The reproductive potential of vitrified-warmed euploid embryos declines following repeated uterine transfers

Abstract

Background: Recurrent implantation failure (RIF) represents a vague clinical condition with an unclear diagnostic challenge that lacks solid scientific underpinning. Although euploid embryos have demonstrated consistent implantation capabilities across various age groups, a unanimous agreement regarding the advantages of preimplantation genetic testing for aneuploidy (PGT-A) in managing RIF is absent. The ongoing discussion about whether chromosomal aneuploidy in embryos significantly contributes to recurrent implantation failure remains unsettled. Despite active discussions in recent times, a universally accepted characterization of recurrent implantation failure remains elusive. We aimed in this study to measure the reproductive performance of vitrified-warmed euploid embryos transferred to the uterus in successive cycles.

Methods: This observational cohort study included women (n = 387) with an anatomically normal uterus who underwent oocyte retrieval for PGT-A treatment with at least one biopsied blastocyst, between January 2017 and December 2021 at a university-affiliated public fertility center. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy and comprehensive 24-chromosome analysis of preimplantation embryos using Next Generation Sequencing (NGS). Women, who failed a vitrified-warmed euploid embryo transfer, had successive blastocyst transfer cycles (FET) for a total of three using remaining cryopreserved euploid blastocysts from the same oocyte retrieval cycle. The primary endpoints were sustained implantation rate (SIR) and live birth rate (LBR) per vitrified-warmed single euploid embryo. The secondary endpoints were mean euploidy rate (m-ER) per cohort of biopsied blastocysts from each patient, as well as pregnancy and miscarriage rates.

Results: The mean age of the patient population was 33.4 years (95% CI 32.8-33.9). A total of 1,641 embryos derived from the first oocyte retrieval cycle were biopsied and screened. We found no associations between the m-ER and the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45). Pairwise comparisons showed a significant decrease in the sustained implantation rate (44.7% vs. 30%; P = 0.01) and the livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02) between the 1st and 3rd FET. The cumulative SIR and LBR after up to three successive single embryo transfers were 77.1% and 68.8%, respectively. We found that the live birth rate of the first vitrified-warmed euploid blastocyst transferred decreased significantly with the increasing number of previously failed IVF attempts by categories (45.3% vs. 35.8% vs. 27.6%; P = 0.04). A comparable decrease in sustained implantation rate was also observed but did not reach statistical significance (50% vs. 44.2 vs. 37.9%; P = NS). Using a logistic regression model, we confirmed the presence of a negative association between the number of previous IVF failed attempts and the live birth rate per embryo transfer cycle (OR = 0.76; 95% CI 0.62-0.94; P = 0.01).

Conclusions: These findings are vital for enhancing patient counseling and refining management strategies for individuals facing recurrent implantation failure. By tailoring interventions based on age and ovarian reserve, healthcare professionals can offer more personalized guidance, potentially improving the overall success rates and patient experiences in fertility treatments.

Trial registration number: N/A.

Keywords: Euploid blastocyst rate; Live birth rate; Preimplantation genetic testing for aneuploidy; Recurrent implantation failure; Sustained implantation.

Fig. 1

Flow diagram representing the implantation of vitrified warmed euploid blastocysts after up to three consecutive uterine transfers

Fig. 2

Mean euploidy rate per cohort of biopsied blastocysts from each patient according to the number of previously failed IVF cycles (0/1–2/≥3) and among different ranges of maternal age at oocyte retrieval ≤ 29/30–34/35–39/≥40). General linear regression analysis found no associations between m-ER and the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45)

Fig. 3

Clinical outcomes of euploid blastocyst transferred during the first, second, and third cycles. Using Wilkinson paired ranked test, pairwise comparisons between the 1st and 3rd FET showed a significant decrease in the sustained implantation rate (46.7% vs. 30%; P = 0.01) and the livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02)

Fig. 4

Clinical outcomes of the first vitrified warmed euploid blastocyst transferred: Data clustered according to number of previous failed IVF cycles. Using the Kruskal Wallis test, the livebirth rate per single euploid embryo was found to decrease significantly with an increasing number of previously failed IVF attempts (45.5% vs. 35.8% vs. 27.6%; P = 0.04)