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Objective: To determine whether elective frozen embryo transfer (eFET), or the 'freeze-all' strategy, associated with better cumulative clinical outcomes compared with fresh embryo transfer (ET)., Methods: A total of 7,236 IVF cycles that were followed by a fresh ET or eFET between 2013 and 2017. The patients were subjected to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone (GnRH) antagonist protocol and cleavage-stage ET. Embryo cryopreservation was performed on day 3 by vitrification using an open system. A comparison of cumulative outcomes between the eFET (n=4,065cycles) and the fresh ET groups (n=3,171cycles) were performed. The analysis was performed in four groups of patients based on the number of retrieved oocytes: Group 1: poor responders (1-3 oocytes); Group 2: suboptimal responders (4-9 oocytes); Group 3: normal responders (10-15 oocytes); and Group 4: hyper-responders (>15 oocytes). The primary outcome was the cumulative live birth rate (CLBR) per stimulated cycle., Results: There were a total of 10,283 ETs (n=5,639 eFET group; n=4,644 fresh group). The freeze-all strategy is associated with improved CLBRs in normal and hyper-responders, but not in suboptimal and poor responders. In Group 1, there were 351 IVF cycles and 387 ETs in total, and the CLBR was 14.3% and 17.7% (p=0.584) for the eFET and fresh group, respectively. In Group 2, there were 2,074 IVF cycles and 2,465 ET in total, and the CLBR was 25.1% and 23.3% (p=0.083) in the eFET and fresh group, respectively. There was a significant difference in the CLBR in Groups 3 and 4, favouring the eFET strategy. In Group 3, 2226 IVF cycles and 3243 ET were performed. The CLBR was 40.5% in the eFET and 36.6% in the fresh group (p<0.001). In Group 4, there were 2547 IVF cycles and 3,188 ET in total, and the CLBR was 52.2% and 47.7% (p<0.001) in the eFET and fresh group, respectively. The number needed to treat to achieve one additional live birth was 25.9 in Group 3 and 22.3 in Group 4., Conclusions: The implementation of the freeze-all strategy should be individualized. The freeze-all strategy is associated with improved CLBRs in normal and hyper-responders, but not in suboptimal and poor responders.

Introduction: Progesterone is an essential hormone involved in the process of implantation and pregnancy maintenance. Evidence from recent studies has supported the importance of serum progesterone level around the time of embryo transfer in hormonal replacement therapy frozen embryo transfer cycles and recommended the need for individualised luteal support. Low progesterone around the time of embryo transfer is found to be associated with decreased rate of pregnancy after frozen embryo transfer. This single-centre, longitudinal, randomised, interventional controlled study aims to compare the rate of ongoing pregnancy between two groups of women with progesterone level below 10 ng/mL on the day of frozen embryo transfer: the study group using 800 mg vaginal micronised progesterone supplemented with 50 mg intramuscular progesterone per day and the control group using only 800 mg vaginal micronised progesterone., Methods and Analysis: We enrol patients who are undergoing frozen embryo transfers with blastocyst-stage or cleavage-stage embryos and who satisfy the inclusion and exclusion criteria. After signing the informed consent, participants are randomised into two groups: the study group using vaginal micronised progesterone supplemented with progesterone intramuscular 50 mg per day and the control group using only vaginal micronised progesterone. Randomisation will be performed using R software at a 1:1 allocation ratio. Sequentially numbered, opaque sealed envelopes are used for allocation. The primary outcome is the rate of ongoing pregnancy. To demonstrate a difference of 10% with regard to rate of ongoing pregnancy, at least 370 participants per arm are required (type I error α=0.05, power=0.8). Assuming a dropout rate of 10%, a total of 824 patients (412 per group) will be invited., Ethics and Dissemination: This study was approved by the Ethics Committee of Tu Du Hospital on 17 May 2021 (reference number: 1251/QĐ-BVTD). All participants provide informed consent before being enrolled in the study. The results of our study will be submitted to reproductive medicine conferences and journals., Trial Registration Number: NCT04897269., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Elective