Clomiphene citrate for infertility

Examples

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Brand Name	Chemical Name
Serophene	clomiphene citrate

How It Works

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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 three to six monthly cycles. It may take several cycles to find the right dose to stimulate ovulation. Once that dose is determined, a woman will take the drug for at least three more cycles. If she does not become pregnant after six cycles, it is unlikely that further clomiphene treatment will be successful.

Why It Is Used

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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 for 5 days early in a woman's menstrual cycle, 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 medications 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; achieving a healthy weight can trigger ovulation.¹ If that isn't successful, using metformin to correct insulin metabolism often starts ovulation; if not, continuing metformin increases the likelihood that clomiphene will stimulate ovulation.²

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

How Well It Works

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Unexplained infertility. There is limited evidence that clomiphene makes pregnancy more likely for couples with unexplained infertility.³ 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.⁴

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:

• And obesity often begin ovulating when they reduce their body mass index (BMI) with diet and exercise.¹
• With severe insulin resistance may increase their chances of ovulating with clomiphene and metformin combined.^{1, 2}

Couples who have additional causes of infertility have a decreased chance of conceiving with clomiphene therapy alone.

Side Effects

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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 medication 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.⁴ This compares to a 1% to 2% chance in the general North American and European population.³ Multiples resulting from clomiphene treatment are almost exclusively twins; triplets are rare.⁴

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.⁴

Clomiphene has not been observed to harm the fetus.⁴

Ovarian cancer risk?

A 1994 study has suggested that 12 or more cycles of clomiphene increase the risk of ovarian tumors. Studies since then have found no link between clomiphene and ovarian cancer.³ The issue is still being studied. Few specialists recommend long-term use of clomiphene.

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

What To Think About

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Many women try clomiphene therapy before beginning a series of infertility tests. However, 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.⁴

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.⁴

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

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Citations

1. American College of Obstetricians and Gynecologists (2002). Management of infertility caused by ovulatory dysfunction. ACOG Practice Bulletin No. 34. Obstetrics and Gynecology, 99(2): 347–358.

2. Barbieri RL (2003). Metformin for the treatment of polycystic ovary syndrome. Obstetrics and Gynecology, 101(4): 785–793.

3. Duckitt K (2004). Infertility and subfertility. Clinical Evidence (11): 2427–2458.

4. Speroff L, Fritz MA (2005). Induction of ovulation. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 1175–1213. Philadelphia: Lippincott Williams and Wilkins.

Credits

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Author	Shannon Erstad, MBA/MPH
Author	Lila Havens
Editor	Kathleen M. Ariss, MS
Associate Editor	Michele Cronen
Associate Editor	Pat Truman
Associate Editor	Terrina Vail
Primary Medical Reviewer	Joy Melnikow, MD, MPH - Family Medicine
Primary Medical Reviewer	Kathleen Romito, MD - Family Medicine
Specialist Medical Reviewer	Kirtly Jones, MD - Obstetrics and Gynecology
Last Updated	April 7, 2006