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Top 10 Facts about Clomiphene Citrate (Clomid, or Serophene)


Clomiphene citrate (CC), marketed, as Clomid or Serophene, is the most commonly used drug for ovulation induction. It was first synthesized in 1956 and was approved for clinical use in the United States by the Food and Drug Administration in 1967. Here are the Top 10 facts about CC.

  1. It is the first-line treatment for women with absent or irregular ovulation (WHO group II). The vast majority (80%) of these patients have menstrual irregularity due to polycystic ovary syndrome (PCOS). CC recently has been widely used in women with unexplained infertility that have regular menses (and ovulation) to stimulate multiple follicular development and ovulation.
  2. How does CC work? CC acts as an anti-estrogen at the level of the hypothalamus (in the brain). CC occupies the hypothalamic estrogen receptors causing a misinterpretation of the estrogen levels, which are perceived to be low. The hypothalamus then releases more of follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH in turn stimulate follicle growth in the ovary followed by ovulation.
  3. What is the usual dose of CC? CC is given orally in a dose of 50 – 150 mg per day for 5 days from day 2, 3, 4 or 5 of the cycle. The results with CC are similar whether it is started on day 2 or through 5 of the cycle. In patients that do not ovulate, CC can be started at 50 mg daily. However, when used in patients with regular menses, the starting dose is usually 100 mg daily to maximize the chance of development of multiple follicles. Most physicians will not use a daily dose of more than 150 mg (3 tablets). There are treatment options for these CC “resistant” patients.
  4. How is CC treatment monitored? CC treatment is usually monitored (urinary LH kits, follicular ultrasounds, blood hormone levels) to ensure its effectiveness in ovulation induction. Ovulation can be triggered with a timed injection of human chorionic gonadotropin (hCG). Ovulation will occur around 36 – 39 hours later facilitating the timing of intrauterine insemination (IUI).
  5. What are the success rates with CC? Although the ovulation rate with the use of CC is 57%–91%, the pregnancy rate is only 27%– 40%. The discrepancy between the ovulation and pregnancy rates is explained partly by the antiestrogenic effect of CC on the cervical mucus and endometrium.
  6. What is the pregnancy rate (PR) with CC? The PR is lower (6 – 8% per cycle) in older patients (> age 35 y), obese patients and in couples with male factor infertility. In younger patients the PR approximates 12% per cycle. Most of the pregnancies are single (92%) and the rest are twin. Triplets are rare with CC treatment but can occur.
  7. How many cycles of CC can I do? Most CC pregnancies will occur in the first 3 cycles. CC treatment generally should be limited to the minimum effective dose and to no more than six ovulatory cycles. Failure to conceive after successful CC-induced ovulation is indication for further evaluation to exclude other contributing causes of infertility.
  8. What are the side effects with CC? Unpleasant side effects of CC are few and far between, although some women will complain of hot flushes and some of nausea. CC is, however, usually very well tolerated. While mild ovarian enlargement is relatively common, in almost 40 years of practice, I have never seen a full blown ovarian hyperstimulation syndrome (OHSS) as a result of CC treatment. Occasional cyst formation can be treated conservatively. Patients with visual symptoms (2%) including flashes or dark spots should discontinue use of CC.
  9. Are there other risks with CC? There is no evidence that CC treatment increases the overall risk of birth defects or of any one anomaly in particular. There is no increase in the risk of miscarriage (10 to 15%).
  10. Is there an increase in the risk of ovarian cancer with CC? In 2006 The Practice Committee of the American Society for Reproductive Medicine discussed the possible risk of ovarian cancer with CC treatment. Two epidemiologic studies published early in the last decade suggested that the risk of ovarian cancer might be significantly increased in women exposed to ovulation inducing drugs, but subsequent studies have failed to corroborate those findings.

A recent pooled analysis of eight case-control studies concluded that neither fertility drug use nor use for more than 12 months was associated with invasive ovarian cancer. Patients with concerns should be counseled that no causal relationship between ovulation inducing drugs and ovarian cancer has been established and no change in prescribing practices is warranted. In any case, prolonged treatment with CC is generally futile and should therefore be avoided.

To see a fertility specialist with decades of experience diagnosing and treating infertility, make an appointment at one of InVia’s four Chicago area fertility clinics.


Infertility Infertility treatment Ovulation Induction Top 10

Dr. Vishvanath Karande

Dr. Vishvanath Karande

Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.



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