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Erschienen in: Gynäkologische Endokrinologie 2/2015

01.05.2015 | Leitthema

FSH-Rezeptor-Polymorphismen und kontrollierte ovarielle Stimulation

verfasst von: Dr. A. Cordes, Prof. Dr. L. Kiesel, PD Dr. A. Schüring

Erschienen in: Gynäkologische Endokrinologie | Ausgabe 2/2015

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Zusammenfassung

Um die ovarielle Antwort auf eine Stimulationstherapie im Rahmen der assistierten Reproduktion präziser vorherzusagen, wurden in den letzten Jahren genetische Polymorphismen der Gonadotropinachsen untersucht. Der am besten untersuchte Polymorphismus ist dabei der FSH-Rezeptor-Polymorphismus Asn680Ser. Diese Übersichtsarbeit fasst den aktuellen Kenntnisstand vor dem Hintergrund der verfügbaren Evidenz zusammen und gibt einen Ausblick auf mögliche zukünftige klinische Anwendungen genetischer Varianten der FSH-Achse.
Literatur
1.
Zurück zum Zitat Achrekar SK, Modi DN, Desai SK et al (2009) Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women. Fertil Steril 91:432–439CrossRefPubMed Achrekar SK, Modi DN, Desai SK et al (2009) Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women. Fertil Steril 91:432–439CrossRefPubMed
2.
Zurück zum Zitat Achrekar SK, Modi DN, Meherji PK et al (2010) Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea. J Assist Reprod Genet 27:317–326CrossRefPubMedCentralPubMed Achrekar SK, Modi DN, Meherji PK et al (2010) Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea. J Assist Reprod Genet 27:317–326CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat Altmäe S, Hovatta O, Stavreus-Evers A et al (2011) Genetic predictors of controlled ovarian hyperstimulation: where do we stand today? Hum Reprod Update 17:813–828CrossRefPubMed Altmäe S, Hovatta O, Stavreus-Evers A et al (2011) Genetic predictors of controlled ovarian hyperstimulation: where do we stand today? Hum Reprod Update 17:813–828CrossRefPubMed
4.
Zurück zum Zitat d’Alva CB, Serafini P, Motta E et al (2005) Absence of follicle-stimulating hormone receptor activating mutations in women with iatrogenic ovarian hyperstimulation syndrome. Fertil Steril 83:1695–1699CrossRefPubMed d’Alva CB, Serafini P, Motta E et al (2005) Absence of follicle-stimulating hormone receptor activating mutations in women with iatrogenic ovarian hyperstimulation syndrome. Fertil Steril 83:1695–1699CrossRefPubMed
5.
Zurück zum Zitat Behre HM, Greb RR, Mempel A et al (2005) Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation. Pharmacogenet Genom 15:451–456CrossRef Behre HM, Greb RR, Mempel A et al (2005) Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation. Pharmacogenet Genom 15:451–456CrossRef
6.
Zurück zum Zitat Binder H, Dittrich R, Hager I et al (2008) Association of FSH receptor and CYP19A1 gene variations with sterility and ovarian hyperstimulation syndrome. Reproduction 135:107–116CrossRefPubMed Binder H, Dittrich R, Hager I et al (2008) Association of FSH receptor and CYP19A1 gene variations with sterility and ovarian hyperstimulation syndrome. Reproduction 135:107–116CrossRefPubMed
7.
Zurück zum Zitat Broekmans FJ, Verweij PJ, Eijkemans MJ et al (2014) Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. doi:10.1093/humrep/deu090. (Epub 2014 Jun 5) Broekmans FJ, Verweij PJ, Eijkemans MJ et al (2014) Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. doi:10.1093/humrep/deu090. (Epub 2014 Jun 5)
8.
Zurück zum Zitat Casarini L, Pignatti E, Simoni M (2011) Effects of polymorphisms in gonadotropin and gonadotropin receptor genes on reproductive function. Rev Endocr Metab Disord 12:303–321CrossRefPubMed Casarini L, Pignatti E, Simoni M (2011) Effects of polymorphisms in gonadotropin and gonadotropin receptor genes on reproductive function. Rev Endocr Metab Disord 12:303–321CrossRefPubMed
