(Testimony of Francine Coeytaux, MPH, Pro-Choice Alliance for Responsible Research, before a joint hearing of the California Senate Subcommittee on Stem Cell Research Oversight, the Senate Health Committee, and the Assembly Health Committee)

Good afternoon. I appreciate the opportunity to address your committees. My name is Francine Coeytaux. The last time I stood before you, Senator Ortiz, I was here on behalf of the California Advisory Committee on Human Cloning. Thank you for inviting me again.

Today I come wearing several hats:

The first is as a social scientist and women's health advocate. My expertise is in public health, acceptability research and the intersection of science, politics and the interests of women. I have spent the last twenty years working on the development and public introduction of new reproductive technologies including: NORPLANT, emergency contraception, microbicides and the abortion pill. I am a founder of the Pacific Institute for Women's Health based here in California whose mission it is to improve the health and wellbeing of women worldwide. I also helped found the Reproductive Health Technologies Project, an organization based in Washington DC which focuses on consensus-building among constituencies often at odds in their viewpoints on women's reproductive health matters, especially issues regarding the historical use or misuse of reproductive technologies. From December 1998 to January 2002 I served as an appointed member of the California Advisory Committee on Human Cloning, where we vigorously examined and debated the very issues that are now before this committee.

Second, I am here as a representative of the Pro-Choice Alliance for Responsible Research. A coalition of advocates, scientists and health professionals, we seek to promote responsible research in the fields of genetics and reproduction.

Finally, I am here as a mother. My husband, a neuroscientist at UCLA, and I have sixteen year old twins, a boy and a girl. Our daughter, Sabine, was born with a chromosomal abnormality. Because of this, we have firsthand experience with the heartbreaking decisions parents are faced with when trying to avail themselves of new scientific breakthroughs that might help cure or alleviate the suffering of their children. Frankly, it is because of this convergence of my professional and personal interests that I have recently applied myself to addressing the many red flags that Proposition 71 raised for me.

I am here today, on behalf of the Pro-Choice Alliance, to urge you to use your legislative authority to demand and require the highest ethical and medical standards for protection of the health of women who will be asked to donate eggs for research purposes. Our request is simple, reasonable and can be implemented without obstructing the progress of the science. Women will be the first human subjects of Proposition 71 funded research. We are asking that mechanisms be put in place to ensure that women who provide eggs be accorded all established protections for human research subjects; that as research subjects, they be given full information in advance about the direct and indirect risks of the research; and that their recruitment never be coercive. We sincerely believe these safeguards must be put in place in order to protect the health of the research subjects, the reputations and credibility of the scientists involved, and in general to advance the promise of stem cell research.

We support most embryo stem cell research and also support the use of otherwise-discarded embryos from IVF clinics. We have had this position since before the election. However, we do have deep reservations about the long term health consequences for women of embryo stem cell research that involves somatic cell nuclear transfer (SCNT), also referred to as embryo cloning, or "therapeutic" cloning as it is currently done. Specifically authorized by Proposition 71, somatic cell nuclear transfer will require extracting eggs from thousands of healthy women for research purposes.

Those who oversee the ethical conduct of research, especially members of Institutional Review Boards (IRBs) and now members of the ICOC, have a duty to carefully weigh the "risk/benefit" ratio when making decisions about whether to approve a research protocol. Embryo cloning research poses significant challenges in this regard.

On the benefit side, stem cell research holds much promise. And it is on the basis of the public's hopes that Proposition 71 passed. But now, with the campaigning behind, the promoters of the Institute for Regenerative Medicine need to stop exaggerating the promise and attempt to realistically describe and weigh the potential gains. Particularly disingenuous in the oversell is the failure to convey the information credible scientists acknowledge - that the benefits are hypothetical and only a distant promise. Preying on the hopes of families who have loved ones with immediate needs may have been a good campaign strategy but is exactly what we must avoid when laying out the potential benefits in a risk analysis.

On the risk side of the equation, attention is lacking to the substantial risks to women's health posed by the advent of embryo cloning. Omitted from the current polarized debate is any discussion of the thousands of women who will need to undergo egg extraction procedures to provide eggs for such embryo cloning. Among our primary concerns are the serious and substantial risks to women's health posed by the practice of multiple egg extraction to harvest eggs for SCNT and the inability to obtain true informed consent from egg donors given the current lack of adequate safety data.

What are the risks of multiple egg extraction? Stimulation drugs may cause Ovarian Hyper-Stimulation Syndrome (OHSS) in about 3-8% of patients. It can progress rapidly to a life-threatening condition days after completion of egg collection. OHSS has been associated with death and has been reported in younger women.

Risks associated with Lupron™ (leuprolide acetate) - the drug used to "shut down" the ovaries before stimulation with other drugs - include depression, memory loss, liver disorders, bone loss, and severe muscle, joint and bone pain. Some of these problems persist long after the drug is first used, and the FDA has not yet followed up on the thousands of reported adverse drug reactions, including hundreds of hospitalizations. For a number of years, many of the women adversely affected by Lupron shared their experiences on the Internet as part of the "Lupron Victims Network."

Supporters of embryo cloning are quick to point to the fact that the procedures for multiple egg extraction are the same as those being performed in infertility clinics where thousands of women undergo "in vitro fertilization" (IVF) procedures for reproductive purposes. But there are huge problems with this argument:

First and foremost, infertility treatment is not a good model because it has been totally unregulated. As a result we are faced with a paucity of long term safety data accompanied by numerous reports of serious and occasionally irreversible problems experienced by women using these drugs.

