P–654 What is the best luteal phase support in frozen-thawed embryo transfer cycle?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Vidal ◽  
C Dhakal ◽  
J Weiss ◽  
D Lehnick ◽  
A Koh. Schwartz

Abstract Study question What is the best progesterone administration for luteal phase support (LPS) in frozen-thawed embryo transfer cycle? Summary answer Different modes of hormonal luteal phase support do not affect clinical pregnancy rate (CPR) or live birth rate (LBR) in frozen-thawed embryo transfer (FET) cycles. What is known already FET has increased substantially over the last years. To support implantation, endometrial and embryo maturities must be synchronized; therefore, endometrial and follicular maturation are monitored either within the artificial cycle. Estrogen and progesterone are sequentially administered. The optimal endometrial preparation strategy remains unclear; this study aims to compare the reproductive and pregnancy outcomes between five different regimens of hormonal LPS for FET treatment. Study design, size, duration Single centre retrospective cohort study conducted between 2013 and 2019. Included were women (N = 402) aged 18–45 years undergoing FET. After an optimal endometrial preparation and endometrial thickness, the LPS was started. Thereafter, five different progesterone applications were compared: (1) oral dydrogesterone (10mg tid), (2) vaginal progesterone gel (90mg/d), (3) dydrogesterone (10mg tid) plus vaginal progesterone gel (90mg/d), (4) vaginal progesterone capsules (200mg tid), or (5) subcutaneous injection of 25mg daily. Participants/materials, setting, methods An ultrasound was performed 14 days of estrogene ( > =4mg/d) preparation. If the endometrial thickness was ≥7 mm and there was no dominant follicle, luteal support commenced four days before FET. Fourteen days after transformation, a serum beta-hCG test was performed. If positive (> 50 IU/L), a transvaginal ultrasound was performed to confirm clinical pregnancy, defined as gestational sac with fetal heart movement. CPR was assessed and delivery reports for LBR were collected later. Main results and the role of chance In total, 402 patients on an artificial cycle were included (mean age, 35 years (y); range, 26–46 y; standard deviation, 4.1 y). No differences in endometrial thickness and cause of infertility were found between groups. Multivariate logistic regression analysis revealed that the odds ratios (ORs) with 95% confidence intervals (CIs) for the CPR was significantly higher in the dydrogesterone only group (OR, 3.25; 95% CI, 1.7–6.2; p < 0.001) and in the combined group (3) (OR, 7.55; 95% CI, 2.7–21.10; p < 0.001). Statistically significant differences in live birth rate could not be found between the five groups; they were 33%, 54%, 8.3%, 4%, 0% for groups 1, 2, 3, 4, and 5 respectively. Overall satisfaction and tolerability were significantly higher in oral dydrogesterone compared to the vaginal progesterone. Limitations, reasons for caution This is a retrospective single-center study. Also, potentially confounding variables like ethnicity, parity, BMI were not accounted for, possibly contributing to bias. Further prospective randomized studies are needed. Wider implications of the findings: Oral dydrogesterone was found to be effective with equal CPR and LBR. Benefit is well-tolerated and accepted among patients; however we did not observe significant differences in the rates of live birth between the five regimens for used for LPS in women undergoing frozen-thawed embryo transfers. Trial registration number BASEC Switzerland 2020–01527

