Objective: Human papillomavirus (HPV) is a widespread sexually transmitted infection primarily affecting women. While its link to cervical cancer is well-established, its potential role in other gynecological diseases, such as polycystic ovarian syndrome (PCOS), irregular menstruation (IM), endometrial cancer (EC), and endometriosis, remains underexplored. Observational studies may be subject to residual confounding, but Mendelian randomisation (MR) utilises genetic variants as instrumental variables to strengthen causal inference and mitigate confounding bias. Design: A two-sample MR study. Setting: Summary statistics from published genome-wide association studies (GWAS) in European ancestry populations. Population or sample: Genetic instruments for HPV susceptibility were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS database. Methods: Inverse-variance weighted (IVW) MR was used to assess the causal association between HPV and gynecological diseases. Sensitivity analyses, including weighted median and MR-Egger, were performed to assess robustness. Steiger tests were conducted to confirm the direction of causality. Main outcome measures: Female-specific genetic association estimates for gynecological diseases were extracted from large-scale GWAS datasets. Results: Genetically predicted HPV susceptibility was associated with an increased risk of EC (odds ratio [OR] 1.0973, 95% confidence interval [CI] 1.0030–1.2005, P = 0.0429) and endometriosis (OR 1.0610, 95% CI 1.0029–1.1225, P = 0.0392). Scatter plots and forest plots supported HPV as a risk factor for EC and endometriosis. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy. Each single nucleotide polymorphism (SNP) had a minimal influence on the overall results. Steiger tests confirmed the validity of the causal direction. However, no causal relationship was found between HPV and PCOS or IM. Conclusions: This study provides evidence that genetically predicted HPV susceptibility is a risk factor for EC and endometriosis, while no causal relationship was identified for PCOS or IM. These findings offer novel insights into HPV-related gynecological disease prevention and treatment strategies.

Objective: To evaluate whether acupuncture pretreatment followed by letrozole leads to a higher live birth rate in PCOS when compared with letrozole alone. Design: Multicenter randomised controlled trial. Setting: Three hospitals in China. Population or Sample: Anovulatory women with PCOS aged from 20 to 40 years who had at least one patent tube. Methods: Participants were randomly assigned to receive acupuncture pretreatment followed by letrozole (pretreatment group) or letrozole alone (control group). Acupuncture pretreatment was given three times per week for 16 weeks, and letrozole was given five days per cycle for up to four cycles. Main outcome measures: The cumulative live birth rate (defined as a delivery after 20 weeks’ gestation). Results: The cumulative live birth rate was 41.1% (79/192) in the pretreatment group and 34.4% (66/192) in the control group with no significant difference between groups but was significantly higher in the pretreatment group (48/98, 49.0%) among those with baseline HOMA-IR <2.14, when compared with the control group (19/66, 28.8%). No significant differences were found between groups stratified by the letrozole cycle number, body mass index, age, PCOS phenotype, or hyperandrogenism. Conclusions: Acupuncture pretreatment followed by letrozole did not increase the cumulative live birth rate of anovulatory women with PCOS when compared with letrozole alone but may increase the cumulative live birth rate in those whose baseline HOMA-IR is <2.14. Key words: acupuncture, letrozole, live birth, PCOS, pretreatment