Preparation For Frozen-thawed Embryo Transfer Research Articles

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations.

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen-thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.

Reproductive and Obstetric Outcomes Following a Natural Cycle vs. Artificial Endometrial Preparation for Frozen-Thawed Embryo Transfer: A Retrospective Cohort Study.

Background: The proportion of frozen embryo transfer cycles has consistently grown in recent decades. Some adverse obstetric outcomes after frozen embryo transfer could possibly be explained by different approaches in endometrial preparation. The aim of the present study was to investigate reproductive and obstetric outcomes after frozen embryo transfer, comparing different endometrial preparation strategies. Methods: This retrospective study included 317 frozen embryo transfer cycles, of which 239 had a natural or modified natural cycle and 78 underwent artificial endometrial preparation. After excluding late abortion and twin pregnancies, the outcomes of 103 pregnancies were analyzed, 75 of which were achieved after a natural cycle/modified natural cycle, and 28 were achieved after an artificial cycle. Results: The overall clinical pregnancy rate/embryo transfer was 39.7%, the miscarriage rate was 10.1%, and the live birth rate/embryo transfer was 32.8%, without significant differences in reproductive outcomes between natural/modified cycle and artificial cycle groups. The risks of pregnancy-induced hypertension and abnormal placental insertion were significantly increased in pregnancies achieved after the artificial preparation of the endometrium (p = 0.0327 and =0.0191, respectively). Conclusions: Our study encourages the use of a natural cycle or modified natural cycle for endometrial preparation for frozen embryo transfer in order to ensure the presence of a corpus luteum able to orchestrate maternal adaptation to pregnancy.

Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization

Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.

Randomized Clinical Trial Comparing Oral Dydrogesterone to Micronized Vaginal Progesterone for Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycle

Background: The objective was to compare the use of micronized vaginal progesterone 800 mg daily and oral dydrogesterone 40 mg daily in the endometrial preparation for frozen-thawed embryo transfer (FET). Methods: Prospective randomized study with women undergoing FET along with hormone replacement therapy for endometrial preparation, between September 2019 and February 2021. A total of 73 patients were randomly selected and orally received 40 mg/day dydrogesterone (DYD group, n = 36) or 800 mg/day micronized vaginal progesterone (MVP group, n = 37) after endometrial preparation with transdermal estradiol. The main outcome was a viable ongoing pregnancy with 12 weeks of gestation. Biochemical pregnancy, clinical pregnancy and live birth rates were the secondary outcome. Results: The reproductive outcomes in FET cycles were similar, with pregnancy and Live birth rates in the didrogesterone and MVP treatment groups being respectively: Biochemistry (38.9%/37.8%; p = 0.189 [95% confidence interval (CI) = –23.4–21.2]), Clinical (33.3%/35.1%; p = 0.192 [95% CI = –20.0–23.6]); 12 Weeks Pregnancy (33.3%/32.4%; p = 0.196 [95% CI = –22.4–20.6]); Live birth (33.3%/32.4%; p = 0.196 [95% CI = –22.4–20.6]). Conclusions: 40 mg/day dydrogesterone and 800 mg/day MVP revealed similar reproductive results in FET cycles. The use of oral dydrogesterone is a reasonable option, may be more accepted by patients in terms of ease of use and lower cost. Clinical Trial Registration: U1111-1247-1845.

The Effect of Intrauterine Infusion of Plasma Enriched Platelet on Live Birth Rate in Patients with Implantation Failure: A Retrospective Uncontrolled Study

Background & Objective: Autologous platelet-rich plasma consists of concentrated autologous plasma and several cytokines and growth factors released by activated platelets in injury and inflammation. There is an increasing trend towards the effectiveness of intrauterine PRP infusion in repeated implantation failure patients. The aim of the present study was to describe the impact of intrauterine platelet-rich plasma infusion on the live birth rate in patients with repeated implantation failure.Materials & Methods: The present retrospective uncontrolled study was performed on 96 patients with more than two failed intracytoplasmic sperm injection cycles at Mehr medical institute between 2019 and 2021. Forty-eight hours before embryo transfer, patients received 1 mL lympho-platelet-rich plasma through an intrauterine insemination catheter. Patients were evaluated for pregnancy rate. Endometrial preparation for frozen-thawed embryo transfer was performed.Results: Participants' basal and stimulation characteristics, including gonadotropin dosage, the total number of oocytes, metaphase II oocytes and embryos, endometrial thickness, embryo transfer, quality of transferred embryos, and blastocyst transfer rate were evaluated. A total of 33 and 27 chemical (34.3%) and clinical pregnancies (28.1%) were achieved. Twenty (20.8%) and nineteen (20%) cycles resulted in ongoing pregnancies or live births, respectively. Conclusion: The current study suggests that platelet-rich plasma infusion 48 hours before frozen-thawed embryo transfer may be a good option for repeated implantation failure patients and results in 20% live birth.

