P–239 In vitro maturation of human oocytes: a systematic review and data analysis
Authors: Nikiforov D , Pors S E , Cadena. Moreno J , Ydin. Andersen C 
Published: August 2021

Abstract

Study question
Based on published studies, how effective is in vitro maturation (IVM) in different patient groups, and how does the maturation rate correlate with culture conditions?

Summary answer
Clinical IVM is most effective when patients receive only hCG trigger prior to oocyte collection. Multiple additional parameters influencing the outcome were identified.

What is known already
Despite being used for more than fifty years, the overall efficacy of human IVM has not yet been determined, and results are often conflicting. Indeed, IVM is still perceived skeptically by many embryologists and doctors and not widely used in clinical practice. This review aims to collect all available data in the literature regarding the efficacy of IVM analyzing characteristics of patients, treatment, or laboratory conditions that may influence the MII-rate (MR). Study design, size, duration: A systematic search was performed in the PubMed database following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to studies in the English language published before October 2020 using the following keyword: “oocyte in vitro maturation».

Participants/materials, setting, methods
Inclusion criteria for studies were: reporting data obtained on immature human oocytes, which transitioned to the MII stage after IVM. The requirement was that the numbers of cultured and matured oocytes were reported. If available, additional data were collected including patients’ characteristics (for example PCOS), hormonal stimulation prior to the procedure (administration of some FSH or hCG trigger or both), oocyte freezing before or after IVM, type of culture medium and supplements, etc.

Main results and the role of chance
A total of 350 publications were selected from 6866 search results, 436 abstracts, and 422 full read articles. Selected studies cover 21153 patients and 157420 immature oocytes cultured. It has been demonstrated that oocytes collected in vivo from adult, non-PCOS patients, who received only hCG trigger prior to the procedure had a statistically higher MII rate (66%) than oocytes from patients who received no gonadotropins or some FSH, or a combination of some FSH and hCG trigger (59%, 60% and 58% respectively). The same was valid for PCOS patients: MR in the trigger only cohort (66%) was significantly different from other cohorts. MR for in vivo collected oocytes (61%) from adult non-PCOS patients was significantly different from ex vivo collected oocytes (33%). MI stage oocytes at the moment of collection matured with a statistically higher rate (N = 4322, 73%), than GV oocytes (N = 3328, 54%). When in vitro matured oocytes were vitrified, their average survival rate was 81% (data from 50 studies on 1701 oocytes). Additionally, immature oocytes survived vitrification with a 75% rate (data from 30 studies on 4457 oocytes). Overall, ICSI fertilization rate for IVM oocytes was 69% (N = 59914). A total of 747 babies born from IVM were reported.

Limitations, reasons for caution
Among selected publications only 2 were randomized controlled trials and therefore the main challenge of this review is striking differences in setups among included studies. However, despite not being a meta-analysis, this study calculated MR for the most frequent treatment modalities and additional individual factors, which might influence MR.
Wider implications of the findings: This review provides data regarding IVM efficiency in different cohorts of patients, performed under different culture conditions. Additional laboratory parameters influencing MR have been identified. Based on this new data, target groups benefiting the most were identified, and prognosis regarding the success of their treatment with IVM might be estimated.

Trial registration number
n/a