BMP-6 and SMAD4 gene expression is altered in cumulus cells from women with endometriosis-associated infertility.

INTRODUCTION: 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 ß (TGF-ß) superfamily are responsible for this communication and play an important role in folliculogenesis. Members of the TGF-ß 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-ß 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 TGFß3; receptors AMHR2, BMPR2, and TGFßR3; and intracellular signalling: SMAD3 and SMAD4. MATERIAL AND METHODS: The gene expression of AMH, BMP-6, GDF-9, INHA, INHBB, TGFß3, AMHR2, BMPR2, TGFßR3, 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. RESULTS: 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). CONCLUSIONS: 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.

PIWIL2 is overexpressed in adenomyotic lesions of women with diffuse adenomyosis.

PURPOSE: Adenomyosis has been studied throughout the years, however, its aetiology and physiopathology are still unknown. The aim of this study was to identify the presence of PIWI proteins in women with adenomyosis. METHODS: We included 72 participants to be part of this study and were divided into two groups based on their anatomopathological diagnosis, control (n = 36) or adenomyosis (n = 36). All samples were tested for PIWIL1, PIWIL2 and PIWIL4 proteins by immunohistochemistry. The evaluation of protein expression was performed by the digital histological score (DHSCORE) and by the pathologist's analysis. RESULTS: The participants had a mean age of 44.28 ± 5.76 years and 45.81 ± 4.86 years in the control and adenomyosis groups, respectively (p ≥ 0.05). Other clinical characteristics of the participants showed no statistical difference as well. PIWIL2 is highly expressed in the adenomyosis in comparison to the control group (p = 0.0001). The PIWIL1 is downregulated in the adenomyosis (p = 0.003) and PIWIL4 showed no difference in its expression (p = 0.05). CONCLUSION: PIWIL2 might be involved in cellular survival and PIWIL1 may be downregulated due to the loss of tissue's function and response to the hostile environment of the myometrium. This is the first time that PIWI proteins are studied in the adenomyosis.

Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms.

PURPOSE: 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-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Recurrent miscarriage is associated with the dopamine receptor (DRD2) genotype.

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.

LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility.

PURPOSE: To verify if polymorphisms of LH (Trp8Arg/Ile15Thr), LH receptor (insLQ), and FSH receptor (Asn680Ser) are associated with endometriosis and infertility. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Accuracy of magnetic resonance in deeply infiltrating endometriosis: a systematic review and meta-analysis.

OBJECTIVE: To estimate the accuracy of pelvic magnetic resonance imaging (MRI) in the diagnosis of deeply infiltrating endometriosis (DIE). METHODS: A comprehensive search of the Medline, Pubmed, Lilacs, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, and ISI Web of Science databases was conducted from January 1990 to December 2013. The medical subject headings (MeSHs) and text words "deep endometriosis", "deeply infiltrating endometriosis", "DIE", "magnetic resonance", and "MRI" were searched. Studies that compared the parameters of pelvic MRIs with those of paraffin-embedded sections for the diagnosis of DIE were included. RESULTS: Twenty studies were analyzed, which included 1,819 women. Pooled sensitivity and specificity were calculated across eight subgroups: for all sites, these were 0.83 and 0.90, respectively; for the bladder, 0.64 and 0.98, respectively; for the intestine, 0.84 and 0.97, respectively; for the pouch of Douglas, 0.89 and 0.94, respectively; for the rectosigmoid, 0.83 and 0.88, respectively; for the rectovaginal, 0.77 and 0.95, respectively; for the uterosacral ligaments, 0.85 and 0.80, respectively; and for the vagina and the posterior vaginal fornix, 0.82 and 0.82, respectively. CONCLUSION: In summary, pelvic MRI is a useful preoperative test for predicting the diagnosis of multiple sites of deep infiltrating endometriosis.

