The Pew Charitable Trust has awarded $750,000 to the Genetics and Public Policy Center for a new project focused on consumer protections for applications of genetic testing.
Ovarian stimulation and oocyte retrieval are used most often for couples attempting to use in vitro fertilization to have a biologically related child. In IVF, oocytes (eggs) are removed from a woman’s body after she has taken drugs to stimulate egg production. Eggs are fertilized in a laboratory dish, and one or more resulting embryos are transferred to the woman’s uterus to initiate a pregnancy.
To date, more than one million babies have been born worldwide as a result of IVF and in 2003 U.S fertility clinics reported 112,872 IVF cycles. Although there has been considerable medical literature exploring the possible health effects of in vitro fertilization to babies born from this technology, the potential health risks to the women who undergo this process have been less extensively studied.
No medical procedure is without risks, and ovarian stimulation and oocyte retrieval is no exception. Possible shortterm risks include excessive hyperstimulation resulting from the drugs used to stimulate ovulation. Possible longerterm risks include reproductive or gynecological cancers. It is clear from the rapid growth of IVF that, for many women and couples, the potential risks of IVF are outweighed by the benefit of being able to give birth to a biologically related child or children.
IVF techniques have been used not only to help couples have their own children, but also to provide oocytes that can be donated to an infertile couple seeking to have a baby using a donor egg. More recently, ovarian stimulation and oocyte retrieval have been used to collect oocytes for use in embryonic stem cell research.
Each of these procedures raises issues about the impact and risk of ovarian stimulation and oocyte retrieval for women. This paper explores what is and what is not known about the risks of ovarian stimulation and oocyte retrieval, for both a prospective mother and a prospective egg donor. However, as this white paper describes, more conclusive data about the risks of ovarian stimulation and oocyte retrieval to women are needed.
The primary known shortterm risk of ovarian stimulation is ovarian hyperstimulation syndrome (OHSS). Controlled ovarian hyperstimulation (also know as COH) modulates the woman’s follicular development cycle with hormones to induce the ovary to produce more than one follicle simultaneously and therefore produce more eggs. Women react differently to the many different drug protocols that are used, and for some, the drugs cause OHSS, which brings severe and sudden health risks to the patient, ranging from mild symptoms of abdominal discomfort to renal failure and death.
All women who undergo ovarian stimulation are at risk for this condition. However, some data demonstrate that OHSS may occur less frequently among women who undergo COH for oocyte donation, as compared to those who continue on with IVF for the purpose of having children. Sauer et al (1996) found that fewer than 2 percent of oocyte donors developed severe OHSS following a standard stimulation cycle, less than the rate of OHSS among IVF patients, which ranges from 2 percent to 50 percent. Other research has supported this finding. (Morris et al., 1995). It has been suggested that the subsequent development of OHSS is directly related to the presence of a hormone called human chorionic gonadotropin (HCG) and that the production of endogenous HCG by a woman following embryo transfer may increase the risk of OHSS (Sauer et al., 1996; Morris et al., 1995).
OHSS is generally classified into three categories based on severity, from mild to severe (Navot et al, 2001). Mild OHSS is associated with only minimal pain and other mild symptoms and is often regarded as an acceptable endpoint of the controlled ovarian hyperstimulation. “Mild OHSS is routinely inflicted on a large proportion of women undergoing so called COH, thus mild OHSS is nothing more than an acknowledgement that COH has indeed been achieved” (Navot et al, 2001). Moderate OHSS involves abdominal pain and bloating, nausea, and diarrhea. Clinically, any indications of fluid shifts are detectable only with an ultrasound. This stands in contrast to severe OHSS in which fluid shifts are apparent in the abdomen and throughout the body tissues and organs. Symptoms include severe abdominal bloating, distention and pain, shortness of breath, abnormally low blood pressure and high pulse rate. This massive shift in volume out of the blood vessels and into the surrounding tissue results in impaired organ function, most notably in the liver and kidney. Hospital management is indicated for moderate OHSS, with the strategy of preventing further escalation of clinical signs and symptoms, and additional care measures offered by an intensive care unit are often required for the management of OHSS. OHSS management includes supportive therapy for decreased blood volume and organ dysfunction until these systems return to normal function (Gardner et al., 2001).
New drug protocols are being developed to decrease the risk of OHSS. One example is the use of drugs such as gonadotropin releasing hormone (GnRH) antagonists. This class of drugs directly blocks cellular receptors and prevents an initial hormonal surge thought to induce the OHSS cascade of events. Another technique that may reduce the risk of OHSS is withholding the administration of HCG to trigger final oocyte maturation before retrieval (Orvieto et al 2005; Navot et al, 2001). In addition, recent research has resulted in the discovery of a gene that codes for the Follicle Stimulating Hormone (FSH) receptor. Identification of this gene may provide important predictive information about an individual patient’s response to ovarian stimulating drugs and allow for better dosing to prevent OHSS (Greb et al., 2005; Daelmans et al., 2004). In the future, knowing more about this gene may help identify women who are at increased risk for OHSS and help reduce occurrence of OHSS.
There are also short-term health risks associated with the oocyte retrieval process, including those from bleeding, infection, and anesthesia. (Sauer, 2001). Pain and anxiety are other issues that have been less well studied (Jordan et al.,
Some studies have followed women who have undergone ovarian stimulation and oocyte retrieval for long periods of time to assess the long-term increased health risks of these procedures. These studies have focused on whether there is an increased risk for gynecological malignancies such as ovarian, breast, or endometrial cancer. Though some studies have focused on egg donors, most of these data have been collected from infertile women undergoing these procedures as a part of IVF in order to have a child. Although the procedures involved in ovarian stimulation and oocyte retrieval are the same regardless of the purpose, women undergoing these procedures as a part of IVF may have underlying physiological differences from fertile women who undergo the procedures to donate eggs either to an infertile couple or to embryonic stem cell research. For example, as a result of the underlying infertility, infertile women may be at greater risk for long-term health issues, such as gynecological cancers. Thus, it is unclear whether the risks identified in women undergoing IVF may be translatable to fertile women going through ovarian stimulation and oocyte donation for other reasons.
Studies on the risk of gynecological cancers—such as breast, ovarian, and uterine malignancies—dominate the
literature about the potential long-term risk of COH. However, the association with non-gynecological malignancies also has become an area of growing interest. There has been very limited discussion of the other longterm medical risks (e.g. the development of hypertension or diabetes).