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.

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.

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.

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.

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.

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.

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.

Psychotropic medication use among women seeking assisted reproductive technology (ART) therapy: A cross-sectional study.

Background Infertility is associated with increased anxiety, depressive symptoms and mood disorders. Unfortunately, mental health is not often addressed in infertility treatment and infertile patients could be at higher risk of self-administration of not prescribed drugs or/and be exposed to alternative emotional treatments. Therefore, the aim of the present study is to investigate the use of psychotropic medication and to evaluate the frequency of psychiatric diagnosis among infertile women seeking assisted reproductive technology (ART) therapy. Methods All infertile women starting treatment at an ART clinic who agreed to participate in the study were included. Patients were submitted to a structured psychiatric interview, the Mini International Neuropsychiatric Interview (M.I.N.I.). Current and lifetime use of psychotropic medication were assessed. Results Ninety patients who agreed to participate completed the research protocol.  A total of 12/90  were on current use of psychotropic medication.Thirty-six out of ninety patients  had at least one psychiatric disorder. Mood disorders were detected in 19 of the 90. Anxiety disorders were highly frequent, reaching 27/90 of the patients, as agoraphobia the most common diagnosis (12/90). Limitations The study has several limitations, such as the absence of a control group of fertile patients and strict inclusion criteria, in which only subjects that spontaneously agreed to participate were enrolled. Conclusion Women suffering from infertility seeking ART treatment are at high risk for depression and anxiety disorders and a considerable number of them are in use of medication. Its implications on infertility treatments and offspring are uncertain.

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.

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.

The graduated embryo score of embryos from infertile women with and without peritoneal endometriosis / Escore embrionário graduado em embriões de mulheres inférteis com e sem endometriose peritoneal

Abstract 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. Themean GESwas 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 outcomemeasure 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 meanGESwas similar inbothgroups (71 ± 19.8 versus 71.9 ± 23.5; p= 0.881). Likewise, the fertilization ratewas 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.

Resumo 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 EEGfoi realizada para avaliar todos osembriõesemtrêsmomentos: de 16 a 18 horas, 25 a 27 horas e 64 a 67 horas.A avaliaçãoembrionária foi realizada de acordo comos 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 EEGmédio 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 EEGmédio não foi influenciada pela endometriose peritoneal. Da mesma forma, os resultados reprodutivos avaliados foram semelhantes entre pacientes inférteis com e sem endometriose.

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.

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.

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.

GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

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.

Antral follicle responsiveness assessed by follicular output RaTe(FORT) correlates with follicles diameter.

BACKGROUND: The antral follicle count is a marker of ovarian reserve. Follicular Output RaTe (FORT) evaluates the proportion of follicles responsive to exogenous follicle stimulating hormone (FSH) during controlled ovarian stimulation. Our objective was to evaluate whether the diameter (AFC6: ≤ 6 mm or AFC > 6: > 6 mm) of the follicular cohort could be a predictor for ovarian responsiveness, assessed by FORT, in a prospective cohort with 92 women with IVF indication, regular cycles and no abnormality in both ovaries. RESULTS: The mean age (±SD) of the women was 36.03 years (± 3.87 years), the median FORT was 43.30%. We found correlation between the FORT and AFC6 (r = - 0.237, P 0.023) but not between the FORT and AFC > 6 (r = - 0.055, P 0.602). CONCLUSIONS: The inverse correlation between FORT and AFC6 suggests that those follicles were less responsive to the exogenous FSH.