by personhood. This conclusion relies on that same manslaughter logic I described above, by the way, so I must conclude you accept recklessness
We must therefore conclude that any other procedures which have a similar potential for embryo destruction must likewise be prohibited by personhood. Since cryopreservation presents a far greater potential for embryo destruction than IUDs, it's that much clearer that they would become illegal.
You simply cannot have it both ways. You cannot say that IUDs and birth control pills should be outlawed but cryopreservation should be permitted. You have made the former claim, so the latter must also be true.
Indeed, I suspect that you understand this perfectly well, and that you're just attempting to be uselessly argumentative. Certainly, every other personhood advocate seems to understand it.
Bill
There is only one reason that some of the personhood amendments have included exceptions for IVF procedures that do not cause the death of an innocent person. Organizations such as Parents Against Personhood have been telling the voters that a personhood amendment would end all IVF treatments, and the leaders of various personhood organizations around the country have attempted to overcome that misconception by providing assurances to the contrary within the text of the amendment.
Your comment about the Attorney General of Arkansas is incorrect. He did not conclude "that both birth control and IVF procedures which can potentially 'cause the death of a person' would be affected." The actual text of Mr. McDaniel's opinion can be found at http://ag.arkansas.gov/opinions/docs/2011-163.html. In that opinion, Mr. McDaniel very clearly stated that his office was not authorized to "make legal determinations concerning the merits of the act or amendment." The sole purpose of his review of the amendment was "to ensure that the popular name and ballot title honestly, intelligibly, and fairly set forth the purpose of the proposed amendment or act." In regards to IVF procedures he stated that "it is unclear precisely what procedures would be allowed and under what circumstances. It is consequently impossible for me to summarize your measure in a ballot title." In accordance with the authority of his office, the Attorney General concluded only that the effect of the personhood amendment was too unclear for him to summarize it in a ballot title. He presented no conclusion at all about whether or not IVF would be affected.
I do not dispute that some members of the Yes on 26 coalition thought that the personhood amendment would ban embryo cryopreservation. I simply recognize that they are as mistaken in that conclusion as you are in concluding that a personhood amendment would ban all IVF procedures. As I pointed out previously, the option of embryo cryopreservation would remain available under a personhood amendment as an option for preserving the life of the embryo in certain unfortunate situations.
You are very much in error to equate the intent of IVF with that of hormonal contraceptives. It should be obvious that the intent of the one is the initiation and preservation of pre-implanted embryos while the intent of the other includes the destruction of pre-implanted embryos. Randy Alcorn's book, "Does the Birth Control Pill Cause Abortions?" documents this intent very thoroughly, and you can read it online at http://www.aboverubies.co.za/bcpill.pdf.
Atlee
The following people have publicly claimed or agreed with others' statements that 26 would not permit cryopreservation: Steve Crampton (the Liberty Counsel attorney who wrote the Mississippi language) and Keith Mason (president of Personhood USA), Dr. Beverly McMillan (OBGYN, president of Pro-Life Mississippi), and Dr. Eric Webb (OBGYN, Yes On 26 spokesman).
So yes, I do tend to assume that they know exactly what they intend, and in the case of Mr. Crampton and Mr. Mason, what is legally possible. These are not random campaign members -- these are key spokespeople and thought leaders of the entire personhood movement.
Nor does this pass the test of basic logic. If cryopreservation remains an available option, there is no need or legal justification for fertilization limits like those from SB 169.
The state of Mississippi does not have the power to dictate how patients conduct their private medical treatment. That's constitutionally protected exercise of liberty and privacy rights. Personhood would mean that those rights no longer apply in the case where those rights conflict with embryonic rights, but it wouldn't completely invalidate them. If there is no conflict with anyone else's fundamental rights, the right to liberty and privacy would still apply.
There is no plausible way to claim that fertilization by itself would possibly conflict with any other rights. If I have two zygotes, making a third does not harm either of the existing two, any more than deciding to have a third baby infringes on the rights of your two born children. The only possible conflict with embryonic right to life comes when it's time to decide what to do with embryos which aren't being transferred to the mother's uterus.
If embryos can be frozen at will, and if being frozen doesn't conflict with those embryos' right to life, there can be no possible justification for imposing on patient's rights to create embryos.
Also, you're wrong about birth control. Patients' and doctors' *intention* when using BCP, IUDs, and emergency contraception is to prevent ovulation and fertilization, since this is the primary biological mechanism. Implantation prevention is an unintentional side effect, and the medical profession can't even come to consensus over it.
Ovulation and fertilization prevention are, as you yourself have agreed, perfectly legal acts. They cannot be said to violate embryonic rights, because there is no embryo to have rights. Therefore, intentions behind cryopreservation and BCP usage are equally benign with respect to embryonic personhood.
If the occasional, not-well-documented accidental side effects of one must mean that it is prohibited, the common and exhaustively documented known side effects of the other must mean that it is likewise off-limits.
Bill
You must realize, of course, that I cannot provide specific responses to vague claims about the comments of other individuals. If you would care to provide original source quotations from the individuals that you listed, then I would be more than willing to discuss the accuracy of their opinions. In the meantime, I would like to remind you of one of your own statements which can be found in the FAQ section of the Parents Against Personhood website. You very correctly stated that "A law says what it says, not what personhood advocates say in their brochures, Facebook pages, or Youtube videos."
Let me remind you once again that Georgia's Ethical Treatment of Human Embryos Act was not a personhood amendment. The limitation on IVF presented in the first draft of that bill was stated to be "In the interest of reducing the risk of complications for both the mother and the transferred in vitro human embryos." This is fully consistent with the finding in both Roe v. Wade and Planned Parenthood v. Casey that "the State has legitimate interests from the outset of the pregnancy in protecting the health of the woman and the life of the fetus that may become a child." (http://laws.findlaw.com/us/505/833.html) This limitation had nothing to do with personhood; it was based solely on the right of the state to protect its legitimate interest in the well-being of an unborn child.
This, of course, directly refutes your claim that the state "does not have the power to dictate how patients conduct their private medical treatment." As the Court stated in Casey, "The very notion that the State has a substantial interest in potential life leads to the conclusion that not all regulations must be deemed unwarranted." The Court reviewed the Casey decision in their opposition to assisted suicide in Washington v. Glucksberg, and they concluded: "That many of the rights and liberties protected by the Due Process Clause sound in personal autonomy does not warrant the sweeping conclusion that any and all important, intimate, and personal decisions are so protected." (http://laws.findlaw.com/us/000/96-110.html)
In regards to birth control, a ban on the current crop of hormonal contraceptives would not be implemented because of the intent of the doctors and their patients but rather because of the intent of the developers and manufacturers. Many doctors and most patients are ignorant of the malicious intent with which these forms of birth control are produced, and they cannot be held criminally liable for acting in good faith on that ignorance. The developers, on the other hand, have been very open (albeit in the scientific literature instead of the popular press) about the intent behind their products. Mr. Alcorn has done an excellent job documenting this intent, and evidence such as that presented in his book would have to form the basis for any ban on hormonal birth control.
Bill
Well, Atlee. It has been over a week since my last comment. Am I to assume from your silence that you have resigned from the discussion?
Atlee
No, I have simply been very busy with professional and family commitments which take precedence over internet nit-pickery.
Yes, SB-169 absolutely was a personhood bill. It declares that a "living in vitro human embryo is a biological human being". That's ascribing personhood rights to some embryos (and by extension, to all embryos, since presumably you agree that the location of the embryo does not affect its legal status).
Without personhood, the state does not have the power to forbid the disposition of a frozen embryo. Legally speaking, either an embryo is property, in which case the parents can deal with it as they like, or it is classed with in vivo embryos of the same gestational age, and Roe protects the mother's right to terminate the pregnancy and destroy the embryo (pursuant to the limits of Casey). In order for the state to absolutely forbid embryo disposition, it must first declare its personhood.
Personhood.Net agrees, and says that the first objective of SB-169 was "to recognize all human embryos as having the legal right to life and legal protection under the laws of the State of Georgia":
http://www.personhoodamendmentga.com/index.php?option=com_content&view=article&id=234%3Aethical-treatment-of-embryos-act&catid=128%3Amodel-legislation&Itemid=610
I furthermore continue to find it absolutely unfathomable that you believe the state has a sufficiently valid interest in protecting the well-being of an unborn child to justify severe restrictions on IVF in the name of reducing multiple births, but that the state would not and should not act on that interest to prevent cryopreservation.
Let's recall that the intention of transferring multiple embryos is even more benign than cryopreservation -- you're actively attempting to give them the opportunity to become babies, not just preserving them for possible later use. The absolute risks of multiple birth are far, far lower than that of embryo cryopreservation.
So you're saying that the same bill which justifies strict restrictions on private medical treatment in the name of averting relatively low risks to fetal life, somehow does not prohibit a far greater and more immediate threat to fetal life? It defies logic.
What's more, it defies your own logic. You approvingly cite Randy Alcorn's book, in which he says "The chances of the embryo’s death is in no way lessened by the
prescribing physician’s or the mother’s or anyone else’s intentions... We must never argue for the legitimacy of a course of action based on our sincerity and good intentions. We must act instead in light of the actual evidence that indicates what consequences may come from the action itself. "
As long as cryopreservation remains an option, fertilization limits cannot be justified by the state's interest in protecting fetal health. You could fertilize a hundred eggs, but that poses no threat to fetal health until you try to transfer them into the uterus. If you are free to cryopreserve any extra embryos above the number you intend to transfer, the state has no interest, because no risk exists. Your right to privacy still permits unlimited fertilization, and will continue to do so unless you are required to transfer all embryos immediately.
Tell me, Bill, do you consider that the existing legal framework, and the findings of Casey, authorize the state to forbid a woman from going through intrauterine insemination? Why or why not?
Bill
You are mistaken. The claim that a human embryo is a biological human being is not a statement of personhood but rather a simple declaration of scientific fact. Of course the human embryo is biologically human. That's why it is called a human embryo in the first place. To claim that this recognition is an admission of personhood is to claim that Peter Singer believes in the personhood of infants because he recognizes them as being biologically human. Nothing could be further from the truth, however, for Mr. Singer has boldly declared that “Human babies are not born self-aware, or capable of grasping that they exist over time. They are not persons.” (http://www.equip.org/articles/peter-singer-s-bold-defense-of-infanticide)
In regards to your statement on forbidding embryo disposition, I suspect that you have chosen the wrong word to convey your intended idea. There is nothing in Georgia's Ethical Treatment of Human Embryos Act which prohibits embryo disposition. Perhaps you intended to use the word "disposal." In which case, I will refer you back to my previous comment in which I explained the legal right under Roe and Casey which permits Georgia to pass such a law.
Your quote from Personhood.net further emphasizes the differences between the Ethical Treatment of Human Embryos Act and a personhood bill. The distinguishing characteristic of every personhood bill is the establishment of Fourteenth Amendment protection for unborn children. The Georgia bill did not make any attempt to establish Fourteenth Amendment protection. It sought only to establish "protection under the laws of the State of Georgia" and made no reference to federal law or the Constitution.
Let me point out that by merely recognizing and explaining to you the legal justification for the Georgia bill, I am not in any way claiming that I agree with that bill or that I think that similar bills should be passed in other states. I am simply pointing out the error of your claims regarding this bill. For example, you are mistaken to claim that it is illogical to state that a bill can avert a relatively low risk without placing any restriction on a much higher risk. In reality, this happens all the time, and the Georgia bill provides an excellent example. The legal codes of every state in the union are full of statements like this one found in the Georgia bill:
"Nothing in this article shall be construed to affect conduct relating to abortion as provided in Chapter 12 of Title 16; provided, however, that nothing in this article shall be construed or implied to recognize any independent right to abortion under the laws of this state."
Obviously, this statement is an admission that the Georgia bill would restrict a particular activity with a lower risk of danger to the unborn child than another activity which is not restricted but which poses a much higher risk of danger to the child. This is not illogical. It is simply a statement of the scope of that particular bill.
You are also mistaken to conclude that my citation of Mr. Alcorn's book constitutes a full endorsement of every comment which he makes in that book. I did not cite Mr. Alcorn for his legal advice. I cited him for the evidence that he presents. Furthermore, it is obvious from the quote which you provided that he is not speaking in a legal context but rather in an ethical context. There are many things which are legal but still unethical and vice versa. I personally think that the quoted statement is somewhat oversimplified, and I'm sure that I could have convinced Mr. Alcorn to phrase it differently had he sought my advice prior to publishing the book. However, that statement does not in any way diminish the validity of the evidence presented in the book, nor does it make my reference to that evidence illogical.
I agree with your claim that the right to privacy (or, to be more exact, the Fourth Amendment right to be secure in our persons and effects) permits unlimited fertilization. The human gametes are not people they are possessions. Therefore, their use is subject to the laws governing the use of private possessions and not to those governing the interactions of people. This applies equally to all forms of insemination. However, once fertilization has occurred the newly created organism becomes a human person. At that point, our interactions with him are no longer governed by the laws of private property but rather by those laws which regulate our interactions with each other.
After the previous debate between Bill Fortenberry of the Personhood Initiative and Atlee Breland of Parents Against Personhood, Bill made several attempts to elicit further responses from Atlee. He finally posted a challenge to the Parents Against Personhood wall on facebook, and the following conversation ensued:
Bill
I'm still waiting for Atlee to uphold her promise to finish the conversation linked below:
http://www.personhoodinitiative.com/debate-2.html
Atlee
Said conversation is over 2000 words and counting. It's a BIG topic, involving a lot of research and writing to really do it comprehensive justice. I've been working on it in between higher-priority tasks related to the new site, to say nothing of my family, my career, and the holidays.
And actually, I have a question for you, Bill, which is directly relevant to this topic. Considering that the process of fertilization takes about 24 hours from the time that sperm penetrates the zona pellucida of the egg for the DNA to completely combine, exactly when during that process do you consider personhood to begin?
Do you believe that personhood begins at the moment the sperm enters the oocyte's cytoplasm, at any particular point during the DNA fusion, when the merge is complete and a polar body is extruded, or from when the zygote completes its first mitosis?
Rebecca Kiessling strongly implied during the MC Law Symposium that she considered personhood to begin as soon as the sperm entered the egg, although her grasp of the biology seemed to be rather shaky. You frequently reference the "moment of fertilization", as does most personhood legislation, so I want to be sure I understand exactly what you mean by that.
Bill
Fertilization is actually a single moment rather than a process. There is a process leading up to that moment and a process which commences from that moment, but fertilization itself is the singular event of sperm-egg membrane fusion. Here is an article detailing the process leading up to that single moment of fertilization: http://www.biolreprod.org/content/68/1/1.full, and here is another describing part of the process which begins at that moment: http://dev.biologists.org/content/124/1/233.full.pdf.
In regards to our previous conversation, I must say that I find your explanation troubling. It seems as if you are admitting that you initiated a nation wide campaign against personhood before taking time to ensure that your campaign was scientifically sound. Your entire campaign seems to be predicated on a single assumption which I have demonstrated to be false. Your admission that answering this challenge takes a lower priority than the new website seems to indicate that you are more concerned with the popularity of your campaign than with the truth. I fear that you are letting pride and ambition cloud your judgement, but I hope that you will allay my fears by returning to our discussion soon.
