PGT-A and euploid transfer is more efficient than untested transfer in patients obtaining 1 or 2 blastocysts: a propensity score matching-based study

Study question Does PGT-A and euploid transfer involve any clinical advantage with respect to untested transfer inpatients obtaining 1 or 2 blastocysts? Summary answer PGT-A involved less transfers, less miscarriages, and a shorter time from oocyte retrieval to cycletermination without affecting the cumulative-live-birth-rate per patient. What is known already Meiotic chromosomal aneuploidies are the main cause of implantation failures and miscarriages andshow a U-shaped association with women fertility. Their prevalence increases from 25-30% in women <35 years to > 90% around menopause. In IVF, PGT-A via comprehensive-chromosome-testing techniques allows identifying euploid blastocysts, whose live-birth-rate (LBR) per transferand miscarriage-rate (MR) per clinical pregnancy are respectively higher and lower than untestedblastocysts. From an intention-to-treat perspective, PGT-A cannot improve the cumulative-live-birth-rate (CLBR), but no report exists either of an impact on this key clinical outcome.Nevertheless, more data are needed about PGT-A performance in couples producing 1 or 2 blastocysts. Study design, size, duration We gathered a dataset of 369 non-PGT and 1461 PGT-A cycles with 1-2 blastocysts obtained bynaïve patients (April-2013 to July-2022). Patients were matched 1:1 for maternal age (36±3.1 years)and number of MII-oocytes inseminated (5.7±3.3) through propensity-score-matching, thereby producing a database of 242 cycles per arm. The primary outcome was LBR per transfer. Secondary outcomes were MR per clinical pregnancy, CLBR per concluded cycles and the time to cycle termination. Participants/materials, setting, methods ICSI of all own metaphase-II oocytes retrieved and blastocyst culture were systematically conducted. In the PGT-A group, trophectoderm biopsy without day3 zona-pellucida drilling andcomprehensive-chromosome-testing to assess full-chromosome non-mosaic aneuploidies wereperformed. Blastocyst cryopreservation was conducted via vitrification. Only euploid/untestedsingle transfers were conducted. The groups were comparable also for BMI, FSH, AMH, sperm factor, cumulus-oocyte-complexes, 2PN-zygotes, maturation, fertilization and blastulation rates. 99 and 143 patients obtained 1 and 2 blastocysts, respectively, in both groups. Main results and the role of chance The 242 non-PGT patients transferred 1.45±0.5 blastocysts. 57% and 43% performed one (N = 139) and two (N = 103) transfers, respectively. 165 patients (68%) did not undergo a fresh transfer because of OHSS risk (25%), premature progesterone elevation (20%), inadequate endometrium(23%), fever/COVID-19 (5%), couple’s will (27%).In the PGT-A group, the euploidy rate was 48.8±43.3%, 0.8±0.7 euploid blastocysts were obtained, and 0.6±0.6 transferred (N = 151) (p = 0.01 versus non-PGT). 45% of the PGT-A patients did not have euploid blastocysts (N = 110/242), 47% and 8% underwent one (N = 113) and two (N = 19) transfers, respectively. In the non-PGT and PGT-A group, the LBR per transfer was 17% (N = 61/351) versus 41%(N = 62/151; Multivariate-OR:3.9, 95%CI 2.4-6.3, adjusted-p=0.01; post-hoc power=99%). The MR was 30% (N = 26/87) versus 16% (N = 12/74; Multivariate-OR adjusted for blastocysts’ quality and day: 0.4,95%CI 0.2-0.9, adjusted-p=0.03), respectively. To date, 94% (N = 228/242) and 92%(N = 223/242) of the cycles were concluded (p = 0.5) and the CLBR was 25% (N = 57/228) versus 27%(N = 60/223; Multivariate-OR adjusted for maternal age:1.1, 95%CI 0.7-1.7, adjusted-p=0.6). The days between oocyte retrieval and cycle termination (PGT-A report without euploid blastocysts, last transfer without LB or first transfer with LB) were 125.1±144.4 and 74.5±95.6 (p = 0.01; confirmed adjusting for maternal age and number of blastocysts obtained in a linear regression). Limitations, reasons for caution Retrospective design. The mean maternal age at our private IVF center is 39 years with ≈70% requesting PGT-A. Nevertheless, all women are counseled about their age-specific prevalence ofaneuploidies. Wider implications of the findings PGT-A to assess full-chromosome non-mosaic aneuploidies and non-PGT involve similar CLBR incouples obtaining 1 or 2 blastocysts, but the former approach is faster (shorter time to cycletermination), safer (less miscarriages) and more efficient (less transfers). A cost-effectivenessanalysis is in our pipeline. Trial registration number not applicable