P–271 Should intracytoplasmic sperm injection (ICSI) of delayed mature oocytes become a routine practice in the IVF Laboratory?
Authors: Elkhatib I , Munck N D , Abdala A , Arnanz A , Eldamen A , Melado L , Lawrenz B , Bayram A , Fatemi H 
Published: August 2021

Abstract

Study question
Do delayed mature oocytes result in similar euploid blastocyst rates as their immediate mature sibling oocytes?

Summary answer
Once a blastocyst is obtained, delayed mature oocytes have similar euploid rates compared to immediate mature oocytes.

What is known already
Intracytoplasmic sperm injection (ICSI) of metaphase II oocytes few hours post oocyte retrieval is standard practice in IVF laboratories. Immature metaphase I (MI) and prophase I (GV) oocytes are usually discarded. Immature oocytes may mature overnight, after which ICSI can be performed. Studies demonstrated lower fertilization and blastulation rates for these delayed mature oocytes. However, live births have been reported from blastocysts transferred. The evidence available is not compelling, since most of the studies had either low sample size, no preimplantation genetic testing for aneuploidies (PGT-A), or the outcome was not compared to sibling MII oocytes at time of denudation.

Study design, size, duration
A single-center retrospective sibling oocyte study was performed between January 2019 and December 2020 at ART Fertility clinics Abu Dhabi, UAE. A total of 345 PGT-A cycles, with at least one delayed mature oocyte inseminated by ICSI, were included: 2506 immediate mature oocytes and 669 delayed mature oocytes.

Participants/materials, setting, methods
Following controlled ovarian stimulation, MII oocytes at the time of denudation were inseminated by ICSI/IVF (immediate mature). Immature oocytes (MI/GV) were cultured for 16–24 hours in fertilization medium and injected the next day if matured (delayed mature). Trophectoderm biopsy was performed on day 5/6/7 and samples were subjected to Next Generation Sequencing to screen the ploidy state of the blastocyst.

Main results and the role of chance
The 345 controlled ovarian stimulation cycles resulted in the insemination of 2506 MII oocytes on the day of oocyte retrieval (Day0) and 669 delayed mature oocytes on day 1. Normal fertilization rate was significantly higher in the immediate mature oocytes compared to delayed mature oocytes (68% vs 56%, p &lt; 0.0001). Similarly, the usable blastocyst rate was significantly higher in immediate mature oocytes (59% vs 19%, p &lt; 0.0001). On day 5 of development, a significantly higher-good quality blastocyst formation rate was obtained from immediate mature oocytes (65% vs 27%, p &lt; 0.0001). The rate of good quality blastocyst on the day of biopsy was significantly higher in the immediate mature oocytes group (76% vs 62%, p &lt; 0.015).
Fisher’s Exact Test was performed to compare the euploid rate of blastocysts biopsied on day 5/6/7 originating from immediate mature oocytes or sibling delayed mature oocytes. The euploid potential of blastocyst biopsied showed no significant difference between the two groups (p = 0.388).

Limitations, reasons for caution
The timing of MI/GV oocytes transition to MII stage was not recorded since the incubation was done in a benchtop incubator. Furthermore, the same sperm sample was used to inseminate immediate and delayed mature oocytes, which might contribute to the compromised embryo development due to increased sperm DNA fragmentation.
Wider implications of the findings: Insemination of delayed mature oocytes by ICSI, should be considered as a tool to increase patients’ chances of obtaining a euploid embryo. Especially in cases where low yield of euploid embryos is expected.

Trial registration number
Not applicable