The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET).
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SUBMITTER: Melo P
PROVIDER: S-EPMC9733530 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET).
Melo Pedro P Wood Simon S Petsas Georgios G Chung Yealin Y Easter Christina C Price Malcolm J MJ Fishel Simon S Khairy Mohammed M Kingsland Charles C Lowe Philip P Rajkhowa Madhurima M Sephton Victoria V Pandey Shilpi S Kazem Rahnuma R Walker David D Gorodeckaja Julija J Wilcox Mark M Gallos Ioannis I Tozer Amanda A Coomarasamy Arri A
Human reproduction open 20221128 4
<h4>Study question</h4>What is the association between serum progesterone levels on the day of frozen embryo transfer (FET) and the probability of live birth in women undergoing different FET regimens?<h4>Summary answer</h4>Overall, serum progesterone levels <7.8 ng/ml were associated with reduced odds of live birth, although the association between serum progesterone levels and the probability of live birth appeared to vary according to the route of progesterone administration.<h4>What is known ...[more]
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Project description:Study questionDoes supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate?Summary answerSupplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births.What is known alreadyProgesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited.Study design, size, durationThis is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate.Participants/materials, setting, methodsWomen, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer.Main results and the role of chanceThere were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration.Limitations, reasons for cautionThe study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos.Wider implications of the findingsSupplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine.Study funding/competing interest(s)The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmö, Sweden. The authors have no personal conflicting interests to declare.Trial registration numberNL4152.Trial registration date5 December 2013.Date of first patient’s enrolment18 February 2013.
| S-EPMC9527461 | biostudies-literature
Project description:BackgroundConflicting evidence still prevails concerning the effect of preovulatory elevated progesterone (EP4) on reproductive outcomes in fresh embryo transfer (ET). However, few studies have analyzed the effect of EP4 on the likelihood of pregnancy using multivariate regression approach. The potential confounding factors tested in these studies were limited to either patient's characteristics or to stimulation related parameters. Yet, several studies have shown that postovulatory parameters such as midluteal progesterone (P4) level may be considered as a proxy variable of endometrial receptivity as well.ObjectiveThe aim of the present study was to estimate the independent effect of preovulatory P4 effect, if any, on the probability of live birth (LB) by considering the midluteal endocrine profile when controlling for the potential confounding factors.MethodsThis is a secondary data analysis of a cohort of fresh IVF/ICSI cycles triggered with GnRH agonist (n = 328) performed in a single IVF center during the period 2014-2016. Patients contributed only one cycle and were stratified into four groups according to preovulatory P4 quartiles. We assessed the association between preovulatory P4 and the odds of LB calculated by logistic regression analysis after controlling for the most clinically relevant confounders. The primary outcome measure: Live birth rates (LBR).ResultsBoth preovulatory and midluteal P4 were significantly correlated with the ovarian response. Logistic regression analysis showed that preovulatory serum P4 did not have a significant impact on LBR. In contrast, midluteal serum P4 level was an important independent factor associated with LBR. The optimal chance of LBR was achieved with midluteal serum P4 levels of 41-60 ng/ml, [OR: 2.73 (1.29-5.78); p< 0.008].ConclusionThe multivariate analysis suggests that the midluteal P4 level seems to impact LBR more than the preovulatory P4 level in women undergoing IVF treatment followed by fresh ET.
| S-EPMC7877612 | biostudies-literature
Project description:BackgroundStudy objectives included the development of a practical nomogram for predicting live birth following frozen-thawed embryo transfers in ovulatory women.MethodsTotally, 2884 patients with regular menstrual cycles in our center were retrospectively enrolled. In an 8:2 ratio, we randomly assigned patients to training and validation cohorts. Then we identified risk factors by multivariate logistic regression and constructed nomogram. Finally, receiver operating characteristic curve analysis, calibration curve and decision curve analysis were performed to assess the calibration and discriminative ability of the nomogram.ResultsWe identified five variables which were related to live birth, including age, anti-Müllerian hormone (AMH), protocol of frozen-thawed embryo transfer (FET), stage of embryos and amount of high-quality embryos. We then constructed nomograms that predict the probabilities of live birth by using those five parameters. Receiver operating characteristic curve analysis (ROC) showed that the area under the curve (AUC) for live birth was 0.666 (95% CI: 0.644-0.688) in the training cohort. The AUC in the subsequent validation cohorts was 0.669 (95% CI, 0.625-0.713). The clinical practicability of this nomogram was demonstrated through calibration curve analysis and decision curve analysis.ConclusionsOur nomogram provides a visual and simple tool in predicting live birth in ovulatory women who received FET. It could also provide advice and guidance for physicians and patients on decision-making during the FET procedure.
