Egg donation:

Repetitive Oocyte Donation

The Practice Committee of the American Society for Reproductive Medicine, Birmingham, Alabama

According to the 1997 U.S. results reported in the ASRM/ SART Registry, donor oocytes were used in 6,643 cycles (approximately 9% of all ART cycles) (1). Women may choose to donate oocytes on a number of occasions. This discussion will address the issue of whether limits should be advised on the number of cycles/donations that a given oocyte donor may undergo. Although existing data cannot permit conclusive recommendations, a concern for the issues of safety and the well-being of oocyte donors warrants consideration.

INTRODUCTION

The practice of oocyte donation has potential risks. These include the possibility of transmitting an infection to the donor, her partner, or any resulting infant and the possibility that any offspring, who might be unaware of their genetic heritage, could potentially marry and procreate with an un¬recognized half-sibling. The donor is subjected to the risks of controlled ovarian hyperstimulation and the oocyte retrieval procedure. Whereas the recipient derives a clear and tangible benefit from oocyte donation, the donor derives benefit only through a sense of altruism and/or financial compensation for her services. Thus, the question arises as to whether to limit the number of times that a given oocyte donor might donate her gametes. In the absence of definitive, long-term follow-up, there is nonetheless a motivation on the part of ART practitioners to develop a consensus for what could be considered a prudent approach. Unusual circumstances may be considered on an individual basis such as the case of a donor who would surpass the maximum number of dona¬tions proposed by a guideline if she were subsequently to donate oocytes to her own sister.

INADVERTENT CONSANGUINITY

Inadvertent consanguinity resulting from oocyte donation could occur if: [1] a given donor has donated to two or more families and [2] the offspring were unaware of their specific genetic heritage. Previous guidelines on therapeutic donor insemination and oocyte donation, published by the Ameri¬can Society for Reproductive Medicine, have advised an arbitrary limit of no more than 25 pregnancies per sperm or oocyte donor, in a population of 800,000, in order to mini¬mize risks of consanguinity (2-4). This suggestion may require modification if the population using donor gametes represents an isolated subgroup or the specimens are distrib¬uted over a wide geographic area.

HEALTH RISKS TO THE OOCYTE DONOR

Controlled ovarian hyperstimulation entails both known and theoretical risks, which can only be obviated by the exclu¬sive use of unstimulated cycles, an uncommon and ineffi¬cient practice. In the short-term, there is the risk of ovarian hyperstimulation syndrome (OHSS), which is reported to be associated with approximately 1 % of cycles. The incidence and severity of OHSS may in fact be lower in oocyte donors (5), in part due to the absence of conception in their stimu¬lated cycles.

There continues to be some concern that the use of controlled ovarian hyperstimulation might increase the long-term risk of ovarian cancer (6). Recently published data have not demon¬strated an association between the use of ovulation-inducing agents and ovarian cancer (7), although definitive conclu¬sions await further follow-up. The only study which specif¬ically suggested that the repetitive use of fertility medica¬tions presented greater risk than short-term use addressed the administration of clomiphene citrate (and not exogenous gonadotropins). In that study, the risk of ovarian cancer was significantly increased only when treatment exceeded 12 cycles (8). Limitation of the participation of a given donor to approximately six stimulated cycles would appear reason¬able, particularly as the donor might herself eventually re¬quire fertility therapy (e.g., in the event of delaying child¬bearing to her late reproductive years, or should a future partner have a severe male factor).

The oocyte retrieval procedure itself also poses some risks for the donor. The health risks associated with the low levels of anesthesia generally employed for oocyte retrieval in a young, healthy population should be very small. However, idiosyncratic reactions to anesthetic agents and other anes¬thetic complications (e.g., aspiration) may occur. At present, there is no documentation of any long-term sequelae of follicle aspiration. There is a real, albeit small, risk of acute complications including pelvic infection and intraperitoneal hemorrhage (9). It is expected that the aggregate risk of any of these acute adverse events after a given number of pro¬cedures is simply additive. It is not presently known whether repetitive follicular aspirations could affect the donor's fu¬ture fertility. Lastly, oocyte donation may entail potential psychological risks (ambivalence, regret, etc.). These latter risks should be minimized by appropriate pre-treatment screen¬ing and counseling.

CONCLUSIONS

Currently, there are no clearly documented long-term risks associated with oocyte donation, and as such, no definitive data upon which to base absolute recommenda¬tions. However, because of the possible health risks out¬lined in the preceding discussion, it would seem prudent to consider limiting the number of stimulated cycles for a given oocyte donor to approximately six, and to further strive to limit successful donations from a single donor to no more than 25 families per population of 800,000, given concerns regarding inadvertent consanguinity in off¬spring. Clearly, restrictions on the number of stimulated cycles that a given donor should undergo will in most instances be the limiting factor.

Acknowledgments: This report was developed under the direction of the Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology as a service to their members and other practicing clinicians. While this document reflects appropriate management of a problem encountered in the practice of repro¬ductive medicine, it neither defines the standard of practice nor does it dictate the only appropriate course of medical care. Other plans of man¬agement may be appropriate, taking into account the needs of the individual patient, available resources, and institutional or clinical practice limitations. Accepted by the Practice Committee of the American Society for Reproductive Medicine, May 2000, and approved by the Board of Directors of the American Society for Reproductive Medicine, July 2000.

REFERENCES

1. Society for Assisted Reproductive Technology, The American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 1997 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry.

2. de Boer A, Oosterwijk JC, Rigters-Aris CA. Determination of a maxi¬mum number of artificial inseminations by donor children per sperm donor. Fertil Steril 1995;63:419-21.
3. Curie-Cohen M. The frequency of consanguineous matings due to mul¬tiple use of donors in artificial insemination. Am J Hum Genet 1980;32: 589-600.

4. The American Society for Reproductive Medicine. Guidelines for ga¬mete and embryo donation. Fertil Steril 1998;70(Suppl 3):1S-6S.

5. Sauer MV, Paulson RJ, Lobo RA. Rare occurrence of ovarian hyper¬stimulation syndrome in oocyte donors. Int J Gynaecol Obstet 1996;52: 259-62.

6. Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovar¬ian Cancer Group. Am J Epidemiol 1992;136:1184-203.

7. Venn A, Watson L, Lumley J, Giles G, King C, Healy D. Breast and ovarian cancer incidence after infertility and in vitro fertilization. Lancet 1995;346:995-1000.

8. Rossing MA, Dating JR, Weiss NS, Moore DE, Self SG. Ovarian tumors in a cohort of infertile women. N Engl J Med 1994;331:771-6.

9. Bennett SJ, Waterstone JJ, Cheng WC, Parsons J. Complications of transvaginal ultrasound-directed follicle aspirations: a review of 2670 consecutive procedures. J Assist Reprod Genet 1993;10:72-7.

FERTILITY Committee Opinion

Reviewed June 2006. Released November 2000. No reprints will be available.
Correspondence to: Practice Committee, American Society for Repro¬ductive Medicine, 1209 Montgomery Highway, Birmingham, Alabama 35216.S216 Fertility and Sterility® Vol. 86, Suppl 4, November 2006
Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc. 0015-0282/06/$32.00 doi:10.1016/j.fertnstert.2006.08.037& STERILITY®