Artificial Versus Modified Natural Cycles for Endometrial Preparation for Frozen-Thawed Embryo Transfer

Artificial Versus Modified Natural Cycles for Endometrial Preparation for Frozen-Thawed Embryo Transfer

P-675 Determining endogenous progesterone levels on the day of HCG triggering in modified natural cycles before frozen-thawed blastocyst transfer. Results and influence on clinical pregnancy rates

Abstract Study question Is the endogenous progesterone level (EPL) on the day of hCG administration associated with pregnancy outcomes in modified natural cycles before embryo transfer? Summary answer The present analysis suggested the negative effect of EPL on clinical pregnancy when progesterone was above 1,1 ng/ml on the day of HCG triggering. What is known already Endogenous progesterone levels (EPL) experience an abrupt increase following the ovulatory LH surge. It is described that this change in basal EPL contributes to modulating the endometrial receptivity in preparation for embryo implantation. Several authors reported a negative impact on the pregnancy of high serum EPL on the day of HCG. These studies revealed accelerated endometrial changes and a subsequent decoupling of the implantation window. These observations involved only patients who underwent ovarian stimulation before the embryo transfer. However, studies based on EPL in modified natural cycles before blastocyst transfer are very limited. Study design, size, duration The present non-interventional pilot cohort study aimed to determine the EPL in patients undergoing an endometrium preparation for frozen-thawed embryo transfer in non-stimulated cycles, and its association with clinical pregnancy rates. A total of 46 participants were included in this analysis. To reduce variability, the mean EPL was calculated excluding 2 outlier values in our dataset. The cut-off value of EPL was established using the Youden-index, and the T-student was used for further statistical comparisons. Participants/materials, setting, methods Patients following our IVF program, who underwent frozen-thawed embryo transfer during the period of study. Our data includes cycles with own and with donated oocytes. The total oocyte average age was 33,5±6,7. All transfers were performed at blastocyst stage. Main results and the role of chance The overall clinical pregnancy rate per embryo transfer was 70,5% (31/44), with an implantation rate of 66,7% (32/48). The mean number of transferred embryos was 1,09, with a single embryo transfer rate of 90,9%. The total mean of EPL was 0,31±0,26 [IC95% 0,23-0,39], with patients who achieved a clinical pregnancy (0,30±0,21; n = 31) showing significantly lower EPL (p-value=0,04) than the non-pregnant participants (0,41±0,40; n = 10). Three out of 44 patients had a biochemical pregnancy, with a mean EPL of 0,12±0,01. EPL cut-off value was establish at 1,1 ng/ml. The evaluation of the total dataset (n = 46 patients, including 2 outliers) showed that 8,7 % of a total of these cases had an EPL above the threshold of 1,1 ng/ml. The clinical pregnancy rate in this subgroup of patients was 25,0%. Limitations, reasons for caution This study includes a limited number of cases. Further analysis is required to confirm the present results and to allow data stratification for additional inter-group comparisons. Wider implications of the findings Evaluating EPL may contribute to improving the clinical outcome in natural modified cycles. We observed that EPL is expected to be lower in non-stimulated than in stimulated cycles, compared to previously published studies. These observations highlight the importance to manage treatment-related EPL thresholds, in particular, to establish transfer decision-making policies. Trial registration number n/a

P-381 A novel natural cycle proliferative phase/progesterone replacement(NC/PR) protocol for endometrial preparation for frozen-thawed embryo transfer(FET) Can it improve pregnancy outcomes : a prospective comparative study

