Pregnancy and perinatal complications in untreated subfertile couples following singleton spontaneous conception: a narrative review.
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BACKGROUND: Literature shows that ovulation induction, intrauterine insemination, and assisted reproductive technology are independently associated with increased risks for pregnancy, perinatal, and childhood health complications. However, the independent association of couples’ subfertility/infertility with these risks has not been yet isolated precisely. This narrative review aims to ascertain the independent association of female and male reproductive disorders displayed by untreated subfertile couples with pregnancy, perinatal, and childhood complications following singleton spontaneous conception. METHODS: An English-language scientific literature search indexed in PubMed database on publications from inception to August 2025. The studies were identified using a combination of search terms related to female and male reproductive disorders, spontaneously conceived singletons, hormonal treatment, and pregnancy, perinatal, and childhood complications. RESULTS: Polycystic ovary syndrome manifests as the reproductive disorder with the highest number of associated pregnancy and perinatal complications. In particular, gestational diabetes mellitus, pregnancy-induced hypertension/eclampsia/preeclampsia, and low birthweight. Endometriosis is also associated with preeclampsia, whereas diminished ovarian reserve and low semen quality are associated with miscarriage. The level of certainty in the estimate of the effect sizes in the reviewed studies is rated either low or low to moderate. CONCLUSION: This narrative review evidences the independent association of female and male reproductive disorders exhibited by untreated subfertile couples with pregnancy and perinatal complications following singleton spontaneous conception. However, the literature search has not found studies analyzing the potential health complications that may exhibit the resultant naturally-conceived singletons during childhood. Further large prospective, multicenter cohort studies adjusted for important confounding variables, with strict definitions of subtypes/phenotypes within each reproductive disorder, well-defined control group consisting of only fertile women/men, and experimental groups of women/men displaying particular reproductive disorders without male/female factor-co-pathologies are warranted to fill this knowledge gap.