O-020 Investigating the effect of advanced sperm preparation techniques on embryo developmental potential and clinical outcomes: a network meta-analysis of randomized controlled trials
Authors: Simopoulou M , Maziotis E , Trypidi A , Charitaki D , Grigoriadis S , Pantou A , Agapitou K , Dafopoulos K , Konstantinos N , Souretis K , Pantos K , Sfakianoudis K 
Published: July 2024

Abstract

Study question
Are embryological and clinical outcomes affected when employing Magnetic-Activated Cell-Sorting (MACS), Density Gradient Centrifuge (DGC)-Zeta and Microfluidic Sperm Selection (MSS) instead of DGC and Swim-Up?

Summary answer
MACS and MSS enhance both laboratory and clinical outcomes, while DGC-Zeta seems to improve only clinical outcomes, in comparison to conventional sperm preparation techniques.

What is known already
Sperm preparation techniques have been developed to enhance sperm selection process towards improving IVF laboratory and clinical outcomes. Based on centrifugation and sperm migration, DGC and swim-up constitute the standard methods for improving sperm parameters, nonetheless disregarding molecular aspects. Certain techniques, namely MACS, DCG/Zeta and MSS have been proposed to effectively select non-apoptotic sperm with intact chromatin and high DNA integrity claiming their place in routine clinical practice. Concurring on the efficacy of these adjunct methods from the standpoint of embryo developmental dynamic and clinical outcomes is both pertinent and imperative.

Study design, size, duration
A systematic search of the literature was performed in the database Pubmed/Medline up to December 2023. Only full-text manuscripts published in English where randomization was performed on oocytes or patients were eligible. Studies reporting on semen samples obtained by surgical techniques were excluded. A total of 20 RCTs were included in this network meta-analysis. Other reported sperm preparation techniques were excluded due to the limited number of available Randomized Controlled Trials (RCTs).

Participants/materials, setting, methods
All RCTs providing results on the aforementioned sperm preparation techniques were included. The outcome measures were fertilization, cleavage, blastocyst formation, clinical pregnancy, and live-birth rates. To evaluate the network estimate both direct and indirect effects were assessed. When heterogeneity was I2=0% the fixed-effects model was preferred. In any other case the random-effects model was employed. To rank the sperm preparation techniques' efficiency, the frequentist method employing the P-score was opted for.

Main results and the role of chance
The 20 included RCTs presented with a total of 17 different designs and 8 different combinations of sperm preparation techniques. Seventeen studies reported on fertilization rate providing no statistically significant difference between the sperm preparation techniques albeit with high heterogeneity I2=69%. Regarding cleavage rate (n = 10 studies), only MACS/DGC presented with an improved outcome when compared to DGC (RR: 1.43; 95%CI: 1.16-1.76; I2=96%). MACS/DGC presented with the highest efficiency (P-Score=0.90), followed by combination of MACS/DGC/swim-up (P-Score=0.83). Both MSS and MACS/DGC presented with significantly higher blastocyst formation rate compared to DGC (MSS: RR:1.14;95%CI:1.02-1.29; MACS: RR: 1.37; 95%CI: 1.04-1.82; I2=0%). According to P-Score, MACS/DGC was presented as the most efficient technique (P-Score=0.89) followed by MSS (P-Score=0.44). Regarding clinical pregnancy rates, the 12 studies featured low heterogeneity (I2=0). MACS/DGC presented with higher clinical pregnancy rates compared to DGC (RR: 1.30; 95%CI: 1.09-1.36) and the combination of DGC/swim-up (RR: 1.55; 95%CI: 1.12-1.95). MSS presented with enhanced results compared to swim-up (RR: 1.37; 95%CI: 1.11-1.69) and DGC-Zeta presented with higher clinical pregnancy rates compared to DGC (RR: 1.76; 95%CI: 1.28-1.92). The most efficient technique was DGC-Zeta (P-Score=0.98), followed by MACS/DGC (P-Score=0.82). Regarding live-birth rates no statistically significant difference was observed, albeit high heterogeneity was observed (I2=51%).

Limitations, reasons for caution
The blastocyst formation rate and the live-birth rate outcomes should be interpreted with caution due to the limited number of RCTs. The indirect effect estimates may pose as an intrinsic limitation of the network meta-analysis, especially in cases with limited direct data.

Wider implications of the findings
This data demonstrates that the combination of MACS/DGC provided enhanced laboratory and clinical outcomes compared to conventional techniques. Investigating sperm selection techniques that assess advanced sperm characteristics rather than parameters alone is timely and essential. To concur on optimal practice further RCTs directly comparing MSS, MACS and DGC-Zeta are required.

Trial registration number
Not applicable