| S-EPMC11348591 | biostudies-literature
Project description:BackgroundThe number of frozen embryo transfer cycles is increasing, but the optimal method of endometrial preparation for frozen embryo transfer remains controversial. Few studies have investigated the healthy live birth outcome after the natural ovulation regimen vs the programmed regimen.ObjectiveThis study aimed to explore whether the likelihood of a healthy live birth after frozen embryo transfer differs between the natural ovulation regimen and the programmed regimen.Study designWe conducted a retrospective cohort study including 7824 ovulatory women who underwent the first frozen embryo transfer cycle of single-blastocyst transfer with endometrial preparation by natural ovulation regimen vs programmed regimen, between June 2017 and June 2021. Propensity score matching was used to control for confounding variables in a 1:1 ratio. The primary outcome was healthy live birth, defined as birth of a live, singleton infant born at term, with an appropriate birthweight for gestational age.ResultsThe natural ovulation regimen resulted in a higher probability of achieving healthy live birth compared with the programmed regimen (35.8% vs 30.6%; P<.0001). In addition, a higher rate of singleton live birth was observed after the natural ovulation regimen relative to the programmed regimen (49.6% vs 45.7%; P=.003). Women with the natural ovulation regimen were also less likely to experience clinical pregnancy loss (16.0% vs 19.7%; P=.005) and hypertensive disorders of pregnancy (3.9% vs 6.0%; P=.004) compared with women with the programmed regimen. Singletons born after the programmed regimen had greater mean birthweight (3441.50±539.97 vs 3394.96±503.87; P=.020) and higher risk of being large for gestational age (23.3% vs 18.7%; P=.003) than those conceived after the natural ovulation regimen.ConclusionThe natural ovulation regimen may be superior to the programmed regimen with regard to higher likelihood of healthy live birth and lower risk of pregnancy loss and maternal hypertensive disorders of pregnancy.
| S-EPMC10236214 | biostudies-literature
Project description:In recent years, the freeze-all strategy has been widely adopted and applied. However, with the exception of age, the factors that affect the outcomes of frozen embryo transfer are still unclear. Therefore, the identification and mitigation of factors that influence the live birth rate after frozen embryo transfer is a good way to increase the "take-home-baby" rate of frozen embryo transfer. The objective of this study was to identify factors affecting the live birth rate after cleavage-stage frozen embryo transfer in young ovulatory women. This was a secondary analysis from a previously published multicenter randomized controlled trial (ChiCTR-IOR-14005406) that was originally designed to compare the live birth rate and perinatal complications after fresh embryo transfer to those after frozen embryo transfer among ovulatory women. This study was carried out using a portion of the data from the original randomized controlled trial, which included 917 young women who underwent cleavage-stage frozen embryo transfer. The 16 clinical candidate variables potentially affecting the live birth rate after frozen embryo transfer were analyzed. Univariable analysis and multivariable analysis were performed to assess the relationship between predictive factors and outcomes, with the aim of identifying independent predictors of live birth after frozen embryo transfer. In this study, the live birth rate was 53.0% (486/917). Three independent predictors were ultimately identified as the main factors affecting the live birth rate of ovulatory young women. Infertility duration [odds ratio (OR): 0.933, 95% confidence interval (CI): 0.876-0.995, p = 0.033], endometrial thickness before frozen embryo transfer (OR: 3.375, 95% CI: 1.556-7.321 p = 0.002), and the number of embryos transferred (OR: 2.653, 95% CI:1.226-5,743, p = 0.013) were the major factors contributing to the live birth rate after cleavage-stage frozen embryo transfer among young women. The cut-off point for infertility duration was 4.5 years, and the cut-off point for endometrial thickness was 0.89 cm. Infertility duration, endometrial thickness and number of embryos transferred might affect the live birth rate after frozen embryo transfer among young women. This result could help inform clinical decisions and counseling to increase the live birth rate after frozen embryo transfer among young women.
| S-EPMC7105776 | biostudies-literature
Project description:PurposeTo evaluate whether endometrial compaction using sequential transvaginal ultrasound is associated with improved live birth rates in medicated single euploid frozen embryo transfer (FET) cycles.MethodsProspective observational cohort study at a private fertility clinic. Patients who underwent FETs between January and December 2018 were assessed for inclusion. The change in endometrial thickness between the end of the estrogen phase and the day before embryo transfer, measured by sequential transvaginal ultrasound, was used to categorize cycles with compaction (≥ 5%), no change, or expansion (≥ 5%). FET cycle outcomes were then compared between groups. The primary outcome was live birth. Secondary outcomes include clinical pregnancy rate and rate of spontaneous abortion.ResultsOf the 259 single euploid medicated FETs performed during the study period, only 43/259 (16.6%) of the cycles demonstrated ≥ 5% compaction, whereas 152/259 (58.7%) expanded and 64/259 (24.7%) were unchanged. Live birth rates did not differ between cycles with compaction (58.1%), no change (54.7%), or expansion (58.6%), p = 0.96. Clinical pregnancy and spontaneous abortion rates were also similar between groups.ConclusionThe vast majority of cycles did not demonstrate endometrial compaction. Endometrial compaction is not associated with live birth rate or spontaneous abortion rate in medicated single euploid FETs in this cohort.
