GENEWATCH
 
DANGEROUS HARVEST
By Diane Beeson
 

Historically, manipulation of women's bodies by others for profit has taken many forms. One such practice with a long and tragic history is the overzealous prescribing of synthetic hormones. Defined as treatments, rather than experiments, the first synthetic hormone, diethylstilbestrol (DES), and post-menopausal hormone replacement therapy were prescribed to women for decades before their deadly side effects were documented and their use finally curtailed. A current form of hormone abuse encourages financially strapped college students to "donate" their eggs by offering thousands of dollars and skillful appeals to their altruism. Now, biotech entrepreneurs are partnering with fertility clinics in hopes of acquiring eggs for research cloning, making oocytes an even more highly coveted natural resource. Are we repeating a historical pattern in which the casualties from medical misuse of hormones must reach epidemic proportions before the damage they cause is officially acknowledged?

In this article I will briefly review known short-term risks and the more poorly understood long-term risks of egg donation. I will describe some of the efforts that have been made to increase the integrity of the currently empty ritual of "informed consent" by which this expanding trade is being justified. I will conclude by considering some implications of the growing trade in human eggs.

A Few of the Casualties

Calla Papademous answered an ad in the Stanford University newspaper promising $50,000 to a tall, athletic young woman with an SAT score over 1400.1 Thinking she had found a way to repay some of her student loans she answered the ad and was accepted. After only a few days on Lupron, commonly prescribed for egg donation but unapproved by the FDA for this purpose, she suffered a massive stroke. Today, after extensive therapy, she is rebuilding her life, but still suffers some permanent brain damage, physical disability, and is infertile. Since she failed to produce the eggs she was offered only $750.

Alexandra X., featured in the documentary Eggsploitation, was a graduate student in need of money to pay expenses while finishing her dissertation in biology. She was happy to receive $3,000, and thought she had successfully completed the process only to collapse in pain on the floor of a friend's house eight or nine days after the retrieval. After fertility clinic staff where her eggs had been removed repeatedly dismissed her symptoms as "normal," she was finally hospitalized with internal bleeding and rushed into surgery just in time to save her life, but only one of her ovaries. Five years later, in her early thirties, with no family history of the disease, she was diagnosed with stage 2-B breast cancer.

Deaths from early-onset reproductive and other cancers have been documented in a number of former egg donors and in many women who have undergone essentially the same ovarian hyperstimulation and egg retrieval as part of their own in vitro fertilization. Consider Stanford student Jessica Wing, who was stricken with fatal colon cancer shortly after her third egg retrieval and died at age 32. Her physician mother, Jennifer Schneider, had genetic tests conducted, which ruled out any genetic susceptibility to the disease. Based on this and further research into the issue, she has challenged the adequacy of current standards of informed consent and has become an advocate for better prospective studies of egg donors.2 

Just how common are tragedies such as those described above? No one knows. We cannot be sure that early onset cancers, such as Jessica Wing's, are related to earlier ovarian stimulation. Nor can we be sure they are not caused by the radical disruption of the endocrine system that characterizes typical egg harvesting protocols-no one is keeping track of egg donors once they leave the clinics.

What we do know is that the American Society of Reproductive Medicine acknowledges significant risks in its professional literature. Its Ethics Committee states that donors are "exposed to risks of morbidity and a remote risk of mortality from COS [controlled ovarian stimulation] and oocyte retrieval" and that "it is possible that fertility drugs could increase a woman's future health risks, including the risk of impaired fertility."3 We also know that an unknown number of women have died during the development and application of these practices,4 which have now been refined to the point that fatalities appear to be rare. But then again, no one is counting.

How invasive is the process?

