Clinical Characteristics and Associated Risk Factors for Diminished Ovarian Reserve among Chinese Women: A Matched Case-Control Study

Fan Zhao¹Penghao Li²Ruobing Mei^3,4,5Chongbi Huang¹Dongsen Hu²Tony Cheung⁴Yajiao Lu¹Pulin Luo²Lucas Gonzalo Garay⁴Ying Yang¹Dandan Zhao¹Juan Yang²Jing Li^1*Leesa Lin^3,4,5

• ¹Sichuan University, Chengdu, China
• ²Sichuan Jinxin Women's and Children's Hospital, Chengdu, China
• ³London School of Hygiene & Tropical Medicine, London, United Kingdom
• ⁴Laboratory of Data Discovery for Health, Hong Kong, Hong Kong, SAR China
• ⁵The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China

Background: Diminished ovarian reserve (DOR) has emerged as a significant reproductive challenge and a broader societal concern. Most previous studies have focused on ovarian reserve markers, while limited research has examined DOR as a primary outcome, and the potential association between TORCH infections (toxoplasmosis, others, rubella, cytomegalovirus, herpes) and DOR risk remains unclear. Methods: A matched case–control study was conducted among women aged 20–47 years who sought assisted reproductive technology at a maternity hospital in Sichuan, China, between January 2022 and August 2024. DOR was diagnosed according to the Consensus on clinical diagnosis and management of diminished ovarian reserve from China. Age-matched controls (1:1) with normal ovarian reserve were selected. Conditional logistic regression was used to identify factors associated with DOR, with multivariable models adjusting for confounders. Subgroup analyses by age and body mass index (BMI) were conducted to examine robustness and effect modification. Results: A total of 3,751 DOR cases were matched to 3,751 controls (median age: 36 years). DOR group had significantly higher FSH, E2, and LH levels (P < 0.01), and lower AFC, AMH, PRL, and T levels (P < 0.001) compared to controls. Multivariable logistic regression showed that non-Han ethnicity (OR = 1.278, 95% CI: 1.115–1.466), manual labor (OR = 1.181, 95% CI: 1.002–1.392), obesity (OR = 1.316, 95% CI: 1.044–1.660), light menstrual flow (OR = 1.262, 95% CI: 1.111–1.435), and T. gondii infection (OR = 2.292, 95% CI: 1.683–3.122) were independently associated with DOR. In women aged 20–35 years, ≥2 pregnancies (OR = 0.712, 95% CI: 0.615–0.824), and infections with T. gondii (OR = 23.750, 95% CI: 13.330-42.316), CMV (OR = 8.189, 95% CI: 5.821-11.521), and RV (OR = 8.132, 95% CI: 5.806-11.390) were strongly associated with DOR, with no such associations observed in the 36–47 years group. Significant age interactions were detected (P < 0.05). Conclusion: Ethnicity, obesity, menstrual flow, pregnancy history, and TORCH infections were significantly associated with DOR, with age-related effect modification observed for pregnancy history and infections. Prospective studies are needed to elucidate the underlying mechanisms, particularly the role of infections and immune response.