Abstract Study question Can a novel protocol for endometrial preparation- NC/PR-FET, lead to better pregnancy outcomes than artificial cycle (AC)-FET, with similar ease of cycle monitoring and scheduling? Summary answer NC/PR-FET protocol gave comparable clinical pregnancy rates (CPR), significantly less early miscarriage rates (MR) and significantly more live birth rates (LBR) compared to AC-FET protocol. What is known already AC-FET is the most common protocol for endometrial preparation due to flexibility, easy monitoring, and high pregnancy rates albeit with evidence of higher obstetrical risks e.g., miscarriage, pre-eclampsia versus NC-FET. This risk could be due to suboptimal hormonal administration in AC-FET leading to impaired endometrial maturation, predecidualization, and altered endometrial function. Studies indicate, estradiol may have a stronger negative effect(versus progesterone) on the endometrial transcriptome. Hence, we studied a novel protocol with NC-estrogen (but with progesterone similar to AC-FET), for better endometrial maturation, predecidualization along with simple monitoring and flexible ET scheduling. Previously, a proof-of-concept case-series has been reported. Study design, size, duration The prospective comparative study was conducted at a tertiary center (Jan2019-Dec2021) with 126 patients (both autologous [AO] and donor oocytes [DO]):79 (AC-FET) and 47 (NC/PR-FET) with similar ICSI, vitrification, ET protocols. 2 or 3 Grade A cleavage stage embryos were transferred. CPR, implantation rates(IR), early MR (≤13 weeks, miscarriages/clinical pregnancies) and LBR (≥28 weeks, LBs/ETs) were compared. Serum progesterone was studied on day 5 post-ET. Antenatal care and most deliveries were at the same institute. Participants/materials, setting, methods Patients were non-smokers with normal hysteroscopy. In AC-FET, oral estradiol (6-8mg) was initiated from day 1-2 (for 10-17 days). In both groups, when endometrium ≥7mm and S.progesterone<1ng/ml, intramuscular progesterone was initiated(daily till day 4 post-ET, then every 3rd day till week 8). ET was scheduled on day 4 of intramuscular progesterone, and concurrently, vaginal progesterone was added (till week 10). Chi-square, t-tests, and multiple regression was used for statistical analysis and 2-tailed P <.05 indicated statistical significance. Main results and the role of chance Mean age and BMI were comparable in NC/PR-FET and AC-FET groups: 34.48±4.69 years vs. 33.58 ± 5.62 years (P =.35) and 26.27 ± 3.62 kg/m2 vs. 27.34 ± 4.61kg/m2 (P =.18) respectively. Similarly, the source of oocytes (%AO) and % singletons were also comparable in NC/PR-FET and AC-FET groups: 57.4% vs. 46.8% (P = .25), and 78.1% vs. 75% (P= .75) respectively. There were 3 ectopic pregnancies overall. The CPRs and IRs were comparable: 68.09% (NC/PR-FET) vs. 60.76% (AC-FET) (P=.41) and 32.30% (NC/PR-FET) vs. 28.96% (AC-FET) (P=.45) respectively. The early MR was significantly more in AC-FET vs. NC/PR-FET: 29.17% vs. 6.25% (P =.012). Consequently, LBRs were significantly more in NC/PR-FET vs. AC-FET: 59.57% vs. 39.24% (P =.028). After adjusting for age, BMI, AO/DO, this difference remained significant (AOR 2.66; 95% CI 1.21-5.81; P =.014) Mean serum progesterone was comparable in all patients in both groups: 38.50 ± 13.6ng/ml (NC/PR-FET) vs. 40.98 ± 28.64 ng/ml (AC-FET) (P =.57). Serum progesterone levels were also comparable in patients who were pregnant in both groups: 38.51 ± 14.79 (NC/PR-FET) vs. 42.25 ± 32.63 (AC-FET) (P =.53).Also, in the AC-FET group serum progesterone was comparable in patients who aborted,44.23 ± 31.60 vs. those who didn’t, 41.48 ± 33.44 (P =.79). Limitations, reasons for caution This was a single center study. Due to limited sample size, we could not control for many potential confounders (e.g., multiple pregnancies). For the same reason, we could not compare obstetrical risks as a study outcome. Wider implications of the findings This study shows significantly better pregnancy outcomes with a novel NC/PR-FET protocol vs. AC-FET. This needs to be validated in larger studies. Since suboptimal hormone administration in AC-FET could be causal factor for pre-eclampsia, larger studies can test if the NC/PR-FET protocol can lead to better obstetrical outcomes. Trial registration number not applicable

Comparison of natural and artificial cycles in frozen-thawed embryo transfer: A retrospective analysis of 1696 cycles.

