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Objective: This paper aimed to assess the correlation between LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15 polymorphisms, which are related to follicular development, and decreased ovarian response in women undergoing controlled ovarian hyperstimulation (COH) for IVF. Methods: This age-matched case-control study included three or four controls per woman undergoing COH. Controls were women with normal ovarian response (NOR) and cases were women with poor ovarian response (POR) in oocyte retrieval (three or fewer oocytes). DNA was extracted from peripheral blood and potential associations with gene polymorphisms related to follicular development (LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15) were analyzed. Results: Sixty-six patients were included, 52 in the NOR and 14 in the POR group. Two GDF9 polymorphisms were associated with follicular response after COH, one associated with POR - the presence of a mutant polymorphism in heterozygosis and homozygosis of the GDF9 398-39 (C to G) [23% NOR versus 68% POR (OR 4.01, CI 1.52-10.6, p=0.005)] - and another associated with protective response - the presence of normal homozygosis of GDF9 (C447T) [19.2% NOR versus 50% POR (OR 0.34, IC 0.14-0.84, p=0.019)]. No additional associations were found between the other analyzed polymorphisms and POR. Conclusions: This study found that GDF9 appears to play an important role in follicular development, whereas polymorphisms in its DNA chain may negatively affect ovarian reserve, such as 398-39 (C to G), or positively, as seen in C447T.

Objective Endometriosis is associated with infertility, even without an anatomical abnormality. Furthermore, the peritoneal (mild) phenotype of this disease is the most prevalent and linked to infertility. The present study aimed to investigate the p63 gene and protein expression in granulosa cells from pre-ovulatory follicles in patients with endometriosis and infertility submitted to in vitro fertilization. Methods Twenty-eight patients participated in the study and were divided into two groups according to the presence or absence of endometriosis. The p63 gene-expression levels assessment was performed by real-time PCR (qPCR) using the TaqMan assay, and we used immunofluorescence to check the p63 protein expression after IVF. Results There was no significant difference between the groups regarding age, hormonal levels, oocyte standards, and p63 gene expression. The control group showed an RQ of 1.000 (0.431 to 2.323) and the study group showed an RQ of 0.725 (0.249 to 2.105), p>0.05. Both groups showed a weak expression of the p63 gene (p>0.05). Conclusions This study described that endometriosis may not affect the p63 gene expression. Moreover, after follicular recruitment and growth, we found a weak expression of this protein, suggesting it is not part of oocyte maturation and development control.

Oocyte competence and quality depend on communication between the oocyte and the cumulus and theca cells. In the preantral phase, the members of the transforming growth factor β (TGF-β) superfamily are responsible for this communication and play an important role in folliculogenesis. Members of the TGF-β superfamily are related to endometriosis (overexpression in the ectopic endometrium); however, few studies have explored these proteins as influencing fertility in endometriosis. Considering endometriosis-related infertility and to better understand the role of the TGF-β superfamily members in the antral phase in women with endometriosis, this research investigated the gene expression of the genes for ligands AMH, BMP-6, GDF-9, INHA, INHBB, and TGFβ3; receptors AMHR2, BMPR2, and TGFβR3; and intracellular signalling: SMAD3 and SMAD4.The gene expression of AMH, BMP-6, GDF-9, INHA, INHBB, TGFβ3, AMHR2, BMPR2, TGFβR3, SMAD3, and SMAD4 in cumulus cells was investigated through quantitative real-time PCR in a case-control study including infertile women with and without peritoneal endometriosis undergoing in vitro fertilization.Age and outcomes of assisted reproduction were similar between the groups (P .05). However, women with endometriosis showed reduced expression of BMP-6 and SMAD4 (P .05) in cumulus cells compared with the control group, other genes did not present altered gene expression in women with endometriosis (P .05).The reduced expression of BMP-6 and SMAD4 in women with peritoneal endometriosis compared with the control group indicates that granulosa (cumulus) cell function could be altered in these women.

Objective The study looked into the possible influence of GDF9 polymorphisms on ovarian response in women with a normal ovarian reserve undergoing controlled ovarian hyperstimulation for in vitro fertilization (IVF). Methods This cross-sectional study included 67 women with normal ovarian reserve aged 30-39 years submitted to controlled ovarian hyperstimulation for IVF. We sequenced four polymorphisms in the GDF9 gene (C398G, C447T, G546A, and G646A) and analyzed their influence on follicular and oocyte outcomes. Results The mutant allele C398G decreased the total number of follicles >17mm (6.49 vs. 4.33, p=0.001), total number of follicles (10.11 vs. 7.33, p=0.032), number of MII oocytes retrieved, and serum progesterone levels on trigger day. The C447T polymorphism was associated with a greater number of follicles between 12 and 14 mm on the day of r-hCG, while the G546A polymorphism was associated with lower serum progesterone levels on trigger day. Conclusions GDF9 gene polymorphisms C398G and C447T adversely affected ovarian response in women undergoing controlled ovarian hyperstimulation. These findings show that in addition to playing a role in the early stages of folliculogenesis, GDF9 polymorphisms have an important impact on the final stage of oocyte development.

