Meeting Transcript
March 7, 2003

Sheraton National Hotel
900 South Orme Street
Arlington, VA 22204

COUNCIL MEMBERS PRESENT

Leon R. Kass, M.D., Ph.D., Chairman
American Enterprise Institute

Rebecca S. Dresser, J.D.
Washington University School of Law

Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School

Francis Fukuyama, Ph.D.
Johns Hopkins University

Robert P. George, D.Phil., J.D.
Princeton University

Alfonso Gómez-Lobo, Ph.D.
Georgetown University

William B. Hurlbut, M.D.
Stanford University

Charles Krauthammer, M.D.
Syndicated Columnist

William F. May, Ph.D.
Southern Methodist University

Paul McHugh, M.D.
Johns Hopkins Hospital

Gilbert C. Meilaender, Ph.D.
Valparaiso University

Michael J. Sandel, D.Phil.
Harvard University


INDEX

• Welcome and Opening Remarks
  
  
• Session 5: Biotechnology and Public Policy: Professional Self-Regulation.
  
  
• Session 6: Biotechnology and Public Policy: Professional Self-Regulation.
                                                             
• Public Comment
  
  

Welcome and Opening Remarks

CHAIRMAN KASS:The sessions this morning are devoted to the topic of professional self-regulations in the field of laboratory assisted reproduction. This is part of our project on the existing regulation of uses of biomedical technologies touching the beginnings of human life.

I just remind you we've embarked on this project partly growing out of suggestions in the cloning report, partly following up on our interest to see where in the existing system there is attention to the kind of ethical questions that concern this council, and we have decided to look at that intersection of assisted reproductive technologies, the growing knowledge of human genetics and work in developmental biology and embryo research.

We have in previous meetings looked at these issues as they are dealt with by IRBs. At a previous meeting we heard from representatives, from people commenting on the role of the FDA, and today at long last we have an opportunity to go to the center of the discussion, the profession and the industry surrounding this profession, which is at the center of this work, the people who work in the area of assisted reproductive technologies.

Session 5: Biotechnology and Public Policy: Professional Self-Regulation

CHAIRMAN KASS: The focus for this discussion is going to be really on professional self-regulation, a topic that is of interest to this council in more general terms because many members of the counsel and others in the public generally have held that professional self-regulation has to be at the center of any sort of regulation of these technologies.

And one heard something yesterday in Dr. Hyman's presentation when the question was, well, how are we going to deal with some of these difficulties, and the question was raised about the adequacy of medical practice in keeping up with the requisite knowledge and procedures to make sure that the psychopharmacological agents are not misused and misprescribed.

This profession, as I indicated in the memo to council members, is also subject to certain kinds of regulatory constraints imposed from without, and just to remind you, there is the Fertility Clinic Success Rate and Certification Act of 1992, which requires that the clinics that practice assisted reproductive technology supply data on the success rates, and these data are published by the CDC.

To the extent that they use various kinds of drugs and culture media, they are subject to the requirements of the FDA. The profession and industry are subject also to the Clinical Laboratories and Improvement Act requirements of quality control, and there are also in some cases some state laws.

Those things are to be understood as given, and what we really want to focus our conversation today on is how the profession regulates itself. How does it do so regarding what sorts of concerns in the name of what sorts of goods and standards and how effectively it does so; what are the strengths, and what might be the possible weaknesses and room for improvement regimen?

We're very fortunate to have help us with these questions Dr. Sandra Carson, who is the Chief of Baylor's Assisted Reproductive Technology Program and is the President of the American Society for Reproductive Medicine.

Dr. Carson, welcome to you.

We also have Professor George Annas, who is the Chair of the Department of Health Law, Bioethics, and Human Rights at Boston University School of Public health, a lawyer by profession and a person who has in the past been a consultant, an ethics consultant, to the American Society for Reproductive Medicine.

The procedure will be in the first session we will hear from Dr. Carson. We will then have discussion in which I think, Professor Annas, you're invited to participate, and then we will after a break have presentation by Professor Annas. Dr. Carson, you will join us, I hope, for that, and we'll carry on from there.

Dr. Carson, thank you very much for coming. We look forward to the presentation.

Dr. Carson, I think you have to press the button.

DR. CARSON: Thank you very much. I appreciate your invitation to be here.

Unbeknownst to Dr. Kass, he has given the information on my first slide, which was behind him as he was speaking.

(Laughter.)

DR. CARSON: So let's move right on to the discussion at hand and that is self-regulation. You have asked me 35 questions to answer in the next 40 minutes, and I think I have covered all of them, and in doing so, I would like to group them into three separate categories.

First, to discuss how we, as the American Society of Reproductive Medicine, come to the contents of our guidelines and policies, and then the policies and guidelines themselves will cover many of the questions that you asked specifically about reproductive medicine.

And then finally, I'd like to describe to you how we implement those policies and guidelines and oversee that implementation.

The American Society for Reproductive Medicine was founded in 1944 and is a professional organization of approximately 9,000 members. We are not only physicians, but also scientists, nurses, and collaborative fields that span the specialties of OB-GYN, urology, psychiatry, andrology, and embryology. And we have 25 percent international members.

Our society has four sub-societies or affiliate societies: the Society of Assisted Reproductive Technology has as its members all but 25 of the IVF programs in this country. The Society for Reproductive Endocrinology and Infertility has Board certified reproductive endocrinologists as its members. The Society of Reproductive Surgeons primarily focuses on reproductive surgery. And the Society of Male Reproduction and Urology has urologists as its members.

Membership in these four affiliate societies are overlapping, and all contribute to our 12 special interest groups and professional groups.

Our mission is primarily education, research, and practice standards, but we also advocate for patients and physicians. All of our points of mission focus on balancing the safety and efficacy of our medical procedures with reproductive therapeutic choices and patient confidentiality.

I think it's important to realize what the ASRM is not, and we are not a patient advocacy organization, although we do advocate for patients. We're also not a regulatory agency, but we do self-regulation as you'll see.

Although we don't fund research, we facilitate its conduct and presentation, and we are also not a certification body. We don't issue certification for either laboratories or practices per se.

The ASRM leadership is an executive committee, which consists of the five members of the presidential chain and the board of directors. The board of directors has six elected member and one appointed member from each affiliate society, as well as an elected secretary and treasurer. The executive committee also sits on the board of directors.

Except for the three executive committee members who receive a small stipend to defray secretarial costs, all of our leadership are volunteers. They volunteer their time to the ASRM.

Also voluntary are our three standing committees and our 26 appointed committees. Among our appointed committees are four committees which will be important today: our practice committee, ethics committee, continuing medical education committee, and patient education committee.

We're particularly proud of our ethics committee, again, all highly selected volunteers, which consists of individuals from many disciplines who are ethicists physicists, scientists, mental health care providers, lawyers, as well as member of the lay public.

One of our members, we were very disappointed, resigned to become a member of this committee, and the next speaker was once a member of our ethics committee. So these are very distinguished people that help us a lot in incorporating safety, efficacy, and privacy in all of our guidelines, statements, and policies.

Our documents begin at either our practice committee or ethics committee, and both committees review most of these documents. After the first draft of the composition, the document is reviewed by a designated affiliate society or a special interest group as appropriate. Both the publication and executive committees then review the document, and it goes back to either the practice or ethics committee for the next draft.

The final draft is approved by the board of directors to make sure that it is in compliance with all ASRM previous documents, as well as current policies.

Our documents come in a variety of forms. The committee opinions are probably -- and we'll be reviewing many of these today. Some are in your folder, and I'll point them out to you. Some I've passed out this morning.

The committee opinions are listed behind Tab 13. They're evidence based documents which comprise our practice activities.

The committee reports and statements are also behind that tab on pages 2 to 3, and the ethics committee reports are listed behind Tab 14 in your folder.

These are society opinions on definitions and procedures.

Our technical bulletins are being Tab 13, and our six to eight page presentation of a diagnostic or a therapeutic procedure. These are rarely reviewed by the ethics committee as they are usually just a statement that describes the procedure and a "how to."

Similarly, our educational bulletins, the titles of which are listed behind Tab 13, are a literature review that we write when evidence based data is not available. Again, these are about our practice activities.

We have guidelines, minimal standards that are listed behind Tab 14, and our joint reports are also issued usually with another society. Our first four joint reports are listed behind Tab 14 on page 4, and are with the American Urologic Association.

We also are currently working with the FDA and, of course, also work with the CDC to issue joint statements.

All of our documents are mailed to our members, and they're also published in our monthly journal, Fertility and Sterility. We're very excited to have a new journal gestating which will be born at our annual meeting this year. So we'll have yet another way to distribute this information to our members.

We have a quarterly newsletter, the "ASRM News," which usually does not publish our statements, but is a way that we can get guidelines and rapid information to our members.

All of our ethics committee documents and our practice documents -- excuse me -- and our technical bulletins are published in Fertility and Sterility.

We also have an award winning Web site, the address of which I've listed on the slide, can be accessed by not only our members, but also members of the public.

Our main concern in self-regulation is the goal of building healthy families. We realize that reproductive medicine is a sensitive and intimate area of life and of medicine. We work very heavily to produce well balanced technical bulletins and have become more and more reliant on our ethics committee for guidelines.

There is another procedure you might be familiar with, LASIK, which is an office based surgical procedure in which myopic individuals have their eyesight corrected with laser, a very good analogy of IVF because this procedure is usually not reimbursed by insurance. It's done in the office and can have a potentially significant side effect, blindness.

But unlike IVF, you'll see advertisements sprinkling the Sunday newspaper about how inexpensively you can get laser, without any information about its outcome or its side effects.

But we feel that the nature of reproductive medicine, as sensitive and intimate as it is, deserves the self-regulation that we give it, and perhaps LASIK isn't quite as intimate or important.

We also feel that self-regulation is important in such a rapidly advancing field because it's more adaptable in speed and innovation than government regulation. For example, as we'll see later, the CDC budget this year did not include -- excuse me -- in 2001 did not include a budget for validation of our data.

And so, therefore, our affiliate society, SART, underwrote the expense to validate the data. Once more, the federal budget did allocate funds to validate the registry, and I'll be talking about that in the third part of my discussion.

We do actively discourage some procedures. Our ethics committee guides us in this as well as our practice committee. We discourage preimplantation genetic diagnosis for elective sex selection, and I have passed out the document about this. Obviously in this short time we can't go through the specifics.

We discourage oocyte donation after natural menopause predominantly because of the risks to the mother, both physical and psychological; also the unknown risks to the child, social and psychological.

However, we are questioning whether this is a gender biased opinion. Although we would provide care to the 53 year old man who has a 40 year old wife, are we being biased in denying the reverse?

We also have new information about the risks, both physical risks and psychological risks, that the woman undertakes. So we're going to reevaluate this position this year.

We have discouraged posthumous reproduction in the absence of advanced directives, but are flexible enough to realize that there are some instances when full informed consent is present that this may be acceptable.

And we have discouraged reproductive cloning.

In our practice documents, you asked what standard we held to document when experimental medicine becomes the clinical standard, and our practice committee has determined that a clinically proven procedure would allow us to call experimental medicine the standard of care, where after extensive review by either our affiliate society practice committee or our ASRM practice committee, there's proven safety and efficacy.

These committees review all of the existing literature, heavily relying on randomized clinical trials, of course, and if safety and efficacy of a therapy is proven after at least two peer reviewed published studies by different investigator groups shows the risk-benefit ratio to be acceptable, then our committee will elevate the procedure from experiment to practice.

ICSI is one such procedure that does carry inherent risks, but has been deemed by our committee as no longer experiment, but yet having known risks.

These risks should be, of course, explained to the patients, as we do. The first is that there is a higher sex chromosomal abnormality rate, about .8 percent, in those babies born after ICSI compared to the live born population, about .2 percent.

The Bailey developmental scale in ICSI babies, if you will, lags behind those of fertile control at one year of age, but is similar at two years of age.

In addition, if a man has an absent vas deferens because he carries the cystic fibrosis gene mutation, this mutation may be passed on to his offspring after ICSI, as would a Y chromosomal deletion that can also be heritable.

Therefore, our committee recommends that genetic counseling in couples with identified genetic disorders be conducted before these couples proceed with ICSI.

The practice committee reports have also looked at pre-implantation genetics diagnosis and blastocyst production and transfer and feel that there's enough information for clinics to proceed with these two procedures.

I've also passed out those documents to you.

The practice committee has discouraged procedures, such as IVIG for recurrent spontaneous abortion, as well as measuring antisperm antibody titers before IVF because these procedures are ineffective, and therefore, these documents never made it to review by the ethics committee because they're nonefficacious.

However, we would think that they probably are ethical if they would work.

Now, you've asked me particular questions about many of our procedures which are listed in the contents of our guidelines and policies, and I would like to go through now and address the specific questions that you've asked.

But let me first say that our overall concerns are providing families with healthy children, healthy parents, and also healthy third parties that may participate in the reproductive process. This is especially important that we maintain patient confidentiality and reproductive choices for these couples.

A document that we have, again, that I passed around to you list the elements of informed consent that we ask our members to give their patients prior to assisted reproductive technology. Of course, all consents, like the standard surgical consents, should be in writing, signed, and witnessed.

They should give patients information about the alternative procedures, as well as a description about the procedures itself, including the efficacy and the risks not only to the patient, but also the possible risk to the subsequent child.

We recommend that our members disclose the financial obligations. These procedures are expensive, and that they also discuss nonmedical therapies, either pursuing a childless marriage or adopting a baby.

In addition, we require that our members inform patients in writing of the federal reporting requirements. Because of the widened law, as Dr. Kass had mentioned, all of the IVF procedures in this country need to be reported and are reported with a personal identifier that has been given the highest federal confidentiality status, the 308(d) status.

Patients do, however, have an option that they may refuse their outcome reporting to be linked to their personal identifier. However, this must be noted in the informed consent.

We also require that programs have patients write the documentation of their choices for their embryo disposition, and we'll be talking about that in the next few slides.

Behind Tab 16 is our document which lists the minimal standards for IVF. This document, as you can see, is quite extensive. It goes over the personnel required for an IVF team. It goes over the training for physicians, embryologists and technicians. It talks about laboratory facilities and quality assurance, giving individualized procedures for the measurement of toxins and compositions of even the water that goes in IVF media.

We require maintenance on all laboratory instruments and techniques be done every six to 12 months by a certified individual, and all of the embryo tanks which store cryopreserved embryos should have an alarm on it in the case of power failure and emergency power on all of our equipment that stores human embryo.

The standards also include safety standards for technicians and patients, including double verification of identity.

In addition, we are concerned about the safety of those embryos. We require that non-powdered gloves be used; that the laboratory be a clean room, that is, this is the ceiling of our own laboratory, having both a fluorescent and an incandescent light. When the embryos are out, all fluorescent lights are extinguished.

The room is 95 percent HEPA filtered compared the 80 percent HEPA filtering of an operating room.

