P-251 Cumulus cell analysis as a non-invasive oocyte selection strategy to reduce the number of oocytes/embryos cultured and increase pregnancy rates
Authors: Adriaenssens T , Van Vaerenbergh I , Reis M , Van Landuyt L , Verheyen G , Debrucker M , Camus M , Platteau P , De Vos M , Coucke W , Vanhecke E , Rosenthal A , Smitz J 
Published: June 2022

Abstract

Study question
Can non-invasive gene expression analysis of cumulus cells (CC) improve efficiency in ART by prioritizing oocytes for further culture and fresh single embryo transfer?

Summary answer
CC analysis can be used for the selective processing of oocytes. This may reduce culture work and improve the outcome in ICSI elective SETs (eSET).

What is known already
In an interventional, blinded, prospective cohort study (Van Vaerenbergh et al. 2021), 113 patients underwent a fresh Day3 eSET with embryos ranked and transferred based on morphology and CC gene expression (Aurora Test), while 520 control patients underwent a Day3 eSET without the Aurora Test. This resulted in a significant higher clinical pregnancy of 61% in the patients with eSET based on CC ranking applied on good morphology embryos, compared to 29% in the controls with eSET based on embryo morphology only. Live birth rate was also significantly increased, while time-to-pregnancy was significantly reduced with 3 transfer cycles.

Study design, size, duration
In a retrospective analysis, in a subset of patients with at least 6 growing follicles and at least five 2PN oocytes (n = 80), it was investigated whether the Aurora Test, used to select transferrable Day3-embryos, could also be applied to select oocytes on Day0/1. The effect of processing only the three highest ranked oocytes (based on the Aurora Test) on embryo development and clinical pregnancy was studied compared to processing all oocytes.

Participants/materials, setting, methods
Patients included in this single centre study had their first or second GnRH-antagonist ICSI cycle, were younger than 40y, had normal BMI, were stimulated with HP-hMG and scheduled for Day3 eSET. Two-sided statistical analysis (p &lt; 0,05) was performed between a strategy of processing only the top 3 Aurora ranked oocytes, according to CC gene expression, and a strategy of processing all available oocytes.

Main results and the role of chance
On average, 8 MII oocytes were obtained per patient and the average fertilization rate was 83%. In total, 407 good quality embryos (GQE) on Day3 were generated from these 80 patients when utilising all 639 oocytes. Processing the three top-ranked oocytes only (240/639 oocytes) would have reduced the number of embryos to 169 GQE and would have resulted in 2.1 GQE on average on Day3 per patient; 75/80 (94%) patients would have had a fresh Day3 transfer resulting in a 63% clinical pregnancy rate. Processing all 639 available 2PN oocytes (standard of care) resulted in a fresh Day3 transfer in all 80 patients and a similar 64% clinical pregnancy rate (ns). However, 399 more oocytes would need to be processed. The strategy of restricting the number of oocytes to be processed would not have compromised cumulative cycle outcome. Considering all subsequent freeze/thawing cycles the cumulative clinical pregnancy rate calculated per all 80 patients would increase to 90%.

Limitations, reasons for caution
The limitation of this approach is that the Aurora Test requires individual oocyte denudation and individual oocyte vitrification. Secondly, this new strategy should be validated in a prospective study.

Wider implications of the findings
By applying this oocyte selection strategy patients would benefit from a high pregnancy rate in the fresh transfer cycle, while the lab would see reduction in embryo culture work, because freeze/thawing cycles and culture of embryos with lower competence would be prevented.

Trial registration number
NA