AMH and AMHR2 Polymorphisms and AMH Serum Level Can Predict Assisted Reproduction Outcomes: A Cross-Sectional Study

Abstract

Background: In human assisted reproduction, the ovarian response to exogenous recombinant Follicle-stimulating Hormone (FSH) therapy is variable and difficult to predict. The standard protocol of ovarian hyperstimulation can result in satisfactory response; however, an unsatisfactory response necessitates FSH dose adjustment or results in ovarian hyperstimulation syndrome (OHSS). Polymorphisms in AMH and AMHR2 genes appear to affect hormone biological activities, thus affecting follicle recruitment and development, leading to infertility. We aimed to evaluate AMH and AMHR2 polymorphisms in infertile women, and correlate those findings with AMH, FSH and estradiol serum level response to controlled ovarian hyperstimulation (COH), as well as assisted reproduction outcomes. Methods: A cross-sectional study comprising 186 infertile women that underwent one cycle of high complexity assisted reproductive treatment. Blood samples were collected and a TaqMan assay was used for AMH G146T/rs10407022 and AMHR2 A-482G/rs2002555, A10G/rs11170555, C1749G/rs2071558 and G4952A/rs3741664 genotyping, and FSH, estradiol and AMH levels were measured. The findings were correlated to human reproduction outcomes. Results: AMH rs10407022 and AMHR2 rs2002555 polymorphisms were not associated with hormonal measurements, whereas AMHR2 rs11170555 and rs3741664 were positively associated with AMH, estradiol and FSH levels. The genotype distribution of AMH and AMHR2 genes according to Controlled Ovarian Hyperstimulation did not show a positive association. However, an association with AFC, degree of oocyte maturation (allele G of AMHR2 rs2071558) the number of embryos produced (alleles T and G of AMH rs10407022 and AMHR2 rs2002555, respectively) and frozen embryo (allele G of AMHR2 rs11170555) were found to be statistically associated. Considering COH, serum AMH and AFC were a positive predictor to OHSS. Regarding serum AMH and assisted reproduction outcomes, a positive correlation with all variables studied was found. Comparing AFC and AMH as predictors of human reproduction outcomes, the AFC was less effective than serum AMH. Considering pregnancy rates, no marker was positively associated. Conclusion: AMHR2 polymorphisms were associated with estradiol, AMH and FSH measurements, as well as number and quality of embryos, while AMH polymorphisms was associated with number of embryos produced. Serum AMH was correlated with nearly all variables analyzed in assisted reproductive treatment, demonstrating that it represents a better biomarker of OHSS and human reproduction outcomes compared to AMH and AMHR2 polymorphisms.

Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients

“…Overexpression of AMHR2 increases the binding of AMH to it, which attenuates follicular or oocyte maturation34. Therefore, AMHR2 is a possible indicator for the quality of embryo35. In PCOS oocytes, hormone receptors including LHCGR, FSHR, AMHR2, KAT2B, and OXTR were downregulated in the MII stage, which reflects the ability of oocyte to respond the higher hormone surge and protect the progress of oocyte mutation.…”

A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients

“…Despite limited data on the role of hormonal in predicting OHSS, these markers have being increasingly utilized in predicting ovarian response to stimulation. AMH levels have been previously evaluated (23,24) and the results obtained presented much promise. A previous study demonstrated that AMH levels can identify women at high risk of developing OHSS (sensitivity 90.5%, specificity 81.3%), as a useful predictor of developing OHSS (12).…”

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice

“…In our study, clinical pregnancy was defined as the presence of an intrauterine gestational sac on the trans-vaginal ultrasound examination. We did not measure AMH concentrations [23][24][25].…”