All aspects of patient care, quality control, quality assurance, and minimal standards are recorded. You can see scenes from our own laboratory. The microscope, centrifuges, and refrigerators all have flow sheets and are checked both at the beginning and the end of the day and quality records kept.

All of these records are stored, and they're gone over by our inspections of our laboratory by the certification procedures outlined by the College of American Pathologists, CAP, and ASRM.

The guidelines and standards we have for gamete and embryo donation are listed behind Tab 17, another large document which we can't go over in detail this hour, but lists the indications for gamete and embryo donation, the screening and evaluation for the donors, the counseling for donors and recipients, the elements of the informed consents, and the management of each procedural type.

Among our documents are also an ethics committee report discussing the financial incentives for the recruitment of oocyte donors. This document is behind Tab 198. The document points out that a program does have specific responsibilities to the donor, the oocyte donors, including insuring coverage for treatment for any medical complication that might occur, and also having psychological services available for donor consultation.

We require that all advertisements for donors be accurate and not misleading, and for those institutions who use an independent donor agency, that is, a lot of agencies have been born that have only oocyte donors who provide oocytes for a number of programs not only in their area, but nationally; we require that our member program check those agencies and make sure that they adhere to ASRM guidelines. Our members are not off the hook, if you will, for making sure that these women have the same screening and the same informed consent as their own local donors.

The financial incentives given to the recruitment of donor oocytes poses a number of possible risks. The issues include being fair to the donor and also being sure that we don't devalue human life by allowing oocytes to become commodities, and both our ethics and practice committee has addressed these issues.

They don't want to set the price to high, however, because this poses the risk of possibly providing inaccurate medical information by the donor, and also if the price is too high, we're fearful that the donor might not really consider the significant medical risks that this procedure may entail.

We also don't want to promote certain traits as desirable and worth more money, which may ultimately lead to an objectification of children who have intrinsic dignity and worth. So we are very careful about this.

And our ethics committee came up with the following guidelines. First, let me take a step back and explain to you that there are two ways that a woman may receive or may be an oocyte donor and receive compensation.

The first is to defray cost for her own in vitro fertilization program. For example, if she is infertile but cannot afford IVF, it's possible that she may give a portion of her eggs to another woman and have the other woman, the recipient defray the donor's cost of IVF.

And in this procedure, our ethics committee has recommended that if about 50 percent of the oocytes should be shared and a 50 to 60 percent of the cost of the donor IVF then be defrayed.

Probably the most common oocyte donor remuneration, however, is that to the oocyte anonymous donor, the woman who is fertile and willing to share her fertility with another infertile couple.

The payment is not for the oocytes per se, but for the inconvenience, physical and emotion demands that the procedure entails. And in order to come up with this, our ethics and practice committee has correlated donor oocytes with donor sperm. They've estimated in 1993 that it takes about 56 hours for a woman to donate oocytes compared to one hour for sperm donation.

In 2000, the average sperm donor was given about 60 to $75. Therefore, multiplying this out, this would lead to about a $4,200 compensation for oocyte donors. Therefore, our committees recommend that oocyte donors be paid compensation of up to $5,000, and those paid more than $5,000 should be justified in writing in the medical record.

Also, payments above $10,000 our committees feel is inappropriate.

These are our 2000 guidelines, and of course, these are going to be reviewed at either this or next year.

Many oocyte donors enjoy the experience and like to help other people and would like to do it more than once. We have to, in allowing repetitive oocyte donations, have to take into consideration the safety and well-being of the donors, and again, I've passed out this document for you about our practice committee opinion.

Probably the most important risk that is somewhat unknown is the risk of inadvertent consanguinity. Our recommendation from the practice committee is based on the 1993 standard regarding sperm donations when a somewhat arbitrary limit of 25 pregnancies per donor per 800,000 population was recommended as the mathematical risk to avoid inadvertent consanguinity.

Therefore, our practice committee has recommended that oocyte donors be limited to less than six aspirations, to decrease any medical risk of the procedures, as well as be limited to successful donations to fewer than 25 families.

We also have patient counseling documents from our patient education committee. These are in the form of both patient fact sheets and brochures that are available on our Web sites, and I encourage you and invite you all to visit our Web site to see how the patients view these.

Our most recent patient fact sheet details the challenges of parenting multiples, including psychological, social, and economic issues.

You've asked me to detail to you our recommendations for the numbers of embryos that we recommend be transferred at IVF, and these are listed behind Tab 22 and come from taking into consideration the risks both to the mother and to the children.

We recommend that the numbers of embryos transferred be written in the medical record and patients be provided informed consent.

We also recommend that each program individualize their number based on their own rates of multiple pregnancy and pregnancy success.

We also realize that each program will have individual differences in their patient population and that the number of embryos transferred should vary from program to program based on patient characteristics.

But, in general, with a favorable prognosis, we recommend two fresh embryos be transferred on day three or three cryopreserved embryos; with patients who have an average prognosis, four embryos; and with a poor prognosis, five embryos.

Prognosis is mainly based on patient age and the presence or absence of male factor infertility.

Patients who have embryos in excess of the numbers transferred have the option of cryopreserving their embryos for their next baby. They should all be provided, of course, written, signed, and witnessed informed consent and be told of the alternative cryopreservation, and that is donation of the embryos to another couple or possibly to research.

The ASRM realizes that each state has definitions of embryo abandonment, but we recommend overall, in general, that if a couple does not have any contact with the program for five years and the program has reasonably tried to contact the couple over this course, then these should be considered abandoned embryos.

The program has the option to discard them or if they have prior consent from the couple, the embryos may be used for research protocols, of course condoned by the institution's research review board, but they should not be used in any case for stem cell research.

Currently SART and the RAND Corporation has in press a survey of the IVF clinics in the United States to estimate the number of cryopreserved embryos currently in the United States in our member clinics. This will be published, I believe, in August in Fertility and Sterility.

No, I do not, but look April -- I mean August Fertility and Sterility. We'll be able to.

I apologize for this term. It's hard to come up with a term for the embryos that are not donated to another couple, that are not being donated to the couple and not cryopreserved, and we term these "spare embryos."

Our ethics committee report for donating spare embryos to research is behind Tab 20 in your folder.

Our ethics committee, from among the choices comes from the perspective that embryos are potential human beings worth special respect, but not entitled to the same rights as persons. So with this in mind, they have determined that embryo research should not be conducted longer than 14 days after fertilization. There should not be buying or selling of embryos; that the research should be worthy research with some potential significant outcome using the smallest number of human embryos as possible, of course under the auspices of an IRB; and the investigators are also told to document that they have no satisfactory alternatives to using human embryos.

It is recommended that embryo research be conducted on cryopreserved embryos. So the couple has a full decision to make the donation without any other emotional or interfering aspects. What the ethics committee realized, however, is there might be instances where fresh embryos are available, and that the couple no longer wants to proceed with an embryo transfer of fresh embryos.

For example, this might be if the embryos themselves are abnormal. Also, in the event of any future tragedy, such as divorce or death.

In either case, the decision of donating spare embryos to research must be made by the couple after their decision not to cryopreserve them or to donate them to another couple.

In addition, both partners must agree.

The informed consent, we feel, should be obtained by a person other than the researcher or the fertility doctor taking care of the patients. The risk and benefits should be explained to include delayed regret of embryo destruction, and the patient should know the nature and the purpose of the research.

The patient should also be assured that their status and their care will not be affected by their denial to donate embryos to research, and our committee has also gone to include some points about embryos donated for any future stem cell research, and that is they feel it's important that the couple be known that their identity in the course of stem cell research may be uncovered, and that their cell line, even though the inner cell mass will be destroyed, the cell line may live indefinitely. There may be a possible commercial value to these cells, and that confidentially must be insured with identifiers.

You've also asked that I review what documents we have regarding the safety and risks of ART. Of course, in all of our documents we cover safety, efficacy, and privacy as I've shown you.

Also, this year both the ASRM and SART practice committee have reviewed the articles looking at IVF and birth defects, and the review is pending publication in Fertility and Sterility.

The major problem with these studies is that the control group consisted of fertile individuals rather than infertile individuals. So it may be the infertility itself that is increasing the risk of offspring in this group rather than the procedure.

The ASRM/SART/CDC registry, which the 1999 births are included in your folder. I have brought with me the 2000 registries for your perusal, and I'll pass it around for you.

This registry does collect congenital anomalies of IVF and ICSI births. However, it is a non-rigorous collection. The data that we do collect we feel is inadequate to come with a truly scientific evidence based review of the birth defect risks. It's a start, but it's not the best we can do.

The best we can do would be expensive, and this is nonfunded. Not even our registry is really funded. So we would be willing and very excited to take on the task, but would need federal funding to do it; would have to have neonatologists examine these babies; would have to have epidemiologists come up with study designs and assess the risks and help us with this; and we would also, of course, have to have statisticians and child development specialists assess these babies later.

We do have ICSI follow-up studies in progress, and we are trying to collect data, and again, with a larger budget, we could get very rigorous data.

We participate in several international registries of both IVF and ICSI data.

Now, finally, I would like to review with you how we implement these policies and the oversight which we use to make sure that our membership are following our guidelines.

First of all, our ART registry began as an ASRM initiative in 1985. We reported in Fertility and Sterility in 1998 the very first IVF registry in the world. We had 41 centers reporting, and there were almost 3,000 IVF cycles. The pregnancy rate per cycle was 17 percent in 1986. The chromosomal and congenital anomalies were reported in this issue.

In 1992, as Dr. Kass stated, the Fertility Success Rate and Certification Act was passed, and this led to the registry. This is the current registry published this year, 2003, of the 2000 cycles in the United States, and every clinic in the United States, every SART member reports how many patients they did, the births, and the multiple births.

And there is no other country that actually you can look up to see the individual clinics and their success rates.

This is funded mostly by SART, but also has some funds for validation by the federal government, and publication is, of course, funded by the CDC.

This registry now includes over 99,000 cycles. There are 383 reporting clinics and 25 non-reporting clinics. The live birth per aspiration rate is now almost 30 percent. The multiple pregnancy rate is about 31 percent.

We implement our guidelines and policies by essentially two techniques. One is by laboratory inspections. Our laboratories are inspected by a team from CAP/ASRM very three years, and the inspector looks at all of the records and quality assurance and control procedures and all of our consent forms that I showed you on a previous slide.

I've brought with you our own laboratory, which has been inspected this year, and we passed, and although I don't want this in the public records, just for your own information, you can review this, and I'll pass this around so that you can see the detail that this eight hour inspection conducts. And I'll pass that around for you.

We also conduct on-site validation. There are ten teams of validators consisting of members and non-members and members of the CDC that go to 30 programs each year and look at all of the charts from the live births, as well as 60 random charts from each program.

This is the program that was not funded for the 2000 cycles from the CDC. So SART incurred the expense to participate in self-validation. What we did was asked our member programs to submit their names, and we randomly gave them numbers from their reported data of ten charts that they were asked to go over and validate themselves and then report to us their results and error rate.

And interestingly enough, the same error rate from on-site validation occurred in our self-validation. The CDC was quite impressed with this procedure. It was completely SART funded and represented 62 percent of the over 99,000 cycles conducted in this country and felt that the technique was appropriate and agreed, therefore, to go ahead and publish the 2000 results.

Our SART oversight committee looks at the reports of the validation site visits, looks at all consent procedures, and makes sure that the IVF programs, the member programs in this country, are adherent to all ASRM/SART policies.

Their advertising subcommittee checks advertising violations which are listed behind Tab 21 in your folder.

SART is not a punitive society. They focus on education and correction. The committee reviews found that most errors are really human errors. They don't feel that there has been really any effort to be deceptive on the part of the clinic; that most of these are human errors or consent errors.

SART encourages correction, of course, and education for where the error occurred. Each program has one year to correct the mistake and implement new policies. SART offers voluntary training by a SART member at the program's expense, and if the procedure is not corrected in one year, then the program loses SART membership.

Thirty-one programs over the last five years have lost SART membership. Seven of them were in the last year, and most of them lose SART membership because they fail to report to the registry.

There's an occasional program with an advertising violation and also a lab accreditation failure. SART does require CAP/ASRM laboratory accreditation to be a member.

Many of the programs have been reinstated into the organization, and this year SART is also instituting a training program for programs that fall below the 95 percent confidence limits of the registry outcome. In 2004, this will be mandatory training.

The compliance to the guideline is largely adhered to because of the effect it has had on patients and insurers. This registry is available on the CDC Web site and patients avoid programs who don't report.

In addition, many insurance companies who do reimburse for IVF do not reimburse non-reporting programs.

And finally, patients are becoming more aware of SART membership, and when SART membership is revoked, it sends a message to both patients, as well as colleagues that perhaps there's something wrong and is a powerful incentive for programs in this country to adhere to our guidelines.

We can also look at the effect of guidelines in the multiple pregnancy range. In 1997, almost 61 percent of IVF births or -- excuse me -- ART births resulted in a single pregnancy with seven percent resulting in a high order pregnancy.

In 2000, the singleton rate has gone up to 65 percent, and the high order multiples down to about four percent. This isn't perfect, but we think it is efficacious, and with further enforcement, we hope to see the singleton birth rise even further.

There are, of course, some disadvantages to self-regulation in the registry, and the first is that it's a direct cost to the patient. The validation is not reimbursed. So self-validation is voluntary and has to be paid for by members, which is ultimately passed on to the patient.

In addition, a very serious concern is that the clinics themselves could accept patients and change their guidelines to appear more successful, and that's why we encourage clinics not to compare their pregnancy rate outcome with others in the SART registry because some clinics may refuse to do IVF on patients with a low FSH, that is, a low ovarian responsiveness. They may limit the number of patients with male factor infertility or patients of older ages so that their rates are higher due to their patient characteristics.

Now, you've asked me to compare our registry and our self-regulation with particularly that of the U.K. Now, the United Kingdom has the Human Fertilization and Embryo Authority, which licenses IVF programs and licenses their research. They do allow embryonic stem cell research and have licensed clinics to do it. They limit the embryos transferred to three, and all IVF is government supported and regulated. They pay for IVF, and they regulate it. They pay for embryo research, and they heavily regulate it.

Let's look at their outcome. Now, interestingly enough, it's very difficult to get the outcome. They do not have clinic specific reporting as we do, and their reporting doesn't every year report their multiple pregnancy rate. So I can only compare for you their 1998 multiple pregnancy rate and pregnancy outcome, and I've compared it with our 2000 rate. So it's not quite the same comparison.

But you can see that our baby per cycle rate is much higher than that of the U.K. Interestingly enough, our high order multiple pregnancy rate at four percent is higher than their high order multiple pregnancy rate at two percent, but I wonder if this decrease is really worth the substantial decrease in pregnancy rate. Again, they're paying for this treatment.

Now, Europe itself does have a registry. Seven countries in Europe have a national register, and others voluntarily register. This data is extracted from last year's publication of ESHRE, the European Society for Human Embryology and Reproduction, and the numbers aren't exactly correlate because they report their data differently, but you can see that the European pregnancy rate per aspiration is about 24 percent. Our pregnancy rate per cycle is about 31 percent.

