Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET

This study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 ± 0.3 IU/l (mean±SEM), 6.0 ± 0.3 IU/l, and 8.2 ± 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 ± 0.6, 10.2 ± 0.6, and 7.9 ± 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate. Similar content being viewed by others Log in or create a free account to read this content Gain free access to this article, as well as selected content from this journal and more on nature.com or

Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR et al (1995) Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82:959–968 Balasch J, Creus M, Fabregues F, Carmona F, Casamitjana R, Ascaso C, Vanrell JA (1996) Inhibin, follicle-stimulating hormone, and age as predictors of ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Am J Obstet Gynecol 175:1226–1230 de Castro F, Ruiz R, Montoro L, Perez-Hernandez D, Sanchez-Casas Padilla E, Real LM, Ruiz A (2003) Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril 80:571–576 Davis D, Liu X, Segaloff DL (1995) Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone receptor and assessment of their role in FSH receptor function. Mol Endocrinol 9:159–170 Fauser BC (1996) Interference of follicle-stimulation hormone regulation of human ovarian function. Mol Hum Reprod 2:327–334 Fauser BC, van Heusden AM (1997) Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev 18:71–106 Kligman I, Rosenwaks Z (2001) Differentiating clinical profiles: prediction good responders, poor responders, and hyperresponders. Fertil Steril 76:1185–1190 Mayorga MP, Gromoll J, Behre HM, Gassner C, Nieschlag E, Simoni M (2000) Ovarian response to follicle-stimulating hormone stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab 85:3365–3369 Simoni M, Gromoll J, Nieschalg E (1997) The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev 18:739–773 Spearow JL, Barkley M (1999) Genetic control of hormone-induced ovulation in mice. Biol Reprod 61:851–856 Sudo S, Kudo M, Wada S, Sato O, Hsueh AJ, Fujimoto S (2002) Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Mol Hum Reprod 8:893–839 Tinkanen H, Blauer M, Laippala P, Tuohimaa P, Kujansuu E (1999) Prognostic factors in controlled ovarian hyperstimulation. Fertil Steril 72:932–936 Ulloa-Aguirre A, Midgley AR Jr, Beitins IZ, Padmanabhan V (1995) Follicle-stimulating isohormones: characterization and physiological relevance. Endocr Rev 16:765–787 Zambrano E, Zarinan T, Olivares A, Barrios-de-Tomasi J, Ulloa-Aguirre A (1999) Receptor binding activity and in vitro biological activity of the human FSH charge isoforms as disclosed by heterologous and homologous assay systems: implication for the structure-function relationship of the FSH variants. Endocrine 10:113–121

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ10-PG6-01GN13-0002). Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Jun, J.K., Yoon, J.S., Ku, SY. et al. Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet 51, 665–670 (2006). https://doi.org/10.1007/s10038-006-0005-5 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10038-006-0005-5

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