Know about Clomiphene – The most common drug used in infertility

What is clomiphene? Why it is used? How long and how much one can take? Are there any side effects?

Full name is Clomiphene citrate and it is an anti estrogen and by inhibiting the effect of estrogen on pituitary gland increases the necessary hormone, Follicular stimulating hormone or, FSH secretion from the pituitary gland to stimulate ovary and induce ovulation.

Clomiphene is prescribed in doses of 50mg per cycle and increased to 250 mg until ovulation is achieved. 75% of clomiphene pregnancies occur at doses of 50-100mg and in first 3 cycles. Doses more than 150 mg has less pregnancy rates. As per RCOG Guidelines not more then 6 cycles continuously and not more than 12 cycles in life time.


Side effects of this drug are formation of cysts, , can cause visual problems (2%), mood swings, headache (1%), depression, dryness and loss of hair (0.3%) .

Clomiphene is contraindicated in liver disease.

How effective is Clomiphene Citrate (CC) and is its effect is predictable?

Clomiphene remains the first choice treatment for inducing ovulation. Approx. 70% receiving clomi¬phene ovulate and about 35-40% conceive. Frequently it takes a couple of cycles in identifying clomiphene resistant patients. If response to clomiphene can be predicted, it will help in identifying patients requiring alternative treatment earlier.

A number of factors have been studied to predict clomiphene response:

Free androgen index: FAI [testosterone/sex hormone binding globulin (SHBG) ratio ] is an important indicator of clomiphene responsiveness.

High FAI is also usually associated with hyperinsuilaemia and insulin resistance. These two factors together diminishes the CC responsiveness.

Leptin levels: Leptin is a product of the obesity gene and is primarily produced by adipocytes. Leptin plays an important role in regulation of menstrual cycle and it has been shown that it is increased in clomiphene non-responders and unexplained infertility.

BMI: There have been some studies linking the dose requirement of clomiphene and body weight. This again may be related to leptin levels. In very thin women less than 45 kg, clomiphene should be started at lower dose of 25 mg, whereas in obese women higher dose of 100 mg may be required. Obese women are more likely to have poor response with CC.

Ovarian volume and antral count: Ovarian volume and antral foUicle count have also been closeJy linked to ovarian response. Low ovarian volume as well as very high volume f > 10 ml, suggestive of PCOS; are indicators of poor response. Antral follicles are small follicles measuring 2 to 8 mm in the baseline state. They are indicative of the relative number of microscopic primordial follicles remaining in the ovary. If the antral follicle count is <> 30 as in PCOS, chances of hyperstimulation are very high.

In general, an obese, amenorrhoic woman with hyper insulinemia and high FAI is very likely to have a poor response with clomiphene citrate.

This article is also published in India study Channel