| S-EPMC7884553 | biostudies-literature
Project description:Background: The need for endocrine monitoring in artificial cycles for frozen embryo transfer (FET) remains unclear and, more specifically, the value of the late-proliferative phase serum estradiol (E2) levels is with conflicting evidence in current literature. Objective: To investigate whether artificial FET cycles require endocrine monitoring for the serum E2 level prior to initiation of exogenous progesterone administration after an endometrial thickness of 6.5 mm has been reached. Design: One thousand two hundred and twenty-two (n = 1,222) artificial FETs performed in a tertiary center between 2010 and 2015 were subdivided into 3 groups according to the following late-proliferative serum E2 level percentiles: ≤p10 (E2 ≤144 pg/ml; n = 124), p11-p90 (E2 from 145 to 438 pg/ml; n = 977) and >p90 (E2 >439 pg/ml; n = 121). A mixed-effects multilevel multivariable regression analysis was performed to assess the potential effect of the late-proliferative E2 level on the live birth rate (LBR). Results: The level of late-proliferative circulating E2 showed no significant difference in terms of LBR after FET. Specifically, the multivariable regression model demonstrated a LBR of 19.5% for the p11-p90 reference group, compared to 24.4% for the ≤p10 (p = 0.251) and 19.5% for the >p90 group (p = 0.989). Conclusion: In this large retrospective dataset, no association was observed between late-proliferative phase serum E2 levels and LBR following FET in artificially prepared cycles. Although, caution is warranted due to the retrospective nature of the analysis and the potential for unmeasured confounding, we argue that monitoring of the late-proliferative serum E2 levels and using them to guide clinical decision-making (e.g., medication step-up, cycle prolongation or cancelation) may be of questionable value.
| S-EPMC7204383 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen-thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer.Methods/designThis study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen-thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test.DiscussionWe hypothesize that elective embryo cryopreservation and frozen-thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy.Trial registrationClinicalTrials.gov Identifier: NCT01841528.
| S-EPMC4022358 | biostudies-literature
Project description:According to the latest ART report for Europe, about 13% of pregnancies after frozen embryo transfer are multiple. Our objective was to analyse the impact on the multiple pregnancy rate of two eSFET (elective single frozen embryo transfers) versus a DFET (double frozen embryo transfer) in women aged under 38 years, who had not achieved pregnancy in their fresh transfer and who had at least two vitrified embryos of A/B quality.This study was conducted from January 2010 to June 2013 at a public hospital. The couples were divided into three groups. Group DFET: the first cryotransfer of two embryos (105 women); cSFET group: the only cryotransfer of a single vitrified embryo (60 women); eSFET group, individually vitrified embryos: 20 patients included in a clinical trial of single-embryo fresh and frozen transfer and 21 patients who chose to receive eSFET.The clinical pregnancy rate was 38.1% in the DET group and the cumulative clinical pregnancy rate was 43.3% in the eSFET group. There were no significant differences between the DFET and eSFET groups (30.0 vs 34.1%) in cumulative live birth delivery rate. The rate of multiple pregnancies varied significantly between the DFET and eSFET groups (32.5 vs 0%, p?<?0.05).For good-prognosis women aged under 38 years, taking embryo quality as a criterion for inclusion, an eSFET policy can be applied, achieving acceptable cumulative clinical pregnancy and live birth rates and reducing multiple pregnancy rates.
| S-EPMC4250464 | biostudies-literature
Project description:PurposeMosaicism is a prevalent characteristic of human preimplantation embryos. This retrospective cohort study aimed to investigate pregnancy outcomes after transfer of mosaic or euploid embryos.MethodsThe embryos, which had been transferred as "euploidy," were processed using array-based comparative genomic hybridization (aCGH). The original aCGH charts of the transferred embryos were reanalyzed. Mosaic and control euploid embryos were defined according to log2 ratio calls.ResultsOverall, 102 embryos were determined to be mosaic, of which 101 were estimated to harbor no more than 50% aneuploid mosaicism. Additionally, 268 euploid embryos were matched as controls. The rates of live birth (46.6% vs. 59.1%, odds ratio (OR) 0.60, 95% confidence interval (CI) 0.38-0.95), and biochemical pregnancy (65.7% vs. 76.1%, OR 0.60, 95% CI 0.37-0.99) per transfer cycle were significantly lower after mosaic embryo transfer than after euploid embryo transfer. The rates of clinical pregnancy and pregnancy loss and the risks of obstetric outcomes did not differ significantly between the two groups.ConclusionsCompared with euploid embryo transfer, mosaic embryo transfer is associated with a lower rate of live birth, which is mainly attributed to a decreased rate of conception. However, as mosaic embryo transfer yielded a live birth rate of 46.6%, patients without euploid embryos could be counseled regarding this alternative option.
| S-EPMC6338591 | biostudies-literature