Our physicians may recommend one of several medical therapies that can help women trying to get pregnant. These often serve as first line and even second line treatments prior to IVF. These medications are typically used to help induce ovulation in women who have ovulatory dysfunction (Am I ovulating, btw?) or to help superovulate women to increase the chances for pregnancy in a given cycle.
Medications to induce ovulation
Many medications are used to treat infertility. Several are listed below, but talk with your infertility specialist about the purpose for each one. Never take infertility medications or herbal products that have not been prescribed for you.
Clomiphene citrate (Clomid®)
If a male factor has been ruled out, the first step for many couples is to enrich the egg production of the woman. This can be done with oral drugs, the most common of which is clomiphene citrate.
This agent is used to induce ovulation, to correct irregular ovulation, to help increase egg production and to correct luteal phase deficiency. This drug acts as “anti-estrogen” and tricks the pituitary gland into producing more follicle stimulating hormone (FSH) and luteinizing hormone (LH), which, in turn, stimulates the ovaries to produce more eggs and follicles. The widely cited twin rate for women using clomiphene citrate is 5-8% and the triplet rate is 1%.
Over-the-counter ovulation predictor kits can help determine when ovulation will occur. These kits may help time when an increase in sexual intercourse is approrpiate, or an indication to visit the Center for intrauterine insemination (see below).
Historically, clomiphene citrate has been the first line therapy for inducing ovulation in women with PCOS and up to 80% of women with PCOS will respond and ovulate. Recent data pitting clomiphene citrate against letrozole (see below) in women with PCOS showed that live birth rates were higher in the women who took letrozole. The findings of these results suggest that letrozole may be a better first line option.
Clomiphene citrate 100mg with artificial insemination (IUI) remains the first line treatment of choice for unexplained infertility.
Aromatase Inhibitors: Letrozole (Femara®)
In the past, letrozole was used a second line agent for those women who expressed resistance to clomiphene citrate, but it has recently emerged as a first line treatment in certain patient populations.
As noted above, letrozole is a preferred first line ovulation induction agent for women diagnosed with PCOS. Letrozole is an aromatse inhibitor and works by temporarily stopping the conversion of androgens to estrogens, therefore the brain responds by increasing secretion of FSH. It is important to discuss the choice of ovulation induction agent with your MD.
Metformin is a diabetic medication used to reduce insulin resistance and may play a role in women who continue to be resistant to oral ovulation induction medications. Historically, it has been used as a first line agent to induce ovulation but a large and thorough study has shown that clomiphene citrate alone is superior to metformin in ovulation induction. We consider starting metformin if patients show signs or symptoms of insulin resistance/glucose intolerance.
Gonadotropins are fertility medications given by injection that are identical to the natural follicle stimulating hormone (FSH) produced by the pituitary gland, alone or combined with luteinizing hormone (LH), also produced by the pituitary gland. The result of these additional hormones circulating in the body is the stimulation and growth of multiple follicles.
Gonadotropins are helpful for women with various diagnoses:
- Those who are resistant to oral medications
- diagnosis that precludes the use of oral medications
- Empiric therapy (unexplained)
They are also used to induce development and ovulation of multiple follicles in women undergoing assisted reproductive technologies such as in vitro fertilization or intrauterine insemination.
In addition to increasing the number of eggs, timing factors — such as ovulation — are controlled to maximize the chance of becoming pregnant by intercourse or IUI. The use of injectable medications increases the risk of ovarian hyperstimulation syndrome (OHSS) as well as the risk of high order multiples (triplets or more).
Usually three cycles (months) are adequate to determine if gonadotropins will result in a pregnancy. If not, it is recommended the couple move on to other options. Gonatropin/IUI therapy is utilized much less today than in years past for two reasons: 1) A desire to reduce the number of higher order multilples (triplets or more) and 2) the vast improvement in IVF success rates over the last 20 years.
Intrauterine insemination (IUI)
Intrauterine insemination is a medical procedure that places the sperm directly into the uterus. The sperm does not have to travel up the vagina and through the cervix to reach the uterus. The advantage of IUI is that it puts a much larger number of sperm into the uterus than would occur with intercourse. IUI may be useful if the male partner has a low sperm count, but also has a role in empiric use.