Early Prevention and Precision Management of Female Fertility Decline

Development and Evaluation of a Precision Prevention Strategy for Early Female Fertility Decline Based on OvaRePred-Plus: A Multicenter Cluster Randomized Controlled Trial

Female fertility decline has become an important public health issue in China, with a substantial proportion of women of reproductive age experiencing reduced ovarian reserve. However, effective tools for early identification and large-scale prevention of fertility impairment in the general population are still lacking.

This study aims to develop and evaluate a precision prevention strategy for early female fertility decline based on the OvaRePred-Plus model, which integrates ovarian reserve markers, lifestyle factors, and reproductive health indicators. A multicenter, cluster randomized controlled trial will be conducted across six medical centers in China, enrolling women aged 20-40 years identified as having early signs of fertility decline.

Participants will be allocated to either an intervention group receiving a comprehensive health management program (including dietary optimization, nutritional supplementation, physical activity, and sleep improvement) or a control group receiving routine clinical care. The intervention will last for 12 weeks.

The primary outcome is the change in fertility score assessed by the OvaRePred-Plus model. Secondary outcomes include changes in ovarian reserve markers (e.g., AMH), menstrual status, ultrasound parameters, and reproductive outcomes.

This study is expected to provide evidence for a scalable and cost-effective strategy for early prevention and management of female fertility decline.

Inclusion Criteria:

• Women aged 20-40 years
• Diagnosed with infertility or planning assisted reproductive treatment
• Regular menstrual cycles (21-35 days)
• Willing to participate in a 12-week lifestyle intervention program
• Able to provide written informed consent

Exclusion Criteria:

• Known chromosomal abnormalities or genetic disorders affecting fertility
• History of ovarian surgery or severe ovarian damage
• Diagnosed endocrine disorders affecting reproduction (e.g., uncontrolled thyroid disease, hyperprolactinemia)
• Severe systemic diseases (e.g., cardiovascular, hepatic, renal diseases)
• Current pregnancy or breastfeeding
• Use of hormonal medications or supplements affecting ovarian function within the past 3 months
• Participation in another clinical trial within the past 3 months