The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Mullerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the – 482A G SNP in the AMHR2 gene were found to be unrelated.

To verify if polymorphisms of LH (Trp8Arg/Ile15Thr), LH receptor (insLQ), and FSH receptor (Asn680Ser) are associated with endometriosis and infertility.This is a prospective case-control study. Sixty-seven patients with endometriosis and infertility (study group) and 65 healthy fertile patients (control group) were enrolled in the study between July 2010 and July 2013. All patients had their endometriosis diagnosis made or excluded by laparoscopic surgery; study group was submitted to the surgery for infertility investigation and control group for tubal ligation. Day-3 serum hormones were collected from all patients. Analysis of nucleotide mutations for LH polymorphisms (Trp8Arg and Ile15Thr), LHR polymorphism (insLQ), and FSHR polymorphism (Asn680Ser) were performed by PCR.Day-3 FSH, estradiol and LH serum levels were not different between the groups, while CA-125 was higher in patients with endometriosis and infertility. All polymorphisms studied were in Hardy-Weinberg equilibrium. The prevalence of insLQ was significantly higher in patients with endometriosis and infertility (P = 0.005). Allele occurrence in control group was 0.10 versus 0.25 in infertile endometriosis group (P = 0.001). There was no difference regarding Trp8Arg/Ile15Thr (P 0.05) and Asn680Ser (P 0.05) prevalence between groups.This is the first time that prevalence of insLQ was shown to be higher in patients with endometriosis and infertility than in healthy fertile patients. There was no difference in LH and FSHR polymorphisms' prevalence between groups.

Objectives To compare reproductive outcomes using two different soft catheters i.e. Set TDT® and Cook® Sydney IVF. The primary outcome was defined as a positive β-human chorionic gonadotropin (β-hCG) test. Methods Our prospective study recruited 68 patients undergoing in vitro fertilization cycles in a private fertility clinic in Porto Alegre, Brazil, between January 2014 and April 2016. They were divided into two groups according to the catheter that would be used for the embryo transfer, and the groups were matched by age. The total number of patients in each group was: 34 for the TDT and 34 for the Cook Sydney. All the patients were submitted to a β-hCG test 12 days after the embryo transfer for pregnancy outcome evaluation. Results Ten out of 34 patients from the TDT group had a positive outcome for pregnancy, corresponding to 29.4%. The Cook Sydney group had 9 patients out of 34 with positive outcomes, corresponding to 26.5%. Comparing the efficacy of both catheters for the primary outcome, there was no significant difference (p>0.05) between the TDT and the Cook Sydney catheters. Conclusion The TDT and the Cook Sydney catheters efficacies were similar for embryo transfer during assisted reproductive technology cycles.

Background/Aims: To evaluate serum prolactin and CA-125 levels as biomarkers for the diagnosis of peritoneal endometriosis. Methods: A prospective study was performed. Blood samples were drawn from a peripheral vein during the secretory phase of the menstrual cycle (day 19-21 prior to the surgery) to analyze through relative operating characteristic curve the serum prolactin and CA-125 levels for diagnosis of peritoneal endometriosis. The study was performed with 97 participants, 63 women with peritoneal endometriosis and 34 healthy women. Results: The sensitivity and specificity of peritoneal endometriosis diagnosis were equivalent for prolactin (21 and 99%) and for CA-125 (27 and 97%; p = 0.58). These two markers were used in a parallel test utilizing the usual cutoff (prolactin 20.0 ng/ml and CA-125 35 U/I). The sensitivity and specificity were 44 and 99%. However, by utilizing the best cutoff (prolactin 14.8 ng/ml and for CA-125 19.8 U/I), sensitivity, specificity and negative predictive value were 77, 88 and 97%, respectively. Conclusion: Serum CA-125 and prolactin levels assessed together, and considering the cutoff for CA-125 (19.9 U/I) and prolactin (14.8 ng/ml), allow the diagnosis of peritoneal endometriosis with acceptable sensitivity and specificity (77 and 88%) and a high negative predictive value (97%).

