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Polycystic ovarian syndrome (PCOS), a hormonal disorder that interferes with ovulation, is a leading cause of infertility affecting an estimated 5-10% of women. While diagnosis of PCOS requires two out of the three following conditions, PCOS is typically characterized by a history of irregular periods, elevated androgen levels (which may result in increased hair growth or acne), and polycystic appearing ovaries. In many cases, women with this condition are not diagnosed until they seek treatment due to infertility.
The cause of PCOS is not well understood. Recent research suggests that insulin resistance and elevated insulin levels may play a key role in the excess production of androgen by the ovaries. Obesity is also a common feature of this syndrome and in itself has an adverse effect on reproductive outcomes. Losing 5-10% of body weight as a way of increasing insulin sensitivity was shown to be effective in restoring ovulation for 50% of patients over a 6-month period.
To stimulate ovulation, a first line of treatment for women with PCOS has been clomiphene citrate. With clomiphene, about three quarters of women with PCOS will ovulate and 50% of those women will get pregnant. Complications with clomiphene are relatively rare. In addition clomiphene has an advantage over alternative injectable medications because the risk of multiple pregnancies is significantly lower.
The past few years have also seen considerable interest in examining the use of insulin sensitizers to induce ovulation in women with PCOS. By increasing insulin sensitivity and reducing the circulating levels of insulin, the androgen production is also decreased, enhancing ovulation and fertility.
The most commonly used insulin sensitizer for this purpose has been Metformin. Early studies suggested that Metformin alone or in combination with clomiphene might be considered as a potential first line treatment. However, until recently, no large scale studies had been done that directly compared Metformin, clomiphene, and combination drug strategies based on successful pregnancy rates.
To address this question the Reproductive Medicine Network undertook a large multicenter trial with the goal of directly comparing pregnancy rates between these treatment options. This study, published earlier this year in the New England Journal of Medicine, demonstrated that with respect to successful pregnancies, Metformin was not as effective as clomiphene and also that the combination of Metformin and clomiphine did not provide any improvement in successful pregnancy rates. This result was somewhat surprising since the Metformin treatments did demonstrate a higher rate of ovulation induction than clomiphene. However, in the study population, the ovulations that resulted from the clomiphene treatment were twice as likely to result in a successful pregnancy than the ovulations resulting from Metformin.
If initial treatments with clomiphine are unsuccessful, another option is treatment with gonadotropins. Gonadotropins are injectable hormones that directly stimulate the ovary and are very effective at inducing ovulation and improving pregnancy rates. PCOS ovaries are often more difficult to stimulate with gonadotropins and caution needs to be exercised to avoid overstimulation resulting in multiple pregnancies and ovarian hyperstimulation syndrome (OHSS). This treatment is more expensive than clomiphine and requires close monitoring with frequent ultrasounds and checking hormonal levels.
Laproscopic ovarian drilling provides another option if the above approaches have not been successful. This treatment is very similar to ovarian wedge resection, which was one of the earliest infertility treatments for PCOS. This procedure makes several small punctures in the ovary resulting in a significant reduction in androgen levels. Ovarian drilling is not a common treatment for PCOS as it is invasive, and potentially increases the risk of adhesion formation and decreasing ovarian reserve. It has similar pregnancy rates as gondadotropins, though it does involve a lower incidence of multiple pregnancies and ovarian hyperstimulation syndrome.
If other strategies have not been successful, in-vitro fertilization (IVF) can also be undertaken. In addition, many newer treatment strategies such as in vitro maturation are currently being developed as additional lines of treatment for infertility patients with PCOS.
About the Author
Sasmira Lalwani, MD, is a reproductive endocrinologist specializing in the treatment of PCOS at New Jersey Fertility Center.
This article originally appeared in the RESOLVE New England Summer 2007 Newsletter.