Improving ovulation is a key part of treating infertility in people with ovulatory disorders, such as polycystic ovary syndrome (PCOS), hypothalamic amenorrhea, or other hormonal imbalances. Medical therapies to improve, or “induce”, ovulation generally aim to stimulate or regulate the hormones involved in the menstrual cycle. By inducing ovulation, the chances of a successful pregnancy increase either through timed intercourse or in conjunction with other fertility treatments like intrauterine insemination (IUI).
Ovulation induction works by using medications to regulate or stimulate the ovaries. The two main medication categories are oral agents (Clomiphene, Letrozole, Metformin) and injectable drugs (Gonal-F, Follistim, Menopur).
Clomiphene Citrate (Clomid)
- How it works: Clomiphene blocks estrogen receptors in the hypothalamus (in the brain), which tricks the body into producing more follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to ovulation.
- Used for: Polycystic Ovary Syndrome (PCOS) and other disorders of ovulation
- Form: Oral tablets, taken in the early part of the menstrual cycle.
- Success rate: approximately 60-80% ovulation, approximately 8-12% pregnancy per cycle.
- Side effects: Hot flashes, mood swings, ovarian cysts, multiple pregnancy (twins 5-10% incidence, triplets <1% incidence).
Letrozole (Femara)
- How it works: Letrozole is an aromatase inhibitor that reduces estrogen production, leading to an increase in FSH secretion.
- Used for: Often first-line in PCOS; sometimes used if Clomid fails.
- Form: Oral tablets, taken in the early part of the menstrual cycle.
- Success rate: Similar to Clomiphene; may be better than Clomiphene in PCOS patients.
- Side effects: Fatigue, dizziness, headache, hot flashes, multiple pregnancy (twins 3-13% incidence, triplets <1% incidence).
Metformin
- How it works: Improves insulin sensitivity, which can help normalize hormone levels and restore ovulation, especially in women with insulin resistance or PCOS.
- Used for: PCOS, particularly with insulin resistance.
- Form: Oral tablet, taken daily.
- Success rate: May restore ovulation in some women, often combined with Clomiphene or Letrozole.
- Side effects: Gastrointestinal upset (diarrhea, nausea, vomiting)
Gonadotropins - FSH, LH Injections (Gonal-F, Follistim, Menopur)
- How it works: Directly stimulates the ovaries to produce follicles.
- Used for: Clomiphene/Letrozole-resistant cases, hypothalamic amenorrhea (lack of menstrual periods)
- Form: Subcutaneous injections, taken for 7-10 days prior to ovulation.
- Success rate: High response, but also higher risk of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS).
- Side effects: Bloating, OHSS, multiple births (close monitoring with ultrasounds and blood tests is mandatory to reduce this risk).
Human Chorionic Gonadotropin (hCG) “Trigger”
- How it works: hCG mimics the naturally occurring “LH surge” to induce final maturation and release of the egg (ovulation).
- Used for: In combination with gonadotropins or oral ovulation medications.
- Form: Injection, taken once just prior to ovulation.
- Side effects: Risk of OHSS, release of multiple eggs capable of being fertilized, injection site pain.
Dopamine Agonists (Bromocriptine/Parlodel, Cabergoline/Dostinex)
- How it works: Dopamine agonist drugs reduce prolactin levels when “hyperprolactinemia” (too much of the hormone prolactin is produced and released by the pituitary gland in the brain) is suppressing ovulation.
- Used for: Prolactin-secreting pituitary tumors (prolactinomas) or elevated prolactin levels.
- Form: Oral tablets, taken daily.
- Side effects: Nausea, dizziness, fatigue.
Ovulation induction treatment typically spans one menstrual cycle. Throughout treatment with any type of ovulation therapy, close monitoring of your hormone levels and follicle growth through blood tests and ultrasounds is required. This helps determine the optimal time for ovulation and increases your chances of successful conception. Once the eggs are mature and ready for release, you either try to conceive naturally or proceed with other fertility treatments like intrauterine insemination (IUI).
You’ll generally know if the treatment was successful within two weeks of ovulation. If you're trying to conceive naturally or through IUI, a pregnancy test can be done about 14 days after ovulation. Your EIS care team will guide you on when and how to check for results, as well as “next steps” when your pregnancy test is positive!
In addition to the medical therapies described above, ovulation can be improved significantly with lifestyle modifications. Overweight patients often see a resumption of normal menstrual cycles, with spontaneous ovulation, even with modest weight loss. Proper nutrition, exercise and stress reduction all play a positive role in normalizing the menstrual cycle and improving ovulatory patterns. Some vitamins and supplements have shown promise in helping restore optimal ovulatory function for some patients. Dr. Lindheim will discuss these with you, if recommended.