Endometrial injury and rFSH before frozen-thawed embryo transfer: a case report.

Hormonal treatment as endometrial preparation for frozen-thawed embryo transfer (FET) is routinely carried out with oral, transdermal or combined estradiol supplementation; however, in some cases, there is no optimal endometrial development with this type of stimulation. In this case report, our patient failed to respond to conventional endometrial preparation techniques. For this reason, two unconventional techniques were combined to improve endometrial receptivity; endometrial injury, followed by rFSH administration. As a result of this combination, we achieved endometrium thickness, reaching 8.9 mm on day 15 of the cycle, carrying out the embryo transfer of two blastocysts on day-17 of the cycle, achieving clinical pregnancy and carrying it to completion with the birth of a baby.

Fresh versus elective frozen embryo transfer: Cumulative live birth rates of 7,236 IVF cycles.

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.

Can biochemical pregnancy be determined 5 days after frozen-thawed embryo transfer?

OBJECTIVE: To study the predictive value of serum ß-hCG on day 5 after frozen-thawed embryo transfer (FET) to predict pregnancy outcomes and to establish cut-off values for very early biochemical pregnancy diagnosis. METHODS: This retrospective cohort study was performed at a private reproductive medicine centre and we reviewed the medical records of women who underwent FET cycles from January 2018 to June 2019. A total of 116 evaluated cycles had serum ß-hCG levels measured on days 5 and 10 after FET. The predictive value of serum ß-hCG levels measured on day 5 after FET was investigated for very early biochemical pregnancy diagnosis. RESULTS: The standard biochemical pregnancy diagnosis was defined as a ß-hCG ≥25 IU/L on day 10 after FET. We then generated a receiver operating characteristic curve, and the cut-off value of ß-hCG on day 5 for predicting biochemical pregnancies was 4.0 IU/L, with 93.4% sensitivity and 92.7% specificity (AUC, 0.960; 95% confidence interval, 0.923-0.997). CONCLUSIONS: Values for ß-hCG at day 5 after FET ≥4.0IU/L are accurate for the diagnosis of biochemical pregnancy. The use of very early biochemical pregnancy diagnosis in clinical practice enables earlier management, patient counselling, and appropriate follow-up.

Obstetric outcomes after fresh versus frozen-thawed embryo transfers: A systematic review and meta-analysis.

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.

Does freeze-all policy affect IVF outcome in poor ovarian responders?

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.

Embryo stage of development is not decisive for reproductive outcomes in frozen-thawed embryo transfer cycles.

OBJECTIVE: To evaluate if the outcomes of IVF/ICSI in frozen-thawed embryo transfer and fresh embryo transfer cycles differ in relation to cleavage and blastocyst stages. METHODS: Retrospective cohort study to compare IVF/ICSI outcomes between fresh embryo transfer and frozen-thawed embryo transfer cycles, according to the stage of embryo development. Analysis was carried out on 443 consecutive embryo transfer cycles performed between January 1st and December 31st, 2014. Women aged up to 38 and submitted to embryo transfer cycles with fresh (n = 309) or frozen-thawed (n = 134) embryos at a private center for assistance in human reproduction were considered for analysis. Results in each group were stratified according to the stage of embryo development: cleavage stage and blastocyst stage. Main outcome measures were implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate per cycle. RESULTS: In the fresh embryo transfer group, for cleavage stage versus blastocyst stage, respectively, implantation rates were 22% and 47% (p = 0.0005); clinical pregnancy rates were 34% and 64% (p = 0.0057); the ongoing pregnancy rates were 30% and 61% (p = 0.0046) and live birth rates were 28% and 55% (p = 0.0148). There were no significant differences in the rates between cleavage and blastocyst stages in the frozen-thawed group, neither between fresh and frozen-thawed cleavage embryo transfers nor between fresh and frozen-thawed blastocyst transfers. CONCLUSION: Our results confirm that blastocyst transfer is better than cleavage stage in fresh embryo transfer cycles. In frozen-thawed cycles, cleavage or blastocyst stages seem to offer similar reproductive outcomes.

Freeze-all cycle in reproductive medicine: current perspectives.