Atlee
Taking the second part of this first: this is neither true nor correct. Prior to the start of the initiative 26 campaign, I was familiar enough with the basic position of the ASRM on egg freezing to know that medicine consider oocyte cryopreservation to be an experimental treatment with lower success rates.
That's scientifically sound, but not sufficient in the level of detail required for an explanation of this caliber, and a refutation of the numerous incorrect points you have attempted to make about IVF and oocyte cryopreservation. I have a master's degree and the associated experience in writing papers, and they inevitably involve a good deal of research even when one has substantial background knowledge. It's not because that background knowledge is incorrect -- it's because authoritatively building a comprehensive argument for someone without that background knowledge takes time and research.
In any case, anyone who cites studies about elective single embryo transfer to support personhood, or who attempts to dictate medical policy based on case studies which involve a dozen people, has very little standing to attempt to criticize someone else's scientific knowledge.
Furthermore, my priorities are not a question of popularity. It's a question of responsibilities. I have responsibilities to a lot of people, including some specific commitments and deadlines which have required work on the new website. Those take a higher priority, as they should, over an Internet debate on a non-time-sensitive subject.
Whining that you're being ignored is unseemly, particularly on an issue which I have previously stated is of some importance. I'm not just writing about oocyte preservation because I've promised you that I would, but also because I need to be able to address this subject in the context of upcoming campaigns.
Bill
That's very interesting and especially so since the ASRM website contains this statement on oocyte cryopreservation:
"ASRM holds the position that oocyte cryopreservation is 'experimental' due to the limited number of established pregnancies and deliveries from cryopreserved oocytes (2008). However, as of 2010, the number of comparative studies of oocyte cryopreservation published in peer-reviewed journals that demonstrate “there is adequate scientific evidence of safety and efficacy” has exploded. A number of ART programs are offering oocyte cryopreservation as an alternative to embryo cryopreservation to their patients and strongly feel the 'experimental' designation should be removed from this procedure."
And this statement about single embryo transfer:
"ASRM’s Practice Committee recommends: increased use of Single Embryo Transfer (SET) in IVF cycles."
I find your comment regarding studies of only a dozen cases to be interesting as well. If I remember correctly, a great deal of my proof consisted of quotes from the studies that you presented rather than my own. I also seem to recall that one of those studies catalogued over 900 successful cases. That's a far cry from the dozen that you are referring to.
As for your priorities, you are certainly free to choose to focus on whatever you like. I just think that your readers should be skeptical of your position until you find the time to prove your foundational tenet.
Atlee
That's not a position statement. That's a description of the topic of debate at an interactive panel at the ASRM meeting last October (http://www.asrm.org/events/detail.aspx?id=7676), and does not represent the official ASRM position in any way, shape, or form. As is noted in the first sentence, ASRM still holds that oocyte cryopreservation is highly observational.
Seriously, do you not even know the difference between an event description and an official position statement, or are you just throwing anything out there which you think is possibly relevant?
And for the last time, do you still not understand how ESET is completely irrelevant to the discussion at hand? The problem with personhood and IVF success rates isn't that it would prevent you from TRANSFERRING one -- in fact, it would require you to transfer more than one, if you have more than one surviving embryo. The problem is that attempting to FERTILIZE no more than two usually leaves you with zero embryos. ESET simply doesn't apply, because the problem happens at the embryo creation level rather than the transfer level. You cannot do ESET when you have zero embryos, so the comparable success rates (which, I will note, are for a specific group of women, not for the IVF population as a whole) simply don't even apply.
Honestly, I've explained this difference to you already. The fact that you're still talking about ESET (whose effectiveness I have never once disputed) shows either that you're fond of straw men, or that you're lacking the most basic grasp of the process.
I'm specifically referring to the following quote about vitrification from your article: '"Recently, however, several studies have reported better post-thaw oocyte survival, fertilization, and pregnancy rates." The second statement is supported by the citation of two independent studies.'
The two studies referred to as footnotes 27 and 28 of the ASRM opinion state, which you claim demonstrate better rates, respectively involve 12 and 15 patients. The full text of both studies is freely available online at http://humrep.oxfordjournals.org/content/17/12/3149.long and http://humrep.oxfordjournals.org/content/18/6/1250.long.
27 patients are hardly authoritative support for your assertion that oocyte preservation approaches the success rates of fresh IVF. (Indeed, if you actually read those papers, you will note that one has a 66% miscarriage rate, which is far higher than that of fresh IVF.)
As for the other six (actually, seven) studies under discussion, none of them show anything close to comparable results to fresh IVF, because that's not what's under discussion in that specific section. The narrow context of that paragraph is the comparative effectiveness of different techniques, which does not imply that they stack up favorably to current IVF results.
In fact, Fabbri 2000 (a study of slow-freezing method, not the newer vitrification method) supports my contention that fertilization rates are notably lower -- 57% in that study, versus 70% or higher for ICSI with fresh oocytes, with a thaw loss of 46%. The study involved 96 patients. There was great variability in the success rate of the different techniques studied, which underscores that this is still a truly experimental procedure. Pregnancy rates were not reported, so we can draw no conclusions.
Eroglu 2002 shows a 34-47% loss of eggs due to freezing; fertilization was not attempted, so it tells us nothing about fertilization or pregnancy rates. Sahananthan 1988 I haven't been able to get, but given the age of the paper, it's not to be expected that their results are anything but abysmal; nor did this study actually attempt to fertilize eggs. Trad 1998 likewise did not attempt to fertilize. Stachecki 2000 involves mouse oocytes.
Porcu 1997, a case report of a single patient, shows a 66% loss due to freezing, a 50% fertilization rate, and a 50% cleavage rate; from 12 eggs, they got 1 embryo, a rate far lower than would be expected for fresh IVF. Polak de Fried 1998 is likewise a single-patient case report, with a 70% loss due to freezing, a 66% fertilization rate.
So, to summarize those studies, we have: two single-patient case reports, one mouse study, three studies where fertilization wasn't even attempted, and one 96-patient study which shows lower success rates than fresh IVF, a high rate of oocyte loss in the freezing process, and the lack of well-established protocols for lab techniques. To the best of our knowledge, they involve two (2) actual pregnancies.
Exactly how do these seven studies demonstrate the success of oocyte cryopreservation compared to fresh IVF? In my opinion, they all reinforce the experimental nature and relatively poor success rates of oocyte cryopreservation.
Finally, the reference to over 900 successful cases is a population study which involved every child born through oocyte cryopreservation worldwide in the last two decades. Given that current estimates place the number of IVF children born at approximately 4 million, it reinforces that we are talking about an experimental procedure which shows future promise but is a long way from being ready for prime time.
Bill
Let me begin by thanking you for continuing the discussion. As I stated in our previous conversation, it is a pleasure to discuss this topic with someone who has actually done some research in this field.
Now, you are correct in pointing out that the quote I provided was from an ASRM event description. I never claimed otherwise. I did not provide the quote to say that ASRM has changed their position, but rather to demonstrate that their position on this topic has been challenged by those within their own ranks. A study by Noyes et al. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842870/) demonstrates that the 2008 paper which you presented in our previous discussion and which forms the foundation for ASRM's position is both outdated and amazingly narrow in its consideration of oocyte cryopreservation. The ASRM report made no mention of the work reported by Kuwayama et al. in 2005, Borini et al. in 2004, Setti et al. in 2006 or Cobo et al. in 2007 all of which demonstrated significant achievements in oocyte cryopreservation, and as the ASRM event statement admits, the number of studies disagreeing with their conclusion has increased dramatically in the three years since their report. As David Albertini wrote in the most recent issue of the Journal of Assisted Reproduction and Genetics, "The time is right to proceed full speed with adoption of oocyte cryopreservation." (http://www.springerlink.com/content/054n584x156rlw55/fulltext.html)
In regards to your comments on single embryo transfer, let me point out that the combination of this policy with oocyte cryopreservation would allow doctors to thaw and fertilize oocytes one at a time. This may lengthen the process slightly, but with multiple studies demonstrating a greater than 50% pregnancy rate from oocyte cryopreservation methods, the likelihood of having to repeat the process more than twice is very low. Furthermore, a 2009 study demonstrated that embryo cryopreservation can be successfully completed subsequent to oocyte cryopreservation (http://www.ncbi.nlm.nih.gov/pubmed/18692830). This provides doctors with an acceptable option for the rare cases in which the woman is unavailable at the time that the embryo is to be transferred. While neither single embryo transfer nor oocyte cryopreservation represent in themselves a full solution to the conflict between personhood and IVF, the two combined together solve that conflict very well.
By the way, the study of the 936 children born from oocyte cryopreservation bore the title of: "Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies." After studying every reported birth from this method of IVF, the authors were able to demonstrate that oocyte cryopreservation is safer for the child than the current methods of embryo cryopreservation. The fact that this study ranged over a period of two decades is significant in that it thus includes children born from oocyte cryopreservation prior to the current levels of success achieved by that method. In spite of this, the authors still only found 12 cases of birth defects.
Atlee
Do you think that the ASRM isn't aware of those studies? Or did you consider that there are excellent reasons why scientists don't consider those studies to be adequate proof of the reliability and efficacy of this method?
Kuwayama involved 67 patients, who were much younger than the average IVF patient, and transfer practices contrary to ASRM recommendations. Cobo had a population of 30 patients, and more importantly, used donor eggs rather than the eggs of patients with known infertility impairment. Borrini has 68 patients, with a pregnancy rate of just 25%.
Levi-Setti is a larger study, but it shows a pregnancy rate of just 12%, with a really high miscarriage rate of 33%. In fact, I'm very confused about why you cite this as "significant achievment", when the authors themselves note that "Our implantation rate (5.7%) after thawing is impressively lower than our implantation rate after the transfer of fresh embryos (23.2%)."
The Noyes paper is a review and an editorial, not a clinical study, and the studies she cites for efficacy are all likewise very small -- her own clinical studies have involved a total of 46 patients. No doubt you're aware that she runs an infertility clinic which offers an elective egg freezing program, so her interests are not purely academic.
And now we arrive at why I asked you precisely when you consider that fertilization begins. According to your own definition of personhood, every last one of these studies, and in fact all oocyte preservation that's currently being practiced, constitutes embryonic research, most of which has shown that it's harmful to the embryos.
Given that you believe that each egg becomes a legal person at the instant when the sperm is deposited into the cytoplasm via the ICSI needle, I'm surprised, to say the least, that you support the use of oocyte preservation. The overall body of evidence indicates that oocyte preservation offers each individual embryo a reduced chance of survival compared to what it would have if it were fertilized and transferred fresh, because it is less likely to cleave and continue to develop.
While this is unquestionably improving, the fact is that the larger studies performed to date show negative results compared to standard IVF. The only studies which show anything close to equivalent performance involve a scant handful of patients, far too few to reach true statistical significance, or be viewed as solid evidence on which to base clinical practice.
As the Albertini editorial comment you link notes, "With either slow freeze or vitrification, the normalization of protocol has yet to achieve something even remotely reproducible. Visits to IVF clinics around the world over the past 5 years reinforces suspicions regarding the absence of uniformity and variability in protocols." That means that there's still no standard agreement on the various details of the freezing process, and individual clinics are fumbling their way along with no consensus on which methods will ultimately produce a 40% pregnancy rate, and which ones will produce a 5% rate.
Consider if we were talking about a new form of cancer treatment compared to standard chemotherapy, with identical statistics as cryopreserved vs fresh embryos. Would you think it ethical for a hospital to tell a parent that the new treatment was a perfectly reasonable choice for their newborn, or offer it when standard chemotherapy is an available option? Of course you wouldn't. Nor would any review board permit such an experimental practice, with overall worse results and only limited non-significant positive results compared to an existing treatment, to be conducted on newborn infants (or a person of any other age).
No, oocytes don't have moral agency or rights under personhood, and the process of freezing and thawing the oocytes themselves doesn't raise an ethical question. However, isn't it wrong to deliberately take an action which the evidence indicates will result in an increased likelihood of loss of the embryo which will be created from those eggs?
As with embryo freezing, there's no offsetting benefit to the embryo which justifies the risks of being created from a previously-frozen oocyte. It's purely done for the benefit of the mother, and I think we've very firmly established that you don't consider even a grave threat to the mother's life to justify even incidental death to embryos.
Given your general views, and the experimental nature of the research, I think it's philosophically inconsistent of you to support oocyte cryopreservation at this juncture.
Bill
Before we proceed any further in our discussion of the scientific literature, I think that it would be very helpful for you to provide a brief outline of the criteria that a report must meet before you will consider it as evidence in favor of oocyte cryopreservation.
In response to your ethical argument, let me point out that we are not discussing whether in vitro fertilization itself or any given method thereof is ethical but rather if any of these would be deemed illegal under a personhood amendment. In a strict legal sense, neither method of in vitro fertilization would be illegal under that amendment. The only two things currently legal that would then be made illegal would be the intentional harming of an unborn child or the causing of such harm through criminal negligence.
Oocyte cryopreservation is recommended primarily as a support element for single embryo transfer. Relying on this method would allow doctors to extract multiple oocytes to be used for later cycles without having to freeze living embryos. This combination of oocyte cryopreservation and single embryo fertilization would eliminate the step in the standard IVF process which could be condemned under the personhood amendment - the destruction of embryos which are not used by the donor.
The other embryonic deaths that you have described are all naturally occurring and occur in spite of the doctor's efforts to the contrary. A doctor who has taken every reasonable precaution against the death of his patient is generally not prosecuted if that patient happens to die while under his care. A personhood amendment would simply place embryonic deaths in the same legal category as any other death that occurs under a doctor's care. Therefore, naturally occurring embryonic deaths would not be litigable under a personhood amendment.
By the way, I would be more than willing to discuss the ethics of our positions if you would care to provide a statement of your own ethical beliefs in regards to the beginning of life and the destruction of human embryos.
Atlee
You keep failing to understand that single embryo transfer is completely irrelevant. Under personhood, it's legal to transfer two or more embryos if desired and appropriate for the patient's particular situation. There's no requirement to do anything except transfer all of the embryos which are created.
As I've told you, what, five times now, studies of single-embryo transfer have nothing to do with the issue at hand, which is how to operate under fertilization limits which, if applied to current IVF practice, will leave most women with no embryos at all. The topic of debate here is fertilization, which happens several days prior to the point of single-embryo transfer. I suggest you stick to the topic at hand.
Bill
Perhaps I have not been as clear as I thought. Please allow me to repeat my position in an effort to generate more clarity. The IVF process which I am proposing would proceed as follows:
1) Harvesting of oocytes
2) Fertilization of a single oocyte
3) Freezing of extra oocytes
4) Observation of single embryo while waiting for it to develop
5) Transfer of single embryo into womb
6) Observation of mother to determine pregnancy status
7) Thawing and fertilization of a single oocyte to repeat steps 4 - 6 if they are not successful
(Those willing to give birth to multiples would be permitted to fertilize as many oocytes per cycle as they are willing carry to full term.)
