The optimal timing of frozen-thawed embryo transfer: delayed or not delayed? A systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Gao YQ
PROVIDER: S-EPMC10825964 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
The optimal timing of frozen-thawed embryo transfer: delayed or not delayed? A systematic review and meta-analysis.
Gao Yu-Qi YQ Song Jing-Yan JY Sun Zhen-Gao ZG
Frontiers in medicine 20240115
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Project description:PurposeTo compare the effects of different endometrial preparation protocols for frozen-thawed embryo transfer (FET) cycles and present treatment hierarchy.MethodsSystematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs).ResultsTwenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC.ConclusionNatural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.
| S-EPMC8417182 | biostudies-literature
Project description:PurposeTo investigate whether personalized embryo transfer (pET) protocol guided by an endometrial receptivity array (ERA) can improve clinical outcomes of assisted reproduction.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane library for studies in which analytical comparisons of outcomes of pET and standard embryo transfer (sET) groups were undertaken. The references to the included studies were also manually searched. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes were live birth rate (LBR), human chorionic gonadotropin (HCG) positivity, biochemical pregnancy rate (BPR), miscarriage rate (MR), implantation rate (IR), and ongoing pregnancy rate (OPR).ResultsTen studies were included in the meta-analysis, including one randomized controlled trial (RCT) and nine cohort studies. We observed no significant difference in the primary outcome of CPR between the pET and sET groups in unselected patients (RR = 1.07; 95% confidence interval [CI], 0.87-1.30; P = 0.53; I2 = 89%). In terms of secondary outcomes, we likewise noted no significant differences between the groups. Further subgroup analyses indicated that the pET protocol not only significantly reduced the MR for poor-prognosis patients, but it also reduced the CPR in donor cycles, elevated the BPR for good-prognosis patients, non-preimplantation genetic testing (PGT), and programmed cycles, and decreased the proportion of women showing HCG positivity in non-PGT cycles.ConclusionsThis meta-analysis revealed that ERA appears to possess limited guidance in embryo transfer. More high-quality RCTs are therefore needed to investigate the clinical validity and feasibility of ERA in the future.
| S-EPMC10224903 | biostudies-literature
Project description:While widely used for ovulation induction in assisted reproductive technology, the clinical efficacy of letrozole for endometrial preparation prior to frozen-thawed embryo transfer (FET) cycles remains yet to be elucidated. We performed a meta-analysis to compare pregnancy outcomes after letrozole use with those of other endometrial preparation protocols in patients undergoing FET. PubMed, Scopus, Embase and the Cochrane Library were searched for eligible studies. Clinical pregnancy rate (CPR), live birth rate (LBR) and birth defect rate (BDR) were analysed using odds ratio (OR) and 95% confidence interval (CI). A total of 10 studies representing 75 968 FET cycles were included. Comparable CPR and LBR were observed when comparing letrozole administration with natural cycle (OR 1.24, 95% CI: 0.69 - 2.24; OR 1.18, 95% CI: 0.60 - 2.32), artificial cycle (OR 1.46, 95% CI: 0.87 - 2.44; OR 1.39, 95% CI: 0.77 - 2.52), and artificial cycle with gonadotropin-releasing hormone agonist suppression (OR 1.11, 95% CI: 0.78 - 1.59; OR 1.18, 95% CI: 0.82 - 1.68). Pooled results of the limited studies comparing letrozole with human menopausal gonadotropin demonstrated a similar CPR between groups (OR 1.46, 95% CI: 0.29 - 7.21, two studies), but the letrozole group had a statistically lower LBR (OR 0.67, 95% CI: 0.52 - 0.86, one study). No increased BDR was observed in the letrozole group compared to natural cycles or artificial cycles (OR 0.98, 95% CI: 0.60 - 1.61; OR 1.39, 95% CI; 0.84 - 2.28). This pooled analysis supports the use of letrozole as an efficacious and safe alternative to mainstream regimens for endometrial preparation in FET cycles.
