Eduardo Carvalho de Arruda Veiga

To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility. Granulosa cells were obtained from 47 women undergoing in vitro fertilization treatment, including 31 women with female-factor (FFG) and 16 women with male-factor infertility (MFG). Cells from both groups were cultured and divided into four treatment conditions for 96 h: a) control (culture medium without melatonin); b) vehicle (melatonin diluent-ethanol); c) 0.1 µM melatonin; and d) 10 µM melatonin. Expression of 84 genes involved in angiogenesis signaling pathway was analyzed by real-time PCR. Cultured granulosa cells from both groups expressed aromatase and melatonin receptors. In both groups, cell proliferation peaked at 72 h when exposed to 10 µM melatonin. Of the 84 analyzed genes, three showed significant differential mRNA expression. In the MFG, melatonin at 10 µM upregulated VEGF-B mRNA expression in granulosa cells but downregulated PDGFA and HGF mRNA expression, in contrast to the higher expression of these genes in the FFG under identical conditions. Melatonin differentially modulates angiogenesis-related gene expression in granulosa cells, indicating that its effects may depend on infertility type and melatonin dose in women undergoing in vitro fertilization.

Background: The vaginal microbiome is an important factor influencing clinical outcomes in women undergoing assisted reproductive techniques. Objective: Our review aimed to confirm that women with a favorable vaginal microbiome have better reproductive outcomes than women who have an unfavorable vaginal microbiome. Methods: This systematic review and meta-analysis included articles published in the last 10 years, identified through keyword searches in PubMed and MEDLINE using the MeSH terms “vaginal microbiome,” “reproduction,” and “human reproduction.” The search yielded 1735 records. Participants were categorized into women with a favorable microbiome and those with an unfavorable microbiome. To refine the taxonomic resolution at the species level, we additionally performed a bioinformatic analysis of a cohort of 56 women using multivariable association with linear models (MaAsLin2). Results: Women with a favorable microbiome had higher pregnancy rates compared to those with a less favorable microbiome (p = 0.0001, I2 = 0%, RR: 1.59). Live birth rates were also significantly higher in the favorable microbiome group than in the unfavorable microbiome group (p = 0.004, I2 = 0%, RR:1.41), with no evidence of heterogeneity. Women with an unfavorable microbiome had more miscarriages than women with a favorable microbiome (p = 0.04, I2 = 0%, RR: 0.65). Bioinformatic analysis showed that a high relative abundance of Lactobacillus crispatus increased the likelihood of pregnancy approximately sixfold. Conclusions: The favorable microbiome group, particularly participants with a high relative abundance of Lactobacillus crispatus, demonstrated better reproductive outcomes, with a higher clinical pregnancy rate, a higher live birth rate, and a lower rate of pregnancy loss, although there was a low-quality bias.

Introduction: Assisted reproductive technologies are necessary and important for the management of infertility and can be applied with and without the use of strategies such as hormonal pretreatment. However, there is a discussion in the literature on whether hormonal pretreatment in ovarian stimulation protocols can improve the outcome of oocytes and embryos. This study aimed to conduct an integrative review of hormonal pretreatment and its impact on women undergoing assisted reproduction procedures. Methods: We made searches in the PubMed and the Cochrane Library databases. The inclusion criteria were articles published in peer-reviewed journals in English, Portuguese, or Spanish from January 1, 2010 to December 31, 2021 and available as free full texts. We excluded gray literature works, including term papers, theses, and dissertations. We used a narrative synthesis for data analysis. Results: The 189 articles retrieved from the two databases (2010-2021) were narrowed down to eight articles. In most studies, pretreatment seems to play a role beyond stimulation that includes an early inhibition of the FSH peak, a more homogeneous cohort, and better results. Conclusions: Using a pretreatment with combined oral contraceptives (COC) produces conflicting results in assisted reproduction. The COC improves the quantity and quality of eggs, but it neither benefits nor harms reproductive outcomes. Also, the use of COC has contradictory results regarding clinical pregnancy.

To evaluate the association between second trimester plasma cytokine levels in asymptomatic pregnant women and preterm births (PTB) in an attempt to identify a possible predictor of preterm birth. The study design was a nested case–control study including women with singleton a gestational age between 20–25(+ 6) weeks from two Brazilian cities. The patients were interviewed, Venous blood samples were collected. The participants were again evaluated at birth. A total of 197 women with PTB comprised the case group. The control group was selected among term births (426 patients). Forty-one cytokines were compared between groups. When only spontaneous PTB were analyzed, GRO, sCD40L and MCP-1 levels were lower in the case group (p < 0.05). Logarithmic transformation was performed for cytokines with discrepant results, which showed increased levels of IL-2 in the group of spontaneous PTB (p < 0.05). In both analyses, the incidence of maternal smoking and of a history of preterm delivery differed significantly between the case and control groups. In multivariate analysis, only serum GRO levels differed between the case and control groups. Lower second trimester serum levels of GRO in asymptomatic women are associated with a larger number of PTB. This finding may reflect a deficient maternal inflammatory response.