In 2006, the California Institute of Regenerative Medicine asked the Institute of Medicine to convene a conference to provide information on the safety of egg donation. The conference report, "Assessing the Medical Risks of Oocyte Donation For Stem Cell Research," draws on studies of women undergoing ovarian stimulation to extract eggs for their own fertility treatment, and describes the process this way:

The woman self-injects hormones (gonadotropins) to stimulate the growth of ovarian follicles, plus a gonadotropin-releasing hormone (GnRH) agonist to block the normal surge of lutenizing hormone (LH), which could cause the woman to ovulate before the physician retrieves the eggs. . . . A woman subsequently self-injects the hormone human chorionic gonadotropin (hCG, similar to LH) to effect egg maturation. When the eggs are ready the woman is brought into surgery, where she receives intravenous sedation, after which a transvaginal probe is placed in her vagina. A hollow needle emerges from the probe, travels through the back of the vagina and into the ovary, where under the guidance of ultrasound technology, the eggs are aspirated.5

What are the short-term risks?

The ingestion of various drugs in preparation for egg retrieval, and the egg retrieval process itself, entail a variety of physical and psychological risks, including those stemming from the use of anesthesia, and surgical complications such as infection and bleeding. The most common side effect connected with egg donation is ovarian hyperstimulation syndrome, or OHSS. This may include nausea/vomiting, pain, fluid buildup in the abdomen, shortness of breath, and in more serious cases, blood clots, severe pulmonary distress, and kidney (and/or other organ) failure.6

The IOM report cites three prospective studies on women undergoing fertility treatment that estimate the risk for OHSS to range from 2.1 to 4.7 percent.7 At the same time, it acknowledges both that "the data concerning the occurrence of ovarian hyperstimuation syndrome are not particularly good"8 and that the definition of this iatrogenic disorder has been redefined to exclude its mildest manifestations.9 

More recently, a non-industry-sponsored retrospective report of 155 former egg donors found that over 30% reported some degree of OHSS, and 11.6% required hospitalization and/or paracentesis (puncturing of the belly with a needle to draw out fluid), revealing a striking discrepancy between risk rates reported by industry insiders and independent researchers.10

What are the long-term risks?

Less well understood, but of even greater concern to women's health advocates than the short-term effects, are the long-term risks, particularly reproductive cancers. The IOM Report dismisses evidence of increased risks for breast, endometrial, and ovarian cancers found in some studies, but acknowledges concern with regard to uterine cancer. It also acknowledges that the studies that found no increase in risk may have done so due to inadequate long-term follow-up.11 

The IOM Report concludes by admitting that "one of the most striking facts" about ovarian stimulation is how little is known about its long-term effects on women:

Although more than a million IVF cycles have been performed in the United States over the past 20 years ...there are no registries that track the health of the people who have taken part.  ...[T]he studies vary quite a lot in terms of study design, the number of subjects, and outcome, so it is impossible to draw a consistent picture from them.12

In the four years since the IOM conference was held concerns regarding cancer as a potential long-term side effect continue to mount. According to Dr. Louise Brinton of the National Cancer Institute:

There has been little attention focused on the long-term effects of assisted reproductive technologies, which often involve much higher exposures to gonadotrophins than were received by women in previous eras. . . . Since in-vitro techniques have become common only in the last couple of decades, it may be some time before epidemiological studies can amass the follow-up times required to fully address long-term effects.13

She also states:

Although most attention has focused on effects of fertility drugs on ovarian cancer risk, more recent investigations support the need for further attention on breast and endometrial cancers. The need is supported by the recognition that ovulation-stimulating drugs are effective at increasing both oestrogen and progestin concentrations, alterations that have been linked with both of these cancers. Further, a relationship with breast cancer would parallel findings of an increased risk of this tumor among mothers exposed to diethylstilbestrol during pregnancy.14

While Brinton links ovarian stimulation to the DES disaster, prospective egg donors are not likely to know that it took nearly three decades of exposure to this first synthetic hormone before its causal link to elevated cancer rates among both the women to whom it was prescribed and their daughters, and genital abnormalities in many of the sons was documented.15 Ironically, exposure to DES in utero is a known cause of infertility in females, thus contributing to the market for today's fertility industry. In the case of post-menopausal hormone therapy, it was only after decades of demands from women's health advocates that clinical trials belatedly were begun. These trials were stopped in 2002 when it became apparent that women taking estrogen plus progestin were having more strokes, heart disease, and breast cancer.16 The following year, when tens of thousands of women stopped taking these hormones, we witnessed an unprecedented decrease in new cases of breast cancer.17