Now, if we were to use the same units here, our rate would be a little bit higher because some of these cycles never went on to aspiration, but you can get a rough comparison that our IVF tends to be a bit more successful.

The high order multiple pregnancy rate, again, in this country is four percent, in Europe about two percent, but again, their pregnancy rate is lower.

So we do believe in self-regulation. We work very hard at it, and we're very proud of what we've accomplished, but we also realize that there are continuing challenges, and we're very excited to be here, and I'm particularly excited to be invited to hear your discussion because we realize these are very complex issues, and we would like your input about whether we're asking all of the right questions.

I've showed you many of our documents. I've listed in the handouts many of our documents. Is there anything? What areas are we missing? What do we need to further address?

We realize that the United States is a diverse population. There are many ethnic groups, many religious groups, many races, and we have to come up with policies and guidelines that address and respect all of these differences.

Do you think we're including all of the right people? Are we addressing all of those concerns that we should be? We'd like to have your input from this.

And finally, we realize that we don't have taxpayer dollars for this, and we wonder if we're making it available to enough patients, but in doing so, are we presenting an undue burden on the infertility population?

I don't think you can find the outcome of prostate surgery or the outcome of LASIK or even the treatment of heart disease overall, let alone physician or clinic specific countries. By doing such a complete job, are we putting undue pressure and burden emotionally and financially on a select group of patients with one specific disease?

I look forward to hearing your discussion of these and other issues, and thank you very much.

CHAIRMAN KASS: Dr. Carson, thank you very much for a comprehensive and very responsive presentation.

DR. CARSON: Thank you.

CHAIRMAN KASS: I really appreciate the care that you have given this.

The floor is open for discussion. Michael Sandel.

Do you have a microphone, Mike? Yeah.

PROF. SANDEL: Thank you.

I have two small questions of information. The first is you said that you recommend against PGD for elective sex selection, and my question is: do you also recommend against sperm sorting for elective sex selection? And is Microsoft the company that does this a member of your group? Microsort.

(Laughter.)

DR. CARSON: We do not. We do have a guideline, and I have a copy of that. If you're interested, I will give it to you for preconceptual sex selection, and we do not actively discourage preconceptual sex selection, but do have particular mandates for the use of it, and that is that it be used only for family balancing, that the couple realize that it may not be successful and warrant that they will still take care of the child of the undesired gender; that they realize the possible, of course, possible complications that may arise; and that we also recommend this only if a technique becomes available that is documented safe and efficacious.

I do not believe that our practice committee or our ethics committee has felt at this point that the Microsort technique has fully documented efficacy and has recommended at this time that that still be under the auspices of an institutional review board.

PROF. SANDEL: Is that company a member of your group?

DR. CARSON: I do not believe that it is, and we don't have -- we do have a corporate membership, but they are not specifically ASRM members, but to my knowledge, they are not.

PROF. SANDEL: Thank you.

The other question I had had to do with the financial incentives, the way you arrived at the cost guidelines for the payment for the oocyte. The way you did it I was intrigued by this. You took the market rate for sperm and multiplied by 56 the number of hours for the oocyte donation.

Why did you do it that way rather than the other way around? Why didn't you take the market rate for oocytes up to $50,000 and divide by 56 to get the permissible rate for sperm sale, which would have given about $1,000 per sperm?

DR. CARSON: Well, the reason that we didn't do it the other way around first is because when we did this, there was no real market rate for oocytes. This was first initiated in 1993, and I believe the first sperm donation was actually in 1840. So we had a little bit longer experience and much more data on the cost of sperm.

I'm glad you didn't ask about time though.

CHAIRMAN KASS: Mary Ann Glendon.

PROF. GLENDON: Trying to get a full picture of the different methods of regulation of these procedures, I'd like to ask you about, without indicating any approval on my part of what some of my fellow lawyers do. Tort lawyers sometimes think of themselves as providing a kind of regulatory system for areas that are primarily self-regulated, and I wonder if your organization keeps track of litigation in this area, and if you do and if litigation has in any way influenced the structure of your self-regulation. That would be one question.

And the other would be where does litigation concentrate. Does it concentrate of personal injury issues or on consent issues? Can you give me a picture of that?

DR. CARSON: Well, litigation primarily right now is involved with family law and regulation about the third party reproduction and the processes and who the rights of the third parties, the rights of the gestational surrogate, the rights of the ovum donor, as well as the rights of the child whose heritable -- whether frozen embryos are property or not, and most of the litigation I would say is involved with that.

Of course, there is professional liability suits, although -- and we don't -- at ASRM we do keep a tabs on all of our states and the litigation occurring at the state at any federal level. We have in our ASRM newsletter an actual review of the cases. We have a column which looks at all of the cases that are coming up.

We do not have a review of the professional liability cases, which I believe actually in this area are quite, quite low, and we think that it's because of our self-regulation. Our documentation is really quite extreme, and the informed consent, our own informed consent is 20 pages long, and it's a quite detailed informed consent, and we think that the medical liability is actually limited because of our self-regulation.

At ASRM we don't keep a list of those, but we do follow the other laws and let our members know at the states.

We also have a legislative committee, a legislative and government regulations committee that follows these in all of the states so that we have an idea.

CHAIRMAN KASS: Mary Ann, please.

PROF. GLENDON: When you talked about the informed consent, you said that there is very little evidence of any causal relationship between the treatments that are used to encourage the production of oocytes and cancer. Could you say a little bit more about that?

I mean, have there been claims that there is such a connection, and what is the evidence?

DR. CARSON: Yes. There are a number of studies that seem to correlate ovulation induction and infertility with, quote, infertility treatment. The initial study was -- I believe it was the first study -- was an epidemiologic study from cancer that just looked at treatments of infertile women with drugs and subsequent development of ovarian cancer, and they found that there was an increased risk.

But they didn't talk about what treatment, and they didn't describe length of treatment or the disorder causing the infertility.

Subsequent studies have looked at particular drugs and particular diagnosis, and our practice committee has reviewed all of these documents and felt that there was no substantial evidence linking ovulation induction drugs used in ART with subsequent cancer.

There may be some link between the use of one of the oral agents, clomiphene citrate, with an elevated risk for ovarian cancer; also, some indication that actually using this drug long term may actually protect against breast cancer, and the reason for that probably is this drug is very similar to Tamoxifen. It is an estrogen receptor modulator and has some protection against breast cancer, but there is some hint that use for longer than a year might increase the risk of another cancer.

CHAIRMAN KASS: Bill May, then Rebecca.

DR. MAY: You mentioned that the ASRM overall concerns are healthy children, healthy parents, and healthy third parties, but your panel on safety risks of ART mentioned the fact that the registry gathering information on anomalies and so forth is nonrigorous, expensive, and nonfunded. So one worries somewhat about the degree to which concern for healthy children lags behind in terms of the kind of funding that you can do.

Do you feel there should be some collaboration with federal funding here to help bring up the strength of this concern for healthy children in what you do?

DR. CARSON: This is one area that I think would benefit us all greatly, is to have a federally funded program that looks at very rigorous data collection, and I mean right from the beginning.

I mean, do we call a birth defect an extra finger or are we only concerned about serious, life threatening defects, for example, heart defects? There's a range of birth defects that one might consider, and we need to begin with, first of all, deciding what we're going to look for; second of all, who do we count? Who do we use as a surveyor?

You can see where -- well, I would think that an exam by a neonatologist and a geneticist in a medical center, university related in Chicago, might be different from the nurse-midwife examining the baby or a family practitioner in a small town in southern Illinois.

And so the birth defect detection rate would be different from those two people. So how are we going to -- we would have to have funding to get the same level of examination out to all areas of our country, and that's some of the funding that we're talking about.

DR. MAY: So making good on the first of your concerns, that is, healthy children, is something that really has to be worked at.

DR. CARSON: And it will be expensive. We can do it. You know, we have started to do it. We can, of course, always do it better, but it would be very expensive.

CHAIRMAN KASS: Could I just quickly follow on this?

I mean, if I didn't misunderstand, you have indicated that the use of preimplantation genetic diagnosis is now somehow an acceptable procedure, that you're recommended this.

DR. CARSON: The practice committee has looked at preimplantation genetic diagnosis and felt that there is enough data to offer it in the practice setting, and most programs who do preimplantation diagnosis, however, are still going to their local institutional research boards and doing it under the auspices of an experimental program.

But our practice committee does condone its use for medical disease.

CHAIRMAN KASS: Yeah, but we had some presentation, if I'm not misremembering the data that there are roughly 1,000 children born worldwide after the use of this procedure, and even in the absence of federally or other source funding of the outcomes of this, could you say that an interest in the question of the health and safety of the children born following this procedure has been adequately studied for a society that cares about the health of the children born with this procedure to say this is now ready for prime time?

DR. CARSON: Well, I think that our practice committee has -- and I did pass out the document that our practice committee has circulated, and we have, again, recommended that couples have genetic counseling, know the risks of PGD, and also know the chances of success.

True, about 1,000 children have been born after this worldwide, and we would be able to be more certain if we had 5,000 children, but the diseases that we are using this for are quite severe, and I think that the practice committee thinks that they have enough evidence of the incurred risks that we can inform patients of what that risk is compared to their severity of the disease, and the benefits for them would be significant compared to the risk of the procedure.

CHAIRMAN KASS: To follow on this? Yeah, Bill Hurlbut and then we'll come back to the queue.

DR. HURLBUT: As just a paradigm of this, can you tell us what kind of animal studies were done in PGD before it was initiated in clinical trial?

This is a broad question because it's not clear to me how much anticipatory research is done in things like ICSI. Maybe you can include ICSI in this, too.

DR. CARSON: You know, I really don't remember right now the animal studies that were done prior to PGD. I just don't remember that data. For ICSI a number of programs like, for example, our own program requires that all of our ICSI technicians be trained on an animal model prior to doing exams on humans.

The number of animal studies performed with ICSI, I don't believe that there were a lot of animal studies done, but, again, I'm not sure. You know, some of the -- unfortunately some of these techniques don't have an animal model. It's hard. There are very few animal sperm that actually even look like human sperm, and the fertilization techniques in animals are quite different than in humans, and many times we don't have an animal model.

I don't remember the information that you're asking me.

DR. HURLBUT: Well, it seems to me that the degree that you keep assisted reproductive technologies as natural as possible, that's going to be safer. I mean it just seems like a logical equation. It's when you take the situation of ICSI and contrast it to what you might call the sperm marathon with 200 to 300 million sperm competing for fertilization. It seems to me that there would be a logical concern there that you might be bypassing a normal filter of nature and, therefore, it would seem logical that if this is going to be responsibly self-regulated that there be some concern about this and wherever there was a possible animal model, it be done.

And certainly they can do ICSI with other species, right?

DR. CARSON: Sure, we can do ICSI with other species, but we can't necessarily detect the same outcome, but let me go back and say that, first of all, in vitro fertilization is not natural. The eggs are taken out of the body. They're exposed to light; they're exposed to chemicals; they're exposed to a very non-natural environment. This is far from natural.

And I think that it's important that we make sure we realize that because we have to build in the natural safeguards ourselves to prevent some things that may occur that are hazards.

Now, with ICSI, your concern is well taken, yes. We lose the natural barrier that the egg has against abnormal sperm, and we see that in the results that I've presented to you. Nature has, for example, the cystic fibrosis heterozygotes can often have an absent vas deferens, and by doing ICSI we bypass that natural occurring barrier to fertilization and we put at risk the subsequent progeny for carrying that mutation, and it's important that patients be aware of that and be adequately counseled.

And some patients after hearing that avoid the technique altogether.

CHAIRMAN KASS: Let's go down in the queue. Rebecca.

PROF. DRESSER: I wanted to ask her questions. I was on the ethics committee. If people are interested in the internal workings of that, I'd be happy to answer, and I know George would, too.

And I was the primary drafter of the financial incentives paper, but you should understand these are group documents, and they normally took four or five years to get through and then, of course, the other levels of review occurred as well.

Anyway, it might not be --

PROF. SANDEL: So you're not responsible for the one hour figure. Is that what you're saying?

(Laughter.)

PROF. DRESSER: Well, that was actually from the literature, that aspect of it.

One thing I thought might be helpful is to put this in the context of other areas of medicine and how areas like critical care, genetics, pediatrics deal with their own ethical questions.

And I was on the ethics committee for the American Academy of Pediatrics for eight years, and it is a similar model with its advantages and drawbacks in that there are, you know, resources devoted to paying the expenses at least of people to sit around and try to work through some of these ethical problems and eventually issue documents that have some consensus basis from the membership at least of the participants in the policy making.

And then they're published and you cross your fingers that some people might read them and pay attention to them, and in a way it's a similar situation to our council, our cloning report. You know, we did the best we could, and we put it out there, and we hope that people pay attention to it, but it does have limited impact, I think.

So I think that what ASRM is doing is quite similar to what other areas of medical practice do, and in fact, it's probably more detailed and comprehensive than a lot of other areas of medical practice.

Another dimension of this is that SART is more like an accreditation body in that it does have a validation mechanism at least for some of the policies.

Now, I was interested to hear you say that the validation visits involve all of the policies of ASRM because I wondered if people are asked whether they adhere to the ethics statements. I wasn't aware that that was part of it.

And I know one of the frustrations that we had was, for example, our document said any amount over $5,000 should be justified, and by that we meant if somebody has to spend more time in the process and so forth. And heard last year that several legitimate programs were now offering 7,500.

So I wonder if there has been any effort to push people to adhere to those policies and whether you think there should be.

And finally, whether there are perhaps some intermediate steps that could be tried to encourage implementation, such as asking people when they join ASRM to sign a statement that they'll make a good faith effort to follow these policies or require some sort of submission from membership saying, "Here is how we handle these issues," and tell people if they're way, way out, you know, you're not going to be considered eligible.

There is, I think something that's different in this area. There's a kind of a gray market certainly with the payments that are made. The women who are recruited to provide eggs through the advertisements, that's normally through a broker or the couples themselves, and then they come into the clinic, and as you said, the policies say the people at the clinic should make every effort to ascertain that, you know, huge fees are not being offered and so forth.

But there's a limited amount of control, and so there's this gray market here, and then there's the ASRM good citizens who are trying to follow the policies over here, and there is a limited control of the gray market that you have.

So in any event, I just wondered if you could comment on some ways that might increase the ability to implement the policies at least of members, and then there's the whole other issue of the people who don't belong, right, who don't have to follow?

DR. CARSON: I have written down some. I hope I get all of them.

First of all, SART, our validation is to go over all of our guidelines, and again, these are guidelines that are important not as an absolute number, but as a guideline to look at, and if they are not followed, a justification made.

For example, there may be -- let's take just for an example, an instance where a donor is from out of town and a family wants her to donate eggs for a second child, and an arrangement is made to reimburse her because now instead of 56 hours, she's having to travel, having to take off time at work, and that is going up to 100 hours.

