Summary of Intracytoplasmic Sperm Injection (ICSI) Overview

## Introduction Rescue intracytoplasmic sperm injection (r-ICSI) is an emergency laboratory procedure used to salvage conventional in‑vitro fertilization (IVF) cycles that show total or near‑total fertilization failure. The goal is to rescue oocytes that did not show normal fertilization after standard insemination by performing ICSI at a later timepoint and then transferring embryos, usually after cryopreservation and frozen embryo transfer (FET), to maximize outcomes. > Definition: Rescue ICSI (r-ICSI) is the performance of ICSI on oocytes that have not fertilized after conventional IVF, typically done late (e.g., 15–24 h post-insemination) to salvage cycles with fertilization failure. ## Why rescue ICSI matters - It prevents cycle cancellation and can convert an otherwise lost IVF attempt into a pregnancy opportunity. - Recent data suggest substantially improved outcomes when r-ICSI–derived embryos are cryopreserved and transferred as frozen blastocysts rather than transferred fresh. ## Timing and indications ### Typical criteria used in clinical practice - The patient has >4 metaphase II (MII) oocytes showing no signs of fertilization at ~18 h post insemination, and/or - A fertilization rate of <15% per mature oocyte. - If four or more normally fertilized oocytes exist, r-ICSI is usually not performed. > Note: Many centers now freeze all r-ICSI embryos to maintain endometrial synchrony and optimize implantation potential. ## Procedure overview (stepwise) 1. Identify fertilization failure at the usual fertilization check (commonly ~16–20 h after insemination). 2. Select MII oocytes that show no signs of fertilization (no two pronuclei). 3. Perform ICSI on those oocytes (late r-ICSI often at 15–24 h post-insemination). 4. Culture embryos to blastocyst when possible. 5. Cryopreserve embryos and plan a subsequent frozen embryo transfer (FET) for optimal endometrial synchrony. ## Outcomes: what the literature shows - A systematic review/meta-analysis pooling several studies (total ET = 483 in the table) found an overall clinical pregnancy proportion per embryo transfer after frozen cycles following r-ICSI of about $0.36$ with 95% CI $[0.31;0.41]$ and low heterogeneity (I^2 = 0%). - In a large single‑center series (Human Reproduction, 2023), frozen blastocyst transfers of r-ICSI embryos achieved: - Clinical pregnancy rate for all frozen blastocyst transfers: $54.7\%$ (75/137), - Implantation rate: $54.5\%$ (84/154), - Live birth rate: $46.7\%$ (64/137). - Total frozen transfers: 147; combined live birth rate for all frozen r-ICSI transfers: $43.5\%$ (64/147). - Fresh transfers of r-ICSI embryos historically show reduced live birth rates compared to standard ICSI, but FET outcomes after r-ICSI appear comparable to non-r-ICSI FET in some cohorts. Fun fact: Studies report live birth rates after frozen r-ICSI blastocyst transfer approaching $40\text{--}46\%$, markedly higher than older reports based on fresh cleavage-stage transfers. ## Predictors of success - Younger female age is consistently associated with higher chance of pregnancy after r-ICSI. - Embryo quality (higher cumulative embryo score) predicts better outcomes. - Performing blastulation and selection before freezing improves implantation and live birth rates. ## Economic considerations - Older cost-effectiveness work indicated r-ICSI could reduce cost per live birth by about 25% compared with cancelling cycles when evaluated on fresh cleavage-stage transfers. - With improved FET outcomes (higher live birth rates), the cost-effectiveness of freezing and FET after r-ICSI is likely even more favorable, although detailed up-to-date health‑economic modelling is recommended for each program. ## Practical examples and real-world application - Example 1: A patient has 10 retrieved oocytes, 8 MII. At 18 h, none show normal fertilization. The clinic performs r-ICSI on the 8 MII oocytes, cultures to blastocyst, freezes 4 good blastocyst