Objective To compare the prevalence of dopamine receptor D2 polymorphisms in patients with peritoneal endometriosis and in healthy control subjects. Design Case-control study. Setting University hospital. Patient(s) One hundred seven women aged ≥18 years who were enrolled when seeking care for infertility caused by peritoneal endometriosis or for tubal ligation. Intervention(s) We performed DNA extraction of peripheral blood, followed by polymerase chain reaction to confirm single-strand polymorphisms and to sequence two polymorphisms. Main Outcome Measure(s) We sequenced two polymorphisms in exon 7 of the dopamine receptor D2 (DRD2) gene. Polymorphism 1 occurs in nucleotide 3420 (cytosine to thymine, 313 histidine), and polymorphism 2 occurs in nucleotide 3438 (cytosine to thymine, 319 proline). Result(s) The frequency of the DRD2 polymorphism 2 was increased in subjects with peritoneal moderate/severe endometriosis. Analysis of the DRD2 genotypes demonstrates an odds ratio of 2.98 (95% confidence interval 1.47–6.04) for polymorphism 2 in peritoneal moderate/severe endometriosis. Conclusion(s) Our results revealed that an excess of DRD2 polymorphism 2 was found in exon 7 in women with peritoneal moderate/severe endometriosis. The presence of polymorphism 2 could cause a defect in a post-receptor signaling mechanism, resulting in a mild increase in serum prolactin levels. Thus, the potential angiogenic role of prolactin may play a role in the implantation of ectopic endometriosis tissue.

OBJECTIVE To investigate the relationship between AMH blood levels and the likelihood of blastocyst formation. METHODS Two hundred ninety-two patients, 22-44 years of age, undergoing routine explorations during spontaneous cycles that preceded assisted reproductive technologies at our Center, were studied. As the present study did not require previous submission to our Institutional Review Board. Serum AMH and FSH levels were measured and laboratory data was obtained after ovulation induction with an antagonist protocol. Participants were sorted into two different groups paired by age. The first group (No Blasto; n=219) involved women having no blastocyst formation; the second group (Yes Blasto group; n=73) was made up of those women who were considered eligible to undergo 5 days of embryo culture. Furthermore, we analyzed blastulation rate. Patients were divided according to the rate of blastocyst formation

To verify whether carriers of common single-nucleotide polymorphisms (SNPs) of the FSH receptor (FSHR) show reduced responsiveness of antral follicles to FSH administration as assessed by the FORT.We performed a prospective study in a university hospital. Study population consisted of 124 Caucasian IVF-ET candidates. FSHR 307Ala and 680Ser variants were analyzed in haplotypes and as separated genes. Serum FSH, estradiol (E(2)), and anti-Müllerian hormone (AMH) were measured on cycle-day 3. Antral follicle (3-8 mm) count (AFC) and preovulatory follicle (16-22 mm) count (PFC) were performed, respectively, at the achievement of pituitary suppression (before FSH administration) and on the day of hCG administration. Antral follicle responsiveness to FSH administration assessed by the FORT (PFCx100/AFC).Data concerning baseline and IVF-ET parameters were similar between SNPs carriers and controls. Moreover, FORT was similar for different haplotypes Thr307-Asn680 (45.9%) and Ala307-Ser680 (39.4%) and 307Thr/Ala-Ala/Ala (41.1%; 5.0-91.6%) versus 307Thr/Thr (44.4%; 17.3-83.3%) and in 680Asn/Ser-Ser/Ser (40.0%; 5.0-91.6%) versus 680Asn/Asn (42.2%; 8.3-90.0%) carriers.Antral follicle responsiveness to FSH, as far as measured by the FORT, is not influenced by the presence of SNPs of FSHR 307Ala and 680Ser.

The purpose of this research is to compare the prevalence of dopamine receptor D2 polymorphisms in women with recurrent miscarriage (RM) and healthy patients. Fifty-four women were enrolled in this case-control study. We performed DNA extraction of peripheral blood, followed by polymerase chain reaction to confirm single-strand polymorphisms and to sequence two polymorphisms: polymorphism 1 (rs6275) and polymorphism 2 (rs6277) in exon 7 of the dopamine receptor D2 (DRD2). The frequency of DRD2 polymorphism 2 (rs6277) was increased in the subjects with RM. An analysis of the DRD2 genotypes demonstrated an odds ratio of 2.37 (1.05-5.36, 95% confidence interval) for the polymorphism 2 (rs6277) in RM. The mean of the serum prolactin level was higher in the patients with RM (12.5 ng/ml) than in healthy women (8.1 ng/ml) p = 0.03. An excess homozygosity of the DRD2 polymorphism suggests a genetic predisposition to RMs, which could result in a mild serum prolactin increase. Thus, because of the potential role of prolactin in reproductive regulation, this polymorphism could play an important role in early pregnancy implantation and pregnancy maintenance.