9.
Zurück zum Zitat de Castro F, Ruiz R, Montoro L et al (2003) Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril 80:571–576CrossRefPubMed de Castro F, Ruiz R, Montoro L et al (2003) Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril 80:571–576CrossRefPubMed
10.
Zurück zum Zitat de Castro F, Moron FJ, Montoro L et al (2004) Human controlled ovarian hyperstimulation outcome is a polygenic trait. Pharmacogenetics 14:285–293CrossRefPubMed de Castro F, Moron FJ, Montoro L et al (2004) Human controlled ovarian hyperstimulation outcome is a polygenic trait. Pharmacogenetics 14:285–293CrossRefPubMed
11.
Zurück zum Zitat Davis D, Liu X, Segaloff DL (1995) Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function. Mol Endocrinol 9:159–170PubMed Davis D, Liu X, Segaloff DL (1995) Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function. Mol Endocrinol 9:159–170PubMed
12.
Zurück zum Zitat Daelemans C, Smits G, de Maertelaer V et al (2004) Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism. J Clin Endocrinol Metab 89:6310–6315CrossRefPubMed Daelemans C, Smits G, de Maertelaer V et al (2004) Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism. J Clin Endocrinol Metab 89:6310–6315CrossRefPubMed
13.
Zurück zum Zitat Desai SS, Achrekar SK, Pathak BR et al (2011) Follicle-stimulating hormone receptor polymorphism (G-29A) is associated with altered level of receptor expression in granulosa cells. J Clin Endocrinol Metab 96:2805–2812CrossRefPubMed Desai SS, Achrekar SK, Pathak BR et al (2011) Follicle-stimulating hormone receptor polymorphism (G-29A) is associated with altered level of receptor expression in granulosa cells. J Clin Endocrinol Metab 96:2805–2812CrossRefPubMed
14.
Zurück zum Zitat Greb RR, Grieshaber K, Gromoll J et al (2005) A common single nucleotide polymorphism in exon 10 of the human follicle stimulating hormone receptor is a major determinant of length and hormonal dynamics of the menstrual cycle. J Clin Endocrinol Metab 90:4866–4872CrossRefPubMed Greb RR, Grieshaber K, Gromoll J et al (2005) A common single nucleotide polymorphism in exon 10 of the human follicle stimulating hormone receptor is a major determinant of length and hormonal dynamics of the menstrual cycle. J Clin Endocrinol Metab 90:4866–4872CrossRefPubMed
15.
Zurück zum Zitat Genro VK, Matte U, De Conto E et al (2012) Frequent polymorphisms of FSH receptor do not influence antral follicle responsiveness to follicle-stimulating hormone administration as assessed by the Follicular Output RaTe (FORT). J Assist Reprod Genet 29:657–663CrossRefPubMedCentralPubMed Genro VK, Matte U, De Conto E et al (2012) Frequent polymorphisms of FSH receptor do not influence antral follicle responsiveness to follicle-stimulating hormone administration as assessed by the Follicular Output RaTe (FORT). J Assist Reprod Genet 29:657–663CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat Gromoll J, Simoni M (2001) Follicle-stimulating-hormone receptor and twinning. Lancet 357(9251):230 author reply 231–232 Gromoll J, Simoni M (2001) Follicle-stimulating-hormone receptor and twinning. Lancet 357(9251):230 author reply 231–232
17.
Zurück zum Zitat Hanevik HI, Hilmarsen HT, Skjelbred CF et al (2010) Single nucleotide polymorphisms in the anti-Müllerian hormone signalling pathway do not determine high or low response to ovarian stimulation. Reprod Biomed Online 21:616–623CrossRefPubMed Hanevik HI, Hilmarsen HT, Skjelbred CF et al (2010) Single nucleotide polymorphisms in the anti-Müllerian hormone signalling pathway do not determine high or low response to ovarian stimulation. Reprod Biomed Online 21:616–623CrossRefPubMed