Well, in those circumstances, fees above $5,000 may be a given, but that needs to be justified in the record. So, again, the committee has recommended justification.

Now, we've heard reports that on the Internet there are some $40,000 being offered to egg donors, and we don't have any evidence that this has actually occurred. You know, you can do anything on the Internet, and I don't know how any regulation, self-regulation, federal regulation are going to control the outliers like that. But, again, we don't have any documentation that our members are doing that.

For the embryo or for the SART membership, we think that there's a fairly powerful peer motivation and peer pressure to adhere to guidelines. Our SART membership policies or our SART membership is revoked if the policies aren't followed, and if we find anybody.

Members can report and, believe me, do report to a validation and oversight committees of infringements of these policies, and again, our attitude is towards correcting them rather than just being punitive because we feel that if we correct them, then it will be better for everybody.

There are 25 clinics in the United States that don't report and are not SART members. Again, luckily it's not a large number, less than ten percent of the programs, but we would like them to follow our guidelines and get in the fold, too, because it's 25 less we have up there.

In terms of -- what else did you ask? Oh, about signing the consent form. Well, again, we would rather have members come to ASRM and come to SART, participate in the meetings, participate in our committees and be educated and hopefully want to follow the guidelines. I think that, again, SART clinics, SART members do follow these guidelines, and we feel being inclusive and getting them in rather than trying to exclude them or making membership conditional is probably better than giving our guidelines out to the most people and having them follow it.

So it's a little bit a difference in philosophy. Maybe that's not right.

CHAIRMAN KASS: A quick clarification on the general point. The inspections or on site validation procedures do cover the adherence to the ethical guidelines?

DR. CARSON: They cover all of the guidelines, and our guidelines are both from our ethics committee and our validation committee.

CHAIRMAN KASS: But they include that?

DR. CARSON: So they do include those as well, correct.

CHAIRMAN KASS: So that these validation visits would disclose whether or not, for example, a particular member clinic was adhering to your recommendation that PGD for sex selection be discouraged. You would know that from such visits?

DR. CARSON: I can't answer that specifically. I would assume so. They would know that, for example, PGD is being done as a clinical procedure or under the auspices of a research guideline.

I would assume they would also know if it's being done for sex selection because of this, but I haven't read the questions that they asked. So I can't answer it specifically.

CHAIRMAN KASS: But that's one of the -- if I remember the list of the things that the society sort of discourages as by way of practice.

DR. CARSON: Right.

CHAIRMAN KASS: I guess one of the questions, a general question is the effectiveness of these recommendations, and the oversight and "enforcement" may be too strong a word since you prefer really to encourage people to change their ways or to be reeducated in terms of compliance, but I guess one of the questions always about professional self-regulation is how much does it depend upon the goodwill of the compliers, and what do you do about those who, in fact, choose to go their own way.

DR. CARSON: I can say that none of our member clinics are doing preimplantation genetic diagnosis for elective sex selection that we know of, and we survey as best we can.

CHAIRMAN KASS: Thank you.

I have Paul and then Gil and then Robby.

DR. McHUGH: Yes. Thank you for that thorough and data rich presentation.

I was struck by your use of the word "enjoyed" at one stage about particularly the oocyte donors. I want to pick up on that in three different ways.

The first thing is it's hard to imagine anyone enjoying this kind of harmonal treatment and laparoscopic invasion, and so could you tell us what are the complications that rate amongst the oocyte donors, for one?

The second thing is: how many abortions follow artificial impregnation, artificial AIT impregnation?

And finally, do you have any idea about the subsequent stability of families that have enjoyed this treatment?

DR. CARSON: First of all, let me just say that women who are oocyte donors receive drugs to stimulate their ovaries and hormones to stimulate their ovaries. They do not have to go through surgery or laparoscopy. A needle is put into the vagina and the eggs removed under conscious sedation. Some programs use general anesthesia, but most programs use conscious sedation in either an operating room or a specially designed office room for this procedure. It'd done under ultrasound guidance.

And although the donors are frequently not given the outcome, they enjoy sharing their fertility with someone, and I'm not sure that unless you are a voluntary oocyte you would necessarily understand that answer.

DR. McHUGH: I can understand the needle.

DR. CARSON: When the price is set for compensation rather than payment for eggs, they have a lot of self-fulfillment for doing something like this. For example, in our program, we have a donor who also is a blood donor and is a bone marrow donor at M.D. Anderson. She enjoys sharing her health.

The risks of the procedure are quite low because, again, the donors are not quite -- there's a different -- the stimulation is less intense than the stimulation of an infertile woman. The risks of subsequent pregnancy is increased, pregnancy during that cycle of the donor. So the donors are told of that risk and told to abstain from intercourse after eggs are removed.

You've asked about the donors. You've asked about risk. Oh, and family stability.

We don't have long-term data on family stability after in vitro fertilization. There are some studies suggesting that the actual divorce rate is lower. One small study showed that it was the same, but I don't think we have a lot of good evidence based medicine.

DR. McHUGH: The other question was how many abortions follow ART impregnation.

DR. CARSON: Do you mean spontaneous abortions or elective?

DR. McHUGH: Elective abortions.

DR. CARSON: I don't know that number offhand. It is, I believe, in our registry. It is very low, and it is for, almost always for chromosomal abnormalities or genetic abnormalities.

CHAIRMAN KASS: I have a very long queue, and we are at the place where we should break. Since I called on Gil, I'm going to ask other people to -- the questions will persist. The conversation will continue.

And also let me say that our interest here today ought to be primarily on the question of the practice of self-regulation rather than the particular -- even arguing with the substantive judgments or decisions or the details. So let's see if we can make the best use of these questions in order to understand how the society does its own practice of self-regulation and makes it effective.

Gil, and then we'll go to a break, and then we'll continue after.

DR. CARSON: May I answer one other question?

CHAIRMAN KASS: Please, of course.

DR. CARSON: Would you put on this slide?

You know, I wanted to further actually elucidate your comment on elective sex selection. The reason that I'm wondering about it is because we do preimplantation for medical sex selection, and I believe that we can sort it out, but again, without -- thanks. I'm not absolutely certain that I can answer that, but I think we can. I wanted to show you and the committee what this is involved with.

This is a 14 year old boy with Lesch-Nyhan Syndrome, which is an X-linked disease. This is not a cleft lip. He has actually eaten the upper lip because these individuals have an extreme self-destructive behavior, and he is mentally incompetent. His hands and legs are tied down so that he doesn't eat his hands off, and the reason that this couple go through sex selection or PGD for sex selection is to avoid having to see another baby like this.

And so we do recommend preimplantation diagnosis with disease such as this. There are increased risks, but this is the benefit to that couple.

CHAIRMAN KASS: Thank you.

Gil Meilaender.

PROF. MEILAENDER: I think this comes directly to some regulation issues. I want to just think with you or explore with you a kind of analogy that you used that doesn't quite click for me in a way. I don't have any medical training at all, but I don't think LASIK surgery produces children.

Given that that's the case, is it not possible that a society might have good reasons to want to pay attention to, oversee, and regulate ART in a way that it wouldn't have with respect to LASIK surgery since we're talking about a procedure that produces children whose psychological and physical well-being is involved both before and after their birth. We're talking about a procedure that has implications for the way the society understands the relation between parents and children, the familial bond more generally.

I guess I don't see, you know, the analogy to which you recurred on several occasions as being very important or significant. It seems to ignore a great deal of what's peculiar to the procedure that you're talking about.

So I wonder if you could think about that a little bit.

DR. CARSON: I think we might be coming on the same page, but perhaps my description wasn't good. I was using it as an analogy for the physical description of the procedure in that these are considered somewhat elective procedures by many groups. We disagree with that, but many groups would consider this both an elective procedure. It is office based surgery. It is not reimbursed by insurances, and it has significant side effects.

LASIK doesn't produce children, but does it produce blindness, which some would consider a significant side effect, and what I was saying is we don't really know that because we don't have any outcome data.

We also feel that you're right, that IVF is different and that not only does it produce children and has risk to not only the woman, but the child and, furthermore, to a very intimate and personal relationship and a very intimate process, and we do feel that IVF deserves some more self-regulation than, for example, LASIK, which would be otherwise somewhat physically comparable.

PROF. MEILAENDER: Or perhaps even more regulation and oversight from the society itself and not just self-regulation, given the nature of the procedure? Are you prepared to grant that?

DR. CARSON: I'm sorry. I don't understand your question.

PROF. MEILAENDER: Is it possible that because of what the procedure involves it might be that an entire community would have a greater interest in oversight of this procedure and content itself with self regulation of those involved?

DR. CARSON: Well, I think that certainly the community has, as we've seen, there is federal, state, and even local requirements for IVF. We feel that the self-regulation of the field is important because we think that we can be more innovative. We know the procedure more as a group, and we know where to look. We hope that we've asked all of the right questions. We hope we're looking into all of those aspects, and we think that we are doing a good job with self-regulation and want to continue it.

CHAIRMAN KASS: Let's take a slightly shorter break. Ten minutes, please, and let's be prompt.

(Whereupon, the foregoing matter went off the record at 10:11 a.m. and went back on the record at 10:24 a.m.)

Session 6: Biotechnology and Public Policy: Professional Self-Regulation

CHAIRMAN KASS: I'd like to get started and in ten seconds call on George Annas for his response, and afterwards we'll consider the two presentations together, and people who were still in the queue for comment before, I still have your names and you will not be forgotten.

I did want to mention to everyone present that the council's Web site has been redesigned since the last meeting, and I'd like to call your attention especially to a feature of which we are particularly proud: selection of readings from our bookshelf, supervised by Rachel Wildavsky, which now has three sets of readings up there in the spirit of "Toward a Richer Bioethics," in addition of the one on "Among the Generations." We have something on scientific aspirations, and something on the pursuit of perfection. There are things coming along on vulnerability and things on "Many Stages, One Life." So please keep your eye open for what's coming there.

George Annas, thank you very much for joining us. The floor is yours.

MR. ANNAS: Thank you, Mr. Chairman.

I don't look at this so much as a response as another view, let's say, of self-regulation.

CHAIRMAN KASS: Please.

MR. ANNAS: All right. I'm a regulator, and I'm very comfortable regulating things. I've spent my life with physicians. So I'm comfortable trying to regulate physicians, as well.

I do believe most of them need regulation, and often they are very happy to be involved in it, but, on the other hand, as we know from the current debate on medical malpractice, they're not particularly fond of physicians or with lawyers -- I'm sorry -- and not particularly fond of private lawsuits.

So when you look at the area of how to regulate any industry or activity, you have choices of the market, the market in private lawsuits, professional self-regulation if you're a professional, or some form of government regulation, or even as I'm going to suggest at the end, a hybrid, government-private type of regulation similar to that which we have in organ donation and organ transplantation in the United States.

So first, just a bit of my own biases. I started my career part time on the Board of Registration of Medicine in Massachusetts. I spent six years on that board regulating physicians as its vice chairman and chairman of its complaint committee and enjoyed that quite a lot.

Then I was the chair of the Massachusetts Organ Transplant Task Force whose job was to try to produce regulations to introduce liver and heart transplantation into Massachusetts. As many of you know, the most expensive and probably the -- they think they're the best as well. We all think they're the best -- medical system in the world, the most expensive medical system in the world.

And we made it much more expensive by making sure not just one hospital, but four hospitals did liver transplantation in the first year it was introduced.

I am, as you've mentioned, Mr. Chairman, past member of the ethics committee of ASRM and happy to take responsibility for the many documents that came out while I was on the committee. Rebecca has told you those were all consensus documents, and in my years on the committee, our chairman was one of the most distinguished people in the contemporary history of bioethics, Dr. Ken Ryan, who died recently.

But Dr. Ryan was an unbelievable chairman. I mean, he was as knowledgeable as you can be about the field and also knowledgeable about regulation. He was, as many of you recall, the chairman of the first national commission for the protection of subjects of biomedical and behavioral research.

That commission met from 1973 to 1981, and its regulations were essentially all but one adopted and put in the Federal Register and form the basis of the current common rule for all human experimentation that is governed by those regs. in the United States.

And Dr. Ryan ran a terrific committee, and I think the deliberations of that committee speak for themselves.

And there are some problems with self-regulation that the committee, which is, I think, as good as you can do, by the way; I'm not going to critique any members of the committee or any of the motivation of having such a committee, but I'm going to critique the reality of how you put a committee like that into existence and what happens to its rules.

There are a number of critiques of professional self-regulation that I'm sure you're familiar with. The most recent one is by medical historian David Rothman. He wrote a very powerful op-ed piece in the New England Journal of Medicine two years ago called "Medical Professionalism, Focusing on the Real Issues."

And Professor Rothman argued actually that medical professionalism had to be invented. It couldn't be restored; that there really never was a time -- maybe it's a little harsh, but this is David talking, and I'm sure he would defend it -- there never really was a time when physicians could be said not to have bad interest in themselves first.

And, of course, you'd say that's true of everybody in society. When they weren't more interested in their income, their control, their autonomy, and what they could do in terms of practicing medicine without outside interference, and I certainly saw that on the Board of Registration in medicine.

Our Medical Society in Massachusetts, like all the other medical societies around the world, was not very happy about being regulated. And if they were going to be regulated, they wanted a majority. Well, we had five out of seven of our members were physicians. They wanted physicians doing the regulation, and in some sense I don't blame them.

But as David Rothman argues in this piece, in order to do that, you have to go beyond self-interest, and you have to really do things that are in the interest of the public.

David gives six recommendations to invent professionalism. I just want to mention the fifth one because it's specifically relevant to what we're talking about today. He said, "Professional organizations must be persuaded to expand the agenda for which they lobby and advocate." And then he goes on and says nearly all of these organizations advocate for themselves for making sure that insurance or government programs cover whatever it is they do, and as he calls it, the special interest of organizations' members.

And then he suggests something which he says he's gotten more hate mail than for anything he has ever written in his life. He suggests that it's, you know, de riguer for the dermatologist to say we should cover more dermatology services, ophthalmologists say we should cover cataract surgery, et cetera, and for our gastroenterologists to say we should cover colorectal cancer treatment therapy or screening. I'm sorry.

Imagine, he says, what could have happened if these societies had advocated for the well-being of patients without regard for their own self-interest. Support by dermatologists and ophthalmologists for colorectal cancer screening, he said, would carry great weight in the debate over whether to include it as a benefit. Again, he says the barriers to such activities are formidable, and he obviously thinks how the public might respond to advocacy that was driven not by narrow self-interest, but by broader professional vision of patients' welfare.

Now, of course, the hate mail he got was from gastroenterologists. So he went to what in the hell do dermatologists know about colorectal screening and, you know, quite properly so. But the issue is not a technical issue. The issue is what are your goals; whose interest do you care about; and how do you further those interests.

And the notion that professionals, if they're to be professionals have an obligation to go beyond this self-interest that non-professionals go to. That's essentially a trivial -- well, not a trivial point. he makes it very well. It's actually a critical issue. It's can professional committees, can professional self-regulation go beyond the interests of the members and look to protect patient welfare in general.

