Combined assessment of polymorphisms in the LHCGR and FSHR genes predict chance of pregnancy after in vitro fertilization

Human Reproduction

Volumn 31, Issue 3, 2016, Pages 672-683

  Lindgren, I ^a   Baath, M ^a   Uvebrant, K ^a   Dejmek, A ^b   Kjaer, L ^a   Henic, E ^b   Bungum, M ^b   Bungum, L ^c   Cilio, C ^a   Leijonhufvud, I ^b   Skouby, S ^c   Andersen, C Yding ^d   Giwercman, Y Lundberg ^a  

^a LUND UNIVERSITY   (Sweden)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

^c GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^d Rigshospitalet   (Denmark)

Author keywords

female fertility; FSH receptor; in vitro fertilization; LHCG receptor; polymorphism

Indexed keywords

CYCLIC AMP; ESTRADIOL; FOLLITROPIN; FOLLITROPIN RECEPTOR; GANIRELIX; GENOMIC DNA; HUMAN MENOPAUSAL GONADOTROPIN; INOSITOL 1,4,5 TRISPHOSPHATE; LUTEINIZING HORMONE; LUTEINIZING HORMONE RECEPTOR; NAFARELIN; RECOMBINANT FOLLITROPIN; UROFOLLITROPIN;

ADULT; ARTICLE; CLINICAL ARTICLE; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FEMALE FERTILITY; FERTILIZATION IN VITRO; GENETIC POLYMORPHISM; GENOTYPE; GRANULOSA CELL; HUMAN; HUMAN CELL; OUTCOME ASSESSMENT; OVARY FOLLICLE FLUID; POLYMERASE CHAIN REACTION; PREDICTION; PREGNANCY; RECEPTOR GENE; COHORT ANALYSIS; CROSS-SECTIONAL STUDY; GENETICS; IN VITRO FERTILIZATION; PREGNANCY RATE; TREATMENT OUTCOME;

COHORT STUDIES; CROSS-SECTIONAL STUDIES; FEMALE; FERTILIZATION IN VITRO; GENOTYPE; HUMANS; POLYMORPHISM, GENETIC; PREGNANCY; PREGNANCY RATE; RECEPTORS, FSH; RECEPTORS, LH; TREATMENT OUTCOME;

EID: 84960193221     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/dev342     Document Type: Article

References (26)

