Oocyte activation for women following intracytoplasmic sperm injection (ICSI).

Background: Intracytoplasmic sperm injection (ICSI), a type of assisted reproductive technology (ART), is offered as a treatment option for male factor infertility. Over the years, the indications for ICSI have been expanded, despite uncertainty about its benefits and harms compared to the conventional method of achieving fertilisation. Artificial oocyte activation (AOA), which can be performed by chemical, electrical or mechanical intervention, has been employed during ART ICSI treatment where there has been a history of low fertilization rate or total fertilization failure, and it has been reported to improve reproductive outcomes. It is important to evaluate the clinical effectiveness and safety of AOA in women undergoing ART ICSI treatment.

Objectives: To evaluate the benefits and harms of artificial oocyte activation in women affected by infertility undergoing intracytoplasmic sperm injection treatment.

Search methods: We searched the following electronic databases: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO international Clinical Trials Registry Platform (8 August 2024). We also searched reference lists of relevant articles and contacted experts in the field.

Selection criteria: Randomized controlled trials comparing artificial oocyte activation (AOA) (chemical, electrical or mechanical interventions) versus no intervention, placebo or another method of AOA in women undergoing ART.

Data collection and analysis: We used methodological procedures as per Cochrane recommendations. We assessed the risk of bias in the included studies using ROB 2. The primary outcomes were live birth and miscarriage rates. We analyzed data using the risk ratio (RR) and a fixed-effect model. We assessed the certainty of the evidence by using GRADE criteria. We restricted the primary analyses to studies at low risk of bias.

Main results: We included a total of 20 studies, four of which were participant-based randomized trials with 743 participants. The remaining 16 were sibling-oocyte-model randomized studies. We based the main clinical findings of the current review on the participant-based RCTs, and we restricted our primary analysis to studies with a low risk of bias. Based on the one trial with 343 participants that we included in our primary analysis, the evidence is very uncertain about the effect of AOA on the live birth rate when compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.97, 95% CI 1.29 to 3.01; one trial; 343 participants). For a typical clinic with a live birth rate of 18% following ART, the addition of AOA may result in live birth rates between 24% and 55%, but this evidence is very uncertain. The evidence is very uncertain about the effect of AOA on the miscarriage rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 0.99, 95% CI 0.48 to 2.04; one trial; 343 participants). If the miscarriage rate was 9% following ART, addition of oocyte activation may result in miscarriage rates between 4% and 18%, but this evidence is very uncertain. The evidence is very uncertain about the effect of AOA on the clinical pregnancy rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.67, 95% CI 1.20 to 2.32; one trial; 343 participants). The evidence is very uncertain about the effect of AOA on the multiple pregnancy rate per participant compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 1.91, 95% CI 0.48 to 7.67; one trial; 343 participants). The evidence is very uncertain about the effect of AOA on the total fertilization failure rate compared to conventional ICSI without AOA in women undergoing ART ICSI (RR 0.05, 95% CI 0.01 to 0.40; one trial; 343 participants). When we stratified our analysis according to various infertility factors, we found low-certainty evidence that in couples undergoing ICSI treatment who have had a history of low or no fertilization, AOA may help improve the live birth rate while making little or no difference to the miscarriage rate. Further research is needed to confirm or refute this finding. None of the trials reported congenital anomalies (birth defects) as an outcome. Lack of short- or long-term safety data is an important limitation of the review and of the trials in this field. We did not find any trials that compared two different methods of oocyte activation.

Authors' conclusions: We are uncertain about the effect of AOA on the live birth and miscarriage rates in women undergoing ART ICSI. In the subpopulation of those who have had a previous history of low or no fertilization, AOA may result in an increase in the live birth rate when compared to conventional ICSI without AOA, while making little or no difference to the miscarriage rate. There was considerable variation in the protocols used for chemical AOA, which affects the generalizability of the findings. Due to the very low to low certainty of evidence, the results should be interpreted with caution.