In my experience on the ASRM ethics committee, it's certainly possible but very difficult. The ethics committee couldn't do it itself, as Rebecca has pointed out. The Executive Committee gets to approve anything that the Ethics Committee points out, and then after that, what enforcement there is if anyone knows about them is often up in the air.

Nonetheless, t he fundamental question is what's the charge of an ethics committee. What's the charge of having rules for your members, and I spent six years on this committee, as I say. I take full responsibility for everything I did.

On year three, which I think was around 1995, when we had on the agenda things like post menopausal pregnancies, using fetal ova to try to create a pregnancy. On the committee that's one of the few thins the committee said should never be done, which is great, and disposition of embryos, et cetera. All of these issues were on our committee.

And before that committee or just as that committee meeting started, I asked the chairman if I could summarize what I thought the committee's operating assumptions were, and here's what I said, and I thought this was an insightful critique. I said: here's our operating assumptions.

Number one, the ethical acceptability of new reproductive technologies is to be assumed, and the burden of proof is on anyone who would question a new technology to show how its use is unethical.

Number two, the use of a new technology cannot be declared unethical if there are any possible ethical applications of that technology no matter how hypothetical.

Number three, it is assumed that imagined new technologies will ultimately work and will prove beneficial, and that any imagined harm from the technology expected can be controlled unless proven otherwise.

And number four, the major values to be taken into account in evaluating new reproductive technologies are economic-- efficiency, supply and cost-- and not ethical.

Now, I thought this was a critique, and so I was a little surprised when Chairman Ryan turned to me and said, "George, well, of course that's exactly right. That is how we operate and are operating. That is our operating assumptions," and indeed, they were.

And in one sense, you know, you'd say, well, gee, you know, you should have different operating assumptions, and I think we should, but on the other hand, another way to say that is we believe in what we're doing, and the burden of proof should be on other people to prove to us that there is some harm or some other aspect that comes into this.

Well, let me suggest a couple of other operating assumptions that we could have instead of these. Actually Dr. Carson suggested some, which I like a lot. She suggested safety efficacy and privacy. That would actually be better than the ones we worked on, and even better yet, healthy children, healthy parents, and healthy third parties.

That's terrific. That was not in existence when I was there. In fact, I argued at a meeting of this society in Toronto not as a member of the committee, but as a person giving a speech there that the organization should take a firm position that their number one concern was children.

That to my knowledge hasn't happened, but nonetheless the language "healthy children" is a big change from my perspective at least.

And the second thing that I think is necessary and have argued for that is for the group to think more like physicians. Now, what do I mean by that?

Well, even though actually your Chairman and I have argued about the Hippocratic Oath in a prior life here, in terms of the Hippocratic principle, first do no harm, that makes perfect sense to me in terms of doing reproductive technologies, and do no harm to children strikes me as the right principle to use as a starting point.

And then the second principle is to always take the welfare of your patients as the first priority.

Now, if we started with those assumptions instead of the operating assumption of the current chairman of the committee, which is procreative liberty, and John Robertson is an old friend of mine. We go back 30 years, and we've been debating our whole lives and we'll never agree with each other, and I'm not trying to score cheap points against John. Procreative liberty is very important, but it's not the only value. It's not the only value in society, and it's not one that can determine everything that happens because you start with procreative liberty. You take as an assumption that people can do whatever they understand with informed consent that they agree to, and that the only thing that could possibly stand in the way is if someone could prove that there were significant harms to a child that would not have been born but for the procedure.

Sine it is never possible to prove the second thing, you wind up that you can always do -- that the rule is, and this is the operating ethical rule of physicians in general, not just our own physicians, that as long as I want to do it, it's accepted medical practice and my patient gives informed consent, leave me alone.

And that's basic medicine today, and mostly not just here, but mostly all right, and that's why most regulation in medicine is done by private lawsuits and malpractice and why we have even with the Institute of Medicine and four years afterwards talking about 100,000 deaths a year caused by physicians. We have really no movement in the patient safety movement, no real desire by physicians to try to clean up their act in general, and an almost impossible situation where it is seen that the only say we can move forward is to protect physicians against liability and keep errors secret, even though all of the surveys show that patients want to know immediately if doctors have harmed them due to errors.

The other models that are used in the new reproductive technologies, and I have the one handout that I did give you in your materials, pretty much a summary of my views of the field from my 25 years as an outsider, are that it got started off on the wrong foot, and my friend a colleague, Dr. Sherman Elias, a geneticist-obstetrician, and I wrote a piece in JAMA in 1986 on this, that, again, your Chairman was kind enough to review and give us some really good suggestions on.

Then I got started using the artificial insemination by donor model, and that was a big mistake, and we still use that as you heard even in valuing how much a woman's egg is worth. We try to figure out how much a sperm donor's time using sperm is worth, but the sperm donor model was a mistake because historically the first thing doctors did after they used donor sperm was literally to destroy the records.

They don't do that anymore, but the idea was that you had to protect the best interest of the sperm donor, even at the expense of the best interests of the child. So if the child wanted to find out later who his or her genetic father was, it was not possible. That's been more or less changed now. Actually adequate record keeping is required, but it's still extraordinarily difficult for children of AID to find out the identity of their genetic father.

That's a bad model. I mean the last thing you want in medicine is secrecy, it seems to me. You do want confidentiality, but you certainly don't want secrecy from the people involved. You may want it from society in general, but we've used that model not only to figure out how records should be kept, what kind of confidentiality and privacy there should be, but also to move over into a place where I think and have argued unsuccessfully it has no place at all, which is an ovum donation, which is nothing like sperm donation at all. As you've heard, it's a medical procedure with major risks. There's sharp limit of the number of ovum women can donate, and there can be, you know, significant problems to this.

To equate it with sperm donation makes no sense, but nonetheless we say we want gender equality and so we have to do that.

A number of people have mentioned it, even though we want to talk about individual things, this statement at Tab 19 on financial incentives to ovum donors, and I think I was off the committee when it actually came out, but I was certainly honored when it was developed. So it's another one I have to take responsibility for.

But one of the things in there which I thought was critical and the committee was willing to put it in is that every ovum donor should have their own physician. Okay? And what I meant by that and what the committee meant by that is not a physician, you know, who is involved in the IVF procedure, is already committed to the couple or committed to make sure that eggs are gotten for these particular patients, but is committed to this person as a patient, to this woman who's undergoing a significant procedure with significant risks.

And that's because I believe in two things, which is not shared by a lot of people in the field. Number one, that there should be no purchase and sell of eggs; that that's a problem; that that commercialization of eggs is a problem, and it's a subterfuge to call this just giving money for inconvenience.

And, number two, that any physician who's worthy of the name would not subject his patient to a risky procedure just for the sake of being paid for their inconvenience. It can't be done. It can't be justified.

It can barely be justified in kidney donation, live kidney donation. Even that's problematic, but at least there you have someone with a terminal illness whose only option is to undergo dialysis, and it can barely be justified there.

But even there we will not pay that person to donate their kidney. That's a much more vigorous, heroic thing the person does under those circumstances.

So in any event, I think it's problematic. The role of physicians is problematic, and if you're going to be a physician and deal with things like egg donation, you have to, it seems to me, put the best interest of your patient first, do no harm first, and there are some things that you just have to say we can't do.

Yesterday's Wall Street Journal, some of you may have read this. A movement or not a movement, but a trend around the country and certainly in Europe and Australia to do away with the drugs, the hyperstimulation drugs, and then you can only retrieve one egg a cycle and obviously it cuts down on your ability to do that, but it's much, much, much better for the women involved in terms of risk, and it turns out to be much cheaper, too, although long term studies haven't done -- will have to say how successful it is to see in the long run and how much less expensive it is.

But the point is there are alternatives that don't put healthy women at risk for money.

The second problem, and I'll just go through this quickly, is a problem of private contract. Because the entire system is seen as private, personal, and secret, the notion is that instead of having rules that apply to everybody, we should be able to contract and define our own rules.

The New York Task Force on Assisted Reproductive Technology and virtually every task force that's looked at this, public group that's looked at this has said, for example, that they believe that the proper rule should be the rule, and it actually is a rule in at least 48 states of this country, maybe 49, that the woman who gives birth to the child should be considered the child's legal mother for all purposes.

That's not the rule in California, and the rule in California is that the legal mother is the, quote, intended mother. And who is the intended mother? It's whatever the couple, the surrogate or whoever is involved in this decide by contract beforehand who will be the mother.

That to me, as I wrote in this article that you have makes no sense. I think whatever rule we have we have to be able to identify the mother at the time of birth, and she has to be there with the rights and responsibilities for the child, and the only woman who is going to be there at birth is the birth mother obviously, and she's the woman we've always considered the mother, and it seems to me that for the child's sake and her own, that presumption should continue and no private contract should be able to change that.

Nonetheless, this is not just ASRM talking. This is California Supreme Court thinks that that's okay, and again, the California Supreme Court did this on the basis of sperm donation, and they said, "Look. If we can figure out who the father is by contract and keep the name and identity of the sperm donor secret, we should be able to figure out who the mother is by contract as well.

And, again, I think that that analogy does not hold, that the court is wrong about that, but nonetheless that explains why most surrogate mother contracts are done in California, and it also helps explain a tremendous cultural shift between the days of Mary Beth Whitehead when we had pictures and lawsuits and people wondering what was going on, and today when you look on the newsstand today People Magazine, something I read every week. No, but you should read this if you're involved in this. This is a celebration of surrogate motherhood and donor egg when Joan London has hired a surrogate and gotten eggs from someone else to have twins for her and her husband in her second marriage.

I'm not saying there's anything wrong with that, but I'm saying she shouldn't be able to make up who's going to be the mother and who's going to be the father; that we should know who the mother and the father is for the sake of the children, regardless of whether the surrogate is from Ohio, as she is here, or the contract was made in California or that there was some other arrangement. That shouldn't be a matter of private contract.

So those are my primary problems with the current regime. Nonetheless, let me say I think ASRM -- and I actually do believe this -- has done just about as well as you can do in terms of private self-regulation. It is actually a model.

If you go around and look at some of the others, with the exception, I think, of pediatrics, but I think pediatrics is an exception because their patients can't give consent, and they know they have extra obligations to the children patients they have.

And you can't have a contract informed consent model with a child. So with the exception of the American Academy of Pediatrics, all of whose statements are child centers and all of whose statements begin with the best interests of the child is paramount, and almost every other medical specialty has the basic rule that if the doctor and the patient agree to it, it should be permissible using informed consent documents.

Okay. Those are kind of easy questions, you know, because it's easy to say what problems exist and what can be done around the edges. The much harder question, and I'll just throw out a few minutes of this and then we can discuss it, is if you wanted to regulate, number one, is it possible. Could the public actually get involved in this?

And, two, what are the models that exist that could be pursued?

Before you start regulating, before you even think about regulating, obviously the first question you've got to ask is why. What's the problem that you're trying to address because it is very, very, very possible to create more problems than you solve, to be totally counterproductive in doing regulation, just as it's possible to create more problems than you solve doing ethical statements.

By the way, I may have misunderstood this statement that you made, Sandy. If I did, I'm sorry, but it doesn't really matter because the point is that these statements require interpretation. The disposition of abandoned embryos, which I've signed off on and helped writing, and I certainly agree it makes perfect sense to me and we shouldn't keep embryos frozen forever, and that after some period of time when you lose contact with the gamete donors, that you should be able to destroy those embryos, and that the position taken here was five years destroy the embryos. I think that's fine.

We also tried to make it clear, but obviously did not as I read this again that you should not be able to use those embryos for research or to donate to another couple without explicit consent, but I could see how you could reread this and say that the new regulations on embryos for stem cells, which require contemporaneous consent, as I believe all research should, only apply to stem cell research and that this document gives you the right to use these embryos for research for everything else.

For me that would be a misreading of this document. That's not right? Okay, good. I'm glad I misunderstood that.

All right. But the other point is somebody has to read and interpret these, and I could see how someone could read and interpret it that way and say if someone said to them, "Well, you're violating the regulations," they'd say, "No, you have a separate regulation for that. This one is for this."

And if you read them together, as lawyers do all the time, you could interpret it that way.

Okay. So the first question, as to the activities is a very important question, is if you wanted to regulate, do you want to regulate human experimentation and research or do you want to regulate ART, assisted reproductive technologies?

My own bias, and it may mean nothing to you, is that we should have a federal regulatory scheme for cutting edge research. That should include artificial hearts, xenografts, embryo research, research of the kind that local IRBs -- it is simply beyond their competence, not that they don't try hard, and recently we have added to that smallpox vaccine on children, which went to the federal government anyway, and we weren't able to come up with any agreement except not to do it.

But big time, risky, new types of human experimentations seem to me to require a type of regulation that we don't have, and some of the things that are done in ART, especially around embryos, cloning, stem cells, would fall into that rubric as well.

So if you wanted to do that, that would be one kind of a regulatory scheme. There would be no problems with federal authority to do that, and it would fall into the same pattern of the proposals by NBAC to cover all human research, not just federally funded research, but private research as well.

The second type of research -- so that was one way -- the second way to go is to regulate ART. That's much, much harder, but possible because if you do that, you have to break it out in terms of federal regulation and state regulation.

The issues that I'm actually most concerned about: who's the mother? Who's the father? How do we insure the welfare of the children? How do we make sure the child has access to their record, et cetera, to their genetic information?

Those actually turned to all be issues, family law issues which would be the province of the state. So to do that we'd have to go -- we could still write a model situation, but we have to go state by state, and that is not going to change. The Supreme Court is not going to change that, nor do I think should they. Family law issues rightly belong at the state level.

So you couldn't do that on a federal level. The federal level, on the other hand, you could regulate the commercial aspects of assisted reproductive technology, not just the, frankly, commercial aspects like advertising and pricing, outlaw the purchase and sale of gametes, if you wanted to do that, which I do; outlaw the purchase and sale of embryos obviously.

But I think you can also regulate some of the practice, a lot of the practice, the record keeping requirements, the screening requirements, contract requirements, informed consent requirements, and counseling requirements, and you could have uniform rules for everyone, that unlike the ethical rules could be enforced. You could set up a licensing scheme. You don't have to, but you could follow the British model and license ART clinics.

I actually didn't realize there were 25 that weren't even members of ASRM. It should be unacceptable. I mean, they should all be operated under the same set of rules, it seems to me, that we should have national standards for this, and you know, that would be something that a separate agency could do.

Now, historically in other countries that have done this, I know you heard from Patricia Baird. You've heard from the regulators in England as well. It has taken a big time federal national commission to study this issue for years to come up with recommendations which are then adopted by the parliament or congress or whatever their legislative group is.

It would take the same in the United States. I don't think you could just go to Congress.

Could this group do it? If that's what you wanted to do, I think it's possible. You could, but you probably couldn't do anything else. I mean, it's a giant undertaking. It would require input from many, many people. Lots of input from ASRM, as well.

