Fertility Drugs I: Clomiphene Citrate

What is Clomid?

Clomiphene citrate is a synthetic medication that affects the way in which a woman ovulates.

What makes it work?

Chemically, Clomiphene looks somewhat like estrogen. Like all hormones, estrogen works by occupying a receptor in different parts of the body. This occupied receptor then sends a signal telling that organ to do something. For example, in the brain estrogen directs the release of FSH, which controls the ovary’s development of a mature egg. In the uterus, estrogen directs the thickening of the lining. Clomiphene blocks estrogen’s attachment to its receptor.

How is this beneficial?

Clomiphene affects fertility in a positive way by tricking the body into thinking that less estrogen is present than there really is. The body responds by releasing greater amounts of FSH. In women who do not usually ovulate, this extra stimulation can cause ovulation to occur and make a pregnancy possible. In women who usually do ovulate, the clomiphene can produce extra mature eggs, or theoretically improve the maturation of the eggs that are released.

Does clomiphene have any negative effects on fertility?

It can. By blocking estrogen’s activity in the uterus, the lining may be inadequately prepared for implantation of the embryo. Many women also find that their cervical mucous suddenly becomes hostile to sperm penetration.

How well does clomiphene work?

In women who need clomiphene to ovulate, the pregnancy rates are very high, as much as 33% per cycle for the first three cycles. In women who normally ovulate the rates are lower, and depend on many other factors, chiefly age, condition of the female reproductive tract and the male factor.

How long should I use clomiphene?

The pregnancy rates with clomiphene use justify up to three months of treatment for women who normally ovulate on their own, or six months for women who do not usually ovulate without it. There may be exceptions on a case-by-case basis, however.

How is the medication given?

Clomiphene citrate comes in 50 mg tablets that are taken on the fifth through ninth day of the ovulatory cycle. The standard doses are one, two or three pills daily. There are legitimate variations on this dosing regimen, however.

Such as?

The medication can be given days 3-7, 4-8 or extended 3-9 or even longer. It is sometimes combined with injectable medications, such as HCG, human menopausal gonadotropins (Pergonal or Metrodin), or an oral steroid such as Dexamethasone. Occasionally we use higher doses than three pills daily.

What are the short-term side effects of clomiphene?

Some women experience hot flashes, presumably because the action of estrogen is blocked at the level of the skin. Headaches are not uncommon (approximately 10% of women) and moodiness or depression are reported in approximately 5%. It is believed that the incidence of side effects does not change with higher or lower doses.

What about long-term side effects?

Is clomiphene associated with ovarian cancer? The relationship between clomiphene and ovarian cancer has long been a concern and the honest answer is that we still do not know for sure. No significant increase in ovarian cancer rates has been seen since the use of clomiphene became common, although one study published in 1993 implicated clomiphene use for greater than twelve months with a possible increase in cancer risk. For these reasons clomiphene should be used for a relatively short time only.

How about multiple pregnancy rates with clomiphene?

The risk of having a twin pregnancy is approximately doubled with clomiphene use, presumably due to an increase in the number of mature eggs available. Triplets are no more likely than using no medications at all. Is there an increase in birth defects or pregnancy complications? None other than those associated with the higher twin rate.

Prepared by:
David Sable, M.D.
Director
The Institute for Reproductive Medicine and Science of Saint Barnabas Livingston, NJ