Objective:This study aimed to compare the pregnancy outcomes of natural cycles (NC) and artificial cycles (AC) in patients undergoing endometrial preparation for frozen-thawed embryo transfer (FET).Materials and Methods:This retrospective cohort study was conducted in a private infertility clinic between September 2016 and January 2021 and reviewed 1696 FET cycles. Among these FET cycles, endometrial preparation protocols that are performed as the NC (group 1) and AC (group 2) were analyzed. Outcome measures were live birth rates (LBR), clinical pregnancy rates (CPR), implantation rates (IR), and miscarriage rates (MR).Results:The mean serum estradiol level before progesterone supplementation was significantly higher in group 2, whereas endometrial thickness before progesterone supplementation was higher in group 1 (p<0.05). The mean number of transferred embryos and embryo quality score rates regarding cleavage and blastocyst stages were similar in both groups. The IR and MR were similar between groups (p>0.05). Additionally, CPR and LBR were similar in groups 1 (39.2% and 32.8%) and 2 (37.3% and 28.5%) (p=0.517, p=0.134, respectively). Multivariate logistic regression analyses revealed that female age at embryo freezing time and the number of transferred embryos were predictable variables of live birth [odds ratio (OR): 0.970, confidence interval (CI): 0.948-0.991, p<0.05, and OR: 1.359, CI: 1.038-1.780, p<0.05, respectively].Conclusion:Suitable endometrial preparation is essential to obtain successful pregnancy rates; however, no superiority was determined in NC or AC protocols in frozen-thawed cycles. One of these protocols may be performed depending on menstrual regularity and clinical experience.

P–765 Embryo donation pregnancies are at high risk even in young recipients

Abstract Study question Are pregnancies after embryo donation (ED) at higher risk of complications than those issued from autologous frozen-thawed embryo transfer (FET)? Summary answer Even in young women, the risk of pregnancy induced hypertension (PIH) is four time higher in pregnancies after ED versus controls. What is known already After oocyte donation, a higher risk of PIH is well described. It is more controversial after sperm donation. The risk origin remains uncertain, even though an immunological explanation seems most likely. In ED, the fetus being fully allogeneic to his parents may be less well-tolerated. Very few data are reported about pregnancies after ED. The same allogenic model exists in surrogacies, but pregnancy complications are not well described in the literature. Study design, size, duration This anonymous, multicenter, comparative observational retrospective cohort study included all singleton ED pregnancies diagnosed at 7–8 weeks, from January 2003 to December 2018, in six French ART centers. For each, two controls were matched among autologous FET pregnancies. 209 pregnancies were included: 73 ED and 136 controls. Multiple pregnancies were excluded because of their increased associated obstetrical risks. Participants/materials, setting, methods Controls were matched according to pregnancy date, parity and women’s age. The first two singleton pregnancies after each index case meeting the selection criteria were retained. Each center coordinator collected information on infertility, pregnancy pathologies, outcomes and newborns. Statistical methods included univariate and multivariate analyses. According to French practice, all women were under 44 y/o. The main outcome was the percentage of PIH for ED versus controls. Main results and the role of chance ED was indicated for genetic disease in 17 cases (23.3%), double total infertility in 28 cases (38.3%), and double partial/total infertility in 35 cases (47.9%). Groups were comparable in age (mean age: 34.5 ± 8.6 versus 34.5 ± 4.5; p = 0.68), BMI, except for parity (more nulliparity in ED group: 90.4% vs 79.4%; p = 0.04). Pregnancy outcomes were similar for ED and control groups, the percentages of deliveries being 80.8% and 83.8%, respectively (p = 0.58). PIH occurred significantly more frequently among ED than control pregnancies (24.6% versus 11.9%; P = 0.04), with the difference mainly observed for severe forms: preeclampsia and HELLP (17.5% vs 4.6%; p = 0.01). No eclampsia was reported. In contrast, isolated hypertension frequency was comparable (7.0% vs. 7.3%, p = 0.94). Regarding labor and delivery mode, in ED group C-section was more frequent (47.3% vs 29.2%; p = 0.03). In neonatal data, no difference was found between ED and control group for prematurity, weight and height at birth, Apgar score, Small for gestational age, Large for gestational age and sex ratio. Seven neonatal malformations were recorded in ED group and 3 in the control group (NS). Limitations, reasons for caution Retrospective study in a relatively long period when different endometrial preparation for frozen-thawed embryo transfer and embryo cryopreservation method were used. Relatively limited number of ED because of low practice in France. No analysis of embryo stage at transfer (cleaved embryo or blastocyst). Wider implications of the findings: The PIH risk must be acknowledged to inform couples and provide careful pregnancy monitoring. A special care for gestational carrier should also be done since the allogenic situation is the same than in ED recipients. Trial registration number Not applicable

O-182 Higher risk of preeclampsia and pregnancy-induced hypertension with artificial cycle for Frozen-thawed Embryo Transfer compared to ovulatory cycle or fresh transfer following In Vitro Fertilization