Follicular fluid concentration of soluble Human-G Leukocytic Antigen (sHLA-G) in in vitro fertilization cycles of women with and without peritoneal endometriosis.

OBJECTIVE: The objective of this research is to investigate the association between the concentrations of soluble human leukocyte G antigen (sHLA-G) in the follicular fluid (FF) in infertile patients with peritoneal endometriosis submitted to in vitro fertilization. METHODS: We performed a cross-sectional study, including ninety-six women undergoing in vitro fertilization (IVF) ageing ≤ 40 years. Infertile patients were classified into two groups: with endometriosis diagnosed by laparoscopy and without endometriosis due to tubal factor. ELISA measured soluble HLA-G in the FF of a pool of punctured (more than 17mm) follicles from women with endometriosis and without endometriosis who were subjected to ovulation induction for IVF. Embryos obtained after fertilization were classified according to the graduated embryo score (GES). RESULTS: Groups were comparables in terms of age, the number of follicles, AMH, FSH and all included reproductive outcomes. There was no association between sHLA-G concentrations and the average score of the generated embryos (p>0.05). Measurement of sHLA-G in the follicle fluid in women with endometriosis and without endometriosis (tubal factor) showed no significant difference (p>0.05). We also compared sHLA-G per follicle and per embryo, which were not different between both groups (p>0.05). CONCLUSIONS: Patients with peritoneal endometriosis submitted to IVF did not demonstrate an altered sHLA-G in the follicular fluid compared to the follicular fluid sHLA-G concentration in tubal factor patients. Also, this molecule was not linked to any other reproductive outcome.

Transforming growth factor beta-1 (TGF-ß1) expression in patients with adenomyosis.

Objective: To compare Transforming growth factor beta-1 (TGF-ß1) expression in patients with and without adenomyosis. Methods: A prospective design was performed including 49 patients submitted to hysterectomy. Immunohistochemistry was performed on anatomopathological samples staged in paraffin blocks from patients with and without adenomyosis. The sample contained 28 adenomyosis cases and 21 controls. Student's t-test and multivariate logistic regression tests were used for statistical analysis. Associations were considered significant at p < 0.05. Results: We found no significant association between adenomyosis and: smoking (p = 0.75), miscarriage (p = 0.29), number of previous pregnancies (p = 0.85), curettage (p = 0.81), pelvic pain (p = 0.72) and myoma (p = 0.15). However, we did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) (p = 0.02) and previous cesarean section (p = 0.02). The mean TGF-ß1 intensity (mean ± SD) in the ectopic endometrium of women with adenomyosis showed no significant association (184.17 ± 9.4 vs.184.66 ± 16.08, p = 0.86) from the topic endometrium of women without adenomyosis. Conclusion: TGF-ß1 expression was not increased in the ectopic endometrium of women with adenomyosis.

Effect of Dietary Interventions on Endometriosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study aimed to systematically review existing randomized clinical trials on the effect of dietary interventions on endometriosis. A search was performed on the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Clinical Trials, EMBASE, PubMed, Lilacs, and Cielo databases. The search terms were used: "endometriosis", "endometrioma", "diet", "supplements" and "nutrition". Electronic literature searches through databases yielded 866 publications. Two authors performed The study selection independently (and blinded), and disagreements were discussed. Eleven RCTs were included in the systematic review, with 716 women randomized. Most studies reported a positive effect on endometriosis pain scores; however, they were characterized by moderate or high-risk bias. Of these, six RCTs, including 457 women with endometriosis, were included in the meta-analysis. Compared with Placebo, antioxidant use was associated with a reduction in dysmenorrhea (mean difference - 1.95 [CI 95%, -3.78 to -0.13]. Supplementation was not significant for reducing chronic pelvic pain (mean difference - 2.22 [95% CI, -4.99 to 0.55] and dyspareunia (MD - 2.56 [95% CI, - 5. 22 to 0.10]. Both analyses showed a high degree of heterogeneity. Moreover, studies with low risk of bias did not show significant results compared to those on Placebo. The effects of nutrient compounds seem to have the potential to reduce pain in women with endometriosis, mainly to reduce dysmenorrhea. However, the available studies present high heterogeneity and moderate/high risk of bias. More randomized clinical trials are needed to accurately determine dietary interventions' short- and long-term efficacy and safety in managing endometriosis pain.

