potential complications, such as adult respiratory distress, are so rare, Dr. Cedars said, that she could find no data to provide an estimate of the rate of occurrence.

It is also difficult to estimate a mortality rate, but, conservatively speaking, death appears to occur at a frequency between once every 450,000 and once every 50,000 egg donation cycles (among women with severe OHSS). The numbers are misleading, however, because they include patients who become pregnant with the eggs retrieved from their ovaries and later form blood clots during the pregnancy.

Generally speaking, Dr. Cedars warned, the data concerning the occurrence of ovarian hyperstimulation syndrome are not particularly good. For example, there are very few prospective studies—in which an investigator watches a large cohort of women from before the time they undergo ovarian stimulation until long enough afterward to know the final outcome. Three prospective studies that had reasonable sample sizes reported a risk for OHSS to be between 2.1 to 4.7 percent.

Without the control that comes from a prospective study, it is difficult to get a good measure of the rate of occurrence, and it is difficult to know what the risk factors were for each patient. And without knowing what the risk factors are, it is hard to identify groups of women who are particularly likely to suffer from ovarian hyperstimulation.

Finally, very few of the studies divide cases of the syndrome into early- and late-occurring classifications. Early cases of ovarian hyperstimulation occur within three to seven days of the injection of hCG given to start the ovulation process, and these early cases are caused by that hCG trigger. The late form of ovarian hyperstimulation, by contrast, occurs 12 to 17 days after the hCG trigger and happens in women who have become pregnant with their own fertilized eggs put back into the uterus after the egg retrieval process. In this case, the hyperstimulation syndrome is triggered by hCG from the placenta released early in the woman’s pregnancy.

The distinction between early and late is important, Dr. Cedars said, because the risk of severe complications appears to be about 4 to 12 times higher among women with the late-onset hyperstimulation syndrome. It is particularly important for the issue of donating eggs for research purposes, since these donors will not become pregnant immediately after donating their eggs and thus will not be affected by the late-onset type of hyperstimulation syndrome.

Doctors can use a number of strategies to help egg donors avoid hyperstimulation (see Box 2-3), Dr. Cedars said. The first is simply

Front Matter (R1-R16)

Summary (1-6)

1 Introduction (7-12)

2 Potential Risks Associated with Hormone Treatment (13-30)

3 Potential Risks Associated with Egg Retrieval (31-40)

4 Potential Psychological Risks (41-50)

5 Directions for the Future (51-60)

Appendix A References (61-66)

Appendix B Public Workshop on Assessing the Medical Risks of Human Oocyte Donation for Stem Cell Research (67-72)

Appendix C Workshop Attendees (73-76)

Appendix D Glossary (77-84)

Appendix E Biographical Sketches of Committee Members, Invited Speakers, and Staff (85-96)