As far as I can tell, this process would enable the practice of in vitro fertilization to continue under a personhood amendment.
Atlee
Okay, study criteria. For a drug or technique to pass out of the realm of the experimental, it has to meet the criteria of scale and reproducibility.
Results have to be reproducible by other researchers -- that is, doctors in other clinics achieve similar results by following identical techniques. As the Albertini commentary you cite approvingly above notes, "the normalization of protocol has yet to achieve something even remotely reproducible". In practical terms, what that means is that everyone's doing their own thing, and nobody's sorted out which methods truly are superior. There isn't even real consensus whether slow freezing truly is better than vitrification, and Albertini also states that there is a "spectrum of technicalities awaiting resolution that are not commonly evidenced (or popular) in public presentations".
Secondly, trials must be large enough to demonstrate statistical significance, which is usually defined as a p-value of <0.05 in comparison to current practice. If you're working with a group of 20 patients, any one patient's outcome will change your numbers by 5%. If you see a 10% difference in 20 patients, you might repeat the study in a different group of 20 patients and find that due to random chance, two patients have had different results and flipped your numbers 10% the other way.
You simply can't make any solid conclusions one way or another about such a small group of results, where random chance plays such a heavy role. If your results are relatively good, you might decide to repeat your experiment in a larger group. However, your initial trials aren't proof until you've done those larger studies and established that your initial results weren't just a statistical blip.
Think about how many times you've heard a news story about a promising new drug for some condition or another, that subsequently vanishes without a trace. That's what happens here -- the small initial trial shows a good result because of random chance, but larger followup studies don't demonstrate the same success, and the new drug is ultimately not proved superior to existing treatments. Or think about flipping a coin, where you might have a run of "luck" with a short period of very positive results. Keep playing long enough, though, and your results will inevitably move back down to 50-50. (The technical term is regression to the mean.)
It takes hundreds of subjects in each arm of a study to get good statistical significance. In testing drugs, Phase 2 studies usually involve 100-300 patients, and Phase 3 studies involve more than 300-3000 patients. For a drug to be approved for public usage by the FDA, it has to have at least two successful Phase 3 studies.
So when you cite a study like, say, Grifo/Noyes 2010, it really doesn't mean much of anything except that there's reason to perform larger studies. If that one had had three patients flip the other way, which can happen for all sorts of random reasons which have nothing to do with the intervention being studied, it would've showed worse pregnancy rates than controls.
(For the record, please note that while I am not a medical researcher, I do have some formal training and professional experience in probability theory, statistics, and data mining.)
Oh, and you also want to be careful about relying too heavily on meta-analyses, which are attempts to approximate a single larger study by combining the results of several smaller studies.
The reason for this also should be fairly intuitive: if I have three studies that show a 60% result, and three that show a 40% result, you can't add them up to get a 50% result that indicates that my proposed intervention is just as good as the existing strategy. It shows that I need to do more studies so that I can sort out whether it really is significantly better or significantly worse than the existing one, and why the outcomes of the trials were so different.
Meta-analyses have their place, but they're no substitute for looking at the results of the individual studies they examine.
Back to ESET: the question at hand is the efficacy of steps 1-3. Steps 4-6 are irrelevant to the question of continuing under personhood, because they do not differ from current clinical practice.
I will also note at this point that your scheme places a massive physical and financial burden on patients; my best estimate is that each attempt at oocyte thawing would cost $5-7K above and beyond the $10-15K from the initial fresh attempt. Of course cost is not the only consideration, but we must acknowledge that it is significant and will push IVF well beyond many patients' means -- or push them into clinics in other states.
Other points here: you want to make sure that you're not looking at studies which involve donor eggs, for obvious reasons. A lot of the freezing studies are donor-egg studies, and the results obviously don't apply to a standard infertile population.
When you're looking at Italian studies, you also have to keep in mind that they're mostly transferring three embryos at a time on both fresh and frozen cycles. That increases their overall pregnancy rates, but isn't compliant with ASRM recommendations for most patients because of the risk of multiples.
Seriously, there are reasons why ASRM isn't ready to declare this ready for prime time -- and NOBODY is advocating that it should replace current practices. If you suggested that to an embryologist, they'd laugh at the preposterousness of it. It's not because they're not aware of the research, either. It's because they understand the issues involved much better than you or I do, and they know that there's really very little solid data just yet.
As of 2009, over half of the clinics in the US which reported their data on egg freezing either haven't thawed a single egg or haven't achieved a live birth, and just 8 clinics reported more than 10 babies. http://www.nature.com/news/2011/110823/full/476382a.html That, more than anything else, argues that this is still a highly experimental procedure in the US.
Finally, back to the ethics of it: it's criminal negligence to subject a person to a treatment which you have good reason to believe is substantially more likely than standard practice to cause their death, especially when there is no benefit to that individual from such treatment.
For example, suppose we develop a new cancer treatment for children. There's some very thin evidence suggesting it's just as effective as existing treatment, but there's more evidence suggesting that it's less effective, and that it is more likely to cause the child to die from an unrelated cause than current practices. There's no benefit to the child from receiving the new treatment.
It would absolutely be considered medical neglect, as well as a violation of medical ethics, for the child to be subjected to the new treatment instead of the old. The doctor would not be protected, either, because he could have averted the death by providing the superior treatment. (Consider the case of doctors who get sued or charged with wrongful death for failing to perform C-sections in the face of known risk factors, which happens all the time.)
These same arguments all apply to freezing embryos, and other personhood advocates have found them to be unpersuasive in that context. These are "natural" deaths rather than deliberate ones, but the risk to the embryo is judged too high, and could be averted with fresh transfer instead.
Finally, the ethical argument does make a difference here. Doctors aren't allowed to provide unethical treatment, even if it's technically not illegal. They still wouldn't be able to treat patients under such a scenario.
Bill
Thank you for listing the above criteria. I'm sure that it will save us both a great deal of frustration. I have found two, independent studies which meet your criteria with the exception that the first is an Italian study and the second was a study of donor oocytes. Both were reproducible clinical studies demonstrating that there is no statistically significant difference between the results obtained by using cryopreserved oocytes versus fresh oocytes.
In regards to your comment on Italian studies, let me point out that you are mistaken in your understanding of the legal restrictions on IVF in that nation. The Italians were never required to transfer three embryos at a time. They were simply required to transfer every embryo that survived to that point of the procedure. (That requirement was partially lifted in 2009 by the way.) Therefore, they seldom attempted to fertilize more than three oocytes at a time and they had the potential for transferring up to three embryos at a time.
The transfer of up to three embryos at a time does increase the risk of multiples, but it does not have any real effect on the rate of pregnancy per oocyte. It is reasonable to conclude that the Italian study would have had similar results if each embryo had been implanted individually rather than in groups of up to three. If all other variables remained the same, then the embryos which implanted and survived to the 12th week of gestation would most likely have done so regardless of whether they were transferred individually or in small groups.
Furthermore, the restriction against selective transfer does not in any way affect the results presented in table III of the Italian study.
I can see where you are coming from in regards to studies of donor oocytes, but if nothing else, we should at least be able to agree that the second of these studies demonstrates the efficacy of oocyte cryopreservation for healthy oocytes. Having established that, we can then look back to the Italian study and see that it arrived at the same conclusion without relying on donor oocytes.
Here are the links for the two studies:
1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794665/?tool=pubmed
2) http://humrep.oxfordjournals.org/content/25/9/2239.long
Atlee
Check your data. The oocyte cryopreservation arm of Rienzi 2009 involved 40 patients. What's more, as the authors themselves note, this is the first clinical trial demonstrating results in a population of infertile patients, rather than donor egg patients. "Further studies, performed on a larger scale, are however needed to confirm clinical outcomes of vitrified oocytes and the safety of the technique."
I've never claimed that the Italian law required transfer of three embryos. What I've claimed is that common practice in the Italian studies is to transfer three embryos whenever possible, which you can easily verify for yourself by observing that the average number of embryos per transfer is well above 2, even in younger populations.
And yes, I'm aware that the Italian law was declared unconstitutional in 2009.
You may find this study of interest: http://humrep.oxfordjournals.org/content/early/2010/12/08/humrep.deq342.full.pdf . Following the lifting of the restrictions, the authors note that a statistically significantly higher percentage of cycles made it to the point of embryo transfer (meaning that the law left many patients with no embryos at all, exactly as I have contended all along). The overall pregnancy rate improvement following repeal reaches statistical significance.
And no, we can't extrapolate anything about oocyte cryopreservation in an infertile population from donor egg studies. The very criteria that make women eligible to donate eggs (that is, proven egg quality by way of a pregnancy) are precisely what infertile couples lack. Egg quality is a key issue in the success of oocyte cryopreservation.
Rienzi 2009 notes that "The origin of the oocytes involved is, in fact, clearly a determining factor in the results, with an obvious advantage of young donors compared with older infertile women". In support, she cites Kim 2009 (http://www.ncbi.nlm.nih.gov/pubmed/19217099), which shows pretty sub-optimal results for the same technique in leftover oocytes from infertile patients.
Bill
You are correct to point out the statement by Rienzi et al. that "Further studies, performed on a larger scale, are however needed to confirm clinical outcomes of vitrified oocytes and the safety of the technique." In fact, that statement provided sufficient motivation for the same group to publish the results of a larger study just six months later which confirmed their initial findings. The group stated in that study that "high cumulative ongoing pregnancy rates were achieved in a standard infertility program with transfers of embryos derived from fresh and subsequently vitrified oocytes." They also concluded that "The overall efficiency justifies the application of this strategy in routine infertility work."
You can see the results of this larger study at this link:
http://humrep.oxfordjournals.org/content/25/5/1199.full
Atlee
Yes, this meets the criteria I suggested for a Phase 2 study, and I will certainly agree that this individual study showed good results. However, it also shows something very important: the diagnoses of the patients included in this study are remarkably different in some key ways from the larger population of infertility patients.
Compare the patient diagnoses to the CDC's report of diagnoses among patients seeking IVF in 2008 (http://cdc.gov/art/ART2008/sect2_fig16-26.htm#f20), and the difference should be very obvious. Specifically, over 60% of patients in this study had either male factor or tubal infertility, whereas 26% of general infertility patients have either diagnosis. Only 4 individual cases had ovulatory issues, whereas almost 18% of the general infertility population has these diagnoses in isolation. The combined infertility rate (patients with multiple diagnoses) was also very low compared to the US rate, which means there's a further disparity for ovulatory issues.
This is very, very important, because the effectiveness of oocyte cryopreservation is directly related to egg quality and ovulatory issues. Tubal infertility and male factor infertility don't impact egg quality, and patients with these diagnoses are much likelier to get pregnant by IVF than the general population in fresh IVF. Furthermore, it is to be expected that they will have better results from oocyte cryopreservation, as their eggs are expected to be healthier than the general lot of IVF patients, and thus are somewhat more comparable to donor eggs.
This isn't necessarily a fault of the individual clinic, which considered all of their patient population for inclusion. Rather, it is a problem of self-selection in the Italian IVF population. Patients with difficult diagnoses independently choose, or are counseled, to pursue IVF tourism in countries with looser regulations -- and they do so, in huge numbers. (http://www.ivf.net/ivf/restrictive-fertility-law-forces-italian-patients-abroad-o2409.html, http://www.eshre.eu/01/MyDocuments/Shenfield_et_al_2010_Cross_border_reproductive_care_in_six_European_countries.pdf) Italy does approximately 40,000 cycles a year, which means that 10% of all Italian infertility patients seek treatment in just the 27 clinics observed here. Some clinics in neighboring countries now do more than 50%
of their cycles on Italian patients -- and those studies don't include IVF tourism in Asia or India, either.
Bottom line, when you stack the deck with patients who are predisposed to get good results from your intervention, you should expect to get good results from your intervention. It doesn't show that the results of your intervention are universally applicable.
That's why you do larger studies in several hundred patients, and in multiple locations, so that you can weed out external factors like deliberate or unintentional patient selection before you conclude that your new treatment really works in the larger patient pool.
Bill
I think that we've achieved a significant level of agreement here. Let's take a moment to review the discussion to this point and note several points with which we both concur.
1) We both agree with the ASRM that "as of 2010, the number of comparative studies of oocyte cryopreservation published in peer-reviewed journals that demonstrate 'there is adequate scientific evidence of safety and efficacy' has exploded."
2) We seem to agree that oocyte cryopreservation is a valid procedure for donor oocytes.
3) We agree that the efficacy of oocyte preservation has been demonstrated for all categories of infertility except that of ovulatory dysfunction.
We have therefore come to an agreement on the efficacy of my proposed treatment method for cases of fertility preservation as well as for 93.3% of all infertility cases. Your opposition to the personhood amendment therefore rests primarily on your claim that the validity of oocyte cryopreservation has not been demonstrated for 6.7% of the couples seeking fertility treatment. Let me point out that you make this claim in direct opposition to the statement made by Ubaldi et al. that "According to the Cox regression analysis, infertility factors ... did not influence the ongoing pregnancy rates." Nevertheless, let's assume that your claim is valid and that 6.7% of those seeking fertility treatment do not yet know if the methodology that I outlined will enable them to give birth to a child. What implications would this claim have in light of the personhood debate?
According to one of your own articles, the negative effect that a personhood amendment might have on IVF is that it could end the practice of freezing embryos and limit the number of eggs fertilized to the number of embryos that the patient is willing to transfer in a single cycle. You claimed that "these two restrictions would end physicians’ ability to perform IVF." (http://parentsagainstms26.com/start-here/ivf-overview/) This discussion, however, has revealed a different picture.
First, you have yourself admitted that the passage of a similar law in Italy did not end the practice of in vitro fertilization in that nation. In fact, you claim that the 27 clinics in that nation perform about 40,000 IVF cycles per year. Therefore your claim that a personhood amendment would end all IVF treatment is historically inaccurate.
Second, you have agreed that oocyte cryopreservation is an effective alternative to embryo cryopreservation for women who have healthy oocytes. This would allow the majority of women seeking IVF treatment to do so without freezing any embryos. Therefore your claim that a restriction on embryo freezing would end all IVF treatment is scientifically inaccurate as well.
A personhood amendment would definitely have an effect on IVF, but it most certainly would not have the extreme effect of ending the process altogether as you claim. At most, it would delay the availability of IVF treatment for a small percentage of women until further studies have been able to demonstrate the efficacy of oocyte cryopreservation for those suffering from ovulatory dysfunction.
Having established the flaws of your scientific claims, let me now address the ethical component of this discussion. This is where I believe that our real disagreement lies, and it is your ethical view of human embryos that I believe forms the real foundation of your opposition to the personhood amendment.
