Gonadotropins are fertility medications given by injection that contain follicle-stimulating hormone (FSH) alone or combined with luteinizing hormone (LH). During a regularly occurring menstrual cycle, both FSH and LH are produced by the pituitary gland in the brain to naturally stimulate the ovaries to make a single egg each month. When FSH (with or without LH) is given as an injection, it works directly on the ovaries to make multiple follicles (cysts containing eggs). Other fertility medications, such as clomiphene citrate, stimulate the ovaries by working in conjunction with the brain.
Gonadotropins usually are used during fertility treatments such as intrauterine insemination (IUI) or In Vitro Fertilization (IVF). Injections of gonadotropins are started early in the menstrual cycle to cause multiple eggs to grow to a mature size. Human chorionic gonadotropin (hCG), another injectable medication, is then used to trigger the release of the eggs when they are mature. Close monitoring of patients with ultrasound who are using these medications is advised in order to minimize the side effects and risks.
Potential side effects of gonadotropins
- Ovarian Hyperstimulation Syndrome (OHSS)
OHSS is characterized by enlarged ovaries and fluid accumulation in the abdomen after stimulation by gonadotropins and after ovulation occurs. A mild form occurs in 10% to 20% of cycles and results in some discomfort but usually resolves quickly without complications. The severe form occurs approximately 1% of the time. The chance of OHSS is increased in women with polycystic ovary syndrome and in women who become pregnant during the cycle in which gonadotropins are given. When severe, OHSS can result in nausea, vomiting, rapid weight gain, dehydration, blood clots, kidney dysfunction, twisting of an ovary (torsion), fluid collections in the chest and abdomen, and, rarely, even death. In severe cases, hospitalization is often required for monitoring. The condition is temporary, usually lasting only a week or two. Several strategies exist to prevent or minimize symptoms, including withholding further gonadotropin stimulation, delaying hCG administration until hormone levels plateau or decline, or even withholding hCG to prevent ovulation. In IVF cycles in which OHSS is felt likely to develop, an oral medication, cabergoline, may be given to lessen the severity of these symptoms. Another way to shorten the time that a patient may have OHSS symptoms is to consider delaying the embryo transfer in IVF couples by freezing (cryopreserving) the embryo and transferring at a later date when the OHSS symptoms are completely resolved.
- Multiple Gestation
When using injectable gonadotropins alone or with IUI, up to 30% of pregnancies are associated with multiple implantations (twins or more), which only occur in 1% to 2% of naturally occurring pregnancies. The increased risk of multiples is due to the number of eggs that are stimulated during an ovulation induction cycle or due to the number of embryos transferred in an IVF cycle. While most multiple pregnancies are twins, up to 5% are triplets or higher. When a woman has twins or more is at higher risk of miscarriage, preterm delivery, infant abnormalities, handicap due to the consequences of preterm delivery, pregnancy-induced hypertension, bleeding, diabetes, or too little or too much amniotic fluid and other significant maternal complications. There is a higher likelihood of undergoing a Cesarean section. The risk of severe complications increases as the number of fetuses that implant in the uterus goes up.
Half of all twins and 90% of triplets are born prematurely. Babies born prematurely may have many health problems. For example, their lungs may not be strong enough so they may have problems breathing. The blood vessels in their brain might bleed easily. Premature babies also tend to be underweight, may get sick and some even die. Many other birth defects are associated with multiple births as well.
There are ways to reduce the risk of multiple births. During a fertility treatment cycle when fertility drugs are used with timed intercourse or insemination, your doctor will monitor your cycle very carefully. The use of fertility medications makes it more likely that one or more eggs will be fertilized. However, if it appears that too many eggs are developing, your doctor may cancel your cycle ant tell you not to have an insemination or intercourse to eliminate your risk of multiple births.
In Vitro Fertilization (IVF) means that you egg and your partner’s sperm are joined (fertilized) in the laboratory and the doctor places the fertilized eggs (embryos) into your womb. It is much less likely that you will become pregnant with triplets or more if only one or two embryos are placed in your womb. Before the placement of these embryos (embryo transfer), you and your doctor will decide how many embryos to place in your womb. If three or more embryos implant inside your uterus, your doctor may suggest that you undergo a procedure called Selective Reduction. Selective reduction allows you and your doctor to reduce the number of fetuses to one or two. Usually the procedure is done early in the pregnancy to increase the chance of a healthy and successful pregnancy. Choosing to do this procedure is difficult. Couples who are thinking about this option should talk to a counselor.
- Ectopic (Tubal) Pregnancies
While ectopic pregnancies occur in 1% to 2% of naturally occurring pregnancies, in gonadotropin cycles the rate is slightly increased. Ectopic pregnancies can be life threatening and require treatment with medication or surgery. Occasionally a tubal pregnancy can occur at the same time as an intrauterine pregnancy (heterotopic pregnancy) and requires surgery to remove the ectopic pregnancy while not harming the pregnancy inside the uterus.
- Adnexal Torsion (Ovarian Twisting)
In less than 2% of gonadotropin cycles the stimulated ovary can twist on itself since the ovary is heavier from more follicles. This twisting can cut off the blood supply. Therefore, surgery is required to untwist the ovary or in severe cases to remove the ovary and or the tube.
- Gonadotropins and Cancer
Although early studies suggested that the risk of ovarian or other cancers of the female genital tract might be increased when exposed to medications for ovulation induction, current studies have shown no increase in any cancers with the use of fertility medications.
- Local or Generalized Reactions
In some women, the injection may cause a local skin irritation. It is extremely rare to have an actual allergy to medication. Some women may experience breast tenderness, headaches, or mood swings from the gonadotropins.