Treatment, or denial of treatment, for infertility to women of advanced weight is not based on evidence, but rather ignorance and biases of care givers and public health systems. The association between obesity and subfertility is real, but much smaller than recognised. Obesity is not a personal choice, but the result of a complex disease and one that is generally resistant to most treatments. The hypothalamus holds onto weight as the miser holds onto gold. Long-term maintenance of significant weight loss is the exception and not the rule of the treatment of obesity. Further there is no evidence that weight loss prior to pregnancy in women with obesity improves live birth rates or lowers maternal morbidity during pregnancy. In fact, the data suggest taking time to lose weight results in a delayed time to delivery and potentially other adverse events such as increased early pregnancy loss. We should stop advising women with obesity to lose weight prior to conception, because obesity per se is a marginal issue in subfertility; effective therapies to achieve the recommended weight loss are lacking, and even if achieved, there may be no benefit to it.

Introduction

Polycystic ovary syndrome (PCOS) is the most common but least understood endocrinopathy. Although a major genetic contribution is suspected, there have been no clear genes or family of genes identified that cause or contribute to PCOS. This may be due to both the difficulty in phenotyping as well as the limited genotyping studies that have been performed to date. The diagnosis of PCOS has traditionally been based on a history of oligomenorrhea and/or hyperandrogenism, either clinical, i.e., most commonly hirsutism, or biochemical, i.e., elevated circulating total or bioavailable androgens; and/or polycystic ovaries. The criteria that emerged from the 1990 National Institute of Child and Human Development (NIH-NICHD) conference identified PCOS as unexplained hyperandrogenic chronic anovulation, making it in essence a diagnosis of exclusion (Zawadski and Dunaif 1992). The “consensus” definition did not include the polycystic ovary morphology, most commonly today found on ultrasound consisting of multiple 2–8 mm subcapsular preantral follicles and increased ovarian volume (Balen et al. 2003). These ultrasound criteria were recently incorporated in the revised 2003 Rotterdam criteria which require two out of the three above cardinal stigmata for PCOS: oligomenorrhea, hyperandrogenism, and/or polycystic ovaries (The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004).

None of these expert-generated definitions include insulin resistance, a common but not inevitable finding in PCOS. This diagnostic dilemma has hampered clinical and genetic studies of PCOS. The larger the number of distinct phenotypes within the affected category, the more complex the genetic analysis and the greater the likelihood that investigators using different diagnostic criteria will arrive at different conclusions.