Polycystic ovary syndrome, infertility, familial thrombophilia, familial hypofibrinolysis, recurrent loss of in vitro fertilized embryos, and miscarriage

Objective: To study reversible determinants of infertility and recurrent loss of transferred embryos after failure of 7 of 10 embryo transfers, 1 live birth, and 2 miscarriages. Design: Measures of thrombophilia, hypofibrinolysis, reproductive hormones, and androgenic steroids before and after metformin therapy. Setting: Outpatient clinical research center. Patient(s): A 32-year-old amenorrheic, infertile woman with polycystic ovary syndrome (PCOS) who had 7 of 10 embryo transfers fail, 1 premature live birth, and 2 miscarriages at 8 and 17 weeks. Intervention(s): Metformin (2.55 g/d) was given to ameliorate the endocrinopathy of PCOS. Main Outcome Measure(s): Coagulation, insulin, reproductive hormones, and androgenic steroids. Result(s): The propositus had thrombophilia (familial protein S deficiency [free protein S 32%; normal ≥65%]). She also had familial hypofibrinolysis with 4G4G polymorphism of the plasminogen activator inhibitor (PAI-1) gene and high PAI-1 activity (PAI-Fx), 42.5 U/mL, normal