Single nucleotide polymorphisms in the Anti-Müllerian hormone (AMH Ile49Ser) and Anti-Müllerian hormone type II receptor (AMHRII −482 A>G) as genetic markers in assisted reproduction technology

Abstract

Purpose The aim of the study was to evaluate whether the presence Antimullerian hormone (AMH) and Antimullerian hormone type II receptor (AMHRII) single nucleotide polymorphisms (SNPs) Ile 49 Ser and -482A>G respectively are related to the assisted reproduction outcome. Methods A prospective cross-sectional observational study was conducted in order to assess the distribution of AMH and AMHRII SNPs in two cohorts, one of healthy women (N=100) and the control group and the IVF/ICSI group (N=151) consisted of women undergoing IVF/ICSI treatment for infertility. Furthermore, a prospective longitudinal observational study was performed on the latter group to assess possible associations of these SNPs with patients' characteristics and controlled ovarian stimulation (COS) and pregnancy outcome. Results Among non-carriers of the AMH (Ile 49 Ser) polymorphism, basal FSH levels were lower in those with more than two of previous IVF attempts and fertilization rate was statistically higher in those with peak serum E2 levels below 1500 pg/ml, whereas among non-carriers of the AMHRII (−482 A>G) polymorphism, number of follicles was higher in those with more than two previous IVF attempts and total dose of gonadotropins was lower in those with peak serum E2 levels above 1500 pg/ml. Conclusions There was evidence that in specific subgroups of women undergoing IVF/ICSI, AMH and AMHRII SNPs may be related to patients' characteristics and controlled ovarian stimulation and pregnancy outcome and thus may provide a means for the prediction of ovarian response in specific subgroups of women entering an IVF/ICSI program.

Associations of Polymorphisms in Anti-Müllerian Hormone (AMH Ile49Ser) and its Type II Receptor (AMHRII -482 A>G) on Reproductive Outcomes and Polycystic Ovary Syndrome: a Systematic Review and Meta-Analysis

“…Study specific findings of RO and PCOS were variable, with contradictions among the results. Absence of associations between the AMH and AMHRII polymorphisms and ovarian stimulation have been reported [30,35] and contradicted in another study [31]. Regarding ovarian insufficiency, findings of no association [36] were countered by other studies that found associations [33,43].…”

“…We retrieved the remaining 99 abstracts which after review, 73 Table 1 and 2. Nine and six examined RO [16,[30][31][32][33][34][35][36][37] and PCOS [19,[38][39][40][41][42], respectively, and one study examined both [43]. Publication years of the included studies ranged from 2008 to 2016.…”

“…In terms of study context for Ile49Ser, five focused on infertility or ovarian insufficiency [16,33,36,37,43] and three addressed stimulation issues [30,32,35]. One was about assisted reproductive technology [31] and another addressed follicle recruitment [34]. All 16 articles addressed HWE and used blood as tissue source, but none of them explicitly mention about controls being matched to cases.…”

“…These changes affected all comparisons in every genetic model. Of the four comparisons, Ile49Ser in RO was least robust as the pooled ORs were altered with omission of a total of five studies [16,30,31,36,43] in every genetic model. By contrast, -482A>G was non-robust in the dominant model only, attributed to two studies [32,43].…”

“…Hence, reproductive studies in women have focused on the role of serum AMH as marker for ovarian response and reserve [31]. AMH has the advantage of having relatively stable levels throughout the menstrual cycle [49,50] and is more accurate in providing information on the expected ovarian response to controlled stimulation [50].…”