In an article for the Religious Dispatches magazine, you stated that you do not "believe that embryos are fully equivalent to people." (http://www.religiondispatches.org/archive/sexandgender/5249/of_personhood_and_the_pill%3A_what%E2%80%99s_at_stake/) I have yet to read any proof that you may have for this belief, but it is obvious that your views of personhood and IVF flow directly from this ethical foundation. Personhood advocates, on the other hand, have an entirely different foundation upon which we build our case. We believe that the moral equivalence between an embryo and a two-year old child is firmly established by the Bible, the law, judicial precedent and scientific inquiry. I am fairly certain that you have read my Personhood Booklet and that you are aware of the evidence supporting that belief. You have yet to address any of the claims made in that booklet, and I challenge you to do so as well as to present evidence to support your belief to the contrary.
This has been a very interesting discussion, and I thank you for participating. I have thoroughly enjoyed presenting your readers with the scientific evidence that debunks your claim regarding personhood and IVF. The crux of the argument, however, is not the effect that a personhood amendment would have on IVF, but whether or not the human embryo has an unalienable right to life. If the embryo does have a right to life, then a personhood amendment designed to protect that right is fully justified regardless of the cost. ("...That to secure these rights, Governments are instituted among Men...") If the embryo does not have a right to life, then the entire foundation of the personhood movement will crumble.
And so I ask you to meet the above challenge. To support your position on personhood and IVF, can you provide evidence to prove your own ethical position and disprove mine?
Atlee
We concur on none of the above. Let's start with #1: we don't both agree with ASRM, because that's not what ASRM says. That's a description of an interactive panel debate which was held at an ASRM meeting. It was written by the doctors hosting the panel, not by the ASRM, and does not in any way, shape, or form represent the ASRM's official position on the matter.
This has already been explained to you. For you to continue to represent it as an ASRM position, simply because they allowed such a debate to be held, is a deliberate falsehood. It even contradicts your own acknowledgment from your December 16 post that you "did not provide the quote to say that ASRM has changed their position, but rather to demonstrate that their position on this topic has been challenged by those within their own ranks".
ASRM continues to hold the position that oocyte cryopreservation is experimental, and that it needs to be subjected to much larger studies than have yet been performed before being offered without the guidance of an IRB, let alone universally substituted for existing IVF practices.
There's a Commandment against telling lies. I previously assumed it was ignorance, but if you're going to keep repeating it, I must conclude it's deliberate dishonesty.
2) and 3) Did you completely fail to listen to anything I said about how these studies are still too small and too few in number to conclusively demonstrate anything on their own? You need multiple studies of this size, performed at different clinics, to reach something that could be considered scientific consensus. You need them to reach true statistical significance, which I don't think a single one of the studies you've linked does.
It's literally laughable that you talk about the validity of Cox regression testing over the 29 pregnancies in the Ubaldi preservation arm -- just look at how wide those confidence levels are. Anyone with any statistics background at all will correctly note that this is clinically meaningless, and that the p-values indicate that it's perfectly possible to arrive at such a distribution by random chance alone, in such a tiny population.
Once again, you're showing why this truly IS an experimental technology. The very studies on which you're placing all your reliance are too underpowered to provide adequate statistical significance to regard any of their conclusions as scientifically reliable or equivalent to existing procedures. That's the definition of Type II statistical error, and it indicates nothing other than that more studies need to be done.
That's why people who actually understand statistics and research continue to regard this as an experimental area of interest, not as a replacement for existing procedures.
Additionally, check your numbers for ovulatory dysfunction, because you have those totally wrong. As I posted, 18% of the US infertility patient population has ovulatory problems in isolation, and a far larger percentage have ovulatory issues in combination with some other diagnosis such as male factor or endometriosis.
As I have already explained once to you, this is a flaw of the Ubaldi study, as well as all the other Italian studies, and it's a key reason why these can't be taken as predictive of wider clinical experience in the general infertility population.
Finally, in saying that IVF can continue because Italy does 40,000 cycles per year, you're ignoring several very important things about Italy.
1) the cost of undergoing IVF is trivial compared to the US, and is largely covered by insurance. Patients can afford to do a few cycles with a low probability of success, because those cycles cost them hundreds of dollars rather than tens of thousands. When those fail, they move on to clinics in other countries, where they can actually have reasonable odds of success.It's the same reason that US patients do multiple IUI cycles: the success rate is low, but it's relatively cheap. You never know when you might get lucky, and that keeps the clinics in business.
2) We know that the Italian legal restrictions already force a significant percentage of all Italian infertility patients to seek treatment in a foreign country. Over 10% seek treatment in a handful of other European countries, not including all those who travel to Asia, America, or non-reporting European clinics.
3) The Italian doctors inflate their pregnancy rates by medical practices which violate ASRM standards. They consequently saw a tenfold increase in their triplet rate. (Similar practices in Germany have resulted in a shockingly high selective reduction rate. ) They have more triplet births than any other European country, and account for 20% of all European IVF triplets. (http://humrep.oxfordjournals.org/content/suppl/2010/06/22/deq124.DC1/deq124supp.pdf)
4) Italy currently has the lowest overall pregnancy rate of any European country except Turkey. Their overall rate is just 12%, compared to 35% in the US.
When you dramatically reduce success rates, impose potentially frightening legal liabilities, and triple the already high costs of IVF, how many IVF clinics do you think you're going to have left? Given the very different medical and legal realities in America, US physicians won't be able to keep their clinics open and continue treating patients. This opinion is unanimous among all infertility organizations, including the ASRM and RESOLVE.
Bill
Ah, but we are in agreement. You see, I have not claimed that the ASRM has changed their official position. I have simply pointed out that they recognize the large number of scientific papers which take the opposite position. You have now come to admit that statement to be true.
Think back to our first conversation on this topic. Do you remember what you said about oocyte cryopreservation? You stated that:
1) There are only a few clinics who had had limited success with this method of IVF.
2) There is no research on the effectiveness of oocyte cryopreservation for couples with infertility issues.
3) Only two studies have demonstrated success rates comparable to existing IVF, and
4) The largest studies still demonstrate vastly lower implantation rates.
Over the course of the current discussion, however, we have addressed the contents of eight independent studies of oocyte cryopreservation which have demonstrated success rates comparable not just to embryo cryopreservation but to the "gold standard" of fresh IVF transfers. Each of these studies has also included citations of additional studies achieving similar results. Furthermore, you revealed your knowledge of additional studies when you attempted to preemptively reject them. In particular, you made reference to meta-analyses, donor egg studies and studies performed in Italy. In order to preemptively exclude studies in these three categories, you had to at least suspect that there actually were studies in these categories that disagree with the official position of the ASRM.
In fact, simply typing "oocyte cryopreservation" into the PubMed search engine will return 870 articles published since 2008, 53 of which include the exact phrase in their title. Here are some examples of articles that can be found via this search:
Cao et al. 2009 "Comparison of survival and embryonic development in human oocytes cryopreserved by slow-freezing and vitrification."
- Study of 605 oocytes demonstrating statistically significant difference between slow freezing and vitrification in the categories of oocyte survival rate, cleavage rate, percentage of high-quality embryos, percentage of blastocyst development and oocyte abnormalities. Vitrification was superior to slow freezing in every category.
http://www.ncbi.nlm.nih.gov/pubmed/18930218
Smith et al. 2010 "Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing or vitrification."
- Study revealing a much higher pregnancy rate with vitrification over slow freezing.
http://www.ncbi.nlm.nih.gov/pubmed/20171613
Belva et al. 2008 "Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles"
- Study showing significantly higher rate of major malformations in children born from cryopreserved embryos fertilized via ICSI. (According to Noyes et al. 2009, oocyte cryopreservation does not share this risk, and is therefore a safer procedure.)
http://humrep.oxfordjournals.org/content/23/10/2227.full
Virant-Klun et al. 2011 "Slow oocyte freezing and thawing in couples with no sperm or an insufficient number of sperm on the day of in vitro fertilization"
- Study of 22 couples utilizing slow freezing of oocytes with no statistically significant difference in pregnancy rates compared to fresh oocytes.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042381/?tool=pmcentrez
Hodes-Wertz et al. 2011 "Retrospective analysis of outcomes following transfer of previously cryopreserved oocytes, pronuclear zygotes and supernumerary blastocysts"
- Study of 200 cryopreservation cycles including oocyte, pronuclear zygote and day-5 blastocyst cycles. When compared to 400 fresh embryo cycles, the oocyte group showed similar rates of implantation, pregnancy and live birth.
http://www.rbmojournal.com/article/S1472-6483%2811%2900176-3/abstract
Noyes et al. 2010 "Oocyte cryopreservation outcomes including pre-cryo and post-thaw meiotic spindle evaluation following slow cooling and vitrification of human oocytes."
- Study of 32 women seeking oocyte cryopreservation for infertility treatment and achieving a live birth rate of 56%.
http://www.fertstert.org/article/S0015-0282%2810%2900079-8/abstract
As reported in "Oocyte cryopreservation: a feasible fertility preservation option for reproductive age cancer survivors" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941585/?tool=pmcentrez#CR6
Oktay et al. 2006 "Efficiency of oocyte cryopreservation: a meta-analysis."
- Study showing no statistically significant difference in pregnancies and live births from vitrified oocytes as compared to fresh oocytes.
http://www.ncbi.nlm.nih.gov/pubmed/16818031
Kuwayama and Leibo 2008 "Efficiency of the cryotop method to cryopreserve human oocytes; analysis of in vitro and in vivo results at eleven IVF clinics."
- Study of 360 patients achieving live birth following oocyte cryopreservation.
http://www.fertstert.org/article/S0015-0282%2808%2902428-X/abstract
Yoon et al. 2007 "Survival rate of human oocytes and pregnancy outcome after vitrification using slush nitrogen in assisted reproductive technologies."
- Study showing a 43.3% pregnancy rate from 30 cycles using vitrified oocytes.
http://www.ncbi.nlm.nih.gov/pubmed/17350007
Antinori et al. 2007 "Cryotop vitrification of human oocytes results in high survival rate and healthy deliveries."
- Study demonstrating a 32.5% pregnancy rate out of 330 vitrified oocytes from infertile couples
http://www.ncbi.nlm.nih.gov/pubmed/17207335
Garcia et al. 2011 "Efficacy of oocyte vitrification combined with blastocyst stage transfer in an egg donation program."
- Study of 1098 oocytes of which 312 were vitrified prior to fertilization with a pregnancy rate of 61.8%
http://www.ncbi.nlm.nih.gov/pubmed/21303777
Grifo and Noyes 2010 "Delivery rate using cryopreserved oocytes is comparable to conventional in vitro fertilization using fresh oocytes: potential fertility preservation for female cancer patients."
- Study of 22 infertile women who submitted oocytes for cryopreservation resulting in an ongoing pregnancy/life birth rate of 57%.
http://www.ncbi.nlm.nih.gov/pubmed/19439285
Fadini et al. 2009 "Human oocyte cryopreservation: comparison between slow and ultrarapid methods."
- Study of 285 vitrified oocytes which revealed a pregnancy rate of 18.2%.
http://www.ncbi.nlm.nih.gov/pubmed/19712551
Cobo et al. 2008 "Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method."
- Study of vitrified oocytes from 30 donors which produced an ongoing pregnancy rate of 47.8%.
http://www.ncbi.nlm.nih.gov/pubmed/17889865
Surely you must have read each of these as well as many other such articles prior to launching your campaign against personhood, and so it must be that we agree on the vastness of the scientific research which stands in opposition to the official position of the ASRM.
Similarly, we have also reached an agreement on point number two: "that oocyte cryopreservation is a valid procedure for donor oocytes."
You stated that you would accept the results of a study which contained reproducible results for a patient group large enough to establish statistical significance. I provided such a study in the form of a 2010 article by Cobo et al. published in the journal, Human Reproduction (http://humrep.oxfordjournals.org/content/25/9/2239.long). That article described the results of a "randomized, prospective, triple-blind, single-centre, parallel-group controlled-clinical trial, including 600 recipients," and it "confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme."
In response to this study, you said that "no, we can't extrapolate anything about oocyte cryopreservation in an infertile population from donor egg studies. The very criteria that make women eligible to donate eggs (that is, proven egg quality by way of a pregnancy) are precisely what infertile couples lack. Egg quality is a key issue in the success of oocyte cryopreservation." You have neither challenged nor questioned the primary claim of the article - that it confirms the efficacy of oocyte cryopreservation for donor oocytes.
In regards to our third point of agreement, it is significant to note that your disagreement to my claim of agreement consists of only two parts. First, you deny that any of the studies which I presented achieved true statistical significance. Second, you disputed the figure of 6.7% for women seeking infertility treatments for ovulatory problems. I will answer these arguments individually.
In response to your first argument, let me remind you that I presented three separate studies which corresponded to each of the three phases that you suggested in your list of criteria. You described phases 2 and 3 as: "Phase 2 studies usually involve 100-300 patients, and Phase 3 studies involve more than 300-3000 patients." This of course implies that phase 1 studies involve less than 100 patients. The Rienzi et al. study from 2009 was a phase 1 study. In regards to the 2009 study by Ubaldi et al., you said: "Yes, this meets the criteria I suggested for a Phase 2 study, and I will certainly agree that this individual study showed good results." The study from Cobo et al. in 2010 rounded out the criteria by qualifying as a phase 3 study. All three of these studies presented statistically significant results demonstrating the efficacy of oocyte cryopreservation for at least all categories of infertility except that of ovulatory dysfunction.
Your dispute over the 6.7% figure is very interesting. You claim that the CDC report you presented gives an 18% figure for couples seeking infertility treatment as a result of ovulatory problems. Since that report lists ovulatory dysfunction as representing just 6.7% and diminished ovarian reserve as representing 11%, I can only assume that you derived your 18% figure from adding these two. There is, however, a very important difference between ovulatory dysfunction and diminished ovarian reserve.
That same CDC report defines the first category as referring to those women whose "ovaries are not producing eggs normally," and the second as referring to those women for whom "the ability of the ovary to produce eggs is reduced." This distinction of definitions seems to indicate that the first category involves egg quality while the second refers only to egg quantity. Surely you must realize that a diminished quantity of healthy eggs would not have any statistical effect on the success of an IVF program utilizing oocyte cryopreservation. There is therefore no reason to remove the category of diminished ovarian reserve from the list of those for which oocyte cryopreservation has been proven to be effective.
Nevertheless, even if we accept your figure of 18%, that would still leave 82% of infertility cases for which the efficacy of oocyte cryopreservation has been proven. This fact alone fully disproves your claim that a personhood amendment would put an end to all IVF treatments. When we add to this the historical fact that similar legal restrictions did not end all IVF treatments in Italy, the fallacy of your position becomes irrefutable. We both know that IVF can still be completed under a legal restriction against the intentional killing of human embryos because we both know that this was successfully accomplished in Italy.
Atlee
The Nature report I linked earlier supports my position: only 8 clinics in the US have had more than 10 live births from oocyte cryopreservation. Over half the clinics which offer it have never had a live birth at all. I think it's fair to call 8 clinics a "handful", out of several hundred clinics in the US.
