Clomiphene citrate for infertility

Examples

Generic Name Brand Name
clomiphene citrate Clomid, Milophene, Serophene

How It Works

Clomiphene stimulates the release of hormones needed to cause ovulation.

Clomiphene therapy is typically used for 5 consecutive days early in the menstrual cycle, for 3 to 6 monthly cycles. It may take several cycles to find the right dose to stimulate ovulation. After that dose is determined, a woman will take the drug for at least 3 more cycles. If she does not become pregnant after 6 cycles, it is unlikely that further clomiphene treatment will be successful.

Why It Is Used

For women. Clomiphene may be prescribed to:

  • Stimulate ovulation in a woman who does not ovulate or who ovulates irregularly. Her estrogen levels and pituitary gland function must be normal, and her male partner must be diagnosed as fertile.
  • Perform a clomiphene challenge test, which is sometimes used to evaluate a woman's ovulation and egg quality (ovarian reserve). When given early in a woman's menstrual cycle for 5 days, clomiphene elevates a woman's follicle-stimulating hormone (FSH) level. On the next day, an FSH blood level that has dropped back to normal is a sign of a normal ovarian reserve and ovulation. An elevated FSH is a sign of low ovarian reserve. Women with a diminished ovarian reserve can use donor eggs, which greatly improves their chances of giving birth to a healthy child.
  • Stimulate the development of multiple eggs for use with assisted reproductive technology, such as in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT).
  • Regulate ovulation in a woman who ovulates irregularly and/or is going to have intrauterine insemination or artificial insemination.

Clomiphene is sometimes used together with other medicines and infertility treatments.

Before trying clomiphene, women with polycystic ovary syndrome (PCOS) who are overweight are advised to lower their body mass index (BMI) with diet and exercise. Reaching a healthy weight can restart ovulation.1 If that isn't successful, using medicine to correct insulin metabolism may start ovulation. If not, a combination of medicines may help stimulate ovulation.

For men. Clomiphene may be used to treat low sperm counts (oligospermia).

How Well It Works

Unexplained infertility. There is limited evidence that clomiphene makes pregnancy more likely for couples with unexplained infertility.2 Clomiphene may be most effective when it is used to generate multiple eggs before an insemination procedure.

Infrequent or no ovulation. Of women whose infertility is caused only by absent or infrequent ovulation, with clomiphene treatment approximately 80% will ovulate. And within 9 cycles of treatment, 70% to 75% will become pregnant. Experts used to think miscarriage rates were slightly higher in women who became pregnant using clomiphene, but recent studies have not shown this to be true.3

Polycystic ovary syndrome. Clomiphene alone may not be an effective treatment for most women with polycystic ovary syndrome (PCOS) and severe insulin resistance, which is closely linked to obesity. Women with PCOS who are overweight often begin ovulating when they reduce their body mass index (BMI) with diet and exercise.

Side Effects

Side effects of clomiphene include:

  • Ovarian hyperstimulation , ranging from mild, with enlarged ovaries and abdominal discomfort; to moderate, additionally causing nausea, vomiting, or shortness of breath; to severe and life-threatening.
  • Hot flashes.
  • Irritability.
  • Nausea, abdominal pain.
  • Headaches.
  • Thick cervical mucus, which sperm cannot travel through. This can be reversed with medicine or bypassed with intrauterine insemination.
  • Breast tenderness.
  • Blurred vision.
  • Hair loss (very rare).

Women who become pregnant after clomiphene therapy have an approximately 5% to 8% chance of multiple pregnancy.3 This compares to a 1% to 2% chance in the general North American and European population.2 Multiples resulting from clomiphene treatment are almost exclusively twins. Triplets are rare.3

Miscarriage risk?

In some studies, miscarriage rates are slightly higher in women who become pregnant using clomiphene. It is not clear if this is related to an early hormonal effect on the egg or to preexisting conditions such as age or polycystic ovary syndrome, which are found more often in women who take clomiphene. Other studies have not shown an increased miscarriage rate.3

Clomiphene has not been observed to harm the fetus.3

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Many women try clomiphene therapy before beginning a series of infertility tests. But most doctors recommend a careful medical history, physical exam, and semen analysis before beginning clomiphene. If your pituitary, thyroid, and adrenal function have been checked, you have no signs of endometriosis, and your partner's fertility has been confirmed, clomiphene is considered a safe and simple option.3

Most women who become pregnant by using clomiphene do so within 3 cycles, and the majority become pregnant within 6 cycles of clomiphene use.1 Prolonged treatment with clomiphene is usually not helpful. After 3 to 6 cycles, further evaluation or a change in treatment plan is recommended.3

Make sure your doctor knows of any abnormal vaginal bleeding or history of problem ovarian cysts before prescribing clomiphene for you.

Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.

References

Citations

  1. American College of Obstetricians and Gynecologists (2002, reaffirmed 2006). Management of infertility caused by ovulatory dysfunction. ACOG Practice Bulletin No. 34. Obstetrics and Gynecology, 99(2): 347–358.
  2. Al-Inany H (2005). Female infertility, search date April 2004. Online version of BMJ Clinical Evidence. Also available online: http://www.clinicalevidence.com.
  3. Speroff L, Fritz MA (2005). Induction of ovulation. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 1175–1213. Philadelphia: Lippincott Williams and Wilkins.

Last Updated: March 21, 2008

Author: Bets Davis, MFA & Sandy Jocoy, RN

Medical Review: Sarah Marshall, MD - Family Medicine & Kirtly Jones, MD - Obstetrics and Gynecology

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