I'll leave it to you whether you want to pursue that or not, but there are models out there.

The final model and one that I actually think might satisfy both sides, both sides being the public and the profession, is an UNOS model, United Network for Organ Sharing model, which was followed for like almost 20 years in this country. Can we regulate organ transplantation? Isn't that something that we should let private physicians and people do?

And of course, the reason we decided we needed some public input from that is because organs came to be seen as, a very weird word, a natural resource according to our presidential organ transplant task force back in 1986.

And the idea, of course, is that we get organs from everyone, and it seems unfair that everyone shouldn't be, therefore, eligible for organs, and it also does seem -- maybe that's obviously why we do have essentially a system of national health insurance for livers, hearts, and kidney transplants and for nothing else in this country.

But it also seemed that we needed a public transparent method to see who got those organs because it was life or death decisions. There was a shortage. There continues to be a shortage, and the public trust was absolutely essential for this to go forward.

On the other hand, people are suspicious and rightfully so. Too intrusive government regulation in the doctor-patient relationship.

So we wound up with the federal government, Congress, and then regulations under HHS setting the standards for organ transplantation and then having a private group contract it out, the United Network for Organ Sharing, to implement those regulations.

And we can argue about how well that works overall I've been a critic of that as well. Overall it works quite well. I think it does work quite well, and that's a possible model for you to consider as well.

So with that kind of personal critique of self-regulation, self-personal experiences with ASRM and some suggestions of where you could look for different regulatory models, let me open for questions and comments.

CHAIRMAN KASS: Thank you very much for a very responsive and direct and very interesting presentation.

I am somewhat at a loss as to whether we should first have some comments directed to Professor Annas and whether the people who are in queue would yield at least for a few minutes to get some clarification, but I have you.

I have Robby George, Alfonso Gomez-Lobo, Frank Fukuyama, Elizabeth and Bill Hurlbut.

You're taken care of already.

DR. GÓMEZ-LOBO: I yield.

CHAIRMAN KASS: Is there someone who would like immediately to respond to -- Rebecca Dresser and Michael.

PROF. DRESSER: George, I just wondered if you would give us your thoughts on the problem of getting both the state legislatures and Congress to act in this area that is fraught with controversy.

MR. ANNAS: Well, as I say, I don't think it's impossible. It's more likely to get action on the federal level probably than on the state level right now, but it's very, very difficult. I mean that would require like you'd have -- this group, for example, would have to say, "This is our highest priority."

That might not do it even, but if you didn't do that, definitely nothing would happen.

On the state level we've had a remarkable report, which I commend to you. You've probably seen it, the report of the New York State Task Force on Assisted Reproductive Technologies. They recommended 80 different changes in their law.

To the best of my knowledge, none of them have actually taken place yet. So that gives you some idea of how difficult it is to pass legislation even with state group whose charge was to recommend legislation coming up with an exceptionally well articulated program with good reasons.

So this is a very, very difficult thing.

The second thing that happens, and I don't have to tell this group that, is that this becomes very quickly entwined with abortion politics, and you're going to have a lot of people who obviously don't care about this issue, but who for them, you know, physicians and assisted reproduction is not an issue at all will be against any regulation of anything having anything to do with pregnancy and childbirth because they're afraid once you regulate that then you're going to start, you know, cutting back on abortion rights.

And I actually have a lot of sympathy for that view, and I certainly understand it. But it just makes a life of a regulator much harder. so there's those two political realities.

CHAIRMAN KASS: Michael Sandel.

PROF. SANDEL: I found your critique of the existing arrangements very persuasive and thorough. My question is what would be wrong in your view with our adopting the British system?

MR. ANNAS: Yeah, I mean, I don't think actually -- I'm quite fond of the British system. I don't see anything wrong with adopting it. We're not Britain obviously, but -- and I recommended that. I commended that before, and I think that we could go that route, you know, but then you put an awful lot of authority in one group, and no one will support that until they have a pretty good idea who's going to be appointed to run that organization and how the members are going to be chosen and are they really going to have, you know, a say.

I mean that's really the critical thing in England. I mean, they have a different system. Obviously they have a national health service and everything is funded and they don't have the problems. Dr. Carson rightly pointed out that if you want to do all of these wonderful things, you have to pay for them, including, you know, registries of children.

And so one of the questions, having done that, even though it was one of the few things left out of the Clinton plan for national health insurance, could you set up a system to regulate this and fund the procedures and not fund everything else?

So I don't think we can just have the British system just, you know, transplanted here without understanding the whole British system, but it's a good model to look at, absolutely.

CHAIRMAN KASS: On the questions of -- let me just jump in with this business about your, I think, very proper concern for the well-being of children, and several of us were talking previously. To the extent to which one looks really at infertility as a frustration of procreative desire and support of reproductive liberty, the child tends to be sort of forgotten or at least left to the side.

Could you comment on how well you think the current practices of SART actually do safeguard the interests of the child to be one?

And, two, would the implications of some of your comments earlier suppose that, in fact, pediatricians are those whose primary interest is to care for the children really ought to be somehow central to the ethics committee and other practice review committees of the society; that there should be some kind of greater collaboration here if professional self-regulation is, in fact, to address the interests of all concerned, children most especially?

MR. ANNAS: Children, I think, are primarily considered the province of the parents to take care of, you know, in this setting, and of course, I understand that because that's what infertility treatment is for. It's to try to help parents who can't otherwise have children have the children.

All right. And the challenge is how do you get children more focused and their interests more involved here, and you know, that is a challenge. I mean, obviously the pediatricians take them right after they're born and they're no longer in the care of these specialists, and they may have other obstetricians even. They may not even be delivered by the infertility specialist.

So if you wanted to have a physician model of all this, you'd have to have a joint ethics committee, if you will, with the American Academy of Pediatrics, ACOG, the American College of Obstetrics and Gynecology, and in fact, those two groups do have a liaison and do meet together, and actually there is some overlap historically with the ethics committee of ASRM and ACOG, and since many members of ASRM, not all, but lots, are obstetricians as well.

That's the kind of mix you have to get, but you have to get more pediatricians involved. I think obstetricians have been involved.

And the interesting question, actually there are -- you know, my colleague, Michael Grodin who was the liaison member of those two committees for six years reminded me before I came here that one of the things they wrote was a position on surrogate motherhood back in 1994, and they wrote it together, and they wrote it based on the best interests of the child, and his point was that the ultimate statement was very similar to the ASRM statement. There really wasn't any difference, even though they didn't come at it -- they didn't mention the child, but they didn't come at it from the best interests of the child. They came at it: does this make sense for a couple who is trying to have a baby?

Nonetheless, the bottom line from the two was lots of caution and here's what we do, and it wasn't different. The people coming at it just from the interests of the child did not say we should ban it, but both groups came out at the same.

So you may not come out differently on a lot of these things, but you will have other considerations in the mix when you do it.

CHAIRMAN KASS: Thank you.

Elizabeth, please.

Oh, I'm sorry. Then unless there are other immediate respondents, let's declare both presentations open for discussion and, indeed, discussion of the issue as well as the presentations, and I have Robby, George, and then Alfonso.

I've got starting with Robby, and then Frank and Elizabeth and Bill and so on.

Please, Robby.

PROF. GEORGE: Thank you, Leon.

I do have two questions that I'd like to bring Professor Annas and Dr. Carson into conversation on, and, Rebecca, I'd be very pleased if you could chime in on both of these as well.

The first one has to do with the general problem of self-regulation. My own impression is that there's a problem of self-regulation which I do not oppose with any enterprise, and with everybody who has a vested interest in an enterprise, and that is that the enterprise and those with an interest in it have a stake in the reputation and good name of the enterprise and protecting that against embarrassments.

Now, the standard answer to that, whether we're talking about medicine or any other field, think of the police, think of religious institutions, is that, well, look. The long-term interest of the enterprise really is served by good self-regulation and by not covering things up because it all comes out in the end anyway, and it's worse in the long run for everybody concerned even looking at it from a selfish point of view if we get it out.

But, again, looking at police and religious institutions as examples, one finds that, well, often the view taken by those with a vested interest is a relatively short-term view. It's getting through the problem now. It's avoiding damage to the reputation now and putting things off and the long run will just have to take care of itself, and of course, then in the long run, as was said, we're all dead.

So the standard answer doesn't always work so well. Now, what some other institutions, including those I just mentioned, have tried to do about that problem unfortunately too often after significant embarrassments is bring in some sort of external reviewing to the process of self-regulation.

So we're not now talking about government regulation as an alternative to self-regulation, and there may of course also be government regulation going on, but rather involving in the self-regulation outsiders to the enterprise who have an interest in at least some level of expertise, but who may not be entirely tied in with it and may, therefore, have some objectivity and distance.

Think of police review boards, for example. So I'm wondering whether -- this is my first question -- I'm wondering whether this is already a feature of the self-regulation of this enterprise or industry, and if not, whether there are particular reasons why it cannot be here or cannot be done to a larger extent, a greater extent than it is now.

So that's my first one.

CHAIRMAN KASS: Dr. Carson, would you want to respond?

DR. CARSON: Yes.

CHAIRMAN KASS: Push your mic.

DR. CARSON: Thanks.

We do have exactly what you suggest. Our validation teams consist of members as well as non-members. The validation committee, oversight committee, as well as the site team visits have members of the CDC on it as well.

MR. ANNAS: Yeah, I may be reiterating your question a little differently, but I think it would be good to consider -- I never suggested this -- having some consumer groups do some suggestions as well.

Years ago I was on the board of directors of Resolve, for example, which is a support group for infertile couples, and their concerns are different. A lot of them are costs and access and data, but their concerns may be different than a profession.

And another group, which I have a number of groups, these support groups for multiple births, they're obviously mostly all happy with their children, but they do think a lot more can be done and should be done both to tell people about the possibilities of having triplets and quadruplets as well as try to figure out ways that that number can be reduced.

I mean, the number is going down. Down to four percent is great, but I think we'd all like to see it down to close to zero.

PROF. GEORGE: You know, we've heard rumblings on the council, and I've picked up things outside the meeting room here in talking with people about the possibility that as the original IVF babies are now entering their 20s, there are concerns that unanticipated diseases or defects are emerging so that the problem goes beyond simply the multiple birth problem, but perhaps some of the fears that people originally had about IVF are being born out.

If that were true, I take it that it could be a significant embarrassment to this industry and perhaps damage it in the public eye, and it looks to me like that's a particular area where the industry itself probably would be better off if there were some sort of external report on that investigation and report on that in the end rather than the industry itself.

CHAIRMAN KASS: Dr. Carson.

DR. CARSON: Well, let me just point out that ASRM does -- we have active collaboration with both the AIA, American Infertility Association, and RESOLVE, and have a long-term collaboration with RESOLVE. We have members at our meeting, board meetings, and so we have considerable consumer, if you will, and what I like to say, patient input into our policies and guidelines.

In addition, we work with not only the CDC, as I mentioned, but also the FDA, and the FDA now has worked with it, has undertaken upon itself to look at all research procedures with human tissues, including gametes and embryos, and we are working in collaboration with the FDA to help them with some of their guidelines and have their input.

In terms of public disclosure, we actually don't feel that self-regulation is embarrassing, and I think it's because our attitude towards this is not punitive, which is not to say when this all initially started that we weren't very paranoid about what was happening and government regulation.

But I think that what has happened is we're very proud of the product that we have and what has happened, but I think our attitude is not one of making people public spectacles of their mistakes, but rather of correcting it, teaming them with a successful program that has the correct procedure, and then monitoring their outcome and making sure that they did, indeed, correct that procedure.

In terms of long-term outcome, of course, it's something that we worry about. It's something we should worry about with everything in medicine. We can't predict what's going to happen with any medical procedure 20 years from now, and that includes any drug you take or any surgery that you have, and IVF is certainly one of them.

CHAIRMAN KASS: Alfonso Gomez-Lobo and then Frank.

DR. GÓMEZ-LOBO: I had yielded, but I take it back. I had yielded because Dr. Carson was kind enough to answer one of my questions, but I think it's of general interest to do with the appointment of the ethics committee, which of course that would translate if there is, say, something like federal regulation into a similar problem.

And let me repeat the question. How is the ethics committee appointed? The reason to us is, of course, because the impact of the decisions of the ethics committee seem to me to be enormous.

In the report that I read, the committee made -- the report on donating spare embryos for embryonic stem cell research -- the committee took a position in a major dispute concerning the question of respect or, as it's called in the report, special respect for the human embryo.

DR. CARSON: Let me just give you a little bit of history of our ethics committee. the ethics committee was really started in 1985-ish, between 19 -- I'm not exactly sure -- 1983 to 1985, by Dr. Howard Jones, and initially it was really just started as an almost discussion group with any real charge.

And Dr. Jones felt that we should be talking about IVF and talking about the ethical issues and bringing them to this society, and you've heard Dr. Annas' early experience with the ethics committee. Even the first formal committee with Dr. Ryan in charge didn't quite have the charge of an ethics committee that one would expect.

And I'm glad to see that we've, perhaps because of your advice, we've matured into a committee that is now on the right track with looking at the safety, efficacy, and patient confidentiality and privacy of these procedures.

Our committee appointments are actually appointed by the president of our society, but they are upon the recommendation and curriculum vitae review of the chairman of the committee, and the president is submitted recommendations and CVs for the various interest groups.

We have incorporated a member of our affiliate societies on the ethics committee, but now we are going to actually mandate probably that a member of the executive committee of each affiliate society be on the group because we feel that this will promulgate more of the policy into our different subgroups.

CHAIRMAN KASS: Frank Fukuyama.

DR. FUKUYAMA: Well, in listening to these two very interesting and helpful presentations, it struck me that the issue here is actually a lot simpler than a lot of the other issues we've been discussing on this council, which is that here it's not a question of trying to insert complex ethical concerns which may not be shared across the whole society, you know, into some realm of medicine, but it's fairly straightforward, you know, kind of safety issue of the sort that we're quite familiar with from drug regulation.

And I think what stimulated this was a couple of earlier bits of testimony we heard on the council about ICSI in particular and the fact that the clinical practice in that area and possibly some others had actually gotten way out ahead of the underlying, you know, biology and scientific research in embryology and developmental biology and so forth.

And so there could actually be some fairly straightforward, you know, simple safety issues involved here.

And so then if that's the problem, then it falls in this category of asymmetric information which is very familiar, which is the reason the FDA, you know, regulates drugs, and I guess the question I would put is if you think that the FDA, you know, legitimately regulates drug safety, you know, as a federal government agency, why is this any different? I mean, why would you argue that you shouldn't apply the same model?

I mean, forget about the practicalities of whether you can do it or not, but is there any reason in principle why you should prefer self-regulation in this case?

You know, one answer actually is that, well, the FDA shouldn't be in the business of doing this. We should rely on tort law or we should rely on the, you know, self-interest of drug companies not to poison people and to, you know, maintain their reputations.

