Impact of Obesity on Fertility in Polycystic Ovary Syndrome
Introduction: This study presents baseline data from the randomized, double-blind infertility clinical trial known as Pregnancy in Polycystic Ovary Syndrome II (PPCOS II).
Methods: PPCOS II was designed to compare the effects of five cycles of letrozole versus clomiphene in the first-line treatment of infertility in women with PCOS. This report focused on baseline characteristics associated with fertility in 750 women with PCOS and their male partners. The couples had been attempting to conceive for an average of nearly 3.5 years.
Results: The average age of this cohort was 30 years and most of the women (67%) were obese. When obese women’s BMI measurements were divided into 3 categories (ie, 30-34.9, 35-39.9, ≥40), obesity showed a dose-response relationship with the severity of reproductive and metabolic abnormalities associated with PCOS. Increasing levels of BMI were associated with greater increases in blood pressure, fasting glucose and insulin levels, and dyslipidemia, and prevalence of metabolic syndrome. Greater severity of obesity also was linked to decreased LH-to-FSH levels, antimullerian hormone levels, and antral follicle counts and increasing cardiovascular risk. In addition, increasing BMI was linked to greater declines in quality of life.
Conclusion: Obesity worsens reproductive and metabolic abnormalities in women with PCOS.
Tamara L. Wexler, MD, PhD, is an endocrinologist specializing in reproductive and neuroendocrinology, and an Attending in Medicine, Massachusetts General Hospital, Boston, MA.
This study was drawn from a larger multi-center randomized clinical trial, the purpose of which was to test two different treatments head-to-head for ovulation induction in women with known PCOS and trouble conceiving. Thus, all women included in the trial had PCOS diagnosed by 1) ovulatory dysfunction and 2) either hirsutism/high serum androgen or polycystic ovaries by ultrasound. Average age was 30 and average BMI was 35.1±-9.3. The majority of the women (86%) carried a diagnosis of infertility with an average of 3.5 years trying to conceive; 64% were nulligravid, and 80% were nulliparous.
In comparing data from this study, the investigators subdivided the cohort by BMI range (<30, 30-34.9, 35-39.9, ≥40). They found that higher BMI was associated with higher rates of infertility, as well as worse metabolic derangements and decreased QOL (quality of life, as measured by several validated questionnaires). There was no association with race or ethnicity. The authors also noted that subjects with PCOS who did not have hyperandrogenism (ie, those without hirsutism or high serum androgen and who thus were diagnosed by polycystic ovaries on ultrasound in addition to irregular menses) were thinner on average.
The main purpose of the PPCOS II study is comparison of clomiphene citrate to letrozole in women with PCOS seeking conception. It is important to recognize that these findings are not primary outcomes of the PPCOSII trial, but noted by the authors in their evaluation of the subjects’ baseline characteristics.
The findings of this study are relevant for our topic of weight and fertility in identifying an association between higher BMI and infertility, even among women with known PCOS.