Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders?

Abstract

Background Is freeze-all strategy effective in terms of cumulative live birth rates (CLBRs) in all patients? Methods This retrospective single-center study analyzed the CLBRs of 2523 patients undergoing fresh or electively frozen blastocyst transfer cycles. In 1047, cycles, the fresh embryo transfer (ET) strategy was applied for the 1 st ET, whereas electively frozen ET (e-FET) was performed in 1476 cycles. Female age � 37 and blastocysts frozen via vitrification were included. The patients in each arm were further stratified into four subgroups according to the number of oocytes retrieved as follows: Group A: 1-5, group B: 6-10, group C: 11-15 and group D: 16-25 oocytes retrieved. The primary endpoint was the CLBR. The secondary endpoints were the ovarian hyperstimulation syndrome (OHSS) rate and the live birth rates (LBRs) following fresh ETs and e-FETs for the first transfers. Result(s) The CLBR was similar between the fresh ET and e-FET arms in group A (35/76 (46.1%) vs 29/67 (43.3%), p = 0.74) and group B (165/275 (60%) vs 216/324 (66.7%), p = 0.091), whereas significantly higher rates were detected in favor of the e-FET arm within group C (328/460 (71.3%) vs 201/348 (57.8%), p<0.001) and group D (227/348 (65.2%), vs 446/625 (71.5%), p<0.001). The OHSS rate was also found to be higher in the fresh ET arm among group C (12/348 (3.4%) vs 0/460 (0%), p<0.001) and group D (38/348 (10.9%) vs 3/625 (0.5%), p<0.001) patients than e-FET arm. Perinatal and obstetrical outcomes were nonsignificantly different between fresh and e-FET arms. However, the birth weights were significantly lower for fresh ET, 3064 versus 3201 g for singletons (p<0.001)

The freeze-all strategy after IVF: which indications?

“…Same conclusions were drawn in another recent RCT including 1650 ovulatory women (Wei et al, 2019b), and in large retrospective cohort studies (Boynukalin et al, 2020;Li et al, 2019;Zacà et al, 2018). However, subgroup analysis pointed out a potential benefit of the freeze-all strategy on cumulative LBR, in specific clinical scenarios such as in highresponders (Boynukalin et al, 2020) or in blastocyst-stage ET (Zacà et al, 2018), underlining the need for more data to discriminate the clinical situations in which freeze-all could be really advantageous in terms of cumulative LBR. Another important outcome when comparing two different ART strategies, is the time to pregnancy (TTP).…”

“…In a recent meta-analysis from Roque et al, pooling the results of five RCTs (2674 patients), there was no significant difference between the two groups (RR = 1.04; 95% CI: 0.97-1.11) in cumulative LBR (Roque et al, 2019b). Same conclusions were drawn in another recent RCT including 1650 ovulatory women (Wei et al, 2019b), and in large retrospective cohort studies (Boynukalin et al, 2020;Li et al, 2019;Zacà et al, 2018). However, subgroup analysis pointed out a potential benefit of the freeze-all strategy on cumulative LBR, in specific clinical scenarios such as in highresponders (Boynukalin et al, 2020) or in blastocyst-stage ET (Zacà et al, 2018), underlining the need for more data to discriminate the clinical situations in which freeze-all could be really advantageous in terms of cumulative LBR.…”

“…Currently, the cumulative LBR appears to be the most pertinent outcome to evaluate the success of the ART procedure, including the results of fresh and frozen ET cycles (Maheshwari et al, 2015). To date, only few studies comparing the freeze-all and the fresh ET strategies have reported this outcome, and results failed to demonstrate any advantage of the freeze-all strategy in the overall IVF population (Ferraretti et al, 1999;Shapiro et al, 2011aShapiro et al, , 2011bChen et al, 2016b;Vuong et al, 2018b;Zacà et al, 2018;Wei et al, 2019b;Li et al, 2019;Roque et al, 2019b;Boynukalin et al, 2020). In a recent meta-analysis from Roque et al, pooling the results of five RCTs (2674 patients), there was no significant difference between the two groups (RR = 1.04; 95% CI: 0.97-1.11) in cumulative LBR (Roque et al, 2019b).…”

Comparison of Stimulated Cycles with Low Dose r-FSH versus Hormone Replacement Cycles for Endometrial Preparation Prior to Frozen-Thawed Embryo Transfer in Young Women with Polycystic Ovarian Syndrome: A Single-Center Retrospective Cohort Study from China

“… 4 Compared with fresh embryo transfer, FET increase maternal safety, improve pregnancy rates, decrease ectopic pregnancy rates. 5 In addition, FET, avoiding the negative impact of controlled ovarian stimulation (COS) on endometrial receptivity, can provide a more physiologic uterine environment for embryo implantation with a fresh start and regrowth under alternative less intensive endometrial preparation regimens. 6 …”

Comparison of stimulated cycles with low dose r-FSH versus hormone replacement cycles for endometrial preparation prior to frozen-thawed embryo transfer in young women with polycystic ovarian syndrome: A propensity scores matching analysis from 1434 patients

“…FET can profoundly mitigate the risk of ovarian hyperstimulation syndrome (OHSS) and its use has now been extended to include those cycles of pre-implantation genetic diagnosis/screening, late-follicular progesterone elevation and embryo-endometrial asynchrony 4 . Compared with fresh embryo transfer, FET increase maternal safety, improve pregnancy rates, decrease ectopic pregnancy rates 5 . In addition, FET, avoiding the negative impact of controlled ovarian stimulation (COS) on endometrial receptivity, can provide a more physiologic uterine environment for embryo implantation with a fresh start and regrowth under alternative less intensive endometrial preparation regimens 6 .…”