Total Fertilization Failure: A Single Center Analysis.

Our main objective was to identify the male and female parameters associated with total fertilization failure (TFF) in IVF with nonmasculine indications. The present work, IRB equivalent INS 63209, is a case-control study that evaluated all cases with TFF after conventional IVF at the Center for Human Reproduction from January 2010 to December 2019 (n = 154). As a control group, we analyzed all patients who did not experience fertilization failure after conventional IVF in the same period (n = 475). We evaluated various parameters, both male and female, assessed during infertility treatment, and only cases without masculine etiology (normal seminal parameters) were included. Ages (female and male) were not different between the groups. Moreover, AMH (anti-Müllerian hormone), semen volume, preprocessing concentration and preprocessing motility were not significantly different (P > 0.05). However, the number of collected oocytes (study versus control groups, median [25-75 interquartile]: 2 [1-5] and 5 [3-8]); MII (2 [1-4] and 5 [2-7]); and postprocessing motility (85 [70-90] and 90 [80-95]) were significantly different between both groups (P < 0.05). Furthermore, a logistic regression analysis including all significant data demonstrated that the number of collected oocytes was significantly related to IVF failure. Patients with fewer than 5 oocytes had an OR of - 1.37 (- 0.938 to - 1.827) for TFF after conventional IVF. Our results showed that a lower follicular response to controlled ovarian stimulation, evidenced by a decreased number of collected oocytes, was the most important parameter associated with IVF failure in nonmasculine infertility.

Endometriosis and Systemic Lupus Erythematosus: Systematic Review and Meta-analysis.

Endometriosis is a chronic gynaecological condition characterized by inflammatory and immune abnormalities. Likewise, these dysfunctions are important hallmarks of systemic lupus erythematosus (SLE), a condition that also has a high prevalence among women in reproductive age. Therefore, we conducted a systematic review and meta-analysis to investigate the association between endometriosis and SLE. We searched Medline and Web of Science for articles published from database inception to March 1, 2021. Random-effects meta-analysis was performed to provide a pooled risk ratio (RR). Individual study quality was evaluated following the National Heart, Lung, and Blood Institute Quality Assessment Tools (NHLBI QAT). From the 225 articles identified through our search, five studies-assessing 152,355 women-were included. Included studies presented an overall poor or fair quality rating. We observed a significant association between endometriosis and SLE (RR = 2.47, 95% confidence interval: 1.33-4.59, P < 0.004, I2 = 54%). Sensitivity analyses stratifying articles by study design demonstrated that the association was significant in cross-sectional and case-control studies (RR = 5.07, 95% confidence interval: 1.42-18.11, P < 0.012), as well as in cohort studies (RR = 2.07, 95% confidence interval: 1.02-4.20, P < 0.044). In spite of the limited quality of included studies, our results suggest the existence of an association between endometriosis and SLE. These findings can aid medical assessment of patients with endometriosis, as well as provide further insights to better understand this gynaecological disorder.

Corifollitropin alpha was not detrimental to follicular ovarian responsiveness measured by follicular output rate (FORT).

