Ovulation Induction - Clomifene Citrate

What are Clomifene citrate tablets for?

Clomifene citrate (“Clomid”) is used to treat some types of infertility in women who are not ovulating properly or regularly. Clomid is used to help women to develop and release mature egg(s).

How does it work?

Given early in the menstrual cycle, Clomid suppresses the amount of naturally circulating oestrogen. This “tricks” the pituitary gland (in the brain) into producing more follicular stimulating hormone (FSH) and luteinising hormone (LH). These hormones then stimulate the ovary to ripen one or more follicles (a follicle is a fluid-filled sac within which an egg develops) and release one or more eggs.

Description

Clomifene citrate is an orally administered medication. The initial dosage is 50 mg per day for 5 days, usually from day 2 to day 6 of the woman’s menstrual cycle (first day of the cycle being first day of the period). The dosage may be increased in the subsequent cycles if the lowest dose does not result in ovulation.

Use

The lowest dosage is usually used at the beginning of the treatment to minimise side effects and other risks of the treatment (see below). It can be increased in the subsequent cycles if the desired effect is not achieved.

During the treatment cycle, vaginal ultrasound scanning is required to monitor the response of the ovaries to Clomid. This is called “follicular tracking”.

Risks

Clomid is a very safe medication with relatively few contraindications. Women with liver disease should not use clomid. Clomid should not be given to patients with ovarian cysts, since they may grow larger under the influence of clomid. A patient who may be pregnant should not take it, although there is no proof of damage to babies.

Some women who use Clomid get blurred vision or other visual symptoms. In these cases, driving and operating machinery may be dangerous. If symptoms persist, treatment should be stopped.

Other side effects include the development of cysts of the ovaries. They usually subside spontaneously after treatment. Other reported side effects are hot flushes, insomnia and irritability.

What are the serious side effects of clomid?

  • Hyperstimulation of the ovaries - It happens when the ovaries respond excessively to drugs that induce ovulation. The ovaries are enlarged and many large follicles are produced. This will lead to abdominal pain and swelling. In severe cases, there will be retention of fluid in the abdomen and the lungs. It is very unlikely that the severe form of hyperstimulation will occur with Clomid treatment, particularly if monitoring with ultrasound is carried out properly.
  • Multiple pregnancy - About 6% of Clomid-induced pregnancies will be multiple pregnancy. The vast majority of these are twins, although higher multiple pregnancies (e.g. triplets & quadruplets) can occur rarely. It has to be appreciated that multiple pregnancy carries significantly higher risks compared to singleton pregnancy, e.g. miscarriage, premature labour, bleeding problems, high blood pressure, etc.
  • Putative risk of ovarian cancer - The association between ovarian cancer risk and prolonged Clomid use remains uncertain. There is no evidence to suggest an increased risk of ovarian cancer when Clomid is used for less than 12 cycles.  

The role of clomid in "unexplained infertility"

For a woman who has normal spontaneous ovulation, driving the pituitary gland harder with Clomid will not make ovulation any more normal. Current evidence suggests that the treatment of “unexplained infertility” with Clomid will result in little or no benefit. If a woman has taken Clomid without becoming pregnant, further investigations or other forms of treatment should be tried.

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