1. Angers S, Salahpour A, Bouvier M. Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu Rev Pharmacol Toxicol. 2002; 42: 409-435.
2. Camp TA, Rahal JO, Mayo KE. Cellular localization and hormonal regulation of follicle-stimulating hormone and luteinizing hormone receptor messenger RNAs in the rat ovary. Mol Endocrinol. 1991; 5: 1405-1417.
3. Capalbo A, Sagnella F, Apa R, Fulghesu AM, Lanzone A, Morciano A, Farcomeni A, Gangale MF, Moro F, Martinez D et al. The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2.7-fold increased risk of polycystic ovary syndrome in a Sardinian population. Clin Endocrinol (Oxf) 2012; 77: 113-119.
4. Casarini L, Moriondo V, Marino M, Adversi F, Capodanno F, Grisolia C, La Marca A, La Sala GB, Simoni M. FSHR polymorphism p.N680S mediates different responses to FSH in vitro. Mol Cell Endocrinol. 2014; 393: 83-91.
5. Cordell HJ, Clayton DG. Genetic association studies. Lancet. 2005; 366: 1121-1131.
6. Daelemans C, Smits G, de Maertelaer V, Costagliola S, Englert Y, Vassart G, Delbaere A. Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism. J Clin Endocrinol Metab. 2004; 89: 6310-6315.
7. ENSEMBL Genome Browser http://www.ensemble.org ( 23 April 2015, date last accessed
8. Gromoll J, Simoni M. Genetic complexity of FSH receptor function. Trends Endocrinol Metab. 2005; 16: 368-373.
9. Jun JK, Yoon JS, Ku SY, Choi YM, Hwang KR, Park SY, Lee GH, Lee WD, Kim SH, Kim JG et al. Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet. 2006; 51: 665-670.
10. Kuijper EA, Blankenstein MA, Luttikhof LJ, Roek SJ, Overbeek A, Hompes PG, Twisk JW, Lambalk CB. Frequency distribution of polymorphisms in the FSH receptor gene in infertility patients of different ethnicity. Reprod Biomed Online. 2010; 20: 588-593.
11. Lindgren I, Giwercman A, Axelsson J, Lundberg Giwercman Y. Association between follicle-stimulating hormone receptor polymorphisms and reproductive parameters in young men from the general population. Pharmacogenet Genomics. 2012; 22: 667-672.
12. McNeilly AS, Picton HM, Campbell BK, Baird DT. Gonadotrophic control of follicle growth in the ewe. J Reprod Fertil Suppl. 1991; 43: 177-186.
13. Means AR, MacDougall E, Soderling TR, Corbin JD. Testicular adenosine 3': 5'-monophosphate-dependent protein kinase. Regulation by folliclestimulating hormone. J Biol Chem. 1974; 249: 1231-1238.
14. Nordhoff V, Sonntag B, von Tils D, Gotte M, Schuring AN, Gromoll J, Redmann K, Casarini L, Simoni M. Effects of the FSH receptor gene polymorphism p.N680S on cAMP and steroid production in cultured primary human granulosa cells. Reprod Biomed Online. 2011; 23: 196-203.
15. Perez Mayorga M, Gromoll J, Behre HM, Gassner C, Nieschlag E, Simoni M. Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab. 2000; 85: 3365-3369.
16. Piersma D, Verhoef-Post M, Look MP, Uitterlinden AG, Pols HA, Berns EM, Themmen AP. Polymorphic variations in exon 10 of the luteinizing hormone receptor: functional consequences and associations with breast cancer. Mol Cell Endocrinol. 2007; 276: 63-70.
17. Regan L, Owen EJ, Jacobs HS. Hypersecretion of luteinising hormone, infertility, and miscarriage. Lancet. 1990; 336: 1141-1144.
18. Segaloff DL, Ascoli M. The lutropin/choriogonadotropin receptor. . .4 years later. Endocr Rev. 1993; 14: 324-347.
19. Shoham Z, Borenstein R, Lunenfeld B, Pariente C. Hormonal profiles following clomiphene citrate therapy in conception and nonconception cycles. Clin Endocrinol (Oxf) 1990; 33: 271-278.
20. ShortRV. Steroids in the follicular fluid and the corpus luteumof themare A 'two-cell type' theory of ovarian steroid synthesis. J Endocrinol. 1962; 24: 59-63.
21. Simoni M, Gromoll J, Hoppner W, Kamischke A, Krafft T, Stahle D, NieschlagE. 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. 1999; 84: 751-755.
22. Simoni M, Tuttelmann F, Michel C, Bockenfeld Y, Nieschlag E, Gromoll J. Polymorphisms of the luteinizing hormone/chorionic gonadotropin receptor gene: association with maldescended testes and male infertility. Pharmacogenet Genomics. 2008; 18: 193-200.
23. 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: 893-899.
24. Thomas RM, Nechamen CA, Mazurkiewicz JE, Ulloa-Aguirre A, Dias JA. The adapter protein APPL1 links FSH receptor to inositol 1, 4, 5-Trisphosphate production and is implicated in intracellular Ca(2+) mobilization. Endocrinology. 2011; 152: 1691-1701.
25. Valkenburg O, Uitterlinden AG, Piersma D, Hofman A, Themmen AP, de Jong FH, Fauser BC, Laven JS. Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the phenotype of polycystic ovary syndrome. Hum Reprod. 2009; 24: 2014-2022.
26. WorldHealthOrganization.WHOManual for the Standardized Investigation and Diagnosis of the Infertile Couple. Cambridge: Cambridge University Press, 2000.