Author(s):  
Abbas Aflatoonian ◽  
Banafsheh Mohammadi

Background: Luteal-phase support is a complex and controversial issue in the field of reproductive management. Objective: To compare the safety and efficacy of low-dose subcutaneous progesterone with the vaginal progesterone for luteal-phase support in patients undergoing rozenthawed embryo transfer. Materials and Methods: In this cross-sectional study, information related to 77 women that had frozen-thawed embryo transfer was reviewed. The patients were divided into two groups based on the route of progesterone administration used as a luteal-phase support. When the endometrial thickness reached ≥ 8 mm, in one group progesterone (Prolutex) 25 mg/ daily subcutaneous and in another group, vaginal progesterone (Cyclogest®) 400 mg twice or (Endometrin®) 100 mg thrice daily, were administrated and continued until menstruation or in case of clinical pregnancy for 8 wk after the embryo transfer when the fetal heart activity was detected by ultrasonography. Results: The patient’s characteristics were matched and there was no significant difference. The chemical and clinical pregnancy rate was higher in the vaginal progesterone group compared to the prolutex group, but statistically unnoticeable, (40% vs. 29.6%, p = 0.367) and (28% vs. 22.2%, p = 0.581), respectively. C Conclusion: The findings of this study demonstrate that the new subcutaneous progesterone can be a good alternative for intramuscular progesterone in women that dislike and do not accept vaginal formulations as luteal-phase support in assisted reproductive technology. Key words: Progesterone, Subcutaneous, Vaginal, Pregnancy.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Yaprak ◽  
Y E Sukur ◽  
B Ozmen ◽  
M Sonmezer ◽  
B Berker ◽  
...  

Abstract Study question What is the effect of endometrial compaction on live birth rate in frozen-thawed embryo transfer (FET) cycles? Summary answer In FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction. What is known already Most studies conclude that thinner the endometrium poorer the pregnancy outcome. These studies mostly include measurements in the follicular phase. Since endometrial thickness indicates receptivity, one may expect the endometrial thickness measured on ET day to be more important to predict the outcome. However, few studies assessed endometrial thickness on ET day and unlike follicular phase studies conflicting results were obtained regarding pregnancy outcome. The change in endometrial thickness may be more valuable to predict the pregnancy outcome rather than a single measurement. Study design, size, duration Retrospective observational cohort study. 283 FET cycles in which all patients underwent artificial endometrial preparation were reviewed. Participants/materials, setting, methods: The inclusion criteria were artificial endometrial preparation, age between 20–38 years. The same protocol was applied to all patients for the endometrial preparation.The change of endometrial thickness between the end of estrogen phase and embryo transfer day was recorded. Any decrement is defined as endometrial compaction. The patients were grouped according to the changes of endometrial thicknesses as compaction and non-compaction. Main results and the role of chance Among 283 cycles, 89 had endometrial compaction and 194 did not have compaction. The clinical pregnancy, implantation and live birth rates were significantly higher in the compaction group when compared to non-compaction group (P values 0.007, 0.009, and 0.039, respectively). In order to evaluate the results according to the degree of compaction, we divided the patients into 5% compaction slices. The live birth rate was significantly higher in the 5–10% compaction group (P = 0.016). A multivariable logistic regression analysis was performed to examine the independent effects of different variables on live birth chance.In FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction (OR: 2.352, 95% confidence interval {CI} 1.297–4.264, P = 0.005). A receiver operating characteristic (ROC) curve analysis was performed to evaluate whether there was a certain threshold of endometrial thickness at the end of estrogen phase for endometrial compaction to occur. The sensitivity and specificity of 9.25 mm at the end of estrogen phase calculated from the ROC curve were 76.4% and 58.8%, respectively (area under the curve: 0.701, 95% CI 0.640–0.763; P < 0.001). Limitations, reasons for caution The main limitations of the study were its retrospective nature, relatively small sample size and utilization of different ultrasound techniques at different measurements (using transvaginal ultrasound at the end of the estrogen phase and transabdominal ultrasound on ET day). Wider implications of the findings: Recently a cohort study they found that endometrial compaction results in better pregnancy outcomes, similar to our findings. But, this is the first study to suggest a threshold value (9.2) for endometrial thickness before the commencement of progesterone in regards to increase the chance of compaction. Trial registration number Not applicable


Author(s):  
Afsoon Zareii ◽  
Sara Davoodi ◽  
Mahshid Alborzi ◽  
Marzieh Eslami Moghadam ◽  
Elham Askary