I mean, a lot of the same arguments that you make about, you know, the clinics that are in your organization could apply to the drug industry as well, and yet we don't accept that. We say that there's a very severe asymmetric information problem, and therefore, you need, you know, all of these federal incentives to get that information out to consumers about safety and so forth.

So that's the question I would put to either of you.

DR. CARSON: Well, first, although we do work with the FDA, we still feel that self-regulation as we're doing is more innovative in terms of the problems and also much quicker. For example, we also feel it might be more flexible.

For example, let's look at, as an example, the U.K. model. You cannot transfer more than three embryos in the United Kingdom. It's a law. It's regulated and paid for; can't happen.

Well, I think in the United States we regard the embryo as an important tissue, potentially human, but not, as I've said, with the rights of human. But that doesn't mean that we don't protect and consider that embryo important.

And there are some individuals who for personal reasons do not want their embryos cryopreserved and do not want to discard their embryos, and if they have a fourth or fifth embryo, especially if that embryo doesn't look very good and we know that it probably won't result in a high order multiple, that we would transfer that embryo, and we can written in the document exceed the guidelines for the reason and say we're putting back three healthy embryos and one embryo does not look bad because the patient did not want to discard it.

And I think that's something that self-regulation can be flexible enough to have, whereas federal regulation, such as the U.K. guidelines, cannot.

CHAIRMAN KASS: Please.

DR. FUKUYAMA: Just a follow-up question. That's always true of self-regulation. It's always quicker, more flexible, more adaptive, and so forth.

That being said, would you be in favor of ending FDA regulation of pharmaceuticals because, you know, FDA regulation slows down drug approvals, very inflexible? I mean, would you move to a model for drugs, a similar model for drugs?

DR. CARSON: I would move that we can improve it. I wouldn't say -- should I say that the pharmaceutical companies should self-regulate? I don't think so. But I think we can improve the FDA policy.

DR. FUKUYAMA: Why are you different from them? Why is your group self-interest basically different from the group self-interest of the pharmaceutical industry in being able to effectively self-regulate?

DR. CARSON: I think because we are involved with a very intimate practice of medicine rather than an industry. I think it's a profession that takes care of people whose outcome is not financial primarily, but pregnancy, children, healthy families is a very important outcome variable to us and probably our primary outcome variable, and I think that makes us different.

MR. ANNAS: And I'd add to that, you know, the FDA regulates things, as you know. They regulate drugs and they regulate the drug industry, and actually Congress has said they can't regulate the practice of medicine, but I think they could regulate the practice of medicine.

I don't think they can regulate procedures. I really think that's a whole different thing, and one reason why, for example, surgery is not regulated in this country except by the tort system, and surgeons can do whatever they want.

It's not because we think that they're not dangerous. It's because we have no idea how to regulate surgeons, and added to the surgery aspects is this intimacy, family building, privacy, and I just think not only doesn't FDA have the jurisdiction and would never be given the jurisdiction. I think it would be inappropriate to have FDA regulate medical procedures in the doctor-patient relationship.

CHAIRMAN KASS: I have Bill Hurlbut and then Elizabeth.

PROF. BLACKBURN: I had a question about the UNOS model, the moral sharing model. One of the things that is, of course, great pressure on the system is the shortage of supply compared with the medical needs, and first a factual question for Dr. Carson.

I don't know whether there's considered a shortage of donated ova. I just don't know what pressure there is in that.

And then secondly for Dr. Annas, how does that then impact? Are the situations very comparable or how would that change or adjust the kind of model you would use in this situation?

DR. CARSON: There are -- I'm not sure about the word "shortage," but there are certainly much donor recipients, and there are waiting lists for ovum donors.

PROF. BLACKBURN: Thank you.

Yeah, I wasn't even aware if that was the case.

MR. ANNAS: Yeah, I mean, I apply, as I think I intimated, the UNOS model, federal model, of no payment in the purchase and sale of gametes for this.

Would that result in a shortage? I mean, they're not like organs. To get a vital organ, someone has to die in a very horrible way usually. That leaves their organs intact.

We're actually -- I think this is still true -- the only country in the world that has a market in ova and embryos. So other countries have figured out a way to get around the shortage problem, and we could, too.

CHAIRMAN KASS: Bill Hurlbut.

DR. HURLBUT: I appreciate the difficulty of regulating a complex and rapidly changing field and also acknowledge the good intentions of the vast majority of medical people involved, and I'm a physician myself and feel for the goals of this enterprise.

But I'm also troubled and actually have been every since the beginning of IVF and more so with ICSI by what I perceive, as I said earlier, to be the lack of foundational safety studies on this, and then by some of the ongoing practices.

And I mean, if we admit that less regulation is better and more flexible response is better, still this seems to me a very special realm of human existence, and take, for example, ICSI. Your statistics show I think it was 41 percent of births or cycles involved ICSI now. It was something pretty dramatic. Yeah, it was very high. I'll get it out.

But my first question is: do you think ICSI is being overused? And here without accusing anybody of anything, there would be a temptation to, for the sake of your institutional statistics, to have a higher incidence of fertilization, which would be easier to do with ICSI, right?

What do you think?

DR. CARSON: Well, again, it comes on indication. Now, in this report I'll tell you that our institution has the highest percentage of male factor infertility in the country. So you're talking to the medical director of the program with that high incidence, but that's because we work with a urologist who is probably one of the country's leading urologists in male factor infertility, and most of our patients don't -- a third of our ICSI patients don't have any sperm in their ejaculate. He gets the sperm from the testes.

We very frequently -- the average sperm count in the fertile man is around 50 to 60 million per cc, and very few of our patients have more than one million sperm total ejaculate. So they truly cannot have it.

Now, those are truly indicated ICSI procedures. Another indication for ICSI is a poor fertilization in a prior IVF cycle, but there are complications, and you can actually cause the egg itself to divide, and if you do this in an unindicated patient, you may actually decrease your pregnancy rate.

So I don't think that ICSI is one procedure that is overused because overusing it may actually retard your outcome.

DR. HURLBUT: Well, what is the percentage of ICSI in cycles now? Do you know this?

DR. CARSON: I don't have that number off the top.

DR. HURLBUT: I had it somewhere, and I'm sorry I can't find it, but it was surprisingly high to me, and if you consider the male infertility is in the 30 to 40 percent range, not all male infertility requires ICSI.

I mean it just sort of seemed worrisome to me, and the reason I bring it up is because ICSI has been associated with aneuploidy in normal primates. You said earlier that the difference between the outcomes may be due to the patient population that you're dealing with, and yet there are now studies emerging. Richard Schultz is doing studies of this nature that seem to indicate that IVF does carry and ICSI also carries some risks that are not because of the patient population, if you call mice or rats a patient population.

You see what I'm getting at here. I just -- you apparently feel like these may be problems, but they're not big enough to justify larger federal regulation. Is that what I --

DR. CARSON: Well, I think that -- first of all, although male factor infertility does not always require ICSI, by the time treatment gets to IVF, it almost always does because treatments of male factor infertility per se is not with IVF mixing sperm and eggs.

A woman can mix sperm and eggs in her own body. So by the time that couple gets to IVF, almost all major factor infertility does require ICSI.

Go ahead.

DR. HURLBUT: Well, here's another question. If IVF does carry risks associated with it just, say, because of the procedure or because the patient population is more vulnerable to congenital -- producing offspring with congenital abnormalities, is there a point at which one would say that the procedure is unjustifiable?

I mean, in many dimensions of medicine we wouldn't allow a drug to be used, for example, if it carried a certain risk, and there the patient stands to benefit. Here the issue is, you know, there's a whole other patient.

One of my colleagues doing this work was asked a question, and he said, "I don't think of myself as an embryo pediatrician," but nonetheless we have to consider what is being produced here.

How much risk do you feel is acceptable? And do you feel that that risk is being properly assessed by the current method or should that be a decision for the whole society?

I mean these are very urgent issues, and I understand. In my own experience in clinical medicine, I'd say that people who want to have children and can't are among the most suffering patients I've ever seen, and yet there is a baby coming out of this, and that makes this a worrisome terrain for me.

DR. CARSON: Well, I appreciate your concern, and I think you've crystallized the concern of our society and our ethics committee. The problem is that we don't have a good model because those men I described can't have a baby with that. There is no baby without ICSI. If they don't have sperm in the ejaculate, there's just no way to.

Well, now then you can say: should they have a baby? And, again, that's an important ethical question that I think, again, our ethics committee and our practice committee does wrestle with.

Now, if you come to the conclusion that the technology is available to help them have a child and if you come to the conclusion that it is acceptable, then you have to understand that that technology comes with costs, and one of the costs is that there is an increased risk without an animal model of a subsequent progeny, and whether or not that increased risk should be the same for every individual I don't know.

Should we set a limit that we will not have this with -- I've showed you that the increased risk is .8 percent of sex chromosomal anomalies above live born fertile controls. Now, of course, again, we don't know what it would be if somehow some way these patients were able to have babies, and I don't know how we set that risk.

I don't know whether it should be the same for every single individual and whether that's for us to decide and mandate. But we are concerned that we do have follow-up. We try our best to get these outcomes, and our committee do wrestle with the very difficult decisions that you've outlined.

MR. ANNAS: May I follow that one second?

CHAIRMAN KASS: Please.

MR. ANNAS: I've probably never been able to articulate this well, but for some ICSI patients at least, we know at least for the Y chromosomes deletions that all of their male offspring are going to be infertile, and the question that has always fascinated me, and I don't know if I have an answer for it necessarily, is can an infertility expert who sees infertility as a major disease and devoted their life to it produce infertile children? Is that a problem or not?

DR. CARSON: Of course it's a problem. It's something that again, we do discuss in committees, we do discuss with our patients, and we require that all of those patients go through genetic counseling if they have a Y chromosomal deletion.

We also offer preimplantation genetic diagnosis so that those individuals can have females and promulgate that Y deletion.

MR. ANNAS: I guess that's the question. Should you require that?

I know you say the informed consent model. It's a tough question. I don't have an answer to it either.

DR. CARSON: That's a tough one.

CHAIRMAN KASS: I was myself next in the queue.

I would like to go back to something that was implicit in Gil Meilaender's question previously, and it's also triggered by the way Frank, I think, rather modestly put the kinds of concerns that are around the table.

Safety, efficacy, and privacy are goods all of them, but they don't exhaust the goods that are of concern to us in this counsel and certainly don't exhaust, it seems to me, the goods that are of concern to us in the area of assisted reproduction or of reproduction and, therefore, of assisted reproduction, which is to say that one is concerned not just that children be healthy, although health is a good, but it's not the only good.

And I think that we've all gotten so used to the existence of this practice and welcome its blessings in the relief of infertility that it's no longer perhaps so much a part of our consciousness; that this step, beneficial though it is, represents, as you yourself said, a kind of unnatural development in human procreation, one which leads to lots of others.

I mean, there would be no question about embryo research were there not to begin with the extra embryos available. There would be no question of preimplantation genetic diagnosis to screen the embryos were one not already engaged in the practice of having multiple embryos here from which one could then choose.

And it does seem to me that as the society looks without prejudice now, but to look and ask what's going on here, I think the society as a whole would see not just individual infertile couples with the desire to have a child that this technology can satisfy, but the society would see that we've embarked upon a new way of bringing children into the world, a new way of parents prospectively exercising some kind of quality control over their children, not necessarily through designer babies, but even through just the simple question of selection, of which the selection of sex of offspring for nonmedical reasons is already upon us, and if, as Francis Collins suggested in his presentation, the prospects of screening embryos for not just diseases but also for traits at least in some cases he forecast within ten years.

And it seem to me the society might well in thinking about this say, "Look. Well and good safety, efficacy, and privacy, but we don't want as a society to encourage sex selection. The use of sex as a way of preventing sex linked diseases is only incidentally sex selection. If you could identify those diseases in some other way and you could identify the male child who, in fact, was not afflicted, you wouldn't abort or prevent the implantation of all males."

So society seems to rightly say we don't want to go down this route and we also don't want to go down the route of PGD for trait selection, and yet I don't hear anything in the kind of principles that are now of concern to the profession, safety, efficacy and privacy, and after that freedom because you don't want to get in the way of the private reproductive choices of any couple. They are the ones who are sort of going to set the bar for what risks they want to subject their child to, if their desire is powerful enough or they're willing, in fact, to have infertile male children ad infinitum, who is the society to say that their desire and freedom should not rule?

So thinking now not so much from the perspective of the individual couples or of the profession which exists primarily to serve them, but thinking of the community that has a stake in how children are born, what our relation to them is, what kind of control we exercise over their origins. The question is can one be confident that these are matters best left to self-regulation.

I mean, the Canadians have -- I'm not up to date as to whether the bill has passed there or not. I know it was in the third reading and there are amendments proposed. So I suspect it hasn't passed -- but they laid down some fairly strict guidelines about what would or would not be permitted and then left other sorts of things to the question of professional regulation and discretion.

That's a long winded way of asking whether there aren't ethical concerns that are not exhausted by the ones that are highlighted by you that are concerns to the society as a whole, and if so, whether the professional society would welcome the guidance of the community as a whole on those matters, leaving you free with respect to the things that are not thereby set out of bounds.

How are we supposed to think about those sorts of things?

DR. CARSON: Well, actually on my last slide that was actually, I think, my first question to your committee.

I think that you've pointed out these are complex issues, and I don't really know the answers to your questions, and we are concerned about whether we really are asking all of the right questions. What else are we doing?

For example, let me just share a personal vignette. I was absolutely certain I was not going to give candy to my first child and he was going to get carrots and celery and only healthy things to eat.

And then, you know, his grandmother gave him an M&M. Well, that ended that, right?

And this is just to show that my experience as a parent changed radically before and after I was a parent, and of course, most of our couples are not parents, and we as physicians try to guide them and help them make this decision that we have from the experience of being parents, of being professionals, but there's a certain point that you can lead horses to water, but you can't make them drink, and the point of making them drink with regulation and with mandates is set by each different country differently.

And I think personally that the self-regulation is a better model for the instance that I described that allows us to be a little bit more flexible. It allows us to incorporate the different diversity and ethnic values to embryos that our different religious and ethnic groups have in this country.

Without that flexibility and with mandated transfer of only three embryos, we won't be able to respect all of those things. Should they be respected? Should we have a mandate?

I don't know. At current we don't, and those are some of the issues that perhaps we're not looking at enough, and again, we welcome any suggestions that you have in terms of areas that we're not looking at and ways we can accomplish that.

CHAIRMAN KASS: Okay. I just have a couple more unless people -- thank you.

I have Mary Ann and Rebecca Dresser.

PROF. GLENDON: George, I have a question for you. Thank you for your presentation and for identifying yourself in the beginning as somebody who is pro regulation, and I'd like to ask you a question about that.

Because it seems to me that in the background here, not just in ART, but in a whole range of analogous issues, the question isn't just self-regulation or no regulation. It's self-regulation plus which kind of regulation.

