Serum Leptin Levels in Early Pregnancy and Their Association with Unexplained Recurrent Pregnancy Loss: A Prospective Case–Control Study

Background: Recurrent pregnancy loss (RPL) represents a significant reproductive health problem with multifactorial and often unexplained etiology. Recent evidence suggests that leptin, a key metabolic and reproductive hormone, may play an important role in early pregnancy maintenance and placental development. Objective: This study aimed to evaluate serum leptin levels in women with unexplained early recurrent pregnancy loss compared with women with previous normal pregnancies and to assess the potential prognostic value of leptin for pregnancy continuation. Methods: A prospective case–control study was conducted at the Gynecological and Pediatric Hospital in Kirkuk, Iraq, from January to November 2025. A total of 120 pregnant women were enrolled and divided into two groups: 60 women with a history of recurrent pregnancy loss and 60 healthy pregnant controls. All participants were aged 20–35 years and had viable singleton pregnancies between 5 and 12 weeks of gestation. Comprehensive clinical, ultrasonographic, genetic, and laboratory assessments were performed to exclude known causes of miscarriage. Serum leptin levels were measured using enzyme-linked immunosorbent assay. Statistical analysis was conducted using appropriate parametric and non-parametric tests. Results: Women with RPL demonstrated significantly higher serum leptin levels at 5–8 weeks (12.53 ± 3.62 pg/ml) compared with controls (6.26 ± 3.31 pg/ml; p < 0.001). At 10–12 weeks, leptin levels increased further in the RPL group (18.38 ± 5.36 pg/ml vs. 7.23 ± 3.94 pg/ml; p < 0.001). Elevated leptin levels were detected in 68.33% and 76.67% of RPL cases at 5–8 and 10–12 weeks, respectively. Leptin concentrations increased significantly with advancing gestation and with the number of previous miscarriages (p < 0.01). Receiver operating characteristic analysis showed good diagnostic performance of leptin for predicting RPL (accuracy: 78.57%). Conclusion: Serum leptin levels are significantly elevated in women with unexplained recurrent pregnancy loss during early pregnancy and increase progressively with gestational age and miscarriage history. These findings suggest that leptin dysregulation may contribute to the pathophysiology of RPL and may serve as a useful biomarker for early risk assessment.