Corifollitropin alpha has been demonstrated to be non-inferior to other gonadotropins in reproductive outcomes. However, its impact on follicular ovarian responsiveness has never been evaluated. Follicular Output Rate (FORT) is an option for objective assessment of the follicular responsiveness. A prospective study was conducted with 306 infertile patients undergoing in vitro fertilisation. Ovarian stimulation protocol was performed with a single dose of 100 µg (<60kg) or 150 µg (≥60kg) corifollitropin alpha in group 1 (n = 147), and 150-300 IU/day human menopausal gonadotropin in group 2 (n = 150). Comparing ovarian stimulation between corifollitropin alpha and human menopausal gonadotropin, no differences regarding FORT were found (40.0% for group 1 versus 40.83% for group 2; p = 0.930). Patients treated with corifollitropin alpha had a higher number of embryos when compared with human menopausal gonadotropin group (3.0 for group 1 versus 2.0 for group 2; p = 0.04). Other secondary outcomes preset were similar between groups. Therefore, corifollitropin alpha can be an excellent option to simplify in vitro fertilisation treatment due to the "patient-friendly" protocol.

Effectiveness and Cost-effectiveness of Minimal Ovarian Stimulation in-vitro Fertilization versus Conventional Ovarian Stimulation in Poor Responders: Economic Evaluation Alongside a Propensity Score Adjusted Prospective Observational Study.

OBJECTIVE: Information on the pregnancy rate after successive in-vitro fertilization (IVF) cycles and their associated costs is relevant for couples undergoing assisted reproduction treatments (ARTs). This study, therefore, sought to investigate the effectiveness and the cost-effectiveness of two ARTs, the minimal ovarian stimulation IVF (MS-IVF) compared to the conventional ovarian stimulation IVF (C-IVF) from the payer's perspective. METHODS: A 10-months follow-up prospective observational study was conducted in a sample of couples who sought ARTs in a private clinic in Southern Brazil. Women had to satisfy the Bologna Criteria and be older than 35 years. The effect outcome was pregnancy rate per initiated cycle. Medication costs were based on medical records. Costs and effect differences were estimated using seemingly unrelated regressions adjusted for the propensity score estimated based on women's characteristics. RESULTS: All 84 eligible women who agreed to participate received a total of 92 IVF cycles (MS-IVF, n=27[35 cycles]; C-IVF n=57[57 cycles]. The effect difference between MS-IVF and C-IVF was -5.1% (95%CI, -13.2 to 5.2). Medication costs of MS-IVF were significantly lower than C-IVF by €-1260 (95%CI, -1401 to -1118). The probabilities of MS-IVF being cost-effective compared to C-IVF ranged from 1 to 0.76 for willingness-to-pay of €0 to €15,000 per established pregnancy, respectively. CONCLUSIONS: Even though there were no positive effect differences between groups, MS-IVF might be cost-effective compared to C-IVF from the payer's perspective due to its relatively large cost savings compared to C-IVF. However, further investigation is needed to confirm these findings in a larger sample.

COVID-19: A Challenge to the Safety of Assisted Reproduction.

There is an increased risk of becoming pregnant through fertility treatments using assisted reproductive technology (ART) during the COVID-19 pandemic. The aim of this review is to gather comprehensive data from the existing literature on the potential risks of fertility management during the pandemic period, and outline strategies to mitigate them, with a focus on the hormonal and surgical procedures of ART. A comprehensive search of the scientific literature on COVID-19 in relation to fertility was conducted in the PubMed database using the keywords "coronavirus," "COVID-19," "SARS-CoV-2" and "pregnancy," "fertility," "urogenital system," "vertical transmission," "assisted human reproduction," "controlled ovarian stimulation," "oocyte retrieval," "in vitro fertilization," "hormones," "surgical procedures," "embryos," "oocytes," "sperm," "semen," "ovary," "testis," "ACE-2 receptor," "immunology," "cytokine storm," and "coagulation," from January 2020-July 2022. Published data on pregnancy and COVID-19, and the interaction of the urogenital system and SARS-CoV-2 is reported. The immunologic and prothrombotic profiles of patients with COVID-19, and their increased risks from controlled ovarian stimulation (COS) and ART surgeries, and how these procedures could facilitate COVID-19 and/or contribute to the severity of the disease by enhancing the cytokine storm are summarized. Strategies to prevent complications during COS that could increase the risks of the disease in pre-symptomatic patients are considered. The impact of SARS-CoV-2 on pre-symptomatic infertile patients presents a challenge to find ways to avoid the increased hormonal, immunologic, and prothrombotic risks presented by the use of COS in ART protocols during the COVID-19 outbreak. Safe ART procedures and recommendations are highlighted.