The freeze-all strategy has emerged as an alternative to fresh embryo transfer (ET) during in vitro fertilization (IVF) cycles. Although fresh ET is the norm during assisted reproductive therapies (ART), there are many concerns about the possible adverse effects of controlled ovarian stimulation (COS) over the endometrium. The supra-physiologic hormonal levels that occur during a conventional COS are associated with modifications in the peri-implantation endometrium, which may be related to a decrease in pregnancy rates and poorer obstetric and perinatal outcomes when comparing fresh to frozen-thawed embryo transfers. The main objective of this study was to assess the available literature regarding the freeze-all strategy in IVF cycles, in regards to effectiveness and safety. Although there are many potential advantages in performing a freeze-all cycle over a fresh ET, it seems that the freeze-all strategy is not designed for all IVF patients. There is a need to develop a non-invasive clinical tool to evaluate the endometrial receptivity during a fresh cycle, which enables the selection of patients that would benefit from this strategy. Today, it is reasonable to perform elective cryopreservation of all oocytes/embryos in cases with a risk of OHSS development, and in patients with supra-physiologic hormonal levels during the follicular phase of COS. It is not clear if all normal responders and poor responders may benefit from this strategy.

Freeze-all cycle for all normal responders?

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.

Cost-Effectiveness of the Freeze-All Policy.

OBJECTIVE: To evaluate the cost-effectiveness of freeze-all cycles when compared to fresh embryo transfer. METHODS: This was an observational study with a cost-effectiveness analysis. The analysis consisted of 530 intracytoplasmic sperm injection (ICSI) cycles in a private center in Brazil between January 2012 and December 2013. A total of 530 intracytoplasmic sperm injection (ICSI) cycles - 351 fresh embryo transfers and 179 freeze-all cycles - with a gonadotropin-releasing hormone (GnRH) antagonist protocol and day 3 embryo transfers. RESULTS: The pregnancy rate was 31.1% in the fresh group and 39.7% in the freeze-all group. We performed two scenario analyses for costs. In scenario 1, we included those costs associated with the ICSI cycle (monitoring during controlled ovarian stimulation [COS], oocyte retrieval, embryo transfer, IVF laboratory, and medical costs), embryo cryopreservation of supernumerary embryos, hormone measurements during COS and endometrial priming, medication use (during COS, endometrial priming, and luteal phase support), ultrasound scan for frozen- thawed embryo transfer (FET), obstetric ultrasounds, and miscarriage. The total cost (in USD) per pregnancy was statistically lower in the freeze-all cycles (19,156.73 ± 1,732.99) when compared to the fresh cycles (23,059.72 ± 2,347.02). Even in Scenario 2, when charging all of the patients in the freeze-all group for cryopreservation (regardless of supernumerary embryos) and for FET, the fresh cycles had a statistically significant increase in treatment costs per ongoing pregnancy. CONCLUSIONS: The results presented in this study suggest that the freeze-all policy is a cost-effective strategy when compared to fresh embryo transfer.

Frozen-Thawed Embryo Transfer Success Rate is Affected by Age and Ovarian Response at Oocyte Aspiration Regardless of Blastomere Survival Rate.

OBJECTIVE: To identify the factors influencing the success of frozen-thawed embryo transfers, whether originating directly from current cycles or from their matching fresh cycles. METHODS: Analysis of 273 frozen-thawed embryo transfer cycles and their matching fresh embryo transfer cycles, with respect to maternal, embryological and clinical factors, comparing successful to unsuccessful cycles. RESULTS: The cumulative clinical pregnancy and live birth rates following fresh ET and corresponding FETs were 50.5% and 38.8%, respectively. No outcome measure differed between fresh and frozen ET's. Only maternal age, number of oocytes retrieved and fertilized, and number of cleaved embryos in the fresh cycle were correlated with a higher pregnancy or live birth rate in the FET cycle. None of the other parameters had any effect on the outcome. Pre-freezing embryo quality and blastomere survival rate had no effect on pregnancy/live birth rates. CONCLUSION: Clinical pregnancy and live birth rates of fresh and frozen ETs were not significantly different. The only parameters that affected FET success were those resulting from the patient's age and ovarian reserve at the time of oocyte aspiration. Post-thawing blastomere survival rate and type of endometrial preparation for FET did not affect the success rate.