| S-EPMC7428376 | biostudies-literature
Project description:PurposeThis systematic review and meta-analysis aimed to compare pregnancy outcomes between immediate frozen embryo transfer (FET) performed within the first menstrual cycle after oocyte retrieval and delayed FET following subsequent cycles.MethodsPubMed, EMBASE, and Web of Science were searched for eligible studies through January 2020. The main outcome measures were clinical pregnancy rate (CPR), live birth rate (LBR), and pregnancy loss rate (PLR). The effect size was estimated as risk ratio (RR) with 95% confidence interval (CI) using a random effects model. Inter-study heterogeneity was assessed by the I2 statistic.ResultsTwelve retrospective cohort studies involving 18,230 cycles were included. The pooled results revealed no significant differences between delayed and immediate FET in CPR (RR 0.94, 95% CI 0.87-1.03; I2 = 67.9%), LBR (RR 0.94, 95% CI 0.85-1.03; I2 = 67.5%), and PLR (RR 1.05, 95% CI 0.87-1.26; I2 = 42.7%). Subgroup analyses of freeze-all cycles showed a marginal decrease of CPR in delayed FET (RR 0.93, 95% CI 0.86-1.00; I2 = 53.6%), but no significant changes were observed regarding LBR (RR 0.93, 95% CI 0.85-1.02; I2 = 65.2%) and PLR (RR 1.09, 95% CI 0.84-1.41; I2 = 59.1%). No statistical differences were found in effect estimates among other subgroup analyses by ovarian stimulation protocol, trigger agent, endometrial preparation regimen, and embryo stage.ConclusionTiming of the first FET after oocyte retrieval was not significantly associated with pregnancy outcomes. This finding refutes the current common practice to delay FET after oocyte retrieval and reassures patients who wish to proceed with FET at their earliest convenience. Due to the high heterogeneity and observational nature of included studies, further randomized controlled trials are needed to confirm the results.
| S-EPMC7468025 | biostudies-literature
Project description:BackgroundAcupuncture is increasingly used as adjuvant therapy for infertile women undergoing frozen-thawed embryo transfer (FET); however, its effects and safety are highly controversial. This study aimed to evaluate the pooled effects of adjuvant acupuncture on FET pregnancy outcomes.MethodsWe considered only randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture or no adjuvant treatment during FET and the primary outcome was clinical pregnancy rate. Two authors separately selected studies, extracted data, and performed a risk of bias assessment. Pooled data were expressed as risk ratio (RR) or mean difference (MD), with a 95% confidence interval (CI). In addition, we conducted subgroup and sensitivity analyses to investigate the sources of heterogeneity, and we also constructed funnel plots to assess the likelihood of publication bias. Finally, Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was applied to evaluate the quality of evidence.ResultsA total of 14 RCTs with a total of 1,130 participants were included in the study. We found significant effects of acupuncture adjuvant to FET on the outcomes of clinical pregnancy rate (RR = 1.54, 95% CI [1.28, 1.85], I 2 = 34%; 14 trials), biochemical pregnancy rate (RR = 1.51, 95% CI [1.21, 1.89]; 5 trials), endometrial thickness (MD = 0.97, 95% CI [0.43, 1.51]; 12 trials), and endometrial pattern (RR = 1.41, 95% CI [1.13, 1.75]; 7 trials). For live birth rate (RR = 1.48, 95% CI [0.90, 2.43], 4 trials), there were no statistical effectiveness. For subgroup analyses, most variables had tolerable heterogeneity (I 2 = 0%) except for trials that were sham-controlled, performed acupuncture only after FET, or <5 times, which appeared to interpret most of the heterogeneity. Additionally, the quality of evidence of all outcomes in this review ranged from low to moderate.ConclusionAcupuncture could be instrumental in the pregnancy outcomes of FET, and has very few risks of severe adverse events; however, the quality of evidence is unsatisfactory. Further research with rigorous methodological quality should be considered, and the protocols of acupuncture also need more investigations (e.g., appropriate control groups, sessions, and times).