freezing of all good quality embryos and transfer in subsequent cycles, i.e. elective frozen embryo transfer (eFET), has recently increased significantly with the introduction of the GnRH agonist trigger protocol and improvements in cryo-techniques. The ongoing discussion focuses on whether eFET should be offered to the overall IVF population or only to specific subsets of patients. Until recently, the clinical usage of eFET was supported by only a few randomized controlled trials (RCT) and meta-analyses, suggesting that the eFET not only reduced ovarian hyperstimulation syndrome (OHSS), but also improved reproductive outcomes. However, the evidence is not unequivocal, and recent RCTs challenge the use of eFET for the general IVF population., Objective and Rationale: This systematic review and meta-analysis aimed at evaluating whether eFET is advantageous for reproductive, obstetric and perinatal outcomes compared with fresh embryo transfer in IVF/ICSI cycles. Additionally, we evaluated the effectiveness of eFET in comparison to fresh embryo transfer in different subgroups of patients undergoing IVF/ICSI cycles., Search Methods: We conducted a systematic review, using PubMed/Medline and EMBASE to identify all relevant RCTs published until March 2018. The participants included infertile couples undergoing IVF/ICSI with or without preimplantation genetic testing for aneuploidy (PGT-A). The primary outcome was the live birth rate (LBR), whereas secondary outcomes were cumulative LBR, implantation rate, miscarriage, OHSS, ectopic pregnancy, preterm birth, pregnancy-induced hypertension, pre-eclampsia, mean birthweight and congenital anomalies. Subgroup analyses included normal and hyper-responder patients, embryo developmental stage on the day of embryo transfer, freezing method and the route of progesterone administration for luteal phase support in eFET cycles., Outcomes: Eleven studies, including 5379 patients, fulfilling the inclusion criteria were subjected to qualitative and quantitative analysis. A significant increase in LBR was noted with eFET compared with fresh embryo transfer in the overall IVF/ICSI population [risk ratio (RR) = 1.12; 95% CI: 1.01-1.24]. Subgroup analyses indicated higher LBRs by eFET than by fresh embryo transfer in hyper-responders (RR = 1.16; 95% CI: 1.05-1.28) and in PGT-A cycles (RR = 1.55; 95% CI: 1.14-2.10). However, no differences were observed for LBR in normo-responders (RR = 1.03; 95% CI: 0.91-1.17); moreover, the cumulative LBR was not significantly different in the overall population (RR = 1.04; 95% CI: 0.97-1.11). Regarding safety, the risk of moderate/severe OHSS was significantly lower with eFET than with fresh embryo transfer (RR = 0.42; 95% CI: 0.19-0.96). In contrast, the risk of pre-eclampsia increased with eFET (RR = 1.79; 95% CI: 1.03-3.09). No statistical differences were noted in the remaining secondary outcomes., Wider Implications: Although the use of eFET has steadily increased in recent years, a significant increase in LBR with eFET was solely noted in hyper-responders and in patients undergoing PGT-A. Concerning safety, eFET significantly decreases the risk of moderate and severe OHSS, albeit at the expense of an increased risk of pre-eclampsia.

Objective: To evaluate whether the freeze-all strategy affects in-vitro fertilization (IVF) outcome in poor ovarian responders (POR) defined according to the Bologna criteria., Method: This was a retrospective cohort study of patients undergoing IVF treatment between January 2012 and December 2016 at a single center. A total of 433 POR (as defined by the Bologna criteria) fulfilled criteria and were included in the study; of these, 277 patients underwent fresh embryo transfer (ET) and 156 followed the freeze-all policy. All patients underwent controlled ovarian stimulation (COS) following a gonadotropin-releasing hormone antagonist protocol, and cleavage-stage ET. Main outcome measure was ongoing pregnancy rate. Secondary outcomes included implantation and clinical pregnancy rates. The freeze-all strategy was implemented when the progesterone serum level was > 1.5 ng/mL or the endometrium was < 7 mm on the trigger day, or as per patient preference. Patients with previous failed fresh ET also underwent fresh ET or freeze-all strategy considering the indications mentioned above., Results: Mean maternal age in the freeze-all group was 39.5 ± 3.6 years and in the fresh ET group was 39.7 ± 3.8 years (P = 0.54). Mean number of embryos transferred (nET) was 1.53 ± 0.6 and 1.60 ± 0.6 (P = 0.12) in the freeze-all and fresh ET groups, respectively. Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh ET groups (9.6% vs 10.1%, respectively; relative risk (RR), 0.95; 95% CI, 0.52-1.73), nor did the clinical pregnancy rate (14.1% vs 13.7%, respectively; RR, 1.03; 95% CI, 0.63-1.67). Implantation rate was 9.6% and 9.8% (P = 0.82) in the freeze-all and fresh ET groups, respectively. Logistic regression analysis (including maternal age, antral follicle count, number of retrieved and mature oocytes, nET, and fresh ET vs freeze-all strategy) indicated that maternal age (P < 0.001) and nET (P = 0.039) were the only independent variables associated with ongoing pregnancy rate., Conclusions: The freeze-all strategy, compared with fresh ET, had no impact on IVF outcomes in POR patients as defined according to the Bologna criteria. Multicenter studies including large numbers of patients should be carried out to confirm the results of this study and reach conclusions about the potential benefits of the freeze-all policy for poor responders. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate if there are differences in the risks of obstetric outcomes in IVF/ICSI singleton pregnancies when compared fresh to frozen-thawed embryo transfers (FET)., Methods: This was a systematic review and meta-analysis evaluating the obstetric outcomes in singleton pregnancies after FET and fresh embryo transfer. The outcomes included in this study were pregnancy-induced hypertension (PIH), pre-eclampsia, placenta previa, and placenta accreta., Results: The search yielded 654 papers, 6 of which met the inclusion criteria and reported on obstetric outcomes. When comparing pregnancies that arose from FET or fresh embryo transfer, there was an increase in the risk of obstetric complications in pregnancies resulting from FET when compared to those emerging from fresh embryo transfers in PIH (aOR 1.82; 95% CI 1.24-2.68), pre-eclampsia (aOR 1.32, 95% CI 1.07, 1.63), and placenta accreta (aOR 3.51, 95% CI 2.04-6.05). There were no significant differences in the risk between the FET and fresh embryo transfer groups when evaluating placenta previa (aOR 0.70; 95% CI 0.46-1.08)., Conclusion: The obstetric outcomes observed in pregnancies arising from ART may differ among fresh and FET cycles. Thus, when evaluating to perform a fresh embryo transfer or a freeze-all cycle, these differences found in obstetric outcomes between fresh and FET should be taken into account. The adverse obstetric outcomes after FET found in this study emphasize that the freeze-all policy should not be offered to all the patients, but should be offered to those with a clear indication of the benefit of this strategy.

Purpose: The purpose of this study is to evaluate the freeze-all strategy in subgroups of normal responders, to assess whether this strategy is beneficial regardless of ovarian response, and to evaluate the possibility of implementing an individualized embryo transfer (iET) based on ovarian response., Methods: This was an observational, cohort study performed in a private IVF center. A total of 938 IVF cycles were included in this study. The patients were submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone (GnRH) antagonist protocol and a cleavage-stage day 3 embryo transfer. We performed a comparison of outcomes between the fresh embryo transfer (n = 523) and the freeze-all cycles (n = 415). The analysis was performed in two subgroups of patients based on the number of retrieved oocytes: Group 1 (4-9 oocytes) and Group 2 (10-15 oocytes)., Result(s): In Group 1 (4-9 retrieved oocytes), the implantation rates (IR) were 17.9 and 20.5% (P = 0.259) in the fresh and freeze-all group, respectively; the ongoing pregnancy rates (OPR) were 31 and 33% (P = 0.577) in the fresh and freeze-all group, respectively. In Group 2 (10-15 oocytes), the IR were 22.1 and 30.1% (P = 0.028) and the OPR were 34 and 47% (P = 0.021) in the fresh and freeze-all groups, respectively., Conclusion(s): Although the freeze-all policy may be related to better in vitro fertilization (IVF) outcomes in normal responders, these potential advantages decrease with worsening ovarian response. Patients with poorer ovarian response do not benefit from the freeze-all strategy., Competing Interests: The authors declare that they have no conflict of interest.