Frequent polymorphisms of FSH receptor do not influence antral follicle responsiveness to follicle-stimulating hormone administration as assessed by the Follicular Output RaTe (FORT).

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

p63 expression in granulosa-luteinized cells of infertile patients with peritoneal endometriosis submitted to in vitro fertilization.

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.

There is no complete linkage between the polymorphisms N680S and T307A of the follicular stimulating hormone receptor gene in fertile women.

PURPOSE: We conducted a cross-sectional study to evaluate the linkage of FSHR T307A and N680S in a group of fertile women. METHODS: Peripheral blood was obtained from 51 fertile women. DNA extraction and isolation were performed. For the detection of the T307A polymorphism a set of primers (5_-TCTGAGCTTCATCCAATTTGCA-3_and 5_-GGGAAAGAGGGCA GCTGCAA-3) was used and then the product was further amplified by a second PCR-RFLP using another set of primers (5_-CAAATCTATTTTAAGGCAAGAAGTTGATTATATGCCTCAG-3_and 5_-GTAGATTCCAATGCAGA GATCA-3). For the N680S polymorphism the primers (5_-TTTGTGGTCATCTGTGGCTGC-3_ and 5_-CAAAGGCAAGGACTGAATT ATC ATT-3_) were used. Statistical analysis for the association between the polymorphisms was performed by the Spearman test. RESULTS: We calculated the association between the homozygosis at codon 307 and at codon 680 both for T/T-S/S and A/A-N/N. A significant association between the genotypic results at codon 680 with those at codon 307 was found (r = 0.6363, P = 0.001). However, a complete linkage between these two polymorphisms was rejected as there were 12 patients with discordant results from the expected A-N/T-S at codons 307 and 680, respectively. CONCLUSION: The current data demonstrated an association but failed to demonstrate a complete linkage between these two polymorphisms.

The Graduated Embryo Score of Embryos from Infertile Women with and without Peritoneal Endometriosis.

OBJECTIVE: To determine embryo quality (mean graduated embryo score [GES]) in infertile patients with endometriosis undergoing in vitro fertilization with embryo transfer (IVF-ET) compared with infertile patients without endometriosis. METHODS: A case-control study was performed comparing 706 embryos (162 patients) divided into 2 groups: 472 embryos derived from patients without endometriosis (n = 109, infertile patients with tubal infertility) and 234 embryos from patients in the study group (n = 53, infertile patients with peritoneal endometriosis). All patients were subjected to IVF using an oestradiol-antagonist-recombinant follicle-stimulating hormone (FSH) protocol for ovarian stimulation. The mean GES was performed to evaluate all embryos at 3 points in time: 16 to 18 hours, 25 to 27 hours, and 64 to 67 hours. Embryo evaluation was performed according to the following parameters: fragmentation, nucleolar alignment, polar body apposition, blastomere number/morphology, and symmetry. The primary outcome measure was the mean GES score. We also compared fertilization, implantation, and pregnancy rates. RESULTS: Although the number of embryos transferred was greater in patients with endometriosis than in the control group (2.38 ± 0.66 versus 2.15 ± 0.54; p = 0.001), the mean GES was similar in both groups (71 ± 19.8 versus 71.9 ± 23.5; p = 0.881). Likewise, the fertilization rate was similar in all groups, being 61% in patients with endometriosis and 59% in the control group (p = 0.511). No significant differences were observed in the implantation (21% versus 22%; [p = 0.989]) and pregnancy rates (26.4% versus 28.4%; p = 0.989). CONCLUSION: Embryo quality measured by the mean GES was not influenced by peritoneal endometriosis. Likewise, the evaluated reproductive outcomes were similar between infertile patients with and without endometriosis.

