A 25-year-old G2P1 presents for prenatal care at 8+2 weeks’ gestation by menstrual dates with complaints of nausea and vomiting for the past two weeks. Your clinical nurse reassures you the patient is not in acute distress and converses well. There is no history of vaginal bleeding.

A 43-year-old G1P1 is referred by her primary care provider to your hospital center’s high-risk obstetrics unit for preconception counseling for advanced maternal age (AMA). She started folic-containing prenatal vitamins and has recently discontinued five-year use of a copper intrauterine contraceptive device. They wish to attempt spontaneous conception prior to considering fertility evaluation.

Judgments about evidence and the resulting recommendations in healthcare are complex, especially in rapidly evolving fields such as reproductive medicine. Case reports have transformed the treatment of infertility from the first reported case of successful IVF, through ICSI and PGD to uterine transplantation, and in many of these cases there is no need to conduct a prospective trial. Indeed, in many cases it would be impossible or unethical (1). However, there are many interventions where the benefit, if any, is less clear. Recent examples in the treatment of infertility are the use of endometrial scratching or the use of PGT-A in IVF where initial enthusiasm has ultimately been replaced with disappointment. The reason for this change is the inherent bias (both known and unknown) in lower evidence level studies – such as cohort studies or ‘big data’ studies where the different interventions compared are often applied to groups with different prognostic profiles.

Introduction

Polycystic ovary syndrome (PCOS) was first described by Stein and Leventhal (1935), although the overweight, hirsuit, amenorrheic phenotype they originally described, we now realize, probably reflects the severe end of the spectrum of the syndrome. Diagnosis is made primarily by ultrasound and endocrine changes, although there remains some controversy about the significance of ultrasound-only diagnosed PCOS when the clinical phenotype and endocrine pattern are normal (Polson et al. 1988, Abdel Gadir et al. 1992). The ultrasound features of PCOS are enlarged ovaries, thickened ovarian stroma, multiple peripheral cysts (2 –10 mm diameter), and an increased intraovarian stromal blood flow (Adams et al. 1986, Zaidi et al. 1995, Buckett et al. 1999). The endocrine pattern is characterized by raised serum luteinizing hormone (LH) levels in the early follicular phase or raised ratio of LH to follicle stimulating hormone (FSH) and raised levels of testosterone and androstenedione, often associated with reduced levels of sex hormone binding globulin (SHBG) (Hull 1987, DeVane et al. 1975). However, not all these features are present in every case of PCOS and it is clear that the syndrome, primarily anovulation associated with hyperandrogenemia, is an end-point of multiple causes and this is reflected in the unknown etiology of the syndrome.

This heterogeneity has spawned many avenues for treatment of PCOS such as weight loss and lifestyle management, ovulation induction with varieties of agents, the treatment of hyperinsulinemia, the treatment of hyperandrogenemia, and the surgical treatment of PCOS. All these are described elsewhere in this volume.