Multifactorial determinants of infertility: a case control study integrating clinical, hormonal, nutritional, genetic and lifestyle factors in 664 couples

Background: Infertility is a multifactorial reproductive disorder influenced by male, female, genetic, infectious, nutritional and lifestyle factors. Despite advances in reproductive medicine, studies integrating multiple determinants of infertility with comprehensive evaluation remain limited. The present study aimed to evaluate the multifactorial determinants associated with infertility among couples attending a tertiary fertility centre. Methods: This hospital-based case–control study included 412 infertile couples and 252 fertile couples. Participants underwent detailed clinical and laboratory evaluation. This included complete blood counts, hormonal profiling (follicle-stimulating hormone, luteinizing hormone, anti-Müllerian hormone, prolactin, thyroid-stimulating hormone, estradiol and progesterone), semen analysis, infectious disease screening, nutritional assessment (vitamin D, vitamin B12 and ferritin), imaging studies and selected genetic investigations. Associations between infertility risk factors were analysed using the chi-square test. Odds ratios with 95% confidence intervals were calculated and a p-value<0.05 was considered statistically significant. Results: Among infertile couples, primary infertility was observed in 77.2% and secondary infertility in 22.8%. Male factors included abnormal semen parameters in 30.6% of cases. Smoking (odds ratio 3.8, 95% confidence interval 2.2–6.4, p<0.001) and increased sperm DNA fragmentation (odds ratio 4.5, 95% confidence interval 2.0–9.7, p<0.001) were significantly associated with infertility. Among female partners, low ovarian reserve (anti-Müllerian hormone <1.1 ng/mL) was observed in 174 women (42.2%) and was significantly associated with age ≥30 years. Additional contributing factors included endometriosis (18.9%), tubal blockage (14.6%), thyroid dysfunction (9.2%) and hyperprolactinemia (6.3%). Nutritional deficiencies were common, particularly vitamin B12 deficiency (70.9%), vitamin D deficiency (45.4%) and iron deficiency (41.0%). Conclusions: Infertility is a complex condition resulting from multiple interacting determinants including male reproductive factors, diminished ovarian reserve, gynecological disorders, nutritional deficiencies and lifestyle influences. Comprehensive evaluation of both partners is essential for early identification of modifiable risk factors and improved infertility management.