OBJETIVO: Determinar a qualidade do embrião (média de escore embrionário graduado [EEG]) em pacientes inférteis com endometriose submetidas à fertilização in vitro com transferência de embrião (FIV-TE) em comparação com pacientes inférteis sem endometriose. MéTODOS: Realizamos um estudo de caso-controle comparando 706 embriões (162 pacientes) divididos em dois grupos: 472 embriões derivados de pacientes sem endometriose (n = 109, pacientes inférteis com infertilidade tubária) e 234 embriões de pacientes do grupo de estudo (n = 53, inférteis pacientes com endometriose peritoneal). Todos os pacientes foram submetidos à fertilização in vitro usando um protocolo follicle-stimulating hormone (FSH) recombinante de estradiol-antagonista para estimulação ovariana. A média do EEG foi realizada para avaliar todos os embriões em três momentos: de 16 a 18 horas, 25 a 27 horas e 64 a 67 horas. A avaliação embrionária foi realizada de acordo com os seguintes parâmetros: fragmentação, alinhamento nucleolar, aposição do corpo polar, número de blastômeros/morfologia e simetria. A medida de desfecho primário foi o escore médios embrionário (EEG). Também avaliamos como desfechos secundários as taxas de fertilização, implantação e gravidez. RESULTADOS: Embora o número de embriões transferidos tenha sido maior em pacientes com endometriose do que no grupo controle (2,38 ± 0,66 versus 2,15 ± 0,54; p = 0,001), o EEG médio foi semelhante nos dois grupos (71 ± 19,8 versus 71,9 ± 23,5; p = 0,881). Da mesma forma, a taxa de fertilização foi semelhante em todos os grupos, sendo 61% nos pacientes com endometriose e 59% no grupo controle (p = 0,511). Não foram observadas diferenças significativas nas taxas de implantação (21% versus 22%; [p = 0,989]) e nas taxas de gravidez (26,4% versus 28,4%; p = 0,989). CONCLUSãO: A qualidade embrionária medida pelo EEG médio não foi influenciada pela endometriose peritoneal. Da mesma forma, os resultados reprodutivos avaliados foram semelhantes entre pacientes inférteis com e sem endometriose.

Association of FSHR, LH, LHR, BMP15, GDF9, AMH, and AMHR polymorphisms with poor ovarian response in patients undergoing in vitro fertilization.

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.

Randomized controlled trial comparing embryonic quality in rFSH versus hMG in the IVF protocol with GnRH Antagonist.

OBJECTIVE: The aim of the present study is to investigate embryo quality (score) after controlled ovarian stimulation for IVF using rFSH or hMG with the GnRH antagonist protocol. METHODS: Open, randomized, single center study. The patients were randomized to receive rFSH or hMG according to randomized cards inside a black envelope with the name of the respective treatment following a computer generated list (85 patients were allocated to rFSH group and 83 patients to hMG group). Inclusion criteria were patients with IVF indication and normal ovarian reserve. Embryo evaluation was performed on day three, after fertilization based on the Graduated Embryo Score (GES). RESULTS: There were no relevant differences in demographic characteristics. There was no difference in pregnancy rates with 27 (31%) and 25 (30.1%) pregnancies for rFSH and hMG, respectively (p=0.87). The total embryo score was the same for both groups, but the best embryo score was significant higher for the rFSH group (77.33±34.0 x 65.07±33.2 p=0.03). The total number of embryos was statistical different, also in favor of the rFSH group (4.17±3.1 x 3.26±2.4 p=0.04). CONCLUSION: The total embryo score was the same for both groups, but the best embryo score was significantly higher for the rFSH group. Moreover, rFSH was associated with an increased number of embryos.