An exploratory single arm study to evaluate the role of an Ayurvedic treatment protocol as a prerequisite for in vitro fertilization in women with Diminished Ovarian Reserve incorporating multi-omics approaches: Study protocol

Anjaly Muraleedharan^1*Muralidharan Vanuopadath^2*Avani Pillai³Bipin G Nair²Hemavathi Shivapura Krishnarajabhatt¹Chithra Ramachandran⁴

• ¹Department of Stri roga and Prasuti tantra, Amrita School of Ayurveda, Amrita Vishwa Vidyapeetham, Kollam 690 525, Kerala, India, Kollam, India
• ²School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690 525, Kerala, Kollam, India
• ³Department of Reproductive Medicine and surgery, Amrita Institute of Medical Sciences, Kochi 682 041, Kerala, India, Kochi, India
• ⁴Department of Obstetrics and Gynaecology, Amrita Institute of Medical Sciences, Kochi 682 041, Kerala, India, Kochi, India

Introduction: Ovarian reserve depicts the quality and quantity of oocytes remaining in the ovaries and gives an idea about ovarian function at a given time. Because of aging, ovarian reserve diminish physiologically. However, many women face a non-physiologic reduction of ovarian reserve, irrespective of age. To date, standard-of-care treatment options are not available to treat diminished ovarian reserve (DOR). Studies shows that DOR patients mostly undergo in vitro fertilization (IVF) with donor cycles. Hence, identifying effective treatment modalities for DOR is an area of great clinical relevance. This trial will investigate the role of an Ayurvedic treatment protocol in DOR patients prior to IVF. Reports suggest that the factors influencing oocyte maturation can be determined through multi-omics analysis of the follicular fluid. However, the impact of Ayurvedic interventions in improving therapeutic outcomes has yet to be explored in detail. Hence this study also aims to explore whether therapeutic targets can be identified through multi-omics analysis of the follicular fluid collected from the participants after Ayurvedic treatment. Materials and methods: An open label single arm trial will be conducted to explore the role of an Ayurveda treatment protocol as a prerequisite for IVF in women with DOR. Forty women diagnosed with DOR satisfying eligibility criteria will be recruited to the study. Out of them, thirty participants will be undergoing Ayurveda treatment prior to their next IVF, and ten participants will be assigned to control group for follicular fluid analysis. Within subject change in serum Anti-Mullerian hormone and antral follicle count will be the primary outcomes evaluated. The multiomics analysis of follicular fluid will be done in 20 participants recruited to the study (treatment group 10 and control group 10). Discussion: This multidisciplinary exploratory clinical trial will be the first study to explore the role of an Ayurvedic treatment protocol in managing DOR. The multi-omics approaches will be helpful in identifying potential biomarkers associated with treatment response. The information gained through the study might be useful in planning a safe and feasible pre-conception care for DOR patients undergoing IVF. Clinical Trial Registration: ctri.nic.in, identifier: CTRI/2023/11/059872 Registered on 15/11/2023