Abstract Study question Is there an increased risk of preeclampsia after Frozen-thawed Embryo Transfer(FET) compared to In Vitro Fertilization-fresh transfer(IVF-fresh-ET) according to endometrial type of preparation for FET? Summary answer The frequency of preeclampsia and hypertension were significantly higher in the group of artificial cycle (AC-FET) compared to ovulatory cycle (OC-FET) and fresh-ET (P &amp;lt; 0.0001). What is known already Risks of maternal morbidity are known to be reduced in pregnancies resulting from FET compared to fresh-ET except for the risk of preeclampsia, that was reported to be significantly higher in pregnancies resulting from FET compared to fresh-ET or spontaneous conception. Most recent studies demonstrate an equal live birth rate with either OC-FET or AC-FET preparation. Few studies compared the maternal vascular morbidities with the two hormonal environments that preside over the early stages of embryonic development: OC (major role of the corpus luteum) and AC (prolonged hormone replacement with high doses of estrogen and progesterone). Study design, size, duration We conducted a 2013-2018 French nationwide cohort study comparing maternal vascular morbidities in 3 groups of single pregnancies&amp;gt; 22 weeks of gestation (WG): FET with AC or OC preparation, and IVF (conventional or ICSI)-fresh-ET.Data were extracted from the French National Health System database (&amp;gt;99% of national deliveries) in which all hospitalizations are registered, containing information on patient characteristics, diagnoses and treatments. Records were merged anonymously. Access to the database was legally approved. Participants/materials, setting, methods 68 025 deliveries were included: fresh-ET(n = 48 152), OC-FET(n = 9 500), AC-FET(n = 10 373). In OC-FET, a luteal phase support with progesterone was administered for maximum 6 WG if pregnancy. In AC-FET, progesterone was co-administered with estrogen until 12 WG. Embryos were transferred at cleavage or blastocyst stage. Vascular disorders were recorded if hospitalization for preeclampsia/eclampsia or hypertension (history of hypertension excluded). Maternal characteristics were included in multivariate analysis. Adjusted odds ratios(aOR) and 95% confidence intervals(CI) were estimated. Main results and the role of chance Maternal characteristics: In multivariate analysis, patients in the FET groups were older (33.4 years (std=4.3) vs. 33.2 years (std=4.4) for fresh-ET, respectively, P &amp;lt; 0.0001), less often primiparous (aOR=0.68[0.66-0.71], P &amp;lt; 0.0001) or smokers (aOR=0.84[0.75-0.95]) or with premature ovarian insufficiency (POI) (aOR=0.68 [0.58-0.79]), more frequently with polycystic ovaries (PCOS) (aOR=1.25[1.12-1.39]) and comparable for obesity or diabetes. In FET groups, 52.2% were AC-FET. There was no difference for maternal age, parity, obesity, smoking, history of diabetes between AC and OC-FET. Endometriosis (aOR=1.26[1.16-1.38]), PCOS (aOR=1.79[1.50-2.15]) and POI (aOR=2.0[1.48-2.72]) were more frequent in AC-FET. Risks of vascular disorders The rate of preeclampsia (5.3% vs. 2.3% vs. 2.4%, respectively, P &amp;lt; 0.0001) and hypertension (4.7% vs. 3.4% vs. 3.3%, respectively, P = 0.0002) was significantly higher in AC-FET versus OC-FET and fresh-ET. In multivariate analysis, the risk of preeclampsia increased with age, primiparity, obesity, diabetes and POI. The risk was higher in AC-FET versus OC-FET (aOR=2.42 [2.06-2.85]) and fresh-ET (aOR=2.43[2.2-2.7]), P &amp;lt; 0.00001. No difference was found between OC-FET and fresh-ET (P = 0.91). The risk of pregnancy-induced hypertension increased with age &amp;gt;40, primiparity, smoking, obesity and diabetes and was higher in AC-FET versus OC-FET (aOR=1.50[1.29-1.74], P &amp;lt; 0.0001) and fresh-ET (aOR=1.50[1.35-1.67], P &amp;lt; 0.0001) and not different between OC-FET and fresh-ET (P = 0.86). Limitations, reasons for caution While the strength of this study relies in the number and exhaustiveness of subjects analysed, its limitations are its retrospective and register-based nature that did not enable to refine the risk according to details of techniques and treatments in each group. Wider implications of the findings This large nationwide cohort study highlights 2 important information for physicians : i) the possible deleterious role of high supra-physiological and prolonged doses of estrogen-progesterone supplementation on vascular pathologies ii) the protective role of the corpus luteum present in stimulated or spontaneous OC for their prevention. Trial registration number Not applicable

Effect of transdermal estrogen dose regimen for endometrial preparation of frozen-thawed embryo transfer on reproductive and obstetric outcomes.