18.
Zurück zum Zitat Jun JK, Yoon JS, Ku S et al (2006) Follicle stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet 51:665–670CrossRefPubMed Jun JK, Yoon JS, Ku S et al (2006) Follicle stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet 51:665–670CrossRefPubMed
19.
Zurück zum Zitat Kerkela E, Skottam H, Friden B et al (2007) Exclusion of coding region mutations in luteinising hormone and follicle-stimulating hormone receptor genes as the cause of ovarian hyperstimulation syndrome. Fertil Steril 87:603–606CrossRefPubMed Kerkela E, Skottam H, Friden B et al (2007) Exclusion of coding region mutations in luteinising hormone and follicle-stimulating hormone receptor genes as the cause of ovarian hyperstimulation syndrome. Fertil Steril 87:603–606CrossRefPubMed
20.
Zurück zum Zitat Klinkert ER, te Velde ER, Weima S et al (2006) FSH receptor genotype is associated with pregnancy but not with ovarian response in IVF. Reprod Biomed Online 13:687–695CrossRefPubMed Klinkert ER, te Velde ER, Weima S et al (2006) FSH receptor genotype is associated with pregnancy but not with ovarian response in IVF. Reprod Biomed Online 13:687–695CrossRefPubMed
21.
Zurück zum Zitat Lalioti MD (2011) Impact of follicle stimulating hormone receptor variants in fertility. Curr Opin Obstet Gynecol 23:158–167CrossRefPubMed Lalioti MD (2011) Impact of follicle stimulating hormone receptor variants in fertility. Curr Opin Obstet Gynecol 23:158–167CrossRefPubMed
22.
Zurück zum Zitat La Marca A, Sighinolfi G, Argento C et al (2013) Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization. Fertil Steril 99:970–978CrossRefPubMed La Marca A, Sighinolfi G, Argento C et al (2013) Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization. Fertil Steril 99:970–978CrossRefPubMed
23.
Zurück zum Zitat Livshyts G, Podlesnaja S, Kravchenko S et al (2009) A distribution of two SNPs in exon 10 of the FSHR gene among the women with a diminished ovarian reserve in Ukraine. J Assist Reprod Genet 26:29–34 Livshyts G, Podlesnaja S, Kravchenko S et al (2009) A distribution of two SNPs in exon 10 of the FSHR gene among the women with a diminished ovarian reserve in Ukraine. J Assist Reprod Genet 26:29–34
24.
Zurück zum Zitat Loutradis D, Patsoula E, Minas V et al (2006) FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs. J Assist Reprod Genet 23:177–184CrossRefPubMedCentralPubMed Loutradis D, Patsoula E, Minas V et al (2006) FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs. J Assist Reprod Genet 23:177–184CrossRefPubMedCentralPubMed
25.
Zurück zum Zitat Moron FJ, Ruiz A (2010) Pharmacogenetics of controlled ovarian hyperstimulation: time to corroborate the clinical utility of FSH receptor genetic markers. Pharmacogenomics 11:1613–1618CrossRefPubMed Moron FJ, Ruiz A (2010) Pharmacogenetics of controlled ovarian hyperstimulation: time to corroborate the clinical utility of FSH receptor genetic markers. Pharmacogenomics 11:1613–1618CrossRefPubMed
26.
Zurück zum Zitat Nordhoff V, Sonntag B, von Tils D et al (2011) Effects of the FSH receptor gene polymorphism p.N680S on cAMP and steroid production in cultured primary human granulosa cells. Reprod Biomed Online 23:196–203 Nordhoff V, Sonntag B, von Tils D et al (2011) Effects of the FSH receptor gene polymorphism p.N680S on cAMP and steroid production in cultured primary human granulosa cells. Reprod Biomed Online 23:196–203
27.