As for the ovulatory numbers, the reason I'm combining the CDC stats is because Ubaldi did likewise. They don't break ovulatory dysfunction out from diminished ovarian reserve, but lump it all together as "ovulatory". This isn unsurprisingly, given that they literally have only 4 patients meeting those criteria. Still, if we're going to compare apples to apples, we have to combine the patient populations.
Yes, it's ludicrous to make any judgments about 4 cases. That's precisely MY point: you want to modify treatment for over 26,000 American women per year, based on the results of four (4) Italian women. Can there be any better argument for the experimentality of this procedure -- that even your shining exemplar of a study involves numbers of patients which can be counted on one hand.
Re the ASRM: no, the ASRM does not say that. Not even the first part of that statement can be interpreted to reflect the ASRM's acknowledgment of anything. Are you STILL failing to understand that the statement in question was most likely written by the doctors hosting their panel? They don't have scientific committees sign off on debate session descriptions.
Once again, the very height of intellectual dishonesty for you to even attempt to reference this. You should be ashamed of yourself for attempting to imply that the ASRM agrees with you on oocyte cryopreservation's applicability to the general infertility population.
Since you want to talk about Italy and point to it as a shining example: would you like to explain why Italy's overall pregnancy rates are the lowest in Europe, except for Turkey? If oocyte preservation is such a great answer, why does Italy have an overall success rate which is 1/3 of the US overall rate -- and that pregnancy rate is only as high as it is because of practices which would not be permitted by personhood legislation like that proposed by Personhood Mississippi? Would you like to talk about how Italy's laws have driven literally thousands of patients to seek treatment in other countries?
See, that's what happens when you translate individual studies into entire populations: reversion to the mean. That's why you study it in large groups before even proposing it as a reasonable alternative, much less replacing the current standard of care.
Also, let's clarify something very important: if you want to throw around the 870 results for "oocyte cryopreservation" on Pubmed, I think it's only fair to clarify that the vast majority of these aren't human studies. On just the first page of that same search, we have hard corals, goats, mice, cats, and cows, plus several editorial-type articles which don't actually constitute clinical trials.
Seriously, it's nothing short of ridiculous to try to make a study of freeze-dried cow sperm as supportive of human oocyte cryopreservation, just because that study contains the words "oocyte" and "cryopreservation".
You keep throwing around the same handful of studies -- several of the ones listed in your bibliography salad have already been cited elsewhere in this discussion.
Re the birth defect rates, do you know the minimum sample size required to determine equivalence in the birth defect rate across a population of 150,000 cycles? You need 4,000 patients just to tell you whether the confidence interval is 0.5-2. In plain English, that means you'd have to look at at least 4000 patients' results to know whether oocyte cryopreservation is no more than twice as likely to produce congenital anomalies as standard IVF. A sample size of 936 patients can only identify that the birth defects are less than 3.75 times as likely to occur. That is, 936 patients can't even tell you whether birth defects are 3x as likely or half as likely following oocyte cryopreservation versus fresh IVF. It is, quite simply, vastly underpowered to draw any such conclusions as that the two rates are equal. You would need to study four times as many oocyte cryopreservation births to know that for sure -- only you can't, because there haven't been anywhere near that many births.
Once again, this highlights the difficulty of making conclusions based on the success rates of a few dozen patients. Even the largest studies we've discussed fall far, far below the threshold for true statistical significance. That's why we shouldn't base treatment standards for an entire country's worth of IVF patients off of those very preliminary standards.
Finally, I notice you still haven't addressed my contention that the experimental nature of oocyte cryopreservation represents an ethical and legal violation which would not be permissible under personhood.
Let's say that I am a Mississippi IVF clinic which has never performed oocyte cryopreservation. Personhood-style IVF legislation passes, and to try and keep my practice open, I decide to start attempting to preserve oocytes. I buy a VitMaster freezer and Cryotop kits, and start trying it out on my patients. The first round, I get a 10% successful fertilization rate, compared to my normal 70%. That is, 60% of my study population has died, who would have survived if I had performed standard fresh-ICSI. I try again, and get results similar to Levi-Setti 2006: a 12% pregnancy rate, compared to my usual 35% rate, and a 33% miscarrage of that 12% rather than the usual 20%.
Can you identify for me another situation where it would be scientifically and legally acceptable to cause this kind of death rate in human beings, when the usage of a known treatment would have prevented it without offering any disadvantages to the people being studied? Would it be in any way acceptable to perform such experimental treatment on newborns, if only 10% of them survived to age 5 versus 70% with a standard method? Can you explain how performing an equivalent study on newborn human beings would NOT be considered the very height of criminal neglect?
We routinely charge mothers for manslaughter when they engage in practices like drug abuse which raise their miscarriage rate by 20%, let alone by 300%. In fact, you have already stipulated that embryo cryopreservation ought not to be allowed under personhood, because up to 50% of the embryos involved don't survive the process, and this fits the legal definition of manslaughter. By that definition, oocyte cryopreservation would be equally impermissible.
Under personhood, oocyte cryopreservation is research involving live human beings, because all cryopreserved eggs become legal persons the moment that the ICSI micropipette is withdrawn. Subjecting them to cryopreservation beforehand is ethically no different than subjecting embryos to cryopreservation -- it's a procedure which materially threatens a person's basic rights.
You have previously concluded that even unintended death of embryo is not justifiable under personhood, even for so important a case as protecting the mother's life and fertility. If surgical removal of an ectopic pregnancy is not permissible, how much less permissible must it be to perform life-threatening experimentation on human beings, for no greater reason than the continuation of IVF?
It is thoroughly morally inconsistent for you to support oocyte cryopreservation.
Bill
Your ethical argument is flawed for three reasons.
First, you are mistaken in concluding that oocyte cryopreservation is research involving live human beings. Oocyte cryopreservation involves the freezing of unfertilized eggs. I am not aware of a single personhood proposal that attempts to grant constitutional protection to oocytes. If I ever become aware of such legislation, then I will publicly oppose it. Under a personhood amendment, the right to life begins at fertilization not at ovulation.
Second, I have not "previously concluded that even unintended death of embryo is not justifiable under personhood." What I have stated was that: "A doctor who has taken every reasonable precaution against the death of his patient is generally not prosecuted if that patient happens to die while under his care. A personhood amendment would simply place embryonic deaths in the same legal category as any other death that occurs under a doctor's care." I have also explained that I am not opposed to embryo cryopreservation. I stated very clearly that the "combination of oocyte cryopreservation and single embryo fertilization would eliminate the step in the standard IVF process which could be condemned under the personhood amendment - the destruction of embryos which are not used by the donor." Therefore, a correct statement of the ethics of my position would be that I oppose the intentional killing of living human beings except as permitted by the Giver of life in the Bible.
Third, you are mistaken in your understanding of manslaughter. The Code of Alabama states that:
"A person commits the crime of manslaughter if:
(1) He recklessly causes the death of another person, or
(2) He causes the death of another person under circumstances that would constitute murder under Section 13A-6-2; except, that he causes the death due to a sudden heat of passion caused by provocation recognized by law, and before a reasonable time for the passion to cool and for reason to reassert itself."
[Code of Alabama - §13A-6-3]
Most states have a similar definition, and under a personhood amendment, anyone recklessly causing the death of a human embryo could be charged with manslaughter. However, there is a very important clause in Alabama law which takes precedent over this definition. That clause states:
"Mistake, or unintentional error on the part of a licensed physician or other licensed health care provider or his or her employee or agent or any person acting on behalf of the patient shall not subject the licensed physician or other licensed health care provider or person acting on behalf of the patient to any criminal liability under this section."
[Code of Alabama - §13A-6-1]
In other words, a doctor who has taken every reasonable precaution against the death of his patient cannot be prosecuted in the state of Alabama if that patient happens to die while under his care. A personhood amendment would cause this clause to apply equally to the actions of fertility doctors toward the embryos under their care. Therefore, the scenarios which you describe would not result in criminal charges unless it could be demonstrated that the doctor intended to cause the death of human embryos.
Atlee
Freezing isn't a mistake or an unintentional error. It's a deliberate action which is known to subject an embryo, or an egg, to a higher rate of death than an un-frozen one, even when performed correctly in accordance with medical standards.
It is NOT taking every reasonable precaution against the death of the patient. If you want to take every reasonable precaution, you would only work from fresh eggs, in accordance with currently-accepted medical standards, and would require that the resulting embryos be transferred fresh.
This is exactly the same logic you've already conceded as prohibiting embryo cryopreservation: it causes the death of people. Intention isn't a necessary component of manslaughter.
Legally speaking, the ASRM's opinion carries much more weight here than your (mis)interpretations of these studies. Physicians are protected when they act according to the professional consensus, which would be the ASRM opinion. Until and unless the ASRM issues a statement judging oocyte cryopreservation to be equivalent to fresh IVF for all patients -- not just a reasonable option for certain patients who are willing to accept the risk of embryonic death -- physicians won't be legally protected from charges of using un-proven experimental treatments which put human life at risk.
Here I'm referencing the new language of the 2012 Arkansas and Colorado initiatives: any procedures which "cause the death of a person" are prohibited. There's no requirement that said death be intentional or even direct, as long as they demonstrably cause death. A procedure, or an individual action of a doctor, which causes embryos to die at higher rates would certainly qualify. It doesn't matter whether that procedure is performed pre- or post-fertilization, if it raises the risk of post-fertilization death.
And it doesn't matter whether YOU are personally opposed to embryo cryopreservation. It's a matter of public record that most official voices of the personhood movement consider it to be incompatible with personhood, and have publicly argued or against it.
For example, Les Riley of Personhood Mississippi is currently advocating the passage of legislation identical to Georgia's failed SB-169 from 2009, which explicitly prohibits embryo cryopreservation.
Insofar as any of you are authorities on how personhood ought to be interpreted in practice, it's reasonable to suppose that the courts and the legislature will interpret it as prohibiting embryo cryopreservation.
For the record, Mississippi has a similar code protecting physicians from legal liability for unintentional errors, and it was universally agreed by the Yes On 26 campaign that embryo cryopreservation would nonetheless be prohibited.
(The chief proponent of this stance was an OB-GYN, who might reasonably be assumed to understand how that statute would protect his profession.)
As for the question of the 870 studies, you've fallen victim to the black swan fallacy. I don't need to read all 870 of them if I can readily observe that a substantial number don't involve either oocyte cryopreservation or human clinical trials.
Had you actually read them before advocating your position -- and as the person arguing for a change to the existing procedure, it's far more incumbent on you to do so than it is for me to argue for the status quo -- you would see the same thing. Clearly, therefore, you either have not bothered to actually read the contents of your own search results, or you are happy to try to promote a statistic which you know to be false.
FYI, limiting the Pubmed query to human oocyte cryopreservation with a publication date within the last 3 years knocks the number down to 371 citations. Again, a quick scan of the first few pages is perfectly sufficient to demonstrate that many of them don't actually relate to the practice oocyte cryopreservation, but simply happen to contain both words.
For example, the results contain a study of sperm cryopreservation which mentions that even damaged sperm are still capable of fertilizing oocytes. Surely we can both agree that this is not a study which has any application to the question of oocyte cryopreservation. Another study is a mouse oocyte cryopreservation which mentions the difficulties of translating the results to humans.
Limiting the results to the exact phrase "oocyte cryopreservation", with a publication date of the last three years and a limit of humans-only, knocks it down to 76 citations, the vast majority of which aren't clinical trials. Even those search criteria still include a study on zebrafish, and one on rhesus monkeys. Most of the rest mention oocyte preservation only as a last-ditch option for cancer patients, not an equivalent for IVF.
That's why we keep going around about the same few papers: that's all there are. You keep trying to suggest otherwise, but that's just not what the evidence shows.
As further evidence of your cherry-picking, and in the context of Italy, let's discuss how the Italian National Register confirms poor results from vitrification: http://www.ncbi.nlm.nih.gov/pubmed/20797902. With almost 8700 vitrified oocyte cycles, that is a far larger study than anything we've yet discussed, and is a population analysis rather than a clinical sampling. That means it doesn't just extrapolate results from a sampling of a relatively small group of patients, but actually looks at what happens in real life when the technique is applied to the general patient population.
What happens isn't good at all, in comparison to fresh IVF. The pregnancy rate was about half that following fresh transfer -- and that is true statistical significance, p<0.001, over a large number of cycles. Embryos from vitrified oocytes were about half as likely to implant, again with p < 0.001, and were also significantly less likely to develop into good embryos following fertilization.
This has to be regarded as a more authoritative data source than anything you've yet cited, both because of its size and because it's a population analysis (which is more reliable than a randomized trial).
Then there's http://www.ncbi.nlm.nih.gov/pubmed/20047739, Borini et al from Fert Stert 2010, "Multicenter observational study on slow-cooling oocyte cryopreservation: clinical outcome." This was a multi-center report involving 931 thaw cycles at multiple clinics. Among the findings were that successful fertilization, implantation, and pregnancy rates were all significantly reduced in comparison to fresh cycles. It also notes that success rates differed among clinics, implying that the good results of a few are not widely reproducible.
I'm also given to understand that a meta-analysis will soon be published about elective egg freezing at American clinics -- see http://www.sart.org/news/article.aspx?id=7336. Obviously, I haven't read the actual paper since it hasn't been published, but the results listed in the abstract are pretty dismal in comparison to current CDC statistics.
Even for the 291 vitrified oocytes, the analysis only shows an implantation rate of 18.8% in patients under age 30, compared to an overall implantation rate of 34% in all IVF patients under 35. In other words, the study found an embryo is about half as likely to implant after vitrification, even in a younger and more favorable group of patients. The slow-freezing results are even worse, with no better than a 10% implantation rate.
Obviously, we'd both have to read the study itself and look at the raw data, as well as the component studies, and consider the previously mentioned issues with meta-analyses. However, it has to be considered as adding weight to the argument that oocyte cryopreservation is an inferior technique to fresh fertilization.
Re Nature, the credentials of the writer are absolutely irrelevant, since we're interested in the facts being reported. We can cite Rudick 2009 if you prefer: http://www.fertstert.org/article/S0015-0282(10)00800-9/abstract . We see that 337 live births have been reported, but we also see a couple other interesting things, such as that a majority of these programs only offer cryopreservation only to younger women, thus stacking the deck by excluding the age groups which constitute 40% of the US IVF population (non-donor). Furthermore, we find that most of these patients aren't actually diagnosed with infertility, but women who are electively preserving their eggs.
Furthermore, it's not in dispute that 75 of the responding 143 clinics have never had a live birth, and 11 more have achieved only 1 live birth. Only 8 clinics have achieved more than 80 live births. Arithmetic therefore tells us that the remaining 56 clinics have achieved somewhere between 2-9 live births, and that they collectively account for no more than 246 live births apiece (assuming arguendo that the most successful clinics had only 10 live births apiece). That leaves us with a maximum average of about 5 live births per moderately-successful clinic, total, over a period of however many years they've been offering cryopreservation.
To bring home the scale of what we're talking about, most IVF clinics see at least 5 live births every MONTH. We are still discussing a tiny, tiny number of patients. 337 live births is ridiculously small, compared to the 46,000 live births per year from ART.
