Clomiphene Citrate
How it works
Clomiphene stimulates the release of follicle stimulating hormone which is needed to cause egg development. Clomiphene therapy is typically used for 5 consecutive days early in the menstrual cycle - usually day 2 to 6. Usually a starting dose of 50 mg is chosen but if this is insufficient to achieve ovulation then a higher dose of 100 mg or even 150 mg may be necessary. Once ovulatory cycles are achieved it would be reasonable to expect a pregnancy to occur within 6 cycles of treatment. If pregnancy has not occurred then by that time then it is unlikely that further clomiphene treatment will be successful.
Why it is used
Clomiphene may be prescribed to:
- Stimulate egg production in a woman who does not ovulate or who ovulates irregularly. Before starting treatment the woman should have been fully investigated and been shown to have normal pituitary gland function and her male partner must have had a satisfactory semen analysis.
- There is limited evidence that clomiphene makes pregnancy more likely for couples with unexplained infertility.
- Stimulate the development of multiple eggs for use with assisted reproductive technology, such as intrauterine insemination (IUI) or in-vitro fertilization (IVF).
Clomiphene is sometimes used together with other medicines and infertility treatments.
A proportion of women with polycystic ovary syndrome (PCOS) fail to ovulate or ovulate infrequently. Before trying clomiphene however it is essential women with PCOS who are overweight lower their body mass index (BMI) with diet and exercise. Reaching a healthy weight can restart ovulation without the need for clomiphene.
Evaluating ovarian response to clomiphene
When clomiphene is prescribed it is important check that your ovaries are developing an egg and that you are ovulating. This can be done in 2 ways.
- The first is called 'cycle tracking' and involves the use of ultrasound to visualize your ovaries. You will be seen on a number of days throughout your cycle and a scan should show the follicle enlarging. Once it reaches the right size the egg is released and a scan after ovulation will show the follicle to have disappeared.
- The second method involves a blood test to measure progesterone hormone levels. Progesterone is only released from the ovary after ovulation. Blood levels of progesterone rise and reach a peak approximately 1 week after ovulation. If a pregnancy does not occur then over the next week the levels will fall and menstruation will start. We can therefore measure progesterone levels on day 21 of your cycle and if these levels are high it can be assumed that ovulation has occurred.
Success rate
Of women whose infertility is caused only by absent or infrequent ovulation, with clomiphene treatment approximately 80% will ovulate. And within 9 cycles of treatment, 70% to 75% will become pregnant. Experts used to think miscarriage rates were slightly higher in women who became pregnant using clomiphene, but recent studies have not shown this to be true.
Side effects
Side effects of clomiphene include:
- Hot flushes
- Irritability
- Nausea, abdominal pain
- Headaches
- Breast tenderness
- Ovarian hyperstimulation, ranging from mild, with enlarged ovaries and abdominal discomfort; to moderate, additionally causing nausea, vomiting, or shortness of breath; to severe and life-threatening.
Women who become pregnant after clomiphene therapy have an approximately 5% to 8% chance of multiple pregnancy. This compares to a 1% to 2% chance in the general population. Multiples resulting from clomiphene treatment are almost exclusively twins; triplets are rare.
Miscarriage risk
In some studies, miscarriage rates are slightly higher in women who become pregnant using clomiphene. It is not clear if this is related to an early hormonal effect on the egg or to pre-existing conditions such as age or polycystic ovary syndrome, which are found more often in women who take clomiphene.
Other studies have not shown an increased miscarriage rate. Clomiphene has not been observed to harm the fetus.
