How to identify patients who would benefit from delayed-matured oocytes insemination: a sibling oocyte and ploidy outcome study
Authors: Elkhatib I , Nogueira D , Bayram A , Abdala A , Del Gallego R , Melado L , De Munck N , Lawrenz B , Fatemi H 
Published: August 2023

Abstract

STUDY QUESTION
Which patients might benefit from insemination of delayed-matured oocytes?

SUMMARY ANSWER
Delayed-matured oocytes had a ≥50% contribution to the available cohort of biopsied blastocysts in patients with advanced maternal age, low maturation, and/or low fertilization rates.

WHAT IS KNOWN ALREADY
Retrieved immature oocytes that progress to the MII stage in vitro could increase the number of embryos available during ICSI cycles. However, these delayed-matured oocytes are associated with lower fertilization rates and compromised embryo quality. Data on the ploidy of these embryos are controversial, but studies failed to compare euploidy rates of embryos derived from delayed-matured oocytes to patients’ own immediate mature sibling oocytes. This strategy efficiently allows to identify the patient population that would benefit from this approach.

STUDY DESIGN, SIZE, DURATION
This observational study was performed between January 2019 and June 2021 including a total of 5449 cumulus oocytes complexes from 469 ovarian stimulation cycles, from which 3455 inseminated matured oocytes from ICSI (n = 2911) and IVF (n = 544) were considered as the sibling controls (MII-D0) to the delayed-matured oocytes (MII-D1) (n = 910). Euploidy rates were assessed between delayed-matured (MII-D1) and mature sibling oocytes (MII-D0) in relation to patients’ clinical characteristics such as BMI, AMH, age, sperm origin, and the laboratory outcomes, maturation, fertilization, and blastocyst utilization rates.

PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 390 patients undergoing IVF/ICSI, who had at least one metaphase I (MI) or germinal-vesicle (GV) oocyte on the day of oocyte collection (Day 0), which matured in 20–28 h after denudation were included. MI and GV oocytes that matured overnight were inseminated on the following day (Day 1, MII-D1) by ICSI. Only cycles planned for preimplantation genetic testing for aneuploidy using fresh own oocytes were included.

MAIN RESULTS AND THE ROLE OF CHANCE
Fertilization (FR) and blastocyst utilization rates were significantly higher for MII-D0 compared to delayed-matured oocytes (MII-D1) (69.5% versus 55.9%, P &lt; 0.001; and 59.5% versus 18.5%, P &lt; 0.001, respectively). However, no significant difference was observed in the rate of euploid embryos between MII-D0 and MII-D1 (46.3% versus 39.0%, P = 0.163). For evaluation of the benefit of inseminating MI/GV oocytes on D1 per cycle in relation to the total number of biopsied embryos, cycles were split into three groups based on the proportion of MII-D1 embryos that were biopsied in that cycle (0%, 1–50%, and ≥50%). The results demonstrate that patients who had ≥50% contribution of delayed-matured oocytes to the available cohort of biopsied embryos were those of advanced maternal age (mean age 37.7 years), &lt;10 oocytes retrieved presenting &lt;34% maturation rate, and &lt;60% fertilization rate. Every MII oocyte injected next day significantly increased the chances of obtaining a euploid embryo [odds ratio (OR) = 1.83, CI: 1.50–2.24, P &lt; 0.001] among MII-D1. The odds of enhanced euploidy were slightly higher among the MII-D1-GV matured group (OR = 1.78, CI: 1.42–2.22, P &lt; 0.001) than the MII-D1-MI matured group (OR = 1.54, CI: 1.25–1.89, P &lt; 0.001). Inseminating at least eight MII-D1 would have &gt;50% probability of getting a euploid embryo among the MII-D1 group.

LIMITATIONS, REASONS FOR CAUTION
ICSI of MII-D1 was performed with the fresh or frozen ejaculates or testicular samples from the previous day. The exact timing of polar body extrusion of delayed-matured MI/GV was not identified. Furthermore, the time point of the final oocyte maturation to MII for the immature oocytes and for the oocytes inseminated by IVF could not be identified.

WIDER IMPLICATIONS OF THE FINDINGS
The results of this study might provide guidance to the IVF laboratories for targeting the patient’s population who would benefit from MII-D1 ICSI without adhering to unnecessary costs and workload.

STUDY FUNDING/COMPETING INTEREST(S)
No external funding was received for this study. There are no conflicts of interest to be declared for any of the authors. There are no patents, products in development, or marketed products to declare.

TRIAL REGISTRATION NUMBER
N/A.