Abstract
Abstract Study question In patients > 37 years undergoing IVF/ICSI, does PGT-A improve live birth rates (LBR) and cumulative live birth rates (CLBR)? Summary answer In advanced maternal age women with ≥1 embryo to transfer, PGT-A improves the live birth and cumulative live birth rates. What is known already The age-related rate of aneuploidy remains a major cause of IVF failure. Therefore, PGT-A has been proposed as a method to select embryos with the highest implantation potential. Previous studies have shown that women younger than 37 years old do not benefit from PGT-A given the comparable outcomes in terms of implantation, clinical pregnancy, and live-birth rates. Moreover, PGT-A may also be inherently ineffective given the risk of mitotic mosaicism, sampling errors and misinterpretation of results. However, we are currently lacking solid scientific evidence to support whether this approach benefits advanced maternal age women. Study design, size, duration A multicenter retrospective cohort study was conducted including 9328 patients >37y undergoing their first IVF/ICSI cycle with an oocyte retrieval performed between 1/01/2013-31/07/2021 in a multinational private fertility clinic. The study group (n = 4664) included patients who performed PGT-A. The control group included patients without PGT-A (n = 4664) and was selected by propensity score matching adjusted for age at oocyte retrieval, number of oocytes retrieved and year of oocyte retrieval. Participants/materials, setting, methods The primary outcome was CLBR (delivery of at least one live birth per started cycle, including the fresh and subsequent frozen embryo transfer cycles). The secondary outcomes were LBR and time to pregnancy. The analysis was conducted including all patients with an initiated cycle of ovarian stimulation and also per embryo transfer. Comparisons are presented as adjusted odd-ratios (adjOR) and 95% confidence intervals (95%CI) following multivariable logistic regression (LBR) or cox regression (CLBR) analysis. Main results and the role of chance Patients in the PGT-A group had more oocytes retrieved (11.03±6.82 vs 9.24±6.15, p < 0.001), and a higher number of available blastocysts (2.82±2.21 vs 1.22±2.00, p < 0.001). In the PGT-A group, 13.153 embryos were analysed, with an euploidy rate of 29.30% (n = 3854). In total, 49.83% (n = 2324) patients did not undergo embryo transfer due to unavailable euploid embryos. Considering all patients that initiated ovarian stimulation, the PGT-A group presented a higher unadjusted CLBR per started cycle (27.38% vs 21.81%, p < 0.001). Considering only patients who underwent embryo transfer, a total of 5934 embryo transfers were analysed (n = 3166 in the control group and n = 2768 in the PGT-A group). Following multivariable logistic regression analysis, LBR and CLBR were significantly higher in the PGT-A group (respectively, adjOR 1.56 [95% CI 1.38-1.77], adjOR 1.53 [95% CI 1.39-1.68]). Following the transfer of 5 embryos, the CLBR was approximately 100% in the PGT-A group and 74.51% in the control group. Survival analysis was also perfomed to assess the impact of PGT-A on time to pregnancy. Despite the fact that from 6 months onwards the CLBR was higher in the PGT-A group, the median time to pregnancy was higher in the PGT-A group (3.27 (95%CI 3.16-3.40) vs 2.74 months (95%CI 2.57-3.03). Limitations, reasons for caution This study is limited by its retrospective design and low number of women with more than 3 embryos transferred. Also, the fact that only the first IVF/ICSI cycle was analysed provides a proper patient counselling in this specific context but does not provide data on repeated cycle outcomes. Wider implications of the findings Our findings suggest that, in women older than 37 years with at least one available embryo to biopsy, performing PGT-A may improve the reproductive outcomes in terms of LBR and CLBR, providing a useful clinical tool for embryo selection. Trial registration number not applicable
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