Top

Journal of Assisted Reproduction and Genetics

Published in:

Open Access 01-08-2016 | Genetics

AMH type II receptor and AMH gene polymorphisms are not associated with ovarian reserve, response, or outcomes in ovarian stimulation

Authors: Christian Cerra, William G. Newman, Dalia Tohlob, Helen Byers, Gregory Horne, Stephen A. Roberts, Lamiya Mohiyiddeen

Published in: Journal of Assisted Reproduction and Genetics | Issue 8/2016

Abstract

Purpose

Genetic variation may influence women’s response to ovarian stimulation therapy. The purpose of this study was to investigate any effects of genetic variants in the anti-Müllerian hormone (AMH) and AMH type II receptor genes on ovarian response/treatment outcomes and on current markers of ovarian reserve in individuals undergoing in vitro fertilisation (IVF) treatment.

Methods

In this prospective observational study, we genotyped the AMH c.146G>T, p.(Ile49Ser) and AMHR2 -482A>G variants in 603 unrelated women undergoing their first cycle of controlled ovarian stimulation for IVF and ICSI (intracytoplasmic sperm injection) using gonadotrophins at a tertiary referral centre for reproductive medicine. Pelvic ultrasound and blood hormone levels were taken on days 2–3 of the cycle. Genotypes were determined using TaqMan allelic discrimination assay. Regression analysis was performed to assess the relationship between the genotypes and the ovarian reserve markers (FSH, AMH, antral follicle count) and the early outcomes of response (number of oocytes retrieved and gonadotropin dose) as well as the treatment outcome (live birth).

Results

There were no significant associations between the variants AMH c.146G>T and AMHR2 -482A>G with ovarian response in terms of number of oocytes retrieved (p = 0.08 and p = 0.64, respectively), live births (p = 0.28 and p = 0.52) and/or markers of ovarian reserve.

Conclusions

Genotyping of the AMH c.146G>T and AMHR2 -482A>G polymorphisms does not provide additional useful information as a predictor of ovarian reserve or ovarian response and treatment outcomes.

Mohiyiddeen L, Nardo LG. Single-nucleotide polymorphisms in the FSH receptor gene and ovarian performance: future role in IVF. Hum Fertil (Camb). 2010;13(2):72–8.CrossRef

Elgindy EA, El-Haieg DO, El-Sebaey A. Anti-Mullerian hormone: correlation of early follicular, ovulatory and midluteal levels with ovarian response and cycle outcome in intracytoplasmic sperm injection patients. Fertil Steril. 2008;89(6):1670–6.CrossRefPubMed

La Marca A, Stabile G, Artenisio AC, Volpe A. Serum anti-Mullerian hormone throughout the human menstrual cycle. Hum Reprod. 2006;21(12):3103–7.CrossRefPubMed

Nelson SM, Yates RW, Fleming R. Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles—implications for individualization of therapy. Hum Reprod. 2007;22(9):2414–21.CrossRefPubMed

Rustamov O, Smith A, Roberts SA, Yates AP, Fitzgerald C, Krishnan M, et al. The measurement of anti-Müllerian hormone: a critical appraisal. J Clin Endocrinol Metab. 2014;99(3):723–32. doi:10.1210/jc.2013-3476.Epub2013Jan.PubMed

Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-Mu¨llerian hormone: a new marker for ovarian function. Reproduction. 2006;131:1–9.CrossRefPubMed

Kevenaar ME, Themmen AP, Rivadeneira F, Uitterlinden AG, Laven JS, van Schoor NM, et al. A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity. Hum Reprod. 2007;22(9):2382–8.CrossRefPubMed

Kevenaar ME, Themmen AP, Laven JS, Sonntag B, Fong SL, Uitterlinden AG, et al. Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women. Hum Reprod. 2007;22(6):1547–54.CrossRefPubMed

Voorhuis M, Broekmans FJ, Fauser BC, Onland-Moret NC, van der Schouw YT. Genes involved in initial follicle recruitment may be associated with age at menopause. J Clin Endocrinol Metab. 2011;96(3):E473–9.CrossRefPubMed

10.

Braem MG, Voorhuis M, van der Schouw YT, Peeters PH, Schouten LJ, Eijkemans MJ, et al. Interactions between genetic variants in AMH and AMHR2 may modify age at natural menopause. PLoS One. 2013;8(3):e59819.CrossRefPubMedPubMedCentral

11.

Kevenaar ME, Laven JS, Fong SL, Uitterlinden AG, de Jong FH, Themmen AP, et al. A functional anti-mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients. J Clin Endocrinol Metab. 2008;93(4):1310–6.CrossRefPubMed

12.

Rigon C, Andrisani A, Forzan M, D'Antona D, Bruson A, Cosmi E, et al. Association study of AMH and AMHRII polymorphisms with unexplained infertility. Fertil Steril. 2010;94(4):1244–8.CrossRefPubMed

13.

Hanevik HI, Hilmarsen HT, Skielbred CF, Tanbo T, Kahn JA. Single nucleotide polymorphisms in the anti-Müllerian hormone signalling pathway do not determine high or low response to ovarian stimulation. Reprod Biomed Online. 2010;21(5):616–23.CrossRefPubMed

14.

Karagiorga I, Partsinevelos GA, Mavrogianni D, Anagnostou E, Zervomanolakis I, Kallianidis K, et al. Single nucleotide polymorphisms in the Anti-Müllerian hormone (AMH Ile(49)Ser) and Anti-Müllerian hormone type II receptor (AMHRII −482 A > G) as genetic markers in assisted reproduction technology. J Assist Reprod Genet. 2015;32(3):357–67.CrossRefPubMed

15.

Peluso C, Fonseca FL, Gastaldo GG, Christofolini DM, Cordts EB, Barbosa CP, et al. AMH and AMHR2 polymorphisms and AMH serum level can predict assisted reproduction outcomes: a cross-sectional study. Cell Physiol Biochem. 2015;35(4):1401–12.CrossRefPubMed

16.

Cerra C, Oliver J, Roberts SA, Horne G, Newman WG, Mohiyiddeen L. A single nucleotide polymorphism of bone morphogenic protein-15 is not associated with ovarian reserve or response to ovarian stimulation. Hum Reprod. 2014;29(12):2832–7.CrossRefPubMed

17.

Boudjenah R, Molina-Gomes D, Torre A, Bergere M, Bailly M, Boitrelle F, et al. Genetic polymorphisms influence the ovarian response to rFSH stimulation in patients undergoing in vitro fertilization programs with ICSI. PLoS One. 2012;7(6):e38700.CrossRefPubMedPubMedCentral

Title: AMH type II receptor and AMH gene polymorphisms are not associated with ovarian reserve, response, or outcomes in ovarian stimulation
Authors: Christian Cerra
William G. Newman
Dalia Tohlob
Helen Byers
Gregory Horne
Stephen A. Roberts
Lamiya Mohiyiddeen
Publication date: 01-08-2016
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 8/2016
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-016-0711-7

At a glance: The STEP trials

Springer Medicine

AMH type II receptor and AMH gene polymorphisms are not associated with ovarian reserve, response, or outcomes in ovarian stimulation

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2016

SNP array-based analyses of unbalanced embryos as a reference to distinguish between balanced translocation carrier and normal blastocysts

Are we ready to inject? Individualized LC-CUSUM training in ICSI

Ultrastructural and cytogenetic analyses of mature human oocyte dysmorphisms with respect to clinical outcomes

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Differentially expressed genes in preimplantation human embryos: potential candidate genes for blastocyst formation and implantation

Does combining magnetic-activated cell sorting with density gradient or swim-up improve sperm selection?