| S-EPMC9501879 | biostudies-literature
Project description:BackgroundRecurrent implantation failure (RIF) is a critical problem for assisted reproduction technology. High-quality embryos and the synchronization endometrium both have great significance. How to get the optimal endometrial receptivity is a challenge for implantation and pregnancy of infertile patients with RIF. The objective of this study is to investigate personalized protocol of frozen-thawed embryo transfer (FET) cycles, and its effect on clinical outcomes in patients with RIF.MethodsWe chose 91 RIF patients from January 2017 to June 2019 in the Reproductive Medicine Center of the First Hospital of Lanzhou University. A total of 100 FET cycles were undertaken with a gonadotropin-releasing hormone agonist (GnRH-agonist) protocol combined with hormone replacement therapy (HRT) for endometrial preparation. The patients were divided into two groups: the routine group (cleavage embryo transferred at day 3 after luteal support) included 48 cycles; the personalized group included 52 cycles with delayed endometrial trigger and luteal support (the time of embryo transfer depended on the level of serum hormone and endometrial thickness).ResultsThe data showed the personalized group had longer time for endometrial preparation. On the day of embryo transfer, serum progesterone (P) and the E2/P ratio was significantly different compared with the routine group (P<0.05). The clinical pregnancy rate in the routine group was 35.42% (17/48) and 59.62% (31/52) in the personalized group (P<0.05). The abortion rate was not significantly different.ConclusionsFor women with RIF, personalized timing for transfer of FET resulted in a higher clinical pregnancy rate compared with routine protocol.
| S-EPMC8904980 | biostudies-literature
Project description: Not available
| S-EPMC7333132 | biostudies-literature
Project description: Not available
| S-EPMC7210185 | biostudies-literature
Project description: Not available
| S-EPMC10955253 | biostudies-literature
Project description:The optimal protocol for endometrial preparation in patients with infertility remains unclear. Due to this, the current study retrospectively analyzed 1,589 patients with infertility and regular menstrual cycles to assess reproductive outcomes per embryo transferred and per embryo transfer (ET) cycle following the transfer of frozen-thawed embryos (FET) in a modified natural cycle (mNC) or hormone therapy cycle (HT) with or without gonadotropin-releasing hormone agonist (GnRHa)-induced pituitary suppression. The molecular mechanisms involved were also studied using tissues from endometrial biopsies. Patients who underwent FET were assigned to 5 groups as follows: Group A underwent a mNC (n=276); group B (n=338) received estradiol (E2) and progesterone (P4); group C received 1 cycle of GnRHa, E2 and P4 (n=323); group D received 2 cycles of GnRHa, E2 and P4 (n=329); and group E received 3 cycles of GnRHa, E2 and P4 (n=323). Tissues from endometrial biopsies of 91 patients performed on the day of ET were tested for endometrial receptivity marker mRNA expression and microRNA (miR)-223-3p mRNA. Furthermore, endometrial stromal cells (ESCs) were used for an in-depth study of the molecular mechanisms involved. Among the 5 groups of patients, implantation rates, clinical pregnancy rates and live birth rates were not significantly different. However, endometrial receptivity was enhanced in group E when compared with groups A-D, which was associated with endometrial leukemia inhibitory factor (LIF), osteopontin, vascular endothelial growth factor, integrin β3 and homeobox gene 10 and 11 mRNA upregulation, and miR-223-3p miRNA downregulation. Transfection of ESCs with an miR-223-3p mimic significantly reduced levels of LIF mRNA and protein. In addition, pre-treating ESCs with GnRHa upregulated mRNA and protein expression of the decidualization markers prolactin and insulin-like growth factor binding protein-1 in a time-dependent manner. In conclusion, these results indicated that HT with GnRHa may be a potential endometrial preparation protocol for FET.
| S-EPMC7401479 | biostudies-literature