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Strategies for improving the efficacy of clomiphene induction of ovulation

Mark D Hornstein, MD
William E Gibbons, MD
Section Editor
Robert L Barbieri, MD
Deputy Editor
Kathryn A Martin, MD


Clomiphene citrate is the fertility medication most widely prescribed by gynecologists. Its use results in ovulation and pregnancy rates of 80 and 40 to 50 percent, respectively, when given at standard doses [1]. The US Food and Drug Administration (FDA) has approved use of clomiphene at doses of 50 or 100 mg daily for five days per cycle.

Women who ovulate but who do not conceive should not be considered "clomiphene citrate failures." In one series, 88 percent of women who ovulated with no other infertility factor conceived, while only 8 percent of those with concurrent infertility factors conceived. This observation highlights the importance of performing an evaluation of fertility factors in women who ovulate but do not conceive before moving to other therapies [2].

Current guidelines from a consensus group recommend that women who do not become pregnant with clomiphene should be treated with gonadotropin injections (follicle-stimulating hormone [FSH] or FSH and luteinizing hormone [LH]) or laparoscopic ovarian surgery to reduce androgen secretion by the ovary. As a trend, the use of gonadotropin injections in the treatment of polycystic ovarian disease outside of in vitro fertilization (IVF) is diminishing because of the risk of multiple gestations. Thus, it is worthwhile to review less complex, alternative approaches to treating these women before referring them for resource-intensive interventions. Some of these strategies (eg, weight loss) can also be considered at the initial course of clomiphene therapy. (See "Laparoscopic surgery for ovulation induction in polycystic ovary syndrome" and "In vitro fertilization" and "Diagnosis of polycystic ovary syndrome in adults" and "Treatment of polycystic ovary syndrome in adults".)

Strategies for fertility treatment in the 50 to 60 percent of women with ovulatory infertility who do not become pregnant when treated with clomiphene as a single agent will be reviewed here. An optimal sequence for these strategies has not been determined; the sequence described below reflects our typical approach to these patients. A general overview of ovulation induction with clomiphene citrate is presented elsewhere. (See "Ovulation induction with clomiphene citrate".)


If pregnancy has not occurred after three cycles of clomiphene treatment, it is worthwhile to review the diagnostic studies that were completed by the infertile couple and consider further investigation.


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Literature review current through: Sep 2016. | This topic last updated: May 14, 2015.
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