PurposePrevious studies have reported different methods of estrogen administration during endometrial preparation for frozen‐thawed embryo transfer (FET). This study aimed to investigate a beneficial regimen of transdermal estrogen administration for FET.MethodsWe investigated the reproductive and obstetric outcomes of FET by comparing the increasing dose (ID) group that mimics changes in serum estradiol during the menstrual cycle and the constant dose (CD) group. Transdermal patches were used for estrogen administration in both groups. In our hospital, we targeted 315 cycles of the ID group in which FET was performed in 2017 and 324 cycles of the CD group in which FET was performed in 2018. In all cases, single embryo transfer was performed.ResultsAll were singleton pregnancies. There was no difference in clinical pregnancy rate (28.9% vs 28.2%, P =.837) and live birth rate (17.3% vs 21.4%, P =.201) between the ID and CD groups. Spontaneous abortion rate was significantly lower in the CD group than in the ID group (37.2% vs 23.0%, P =.041). There was no difference in obstetrical outcomes.ConclusionsIt was considered that the simple CD regimen may be more beneficial than the complicated ID regimen.

PREGNANCY OUTCOMES IN LETROZOLE OVULATION INDUCTION FROZEN-THAWED EMBRYO TRANSFER CYCLES AS COMPARED TO NATURAL AND PROGRAMMED CYCLES

The optimal endometrial preparation for frozen-thawed embryo transfer (FET) cycles is controversial and variable among IVF centers. Our aim is to compare pregnancy outcomes between letrozole ovulation induction FET cycles, natural FET cycles and programmed FET cycles in a US-based population. Single academic center retrospective cohort study. 2310 cycles consisting of patients <43 years utilizing embryos created from autologous oocytes between 2015-2020 were included. Blastocyst embryo transfer occurred 6 days after a natural LH surge to >20 mIU/mL in natural and letrozole cycles, or 6 days after the initiation of intramuscular progesterone in programmed cycles. The primary outcome was the ongoing pregnancy rate (OPR), and secondary outcomes included pregnancy rate (PR), implantation rate (IR), clinical pregnancy rate (CPR), and clinical loss rate (CLR). Chi-square test for categorical data and one-way ANOVA for continuous data was used with Bonferroni correction for multiple comparisons. Multiple logistic regression analysis was performed adjusting for age, BMI, anovulation diagnosis, number of embryos transferred and utilization of preimplantation genetic testing for aneuploidy (PGT-A). A two-sided p-value of <0.05 was considered statistically significant. There was a higher proportion of patients with a diagnosis of anovulation in both letrozole and programmed FET cycles compared with natural cycles (p < 0.01). Patients undergoing programmed FET cycles were more likely to be younger, have a higher BMI, and to have more embryos transferred compared to patients undergoing natural FET and letrozole FET cycles (p < 0.01). The OPRs and CPRs were similar between the groups, while the CLRs were higher in the programmed compared with natural and letrozole FET cycles. After adjusting for potential covariates, the probability of clinical loss was still significantly higher in programmed cycles compared with natural and letrozole FET cycles (aOR 1.58; 95% CI, 1.15-2.12; p < 0.01).Tabled 1OutcomeNatural FET (n = 1135)Letrozole FET (n = 88)Programmed FET (n = 1087)p valuePR (%, n)77.8 (883/1135)78.4 (69/88)79.9 (869/1087)0.46IR (%, n)62.1 (877/1413)63.4 (64/101)62.1 (903/1455)0.96CPR (%, n)68.8 (781/1135)67.0 (59/88)69.5 (755/1087)0.87OPR (%, n)60.4 (686/1135)59.1 (52/88)56.9 (619/1087)0.25CLR (%, n)11.5 (90/781)11.9 (7/59)17.5 (132/755)<0.01 Open table in a new tab Letrozole ovulation induction may be a better alternative to programmed FET cycles particularly for anovulatory patients in view of the lower clinical loss rate.

Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen

The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.

8. COMPARISON OF NATURAL CYCLES VERSUS HORMONE REPLACEMENT TREATMENT FOR 2398 FROZEN–THAWED EMBRYO TRANSFER CYCLES FOR PREIMPLANTATION GENETIC TESTING PATIENTS