What's more, we can safely assume that the reporting clinics represent most if not all of the US clinics offering cryopreservation. If you assume that the non-reporting clinics offer cryopreservation and achieve similar results, you would arrive at birth rates more than twice as high as the documented number of live births in the world as a whole as of the publication date. It's a pretty safe bet that the non-reporting clinics do not have large and successful cryopreservation programs.
As for the other link, Boldt is a literature review, not a clinical trial, and offers no new data beyond the studies we've already discussed. It may safely be categorized with other literature reviews such as Saragusty 2011 (http://www.reproduction-online.org/content/141/1/1.full), which note that the overall state of the literature indicates that cryopreservation shows overall results inferior to fresh transfer.
We could keep going: http://www.placentajournal.org/article/S0143-4004(08)00239-7/fulltext?refissn=1472-6483&refuid=S1472-6483%2810%2900785-6, showing an implantation rate of just 8% over 233 transfers in 2007, and a notably poorer pregnancy rate. (Which study, by the way, notes that its own sample of achieved pregnancies is still too small to compare to other ART techniques).
Even Nicole Noyes, whom you have repeatedly attempted to cite in support of cryopreservation, suggests only that it's an option for "appropriate patients", that "comprehensive informed consent" is necessary to inform them of the lower overall rates, and that it should only be offered once individual clinics have "established their own efficacy in the procedure".
I'm not sure how you'd do that last without experimentation on live human oocytes, knowing that you're probably going to screw it up and cause many of them to die in the process. We don't permit doctors to just go practicing new potentially life-threatening techniques on live patients without institutional oversight and formal training. If I'm a heart surgeon, I can't just decide to start offering heart transplants to my patients. I have to go do a fellowship in transplantation first, so that I can reasonably claim to have received the appropriate training to preserve my patients' life and health. If I didn't get that training, I wouldn't be protected under that medical-liability exception you reference above, since I'm working outside my experience, education, and normal scope of practice.
Since we've established that oocyte cryopreservation directly impacts the welfare of what would legally be considered live human beings, it's only reasonable to assume that doctors would be required to complete fellowships in oocyte cryopreservation, or demonstrate comparable clinical experience, before being able to perform it in their own clinics.
There are currently no such fellowship programs in existence, let alone adequate fellowships to train the thousands of US reproductive endocrinologists within a reasonable period of time.
For clarification: when I say that you've conceded that even the unintentional death of an embryo is unjustifiable, I'm referring to your position on ectopic pregnancies.
Many authorities believe that tubal removal surgery is permissible because the purpose is to treat the ruptured tube, and the death of the embryo is an unfortunate and unintended side effect. By arguing that these patients should instead be forced to rupture, you are agreeing that even a serious threat to maternal life is not justification for procedures which have the double effect of embryonic demise, and whose primary purpose is to treat the mother.
If even a direct threat to maternal life and physical health can't justify unintentional risk to the embryo, how much less can we justify risks which are designed only to reduce the risk of multiple birth, or preserve access to IVF?
Re sample sizes, you're using the wrong formula. The one you mention gives you the way to calculate the minimum number of patients required to extrapolate to a population of 150,000 -- which, I might add, also highlights that none of the studies you've presented come anywhere near the requisite sample size.
However, once you actually get the results of your 384 patients, you will then calculate a confidence interval. What I'm pointing out is that the confidence intervals under discussion here are very large, due to the small sample sizes, so you can't go comparing the observed means directly between two studies. You have to expand the sample size so that the confidence intervals don't overlap.
Italy and triplet rates: you're assuming that Italian women don't get selective reduction done elsewhere. This is undoubtedly false.
Also, I've already provided very solid sources to show that 10% of Italian patients seek treatment in just the few European countries under discussion. 4173 Italian couples sought out-of-country treatment in the 27 European clinics studied in 2005, according to the ESHRE's survey -- an increase from 1006 in 2003. It's not "supposedly" anything.
Finally for the night, because it's very late, oocyte cryopreservation DOES involve research on live human beings. Isn't that what you're saying is created the instant that the ICSI needle is withdrawn? You can freeze and thaw them all you like, but the minute you try to fertilize them, personhood means you're dealing with a live human being. Any difference in outcome from that point on (fertilization rates, implantation rates, etc) is affecting the survival rates of live human beings.
Let's say we conduct genetic experiments on oocytes, and identify a chromosome which is necessary for an embryo to develop past 8 cells. We somehow remove that chromosome from our oocytes. They fertilize as normal, becoming people, and every single one of them promptly dies 3 days later as expected. Have we performed research on live human beings? Of course we have, and we've knowingly caused them all to die, even though we didn't do anything to the embryos themselves.
In fact, all of the emergency contraception and hormonal birth control opposition opposition hinges on just this logic. Indirect damage to an embryo, the creation of a hostile environment where it is less likely to survive, is just as bad as directly destroying the embryo, and is therefore the equivalent of any other form of abortion. You've already stated that you agree with this position on hormonal birth control and feel that it is incompatible with personhood
If it's unacceptable to create a sub-standard home for an embryo which indirectly lowers its survival rates without ever directly touching the embryo itself, how can it be acceptable to modify the embryo's precursor components in a way which is much more provably hostile? After all, the evidence for harmful effects of oocyte cryopreservation is much more extensive than that of the abortifacient effect of birth control.
And I'm frankly shocked that you don't oppose embryo cryopreservation, either. You do realize that this process directly destroys up to 50% of the embryos involved, and damages others to the point where they are unable to implant?
How in the world can you justify opposing birth control pills and IUDs as "intentional killing" but consider freezing to be perfectly allowable? This defies logic in a way that I am at a loss to understand.
Bill
You seem to be somewhat confused about my position. First, you claim that I have already conceded that a personhood amendment would prohibit embryo cryopreservation. Then you claim that it doesn't matter if I am not personally opposed to embryo cryopreservation. Then you explain that you are extrapolating my supposed opposition to embryo cryopreservation from my position on ectopic pregnancies. Then you attempt to extrapolate my supposed opposition from a statement that I made in regards to oral contraceptives. And finally, you say that you are shocked that I do not oppose embryo cryopreservation. Perhaps it would help if you focus on the exact wording of the law rather than these wild speculations on the consistency of my morals.
As I have already explained, a doctor in the state of Alabama (and several other states as well) cannot be prosecuted for manslaughter over the death of his patient unless it can be demonstrated that the death was caused intentionally. There is no legal requirement that a doctor always utilize the methods that other doctors think are the best for a given situation. There is no requirement that a doctor conform to the dictates of the ASRM, and there is no restriction against the use of experimental treatments. The key element in medical manslaughter cases in either of our states is that of intent.
This is a very, very important legal distinction to keep in mind. My statements regarding the legality of various actions under a personhood amendment would make much more sense if you consider each of them in light of this explanation. Under a personhood amendment, it would be illegal for a doctor to take any action toward a human child with the intent of killing that child regardless of the child's stage of development. Neither oocyte cryopreservation nor embryo cryopreservation are initiated with the intent of killing a human child. Therefore, no doctor can be prosecuted for manslaughter in the event that a human child dies after being frozen. The only action associated with IVF which would be prosecutable under a personhood amendment is the intentional destruction of those embryos which are not used by the patient seeking infertility treatment.
This is also true of the proposed 2012 personhood amendment in Colorado. You quoted that amendment as stating that "any procedures which 'cause the death of a person' are prohibited. Contrary to your quote, however, the actual text of that amendment states that "the intentional killing of any innocent person is prohibited." (http://personhoodcolorado.com/) Thus, the Colorado amendment agrees with my claim that no doctor would be prosecuted for the death of an embryo under his care unless it can be demonstrated that he caused that death intentionally.
You also completely misrepresented Georgia's SB-169 by claiming that it "explicitly prohibits embryo cryopreservation." First of all, this bill was not a personhood bill but rather, as it was entitled, a bill for the "Ethical Treatment of Human Embryos." The text of that bill states that: "The creation of an in vitro human embryo shall be solely for the purposes of initiating a human pregnancy by means of transfer to the uterus of a human female for the treatment of human infertility or cryopreservation for such treatment in the future." (http://www1.legis.ga.gov/legis/2009_10/fulltext/sb169.htm) This bill does not explicitly prohibit embryo cryopreservation, rather it explicitly permits embryo cryopreservation.
Your misrepresentation of the Georgia bill and the Colorado amendment as well as your misunderstanding of the Alabama statute admits to only two possibilities. Either you have never read either of the first two and were ignorant of the third until I quoted it in this discussion, or you are intentionally attempting to convey a false impression of these documents. In either case, your credibility on matters of legal importance has been seriously compromised. Since your argument against personhood is a legal argument, this series of errors undermines the very foundation of your position.
Your errors in other areas follow a similar pattern. For example, your insistence that I am just repeating the same few studies over and over again indicates that either you have not read any of the studies which I have referenced in order to know that I am not repetitively listing them or you have read them and you are lying about their content. I would prefer to believe the former of the two, but even that is a serious mark against your character. Similarly, I would prefer to believe that you are simply ignorant of the recent advancements of the Italian oocyte cryopreservation studies rather than that you are intentionally presenting results that were obtained several years prior to those advancements as evidence against their efficacy. I would also like to believe that you just don't know the difference between slow freezing and vitrification and that this is why you keep referencing slow freezing studies as evidence against vitrification. Perhaps these beliefs are true. After all, you are directly relying on an absence of knowledge to argue that Italian women "get selective reduction done elsewhere." It might be best if you would take some time to study this issue more thoroughly and reconsider the validity of your position.
By the way, using the formula p +/- 1.96 x √((p(1-p))/n) yields a confidence interval of .0095 for a sample of 936 out of a population of 150,000 with 98.7% responding in the affirmative and only 1.3% responding in the negative.
Atlee
Honestly, it's not my job to teach you basic statistics, or to help you understand what those formulas actually mean.
Your formula tells you that your mean is WITHIN the confidence interval of 95%. That's the whole point of including the 1.96 standard-deviation coeffiicent in the equation. If we repeated the experiment 100 times, 95% of the time, our observed result would fall within 1.96 standard deviations of the mean.
As I have already explained to you twice, you need to calculate the endpoints of the confidence interval, and then determine whether that interval overlaps either the incidence rate of a population, or the confidence interval of the statistic to which you're attempting to compare it.
Do that, and you will see that you need a much larger sample size to arrive at non-overlapping confidence intervals, and therefore to have certainty that your observed outcome is statistically proven superior.
I must, however, acknowledge that I actually made an error in the math, because I did the calculation for the wrong one of Belva's groups. As it happens, I significantly UNDERESTIMATED the necessary sample size. You need 13,150 patients in each study to be able to compare the two, not 4150.
Belva's fresh ICSI group involves 3073 patients, with a birth defect percentage of 1.7%. The confidence interval, with a population of 150,000, is +/- 0.45, meaning that the "real" number is somewhere between 1.25-2.15%. As you can see, the 1.3% result from Noyes 2012 (CI +/- 0.72, 0.58-2.02%) also falls within this range. Therefore, we cannot say that 1.3% is "better" than 1.7%. (And it doesn't matter that it's at the low end of the CI, either.)
In order to make the confidence levels non-overlapping, each study would have to involve 13,150 patients. That would give us a CI of 1.49-1.94% on Belva's fresh ICSI results, and 1.09-1.48% on Noyes' cryo results. Then, and only then, we would be able to say with statistical certainty that the two studies differed, and that oocyte cryopreservation resulted in fewer birth defects than fresh ICSI.
Of course, it's certainly possible to imagine a study involving 13,150 fresh ICSI cycles, because many thousands of babies are born every year following ICSI. However, it is not possible to know the results of 13,150 oocyte cryopreservation births, because that is roughly an order of magnitude larger than the number of such births known to exist.
Bottom line, it is ABSOLUTELY unproven that oocyte cryopreservation shows a superior or even comparable rate of birth defects. If you repeated Noyes on another 936 patients, and Belva on another 3073 patients, you might arrive at a fresh rate of 1.3% and an OC rate of 1.95%.
The only thing we can conclude from Noyes is that oocyte cryopreservation is associated with something less than 2x as many birth defects as fresh ICSI. Of course, over a population of 150,000 cycles a year, that could mean that a switch to oocyte cryopreservation could cause up to an additional 1,155 babies with birth defects.
(I'd say that the arithmetic is left as an exercise for the reader, but since you like to question my math, it's the upper bound of the one CI vs the lower bound of the other, 150000*0.0202 - 150000*0.0125 = 1155.)
I hope this little exercise clarifies for you just how very unreliable the conclusions of ANY of these studies are, and that you're beginning to get a feel for the numbers required to draw truly valid statistical conclusions.
As for my misrepresentation of the Colorado language, please note that I mentioned the *Arkansas* and Colorado initiatives. You can review for yourself the text of the Arkansas initiative at http://www.katv.com/story/16420533/personhood-arkansas-wants-anti-abortion-measure-on-ballot , and clearly note that it refers to "causing the death". I await your apology for calling me a liar.
Furthermore, only the first line of the Colorado initiative refers to "intentional" killing. The lines prohibiting the usage of birth control and IVF practices only mention "killing" a person.
To extrapolate what is meant by this, we can look at the Colorado amendment writers' position on emergency contraception and IUDs. Clearly their intent is to prohibit both forms of contraception. Both have been specifically addressed by previous statements from Personhood USA and Personhood Colorado. As Gualberto Garcia Jones (co-drafter of the amendment) has said in reference to the new language that "It's not that we changed our position. We're just putting it in the language." (http://www.christianpost.com/news/new-colo-personhood-amendment-features-new-improved-language-62627/) I assume you are likewise opposed to both, since you mention being opposed even to oral contraception on your website.
Neither IUDs or emergency contraception are used with the same degree of deliberation as would be involved in discarding a frozen embryo. Women and doctors use them with the INTENTION of preventing fertilization, and the implantation-prevention is a secondary effect.
Therefore, if CO 46 is to prohibit so-called abortifacient contraceptives, we must assume that the mere foreknowledge of a possible embryo-destructive side effect is enough to violate the prohibition against "birth control which kills a person". We may then infer likewise that the knowledge of a much more certain embryo-destructive side effect is enough to violate the prohibition against ART practices which "kill a person".
In a legal context, "intention" has a special meaning. It doesn't require definitive proof that the defendant deliberately set out with the exclusive goal of killing someone else. It only requires that a reasonable person would know that a given action presents a non-trivial possibility of causing serious injury or death to another person, and that the defendant could choose not to take the action.
For example, drunk driving is considered intentional killing, and is prosecutable as a lesser degree of homicide. (Here in MS it's "depraved heart murder", while other places call it "voluntary manslaughter" or "negligent homicide" or the like.) A drunk driver doesn't leave the bar with the deliberate goal of killing someone else in a car accident, but everyone knows that DUI can kill, and he has the ability not to decide to drive. Therefore, if he should be involved in a fatal wreck, he will be charged with manslaughter.
