The Relationship between AMH and AMHR2 Polymorphisms and the Follicular Phase in Late Reproductive Stage Women

Abstract

The objective of this work was the analysis of the relationships between the genotypes of the AMH and AMH receptor type 2 genes, hormone levels and the menstrual cycle in a group of Polish women in the late reproductive stage. The study was conducted using a measurement-based method (body weight and height), laboratory method (serum hormone levels AMH, FSH and E2), and genetic analysis (DNA isolated from whole blood by a salting-out method). The study involved 345 healthy, late-reproductive-stage women from Poland, aged 42.3 ± 4.5 years. The analysis demonstrated that neither the T/T and G/T+G/G genotypes of the AMH Ile49Ser polymorphism (rs10407022), nor the A/A and the G/A + G/G genotypes of the AMHR2 2482 A > G polymorphism (rs2002555), nor the C/C and C/T + T/T genotypes of the AMH polymorphism (rs11170547) were statistically significantly related (p > 0.05) to such factors as age, BMI, hormone (FSH and E2) levels and ovarian parameters (AMH) in the follicular phase. No relationships were found between ovarian parameters (FSH, E2, AMH) and genetic variants of AMH (rs10407022) and AMHR2 (rs11170547, rs2002555) in healthy women in the late reproductive stage.

Association of gene polymorphisms in the anti-Müllerian hormone signalling pathway with ovarian function: a systematic review and meta-analysis

“…The European subgroup (Cerra et al, 2016;Jurczak et al, 2016;Kevenaar et al, 2007bKevenaar et al, , 2008 showed a similar result (WMD 0.09, 95% CI −0.43 to 0.62, I 2 = 42.0%). Subgroup analysis in accordance with population showed no significant statistical association in healthy women (Jurczak et al, 2016;Kevenaar et al, 2007b;Yu et al, 2016), infertile women (Cerra et al, 2016;Peluso et al, 2015,) or patients with PCOS (Kevenaar et al, 2008) (WMD 0.66, 95% CI −0.56 to 1.87, I 2 = 75.2%, P = 0.018; WMD 0.47, 95% CI −0.07 to 1.02, I 2 = 0.0%; WMD 0.50, 95% CI −2.19 to 1.19) (FIGURE 2B). However, for PCOS there was only one study for analysis.…”

“…The remaining 35 studies were screened for eligibility and 17 were excluded according to eligibility criteria. Finally, eight studies involving 3155 participants were included in the meta-analysis (Cerra et al, 2016;Georgopoulos et al, 2013;Jurczak et al, 2016;Kevenaar et al, 2007bKevenaar et al, , 2008Lazaros et al, 2016;Peluso et al, 2015, Yu et al 2016. Ten studies were included in the descriptive review (Alvaro Mercadal et al, 2015;Boudjenah et al, 2012;Braem et al, 2013;Hanevik et al, 2010;Karagiorga et al, 2015;Kevenaar et al, 2007a;Qin et al, 2014;Voorhuis et al, 2011;Wang et al, 2002;Yoon et al, 2013).…”

“…Eight studies evaluating the relationship between the AMH signalling pathway genotype and ovarian reserve were included for meta-analysis (Cerra et al, 2016;Georgopoulos et al, 2013;Jurczak et al, 2016;Kevenaar et al, 2007bKevenaar et al, , 2008Lazaros et al, 2016;Peluso et al, 2015;Yu et al, 2016 With regard to the association between c.146T>G polymorphism in the AMH gene and ovarian reserve, the metaanalysis of six included studies (Cerra et al, 2016;Jurczak et al, 2016;Kevenaar et al, 2007bKevenaar et al, , 2008Peluso et al, 2015;Yu et al, 2016) showed that no significant difference in serum AMH levels was found between the participants with G/G genotype and carriers of the G/T or T/T genotype (WMD 0.42, 95% CI −0.16 to 0.99) with high heterogeneity (I 2 = 57.6%, P = 0.038) (FIGURE 2A). The European subgroup (Cerra et al, 2016;Jurczak et al, 2016;Kevenaar et al, 2007bKevenaar et al, , 2008 showed a similar result (WMD 0.09, 95% CI −0.43 to 0.62, I 2 = 42.0%). Subgroup analysis in accordance with population showed no significant statistical association in healthy women (Jurczak et al, 2016;Kevenaar et al, 2007b;Yu et al, 2016), infertile women (Cerra et al, 2016;Peluso et al, 2015,) or patients with PCOS (Kevenaar et al, 2008) (WMD 0.66, 95% CI −0.56 to 1.87, I 2 = 75.2%, P = 0.018; WMD 0.47, 95% CI −0.07 to 1.02, I 2 = 0.0%; WMD 0.50, 95% CI −2.19 to 1.19) (FIGURE 2B).…”

“…Eight studies (Cerra et al, 2016;Georgopoulos et al, 2013;Jurczak et al, 2016;Kevenaar et al, 2007bKevenaar et al, , 2008Lazaros et al, 2016;Peluso et al, 2015;Yu et al, 2016) involving nine populations provided the data regarding the association between the relation between the AMHRII −482 A>G variant and serum AMH levels. As shown in FIGURE 3, there was no significant difference in serum AMH levels between the participants with A/A genotype and G/A or G/G genotype carriers (WMD -0.04, 95% CI −0.31 to 0.23) with high heterogeneity (I 2 = 55.3%, P = 0.022).…”

New perspectives on the genetic causes of diminished ovarian reserve and opportunities for genetic screening: systematic review and meta-analysis

“…There have been numerous studies to date showing differences in ovarian reserve testing parameters as well as number and quality of oocytes in women with polymorphisms of the AMH and AMHR2 genes (100-103). However, others have not found differences in age at natural menopause, prevalence of POI, and ART outcomes in women with and without these polymorphisms (104)(105)(106)(107)(108)(109). In a meta-analysis by Pabalan et al (97) performed in 2016, the associations of the AMH Ile49Ser variant and AMHR2 482A>G variant on reproductive outcomes initially appeared null, however, after subgroup analysis, pooled effects were found in differing ethnic groups with polymorphisms appearing to be protective in whites and variable in those of Asian descent.…”