Brinton is not the only epidemiologist with concerns about ovarian stimulation. A recent Israeli study found "an association between treatment for ovulation induction and overall risk of cancer, particularly cancer of the uterus."18 But cancers are not the only poorly documented risk. Both cerebral19 and myocardial infarction,20 for example, have been reported in women undergoing ovarian stimulation even in the absence of OHSS. Egg donors interviewed by this author report ovarian cysts, severe mood swings, uncontrollable weight gain, and numerous other life-disrupting symptoms that are ignored in the existing research and were not considered in the IOM report.

The lack of adequate longitudinal data means that "informed consent" functions primarily to protect clinics and professionals from liability, but fails to meaningfully protect egg donors. Ads focusing on financial compensation and altruism, to the exclusion of any suggestion of possible risk, have created a culture on college campuses in which it is widely believed is that egg donation is well established, routine, and completely safe. Furthermore, consent forms, whatever their content, are not likely to be seen by potential donors until long after they have made the decision, based on ubiquitous advertising, to sell their eggs. Alliance for Humane Biotechnology activists last year succeeded in getting support for AB 1317, a bill in the California legislature, to require that ads soliciting egg donors reference existence of medical risk, but the American Society of Reproductive Medicine insisted that the bill exempt brokers and clinics who agree to follow ASRM ethical guidelines. The result? Egg broker ads referencing health risks have yet to be spotted.

Two recent studies, one of advertising and compensation for egg donors, the other a study of compliance and range of fees among egg donor and surrogacy agencies, both found that many of the egg donor agencies in the U.S. routinely violate ASRM's ethical guidelines. Compliance, to the extent it does exist, is self-reported and unverified. The guideline's primary function seems to be to support claims of self-regulation.

Women having their eggs harvested for their own use in the hopes of achieving pregnancy face essentially the same risks from ovarian stimulation as egg donors. The justification for the risk in their case is the hoped-for birth of a child. However, concerns acknowledged by 2010 Nobel Laureate R.G. Edwards about safety and damage that routine IVF may cause to both infertility patients and offspring are fueling international interest in alternative fertility treatments such as minimal stimulation IVF and natural cycle IVF.21

 Scientists push for easier access to eggs

In discussing scientists' interest in acquiring eggs for cloning research, the author of a 2006 Nature article acknowledged that "cloning is a wildly inefficient process" and that egg donations are "an ethical quagmire."22 Long before the demand for eggs reached this point, in 2001, pro-choice women's health advocates, led by Our Bodies Ourselves, sponsored a call for a moratorium on embryo cloning primarily because of its dependence on large numbers of human eggs.23 Three years later Korean stem cell researcher Hwang Woo-suk was found to have used more than 2,200 eggs in his fraudulent effort to harvest stem cells from a cloned embryo. This resulted in 17.7 percent of the women who supplied the eggs suffering adverse health effects. Charges of coercion and human rights violations ensued.24

The large number of human eggs required for cloning research was a driving concern for pro-choice feminists who opposed California's 2004 $3 billion initiative that established the California Institute of Regenerative Medicine. Alarmed at the bill's prioritization of research cloning, a process dependent on women's eggs, a group of women's health advocates, this author included, formed the ProChoice Alliance Against Proposition 71. We submitted for inclusion in the Voter's Handbook a statement arguing against the measure. Proponents of the initiative, including two prominent scientists (one a Nobel laureate), then took legal action in an unsuccessful attempt to keep us from both using the word "cloning" and from relating to voters that embryo cloning relies on a large supply of human eggs.25 Today, scientists are protected from acknowledging that egg harvesting exposes women to significant risks by the fact that the research necessary to determine the extent of the harm has yet to be done.

