P-007 A Four Arm Prospective Randomized Control Trial to Investigate the Role of Advance Sperm Selection Techniques for Raised Sperm DNA Fragmentation Index

Abstract

Abstract Study question Role of Testicular Sperm Aspiration (TESA), Magnetic Activated Cell Sorting (MACS), Microfluidics & Daily ejaculation, to reduce raised Sperm DNA Fragmentation Index (SDF) & evaluate impact on outcomes? Summary answer Amongst the advance sperm selection methods, Microfluidic sperm sorting seems to significantly reduce the SDF and offer the best reproductive outcomes What is known already Raised SDF is known to affect the reproductive outcomes of a couple. There are various sperm processing methods/interventions shown to reduce the sperm DNA fragmentation, but their effectiveness to optimize reproductive outcomes is still debatabl. Study design, size, duration RCT approved by the Institutional Ethical Committee. IEC No.:1312/Inst/TG/2019. Couples undergoing IVF with raised SDF were randomized into four arms by computer generated randomized numbers from October 2019 to May 2022 (n = 466). Of those 373 patients recruited to, TESA (n = 129), MACS (n = 92), Microfluidics (n = 116) Daily ejaculation (n = 36) . Males with SDF > 25% & Age 25-40 yrs were included. Women>37 yrs, BMI >30 and men with Smoking, Binge alcohol, varicocele excluded. Couples with one failed IVF were offered SDF. SDF>25%was considered raised and were included in study. Participants/materials, setting, methods After Oocyte Pick Up (OPU), sample processed for ICSI and was sent for post intervention SDF. TESA done as per SOP of clinic. MACS & Microfluidics done as per instruction from manufacturer. Daily ejaculate group, patient ejaculated daily for 1week prior to OPU and at OPU, fresh ejaculate processed through density gradient. Men with high SDF, after randomization were subjected to OPU, ICSI, Blastocyst Culture, Freeze all policy and Frozen Embryo Transfer with 2blastocysts Main results and the role of chance Primary outcome-magnitude of reduction in SDF post intervention Secondary outcomes – Blastocyst Rate (BR), Implantation rates (IR), Live birth (LBR)Mean of SDF on Raw Semen Sample Vs Post Intervention Sample: TESA – 44% Vs 25.75% Microfluidics - 34.4% Vs 9.8% (p < 0.05; Significant) MACS – 32.2% Vs 27.95% Daily Ejaculation 39.37% Vs 19.66% Microfluidics seem to be beneficial intervention in significantly reducing the SDF. MACS seemed to have offered the least reduction of SDF. BR: This was comparable between all groups with no statistical significance Reproductive Outcomes for TESA, Microfluidics, MACS & Daily ejaculation: IR – 39.3% Vs 57.27% Vs 46.4% Vs 61% (p = 0.1) LBR – 60% VS 65% Vs 64% Vs 61% (p = 0.41) Miscarriage Rates and Multiple Pregnancy rates were comparable between the groups and statistically not significant. We observe that microfluidics was the best sperm processing method as it significantly reduced the DFI and had the best reproductive outcomes. It is noninvasive and can be done easily. Even though there was no statistical significance, Daily ejaculation yielded equivocal outcomes than the other 3 groups. Considering the ease, cost effectiveness and optimal reproductive outcomes Daily Ejaculation can also be offered to patients with raised SDF. Though TESA had acceptable outcomes, considering its invasiveness adequate counselling is warranted. Outcomes for MACS were guarded and be suggested with caution. Limitations, reasons for caution The sample size is small in the daily ejaculate arm as there were many dropouts. The unequal size of the arms would affect the results. So, we are continuing the randomization and intend to look into the results with equal size of the arms in the future Wider implications of the findings Published literature has shown raised SDF to be detrimental to reproductive outcomes. There is an urgent need for an efficient intervention which is safe, economical, easy to use and offers the best reproductive outcomes. Daily ejaculation, a traditional concept which is cost effective needs due consideration over other techniques. Trial registration number CTRI. Trial No.: REF/2021/05/043439