Study question Does the number of available euploid embryos affect the success rate of the first single euploid frozen thawed embryo transfer (FTET)? Summary answer The live birth rate (LBR) following the first single euploid FTET is independent of the number of available euploid embryos. What is known already Preimplantation testing for aneuploidy (PGT-A) is a controversial laboratory technique as an embryo selection tool to increase LBR per transfer and reduce time to pregnancy. There have been many efforts to identify factors predictive of LBR following a euploid embryo transfer. The number of euploid embryos available is known to increase the expected cumulative LBR. However, there is lack of evidence whether the number of available euploid embryos is also significantly associated with chances of live birth for the first euploid FTET cycle. This is important for individualized patient counselling. Study design, size, duration A retrospective analysis of the first, single, euploid FTET of 506 women, between January 2015 to March 2020 following PGT-A was carried out. The indication for PGT-A was advanced maternal age, recurrent miscarriage or implantation failure. Embryos were biopsied on day 5 or 6 and tested with array comparative genetic hybridization or next generation sequencing. The FTET outcomes were compared based on the number of euploid embryos available. Participants/materials, setting, methods 198 women had one euploid embryo available (group 1), 120 women had two (group 2) and 188 women had three or more (group 3). Baseline characteristics were analysed for all participants to adjust for confounders. Reproductive outcomes such as pregnancy rate (PR), clinical miscarriage rate and LBR were compared between the 3 groups for the first euploid FTET. Univariate analysis with Kruskal-Wallis H, chi-square and multivariate logistic regression was performed with SPSS. Main results and the role of chance Baseline characteristics were similar between the groups including age at egg collection (EC), body mass index, use of partner or donor sperm, method of insemination, number of ECs, endometrial preparation protocol and endometrial thickness prior to transfer. Women with three or more euploid embryos were younger at the time of EC compared to groups 1 and 2 (mean age 37 vs 39 and 38). The number of oocytes per EC (15 vs 11 and 11, p < 0.001), the total number of oocytes following batching cycles (20 vs 15 and 16, p < 0.001) and the number of blastocysts biopsied (8 vs 4 and 5, p < 0.001) were significantly higher for Group 3 vs Group 1 and Group 2, respectively. Group 1 embryos were less frequently of excellent and very good morphology and less frequently biopsied on day 5 vs 6. Univariate analysis suggests Group 3 had statistically higher PR and LBR compared to Group 1, but similar miscarriage rate. However, when applying a multivariate logistic regression model, the LBR after first euploid FTET was independent of the number of euploid embryos available but was influenced by age at EC (p = 0.006) and biopsy day (Day 6 vs day 5, OR 0.53, 95% CI 0.33-0.85, p = 0.008). Limitations, reasons for caution The main limitation of this study is its retrospective nature performed in a single centre, and therefore vulnerable to bias and confounding factors that may have not been accounted for. Wider implications of the findings Our findings suggest that the success rate of the first euploid FTET does not depend on the number of euploid embryos but is influenced by the age at EC and the embryo stage at biopsy. This could be useful when counselling women with a low number of euploid embryos available. Trial registration number Not Applicable
Study question Does PGD treatment in couples with a history of RPL due to male translocations improve the outcome, increasing LBR and reducing miscarriage rate and time taken to live birth? Summary answer Live birth rate is significantly increased, miscarriage rate is significantly reduced using PGD. Time taken to achieve live birth rate is shorter in PGD treatment. What is known already Reciprocal translocation are the most common structural rearrangement in infertile men. The specific chromosomes and breakpoints involved might play an important role, often expressed as abnormal semen parameters or repeated pregnancy loss (RPL). The genetic counselling of these men remains challenging. Previous studies and meta-analysis performed showed no difference in live birth rate when comparing natural conception versus PGD treatment. However, the difference in miscarriage rate and time to live birth between PGD and natural conception has not been reported before in the medical literature. Study design, size, duration A systematic review of the literature was conducted through MEDLINE, EMBASE, and the Cochrane database up until December 2020. A comprehensive search yield 287 articles, 25 of which were included for abstract reading, finally, six were included in the meta-analysis. Participants/materials, setting, methods The six selected articles, reported on Live birth rate (LBR), miscarriage rate and time to live birth (TTLB) for natural conception compared to PGD for the same cohort of patients. All of the included articles were of retrospective design. The primary outcome was the comparison in LBR and the second outcome was the analysis in miscarriage rate and TTLB in the PGD group versus natural conception. Main results and the role of chance A total of 1438 couples that conceived naturally, had a LBR of 22.46%, compared with 43,17% among 681 couples that underwent PGD (0.53 95% CI (0.43-0.65) p o < 0,00001). The six articles included in this meta-analysis had significant homogeneity (I2 = 96%). Comparison of miscarriage rates, natural conception represented 1339 miscarriages out of 1836 pregnancies, in comparison with 44 miscarriages out of 558 pregnancies achieved through PGD. The OR showed a 10 fold increase risk of miscarriage when conceiving naturally in couples with a male translocation (10.18; 95% CI (2.88-36.04) p = 0.0003). Regarding TTLB, the difference was not statistically significant, however it did reflect that PGD patients will have a shorter TTLB (3.56 95% CI (-0.88-8.00)p = 0.12). One of the studies included, took into account the waiting list to access PGD funding, prolonging therefore the TTLB in the PGD group. Limitations, reasons for caution The main limitation of this study is the low number of studies. TTLB should be interpreted with caution given that one of the articles included the time of the waiting lists. More studies could demonstrate a shorter time period for these couples to conceive and have a successful ongoing pregnancy. Wider implications of the findings First study to demonstrate the value of PGD in decreasing miscarriage rates in couples with RPL. Specially when counselling couples with history of RPL with male translocations. PGD should be offered in these couples to improve the outcome, and to diminish the physical, emotional and sequelae of RPL and TOP. Trial registration number not applicable
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