Introduction Multiple studies have been performed to evaluate the efficiencies of various endometrial preparation protocols. However, to date, the most appropriate method of endometrial preparation for frozen-thawed embryo transfer (FET) remains debated. To our knowledge, there are no studies comparing FET cycle endometrial preparation protocol for PGT patients, and this study is the first study to compare FET cycle endometrial preparation protocols for PGT patients. Material & methods This retrospective analysis included 2398 FET cycles for 1497 preimplantation genetic testing (PGT) patients with regular menstrual cycles who underwent frozen-thawed single blastocyst transfer from January 2014 to December 2017. The patients were divided into two groups according to the method of endometrial preparation for FET: 586 cycles were natural cycles(NC), and 1812 cycles were hormone replacement treatment (HRT). Reproduction-related clinical outcomes of the two groups were compared. Results The NC group showed a higher clinical pregnancy rate (54.78% vs 51.66%, P=0.188) and live birth rate (45.22% vs 43.21%, P=0.394) than did the HRT group, but these differences were not statistically significant. Moreover, endometrial thickness was significantly greater in the NC group (9.91±2.05 mm vs 8.95±1.53 mm, P Conclusion Our study shows a trend towards higher pregnancy rate and live birth rate for NC compared to HRT. Large randomized controlled trials are warranted to confirm this trend. Additionally, NC is safer than HRT, avoiding ectopic pregnancy and adverse obstetric outcomes.

Modified hMG stimulated: an effective option in endometrial preparation for frozen-thawed embryo transfer in patients with normal menstrual cycles

To evaluate the clinical efficacy of modified human menopausal gonadotropin (hMG) stimulated, hormone replacement therapy (HRT), natural cycling and letrozole ovulation induction during endometrial preparation for frozen-thawed embryo transfer (FET) in patients with normal menstrual cycles. This retrospective analysis included a total of 5070 cycles of patients with normal menstrual patterns who underwent FET between October 2009 and September 2015. The patients were divided into four groups according to the method of endometrial preparation for FET: 1838 cycles were natural, 1666 underwent HRT, 340 underwent letrozole ovulation induction and 1226 underwent modified hMG stimulated. Reproduction-related clinical outcomes in the four groups were compared. The clinical pregnancy rates and live birth rates of patients in the modified hMG stimulated group were significantly higher than that in the other groups p < .05. While abortion rates were not significantly different among all four groups (all p >.05). Modified hMG stimulated resulted in a higher pregnancy rate compared to the other treatment groups. Therefore, modified hMG stimulated may be an effective option in endometrial preparation for FET in patients with normal menstrual cycles.

Can letrozole plus HMG protocol improve pregnancy outcomes in frozen-thawed embryo transfer? An RCT

There are different methods in endometrial preparation for frozen-thawed embryo transfer (FET). The purpose of this study was to compare the live birth rate in the artificial FET protocol (estradiol/ progesterone with GnRH-agonist) with stimulated cycle FET protocol (letrozole plus HMG). This randomized clinical trial included 100 women (18-42 years) randomly assigned to two groups based on Bernoulli distribution. Group I received GnRH agonist [Bucerelin, 500μg subcutaneously] from the previous midlutea lcycle, Then estradiol valerat [2 mg/ daily orally] was started on the second day and was increased until the observation of 8mm endometrial thickness. Finally progesterone [Cyclogest, 800 mg, vaginally] was started. Group II received letrozole on the second day of the cycle for five days, then HMG 75 IU was injected on the7th day. After observing [18 mm folliclhCG10000 IU was injected for ovulation induction. Trans cervical embryo transfer was performed in two groups. The main outcome was the live birth rate. The rate of live birth, implantation, chemical, and clinical pregnancy, abortion, cancellation and endometrial thickness were compared between two groups. Implantation rate was significantly higher in group I. Live birth rate was slightly increased in group I without significant difference (30% vs. 26%). The rate of chemical and clinical pregnancy was similar in two groups. The abortion rate was lower in letrozole protocol but the difference was not statistically significant. The mean endometrial thickness was not different between two groups. Letrozole plus HMG method cannot improve pregnancy outcomes in frozen-thawed embryo transfer but it has only one injection compare to daily injections in artificial method.

Effect of Natural Cycle Endometrial Preparation for Frozen-Thawed Embryo Transfer in Patients with Advanced Endometriosis

