Artificial Oocyte Activation (AOA) Following Intracytoplasmic Sperm Injection (ICSI)

- Methods

This guideline document was generated using a systematic review and meta-analysis of the relevant literature, followed by evidence grading.

1. Registration, reporting, and patient and public involvement

Following the preregistration of the entire project on creating Egyptian IVF laboratory guidelines with the Centre for Open Science (https://doi.org/10.17605/OSF.IO/23KBU) on 21 February 2024, we proceeded to implement the appropriate methodology for studying the impact of AOA on reproductive outcomes as outlined in the guidelines. We documented the findings in accordance with the prescribed protocols. We did not involve patients or the public in any aspect of the design or implementation of this review.

2. Literature search strategy and selection

We formulated an all-encompassing search plan for the pertinent databases: Cochrane Library, PubMed, and Scopus. The search encompassed keywords and different forms of terms associated with 'AOA', 'sperm abnormalities', 'assisted reproduction', 'IVM oocytes', 'ART', 'in vitro fertilisation', 'Intracytoplasmic sperm injection', 'testicular sperm', 'fertilisation failure', 'embryo development', 'pregnancy outcomes', 'embryo implantation', 'live birth', 'neonatal outcomes', and 'birth defects'. We systematically searched for studies examining the correlation between AOA and outcomes of assisted reproduction. Our search was limited to studies conducted in English and involving human subjects. We conducted a comprehensive examination of the references cited in the selected reviews. We conducted a literature search until the date of March 1, 2024. Information regarding the literature search, reviewers, and other relevant details will be documented in separate publications that undergo peer review. The reviewers convened a meeting to establish a standardised selection strategy. Once the eligible citations were identified as duplicates, the full texts were thoroughly examined, and relevant data was extracted.

3. Synthesis of the evidence

We exclusively incorporated primary studies that contained quantitative data. We employed a random-effects model to calculate the magnitude of the association using the odds ratio (OR) across all studies. We utilised the Hartung–Knapp–Sidik–Jonkman method, which is regarded as superior when heterogeneity exists [14].
We classified the evidence using the GRADE (http://www.gradeworkingroup.org) framework, along with a more extensive set of criteria that had been previously published [15, 16]. The WHO Handbook for Guidelines employs the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to evaluate the quality of evidence, create recommendations, and present them [17]. The World Health Organisation (WHO) utilises GRADE methods due to their status as globally recognised standards for generating clear and consensus-based recommendations. Comprehensive information regarding GRADE can be found on the following websites:

■ GRADE working group: http://www.gradeworkingroup.org

■ GRADE online training modules: http://cebgrade.mcmaster.ca/

■ GRADE profile software: http://ims.cochrane.org/revman/gradepro

Table 1 Quality of Evidence in GRADE

Table 2 Significance of the four levels of evidence

Quality	Definition	Implications
High	The guideline development group is very confident that the true effect lies close to that of the estimate of the effect	Further research is very unlikely to change confidence in the estimate of effect
Moderate	The guideline development group is moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different	Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate
Low	Confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the true effect	Further research is very likely to have an important impact on confidence in the estimate of effect and is unlikely to change the estimate
Very low	The group has very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of the effect	Any estimate of effect is very uncertain