Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles

Author(s):  
Elena Labarta ◽  
Giulia Mariani ◽  
Cristina Rodríguez-Varela ◽  
Ernesto Bosch
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Liñá. Tegedor ◽  
I Elkhatib ◽  
A Abdala ◽  
A Bayram ◽  
K Ab. Ali ◽  
...  

Abstract Study question Is the live birth rate (LBR) in euploid frozen embryo transfer (FET) cycles affected by the endometrial thickness (EMT)? Summary answer A significantly higher LBR was observed in patients with an endometrial thickness of at least 7.5mm (46.24% vs. 54.63%) What is known already Parameters assessing the endometrium prior planning a FET include endometrial thickness, pattern and blood flow. The impact of the endometrial thickness on ART outcomes is controversial, with conflicting results published. A recent meta-analysis evaluated whether EMT could predict pregnancy outcomes and suggested that lower EMT was associated with lower incidence of clinical pregnancy rate (CPR), implantation rate (IR) and LBR. Due to heterogeneity of parameters evaluated between different publications, where embryos with unknown ploidy status were transferred, in conjunction with variability of stimulation protocols and the number of embryos transferred, the real effect of the EMT was difficult to infer. Study design, size, duration This was a two-center retrospective observational study including a total of 1522 euploid FET cycles between March 2017 and March 2020 at ART Fertility Clinics Muscat, Oman and Abu Dhabi, UAE. Participants/materials, setting, methods Trophectoderm biopsies were analyzed with Next Generation Sequencing (NGS). Vitrification/warming of blastocysts was performed using Cryotop method (Kitazato). EMT was measured by vaginal ultrasound prior initiating the progesterone administration (± 1 day) and LBR was recorded. Multivariate analysis was performed between LB outcomes and median EMT while controlling for confounding factors. Main results and the role of chance A total of 1522 FET cycles were analyzed: 975 single embryo transfer (SET) and 547 double embryo transfer (DET). The mean age of the patients was 33.38 years with a mean BMI of 27.1 kg/m2. FET were performed in EMT ranging from 3 to 15 mm and 50.52% resulted in a live birth. Though potentially all ranges of EMT were associated with LB, the median EMT in patients with LB was significantly higher than the median EMT of patients without LB (7.6mm vs. 7.4mm; p < 0.001). The dataset was stratified into two groups based on the median EMT (7.5mm): < 7.5mm (n = 744 cycles) and ≥ 7.5mm (n = 778 cycles). A significantly higher live birth rate was observed in ≥ 7.5mm group (46.24% vs. 54.63%. p = 0.0012). In multivariate analysis, EMT, FET endometrial preparation protocol, and number of embryos transferred were the main parameters influencing the chance to achieve LB: OR 1.10 [1.01–1.19], p < 0.015 for the EMT; OR 1.84 [1.47–2.30], p < 0.0001 for Natural Cycle protocol and OR 1.55 [1.25–1.93], p < 0.0001 for DET. Intercept 0.18 [0.07–0.44] p < 0.0002. Female age did not reach significance: OR 1.02 [1.00–1.04], p = 0.056. Limitations, reasons for caution Besides the retrospective nature of the study, the inter-observer variability in EMT assessment between different physicians is a limitation. The physician and embryologist performing the embryo transfer could not been standardized due to the multicenter design of the study. Wider implications of the findings: The EMT in FET may influence the LBR and should be considered as an important factor for the success of embryo transfer cycles. Whether these results can be extrapolated to fresh embryo transfer and to blastocysts with unknown ploidy status, needs further investigation. Trial registration number Not applicable


2011 ◽  
Vol 95 (2) ◽  
pp. 534-537 ◽  
Author(s):  
Kerstin Bjuresten ◽  
Britt-Marie Landgren ◽  
Outi Hovatta ◽  
Anneli Stavreus-Evers

2020 ◽  
Author(s):  
Haixia Jin ◽  
YuanYuan Liu ◽  
WenYan Song ◽  
FuLi Zhang ◽  
Lin Qi ◽  
...  

