Placenta and Reproductive Medicine

Association between human papillomavirus infection and non-cancerous reproductive health outcomes: An umbrella review

2026-04-14T13:27:46+00:00

Human papillomavirus (HPV) infection is well established as a cause of multiple cancers; however, its association with non-cancerous reproductive health outcomes remains uncertain. This umbrella review aimed to comprehensively evaluate the strength and credibility of evidence linking HPV infection to non-cancerous reproductive outcomes based on published systematic reviews and meta-analyses. We systematically searched PubMed, Embase, and Web of Science from inception to March 2024 for systematic reviews and meta-analyses of observational studies examining associations between HPV infection, including specific genotypes, and non-cancerous reproductive health outcomes. The credibility of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and methodological quality was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR). This review was not prospectively registered, which is acknowledged as a limitation. A total of 36 meta-analyses from 11 articles were included. According to AMSTAR, all studies were of moderate to high methodological quality. Our associations were supported by suggestive evidence, indicating that HPV infection, especially with high-risk types, was associated with elevated risks of preterm birth, low birth weight, female infertility, and unknown infertility. However, the certainty of evidence was low or very low for relevant outcomes according to GRADE, and most 95% prediction intervals crossed the null. This umbrella review suggests that HPV infection, especially with high-risk genotypes, may contribute to adverse pregnancy outcomes and infertility, but the evidence is of low to very low certainty. These findings highlight the need for further rigorous research to clarify these associations and determine their implications for public health.

The impact of diet on male semen quality and fertility: A comprehensive review

2026-05-28T10:37:00+00:00

Male factor infertility contributes to approximately 50% of all infertility cases, and global semen quality has declined substantially over recent decades, with modifiable lifestyle factors, particularly diet, implicated as key drivers. This comprehensive review synthesizes evidence from observational studies and randomized controlled trials examining associations between dietary components and male reproductive outcomes, with emphasis on underlying biological mechanisms. Despite growing interest in this field, well-designed randomized controlled trials examining clinically meaningful fertility outcomes remain scarce, and most available evidence derives from observational studies with inherent methodological limitations. Current evidence suggests that healthy dietary patterns, particularly the Mediterranean diet, are associated with superior semen parameters through mechanisms including reduced oxidative stress, improved hormonal profiles, and epigenetic modulation. Specific foods (nuts, fish, fruits, vegetables) and nutrients (omega-3 fatty acids, selenium, zinc, coenzyme Q10, antioxidants) demonstrate beneficial effects on sperm concentration, motility, morphology, and DNA integrity. However, while improvements in conventional semen parameters are well-documented, evidence for enhanced pregnancy and live birth rates remains limited, with meta-analyses showing inconsistent associations between dietary factors and assisted reproductive technology (ART) outcomes. Whether improvements in sperm parameters translate to clinically meaningful increases in live birth rates remains an open question requiring further investigation. Conversely, Western dietary patterns, ultra-processed foods, and specific dietary components (processed meats, trans fatty acids, phytoestrogens at high doses) are associated with poorer semen quality through pro-inflammatory pathways, endocrine disruption, and direct genotoxicity. Notably, pesticide residues in conventionally grown produce may attenuate the benefits of fruit and vegetable consumption via oxidative stress and androgen receptor antagonism. Weight management through dietary intervention significantly improves sperm parameters, with emerging evidence suggesting glucagon-like peptide-1 (GLP-1) receptor agonists may offer additional benefits for obese men. This review identifies critical knowledge gaps—including the paucity of trials with live birth as primary outcome, heterogeneity in study designs, and limited evidence for personalized nutrition approaches—and provides evidence-based dietary recommendations for men planning paternity.

Multi-omics genetic prioritization reveals distinct molecular evidence profiles for candidate targets in female infertility

2026-05-02T19:28:41+00:00

Background: Female infertility is heterogeneous, and genetically supported candidate targets remain limited. Although genome-wide association studies have identified infertility-associated loci, the effector molecules and molecular layers through which these signals act remain unclear. Methods: Using FinnGen female infertility (N14_FEMALEINFERT), we integrated Mendelian randomization (MR) with summary-data-based Mendelian randomization (SMR) using protein quantitative trait locus (pQTL), expression quantitative trait locus (eQTL), and methylation quantitative trait locus (mQTL) data, cross-layer colocalization, public trait lookup, and tractability assessment. Results: Multilayer analyses retained three candidate genes: interleukin 18 (IL18), RELT tumor necrosis factor receptor (RELT), and alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase (ABO). Colocalization revealed distinct molecular evidence profiles across the retained candidates. IL18 showed the clearest transcript-level evidence, with strong eQTL colocalization (posterior probability for a shared causal variant [PP.H4] = 0.833), whereas comparable plasma pQTL or mQTL colocalization support was not observed. RELT showed its strongest support at the methylation layer, with strong mQTL colocalization (PP.H4 = 0.863) and secondary protein-layer support across both pQTL resources. ABO showed supportive MR and protein-layer SMR evidence, but its signal could not be confidently assigned to a single molecular layer. Considering molecular localization, pleiotropy, and tractability, IL18 showed the most favorable translational profile, whereas RELT was retained as a regulatory candidate requiring cautious interpretation. Conclusions: Cross-layer integration prioritized IL18 and RELT as informative candidates for female infertility, with IL18 supported mainly at the transcript level and RELT at the methylation level. This multilayer framework clarified the molecular layer contributing the strongest evidence for each candidate and refined candidate prioritization in a biologically heterogeneous phenotype.

