Abstract
Study question
For patients with less than four two-pronucleate (2pn) zygotes, is there an age-cutoff above which preimplantation genetic diagnosis for aneuploidy (PGT-A) is futile?
Summary answer
Women over 40y with less than four 2pn zygotes should consider transfer of a day 3 embryo over culture to blastocyst with PGT-A.
What is known already
During a typical IVF cycle, there is unavoidable attrition from oocytes retrieved, to embryos obtained, to blastocysts formed such that some patients, particularly those with advanced age or poor ovarian response, may not have blastocysts available to biopsy. While randomized trials have shown improved pregnancy rates with the use of PGT-A in patients of advancing age, these trials primarily included patients with good ovarian reserve and multiple blastocysts available. The optimal age group within poor responders who would benefit most from PGT-A has yet to be determined.
Study design, size, duration
This was a retrospective cohort study of all fresh autologous IVF or IVF/ICSI cycles in which PGT-A was planned from 1/2012 to 3/2020. Only patients with less than four 2pn zygotes were included. A total of 85 cycles from 75 patients were analyzed.
Participants/materials, setting, methods
Number of cleavage-stage embryos, blastocysts, biopsy-quality blastocysts and euploid embryos were assessed, after stratification by age. Adjusted relative risks (aRR) and 95% confidence intervals (CI) were calculated adjusting for BMI, AMH, FSH, stimulation protocol, and ICSI. Poisson regression was used for counts. Generalized estimating equations were used to account for patients contributing multiple cycles.
Main results and the role of chance
There were no differences in number of 2pn zygotes (p = 0.98) or cleavage stage embryos (p = 0.94) across age groups. Patients aged 41–42y had a significantly lower number of blastocysts (1.18 vs. 2.00; aRR 0.59 95%CI: 0.37–0.95) and biopsy-quality blastocysts (0.73 vs. 1.53; aRR 0.50 95% CI: 0.26–0.98) compared to patients <35y.These patients also had fewer euploid embryos available (0.09 vs 0.67), although the difference was not significant in the adjusted model (aRR 0.14 95% CI: 0.01–1.57). None of the patients >42y had euploid blastocysts. When considering the mean and three standard deviations (0.09 [SD 0.3]), 99.7% of patients over 40y have no euploid embryo available for transfer.
Limitations, reasons for caution
This study was retrospective in nature and limited by small sample sizes when patients were stratified by age. A prospective randomized trial of patients with less than four 2pn zygotes to day 3 fresh embryo transfer vs PGT-A frozen embryo transfer is needed to confirm these findings.
Wider implications of the findings: Patients over 40y with less than four 2pn zygotes are at high risk of having no euploid blastocysts. While the literature demonstrates higher live birth rates with the use of PGT-A in women of advancing age, this is inconsequential if there is no embryo available to transfer.
Trial registration number
Not applicable
Obstetric and neonatal outcomes in blastocyst-stage biopsy with frozen embryo transfer and cleavage-stage biopsy with fresh embryo transfer after preimplantation genetic diagnosis/screening