Abstract Background: Achievement of a live birth is the marker of success in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments. For patients with polycystic ovary syndrome (PCOS) who are undergoing these treatments, some predictive models and nomograms have been published. However, further development of these models is required for their useful application in clinical settings.Method: To establish and validate a clinical prediction model and nomogram to predict a live birth rate in women with PCOS undergoing IVF/ICSI. Records on 1193 patients underwent their first IVF/ICSI cycles for PCOS infertility from January 2014 to December 2019.The nomogram was built by a training cohort of 835 patients and tested on a validation cohort of 358 patients. Results: Female age, duration of infertility, total gonadotropin dose, the day of embryo transfer, no. of transferred embryos and the serum testosterone (T) level in PCOS groups were significantly associated with live birth rate. The predictive model was built by female age, duration of infertility, total gonadotropin dose, the day of embryo transfer, no. of transferred embryos, no. of retrieved oocytes, the serum T level, the serum progesterone (P) level, type of fecundation and endometrial thickness on embryo transfer day. The area under the curve (AUC) of the PCOS-specific predictive model in the training cohort was 0.72(95% CI, 0.68-0.76) and the AUC for the validation cohort was 0.63 (95% CI, 0.56-0.69).Conclusions: Our clinical prediction model and nomogram graphically demonstrated the risk factors that were associated with IVF/ICSI live birth rates in patients with PCOS. These findings offer improved clinical guidance for clinicians and patients.


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


2015 ◽  
Vol 104 (3) ◽  
pp. e346-e347
Author(s):  
B. Demir ◽  
I. Kahyaoglu ◽  
U. Yildirim ◽  
I. Kaplanoglu ◽  
L. Mollamahmutoglu

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


2020 ◽  
Author(s):  
Hongyuan Gao ◽  
Jing Ye ◽  
Hongjuan Ye ◽  
Qingqing Hong ◽  
Lihua Sun ◽  
...  

Abstract Background: The low serum progesterone (P) on the day of frozen embryo transfer (FET) is associated with diminished pregnancy rates in artificial endometrium preparation cycles using vaginal micronized P, but it is no consensus whether the strengthened luteal phase support (LPS) for the patients with low P on the FET day in artificial cycles is beneficial. A single centric, large-sample retrospective trial was aimed to investigate the contribution of strengthened LPS to the pregnancy outcomes for the groups of low P levels on the FET day in artificial endometrium preparation cycles.Methods: Women who had undergone first artificial cycle for endometrium preparation after freeze-all in our clinic during 2016 and 2018 were classified into two groups depending on the serum P levels on the FET day, routine LPS was administered for group B (P ≥10.0ng/ml on the FET day, n=1261) and strengthened LPS (routine LPS+ im P 40mg daily) for group A (P <10.0 ng/ml on the FET day, n=1295), the primary endpoint was the live birth rate and secondary endpoints were clinical pregnancy, miscarriage and neonatal outcomes.Results: The results showed the clinical pregnancy rate in group A was lower than group B (48.4% vs 53.2%, aRR 0.81, 95% CI 0.68, 0.96), the miscarriage rate was similar between the two groups (16.0% vs 14.7%, aRR 1.09, 95%CI 0.77, 1.54). The live birth rate was slightly lower than group B (39.5% vs 43.3%, aRR 0.84, 95%CI 0.70, 1.0). The birthweights and other neonatal outcomes were found no difference between the two groups (P>0.05).Conclusions: The strengthened LPS for the section of patients of low P levels on the FET day might help to have a reasonable pregnancy outcome, although the live birth rate was slightly lower than the groups with normal serum P levels on the FET day and usage of routine LPS. Trial registration: no available.


Author(s):  
Nathalie F. Wang ◽  
Leif Bungum ◽  
Sven O. Skouby

Abstract The need for luteal phase support in IVF/ICSI is well established. A large effort has been made in the attempt to identify the optimal type, start, route, dosage and duration of luteal phase support for IVF/ICSI and frozen embryo transfer. These questions are further complicated by the different types of stimulation protocols and ovulation triggers used in ART. The aim of this review is to supply a comprehensive overview of the available types of luteal phase support, and the indications for their use. A review of the literature was carried out in the effort to find the optimal luteal phase support regimen with regards to pregnancy related outcomes and short and long term safety. The results demonstrate that vaginal, intramuscular, subcutaneous and rectal progesterone are equally effective as luteal phase support in IVF/ICSI. GnRH agonists and oral dydrogesterone are new and promising treatment modalities but more research is needed. hCG and estradiol are not recommended for luteal phase support. More research is needed to establish the most optimal luteal phase support in frozen embryo transfer cycles, but progesterone has been shown to improve live birth rate in some studies. Luteal phase support should be commenced between the evening of the day of oocyte retrieval, and day three after oocyte retrieval and it should be continued at least until the day of positive pregnancy test. So, in conclusion still more large and well-designed RCT’s are needed to establish the most optimal luteal phase support in each stimulation protocol, and especially in frozen embryo transfer.


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