Journal of Assisted Reproduction and Genetics

, Volume 23, Issue 4, pp 177–184 | Cite as

FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs

  • Dimitris Loutradis
  • Eleni Patsoula
  • Vassilis Minas
  • Giorgos A. Koussidis
  • Aristeidis Antsaklis
  • Stylianos Michalas
  • Antonis MakrigiannakisEmail author
Assisted Reproduction

Purpose: To examine the frequency distribution of the Ser680Asn polymorphism of the follicle-stimulating hormone receptor (FSHR) gene in ovarian dysfunction (OD) infertile women, “poor responders” (PR) and “good responders” (GR).

Methods: The hormonal profiles and treatment of all patients were analyzed and FSHR polymorphism was examined by PCR and RFLP. Women from all groups were classified as Asn/Asn, Asn/Ser, and Ser/Ser genotypes.

Results: The frequency distribution of Ser/Ser, Asn/Ser and Asn/Asn variants in OD patients was 45.5, 22.7, and 31.8%, respectively. Day 3 FSH levels in OD and GR patients were higher in Ser/Ser and Asn/Asn subgroups. Asn/Ser carriers from OD and GR groups provided more follicles and oocytes compared to other allelic variants.

Conclusions: GR patients carry more often the Asn/Ser genotype. The latter is correlated with more follicles and oocytes in both OD and GR patients. The Ser/Ser variant might be related to higher serum FSH levels, while the Asn/Ser with lower.


FSH receptor gene polymorphisms ovarian response ovarian stimulation. 


