A blastocyst’s implantation potential is linked to its originating oocyte cohort’s blastulation rate: evidence for a cohort effect

Objective

To investigate if blastocysts originating from different follicular cohorts have variable implantation rates, adjusted for oocyte age, morphology and/or ploidy

Design

Retrospective cohort

Subjects

Patients who underwent one or more cycles of autologous ovarian stimulation and in vitro fertilization/intracytoplasmic sperm injection, followed by elective single frozen blastocyst transfer

Exposure

Blastocyst progression rate of a follicular cohort; defined as the total number of expanded blastocyst, euploid blastocyst, Day 5 blastocyst, or Day 5 euploid blastocyst(s) divided by the number of 2 pronuclei (2PN) zygote(s)

Main outcome measures

Implantation, defined as serum human chorionic gonadotropin >5mIU/ml following elective single embryo transfer (eSET)

Results

A total of 4,292 blastocysts were tracked from their follicular cohort origin to their outcome following eSET. The mean age±standard deviation of the study population was 36.2±3.6 years old. The median (interquartile range; IQR) number of oocytes and 2PN zygotes per cohort was 17 (12-24) and 11 (8-16), respectively. The median (IQR) number of total expanded blastocysts and Day 5 blastocysts per cohort was 6 (4-9) and 2 (1-4), respectively. Preimplantation genetic testing for aneuploidy (PGT-A) utilization rate was 63.0%. The median (IQR) number of total euploid blastocysts and Day 5 euploid blastocysts were 2 (1-4) and 1 (0-2), respectively. Median (IQR) overall blastocyst progression rate was 60.0% (43.5-75.0%), euploid blastocyst progression rate 21.4% (13.3-33.3%), Day 5 blastocyst progression rate 20.0% (8.7-35.2%), and Day 5 euploid blastocyst progression rate 9.1% (0.0-18.2%). All blastocyst progression parameters inversely correlated with increasing age. Multivariable mixed-effects logistic regression analyses, adjusting for oocyte age, number of oocytes retrieved, embryo morphology, and PGT-A status, showed a positive association between overall blastocyst progression (adjusted OR 1.04 [95% CI 1.01-1.08], p=0.02), Day 5 blastocyst progression (adjusted OR 1.05 [95% CI 1.01-1.09], p=0.01), and Day 5 euploid blastocyst progression (adjusted OR 1.10 [95% CI 1.03-1.18], p=0.01) and implantation rates.

Conclusions_

Adjusting for age, oocytes retrieved, morphology, and ploidy status, blastocysts from follicular cohorts with high blastocyst progression rates demonstrate superior implantation potential compared to those from cohorts with lower blastocyst progression rates. This observation suggests the presence of a cohort effect, and offers valuable information for patient counseling on an embryo’s implantation potential beyond ploidy/morphology.