Objective: To compare in vitro fertilization (IVF) outcomes between fresh embryo transfer (ET) and frozen-thawed ET (the "freeze-all" policy), with fresh ET performed only in cases without progesterone (P) elevation., Design: Prospective, observational, cohort study., Setting: Private IVF center., Patient(s): A total of 530 patients submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone-antagonist protocol, and cleavage-stage, day-3 ET., Intervention(s): None., Main Outcome Measure(s): Ongoing pregnancy rates., Result(s): A total of 530 cycles were included in the analysis: 351 in the fresh ET group (when P levels were ≤1.5 ng/mL on the trigger day); and 179 cycles in the freeze-all group (ET performed after endometrial priming with estradiol valerate, at 6 mg/d, taken orally). For the fresh ET group vs. the freeze-all group, respectively, the implantation rate was 19.9% and 26.5%; clinical pregnancy rate was 35.9% and 46.4%; and ongoing pregnancy rate was 31.1% and 39.7%., Conclusion(s): The IVF outcomes were significantly better in the group using the freeze-all policy, compared with the group using fresh ET. These results suggest that even in a select group of patients that underwent fresh ET (P levels ≤1.5 ng/mL), endometrial receptivity may have been impaired by COS, and outcomes may be improved by using the freeze-all policy., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This publication will evaluate the available evidence in the literature comparing fresh embryo transfer (ET) and elective frozen-thawed embryo transfer (FET) regarding the possible interference of controlled ovarian stimulation (COS) in implantation and endometrial receptivity, IVF safety, and obstetric and perinatal outcomes., Methods: We performed a review in the literature of the available evidence comparing fresh to elective FET (freeze-all policy)., Results: The improvements made in cryopreservation techniques have led to few or no detrimental effects to the embryo and have resulted in no consequences to the offspring when compared to fresh embryos; this has allowed reproductive practitioners to create the freeze-all policy (when all viable embryos are electively cryopreserved in the fresh cycle and transferred in a posterior cycle). There are increasing concerns about the adverse effects associated with COS over the endometrial and uterine environments, as well as with the safety of COS in pregnancies that have originated from fresh ET during in vitro fertilization (IVF) treatments. COS may contribute to modifications in the endometrium, which might be related to poorer outcomes when fresh ET is performed. It has been suggested that obstetric and perinatal outcomes in pregnancies resulting from fresh ET are poorer when compared with those that occur after FET. In cycles with fresh ET, there is still a risk of ovarian hyperstimulation syndrome (OHSS)., Conclusion: There is growing evidence in the literature suggesting better IVF outcomes, and decreased obstetric and perinatal morbidity when adopting the freeze-all policy instead of fresh ET.

Objective: To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer., Design: Systematic review and meta-analysis., Setting: Centers for reproductive care., Patient(s): Infertility patient(s)., Intervention(s): An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers., Main Outcome Measure(s): The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage., Result(s): We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates., Conclusion(s): Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether the freeze-all strategy affects in-vitro fertilization (IVF) outcome in poor ovarian responders (POR) defined according to the Bologna criteria.Method: This was a retrospective cohort study of patients undergoing IVF treatment between January 2012 and December 2016 at a single center. A total of 433 POR (as defined by the Bologna criteria) fulfilled criteria and were included in the study; of these, 277 patients underwent fresh embryo transfer (ET) and 156 followed the freeze-all policy. All patients underwent controlled ovarian stimulation (COS) following a gonadotropin-releasing hormone antagonist protocol, and cleavage-stage ET. Main outcome measure was ongoing pregnancy rate. Secondary outcomes included implantation and clinical pregnancy rates. The freeze-all strategy was implemented when the progesterone serum level was > 1.5 ng/mL or the endometrium was < 7 mm on the trigger day, or as per patient preference. Patients with previous failed fresh ET also underwent fresh ET or freeze-all strategy considering the indications mentioned above.Results: Mean maternal age in the freeze-all group was 39.5 ± 3.6 years and in the fresh ET group was 39.7 ± 3.8 years (P = 0.54). Mean number of embryos transferred (nET) was 1.53 ± 0.6 and 1.60 ± 0.6 (P = 0.12) in the freeze-all and fresh ET groups, respectively. Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh ET groups (9.6% vs 10.1%, respectively; relative risk (RR), 0.95; 95% CI, 0.52-1.73), nor did the clinical pregnancy rate (14.1% vs 13.7%, respectively; RR, 1.03; 95% CI, 0.63-1.67). Implantation rate was 9.6% and 9.8% (P = 0.82) in the freeze-all and fresh ET groups, respectively. Logistic regression analysis (including maternal age, antral follicle count, number of retrieved and mature oocytes, nET, and fresh ET vs freeze-all strategy) indicated that maternal age (P < 0.001) and nET (P = 0.039) were the only independent variables associated with ongoing pregnancy rate.Conclusions: The freeze-all strategy, compared with fresh ET, had no impact on IVF outcomes in POR patients as defined according to the Bologna criteria. Multicenter studies including large numbers of patients should be carried out to confirm the results of this study and reach conclusions about the potential benefits of the freeze-all policy for poor responders. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]