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Metformin and its use in infertility

Polycystic ovary syndrome (PCOS) is the commonest cause of infertility due to a failure to ovulate regularly. Many women who have PCOS, especially those who are overweight, have raised insulin levels and these exaggerate the symptoms of PCOS and increase the chances of infertility.
The raised insulin levels are caused by a strange association (apparently genetic), between PCOS and a resistance to the action of insulin. In order to compensate, the body raises the levels of insulin in order to maintain the all-important glucose levels at a normal concentration.

Metformin is a medication which is capable of reducing insulin levels by making the body more sensitive to insulin. It is widely prescribed for mild diabetes and for this indication it is a simple, cheap medication taken by mouth which has been used successfully for many years. Similarly, it has been used to treat women with PCOS who are suffering from infertility with the reasoning that lowering insulin levels will improve the chances of fertility. It has indeed been shown capable of restoring ovulation and fertility.

The initial enthusiasm for the treatment of women with PCOS and infertility has, however, been dampened due to the fact that when compared with the usual treatment for this condition, clomiphene citrate, it is far less successful in producing restoration of ovulation and live births. Although it was thought that metformin would be particularly useful for overweight and obese women with PCOS, a change in life style involving loss of weight is actually more effective. Metformin may have some rather unpleasant side-effects such as nausea, vomiting and diarrhea.

When then may metformin be used with some success? As metformin often takes some months to restore ovulation, those who are in no particular hurry to conceive may prefer its use. It also has less chance of producing a twin pregnancy than with the use of clomiphene. In women in whom clomiphene citrate has failed to bring about ovulation, a combination of clomiphene and metformin is sometimes tried before proceeding to treatment with injections of FSH. Finally, for women with PCOS undergoing IVF, when metformin is given, starting weeks before the treatment cycle is started, it has been reported to improve the chances of a live birth.

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