Fertility Treatments - New options.

The recognition that insulin plays a key role in PCOS, as shown on this web site, has led to new treatment options involving insulin sensitizing and lowering drugs. In the past, clinicians would often begin their treatment regimen with several months of clomid. This was often done by OB/GYNs with little monitoring of the cycle and often not accompanied by an intrauterine insemination (IUI). The IUI significantly improves the pregnancy rate by bypassing the thickened cervical mucus caused by clomid and of course has better timing. Please see our infertility web site page; http://www.ivf-indiana.com/education/iui-improves-clomid.html If the patients failed to conceive on clomid they were often referred to Reproductive Endocrinologists (RE) for more advanced treatments. The RE would often begin several cycles of gonadotropins (i.e.Menopur, Repronex, Gonal-f, Follistim), which contain purified FSH and LH in some cases. Often the patients would hyperstimulate or have high order multiple gestations or have their cycle cancelled. When all failed, the use of IVF or GIFT was considered next. All of these treatment strategies were geared towards stimulation of the ovaries either indirectly with clomid (it works at the level of the brain to stimulate the ovaries), or directly with gonadotropins (this basically purified follicle stimulating hormone which stimulates the ovaries). None of them directly treat the underlying mechanism of the disease (i.e. insulin resistance).

Over the past few years, the additions of metformin (glucophage) or thiazolidinediones (Actos, Avandia) have been used to directly treat the elevated insulin, which is present in PCOS patients. Aromatase Inhibitors (i.e. Letrozole) are non-steroidal suppressors of estrogen biosynthesis that have been used in ovulation induction.

Metformin (glucophage) has been used in the treatment of diabetes for about 40 years. The effects of the drug are therefore well known. It is a category B drug in pregnancy (safe, no known fetal malformations in humans). In the liver it suppresses gluconeogenesis (production of glucose), and in muscle and fat cells it enhanced glucose uptake and utilization. This effectively lowers glucose and insulin levels. In studies performed in 1998, 34 % of patients taking metformin alone ovulated (compared to 4 % taking a placebo); and when metformin was combined with clomid, 90 % of the patients ovulated compared to only 8 % that took the placebo. Thus, the combination of metformin and clomid markedly improved ovulation in PCOS patients by correcting the underlying metabolic problem.

Thiazolidinediones (TZDs - Actos, Avandia) effectively lower insulin levels by effects of target cells that occur downstream from the actual binding of Insulin to the insulin receptor. Insulin resistance is therefore decreased.

Aromatase Inhibitors (Letrozole or Femara). Please refer to our infertility web site http://www.ivf-indiana.com/education/letrozole.html for information on ovulation induction with aromatase inhibitors in PCOS. In the last several years a number of studies have been published. Many are poorly controlled and therefore it is difficult to tell if this treatment is superior to clomid, in spite of the claims made by some. At present, the drug is not FDA approved for this indication and the manufacturer states it should not be used in women that may conceive.