# ICSI with surgically retrieved sperm in azoospermia: protocol for a systematic review and meta-analysis of reproductive, perinatal, long-term, and paternal outcomes

## TL;DR

This study will compare outcomes of ICSI using surgically retrieved sperm versus ejaculated sperm in men with azoospermia, focusing on reproductive, perinatal, and long-term effects.

## Contribution

A systematic review and meta-analysis protocol to evaluate the efficacy and safety of ICSI with surgically retrieved sperm in azoospermia patients.

## Key findings

- The study will assess live birth rates and other outcomes in ICSI using surgically retrieved sperm.
- It will evaluate perinatal and long-term offspring outcomes to address current evidence gaps.
- The protocol follows PRISMA-P and PRISMA 2020 guidelines for systematic review and meta-analysis.

## Abstract

Azoospermia affects ~ 1% of men and represents a major cause of severe male infertility. Intracytoplasmic sperm injection (ICSI) with surgically retrieved sperm from the testis or epididymis enables biological fatherhood in obstructive (OA) and non-obstructive azoospermia (NOA) patients. However, comparative studies versus ejaculated sperm remain fragmented, particularly for neonatal and long-term offspring outcomes. This study aims to address the existing evidence gap regarding the outcomes of ICSI cycles using surgically retrieved versus ejaculated sperm in men with azoospermia by evaluating reproductive, perinatal, long-term offspring, and paternal outcomes.

A systematic review and meta-analysis will be conducted following the PRISMA-P and PRISMA 2020 guidelines. Eligible studies will include randomized and non-randomized comparative designs of ICSI using surgically retrieved versus ejaculated sperm as single-arm studies for outcomes not applicable to ejaculated sperm. The primary outcome is live birth per oocyte pick-up or per started cycle. The secondary outcomes include reproductive, perinatal, long-term offspring, and paternal outcomes. Searches will be conducted in PubMed, Embase, Scopus, CENTRAL, Web of Science, and ProQuest, supplemented by trial registries, conference proceedings, and grey literature from 1990 onward. The risk of bias will be assessed with RoB 2 and ROBINS-I; certainty of evidence will be assessed with GRADE. Random-effects meta-analyses with restricted maximum likelihood estimation and Hartung-Knapp-Sidik-Jonkman adjustment will be applied, with rare-event models explored as sensitivity analyses.

This protocol describes a systematic approach to evaluate the efficacy and safety of ICSI via surgically retrieved sperm compared with ejaculated sperm, with a particular focus on filling current evidence gaps in perinatal, offspring, and paternal outcomes. The results will contribute to evidence-based counseling, clinical practice, and guideline refinement.

PROSPERO CRD420251142427.

The online version contains supplementary material available at 10.1186/s13643-025-03021-9.