Cross-Partner Associations of Female Reproductive Hormones With Semen Parameters in Unexplained Infertility: An Exploratory Secondary Analysis

Background Unexplained infertility is a couple-level diagnosis made after standard female and male investigations do not identify a specific cause. Subtle cross-partner reproductive patterns may nevertheless be present. This exploratory secondary analysis assessed associations between female reproductive hormones and partner semen parameters in couples with unexplained infertility. Methods This cross-sectional secondary analysis used paired data from 70 couples with unexplained infertility from a previously published case-control study conducted at Ain Shams University Maternity Hospital in Cairo, Egypt, from October 2018 through April 2019. The original study evaluated vitamin D and reported descriptive hormone and semen data; the cross-partner analyses reported here are new. Female follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol (E2), and thyroid-stimulating hormone (TSH) were correlated with partner semen volume, concentration, total count, total motility, progressive motility, and normal morphology using Spearman correlation. Thirty correlations were screened with Benjamini-Hochberg false-discovery-rate (FDR) adjustment. Targeted linear models were adjusted for female age and body mass index (BMI), with 5,000-resample bootstrap confidence intervals. Results Female prolactin was inversely correlated with partner progressive motility (rho = -0.472, FDR q < 0.001) and normal morphology (rho = -0.595, FDR q < 0.001). TSH correlated positively with progressive motility (rho = 0.331, FDR q = 0.038) and morphology (rho = 0.419, FDR q = 0.003). E2 was nominally correlated with sperm concentration (rho = 0.284, p = 0.017) but did not survive FDR adjustment (q = 0.103). In age- and BMI-adjusted models, prolactin remained inversely associated with progressive motility (B = -0.401, bootstrap 95% CI -0.687 to -0.147) and morphology (B = -0.929, bootstrap 95% CI -1.282 to -0.620). The adjusted TSH association with morphology persisted (B = 4.076, bootstrap 95% CI 0.250 to 8.016), whereas the bootstrap interval for progressive motility included the null. Conclusions Female prolactin showed the most consistent inverse couple-level association with partner progressive motility and normal morphology. These cross-sectional findings do not establish biological effects of female hormones on male semen quality and should be regarded as hypothesis-generating pending independent prospective replication.