PGS is the most pivotal strategy promotingthe clinical success rates of ART cycles in AMA patients. Additionally, another option to increase pregnancy rates is ET in the presence of a euploid embryo. In this study,clinical pregnancy, ongoing pregnancy, and live birthrates were statistically higher in the frozen ET group in AMA patients.
Currently, the frozen-thawed ET strategy has been trending due to improved implantation and pregnancy rates. Optimal endometrial preparation has a critical role in accomplishing successful results in frozen ET, and the impaired results after fresh ET strategy point out the importance of the endometrial receptivity and implantation window [ 13]. [In review study of Evans J, it was stated that the endometrial receptivity was reduced during COH cycles, and FET had higher beneficial outcomes regarding the mother and baby(8). Roque M analyzed 530 cycles, compared the fresh transfer and frozen transfer outcomes, and reported a 1,33 RR of implantation rate and 1,28 RR ofongoing pregnancy rate for the frozen group. Additionally, this study suggests that the implantation failure could be resulting from COH(14). Both the CPR (RR 1.31; 95% CI 1.10– 1.56) and ongoing pregnancy rates (RR 1.32;95% CI 1.10 − 1.59) were higher in the eFET group than fresh embryo transfer group according to a systematic review subjecting three randomized controlled trials and a total of 633 women. In this review, the miscarriage rates (RR 0.83; 95% CI 0.43 − 1.60) did not reveal a significant difference(16). Freezing all embryos ensures that all blastocysts are included in the embryo cohort transferability, which results in a higher proportion of successful ET [9]. Recently, Coates et al. study revealed that frozen-thawed euploid embryo transfer after PGS had higher pregnancy outcomes. (9) Our study also demonstrated that AMA patients had higher implantation and pregnancy rates via frozen single euploid embryo transfer.
It is known that ART success declines relatively in women at the age of forty and older. It has been shown that the most important reason for the decrease in fertility in this age group is related to the increased risk of age-related aneuploidy. [1] Lee HL et al. analyzed AMA and ART results, in which the mean participant age was 41.2 and 41.3 for study groups, retrospectively. Biopsies were taken from 451 blastocysts in the PGS group (n:170), and as a result of the ploidy analysis, 20.4% of the blastocysts were found to be euploid, while aneuploidy was observed in 74.3% of the blastocysts, 3% of the remaining blastocysts could not be diagnosed and 2.2% had chaotic profiles after amplification. Implantation rates and live delivery per transferred embryo incidence were significantly higher for the PGS group (10). Ma GC et al. analyzed rapid array comparative genomic hybridization (aCGH) in the selection of blastocysts for fresh SET and compared the results with the methodsusing vitrified embryo transfer cycle as a pilot study. Despite the small sample size (8 for fresh and 13 for the frozen group) and non-randomized character of the study, the revealed clinical pregnancy rate ( 87.5% in the fresh transfer group and 76.9% in the frozen embryo transfer group) was successful (15). Capalbo A demonstrated that aneuploidy rates were significantly higher at advancing age females (odds ratio (OR) ¼ 1.12 ) and pregnancy rates were 57.3% and 75.6% in euploid ET when mean age was 38.8 and 36.1 respectively (6). For euploid embryos, implantation potential was higher in AMA patients [10]. In fresh or frozen-thawed cycles, only one selective euploid ET increased the pregnancy rates [6, 15]. Moreover, single euploid ET reduced the chance of multiple pregnancies, which was associated with increased abortion rates and premature deliveries with newborn complications. In our study, a single ET strategy was chosen in both groups, and the euploid embryo rates of the groups were similar. The main difference between the groups was the transfer strategy, and endometrial receptivity was vital for implantation. Our study revealed high implantation rates in the frozen ET group.
In literature, too many studies compared the outcomes of fresh and frozen ET [16], but the number and sample size of studies comparing two transfer strategies with euploid embryos are limited. Although this study is retrospective, it has the largest number of participants comparing fresh versus frozen ET results for euploid embryos. Only one prospective randomized controlled study investigated fresh vs. frozen ET for euploid embryos. Coates A et al. analyzed the fresh vs. frozen transfers after PGS with next-generation sequencing(NGS) in their prospective randomized controlled study in a total of 179 patients. The mean transferred embryo numbers were 1,4 for the fresh ET group and 1.5 for the frozen ET group (p = 0,27). Ongoing PRs (62.2% vs. 40.9%) and live birth rates (61.5% vs. 39.8) were significantly higher in the freeze-all group than the fresh group (p < 0,01 and p < 0,01 respectively). The results were significantly higher in the frozen ET group than the fresh group according to the subgroup analysis of day-5 biopsied euploid blastocyst; however, the difference was not significant. The authors explained the result with the small sample size.We included 317 participants and found that ongoing pregnancy rates and live birth rates were significantly higher in the frozen group. Although our study is the first to choose the single ET strategy that compares fresh or frozen, the results were comparable with Coates A et al.'s study. The most significant effects on the success rates of ART are the embryo and endometrium. It is also known that a higher estrogenic environment may cause reduced endometrial receptivity and decreased pregnancy outcomes [16]. Our study considers all of the factors and may solely examine the effect of the endometrial factor on pregnancy outcomes. Frozen-thawed single euploid ET strategy results in higher implantation rates and pregnancy rates compared to fresh single euploid ET in our study. Additionally, this transfer strategy reduces the risk of ovarian hyperstimulation syndrome and multiple pregnancies, which is a critical condition and has high morbidity and mortality rates in ART.