A series of international and national declarations and regulations affirm the importance of informed consent and the prohibition of undue inducement or influence. Disregarding these principles is considered a violation of human rights. These international standards inform the National Academy of Science's guidelines recommending that "[n]o payments, cash or in kind, should be provided for donating oocytes for research purposes."26 Nevertheless, in 2009 New York became the first state to disregard the NAS guidelines. At a hearing of the state's Ethics Committee to consider the ethics of payment, physician Jennifer Schneider described her daughter's tragic premature death following her third egg donation. She challenged the committee: if it chose to ignore NAS Guidelines, would it at least recommend the establishment of a donor registry to facilitate monitoring the long-term effects of egg donation?27 The committee made no such recommendation.

In 2006, the ProChoice Alliance for Responsible Research led a successful effort to pass California law SB 1260, which tightened restrictions on compensation for eggs (beyond expenses) for non-CIRM-funded research and closed a loophole in CIRM's regulations that could have allowed the use of non-CIRM money to acquire eggs. Since then, CIRM Director Alan Trounsen has made it clear he hopes to change this.28 In June of this year CIRM held a workshop in which legal and ethical obstacles to achieving Somatic Cell Nuclear Transfer were discussed. The public was excluded from this workshop, in what one commentator called an apparent violation of the "the spirit and probably the letter of the California State Constitution and state open meeting laws."29 Minutes of this meeting make it clear that despite acknowledging medical and ethical barriers to procuring eggs from human donors through ovarian stimulation, many scientists are intent on pursuing research using human eggs.30 And most recently a lobbyist for the American Society of Reproductive Medicine volunteered that the ASRM was considering sponsoring legislative changes to remove prohibitions on payment for eggs for research in California.31

One of the implications of the expansion of the egg trade to procure eggs for research is that, unlike the eggs sought for reproduction, the genotype of the donor is usually irrelevant. This means the market can be expected to move beyond college campuses and into the poorest communities, both in the US and around the globe, where financial inducements may be even more irresistible and social conditions may further compromise the integrity of these transactions.

 Alliance for Humane Biotechnology is one of several organizations attempting to alert the public and policy makers of the risks to which egg donors are being exposed. Earlier this year AHB was contacted by a young man worried about his girlfriend who, after donating eggs, suffered a seizure, mood swings, shortness of breath, and blurred vision. He wanted advice on what she should do-having no medical insurance and a denial from the clinic that her symptoms were caused by the egg harvesting. While examples of casualties abound, those profiting from the practice of egg donation continue to dismiss the accounts as anecdotal. This will likely continue until an independent national registry of women undergoing ovarian stimulation is established and adherence to ethical standards is enforced by independent oversight.                 

 

Diane Beeson, PhD, is chair of the Department of Sociology and Social Services at California State University, East Bay.

Acknowledgement: The author is indebted to Tina Stevens for a close reading, helpful suggestions, and generous editorial assistance.

 

 

1. Hamilton, J. 2000. What are the costs?  Stanford Magazine. http://www.stanfordalumni.org/news/magazine/2000/novdec/articles/eggdonor.html

2. Schneider, Jennifer. 2008. Fatal colon cancer in a young egg donor: A physician mother's call for follow-up and research on the long-term risks of ovarian stimulation. Fertility and Sterility, 90:2016.

3. ECASRM (Ethics Committee of the American Society for Reproductive Medicine). 2007. Financial Compensation of oocyte donors. Fertility and Sterility. Vo. 88,No. 2, August. pp. 305-309.(quote on p. 6).

4. Andrews, L. 2000. The Clone Age: Adventures in the New World of Reproductive Technology. New York:Henry Hold and Co. p. 35. ; Corea, G. 1988. The Mother Machine: Reproductive Technologies from Artificial Insemination to Artivicial Wombs. London: The Women's Press, p.318.

5. Guidice L., Santa E. and R. Pool (Eds.) 2007. Assessing the Medical Risks of Human Oocyte Donation for Stem Cell Research: Workshop Report. Institute of Medicine and National Research Council of National Academies. Washington, DC: National Academies Press. Pp. 10-11.

6. Guidice L. p. 19

7. Guidice, p. 20

8. Guidice, p. 20.

9. Guidice, p. 18.

10. Kramer, W., J. Schneider, and N. Schultz. 2009. "US oocyte donors: retrospective study of medical and psychosocial issues." Human Reproduction. September.