Background: Since progesterone alone does not seem to be enough for luteal phase support (LPS), especially in frozen embryo transfer (FET) cycles, so gonadotropin-releasing hormone agonist (GnRH-a) is suggested as an adjuvant therapy in combination with progesterone for LPS. Objective: To evaluate the effects of the administration of GnRH agonists with vaginal progesterone compared to vaginal progesterone alone in luteal phase support of the frozen-thawed embryo transfer cycles. Materials and Methods: In this randomized controlled clinical trial, 240 infertile women who were candidates for FET were evaluated into two groups (n = 120/each). Group I received 400 mg vaginal progesterone twice a day from the time of transfer. The second group received vaginal progesterone and also 0.1 mg diphereline on days 0, 3, and 6 of FET for LPS. Finally, the clinical and ongoing pregnancy rates, and the implantation, and spontaneous abortion rates were compared in two groups. Results: Results showed that there was no significant difference between the mean age of women and the duration of infertility (p = 0.78, p = 0.58, respectively). There were no significant differences between groups in the terms of implantation and spontaneous abortion rates (p = 0.19, p = 0.31, respectively). However, in terms of clinical and ongoing pregnancy rates, the significant differences were seen between groups (p = 0.008 and p = 0.005, respectively). Conclusion: Co-administration of GnRH-a and vaginal progesterone in LPS may be superior to vaginal progesterone alone in women who underwent a frozen-selected embryo transfer cycle. Key words: Luteal phase, Fertilization in vitro, Embryo transfer.


Author(s):  
Maëliss Peigné ◽  
Emmanuel Devouche ◽  
Xavier Ferraretto ◽  
Solenne Gricourt ◽  
Dominique Luton ◽  
...  

2016 ◽  
Vol 295 (1) ◽  
pp. 239-246 ◽  
Author(s):  
Afsoon Zarei ◽  
Parastoo Sohail ◽  
Mohammad Ebrahim Parsanezhad ◽  
Saeed Alborzi ◽  
Alamtaj Samsami ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Turkgeldi ◽  
B Shakerian ◽  
S Yildiz ◽  
I Keles ◽  
B Ata

Abstract Study question Does endometrial thickness (EMT) predict live birth (LB) after fresh and frozen-thawed embryo transfer (ET) and is there a lower EMT cut-off for ET? Summary answer Once intracavitary pathology and inadvertent progesterone exposure is excluded, EMT is not predictive for LB. EMT is not linearly associated with probability of LB. What is known already EMT is commonly used as a marker of endometrial receptivity and in turn, assisted reproductive technology treatment success. ET is often cancelled or postponed if EMT is below an arbitrary cut-off. However, the available evidence on the relationship between EMT and LB rates is conflicting and too dubious to hold such strong stance. An overwhelming majority of the studies on the subject are retrospective, they use different arbitrary cut off values ranging between 6 to 9 mm with heterogeneous stimulation and transfer protocols. Study design, size, duration Records of all women who underwent fresh or frozen-thawed ET in Koc University Hospital Assisted Reproduction Unit between October 2016 - August 2019 were retrospectively screened. All women who underwent fresh or frozen-thawed blastocyst transfer during the study period were included. Every woman contributed to the study with only one transfer cycle for each category, i.e., fresh ET and frozen-thawed ET. Participants/materials, setting, methods After ruling out endometrial pathology, EMT was measured on the day of ovulation trigger for fresh ET cycles, and on the day of progesterone commencement for frozen-thawed ET. ET was carried out, regardless of EMT, if there was no suspicion of inadvertent progesterone exposure, i.e., due to follicular phase progesterone elevation in fresh or premature ovulation in frozen ET cycles. Main results and the role of chance 560 ET cycles, 273 fresh and 287 frozen-thawed, were analyzed. EMT varied from 4mm to 18mm. EMT were similar between women who achieved a LB and who did not after fresh ET [10.5 (9.2 – 12.2) mm and 9 (8 – 11) mm, respectively, p = 0.11]. Ovarian stimulation characteristics and proportion of women who received a single embryo were similar (69% vs 68.3%, respectively, p = 0.91). Women who achieved a LB was significantly younger than those who did not [35 (32–38) and 37 (33–41), respectively, p < 0.01]. Women who had a LB and who did not after frozen-thawed ET had similar EMT of 8.4 (7.4 – 9.7) mm and 9 (8 – 10) mm, respectively (p = 0.38). Women who achieved a LB were significantly younger than those who did not [32 (29–35) vs 34 (30–38) years, p = 0.04]. The proportion of women who received a single ET was similar between women who achieved a LB and who did not after a FET [86/95 (90.5%) vs 181/192 (94.3%), respectively, p = 0.26]. Area under curve values of EMT for predicting LB in fresh, frozen-thawed and all ET were 0.56, 0.47 and 0.52, respectively. EMT and LB rate were not linearly correlated in fresh or frozen-thawed ET cycles. Limitations, reasons for caution Although our study is retrospective, no women was denied ET due to EMT in our center. Only patients undergoing ET were included in the analysis, which may introduce bias due to the selection of couples who were competent enough to produce at least one blastocyst fit for transfer. Wider implications of the findings: Since women with thin endometrium had reasonable chance for LB even in the absence of a cut-off for EMT in this unique dataset, delaying or denying ET for any given EMT value alone does not seem justified. Further studies in which ET is carried out regardless of EMT are needed. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Cedri. . Durnerin ◽  
M Peigné ◽  
J Labrosse ◽  
M Guerout ◽  
C Vinolas ◽  
...  