Zurück zum Zitat Perez Mayorga M, Gromoll J, Behre HM et al (2000) Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab 85:3365–3369PubMed Perez Mayorga M, Gromoll J, Behre HM et al (2000) Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab 85:3365–3369PubMed
28.
Zurück zum Zitat Schüring AN, Busch AS, Bogdanova N et al (2013) Effects of the FSH-β-subunit promoter polymorphism -211G-G- >T on the hypothalamic-pituitary-ovarian axis in normally cycling women indicate a gender-specific regulation of gonadotropin secretion. J Clin Endocrinol Metab 98:2012–2780 Schüring AN, Busch AS, Bogdanova N et al (2013) Effects of the FSH-β-subunit promoter polymorphism -211G-G- >T on the hypothalamic-pituitary-ovarian axis in normally cycling women indicate a gender-specific regulation of gonadotropin secretion. J Clin Endocrinol Metab 98:2012–2780
29.
Zurück zum Zitat Simoni M, Gromoll J, Höppner W et al (1999) Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J Clin Endocrinol Metab 84:751–755PubMed Simoni M, Gromoll J, Höppner W et al (1999) Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J Clin Endocrinol Metab 84:751–755PubMed
30.
Zurück zum Zitat Simoni M, Nieschlag E, Gromoll J (2002) Isoforms and single nucleotide polymorphisms of FSH receptor gene: implications for human reproduction. Hum Reprod Update 8:413–421CrossRefPubMed Simoni M, Nieschlag E, Gromoll J (2002) Isoforms and single nucleotide polymorphisms of FSH receptor gene: implications for human reproduction. Hum Reprod Update 8:413–421CrossRefPubMed
31.
Zurück zum Zitat Sudo S, Kudo M, Wada S et al (2002) Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Mol Hum Reprod 8:893–899CrossRefPubMed Sudo S, Kudo M, Wada S et al (2002) Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Mol Hum Reprod 8:893–899CrossRefPubMed
32.
Zurück zum Zitat Tüttelmann F, Laan M, Grigorova M et al (2012) Combined effects of the variants FSHB -211G >T and FSHR 2039A >G on male reproductive parameters. J Clin Endocrinol Metab 97:3639–3647CrossRefPubMed Tüttelmann F, Laan M, Grigorova M et al (2012) Combined effects of the variants FSHB -211G >T and FSHR 2039A >G on male reproductive parameters. J Clin Endocrinol Metab 97:3639–3647CrossRefPubMed
33.
Zurück zum Zitat Wunsch A, Ahda Y, Banaz-Yas’ar F et al (2005) Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle stimulating hormone receptor. Fertil Steril 84:446–453CrossRefPubMed Wunsch A, Ahda Y, Banaz-Yas’ar F et al (2005) Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle stimulating hormone receptor. Fertil Steril 84:446–453CrossRefPubMed
34.
Zurück zum Zitat Wunsch A, Sonntag B, Simoni M (2007) Polymorphism of the FSH receptor and ovarian response to FSH. Ann Endocrinol 68:160–166CrossRef Wunsch A, Sonntag B, Simoni M (2007) Polymorphism of the FSH receptor and ovarian response to FSH. Ann Endocrinol 68:160–166CrossRef
35.
Zurück zum Zitat Yao Y, Ma CH, Tang HL et al (2011) Influence of follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphism on ovarian function and in vitro fertilization outcome: a meta-analysis. Mol Genet Metab 103:388–393CrossRefPubMed Yao Y, Ma CH, Tang HL et al (2011) Influence of follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphism on ovarian function and in vitro fertilization outcome: a meta-analysis. Mol Genet Metab 103:388–393CrossRefPubMed
Metadaten
Titel
FSH-Rezeptor-Polymorphismen und kontrollierte ovarielle Stimulation
verfasst von
Dr. A. Cordes
Prof. Dr. L. Kiesel
PD Dr. A. Schüring
Publikationsdatum
01.05.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Gynäkologische Endokrinologie / Ausgabe 2/2015
Print ISSN: 1610-2894
Elektronische ISSN: 1610-2908
DOI
https://doi.org/10.1007/s10304-015-0007-5

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