Clomiphene Citrate. This drug, commercially known as Clomid or Serophene, is the first alternative for treating women with anovulation or with oligo-ovulation. This drug blocks the effects of estrogen throughout the body. Therefore, the pituitary gland detects that there are low levels of estrogen in the blood stream. The pituitary’s response to low estrogen levels is to increase the output of FSH in order to provide more stimulation to the follicles and thus produce more estrogen. From a clinical perspective this rise in FSH is very important since it is sufficient to stimulate the follicles to complete normal development and eventually ovulation.

Usually, in the first Clomiphene Citrate (CC) stimulated cycle, women who have ovulatory problems take one pill per day for five days on days five through nine of the menstrual cycle. However, this timing may be adjusted also for specific patients. In the absence of proper stimulation the dosage is systematically increased until the effective dose is determined. In some cases the dose may need to go as high as five pills per day. During the CC therapy the patient is monitored to determine if ovulation did occur. Basal body temperature and ovulation predictor kits (OPKs), are useful elements to determine the mid-cycle surge of LH. The OPKs have the added advantage of turning positive prior to ovulation, which allows a more precise timing of intercourse or insemination. The ultimate test for ovulation is determining blood progesterone levels five to ten days later. This test not only confirms that ovulation took place but also it may reaffirm that progesterone support, during the second half of the cycle, is adequate.

Most of the pregnancies will occur in the first three CC stimulated cycles and very few pregnancies will be achieved beyond the sixth ovulatory cycle. Therefore, it is recommended to have no more than three CC stimulated cycles and change to gonadotropin induced cycles in subsequent attempts. Clinical research has shown that combining CC therapy with intrauterine insemination will increase the odds of pregnancy. With proper monitoring and stimulation five to ten percent of the pregnancies will be twins. In some cases, higher order pregnancies (triplets or more) may occur if not followed properly.

Some of the side effects of CC therapy are associated with the "artificial" blockage of estrogen’s favorable effects on mucus production by the cervix. In some cases, the treatment may result in a hostile environment for the sperm reaching the site of fertilization after intercourse. This problem may be averted with intrauterine insemination. In other cases, due to the blockage, the endometrium may not be receptive for implantation. Therefore, pregnancy rates are lower, even with IUI, than injectable gonadotropin therapy. Other side effects include hot flashes, upset gastrointestinal tract, headaches, visual disturbances, mood swings and breast tenderness. As indicated earlier, the major side effect of CC therapy is the probability of a high order pregnancy.