Second, the health risks involved in multiple egg extraction for fertility purposes are at least offset by a clear direct benefit. In the case of IVF, the best infertility clinics can now offer 30-40% success rates, so that women undergoing multiple egg extraction - whether to achieve a pregnancy themselves, or to be an egg donor for another woman - do know that there is a clear potential direct benefit, and one that is of inestimable value: a baby. Harvesting a woman's eggs for research has no direct benefit to the research subject. Not only is the benefit not direct to the egg provider, but it is neither immediate nor certain. The potential of embryonic stem cell research to cure and treat disease is still only a possibility. Therefore the balance of risks and benefits of egg extraction for research must be evaluated very differently than one might do for egg extraction for fertility purposes.

Third, the issue of reimbursement for eggs has been a cause for concern in the women's health community for years. Even though fertility clinics continue to assert that the fees are not incentives but "reimbursements", it is not uncommon to see ads offering thousands of dollars to women who fit certain descriptions and willing to undergo multiple egg extraction. Most of these ads are targeted to highly educated and privileged young women, and some might argue thus dampening the coercive nature of the payment. This will not be the case in a market for eggs for the purposes of embryo cloning. In SCNT the egg is stripped of the donor's genetic material so the focus will simply be to recruit young, healthy women. And if financial payments are made even in the guise of "reimbursement," in all likelihood the majority of women offering their eggs will be poor women. The tremendous potential for the recruitment of donors with financial incentives that can only be construed as coercive has been exacerbated by the infertility field and must be addressed. Frankly, the IVF industry serves more as an example of how not to proceed than as a model.

The lack of regulation of the infertility field is a concern shared by a former Chief Medical Officer of the Food and Drug Administration, Dr. Suzanne Parisian (also a former researcher in genetics and developmental biology.) In her 3-page letter, released this past week and of which you have a copy in your briefing package, she emphasizes that "many of the drugs used during these procedures have not been adequately studied for long term safety, nor do some of these drugs have FDA approval for these specific indications. This is not widely understood and has led to significant misunderstanding about the risks involved for women who donate eggs either for reproductive purposes or for SCNT research."

Pharmaceutical firms have not been required by either the government or physicians to collect safety data for IVF drugs regarding risk of cancer or other serious health conditions despite the drugs having been available in the United States for several decades. In addition, many of the drugs being used are being used "off label", meaning that they were never approved by the FDA for multiple egg extraction. For example, Lupron™, perhaps the most commonly used drug in IVF treatment, although approved for several specific uses, is NOT approved for use in these procedures for multiple egg extraction. Essentially, a whole industry has arisen and flourished now for over a decade with few of the regulatory oversights we have come to expect of medical practice in the United States. Lack of FDA approval and/or review of these drugs as part of egg extraction procedures should be a major concern of anyone considering SCNT research.

Given recent attention to the harm that can result when clinical trial data are withheld - just consider the track record with Vioxx™, Celebrex™, and the anti-depression drugs known as SSRIs - the public should demand that companies release all available safety data for drugs used in egg extraction. This would include the release of unpublished data on leuprolide acetate collected some years ago by TAP Pharmaceuticals.

In summary, because we have such an incomplete picture of the risks to women's health, we believe that at this date, no woman can give truly informed consent to participate in egg extraction for research purposes.

The Pro-Choice Alliance for Responsible Research and our Coalition partners would like to make the following recommendations to the California state legislature:

1. California researchers should be required to adopt the safest and most ethical approaches to collecting eggs for SCNT or other research.

2. Extraction at the time of an ovariectomy or a tubal ligation would be far safer and more ethical than conventional multiple egg extraction procedures. Even single egg extraction with natural cycling (involving no hormonal manipulations of the ovary) would be safer than conventional methods.

3. Before undertaking multiple egg extraction from healthy women, all data on drugs used in such procedures should be reviewed by a neutral, knowledgeable, and independent oversight body whose sole purpose is to protect the safety and rights of women wishing to provide eggs. In order to accomplish this review, pharmaceutical firms must be required to disclose the FDA-approved indications and all available safety data on these drugs.

4. Before undertaking multiple egg extraction from healthy women, better quality data should be gathered that would make true informed consent possible for women considering providing eggs for research.

5. Every woman who provides eggs for research should have her own physician who is independent of the research and the research institution, and whose only job is to look out for the well-being of the woman.

The California legislature's groundbreaking legislation banning human reproductive cloning and allowing non-reproductive cloning was what made Proposition 71 possible. The Human Cloning Committee explicitly recommended that "California regulate all human non-reproductive cloning in the State, public or private. That regulation should do at least three things: a) prohibit the use of pre-embryos after development of the primitive streak, b) ensure that the persons providing cells for this purpose gave informed consent, and c) require that the research be permitted by an approved Institutional Review Board (IRB)." We believe it is now your responsibility to regulate the use of this technology. So far, in spite of our repeated attempts to raise the issue, the Institute for Regenerative Medicine has refused to acknowledge, much less discuss, the challenges inherent in developing standards which guarantee true informed consent for women considering the donation of eggs for this research. Instead, we have seen an exaggeration of the benefits and a dismissal of any risks. We urge this committee to take steps to ensure that California women are not harmed as this vast experiment in medical research moves forward.

Thank you.