The most common infertility medication is clomiphene citrate brand name Clomid. This is used for women who are not ovulating. Glucophage aka metformin can be added to the Clomid for women that do not ovulate with Clomid alone. Clomid comes as 50mg tablets. The standard dose is to use 50 mg per day for 5 days. Sometimes 100 mg or even 150 mg of Clomid is necessary.
An important concept when using Clomid is cycle days. The first day of menstrual bleeding is considered cycle day 1 and each subsequent day is the next cycle day. So cycle day 5, for example, would be the 5th day from when the menstrual period started. I encourage my infertile patients to put a 1 on the calender at the first day of bleeding and then fill in the calender counting from there. That way when instructions are given in cycle days everyone understands the timing for the medications and lab tests.
Clomid is classically taken for 5 days on cycle day 5-9 although some doctors prefer to prescribe it on cycle day 3-7. Clomid works by tricking the brain into seeing estrogen levels drop while the Clomid is being taken and then when the medication is stopped it appears to the brain that the estrogen levels suddenly rise. A drop in estrogen levels early in the cycle followed by a sudden rise stimulates the ovary to make an egg and eventually to ovulate. When Clomid is taken cyles day 5-9, ovulation (release of the egg from the ovary) is expected around cycle days 14-16.
The ideal frequency of sexual intercourse to achieve pregnancy is every other day. More frequent then that can dilute the sperm, less frequent runs the risk of missing the critical time near ovulation. It is recommended that patients have intercourse every other day for about 10 days from the last day of Clomid. This is called “timed intercourse”. This helps assure that sperm will be available when ovulation occurs so that the egg can become fertilized. I tell my patients that they don’t have to be totally rigid about the timed intercourse. If the couple is feeling romantic on a day that is not scheduled for intercourse, it is fine to be intimate anyway. If a day is missed, try to have sex on the next day. I don’t think this will negatively impact the chance of pregnancy and can be important for the relationship between the couple.
Progesterone levels increase after ovulation and stay increased throughout pregnancy. If pregnancy does not occur the progesterone levels will fall and a new cycle will start. Progesterone is checked with a blood test on cycle day 21. A high level confirms ovulation has occurred and that the Clomid has done its job. If the progesterone level on cycle day 21 is low, ovulation did not occur and the dose of clomid may need to be increased for the next cycle.
If a woman fails to ovulate with Clomid, Glucophage (metformin) may be helpful. About 80% of women that do not ovulate with Clomid alone will ovulate with a combination of Clomid and Glucophage. Glucophage is originally a medication used for diabetes but it has been shown to be a very effective addition to Clomid for the anovulatory women. The typical effective dose of Glucophage is 500mg three times per day. If started directly at this dose it can cause diarrhea and nausea so it is started at a smaller dose and gradually increased. Once the target dose of 500 mg three times per day is achieved, Clomid cycle can be restarted. The Glucophage is taken every day until pregnancy occurs.
Clomid is a very safe medication with minimal side effects. It does increase the risk of twins to about 7% but higher order multiples like triplets or more is very rare with Clomid. Some women get headaches, hot flashes, or mood swings during the 5 days of Clomid, but for most women these symptoms are minimal. There was a study that linked Clomid to an increased risk of ovarian cancer. This study was flawed and that link is not believed to exist. Women that have fewer children are known to have an increase risk of ovarian cancer. Women that have been exposed to clomid tend to have fewer children because they have infertility. It is the association of less children rather than the Clomid itself that linked to ovarian cancer.
The typical way that Clomid is used is to take Clomid on cycles day 5-9. This is followed by timed intercourse (every other day) for 10 days. A blood test for progesterone is done on cycle day 21. The patient returns to the office at the end of the cycle to review the progesterone levels and check for pregnancy.