Who should be treated with medicines to induce ovulation? This is called ovulation induction and may be done for two reasons. The first is when a woman doesn’t ovulate regularly. The medicines make the ovary release eggs. The second is when a woman ovulates on her own, but still isn’t able to get pregnant. In that case, medicines may be given to help her release more than one egg as a part of a treatment for unexplained infertility.
What oral medicines are used for ovulation induction? The most commonly used medicines are the oral agents: clomiphene (CC) citrate, and aromatase inhibitors (AI) such as letrozole. Other type of medications called gonadotropins (injectable) can also be used.
How do these medicines work?
During the first days of a normal menstrual cycle, estrogen (hormone) levels are low and your pituitary gland produces follicle-stimulating hormone (FSH) in response to these low estrogen levels. As FSH levels rise, one main follicle (a small cyst that houses an egg) grows and releases estrogen. This will trigger the release of an egg later in the cycle from that follicle.
CC and AIs work by either lowering estrogen levels or by making the brain think they are low. CC works by helping cells resist estrogen. AIs work by blocking certain kinds of hormones (androgens) from changing to estrogen. Low estrogen levels tell the pituitary gland to produce FSH, which helps a follicle to grow and release an egg.
Women who don’t ovulate regularly because of polycystic ovary syndrome (PCOS) produce too much insulin and androgens. ISAs help lower insulin and androgen levels to help with follicle growth.
Risks of taking these medications:
- The most common risk of using this medication is multiple pregnancy. The chance of twins is 5%-8% with CC; the chance of triplets or a higher-order multiple pregnancy is less than 1% with these medicines. IAs do not seem to increase the risk of multiple pregnancies by much, if at all.
- Ovarian cysts may occur and can sometimes become large and painful; however, it is uncommon for these cysts to require any treatment.
- There is no link between these medicines and ovarian cancer.
- There is no known increase in birth defects in women who have taken these medicines to induce ovulation.
Ultrasound monitoring may required
We will decide how much monitoring you need based on your history and reason for infertility. To see when an egg may be ready to be released.
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.
The success of these medicines depends on many factors. In women not already ovulating, almost 80% of women who use CC or AIs over several months will ovulate. Some women will need increasing doses of the medicines. Pregnancy rates depend on your age, the length of infertility, and cause of infertility. These medicines are generally more effective in women who do not ovulate regularly. In women who already ovulate, pregnancy rates tend to be lower especially if the medicines are not combined with other treatments like insemination.
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).
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:
- 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 embryos 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.
- 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.
- 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.
- Gonadotropins and Cancer. 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.