Abstract Study question What is the effect of intra-ovarian platelet rich plasma(PRP) on live birth rate(LBR) in POSEIDON-3 versus POSEIDON-4 group? Summary answer Intra-ovarian PRP improves the live birth rate in low prognosis patients irrespective of age, this giving them hope of their own biological child. What is known already With the emerging regenerative medicine promising various treatment modalities, PRP is considered a novel therapeutic option. Various anecdotal cases have been reported, demonstrating successful pregnancy outcomes after the PRP treatment. But the data still remains elusive, especially for women of Asian ethnicity, who have a rapid decline in ovarian reserve when compared to the Caucasian population. Consequently, we attempt to compare the effects of autologous PRP on LBR in POSEIDON-3 versus POSEIDON-4 groups. Study design, size, duration After ethical approval, a prospective interventional study was conducted at ART Centre, Department of Obstetrics and Gynaecology of a tertiary care institute during a period from July 2020 to April 2022. 72 women between the ages of 20 and 40 years with idiopathic poor ovarian reserve (AMH 1.2<ng/ml; AFC<5) and a normal adequate uterine cavity were enrolled, and those with a history of radiotherapy, chemotherapy, endometriosis, or ovarian/tubal surgery were excluded. Participants/materials, setting, methods Women between 20-40 years of age with low ovarian reserve received 1.5 ml-PRP prepared from 30 ml venous-blood, was instilled in each ovarian stroma between day 6-10 of menses. Patients were followed up for 3-consecutive months to assess ovarian-reserve parameters (FSH, AMH, AFC). Patients showing significant improvement (AFC>5) were enrolled in antagonist-IVF cycles and categorised into two groups: POSEIDON-3 vs 4 groups. Paired/signrank test and Independent/ranksum test compared clinical parameters between the two groups. Main results and the role of chance The mean age and BMI of the recruited women were 31.7 + 4.2 years and 24.89 + 3.73 kg/m2. Out of 72 participants, 16.67% responded in 1st month of follow-up(AFC: 5 vs 3,p<0.001), 43% in 2nd month(AFC: 6 vs 3,p<0.001)(AMH: 1.02 vs 0.99,p=0.02) and 12.5% in 3rd month(AFC:4 vs 3,p<0.001)(AMH:0.89 vs 0.85,p=0.01). 20 participants showed no improvement in AFC, AMH, or FSH. Excluding one, 43 underwent antagonist cycle. Despite the evident age-difference between the POSEIDON-3 and 4 groups(29.6 vs 36.6 years), the POSEIDON-4 group women were more obese (27.4 + 1.30 vs 23.3 + 0.49,p=0.0007). Although the number of oocytes retrieved was similar (6.35 + 1.83 vs 5.75 + 1.35,p=0.21), the E2 levels on the day of trigger were significantly low in POSEIDON-4 patients (1082.33 + 273.03 vs 1727.16 + 867.79,p=0.01). Also, the dose of HMG requirement was higher in POSEIDON-4 (1450 + 96.53 vs 1190.3 + 66.49,p=0.04) thus depicting the effect of advanced age. Otherwise, there was no significant difference in dose of rFSH requirement (2705.6 + 48.93 vs 2737 + 54.74,p=0.71), fertilisation rate (60.86% vs 57.86%,p=0.66), biochemical pregnancy rate (30.7% vs 29.03%,p=0.78), CPR (25% vs 25.8%,p=0.95) and LBR (22.6% vs 16.66%,p=0.66) between the two-groups. No adverse events reported. Limitations, reasons for caution Our study was a non-randomized study with no control/sham, arm as doing so would be unethical and impose a financial burden on the patients with no guaranteed clinical success. Wider implications of the findings With the impetus to provide a biological child to the women with poor ovarian reserve, ovarian-rejuvenation with PRP seems to be a promising treatment. It can be concluded that PRP improves the ovarian reserve which translates into better reproductive outcomes in women who were planned and counselled for donor-oocyte IVF. Trial registration number Not applicable