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Prediction of Severity of Symptoms in Iatrogenic Ovarian Hyperstimulation Syndrome by Follicle-Stimulating Hormone Receptor Ser⁶⁸⁰Asn Polymorphism

Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire (C.D., G.S., V.d.M., S.C., G.V.) and Laboratory of Research on Human Reproduction (Y.E., A.D.), Faculté de Médecine; and Fertility Clinic (Y.E., A.D.) and Medical Genetics Department (G.S., G.V.), Hôpital Erasme, Université Libre de Bruxelles, B-1070 Brussels, Belgium

Address all correspondence and requests for reprints to: Dr. Anne Delbaere, Clinique de Fertilité, Hôpital Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium. E-mail: adelbaer{at}ulb.ac.be.

The ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of ovarian stimulation treatments for in vitro fertilization (IVF). Recently, three different mutations of the FSH receptor (FSHr) have been identified in patients who presented recurrent spontaneous OHSS. This prompted us to study a possible association between coding polymorphisms of the FSHr and the occurrence of iatrogenic OHSS. We sequenced the region of the FSHr gene encompassing the A³⁰⁷T and S⁶⁸⁰N polymorphisms of exon 10 of FSHr in 37 Caucasian females who developed OHSS after an IVF cycle in our fertility clinic, 130 Caucasian female patients who were treated by IVF but never developed OHSS, and 99 Caucasian female controls. The FSHr allele frequencies in the Caucasian control population were identical to what has already been published (39% S⁶⁸⁰ 61% N⁶⁸⁰). The control IVF population was enriched in the S⁶⁸⁰ allele compared with the Caucasian control population (51% S⁶⁸⁰; 49% N⁶⁸⁰; P = 0.016). The OHSS population had a even higher enrichment in the S⁶⁸⁰ allele compared with the Caucasian control population (57% S⁶⁸⁰; 43% N⁶⁸⁰; P = 0.010). These results were unexpected, because the frequency of the S⁶⁸⁰ allele was previously found to be increased among poor responders to FSH stimulation. In a second phase, we studied FSHr allele frequencies according to the severity of OHSS. Interestingly, a significant enrichment in the allele N⁶⁸⁰ was observed as the severity of OHSS increased (P = 0.034). Bearing in mind the limitations of the small number of patients studied and the possibility of sampling biases, these results suggest that the genotype in position 680 of the FSHr cannot predict which patients will develop OHSS, but could be a predictor of severity of symptoms among OHSS patients.

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