Abstract Study question Does systematic dydrogesterone supplementation in artificial cycles (AC) for frozen-thawed embryo transfer (FET) during Covid–19 pandemic modify outcomes compared to prior individualized supplementation adjusted on serum progesterone (P) levels ? Summary answer Systematic dydrogesterone supplementation in AC for FET is associated with similar outcomes compared to prior individualized supplementation in patients with low P levels. What is known already In AC for FET using vaginal P for endometrial preparation, low serum P levels following P administration have been associated with decreased pregnancy and live birth rates. This deleterious effect can be overcome by addition of other routes of P administration. We obtained effective results by adding dydrogesterone to vaginal P and postponing FET by one day in patients with low P levels. However, in order to limit patient monitoring visits and to schedule better FET activity during Covid–19 pandemic, we implemented a systematic dydrogesterone supplementation without luteal P measurement in artificial FET cycles. Study design, size, duration This retrospective study aimed to analyse outcomes of 394 FET after 2 different protocols of artificial endometrial preparation. From September 2019 to Covid–19 lockdown on 15th March 2020, patients had serum P level measured on D1 of vaginal P administration. When P levels were < 11 ng/ml, dydrogesterone supplementation was administered and FET was postponed by one day. From May to December 2020, no P measurement was performed and dydrogesterone supplementation was systematically used. Participants/materials, setting, methods In our university hospital, endometrial preparation was performed using sequential administration of vaginal estradiol until endometrial thickness reached >7 mm, followed by transdermal estradiol combined with 800 mg/day vaginal micronized P started in the evening (D0). Oral dydrogesterone supplementation (30 mg/day) was started concomitantly to vaginal P in all patients during Covid–19 pandemic and only after D1 P measurement followed by one day FET postponement in patients with P levels <11 ng/ml before the lockdown. Main results and the role of chance During the Covid–19 pandemic, 198 FET were performed on D2, D3 or D5 of P administration with dydrogesterone supplementation depending on embryo stage at cryopreservation. Concerning the 196 FET before lockdown, 124 (63%) were performed after dydrogesterone addition from D1 onwards and postponement by one day in patients with serum P levels <11 ng/ml at D1 while 72 were performed in phase following introduction of vaginal P without dydrogesterone supplementation in patients with P > 11 ng/ml. Characteristics of patients in the 2 time periods were similar for age (34.5 + 5 vs 34.1 + 4.8 years), endometrial thickness prior to P introduction (9.9 + 2.1 vs 9.9 + 2.2 mm), number of transferred embryos (1.3 + 0.5 vs 1.4 + 0.5) , embryo transfer stage (D2/D3/blastocyst: 8/16/76% vs 3/18/79%). No significant difference was observed between both time periods [nor between “dydrogesterone addition and postponement by 1 day” and “in phase” FET before lockdown] in terms of positive pregnancy test (39.4% vs 39.3% [44% vs 30.5%]), heartbeat activity at 8 weeks (29.3% vs 28% [29% vs 26.4%]) and ongoing pregnancy rates at 12 weeks (30.7% but truncated at end of October 2020 vs 25.5% [26.6% vs 23.6%]). Limitations, reasons for caution Full results of the Covid–19 period will be further provided concerning ongoing pregnancy rates as well as comparison of live birth rates and obstetrical and neonatal outcomes. Wider implications of the findings: These results suggest that systematic dydrogesterone supplementation is as effective as individualized supplementation according to serum P levels following administration of vaginal P. This strategy enabled us to schedule easier FET and limit patient visits for monitoring while maintaining optimal results for FET in AC during the Covid–19 pandemic. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Ho ◽  
T Pham ◽  
K Le ◽  
T Ly ◽  
H Le ◽  
...  