BackgroundThe aim of this study was to investigate the effect of natural cycle (NC) endometrial preparation for frozen-thawed embryo transfer (FET) in women with advanced endometriosis.Material/MethodsThis retrospective study included 179 patients with stage III–IV endometriosis who underwent 233 FET cycles at a tertiary care academic reproductive medical center between March 2011 and August 2013 (group A). The control group included 258 patients with tubal factor infertility who underwent 300 FET cycles (group B). Both groups were prepared for FET using a NC protocol. Rates of implantation, clinical pregnancy, live birth, ongoing pregnancy, miscarriage, and pregnancy complication were recorded.ResultsThe implantation rate (A: 36.0%, B: 30.4%, P=0.06), the pregnancy rate (A: 50.2%, B: 45.3%, P=0.263), and the live birth rate (A: 39.91%, B: 39.0%, P=0.428) were similar between the stage III–IV endometriosis and tubal factor infertility groups. No differences were observed in ongoing rates of pregnancy, miscarriage, and pregnancy complications, independent of endometriosis severity. No congenital birth defects were found. When high-quality embryos are transferred, pregnancy results were not affected by active endometriosis. Although severe endometriosis did not affect birth rate, higher frequencies of premature delivery (mean gestational age A: 37 weeks, B: 38.3 weeks, P=0.044) and low birth weight were observed (<2500 g A: 26.4%, B: 16.6%, P=0.047).ConclusionsThere was no difference in pregnancy outcomes between patients with endometriosis and those with tubal infertility. Pregnancy outcomes in patients with endometriosis were not affected by endometriosis severity. Pregnancy outcomes were not affected by active endometrial cyst.

The future of IVF: vitrified-warmed blastocyst transfer

Introduction: The development of blastocyst vitrification has significantly changed the approach to embryo transfer. In cases where there is a high risk for developing ovarian hyperstimulation syndrome, all embryos can be vitrified and transferred in subsequent menstrual cycles. On the other hand, vitrification of surplus embryos at the time of transfer allows for higher cumulative pregnancy rates. The optimal method of endometrium preparation for frozen-thawed embryo transfer (FET) still remains uncertain. The aim of this study was to compare the outcomes of vitrified-warmed blastocyst transfers in natural and artificially prepared cycles. Methods: All vitrified-warmed blastocyst transfers performed in the last two years (2013 and 2014) at our IVF centre were included in this retrospective study. In women with predictable and regular ovulatory cycles, FETs were performed in natural cycles without hCG triggering. In patients with irregular and anovulatory cycles, FETs were performed in artificially prepared cycle using the combination of oestradiol and micronized progesterone without GnRH agonist suppression. Patients’ characteristics, treatment parameters and pregnancy outcomes were compared using Pearson's Chi-squared test and Student's t-test. Results: In the study period, 835 vitrified-warmed blastocyst transfers were performed in natural and 278 in artificially prepared cycles. There were no statistically significant differences in patients’ characteristics and treatment parameters between both groups, with the exception of the average number of transferred embryos (1.30 in natural cycles vs. 1.41 in artificial cycles, p < 0.05). The biochemical pregnancy rate observed was higher in artificial cycles (8.90% vs. 17.64%), but there were no statistically significant differences in clinical pregnancy rate (36.03% vs. 34.89%), implantation rate (31.26% vs. 28.94%), abortion rate (14.54% vs. 21.00%) and live birth/ongoing pregnancy rate (30.53% vs. 25.18%) in natural compared to artificial cycles. Conclusion: Vitrified-warmed blastocyst transfers in natural and artificially prepared cycles are equally successful in terms of implantation, ongoing pregnancy and live birth rate. The outcome of vitrified-warmed blastocyst transfer in natural as well as artificial cycles appears to be comparable to blastocyst transfer in fresh IVF cycles.

Different endometrial preparation protocols yield similar pregnancy outcomes for frozen-thawed embryo transfer in patients with advanced endometriosis

Objective To explore the different endometrial preparation for frozen-thawed embryo transfer (FET) in women with advanced endometriosis (EMS). Methods The pregnancy outcomes of patients with advanced EMS (542 cycles), who were prepared for FET, were retrospectively assessed. Included patients underwent a total of 233 FET cycles (180 patients) using natural cycle (NC), a total of 142 FET cycles (115 patients) using letrozole (LE) ovulation induction, and a total of 167 FET cycles (137 patients) using hormonal replacement treatment (HRT) for endometrial preparation. Results There were no significant diffenences in the clinical pregnancy rate (LE: 49.30%, NC: 50.21%, and HRT: 43.11%, P=0.343), the implantation rate (LE: 29.26%, NC: 36.03%, and HRT: 29.55%, P=0.084), and the live birth rate (LE: 38.02%, NC: 39.11%, and HRT: 35.33%, P=0.648) among the three groups. No statistically significant differences were observed in the ongoing pregnancy rate, the miscarriage rate, and the pregnancy complication rate. The single birth weight in patients using NC-FET was lower than that in patients using HRT-FET (P=0.044) and a higher twin birth weight in patients using LE-FET were observed compared with other groups (P=0.022). The rate of birth weight Conclusion Different endometrial preparation protocols without ultra-long GnRH-a down-regulation for FET yield similar pregnancy outcomes in patients with EMS. A tailored endometrial preparation protocol should be recommended according to different patients’ situation.