Likewise, a woman and her doctor should reasonably know that using an IUD does sometimes cause the post-fertilization loss of an embryo. She has the simple option of choosing not to use an IUD. Therefore, it would be likewise considered an intentional and reckless act.
It's not first-degree murder as we usually think of it, but it is most definitely "intentional killing" in the eyes of the law, and would thus violate personhood.
Similarly, a doctor who performed a procedure on a newborn infant which had a known 50% death rate, and which offered no benefits to that infant, and which was not medically necessary for that infant, would be charged with lesser homicide in about 10 seconds flat. Can you even pretend that this doctor would be protected by the Alabama medical statute? Of course you can't, nor should he be.
This, BTW, is exactly how Dr. Conrad Murray was convicted for Michale Jackson's death.
You're referring to the wrong version of the ETEA. The version to which I'm referring is that located at http://personhood.net/index.php?option=com_content&view=article&id=235&Itemid=609 . This is the specific version previously cited by Les Riley in Facebook postings as "model legislation".
It was drafted by the Bioethics Defense Fund, and as you can read for yourself at http://www.bdfund.org/octomom-abuses, the drafters are quite clear that it was intended explicitly to stop embryo cryopreservation.
I await your apology for calling me a liar. I have not misrepresented or misunderstood either the Georgia or the Arkansas/Colorado legislation.
As for your position, you conceded that embryo cryopreservation would be prohibited in the first conversation we had about it, where we discussed it in the context of single-embryo transfer. I will note that this was subsequently backed up by the Yes On 26 campaign's "medical talking points", where it was explicitly noted in no uncertain terms: http://yeson26.net/media/4818/amdt26_discussion_points.pdf .
Mississippi has an identical statute to protect physicians from criminal liability. However, clearly Personhood Mississippi, which cited that same law in other contexts and was therefore aware of its existence, did not believe that the statute in question would permit physicians to continue embryo cryopreservation.
If you think they're incorrect, you are by all means free to take it up with them and have that argument amongst yourselves. However, I will take them at their word when they tell me what they intend for their law to do, and what they feel it will be able to do.
It's not inconsistent to believe that the law would prohibit cryopreservation, while still thinking that cryopreservation ought to be legal. One is a moral judgment, and the other is a legal judgment. Therefore, I don't think it illogical of you to believe that cryopreservation should be permitted while acknowledging that it won't be.
What I do think is illogical are your statements that a secondary effect of a contraceptive which occasionally causes embryo loss is abortifacient and impermissible, and that even a direct and immediate threat to maternal life doesn't justify the known double effect of embryonic death, but that it would be morally and legally acceptable for a physician to perform an action with a much higher risk than contraceptive usage, for a much less urgent reason than ectopic pregnancy.
Do you care to explain how you can "advocate for a ban on any form of birth control which can be proven to cause the deaths of innocent children", yet support a practice which much more provably causes the "deaths of innocent children"? When my doctor is banned from prescribing me birth control pills which have maybe a 5% chance of killing an embryo, how can he possibly be then be allowed to freeze embryos and destroy 50% of them?
You simply cannot have it both ways. Either that statute protects physicians' ability to prescribe possibly-abortifacient birth control, or it prohibits them from freezing embryos.
As for re-citing the same handful of studies, you've cited Cobo 2008 at least twice in this discussion already. You keep citing Nicole Noyes and Grifo as though these are different clinical trials rather than different presentations of the same dataset, when I have previously noted that Noyes has performed only 46 cycles at her clinic. My goodness, you cite Noyes twice in that same post, and follow it up with Hodes-Wertz, which is yet another presentation of those same NYU patients!
You've approvingly cited studies like Fadini 2009, which shows a pregnancy rate about half that currently found in the US even with vitrification. You cite a meta-analysis, Otkay 2006, and claim it proves the superiority of vitrification, when it explicitly says that it did not include vitrification due to there only having been ten (10) babies worldwide born from vitrification as of that publication date. You further claim it shows no significant differences, when the authors themselves find "significantly lower rates" with frozen vs fresh eggs (in fact, the pregnancy rate was 1/3 that of fresh).
You keep including donor studies. You make erroneous statistical judgments based on ridiculously small numbers -- roughly half of the studies you've cited as "demonstrating" something include less than 30 cycles. You cite Cao, which didn't actually transfer any of the created embryos and thus has nothing to tell us about pregnancy rates. You've stated in the IVF article on your site that your claims are "supported" by six additional studies which turn out to be nothing of the sort. You've implied that I'm lying when I note that you rest your claims on studies of a dozen people, when you have in fact done just that in the article on your site.
You've grossly misrepresented the number of studies on oocyte cryopreservation, and failed to acknowledge that less than 10% of them are actually referring to human oocyte cryopreservation, and still fewer are clinical trials (rather than literature reviews or editorials). You've completely failed to acknowledge any of the studies that I have cited which contradict your point.
You claim I am citing studies on slow freezing rather than vitrification, when I specifically cite the Italian National Register study, Scaravelli 2010, which specifically includes vitrification. You criticize me for citing slow freezing studies, when you've been perfectly happy to do so yourself. You've ignored the fact that a bare handful of US clinics have achieved even very modest successes.
You claim I'm ignorant of the "success" of the newer methods, or that I'm lying, when the fact is that you've cited only one vitrification study of even quasi-respectable size involving infertility patients with their own eggs, Ubaldi 2010. I have discussed at length the issues there, starting with the fact that it is still quite small, and that it involves demographics and practices very different from the US population. (Extra credit pop quiz: what is the 95% CI on the warmed pregnancy rate) The study itself acknowledges that it is the largest of its kind, and its results have not been duplicated at other clinics. Obviously, therefore, we cannot form any universal judgments based on it alone, and must rely on the body of previous evidence.
And yet somehow *I'm* the one who's misrepresenting the body of scientific knowledge? Truly, it beggars belief that you think there's adequate evidence to abolish the current standard of medical care and replace it based on such thin evidence.
"There is no legal requirement that a doctor always utilize the methods that other doctors think are the best for a given situation. There is no requirement that a doctor conform to the dictates of the ASRM, and there is no restriction against the use of experimental treatments."
This is absolutely, fundamentally, untrue. Doctors in Alabama, as elsewhere, are still required to conform to accepted standards of medical practice. The physician-liability statute only accounts for mistake or unintentional error, and does not except the physician from the responsibility to follow the standards of care.
The standard of care is formed by the medical consensus. When a physican uses a treatment which is classified as "experimental", and which is not overseen by an institutional review board, he opens himself up to liability (civil, if not necessarily criminal) for any negative outcomes. If I hang out my shingle and start offering oocyte cryopreservation with no formal training, experience, or institutional review, you can then sue me into oblivion if I screw up and destroy your eggs or embryos. You probably can't have me arrested -- note the distinction between this kind of unintentional error and the deliberate choice to freeze embryos -- but I'm certainly not protected.
Furthermore, if a doctor has any intention whatsoever of collecting data that he might possibly someday choose to publish, or even discuss at an academic conference, federal regulations REQUIRE him to have IRB oversight.
Finally, there's the issue of medical malpractice insurance policies, which often restrict doctors from offering experimental or less-successful techniques. Consider the exhaustively documented issue of VBACs, where both doctors and hospitals are often forbidden by their insurance companies from offering them to their patients. This is a civil issue rather than a criminal one, but it's just as real when it comes to determining whether a given doctor will be able to continue practicing.
Bill
You are once again mistaken in regards to the legal effect that a personhood amendment would have on IVF.
The Arkansas language does not state that "any procedures which 'cause the death of a person' are prohibited." Instead, it states that "This Amendment shall have no effect on in vitro fertilization or other methods of assisted reproduction that do not cause the death of a person." It is not legally plausible to conclude that this statement constitutes a ban on embryo cryopreservation. This clause does not make any statement at all about what effect the amendment would have on in vitro fertilization methods that result in the death of an embryo. It just states that it will have no effect on those that do not. The effect on those treatments that do result in death is explained in the previous section of the amendment which states that "the word 'person' shall apply to all human beings, including the unborn." Therefore, the Arkansas amendment would require the same proof of intent for charges of manslaughter or homicide of embryos as is currently required in other cases involving the death of a patient.
Similarly, there is no prohibition against embryo cryopreservation in the Colorado amendment. The line which you are referring to (2,b) states that "only in vitro fertilization and assisted reproduction that kills a person shall be affected by this section." This line does not state how those particular processes will be affected; it just says that the effect of the amendment would apply. To discover the effect of the amendment, we have to read the line (2) which states that effect: "Effect. The intentional killing of any innocent person is prohibited." That's it. There is no other effect of the Colorado amendment. It does not ban embryo cryopreservation or any other IVF method that may result in natural or incidental embryonic deaths. It only prohibits intentional killing.
The same is true of Georgia's Ethical Treatment of Embryos Act. Even the introductory form of that bill which you cited states very clearly that "The in vitro human embryo shall not be intentionally destroyed." There is no prohibition against unintended death, nor is there a prohibition against embryo cryopreservation. In fact, this bill specifically recognizes the existence of "legal rights and duties regarding the disposition of in vitro human embryos that were not transferred due to either of the fertility patient's death, divorce, abandonment, or dispute over the custody of the in vitro human embryo," and cryopreservation is not excluded as an option in such cases.
Your claim that the authors of this bill explicitly intended for it to stop embryo cryopreservation is not founded on a statement by the Bioethics Defense Fund but rather on a single comment by pro-life blogger Jill Stanek. To the best of my knowledge, Mrs. Stanek is not directly affiliated with the Bioethics Defense Fund, nor was she involved in drafting the Georgia bill in any way. Her comment that Georgia's SB169 would end embryo cryopreservation was simply in error.
In each of these cases, the importance of intention is abundantly evident, but you seem to have an improper understanding of what is meant by the legal term of "intent." I have not been able to find your definition in any legal dictionary, and your example of a homicide caused by a drunk driver does not apply because the unintended homicide was the natural result of the criminal act of driving under the influence of alcohol which was initiated intentionally. Thus, the homicide though not specifically intended falls under the general intent of the crime of driving under the influence. The key difference between this situation and that of deaths resulting from embryo or oocyte cryopreservation is that these deaths do not come about as the natural result of some other criminal act. These deaths occur in the absence of any criminal intent of any sort at all, and in fact, occur in spite of strong intention to prevent these deaths.
In contrast to your definition, Black's Law Dictionary defines intent as a "state of mind in which a person seeks to accomplish a given result through a course of action," and Morissette v. United States presents an excellent case study of this concept. Morissette was convicted for taking government property that he had thought was abandoned. On appeal to the Supreme Court, his conviction was overturned on the grounds that although he did take government property with full knowledge of his actions, he did so without any intent to commit a crime. In the process of presenting their decision, the Court deliberated upon the necessity of proving criminal intent in all cases involving serious crimes. You can read the full text of their decision at: http://laws.findlaw.com/us/342/246.html.
The decision of the Court in Morissette has been instrumental in several other decisions including Vacco v. Quill in which the Court upheld New York’s prohibition against assisted suicide. In Vacco, the Court stated that the intent of the doctor is the key difference between the legally permissible action of administering pain killers that may hasten the death of a patient and the illegal action of administering a lethal dose of medication in order to kill a patient. (http://laws.findlaw.com/us/000/95-1858.html) Likewise, the Court stated in Gonzales v. Carhart that the federal ban against partial birth abortion "contains scienter requirements concerning all the actions involved in the prohibited abortion ... If either intent is absent, no crime has occurred. This follows from the general principle that where scienter is required no crime is committed absent the requisite state of mind." (http://laws.findlaw.com/us/000/05-380.html) All of these cases support the conclusion that under a personhood amendment, no doctor would be prosecuted for the death of an embryo in his care unless it could be demonstrated that he intentionally caused that death.
I find it very interesting that you are comparing the results of the Noyes study with only the fresh ICSI group from Belva's study. I have never claimed that oocyte cryopreservation produces better results than the use of fresh oocytes, nor was this the claim put forth in the Noyes paper. Her claim, rather, was that there is not a statistically significant difference between these two groups. The claim that you should be trying to disprove is my statement that oocyte cryopreservation is safer than ICSI with subsequent embryo cryopreservation. In other words, you should be looking for some way to prove that the 6.4% malformation rate reported by Belva is not significantly higher than the 1.3% reported by Noyes.
In regards to your comments on the studies that I have cited...
I have made reference to two separate articles by Cobo et al. The first was an article entitled "Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method." I made two references to this article: one to point out that it was not mentioned in the ASRM position statement and another to include it in a sampling of articles on cryopreservation. The other article by Cobo et al. which I have referenced was a 2010 article entitled, "Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial," and I listed it as an example of a study meeting your phase three requirements.
I have mentioned six different articles which were co-authored by Nicole Noyes. The first was actually presented by you as evidence to support your position before I pointed out that it provides far more support for my position. The second was presented as direct opposition to the ASRM position paper that you presented. The other four were included in a sampling of articles on cryopreservation.
I made no claim in regards to those four other than that they exist, however, your claim that these studies are all from the same dataset is not correct and neither is your claim that I presented them as such. If you would be so kind to read through that list again, you would notice that I specifically linked the two listed as "Noyes et al." since the results of one were reported again in the other. However, the latter of those two also reported results for an additional 50 cryopreservation cycles. Similarly, the article listed as "Griffo et al." also differs enough from the other Noyes articles to warrant its reading as well, and it was included in the list for that reason. The Hodes-Wertz article, on the other hand, directly refutes your comments. That article reported the results of 200 cryopreservation cycles which, of course, we know includes the cycles reported in previous Noyes papers because we are told so right in the abstract of the Hodes-Wertz article. This article, however, includes the results of several additional cycles that were not reported in the other studies, and it decisively refutes your claim "that Noyes has performed only 46 cycles at her clinic."
You are mistaken to state that I approvingly cited the Fadini study. I neither approved of nor dismissed the Fadini study. I simply listed it in a sampling of articles on cryopreservation.
You are correct in pointing out my erroneous explanation for the Oktay analysis. I'm not sure what happened there, but I suspect that it was a copy and paste error. This analysis was also listed solely as part of a sampling of articles on oocyte cryopreservation.
I've already explained why I include donor studies, and the correct application of the Ubaldi study to this discussion.
Cao was cited simply as a sampling of articles on oocyte cryopreservation.
The "IVF article" on my site is not an article at all but rather a copy of our previous discussion on this topic. It does not state that my claims are supported by six additional studies. It states that the ASRM position paper cites six studies which support the ASRM's claim that "Numerous studies have also reported improved oocyte survival."
Neither does that "article" rest my claims on studies of a dozen people. I simply pointed out that the ASRM claimed that "several studies have reported better post-thaw oocyte survival, fertilization, and pregnancy rates," and I mentioned that they supported that statement by citing two independent studies. If you think that those two studies should not have been cited in support of that statement, then perhaps you should write to the ASRM and tell them so.
By the way, the Scaravelli paper that was published in 2010 only analyzed data from 2005-2007, a time period which precedes many of the advances made in oocyte cryopreservation in general and vitrification in particular over the past 4 years.