And you a few minutes ago said "except for the tort system," and I wanted to come back to that and ask you whether when you discussed the weaknesses of self-regulation you also had in mind the weaknesses of the tort system, you as a lawyer had in mind the weaknesses of the tort system as a method of regulation in the medical area.

Because it seems to me that that system might just be the worst of all possible worlds, and I say that partly because my colleague at Harvard Law School, Paul Weiler, did a study of medical malpractice litigation, which showed, on the one hand, that most injuries from medical malpractice remain uncompensated, but on the other hand, the awards that are given in medical malpractice cases are often on little evidence and grossly excessive.

MR. ANNAS: Well, certainly I don't agree with everything your colleague found in his study, and Troy Brennan and others have done other studies, but there are certainly problems with the malpractice system. Nobody likes the system. It mostly leaves most people uncompensated and only works well for quite public injuries which have large payouts, and even then we can wonder whether they're too large.

And it doesn't work at all, as far as we can tell, or very poorly for deterrence, for quality assurance.

Everybody agrees with that more or less, but nobody agrees what to do about that, and that's one of the debates we're having now in this area, but I agree it's not a good system, but you can't just throw it out. You have to replace it with something that's better, and you need to know what your goals are in terms of compensation and quality control and giving the public a form in which to vent its frustrations.

But in terms of reproductive technologies in general, it works even worse there. At least historically it has worked terrible there because people wanted to keep their infertility a secret. That's no longer the case, but historically that was the case.

So you have hardly any suits at all involving artificial insemination by donor, and even to this day most of the lawsuits -- Dr. Carson is exactly right -- involve what essentially are custody disputes, you know, who's going to get the baby when it's all over.

You see hardly any lawsuits involving problems with the child. Most of those are not going to be directed at the IVF clinic anyway. They'll probably be directed at the obstetrician or at the hospital.

So if you want to regulate new uses of like ICSI, you can't do it with tort, which is too blunt. I mean, maybe it will turn out that there are problems and there will be a class action lawsuit in 20 years or something, but it's not going to do any good for current practice.

DR. HURLBUT: Let me just clarify the record on this. I found the statistics.

MR. ANNAS: Okay, good.

DR. HURLBUT: It was slightly higher than I had thought. The total of all the cycles done was 42.6 percent. So there might be reason to think ICSI is being overused.

DR. CARSON: And malpractor infertility is about 40 percent of infertile couples.

DR. HURLBUT: Not all male factor requires ICSI. So that could be said.

DR. CARSON: that's correct, but also some of those couples are repeat cycles, are repeat cycles. So if a woman doesn't get pregnant, she goes through another cycle, and that would be another ICSI.

DR. HURLBUT: Okay, but do you think ICSI might be being overused is really the question. No?

I mean, I'm asking you. I'm not --

DR. CARSON: I don't think so because I think the overuse might cause a problem, and so the motivation to have a higher success rate would not be achieved.

CHAIRMAN KASS: Before I call on Rebecca, George, would you mind? I had meant really when I had put the question to Dr. Carson also to address the question to you, my own question about whether or not the criteria of safety, efficacy, privacy, and in some way freedom of choice are sufficient in this area, given what's actually at stake and whether you yourself think that one could rely on professional regulation to perhaps set some of the boundaries toward appropriate and less appropriate uses of this technology, especially when you combine it with prospects of selection and the like.

I mean, is this a matter to be left to the private choices of the consumers or do you yourself favor or think it's reasonable to develop some kind of --

MR. ANNAS: It sounds like a leading question to me.

CHAIRMAN KASS: I don't know the answer. I don't know what you would say.

MR. ANNAS: Well, that's okay.

Safety and efficacy are obviously things that we should take for granted. That's what FDA does with drugs and devices and we shouldn't expect physicians to offer procedures that aren't safe and effective.

The problem with this area has been that the federal government never funded any research. So we're doing kind of research and practice together. So safety and efficacy are reasonable goals, but you wouldn't expect from any physician.

Privacy has some unique aspects in this particular area, but has tended to mean let the couple decide whatever they want to do, and that's fine as far as it goes as long as the interests of children and society are factored in there.

And the question is: how do you get the interests of children, which I have always thought should be first, but it's hard to put them first; how do you get them accounted for?

But the British system you heard a presentation. In the British system, there it's in their statute that the best interests of children shall be the number one concern of their regulatory agency, and that the interests of the nation shall take precedent, whatever those are, shall take precedence over the interests of the couples, a very interesting concept as well, you know. So see how they figure that on what the interests of the nation are exactly. It's a good question.

But there the regulatory agency is tasked to figure that out and to have that reflected in their decisions.

And I certainly think that -- and I doubt SART disagrees -- that we have to broaden the players and the discussion into how we set these rules.

I mean, not to come back to my colleague John Robertson, but he is the chairman of the ethics committee, and I was pretty flabbergasted to read in the January 2003 issue of Nature and Genetics that he believes as a personal matter, not speaking for the society, that PGD is perfectly appropriate to use for deafness and it's perfectly appropriate to use it to help a deaf couple have a deaf child, to have a healthy child, but to have a deaf child.

That strikes me as something physicians cannot be involved with. There's no way to say that that is a technology or that that is a health child. Even if the deaf community considers it a healthy child, the greater society does not and I don't think should promote the technology for those type of researchers.

He also says he believes that and he says evidence indicates that when new uses of PGD help parents to have healthy, wanted children, society will accept them.

Well, we need society to say that, not to have some person with a preformed view say that.

CHAIRMAN KASS: Thank you.

Rebecca Dresser, please.

PROF. DRESSER: On Mary Ann's point, one thing I've heard about the tort system in this area is that if you're looking at harm to a child, the difficulties in proving caution are so high or so severe that lawyers won't take the case, and they just don't get into the system.

PROF. GLENDON: Can I just?

PROF. DRESSER: Sure.

PROF. GLENDON: What I was thinking about really is down the line the harm to the women that may appear later on as a result of the massive hormone injections.

PROF. DRESSER: Yeah, that's a possibility.

The other point I wanted to make is I think this discussion brings home something I keep harping on. This safety and efficacy is an ethical judgment. I mean, it's balancing. Are the risks so great that the benefits don't justify doing the procedure, or what are the benefits? How valuable are they?

And here in this area, how much value you put on the opportunity to have a biological child makes a huge difference. If you don't think that's very valuable, then the ICSI risk is unjustified and the ICSI is unsafe.

If you think that is incredibly valuable, then a 15 percent risk in ICSI of certainly infertility, which, you know, people can have a very good quality of life if they're infertile; so that risk would not be so high, and you would say -- or too high -- and you would say the procedure is justified.

So who gets to value risks and expected benefits is crucial in this area, and you know, the FDA does it with drugs, with their advisory committees which do often include patient representatives. They have gotten a little bit more diverse in terms of the value judgments.

In this committee, the ASRM ethics committee, the people on the committee are balancing these things, and whether they're the appropriate ones to be doing it is a good question, and obviously the infertility patients are valuing these things, and they're putting an incredibly high value on having a biological child.

So I think we should keep remembering that the safety and efficacy, oh, well, that's something different than ethical. To me that --

CHAIRMAN KASS: No, I regard them as --

PROF. DRESSER: -- that's crucial.

CHAIRMAN KASS: I regard them as ethical concerns.

PROF. DRESSER: So if we could ever get the legislature or Congress to take a stand on, you know, the value of the healthy child in this context is paramount, and you know, we will accept very few risks to the physical health of the child or the psychological health. That would be, you know, in a democracy that would probably be ideal, but it has been difficult to get our legislators to take a stand on something like that.

CHAIRMAN KASS: Well, having the somewhat ill deserved reputation I have of being an enemy of IVF is tied to a paper written in 1971 in the New England Journal after the first successful laboratory fertilization by Edwards, I guess seven years before Louise Brown.

The question was whether this was unethical experimentation on the unborn, question mark, and the sole concern was, in fact, George Annas' concern to say that one shouldn't be simply guided by our sympathy for the powerful desires of the parents. There is a third party here for whom it's not yet clear that the prospective parents who don't yet have the living child in front of them to care for have the best interests of that child in mind until, as Dr. Carson says, the child is there.

Look. Unless someone wants to add, we're late. We had originally budgeted half an hour here for the council amongst itself to discuss the fruits of this discussion. Our guests have been forthcoming and we've not been shy, but I don't think we've cheated ourselves out of this.

Let me simply say that we will build in our discussion of strengths and possible weaknesses of professional self-regulation when the staff brings to the council at our next meeting its preliminary document for discussion on our review of the current situation of regulation in this area, with special attention to the ethical issues, including safety and efficacy.

Let me thank Dr. Carson and Professor Annas very much for your presence, for your generosity, for your clear presentation, and the wonderful way in which you responded to the questions. Thank you very much.

If I could ask counsel members, briefly we have only one presentation, one person to speak in the public session, and that is Richard Doerflinger from the U.S. Conference of Catholic Bishops.

Thank you both very much.

(Applause.)

Public Comment

CHAIRMAN KASS: Mr. Doerflinger, welcome back.

MR. DOERFLINGER: Thank you.

I found myself nodding in agreement with Dr. Annas until he said something nice about the British system. So I wanted to comment on that.

I've been involved in the debates about federal funding of IVF and embryo research for some 20 years. From my perspective, the reason why IVF remains one of the most under regulated industries in the nation is that proponents of regulation always started out by assuming that when you regulate it you have to use the British system. That is, in order to regulate, you have to fund.

In the British system it's all or nothing. There is no private sector in embryo research, and so either you ban it or you have the government actively support and sponsor and license it, which means that in order to regulate abuses, you have to first make a decision that we have a sufficient consensus to provide active government support for this.

Now, in the British system where socialized medicine is the norm, that's not necessarily taken as a moral decision, but in the United States because of our less socialized system, it is.

And there are a great many issues where the way in which our society has dealt with matters of moral ambivalence, matters where there is not sufficient consensus to ban but there is not sufficient consensus to give positive approval, is precisely to allow something to happen in the private sector, but not to fund it.

One might interpret our Supreme Court's decisions on abortion along those lines, that the Court said you cannot ban abortion, but that states and the federal government may use their funding power to express a preference for childbirth over abortion and actually to discourage abortion short of actually placing active barriers in its way.

Now, I think that system, though I disagree with the Supreme Court's decision about that in the context of abortion, that flexibility, shows respect for the pluralism of our society, where a lot of different things are in those gray areas-- either because they really are morally ambivalent, or because gray is what you get when you mix together ASRM's view of the embryo as important tissue and my view of the embryo.

That pluralism and that flexibility should not be lost. I think the reason why we don't have regulation now of IVF is that the insistence has been we have to give our positive approval relating to some of it in order to prevent the worst of it.

I don't think that works necessarily as a matter of practice, because it simply means that you give a baseline and then private funding is used to do all the stuff the federal government is too hesitant to provide funding for.

The private sector then moves back in and says, "why don't the federally funded researchers get with the program now that we've established the new baseline, and begin providing funding?"

I certainly don't think self-regulation is the answer. I think the ASRM ethics committee is an example of a group that is ethically actually willing to go beyond what many of its own members might be comfortable with. The chairman of the ASRM ethics committee, John Robertson, has written at length that people have a constitutional right to do reproductive cloning. I think that's not a widely held view among many. And when the Norfolk, Virginia IVF clinic announced it was creating embryos solely for research purposes, to the great consternation of many ethicists and members of Congress, the first announcement that came out in that report was that the ASRM found this to be consistent with its own ethics standards.

There has been a great deal of commentary in the bioethics literature about industry ethicists telling industry what it wants to hear, and that being the reason why they're hired in the first place.

So between the extremes of self-regulation left untrammeled, and the British system where there's no flexibility, no middle line between federal funding and implied federal approval versus complete ban, I hope this council can find its way to respect the intricacy of the American system and find a way to set restraints on some of the worst abuses in a way that people like me, for example, would not have to oppose because it involves actively approving some of it.

Thank you.

CHAIRMAN KASS: Michael Sandel, do you?

Mr. Doerflinger, would you come back? Mr. Sandel would like to ask a question.

PROF. SANDEL: Did I understand you correctly to suggest that you would favor or support a compromise that might regulate, federally regulate embryo research, even though you might oppose that research, provided it were not federally funded, or did I misunderstand?

MR. DOERFLINGER: Well, I think a federal regulation that said, for example -- and I don't know how you would have to find the federal jurisdiction to do this, perhaps through the interstate commerce clause -- a federal law that said -- well, there's a federal law proposed right now that has passed the House that says you may not do research involving cloning of embryos. That leaves the field of both privately and publicly funded research involving so-called spare embryos completely alone.

I consider that, from the total field of embryo research, that's a regulation. It's a law against one of the worst abuses that involves positively creating embryos for research, possibly in great numbers, and leaves the rest of the field alone.

Leaving the rest of the field alone is not by itself a mark of moral approval. It may just be a decision that there's no sufficient consensus to act against it.

And I'm something of a fan of Thomas Aquinas, who said there is a large area of moral wrong, that it may not be feasible or even appropriate to pass civil laws against.

So there are a lot of opportunities. The FDA is one model in which, by achieving a consensus on one particular area that goes beyond the societal consensus one is not necessarily approving, but only leaving for another day, things that go short of that.

Does that make sense?

CHAIRMAN KASS: I think the comment raises for us, I think, a difficulty that when we're at the point where we would want to offer recommendations we would have to face the various obstacles that George Annas alluded to, various parties on all sides who, on the one hand, don't want the kind of opening that would lead to certain curtailment and, on the other hand, don't want to pronounce with public blessings those things that they regard to be a moral problem we will have to grapple with.

Let me thank once again our guests. Let me thank members of the council for your loyalty and stalwart participation, members of the public for joining us. Safe travel and godspeed. We'll see you --

PROF. GEORGE: Could I just take one moment before we break to fulfill a promise to President Didier Sicard of the French Bioethics Council?

CHAIRMAN KASS: Please.

PROF. GEORGE: Yes. I was received very graciously representing the council and the United States at the 20th anniversary of the Comite Consultatif National d'Ethique, the French Bioethics Council. President Sicard asked me, in particular, to convey regards and compliments to Chairman Kass and to the council.

He and a number of other representatives who were there representing various nations from Japan to Luxembourg indicated that they had read with considerable interest our report on human cloning, and we were congratulated consistently by people for the thoroughness of the report and for its analytic rigor.

And people in particular noted that this was true across the range or spectrum of opinions represented on the report.

I did get the -- I hope I'm not deceiving myself -- but I did get the very clear sense that this was not simply polite talk or "politesse."

There was a certain amount of diplomatic nicety going on in other regards, I think, pertaining to my being there at this time as a representative of the United States, but with regard to the compliments that were paid to the cloning report, as I say, my impression was that they were very sincere.

So it really is a pleasure for me to fulfill this promise to President Sicard and to convey compliments and regards to the council and to Chairman Kass.

CHAIRMAN KASS: Thank you.

The meeting is adjourned.

(Whereupon, 12:06 p.m., the meeting in the above-entitled matter was adjourned.)