Abstract Study question Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone? Summary answer Luteal phase support with oral dydrogesterone added to vaginal progesterone improves live birth rates and reduces miscarriage rates compared with vaginal progesterone alone. What is known already Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During in vitro fertilization (IVF), exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET. Study design, size, duration Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020. Participants/materials, setting, methods We studied 1364 women undergoing IVF with FET. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints. Main results and the role of chance The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% confidence interval [CI] 0.99–1.27, p = 0.06; multivariate analysis RR 1.30 (95% CI 1.01–1.68), p = 0.042), with a statistically significant lower rate of miscarriage at < 12 weeks (3.4% vs 6.6%; RR 0.51, 95% CI 0.32–0.83; p = 0.009). Birth weight of both singletons (2971.0 ± 628.4 vs. 3118.8 ± 559.2 g; p = 0.004) and twins (2175.5 ± 494.8 vs. 2494.2 ± 584.7; p = 0.002) was significantly lower in the progesterone plus dydrogesterone versus progesterone group. Limitations, reasons for caution The study were the open-label design and the non-randomized nature of the sequential administration of study treatments. However, our systematic comparison of the two strategies was able to be performed much more rapidly than a conventional randomized controlled trial. In addition, the single ethnicity population limits external generalizability. Wider implications of the findings Oral dydrogesterone in addition to vaginal progesterone as luteal phase support in FET cycles can reduce the miscarriage rate and improve the live birth rate. Carefully planned prospective cohort studies with limited bias could be used as an alternative to randomized controlled clinical trials to inform clinical practice. Trial registration number NCT03998761


2021 ◽  
Author(s):  
xiaoyue Shen ◽  
Min Ding ◽  
Yuan Yan ◽  
Shanshan Wang ◽  
jianjun Zhou ◽  
...  

Abstract Background To evaluate the frozen-thawed embryo transfer (FET) outcomes of repeated cryopreservation by vitrification of blastocysts derived from vitrified-warmed day3 embryos in patients who experienced implantation failure previously. Methods We retrospect the files of patients who underwent single frozen-thawed blastocyst transfer cycles in our reproductive medical center from January 2013 to December 2019. 127 patients transfer of vitrified-warmed blastocysts derived from vitrified-warmed day3 embryos were defined as twice-cryopreserved group. 1567 patients who transfer blastocysts that had experienced once vitrified-warmed were used as once-cryopreserved group. None of them was pregnant at the previous FET. The outcomes were compared between two groups after a 1:1 propensity score matching (PSM). Results The clinical pregnancy rate was 52.76%, live birth rate was 43.31% in twice-cryopreserved group. After PSM,108 pairs of patients were generated for comparison. The clinical pregnancy rate, live birth rate or miscarriage rate was not significantly different between two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect FET outcomes in terms of clinical pregnancy rate (OR 0.83, 95%CI 0.47-1.42), live birth rate (OR 0.93, 95%CI 0.54-1.59), miscarriage rate (OR 0.72 95%CI 0.28-1.85). Furthermore, the pregnancy complications rate, gestational age or neonatal abnormalities rate between two groups was also comparable, while twice vitrification-warming procedures might increase the macrosomia rate (19.6% vs. 6.3%, P = 0.05). Conclusion Transfer of double vitrified-warmed embryo at cleavage stage and subsequent blastocyst stage did not affect live birth rate and neonatal abnormalities rate, but there was a tendency to increase macrosomia rate, which needs further investigation.


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