Elevated Activity Levels of Activating Autoantibodies to the Gonadotropin Releasing Hormone Receptor in Patients with Polycystic Ovary Syndrome

ABSTRACT Objectives (1) To confirm the correlation of gonadotropin releasing hormone receptor (GnRHR) activating autoantibody (AAb) activity with polycystic ovary syndrome (PCOS) diagnosis in large, well-defined cohorts, (2) to evaluate suppression of AAb activity with GnRH antagonist medication in GnRHR transfected cells exposed to serum of PCOS patients. Design Cross-sectional, matched case-control Setting University-based research facility Patients Sera from 200 patients with PCOS from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial and from 200 race, parity, age, and body mass index (BMI) matched ovulatory, unexplained infertile control patients from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) trial were obtained and utilized for this study. Intervention(s) GnRHR AAb activity was determined using the GeneBLAzer cell-based fluorescence resonance energy transfer (FRET) assay with and without cetrorelix, a GnRH antagonist. Main Outcome Measure(s) (1) GnRHR AAb activity in PCOS patients as compared to controls, (2) Demonstrate the effectiveness of GnRH antagonist in suppressing GnRHR AAb activity. Result(s) GnRHR AAb activity levels in the PCOS group were significantly higher than in the control group, p=0.0017. With cetrorelix, GnRHR AAb activity was largely suppressed in the PCOS group (p Conclusion We have confirmed higher GnRHR AAb activity levels in the sera of a large cohort of PCOS patients compared to unexplained infertile controls. Addition of cetrorelix resulted in significant suppression of AAb activity levels in PCOS patients as a group but controls were unaffected. GnRHR AAb, along with patient age and AMH, may provide a promising future diagnostic test for PCOS.