Neurodevelopmental effects of maternal folic acid supplementation: a systematic review and meta-analysis.

Folic acid, a water-soluble vitamin B nutrient, plays an important role not only in maintaining a healthy pregnancy but also in offspring brain development and function, however, it remains unclear whether maternal folic acid (FA) supplementation associated with the risk of different postnatal neurodevelopmental outcomes. Here, we performed a systematic review and meta-analysis on the impact of maternal FA supplementation on a wide range of postnatal neurodevelopmental outcomes which include intellectual development, risk of autistic traits, ADHD, behavior, language, and psychomotor problems, using studies extracted from the following databases, including MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, and PsychInfo. Thirty-two cohort studies and seven case-control studies were included in this meta-analysis. In the present study, we found that prenatal FA supplementation had a positive impact on offspring's neurodevelopmental outcomes, including improved intellectual development and reduced risk of autism traits, ADHD, behavioral, and language problems. We also found that FA over-supplementation was not associated with an improvement in offspring's brain development, and may have a negative impact on offspring's neurodevelopmental outcomes. This study proved the first panoramic review on the relationship of FA supplementation with offspring's neurodevelopment. Further studies focusing on different dosages and periods of FA supplementation are needed.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1993781 .

Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment.

BACKGROUND: The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. METHODS: Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA- group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. RESULTS: There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. CONCLUSION: The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

The Genetic Association of Polycystic Ovary Syndrome and the Risk of Endometrial Cancer: A Mendelian Randomization Study.

The association between polycystic ovary syndrome (PCOS) and endometrial cancer remains unclear. We aimed to investigate the causal association between genetically predicted PCOS and endometrial cancer risk in two ethnic groups through a two-sample Mendelian randomization (MR) approach. Our study includes 13 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for PCOS in Europeans, and another 13 SNPs are used as IVs for PCOS in Asians. Outcome data were obtained from the largest published meta-GWAS of European ancestry to date, as well as from the BioBank Japan Project of Asian ancestry. Our study demonstrates that genetically predicted PCOS is not causally associated with the risk of overall endometrial cancer in either Europeans or Asians (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.85-1.01, p = 0.09 and OR = 0.98, 95% CI 0.84-1.13, p = 0.75, respectively). Subgroup analyses according to histotype further illustrate that PCOS might not be associated with the risk of either endometrioid endometrial cancer or non-endometrioid endometrial cancer in European ancestry. No pleiotropy is found in our study, and a sensitivity analysis shows similar results. Our results indicate that genetically predicted PCOS might not be associated with the risk of endometrial cancer.

The Association Between Genetically Predicted Systemic Inflammatory Regulators and Polycystic Ovary Syndrome: A Mendelian Randomization Study.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic diseases among women of reproductive age. Inflammation may be involved in the pathogenesis of PCOS, but its exact relationship with PCOS remains unclear. Herein, we investigate the causal association between systemic inflammatory regulators and PCOS risk through a two-sample Mendelian randomization (MR) approach based on the latest and largest genome-wide association study (GWAS) of 41 systemic inflammatory regulators in 8293 Finnish participants and a GWAS meta-analysis consisting of 10,074 PCOS cases and 103,164 controls of European ancestry. Our results suggest that higher levels of IL-17 and SDF1a, as well as lower levels of SCGFb and IL-4, are associated with an increased risk of PCOS (OR = 1.794, 95% CI = 1.150 - 2.801, P = 0.010; OR = 1.563, 95% CI = 1.055 - 2.315, P = 0.026; OR = 0.838, 95% CI = 0.712 - 0.986, P = 0.034; and OR = 0.637, 95% CI = 0.413 - 0.983, P = 0.042, respectively). In addition, genetically predicted PCOS is related to increased levels of IL-2 and VEGF (OR = 1.257, 95% CI = 1.022 - 1.546, P = 0.030 and OR = 1.112, 95% CI = 1.006 - 1.229, P = 0.038, respectively). Our results indicate the essential role of cytokines in the pathogenesis of PCOS. Further studies are warranted to assess the possibility of these biomarkers as targets for PCOS prevention and treatment.

Interleukin-1ß as clinically predictive risk marker for recurrent pregnancy loss in women positive for antinuclear antibody.

AIMS: Antinuclear antibody (ANA) was found to be associated with recurrent pregnancy loss (RPL). This study was designed to explore the immunological predictive indicators of RPL in women with positive ANA. METHODS: A retrospective case-control study in a university hospital from March 2020 to January 2021 was performed, including 56 cases of women with RPL and 56 controls matched for age, all of which were positive for ANA. Levels of cytokines, lymphocyte subsets, immune globulin and complement in peripheral blood among two groups were compared. Statistical analyses in this study were performed using SPSS 25.0. RESULTS: The level of IL-1ß was higher in RPL women compared with controls according to univariable analysis and multivariable regression logistic analysis (7.67 [5.86-11.35] vs 5.00 [5.00-5.00], P = .000). After the cut-off value of IL-1ß was set as 5.66 pg/mL, the prevalence of RPL was significantly elevated in the high IL-1ß group as compared with the low IL-1ß group (P < .05). The sensitivity and specificity of IL-1ß predicting RPL in ANA-positive women were 76.8% and 91.1%, respectively. CONCLUSION: Increased IL-1ß may play roles in the occurrence of RPL among women with positive ANA. The level of the IL-1ß has the potential to be a predictive indicator of RPL in women with positive ANA.

Antiphospholipid antibodies and pregnancy outcome of assisted reproductive treatment: A systematic review and meta-analysis.

PROBLEM: Antiphospholipid antibodies (aPLs) are a group of autoantibodies associated with a variety of pregnancy complications, but the impact of aPL on the outcomes of assisted fertility treatment (ART) is controversial. This systematic review and meta-analysis were designed to explore the association between aPL and ART outcomes and to explore in which stages does aPL play a role. METHOD OF STUDY: PubMed and Cochrane database were systematically retrieved, and odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effect model or fixed-effect model according to the heterogenicity assessed by the Cochran Q and I2  statistic test. Of 246 records identified by the search, 10 case-control studies and 13 cohort studies that explored the association between aPL and in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were analyzed. RESULTS: The results showed that aPL positive rate was higher in females who failed in IVF/ICSI than those who succeeded in IVF/ICSI (OR: 3.62, 95% CI: 1.95-6.74). This study also indicated that females positive for aPL have a higher miscarriage rate (RR: 1.68, 95% CI: 1.24-2.28) than those negative for aPL, but live birth rate, biochemical pregnancy rate, and clinical pregnancy rate were similar between two groups (RR: 1.01, 95% CI: 0.91-1.12; RR: 1.18, 95% CI: 0.57-2.43 and RR: 0.95, 95% CI: 0.80-1.13). CONCLUSIONS: There was higher aPL prevalence in females with adverse IVF/ICSI outcomes. It seems that aPL mainly affects the miscarriage rate, but has little effect on live birth rate, biochemical pregnancy rate, and clinical pregnancy rate. Routine detection of aPL before IVF/ICSI treatment is meaningful.