Environmental exposures and pregnancy loss: A critical gap analysis for unexplained recurrent pregnancy loss

Recurrent pregnancy loss (RPL), defined as two or more pregnancy failures, affects approximately 1-3% of reproductive-age couples worldwide. Despite advances in clinical evaluation, 50-60% of RPL cases remain unexplained, referred to as unexplained recurrent pregnancy loss (URPL), leaving a substantial proportion of patients without an identifiable etiology or evidence-based preventive strategies. Emerging evidence suggests that environmental exposures may represent an underrecognized yet modifiable contributor to URPL; however, the existing literature remains fragmented and methodologically flawed by the homogenization of pregnancy loss. This narrative review and critical gap analysis evaluates the epidemiological and mechanistic evidence linking a broad spectrum of environmental exposures to pregnancy loss. We systematically map the evidence base across ambient air pollutants, heavy metals, endocrine-disrupting chemicals, pesticides, and lifestyle/occupational hazards, with a strict focus on isolating URPL-specific data from general miscarriage cohorts. We further examine the principal biological mechanisms through which these exposures precipitate pregnancy loss, including oxidative stress, maternal immune dysregulation, epigenetic reprogramming, endocrine disruption, and placental vascular impairment. This critical gap analysis reveals that while environmental pollutants consistently increase the risk of sporadic pregnancy loss, URPL-specific evidence remains profoundly scarce. We highlight the urgent need to address the pervasive conflation of sporadic and recurrent loss in existing cohorts, call for future prospective studies prioritizing mixture-based exposures, and propose a forward-looking, non-judgmental framework for preconception wellness that mitigates the psychological burden on URPL patients.