Causality between smoking and female reproductive disorders: A Mendelian randomization study

2026-06-01T15:52:47+00:00

Background: Smoking may impair female reproductive health, but its causal role remains unclear. This study evaluated the causal associations of smoking initiation, lifetime smoking index, and smoking cessation with 15 female reproductive disorders. Methods: Linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), and colocalization analysis assessed genetic correlations and causal associations, and detected shared genetic variants between smoking-related phenotypes and female reproductive disorders. Results: Genetic liability to smoking initiation was associated with higher risks of adenomyosis (odds ratio [OR] = 1.57, P = 0.008), dysplastic lesions involving the cervix, vagina, or vulva (OR = 1.34, P = 0.016), inflammatory disease of the uterus (OR = 1.52, P = 0.016), oligomenorrhea (OR = 2.09, P = 0.032), and torsion of ovary, ovarian pedicle, and fallopian tube (OR = 2.43, P = 0.046). A higher lifetime smoking index was associated with increased risks of dysplastic lesions involving the cervix, vagina, or vulva (OR = 1.55, P = 0.020), cervical dysplastic lesions (OR = 1.70, P = 0.007), excessive, frequent, and irregular menstruation (OR = 1.37, P = 0.003), and inflammatory disease of the uteri (OR = 2.66, P < 0.001). Genetic propensity to smoking cessation resulted in a reduced risk of endometriosis (OR = 0.58, P = 0.015). Colocalization revealed two shared genetic loci (inhibitory synaptic factor 1 [INSYN1] and phosphodiesterase 4B [PDE4B]) between lifetime smoking index and inflammatory disease of the uterus. Conclusion: These findings provide genetic evidence that smoking-related behaviors may causally influence several female reproductive disorders.

Pregnancy outcomes in survivors of hematological malignancies: A systematic review with meta-analysis of thirty-seven cohort studies

2026-05-06T13:01:59+00:00

Background: Reproductive outcomes in survivors of hematological malignancies (HM) are of growing concern, yet evidence from large-scale comparative studies has not been comprehensively synthesized. This systematic review and meta-analysis aimed to assess the impact of a history of HM on pregnancy outcomes. Methods: We searched three databases (inception to Jan 1, 2026) for cohort studies comparing HM survivors with population/sibling controls. Random-effects meta-analysis pooled relative risks (RRs) with 95% CIs; subgroup, meta-regression, sensitivity, and publication bias analyses were performed. Results: Thirty-seven cohort studies were included. Compared with controls, HM survivors had significantly lower rates of pregnancy (relative risk [RR] 0.67, 95% CI: 0.49-0.92) and live birth (RR 0.69, 95% CI: 0.59-0.79). The risks of preterm birth (RR 1.39, 95% CI: 1.24-1.55), low birth weight (RR 1.29, 95% CI: 1.06-1.57), cesarean section (RR 1.23, 95% CI: 1.13-1.35), and gestational diabetes mellitus (GDM; RR 1.27, 95% CI: 1.01-1.58) were significantly elevated. No statistically significant associations were observed for spontaneous abortion, induced abortion, stillbirth, small for gestational age, birth defects, or hypertensive disorders of pregnancy in the main analyses. Subgroup analyses suggested that the risks of preterm birth and low birth weight were more pronounced among leukemia survivors, while lymphoma survivors showed a significantly increased risk of stillbirth. Conclusion: A history of HM is associated with multiple adverse pregnancy outcomes and reduced pregnancy/live birth rates, underscoring the need for targeted oncofertility counseling and reproductive surveillance in this population.

Reproductive health considerations in cervical cancer management: A nationwide analysis of epidemiological trends and histological shifts (1993-2017)

2026-06-03T20:10:41+00:00

Background: Comprehensive evidence regarding the longitudinal trends of cervical cancer (CC) incidence and its histological subtypes in China is limited, particularly concerning the growing clinical demand for reproductive health preservation. This study analyzed incidence patterns (2013-2017) and long-term trends (1993-2017) of CC and its subtypes across China. Methods: Data were extracted from the Cancer Incidence in Five Continents (CI5 XII) and CI5plus databases. Trends in age-standardized incidence rates (ASIRs) were analyzed using Joinpoint regression. A novel estimation model was developed to quantify the national and regional prevalence of patients potentially eligible for fertility-sparing surgery. Results: Between 2013 and 2017, approximately 67,053 new CC cases were diagnosed in China. From 1993 to 2017, the incidence of CC showed a pronounced upward trend (annual percent change [APC]: 7.06). While the incidence peaked in the 50-54 age group, the rising burden in younger cohorts highlights an urgent need for reproductive health considerations. Utilizing our novel fertility-sparing potential estimation model, we identified approximately 7544 patients theoretically eligible for fertility-sparing surgery during 2013-2017. Significant regional clustering of these candidates was observed in high-burden provinces such as Jiangsu and Zhejiang, emphasizing the substantial challenge of infertility risk among young patients. Conclusion: China faces a significant and increasing burden of CC with notable regional variations. There is an urgent need to implement a national, integrated prevention strategy that combines standardized Human Papillomavirus (HPV) vaccination and screening with tailored fertility preservation services. Addressing these reproductive health needs is critical to mitigating the long-term impact of CC, particularly for young women in high-prevalence regions.

Preventing public misinterpretation during the transition from polycystic ovary syndrome to polyendocrine metabolic ovarian syndrome

2026-06-10T08:53:57+00:00