Volume 12, Issue 10 (11-2014)                   IJRM 2014, 12(10): 667-0 | Back to browse issues page

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Davar R, Tabibnejad N, Kalantar S M, Sheikhha M H. The luteinizing hormone beta-subunit exon 3 (Gly102Ser) gene mutation and ovarian responses to controlled ovarian hyperstimulation. IJRM 2014; 12 (10) :667-0
URL: http://ijrm.ir/article-1-482-en.html
The luteinizing hormone beta-subunit exon 3 (Gly102Ser) gene mutation and ovarian responses to controlled ovarian hyperstimulation
Robab Davar1 , Nasim Tabibnejad1 , Seyed Mehdi Kalantar1 , Mohammad Hasan Sheikhha * 2
1- Research and Clinical Center for Infertility, Shahid Sdoughi University of Medical Sciences, Yazd, Iran
2- Research and Clinical Center for Infertility, Shahid Sdoughi University of Medical Sciences, Yazd, Iran , sheikhha@yahoo.com
Abstract:   (2715 Views)
Background: Despite extensive progress in IVF techniques, one of the most difficult problems is the variability in the response to controlled ovarian hyperstimulation (COH). Recent studies show the effects of individual genetic variability on COH outcome.
Objective: To evaluate the correlation between LHβ G1502A polymorphisms in exon 3 of the LH gene and ovarian response to COH.
Materials and Methods: A total of 220 women treated with a long protocol for ovarian stimulation were studied. Three genotypes of GG, GA and AA were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
Results: In total, 34 (17%) patients were poor responders, 154 (77%) were normal responders and 12 (6%) were hyper responders. The most frequent genotype was GA (55.5%) whereas 44.5% of patients showed GG genotype and there was no patient with AA genotype. In total 54.5% of normal responders, 61.8% of poor responders and 50% of hyper responders showed GA genotype.
Conclusion: Our results did not establish a significant relationship between this polymorphism and the ovarian response. Therefore it is still very difficult to use the genotype of patients for prediction of the ovarian response to stimulation.
Keywords: Ovulation induction, LHβ gene, Single nucleotide polymorphisms
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Type of Study: Original Article |
References
1. Society for Assisted Reproductive Technology; American Society for Reproductive Medicine. Assisted reproductive technology in the United States: 2001 results generated from the American Society for Reproductive Medicine/ Society for Assisted Reproductive Technology registry. Fertil Steril 2007; 87: 1253-1266. [DOI:10.1016/j.fertnstert.2006.11.056]
2. Verberg MF, Eijkemans MJ, Macklon NS, Heijnen EM, Baart EB, Hohmann FP, et al. The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF: a meta-analysis. Hum Reprod Update 2009; 15: 5-12. [DOI:10.1093/humupd/dmn053]
3. Yong PY, Brett S, Baird DT, Thong KJ. A prospective randomized clinical trial comparing 150 IU and 225 IU of recombinant follicle-stimulating hormone (Gonal-F*) in a fixed-dose regimen for controlled ovarian stimulation in in vitro fertilization treatment. Fertil Steril 2003; 79: 308-315. [DOI:10.1016/S0015-0282(02)04583-1]
4. Out HJ, Rutherford A, Fleming R, Tay CC, Trew G, Ledger W, et al. A randomized, double-blind, multicentre clinical trial comparing starting doses of 150 and 200 IU of recombinant FSH in women treated with the GnRH antagonist ganirelix for assisted reproduction. Hum Reprod 2004; 19: 90-95. [DOI:10.1093/humrep/deh044]
5. Themmen AP. An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms. Reproduction 2005; 130: 263-274. [DOI:10.1530/rep.1.00663]
6. 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.
7. Jun JK, Yoon JS, Ku S, Choi YM, Hwang KR, Park SY, 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. [DOI:10.1007/s10038-006-0005-5]
8. Alviggi C, Clarizia R, Pettersson K, Mollo A, Humaidan P, Strina I, et al. Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism. Reprod Biomed Online 2009; 18: 9-14. [DOI:10.1016/S1472-6483(10)60418-X]
9. Huhtaniemi I, Alevizaki M. Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab 2006; 20: 561-576. [DOI:10.1016/j.beem.2006.09.003]
10. Huhtaniemi IT, Themmen AP. Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine 2005; 26: 207-217. [DOI:10.1385/ENDO:26:3:207]
11. Loutradis D, Patsoula E, Minas V, Koussidis GA, Antsaklis A, Michalas S, et al. FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs. J Assist Reprod Genet 2006; 23: 177-184. [DOI:10.1007/s10815-005-9015-z]
12. Achrekar SK, Modi DN, Desai SK, Mangoli VS, Mangoli RV, Mahale SD. Poor ovarian response to gonadotrophin stimulation is associated with FSH receptor polymorphism. Reprod Biomed Online 2009; 18: 509-515. [DOI:10.1016/S1472-6483(10)60127-7]