11. Guidice, p. 26.

12. Guidice, p. 13.

13. Brinton, L. 2007. Long-term effects of ovulation-stimulating drugs on cancer risk. Reproductive BioMedicine Online. Vol. 15. No.1, pp. 38-44.

14. Brinton, p.

15. Cody, P. 2008. DES Voices: From Anger to Action. Columbus Ohio: DES Action. P. 17

16. National Institutes of Health. http://www.nhlbi.nih.gov/whi/whi_faq.htm

17. National Cancer institute. 2007. http://www.cancer.gov/newscenter/pressreleases/2007/breastincidencedrop

18. Calderon-Margalit, R. et al. 2008. "Cancer Risk After Exposure to Treatments for Ovulation Induction." American Journal of Epidemiology, (Advance Access published November 26, 2008).

19. Demirol A, Suleyman G, and Gurgan T. 2007. Aphasia: an early uncommon complication of ovarian stimulation without ovarian hyptestimulation syndrome. Reproductive Biomedicine Online. January.

20. Coli, S, et al. "Myocardial infarction complicating the initial phase of an ovarian stimulation protocol." International Journal of Cardiology, Vol. 115, Issue 1, Jan. 31, 2007.

21. Edwards, R.G. 2007. "Are minimal stimulation IVF and IVM set to replace routine IVF? Reproductive Biomedicine Online. Vol. 14, No. 2., Pp. 267-270.

22. Dennis, C. 2006. Cloning: Mining the secrets of the egg. Nature. Vol.439, 9. February. Pp. 652-655.

23. Norsigian J. 2002. Emerging Biotechnologies: Cloning. Testimony to Senate Health, Education, Labor and Pensions Committee. March 5. http://www.ourbodiesourselves.org/book/companion.asp?id=25&compID=67&page=9

24. Son, Bonghee. 2006. "The Hwang Woo-suk case and the significance of a damage claim for victims of egg extraction."  Paper presented at the International Forum Envisioning the Human Rights of Women in the Age of Biotechnology and Science. Seoul, Korea.

25. Memorandum of Points and Authorities in Support of Petition for Writ of Mandate and Alternative Writ of Mandate/Order to Show Cause. 2004 (Undated, no case number) Paul Berg, PhD; Robert Klein; and Larry Goldstein, Petitioners vs. Kelvin Shelly, Secretary of State of California, Respondent, Geoff Brandt, State Printer; Bill Lockyer. Attorney General of California ; Tom McClintock; H. Rex Green John M. W. Moorlach; Judy Norsigian; Francine Coeytaux; Tina Stevens; Does I through X, inclusive, Real Parties In Interest. Also see: Paul Berg, Ph.D; Robert N. Klein; and Larry Goldstein, Petitioners v. Kevin Shelly, Secretary of State of California, Respondent, Case No. 04CS01015, Superior Court of the State of California, "Declaration of Dr. Stuart A. Newman, PhD., in Opposition to Petition for Writ of Mandate and Alternative Writ of Mandate/Order to show Cause," August 4, 2004, p. 2.

26. National Academies of Science. Final Report of the National Academies' Human Embryonic Stem Cell Advisory Committee and 2010 Amendments To the National Academies' Guidelines for Human Embryonic Stem Cell Research. Section 3.4b. http://www.nap.edu/openbook.php?record_id=12923&page=27#p2001b5399970027001

27. Personal communication. December 1, 2010.

28. Dolgin, E. CIRM to Pay for eggs?http://humanebiotech.com/cirmwantseggs.html

29. http://californiastemcellreport.blogspot.com/2010/06/stem-cell-agency-bars-public-from.html

30. CIRM-MRC Human Somatic Cell Nuclear Transfer Workshop Report , June 13-14, 2010. www.cirm.ca.gov/files/PDFs/.../Human_SCNT_Workshop_Report.pdf

31. California Department of Public Health Human Stem Cell Research Advisory Committee Meeting. November 30, 2010.

 
 
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