  1. 1.
    Gharib SD, Wierman ME, Shupnik MA, Chin WW: Molecular biology of pituitary gonadotrophins. Endocrinol Rev 1990;11:177–199Google Scholar
  2. 2.
    Moyle WR, Campbell RK: Gonadotrophins. In Reproductive Endocrinology, Surgery and Technology, EY Adashi, JA Rock, Z Rosenwalks (eds), Philadelphia, Lippincott-Raven, 1996; pp. 683–724Google Scholar
  3. 3.
    Patsoula E, Loutradis D, Drakakis P, Kallianidis K, Bletsa R, Michalas S: Expression of mRNA for the LH and FSH receptors in mouse oocytes and preimplantation embryos. Reproduction 2001;121:455–461CrossRefPubMedGoogle Scholar
  4. 4.
    Patsoula E, Loutradis D, Drakakis P, Michalas L, Bletsa R, Michalas S: mRNA expression for the follicle stimulating hormone receptor and luteinizing hormone receptor in human oocytes and preimplantation stage embryos. Fertil Steril 2003;79:1187–1193CrossRefPubMedGoogle Scholar
  5. 5.
    Dufau ML: The luteinizing hormone receptor. Ann Rev Physiol 1998;60:461–496CrossRefGoogle Scholar
  6. 6.
    Segaloff DL, Ascoli M: The lutropin/choriogonadotropin receptor… 4 years later. Endocrinol Rev 1993;14:324–342CrossRefGoogle Scholar
  7. 7.
    Simoni M, Gromoll J, Nieschlag E: The follicle-stimulating hormone receptor: Biochemistry, molecular biology, physiology, and pathophysiology. Endocrinol Rev 1997;18:739–773CrossRefGoogle Scholar
  8. 8.
    Minegishi T, Nakamura K, Takakura Y, Miyamoto K, Hasegawa Y, Ibuki Y, Igarashi M, Minegish T: Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun 1991;173:1125–1130CrossRefGoogle Scholar
  9. 9.
    Sprengel R, Braun T, Nicolics K, Segaloff DL, Seeburg PH: The testicular receptor for follicle-stimulating hormone: structure and functional expression of the cloned cDNA. Mol Endocrinol 1990;4:525–530PubMedCrossRefGoogle Scholar
  10. 10.
    Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, et al: Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 1995;82:959–968CrossRefPubMedGoogle Scholar
  11. 11.
    Aittomaki K, Herva R, Stenman UH, Juntunen K, Ylostalo P, Hovatta O, de la Chapelle A: Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene. J Clin Endocrinol Metabol 1996;81:3722–3726CrossRefGoogle Scholar
  12. 12.
    da Fonte Kohek MB, Batista MC, Russell AJ, Vass K, Giacaglia LR, Mendonca BB, Latronico AC: No evidence of the inactivating mutation (CS66T) in the follicle-stimulating hormone receptor gene in Brazilian women with premature ovarian failure. Fertil Steril 1998;70:565–567CrossRefPubMedGoogle Scholar
  13. 13.
    Takakura K, Takebayashi K, Wang HQ, Kimura F, Kasahara K, Noda Y: Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome. Fertil Steril 2001;75:207–209CrossRefPubMedGoogle Scholar
  14. 14.
    Perez Mayorga M, Gromoll J, Behre HM, Gassner C, Nieschlag E, Simoni M: Ovarian response to Follicle-Stimulation Hormone (FSH). Stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metabol 2000;85:3365–3369CrossRefGoogle Scholar
  15. 15.
    Scott RT, Hofmann GF: Prognostic assessment of ovarian reserve. Fertil Steril 1995;63:12–14PubMedGoogle Scholar
  16. 16.
    Loutradis D, Elsheikh A, Kallianidis K, Drakakis P, Stefanidis K, Milingos S, Michalas S: Results of controlled ovarian stimulation for ART in poor responders according to the short protocol using different gonadotrophins combinations. Arch Gynecol Obstet 2003, (in press)Google Scholar
  17. 17.
    Simoni M, Nieschlag E, Gromoll J: Isoforms and single nucleotide polymorphisms of the FSH receptors gene: Implications for human reproduction. Hum Reprod Update 2002;8:413–421CrossRefPubMedGoogle Scholar
  18. 18.
    Sudo S, Kudo M, Wada S, Sato O, Hsueh AJ, Fujimoto S: Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Mol Hum Reprod 2002;8:893–899CrossRefPubMedGoogle Scholar
  19. 19.
    McLachlan RI, Robertson DM, Healy DL, de Kretser DM, Burger HG: Plasma inhibin levels during gonadotropin-induced ovarian hyperstimulation for IVF: A new index of follicular function? Lancet 1986;31:1233–1234CrossRefGoogle Scholar
  20. 20.
    Scott RT, Navot D: Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization. Fertil Steril 1994;61:880–885PubMedGoogle Scholar
  21. 21.
    Surrey ES, Bower J, Hill DM, Ramsey J, Surrey MW: Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril 1998;69:419–424CrossRefPubMedGoogle Scholar
  22. 22.
    Ben-Rafael Z, Feldberg D: The poor-responder patient in an in vitro fertilization-embryo transfer program. J Assist Reprod Genet 1993;10:118–120CrossRefPubMedGoogle Scholar
  23. 23.
    de Koning CH, Popp-Snijders C, Schoemaker J, Lambalk CB: Elevated FSH concentrations in imminent ovarian failure are associated with higher FSH and LH pulse amplitude and response to GnRH. Hum Reprod 2000;15:1452–1456CrossRefPubMedGoogle Scholar
  24. 24.
    Jones GS, Muasher SJ, Rosenwaks Z, Acosta AA, Liu HC: The perimenopausal patient in in vitro fertilization: The use of gonadotropin-releasing hormone. Fertil Steril 1986;46:885–891PubMedGoogle Scholar
  25. 25.
    Cameron IT, O'Shea FC, Rolland JM, Hughes EG, de Kretser DM, Healy DL: Occult ovarian failure: A syndrome of infertility, regular menses, and elevated follicle-stimulating hormone concentrations. J Clin Endocrinol Metab 1988;67:1190–1194PubMedGoogle Scholar
  26. 26.
    Buckler HM, Evans CA, Mamtora H, Burger HG, Anderson DC: Gonadotropin, steroid, and inhibin levels in women with incipient ovarian failure during anovulatory and ovulatory rebound cycles. J Clin Endocrinol Metab 1991;72:116–124PubMedCrossRefGoogle Scholar
  27. 27.
    Drakakis P, Loutradis D, Kallianidis K, Bletsa R, Milingos S, Dionyssiou-Asteriou A, Michalas S: A comparative study of the effect of ovarian stimulation protocols with different gonadotropin preparations on the biological and clinical parameters of the outcome of intracytoplasmic sperm injection. Int Clin Exp Obstet Gynecol 2002;4:286–289Google Scholar
  28. 28.
    Loutradis D, Drakakis P, Kallianidis K, Milingos S, Dendrinos S, Michalas S: Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection. Fertil Steril 1999;72:240–244CrossRefPubMedGoogle Scholar
  29. 29.
    Loutradis D, Drakakis P, Milingos S, Stefanidis K, Michalas S: Alternative approaches in the management of poor response in controlled ovarian hyperstimulation (COH). Ann NY Acad Sci 2003;997:112–119CrossRefPubMedGoogle Scholar
  30. 30.
    Laven JS, Mulders AG, Suryandari DA, Gromoll J, Nieschlag E, Fauser BC, Simoni M: Follicle-stimulating hormone receptor polymorphisms in women with normogonadotropic anovulatory infertility. Fertil Steril 2003;80:986–992CrossRefPubMedGoogle Scholar
  31. 31.
    de Castro F, Ruiz R, Montoro L, Perez-Hernandez D, Sanchez-Casas Padilla E, Real LM, Ruiz A: Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril 2003;80:571–576CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Dimitris Loutradis
    • 1
  • Eleni Patsoula
    • 1
  • Vassilis Minas
    • 2
  • Giorgos A. Koussidis
    • 1
  • Aristeidis Antsaklis
    • 1
  • Stylianos Michalas
    • 1
  • Antonis Makrigiannakis
    • 2
    Email author
  1. 1.Division of Human Reproduction, IVF Unit, 1st Department of Obstetrics and GynaecologyAthens University Medical SchoolAthensGreece
  2. 2.Laboratory of Human Reproduction, Department of Obstetrics and Gynaecology, Medical SchoolUniversity of CreteHeraklionGreece

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