Relationships between female infertility and female genital infections and pelvic inflammatory disease Original paper

What was studied?

This population-based nested case-control study investigated the associations between female genital tract infections, selected comorbidities, and infertility using data from the Taiwan National Health Research Database (NHIRD) between 2000 and 2013. The study specifically evaluated whether infections such as pelvic inflammatory disease (PID), bacterial vaginosis (BV), and endometritis, as well as comorbid conditions like obesity, lipid metabolism disorders, and abortion history, were linked to an increased risk of diagnosed infertility. The research leveraged the large scope of the NHIRD, which includes nearly the entire Taiwanese population, to provide robust epidemiological insights. The analysis involved both univariate and multivariate conditional logistic regression to adjust for confounding variables and to isolate the independent associations of different infections and comorbidities with infertility risk in women, stratified by age groups (≤40 and >40 years).

Who was studied?

The study included 18,276 women newly diagnosed with infertility and 73,104 age-matched controls without infertility, all identified from the NHIRD. Controls were matched by age (within three years) and index year and were required to have a history of pregnancy but no prior diagnosis of infertility or use of ovulation stimulants or gonadotropins. Exclusion criteria covered prior hysterectomy, bilateral oophorectomy, cancer, prior chemotherapy or radiotherapy, polycystic ovary syndrome, ovarian failure, endometriosis, adenomyosis, amenorrhea, and Turner syndrome. The mean age of the cohort was 31 years, and the population was predominantly Han Chinese women residing in Taiwan. Patients were further stratified into two age groups (≤40 and >40 years) to assess potential age-related interactions with infertility risk factors.

Most important findings

The most significant finding was a robust association between upper and lower genital tract infections and increased risk of infertility, evident even after controlling for comorbidities and other confounders. Specifically, pelvic inflammatory disease involving the ovary, fallopian tube, pelvic cellular tissue, and peritoneum showed odds ratios (OR) of 4.82 and 6.03 for infertility. Cervical, vaginal, and vulvar inflammation had even higher associations, with ORs of 7.79 and 6.65. Clinicians found that BV and endometritis were associated with infertility in univariate analysis, but multivariate models did not confirm these associations, indicating that other factors or confounders may mediate their effect. Comorbidities such as obesity, lipid disorders, dysthyroidism, and abortion initially showed associations with infertility, but these did not persist after adjustment. Importantly, the study did not examine specific pathogens, but referenced the role of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, and Trichomonas vaginalis as potential microbial contributors to tubal factor infertility.

Key implications

These findings reinforce the central role of female genital tract infections, particularly upper tract involvement and lower tract inflammation, in the pathogenesis of infertility. The lack of an independent association with bacterial vaginosis and endometritis after adjustment suggests that not all genital infections contribute equally to infertility risk and highlights the importance of distinguishing between associative and causal relationships. For clinicians, this underscores the need for vigilant screening, diagnosis, and management of PID and lower genital tract inflammation as part of infertility workups. The study’s population-based design adds weight to these recommendations, advocating for targeted prevention and early intervention strategies that could mitigate the risk of infertility associated with genital tract infections. These microbiome-related insights are particularly relevant for developing microbiome signatures and risk-stratification tools in reproductive medicine.