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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.

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BackgroundIntervertebral disc degeneration (DD) is an important cause of low back pain and its precise aetiology is not fully understood, being attributed to cumulative environmental, biomechanical and genetic effects. The vitamin D plays a key role in regulation of calcium homeostasis and bone mineralization, exerting its biological activities by binding to a high-affinity receptor (VDR). Polymorphisms in VDR gene were previously associated with DD process, however with conflicting results. Here, we aimed to investigate the influence of lifestyle characteristics and VDR TaqI, BsmI, ApaI and FokI polymorphisms as risk factors for DD process.MethodsRetrospective case–control study involving 231 participants: 119 with confirmed DD and 112 healthy controls. Genotyping of VDR polymorphisms was performed by PCR–RFLP and real-time PCR using TaqMan methodology. All patients answered a questionnaire regarding lifestyle characteristics, such as educational level, pain localization, smoking habits, engagement of physical activity, postural and load weight at work and familial history of disc degeneration. The variables were compared between groups and adjusted by age and gender.ResultsThe case group was composed by 52% female and 48% male and the mean age was 40.0 years old, while in the control group 79% was female and 21% male and the mean age was 32.0 years old. Although gender distribution and mean age were different between groups, in the control group all participants were less than 45 years old and there was a prevalence of women in both groups. The factors that could be possibly associated to DD in the Brazilian population studied included smoking habits (26% in cases and 9% in controls, p = 0.003), lack of engagement in physical activity (observed in 77% of cases and 62% of controls, p = 0.018), and loading weight during work routine (58% in cases and 24% in controls, p ≤ 0.001). However, after adjusting by age and gender, only smoking habits remained associated to disc degeneration (p = 0.027). Considering the educational level, 35.2% of cases and 15.6% of controls had only the Elementary School, and 5.5% of DD group and 28.6% of control group had completed College (p = 0.025). In addition, educational level was directly associated to load weight at work (p = 0.012). Regarding VDR polymorphisms, no significant difference in genotype and allele frequencies between groups was observed. The haplotype analysis revealed that the combined wild-type alleles of TaqI, ApaI and FokI polymorphisms—TGT—was observed in a higher frequency in control group (p = 0.039).ConclusionThe findings suggested that smoking habits was a risk factor for disc degeneration in the population studied. Single analysis revealed no significant effects of VDR polymorphisms in disc degeneration process, while the combination of wild-type alleles of TaqI, ApaI and FokI polymorphisms, TGT haplotype, decreased the risk of the disease.

Background/Aims: It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. We aimed to evaluate Ala307Thr and Asn680Ser genotypes of the FSHR gene in infertile women and correlate the findings with the results of ovarian response and assisted reproduction outcomes. Methods: Cross-sectional study covering 149 infertile women submitted to assisted reproduction treatment. Genotyping of FSHR variants were performed using TaqMan methodology by real time PCR. FSH and estradiol were measured by ELFA. The data was analyzed statistically. Results: The frequencies of the FSHR Ala307Thr and Asn680Ser genotypes considering the ovarian hyper stimulation response also did not differ statistically. Considering assisted reproduction outcomes, we observed that the polymorphism Ala307Thr have a statistical difference for the number of MII oocytes and embryos (p=0,051 and p=0.037, respectively), which the genotype Ala/Ala showed more embryos. The polymorphisms did not determine the FSH and estradiol serum levels and the ovarian response in the assisted reproduction treatment. Conclusions: The polymorphisms Ala307Thr and Asn680Ser did not determine the FSH and estradiol serum levels and the ovarian response in the assisted reproduction treatment. However, we observed that the Ala307Thr may influence the number of embryos produced.

BackgroundImportant candidate genes involved in the ovarian response to exogenous FSH are the estrogen receptor genes (ESRs), since the effects of estrogens on follicle growth, maturation and oocyte release. It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. Inspired on this information we aimed to analyze four different polymorphisms in the estrogen receptor genes ESR1: rs2234693/T-397C (PvuII) and rs9340799/A-351G (Xbal) and ESR2: rs4986938/G1082A (RsaI) and rs1256049/A + 1730G (AluI), and their association with assisted reproduction outcomes in Brazilian women that underwent in vitro fertilization (IVF).MethodsA cross-sectional study was performed involving 136 infertile women less than 39 years of age with normal ovarian reserve. Patients were divided according to the same COH protocol for statistical analysis. The Taqman assay was used for PvuII and XbaI of ESR1, and RsaI and AluI of ESR2 genotyping. Serum estradiol and FSH were measured by Elisa assay.ResultsThe PvuII (ESR1) TT and RsaI (ESR2) GG genotypes were associated with a longer induction period and higher doses of medication (p < 0.03). The XbaI (ESR1) AA genotype was associated with better COH results, including a larger number of follicles, mature oocytes, embryos, and good quality embryos (p < 0.05). The AluI GG genotype showed an association with the Ovarian Hyperstimulation Syndrome (OHSS) (p = 0.03). According to the haplotype analysis of ER1 (PvuII/XbaI), we demonstrated that the CA combination increases by 0.68 the number of good quality embryos while the TG decreases it by 0.71 (p = 0.04).ConclusionER polymorphisms have an association with the assisted reproduction outcomes in Brazilian women.

Estrogen plays an important role in the human reproductive system and its action is mediated mainly by two specific receptors: α (ERα) and β (ERβ). There are polymorphic variants in both ER genes, and studies showed their association with reproductive outcomes. We aimed to determine the distribution of ERα and ERβ gene polymorphisms in idiopathic, infertile Brazilian patients in a case-control study comprising 187 idiopathic, infertile Brazilian men with nonobstructive azoospermia (NOA, n = 78) or severe oligozoospermia (SO, n = 109) and 216 fertile men. Detection of ERα (PvuII and XbaI) and ERβ (AluI and RsaI) gene polymorphisms were performed using TaqMan PCR. The results were analyzed statically, and a P-value < 0.05 was considered significant. Single-marker analysis revealed that neither PvuII nor XbaI polymorphisms of the ERα gene were associated either with NOA group (P = 0.662 and P = 0.527, respectively) or SO group (P = 0.777 and P = 1.0, respectively). Regarding ERβ polymorphisms, no statistical difference was observed between the AluI polymorphism and NOA group compared to controls (P = 1.0) or between SO group and controls (P = 0.423). We found similar results with the RsaI polymorphism. Statistical analysis did not reveal a difference between NOA (P = 0.740) and SO (P = 0.920) groups compared to controls. Combined genotypes of ERα and ERβ polymorphisms did not identify a haplotype associated with idiopathic infertility. Thus, in the Brazilian population, genetic variations in both estrogen receptors alpha (PvuII and XbaI) and beta (AluI and RsaI) were not relevant to idiopathic infertility.