Gonadotropins (Repronex, Bravelle, Follistim, Menopur and Gonal F) are used to stimulate ovulation and are used in IVF and other procedures such as IUI. Repronex is composed of two hormones - follicle stimulating hormone (FSH) and luteinizing hormone (LH). Follistim and Gonal F are FSH only. Bravelle and Menopur are mostly FSH with a very small amount of LH. They are products either derived from the urine of Italian postmenopausal nuns or made recombinantly in a laboratory. All products have the same expected pregnancy rates, although a minority of patients will benefit from an LH-containing product.
Gonadotropins are administered as a subcutaneous injection. The dose and length of treatment are determined by your response to the drug. When the eggs are ready, a second hormone injection –of human chorionic gonadotropin (hCG) – is given (also subcutaneous). This hormone stimulates egg release (ovulation). Injection of hCG establishes exact timing for egg release to time intercourse or artificial (intrauterine) insemination approximately 36 hours later. Rarely ovulation will occur prior to hCG administration (and interfere with timing of insemination or intercourse).
Gonadotropins are highly effective in stimulating ovulation. Approximately 90% of women treated with HMG will ovulate. Pregnancy rates vary depending on the presence of other infertility factors and your response. For all-comers, gonadotropin treatment combined with IUI has a pregnancy rate of 18-19% per cycle. The cumulative pregnancy rate is about 30% for 3 completed treatment cycles. Pregnancy rates are about half that if timed intercourse is chosen instead of IUI.
Gonadotropins treatment usually does not cause significant side effects - occasionally it causes headaches or mood changes. There are two main risks of HMG treatment: ovarian cyst formation and multiple pregnancy. The development of small ovarian cysts during treatment is not uncommon and does not usually cause a significant medical problem. The cysts will go away on their own usually within a month. There is a rare risk (less than 1%) of massive ovarian enlargement (hyperstimulation syndrome). In this condition, the ovaries enlarge and may create a significant medical illness with loss of body fluid into the abdomen or chest and are associated with an increased risk of vascular thrombosis (blood clot forming in a vein or artery). This condition may require hospitalization and is potentially serious. The blood test for estrogen - described above as a routine part of management - is intended to prevent the development of massive ovarian enlargement. The blood level of estrogen predicts the risk of ovarian enlargement during the treatment cycle. The drug dose is adjusted accordingly. If the blood estrogen level rises above the safety zone, treatment will be terminated. Ovarian enlargement will only occur if ovulation takes place. Usually, ovulation will not take place unless a second hormone - human chorionic gonadotropin (hCG) - is administered. Again, the overall risk of massive ovarian enlargement is less than 1%, and our monitoring is in party intended to help avoid this problem.
The risk of multiple pregnancies with gonadotropin treatment is approximately 20% but varies significantly depending on your response. The vast majority of these multiple pregnancies are twins. Multiple pregnancy runs a risk of premature birth and neonatal complications or neonatal death. Occasionally, the ultrasound predicts the presence of a high number of eggs during a treatment cycle. A decision may be made to cancel the cycle if the risk of multiple pregnancy is considered by your physician to be too high. The risk of cycle cancellation due to ovarian over response is approximately 5%.
There may be a slight increase in the risk of tubal pregnancy (ectopic) with gonadotropin therapy. If ovarian enlargement occurs, there is a somewhat increased, but quite uncommon, risk of ovarian torsion (the ovary twisting and cutting off its blood supply). In addition, there have been a variety of serious illnesses reported in association with gonadotropin treatment. Their frequency is rare or extremely rare and in some cases a proven link to gonadotropin treatment as the cause is not clear. These medications have been around for decades and are commonplace and FDA-approved for this use.
There are at least two medical publications in the ‘90s suggesting that gonadotropin treatment increases the long-term risk of developing ovarian cancer. There are now recent, more powerful studies suggesting no increase in cancer risk. This issue is new and is evolving - we do not have clear and conclusive evidence one way or the other at this point. Our conclusion is that limited treatments with these medications probably offer little or no risk.