And last but not least, let me point out that I have never accused you of lying. I stated that as a possibility, but I also was very clear in stating that I would prefer to believe that your errors were the result of ignorance. Thus, I presented two possible explanations - one which requirs proof of intent (lying) and one which does not (ignorance). In the absence of any evidence for malicious intent, I would have had no grounds for accusing you of lying, and so I refrained from making that accusation. Once again, it is evident that the issue of intent plays as significant a role in my ethical system as it does in the American legal system.
Atlee
"The Arkansas language does not state that "any procedures which 'cause the death of a person' are prohibited." Instead, it states that "This Amendment shall have no effect on in vitro fertilization or other methods of assisted reproduction that do not cause the death of a person." It is not legally plausible to conclude that this statement constitutes a ban on embryo cryopreservation. "
Actually, that's exactly what it says. It says that "no innocent person shall be denied the right to life", and then goes on to make a specific exception for things which do not 'cause the death of a person'. If it did not prohibit birth control and IVF procedures which DO cause the death of a person, there would be no need to except the ones which do NOT.
But don't take my word for it -- ask the Arkansas attorney general, who has concluded that both birth control and IVF procedures which can potentially 'cause the death of a person' would be affected.
You are similarly incorrect about Jill Stanek and the Bioethics Defense Fund. I'm not citing Jill -- rather, the BDF is citing her directly in their press release, which they would not do if they did not agree with her statement.
I'm not sure why you're arguing this, anyway. It's crystal clear that personhood advocates intend for their measures to prohibit the cryopreservation of embryos. We know this because they have said as much, in no uncertain terms, on multiple occasions. For example, the Yes On 26 campaign published literature which explicitly said that freezing would be prohibited under Initiative 26. Do you dispute that Yes On 26 said so?
As for the question of intent with cryopreservation, it is exactly the same logic as that applying to birth control pills and IUDs.
Using birth control is not a criminal act in and of itself, and isn't done with any malicious intent. However, you yourself have said that birth control methods must be considered abortifacient if they present even a small likelihood of causing embryonic death as a side effect, and that they would be therefore prohibited by personhood. This conclusion relies on that same manslaughter logic I described above, by the way, so I must conclude you accept recklessness
We must therefore conclude that any other procedures which have a similar potential for embryo destruction must likewise be prohibited by personhood. Since cryopreservation presents a far greater potential for embryo destruction than IUDs, it's that much clearer that they would become illegal.
You simply cannot have it both ways. You cannot say that IUDs and birth control pills should be outlawed but cryopreservation should be permitted. You have made the former claim, so the latter must also be true.
Indeed, I suspect that you understand this perfectly well, and that you're just attempting to be uselessly argumentative. Certainly, every other personhood advocate seems to understand it.
Bill
There is only one reason that some of the personhood amendments have included exceptions for IVF procedures that do not cause the death of an innocent person. Organizations such as Parents Against Personhood have been telling the voters that a personhood amendment would end all IVF treatments, and the leaders of various personhood organizations around the country have attempted to overcome that misconception by providing assurances to the contrary within the text of the amendment.
Your comment about the Attorney General of Arkansas is incorrect. He did not conclude "that both birth control and IVF procedures which can potentially 'cause the death of a person' would be affected." The actual text of Mr. McDaniel's opinion can be found at http://ag.arkansas.gov/opinions/docs/2011-163.html. In that opinion, Mr. McDaniel very clearly stated that his office was not authorized to "make legal determinations concerning the merits of the act or amendment." The sole purpose of his review of the amendment was "to ensure that the popular name and ballot title honestly, intelligibly, and fairly set forth the purpose of the proposed amendment or act." In regards to IVF procedures he stated that "it is unclear precisely what procedures would be allowed and under what circumstances. It is consequently impossible for me to summarize your measure in a ballot title." In accordance with the authority of his office, the Attorney General concluded only that the effect of the personhood amendment was too unclear for him to summarize it in a ballot title. He presented no conclusion at all about whether or not IVF would be affected.
I do not dispute that some members of the Yes on 26 coalition thought that the personhood amendment would ban embryo cryopreservation. I simply recognize that they are as mistaken in that conclusion as you are in concluding that a personhood amendment would ban all IVF procedures. As I pointed out previously, the option of embryo cryopreservation would remain available under a personhood amendment as an option for preserving the life of the embryo in certain unfortunate situations.
You are very much in error to equate the intent of IVF with that of hormonal contraceptives. It should be obvious that the intent of the one is the initiation and preservation of pre-implanted embryos while the intent of the other includes the destruction of pre-implanted embryos. Randy Alcorn's book, "Does the Birth Control Pill Cause Abortions?" documents this intent very thoroughly, and you can read it online at http://www.aboverubies.co.za/bcpill.pdf.
Atlee
The following people have publicly claimed or agreed with others' statements that 26 would not permit cryopreservation: Steve Crampton (the Liberty Counsel attorney who wrote the Mississippi language) and Keith Mason (president of Personhood USA), Dr. Beverly McMillan (OBGYN, president of Pro-Life Mississippi), and Dr. Eric Webb (OBGYN, Yes On 26 spokesman).
So yes, I do tend to assume that they know exactly what they intend, and in the case of Mr. Crampton and Mr. Mason, what is legally possible. These are not random campaign members -- these are key spokespeople and thought leaders of the entire personhood movement.
Nor does this pass the test of basic logic. If cryopreservation remains an available option, there is no need or legal justification for fertilization limits like those from SB 169.
The state of Mississippi does not have the power to dictate how patients conduct their private medical treatment. That's constitutionally protected exercise of liberty and privacy rights. Personhood would mean that those rights no longer apply in the case where those rights conflict with embryonic rights, but it wouldn't completely invalidate them. If there is no conflict with anyone else's fundamental rights, the right to liberty and privacy would still apply.
There is no plausible way to claim that fertilization by itself would possibly conflict with any other rights. If I have two zygotes, making a third does not harm either of the existing two, any more than deciding to have a third baby infringes on the rights of your two born children. The only possible conflict with embryonic right to life comes when it's time to decide what to do with embryos which aren't being transferred to the mother's uterus.
If embryos can be frozen at will, and if being frozen doesn't conflict with those embryos' right to life, there can be no possible justification for imposing on patient's rights to create embryos.
Also, you're wrong about birth control. Patients' and doctors' *intention* when using BCP, IUDs, and emergency contraception is to prevent ovulation and fertilization, since this is the primary biological mechanism. Implantation prevention is an unintentional side effect, and the medical profession can't even come to consensus over it.
Ovulation and fertilization prevention are, as you yourself have agreed, perfectly legal acts. They cannot be said to violate embryonic rights, because there is no embryo to have rights. Therefore, intentions behind cryopreservation and BCP usage are equally benign with respect to embryonic personhood.
If the occasional, not-well-documented accidental side effects of one must mean that it is prohibited, the common and exhaustively documented known side effects of the other must mean that it is likewise off-limits.
Bill
You must realize, of course, that I cannot provide specific responses to vague claims about the comments of other individuals. If you would care to provide original source quotations from the individuals that you listed, then I would be more than willing to discuss the accuracy of their opinions. In the meantime, I would like to remind you of one of your own statements which can be found in the FAQ section of the Parents Against Personhood website. You very correctly stated that "A law says what it says, not what personhood advocates say in their brochures, Facebook pages, or Youtube videos."
Let me remind you once again that Georgia's Ethical Treatment of Human Embryos Act was not a personhood amendment. The limitation on IVF presented in the first draft of that bill was stated to be "In the interest of reducing the risk of complications for both the mother and the transferred in vitro human embryos." This is fully consistent with the finding in both Roe v. Wade and Planned Parenthood v. Casey that "the State has legitimate interests from the outset of the pregnancy in protecting the health of the woman and the life of the fetus that may become a child." (http://laws.findlaw.com/us/505/833.html) This limitation had nothing to do with personhood; it was based solely on the right of the state to protect its legitimate interest in the well-being of an unborn child.
This, of course, directly refutes your claim that the state "does not have the power to dictate how patients conduct their private medical treatment." As the Court stated in Casey, "The very notion that the State has a substantial interest in potential life leads to the conclusion that not all regulations must be deemed unwarranted." The Court reviewed the Casey decision in their opposition to assisted suicide in Washington v. Glucksberg, and they concluded: "That many of the rights and liberties protected by the Due Process Clause sound in personal autonomy does not warrant the sweeping conclusion that any and all important, intimate, and personal decisions are so protected." (http://laws.findlaw.com/us/000/96-110.html)
In regards to birth control, a ban on the current crop of hormonal contraceptives would not be implemented because of the intent of the doctors and their patients but rather because of the intent of the developers and manufacturers. Many doctors and most patients are ignorant of the malicious intent with which these forms of birth control are produced, and they cannot be held criminally liable for acting in good faith on that ignorance. The developers, on the other hand, have been very open (albeit in the scientific literature instead of the popular press) about the intent behind their products. Mr. Alcorn has done an excellent job documenting this intent, and evidence such as that presented in his book would have to form the basis for any ban on hormonal birth control.
Bill
Well, Atlee. It has been over a week since my last comment. Am I to assume from your silence that you have resigned from the discussion?
Atlee
No, I have simply been very busy with professional and family commitments which take precedence over internet nit-pickery.
Yes, SB-169 absolutely was a personhood bill. It declares that a "living in vitro human embryo is a biological human being". That's ascribing personhood rights to some embryos (and by extension, to all embryos, since presumably you agree that the location of the embryo does not affect its legal status).
Without personhood, the state does not have the power to forbid the disposition of a frozen embryo. Legally speaking, either an embryo is property, in which case the parents can deal with it as they like, or it is classed with in vivo embryos of the same gestational age, and Roe protects the mother's right to terminate the pregnancy and destroy the embryo (pursuant to the limits of Casey). In order for the state to absolutely forbid embryo disposition, it must first declare its personhood.
Personhood.Net agrees, and says that the first objective of SB-169 was "to recognize all human embryos as having the legal right to life and legal protection under the laws of the State of Georgia":
http://www.personhoodamendmentga.com/index.php?option=com_content&view=article&id=234%3Aethical-treatment-of-embryos-act&catid=128%3Amodel-legislation&Itemid=610
I furthermore continue to find it absolutely unfathomable that you believe the state has a sufficiently valid interest in protecting the well-being of an unborn child to justify severe restrictions on IVF in the name of reducing multiple births, but that the state would not and should not act on that interest to prevent cryopreservation.
Let's recall that the intention of transferring multiple embryos is even more benign than cryopreservation -- you're actively attempting to give them the opportunity to become babies, not just preserving them for possible later use. The absolute risks of multiple birth are far, far lower than that of embryo cryopreservation.
So you're saying that the same bill which justifies strict restrictions on private medical treatment in the name of averting relatively low risks to fetal life, somehow does not prohibit a far greater and more immediate threat to fetal life? It defies logic.
What's more, it defies your own logic. You approvingly cite Randy Alcorn's book, in which he says "The chances of the embryo’s death is in no way lessened by the
prescribing physician’s or the mother’s or anyone else’s intentions... We must never argue for the legitimacy of a course of action based on our sincerity and good intentions. We must act instead in light of the actual evidence that indicates what consequences may come from the action itself. "
As long as cryopreservation remains an option, fertilization limits cannot be justified by the state's interest in protecting fetal health. You could fertilize a hundred eggs, but that poses no threat to fetal health until you try to transfer them into the uterus. If you are free to cryopreserve any extra embryos above the number you intend to transfer, the state has no interest, because no risk exists. Your right to privacy still permits unlimited fertilization, and will continue to do so unless you are required to transfer all embryos immediately.
Tell me, Bill, do you consider that the existing legal framework, and the findings of Casey, authorize the state to forbid a woman from going through intrauterine insemination? Why or why not?
Bill
You are mistaken. The claim that a human embryo is a biological human being is not a statement of personhood but rather a simple declaration of scientific fact. Of course the human embryo is biologically human. That's why it is called a human embryo in the first place. To claim that this recognition is an admission of personhood is to claim that Peter Singer believes in the personhood of infants because he recognizes them as being biologically human. Nothing could be further from the truth, however, for Mr. Singer has boldly declared that “Human babies are not born self-aware, or capable of grasping that they exist over time. They are not persons.” (http://www.equip.org/articles/peter-singer-s-bold-defense-of-infanticide)
In regards to your statement on forbidding embryo disposition, I suspect that you have chosen the wrong word to convey your intended idea. There is nothing in Georgia's Ethical Treatment of Human Embryos Act which prohibits embryo disposition. Perhaps you intended to use the word "disposal." In which case, I will refer you back to my previous comment in which I explained the legal right under Roe and Casey which permits Georgia to pass such a law.
Your quote from Personhood.net further emphasizes the differences between the Ethical Treatment of Human Embryos Act and a personhood bill. The distinguishing characteristic of every personhood bill is the establishment of Fourteenth Amendment protection for unborn children. The Georgia bill did not make any attempt to establish Fourteenth Amendment protection. It sought only to establish "protection under the laws of the State of Georgia" and made no reference to federal law or the Constitution.
Let me point out that by merely recognizing and explaining to you the legal justification for the Georgia bill, I am not in any way claiming that I agree with that bill or that I think that similar bills should be passed in other states. I am simply pointing out the error of your claims regarding this bill. For example, you are mistaken to claim that it is illogical to state that a bill can avert a relatively low risk without placing any restriction on a much higher risk. In reality, this happens all the time, and the Georgia bill provides an excellent example. The legal codes of every state in the union are full of statements like this one found in the Georgia bill:
"Nothing in this article shall be construed to affect conduct relating to abortion as provided in Chapter 12 of Title 16; provided, however, that nothing in this article shall be construed or implied to recognize any independent right to abortion under the laws of this state."
Obviously, this statement is an admission that the Georgia bill would restrict a particular activity with a lower risk of danger to the unborn child than another activity which is not restricted but which poses a much higher risk of danger to the child. This is not illogical. It is simply a statement of the scope of that particular bill.
You are also mistaken to conclude that my citation of Mr. Alcorn's book constitutes a full endorsement of every comment which he makes in that book. I did not cite Mr. Alcorn for his legal advice. I cited him for the evidence that he presents. Furthermore, it is obvious from the quote which you provided that he is not speaking in a legal context but rather in an ethical context. There are many things which are legal but still unethical and vice versa. I personally think that the quoted statement is somewhat oversimplified, and I'm sure that I could have convinced Mr. Alcorn to phrase it differently had he sought my advice prior to publishing the book. However, that statement does not in any way diminish the validity of the evidence presented in the book, nor does it make my reference to that evidence illogical.
I agree with your claim that the right to privacy (or, to be more exact, the Fourth Amendment right to be secure in our persons and effects) permits unlimited fertilization. The human gametes are not people they are possessions. Therefore, their use is subject to the laws governing the use of private possessions and not to those governing the interactions of people. This applies equally to all forms of insemination. However, once fertilization has occurred the newly created organism becomes a human person. At that point, our interactions with him are no longer governed by the laws of private property but rather by those laws which regulate our interactions with each other.