13. Sheikhha MH, Eftekhar M, Kalantar SM. Investigating the association between polymorphism of follicle-stimulating hormone receptor gene and ovarian response in controlled ovarian hyperstimulation. J Hum Reprod Sci 2011; 4: 86-90. [DOI:10.4103/0974-1208.86089]
14. Piersma D, Verhoef-Post M, Look MP, Uitterlinden AG, Pols HAP, Berns EMJJ, et al. Polymorphic variations in exon 10 of the luteinizing hormone receptor: Functional consequences and associations with breast cancer. Mol Cell Endocrinol 2007; 276: 63-70. [DOI:10.1016/j.mce.2007.06.007]
15. 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. [DOI:10.1097/FPC.0b013e3282f4e98c]
16. Liao WX, Roy AC, Chan C, Arulkumaran S, Ratnam SS. A new molecular variant of luteinizing hormone associated with female infertility. Fertil Steril 1998; 69: 102-106. [DOI:10.1016/S0015-0282(97)00445-7]
17. Twigt JM, Hammiche F, Sinclair KD, Beckers NG, Visser JA, Lindemans J, et al. Preconception folic Acid use modulates estradiol and follicular responses to ovarian stimulation. J Clin Endocrinol Metab 2011; 96: E322-E329. [DOI:10.1210/jc.2010-1282]
18. Kim NK, Nam YS, Ko JJ, Chung HM, Chung KW, Cha KY: The luteinizing hormone b-subunit exon 3 (Gly102Ser) gene mutation is rare in Korean women with endometriosis and polycystic ovary syndrome. Fertil Steril 2001; 75: 1238-1239. [DOI:10.1016/S0015-0282(01)01806-4]
19. Van Voorhis BJ. Outcomes from assisted reproductive technology. Obstet Gynecol 2006; 107: 183-200. [DOI:10.1097/01.AOG.0000194207.06554.5b]
20. Fauser BC, Diedrich K, Devroey P. Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update 2008; 14: 1-14. [DOI:10.1093/humupd/dmm034]
21. Themmen APN, Huhtaniemi IT. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 2000; 21: 551-583. [DOI:10.1210/edrv.21.5.0409]
22. Richter-Unruh A, Martens JWM, Verhoef-Post M, Wessels K, Kors WA, Sinnecker GHG, et al. Leydig cell hypoplasia: cases with new mutations, new polymorphism and cases without mutations in the luteinizing hormone receptor gene. Clin Endocrinol (Oxf) 2002; 56: 103-112. [DOI:10.1046/j.0300-0664.2001.01437.x]
23. Altmäe S, Hovatta O, Stavreus-Evers A, Salumets A. Genetic predictors of controlled ovarian hyperstimulation: where do we stand today? Hum Reprod Update 2011; 17: 813-828. [DOI:10.1093/humupd/dmr034]
24. Christofolini DM, Vilarino FL, Mafra FA, André GM, Bianco B, Barbosa CP. Combination of polymorphisms in luteinizing hormone β, estrogen receptor β and progesterone receptor and susceptibility to infertility and endometriosis. Eur J Obstet Gynecol Reprod Biol 2011; 158: 260-264. [DOI:10.1016/j.ejogrb.2011.06.028]
25. Hashad D, Mohamed N, Hashad MM. Luteinising hormone β-subunit gene Gly102Ser variant and oxidative stress biomarkers in Egyptian infertile males. Andrologia 2012; 44 (Suppl.): 484-489. [DOI:10.1111/j.1439-0272.2011.01212.x]
26. Kerkelä E, Skottman H, Friden B, Bjuresten K, Kere J, Hovatta O. Exclusion of coding-region mutations in luteinizing hormone and follicle-stimulating hormone receptor genes as the cause of ovarian hyperstimulation syndrome. Fertil Steril 2007; 87: 603-606. [DOI:10.1016/j.fertnstert.2006.06.060]
27. Maman E, Yung Y, Kedem A, Yerushalmi GM, Konopnicki S, Cohen B, et al. High expression of luteinizing hormone receptors messenger RNA by human cumulus granulosa cells is in correlation with decreased fertilization. Fertil Steril 2012; 97: 592-598. [DOI:10.1016/j.fertnstert.2011.12.027]
28. Bentov Y, Kenigsberg S, Casper RF. A novel luteinizing hormone/chorionic gonadotropin receptor mutation associated with amenorrhea, low oocyte yield, and recurrent pregnancy loss. Fertil Steril 2012; 97: 1165-1168. [DOI:10.1016/j.fertnstert.2012.02.002]
29. Papamentzelopoulou M, Mavrogianni D, Partsinevelos GA, Marinopoulos S, Dinopoulou V, Theofanakis C, et al. LH receptor gene expression in cumulus cells in women entering an ART program. J Assist Reprod Genet 2012; 29: 409-416. [DOI:10.1007/s10815-012-9729-7]
30. Mafra FA, Bianco B, Christofolini DM, Souza AM, Zulli K, Barbosa CP. Luteinizing hormone beta-subunit gene (LHbeta) polymorphism in infertility and endometriosis-associated infertility. Eur J Obstet Gynecol Reprod Biol 2010; 151: 66-69. [DOI:10.1016/j.ejogrb.2010.03.022]
31. Ramanujam LN, Liao WX, Roy AC, Loganath A, Goh HH, Ng SC: Association of molecular variants of luteinizing hormone with menstrual disorders. Clin Endocrinol (Oxf) 1999, 51: 243-246. [DOI:10.1046/j.1365-2265.1999.00791.x]
32. Liu N, Ma Y, Wang S, Zhang X, Zhang Q, Zhang X, et al. Association of the genetic variants of luteinizing hormone, luteinizing hormone receptor and polycystic ovary syndrome. Reprod Biol Endocrinol 2012, 10: 36. [DOI:10.1186/1477-7827-10-36]
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