Evaluation of Amh and AMHR2 gene polymorphisms in infertile women and its correlation with of assisted reproduction outcomes

Abstract

Infertility affects about 20% of couples of reproductive age. The study of polymorphisms in genes that regulate female reproductive function may help clarify the mechanisms responsible for gonadal function and fertility in humans.In human assisted reproduction, response to controlled ovarian hyperstimulation is variable and it is difficult to predict. In young ovulatory women undergoing in vitro fertilization (IVF), the standard stimulation protocol may result in both satisfactory answer, and in an inadequate response that requires adjusting the dose of FSH or ovarian hyperstimulation syndrome, a serious and potentially fatal complication of IVF. Identifying patients with potential to develop hyper-response or inadequate response to standard treatment would be clinically helpful.Several parameters have been postulated as predictors of ovarian response. The level of basal FSH on the third day of the cycle seems to have the best predictive ability, but significant within-person variability from cycle to cycle has been observed. Anti- Mülerian hormone (AMH) is also involved in the regulation of follicular growth. Studies in knockout mice showed that AMH gene, in the absence of AMH, follicles are recruited at a faster pace and are more sensitive to FSH, suggesting that this hormone may inhibit early growth of primordial follicle growth induced by FSH. In addition, studies in normo-ovulatory women showed association of AMH polymorphisms and its receptor AMHR2 with estradiol levels during the early follicular phase of the menstrual cycle suggesting a role in regulating sensitivity to FSH.Other authors also demonstrated that basal levels of AMH is correlated with the total dose of gonadotropin used, estradiol level, the number of mature follicles on the day of hCG, the number of oocytes retrieved and pregnancy rates in women undergoing IVF. It was also suggested that serum levels of AMH could predict poor ovarian response and ovarian hyperstimulation syndrome. Moreover, unlike FSH, although during the menstrual cycle AMH blood have slight fluctuations, it does not interfere in the interpretation of the reservation.Thus, AMH has been currently regarded as a promising biomarker of ovarian status, and predict outcomes of IVF, however, genetic variations in AMH and AMHR2 genes may influence hormone function. Since the same polymorphism may have different patterns of association in different populations, is of great interest to characterize the real relationship between AMH and AMHR2 polymorphisms and serum levels of AMH and estradiol, results of ovarian stimulation and assisted reproduction outcomes in Brazilian women undergoing assisted reproduction treatments. (AU)