Prepregnancy Insulin Resistance and Fertility and Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome

OBJECTIVE: To determine whether prepregnancy insulin resistance and its improvement during ovulation induction are associated with fertility and pregnancy outcomes in women with polycystic ovarian syndrome (PCOS). METHODS: This secondary analysis used data from PPCOS II (Pregnancy in Polycystic Ovary Syndrome II), a multicenter randomized trial. This analysis included women aged 18-40 years with PCOS who were undergoing ovulation induction with clomiphene citrate or letrozole. Insulin resistance was assessed at screening and at end-of-treatment visits by using the homeostatic model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index, and the glucose-to-insulin ratio. The primary outcome was clinical pregnancy, and secondary outcomes included gestational diabetes mellitus (GDM), preeclampsia, and preterm delivery. RESULTS: Among 746 women, higher prepregnancy HOMA-IR quartiles were associated with decreased ovulation (93.5% vs 87.8% vs 75.4% vs 73.8%; P<.001, P for trend <.001), lower clinical pregnancy (36% vs 25.5% vs 23.52% vs 26.5%; P=.005, P for trend=.001) and live-birth rates (35.5% vs 19.7% vs 20.3% vs 18.2%; P<.001, P for trend <.001), and higher risk of GDM (13.8% vs 15.4% vs 22.5% vs 45.7%; P=.002, P for trend <.001). Women in the highest HOMA-IR quartiles experienced delayed first ovulation and more frequent obstetric complications, especially increased risks of GDM. Improvement in the HOMA-IR during treatment was associated with increased odds of clinical pregnancy and reduced risk of preeclampsia. CONCLUSION: Prepregnancy insulin resistance is associated with impaired fertility and increased pregnancy complications in women with PCOS. Assessment and improvement of insulin resistance before fertilization may enhance reproductive success and reduce obstetric risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00719186.