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OBJECTIVE: To utilize vast genetic data to reveal the interplay between 41 systemic inflammatory factors and endometriosis. DESIGN: Bidirectional Mendelian randomization study. MAINS OUTCOME MEASURES: This study obtained believable genetic instrumental variables for systemic inflammatory factors. The effect of systemic inflammatory factors on different endometriosis phenotypes, and the effect of endometriosis on the concentrations of systemic inflammatory factors were investigated. RESULTS: In this mendelian randomization study, we found 20 causal relationships involving 18 systemic inflammatory factors and it was shown that Monocyte chemotactic protein-1, Macrophage inflammatory protein-1a, Granulocyte colony-stimulating factor, Macrophage migration inhibitory factor, Interleukin-4, Interleukin-5, Interleukin-8, Interleukin-9, Interleukin-12p70, Interleukin-16, and Interleukin-17 may be the upstream causes of endometriosis (P<0.05). Additionally, if the definition of exposure in the mendelian randomization was endometriosis, it could suggestively cause an increase in Eotaxin, cutaneous T-cell attracting chemokine, and Interferon gamma-induced protein 10 levels, and a decrease in growth-regulated oncogene-alpha, Interleukin-2 receptor, alpha subunit, platelet-derived growth factor BB, and Interleukin-18 (P<0.05). Reverse causality was not observed between a single systemic inflammatory factor and endometriosis. CONCLUSIONS: Our findings indicate that several systemic inflammatory factors may act as the initiator at the onset of endometriosis. Additionally, several other inflammatory factors are far more probable to involved downstream during disease development.
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Background: Endometrial polyps (EPs) are one of the most common intrauterine benign tumors, and are an important cause of uterine bleeding and female infertility. Previous studies have suggested that endometritis may contribute to the onset of EPs. This study aims to reveal the causal effect of endometritis on EPs by a two-sample Mendelian randomization (MR) study. Methods: Utilizing summarized statistics from genome-wide association studies (GWAS) in the European population, we conducted a Mendelian randomization study. In order to select suitable instrumental variables (IVs) that were significantly related to the exposures, a number of quality control approaches were used. For endometritis, 2144 cases and 111,858 controls were included, while for EPs, 2252 cases and 460,758 controls. Utilizing the inverse variance weighted (IVW) as the primary analysis, the data were subjected to a two-sample MR analysis, and the weighted median (WM) technique and MR-Egger regression were carried out additionally. The sensitivity analysis revealed neither heterogeneity nor horizontal pleiotropy. Results: Four independent single nucleotide polymorphisms (SNPs) from endometritis GWAS as IVs were selected. The IVW data did not agree to a causal association between endometritis and EPs (ß=1.11e-04, standard error [SE] =4.88e-04, P = 0.82). Directional pleiotropy did not affect the outcome, according to the MR-Egger regression (intercept = 0.09, P = 0.10); Additionally, it showed no causation association between endometritis and EPs (ß= -3.28e-03, SE = 3.54e-03, P = 0.45). Similar results were obtained using the weighted-median method (ß=8.56e-05, SE=5.97e-04, P = 0.89). No proof of heterogeneity and horizontal pleiotropy between IV estimates was discovered. Conclusion: In conclusion, by large scale genetic data, the results of this MR analysis provided suggestive evidence that the presence of endometritis is not associated with higher EPs risk.
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Background: The effect of premature progesterone elevation on assisted reproductive technology has been debated. In different ovarian stimulation protocols, ovarian responses, and embryos transferred, conflicting results reside regarding the impact of elevated progesterone on pregnancy outcomes, according to previous studies. In addition, most studies have focused on significantly elevated progesterone levels, eg, above 1.5ng/mL, 1.75ng/mL, 2ng/mL. However, studies focusing on levels that are just slightly elevated are lacking, and some have concluded that such levels have no adverse effects on pregnancy outcomes. Methods: Clinical data of patients who underwent early follicular phase prolonged protocol cycle in vitro fertilization/intracytoplasmic sperm injection treatment were collected. Patients were divided into two groups according to progesterone level on the trigger day of human chorionic gonadotropin (HCG): Group 1: < 1.0ng/mL and Group 2: 1.0-1.5ng/mL. Differences in baseline characteristics, ovulation promotion, and embryo culture, along with clinical pregnancy outcomes, were compared between the two cohorts. Results: A total of 743 participants were included in this study, of which 587 were included in Group 1 and 156 were included in Group 2. In terms of pregnancy outcomes, Group 2 had a significantly lower clinical pregnancy rate and live birth rate per cycle than Group 1 (64.1% vs 75.7%, p < 0.05; 63.5% vs 72.7%, p < 0.05). After correction for maternal age, maternal body mass index, infertility duration, basal follicle-stimulating hormone, anti-Müllerian hormone, antral follicle count, total dose of gonadotropin, days of stimulation, and estradiol level on HCG trigger day, slightly elevated progesterone levels (P > 1.0ng/mL) remained a risk factor for pregnancy failure in fresh single D5 blastocyst transfer under an early follicular phase prolonged protocol cycle. Conclusion: Slightly elevated progesterone levels on HCG trigger day may negatively affect pregnancy outcomes in early follicular phase prolonged protocol cycles.
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(1) Background: A cesarean scar defect may cause localized inflammation of the endometrial tissue, and various researchers believe that the presence of a cesarean scar defect is associated with chronic endometritis. However, there is no report on the possible association between cesarean scar defects and chronic endometritis thus far. This study aimed to assess the role of having a cesarean scar defect in a person's susceptibility to chronic endometritis. (2) Methods: This retrospective propensity-score-matched study comprised 1411 patients with chronic endometritis that were admitted to Henan Provincial People's Hospital in China from 2020 to 2022. Based on whether a cesarean scar defect was present or not, all cases were assigned to the cesarean scar defect group or the control group. (3) Results: Of the 1411 patients, 331 patients with a cesarean scar defect were matched to 170 controls. All unbalanced covariates between groups were balanced after matching. Before matching, the prevalence of chronic endometritis in the cesarean scar defect group and in the control group was 28.8% and 19.6%, respectively. After correcting for all confounding factors, a logistic regression analysis showed that cesarean scar defect occurrence may increase the risk of chronic endometritis (odds ratio (OR), 1.766; 95% confidence interval (CI), 1.217-2.563; p = 0.003). After matching, the prevalence of chronic endometritis was 28.8% in the cesarean scar defect group and 20.5% in the control group. Thus, even after correcting for all confounding factors, the logistic regression analysis still showed that a cesarean scar defect remained an independent risk factor for chronic endometritis prevalence (OR, 1.571; 95% CI, 1.021-2.418; p = 0.040). The findings were consistent throughout the sensitivity analyses. (4) Conclusions: The present results suggest that the onset of a cesarean scar defect may increase the risk of chronic endometritis.
