Project description:ObjectiveTo investigate the impact of endometrial thickness on the embryo transfer(ET) day on the clinical pregnancy outcomes of frozen-thawed embryo transfer cycles which have undergone hormone replacement therapy(HRT-FET).MethodsA total of 10,165 HRT-FET cycles performed between January 2013 to December 2017 in the Reproductive Medicine Center of Henan Provincial People's Hospital were studied retrospectively. All patients were grouped according to their endometrial thickness on the ET day (each group having an increment of 1mm between two neighboring groups). Multivariate regression analysis, curve fitting and threshold effect analysis were performed on all data.ResultsAfter adjusting for the age, duration of infertility, body mass index(BMI), infertility type and number and type of embryos transferred, a significant correlation was observed to be between the endometrial thickness and implantation rates (aOR: 1.08; 95% CI: 1.06-1.10, p < 0.0001), clinical pregnancy rate(aOR: 1.10; 95% CI: 1.07-1.14, p < 0.0001)and live birth rate (aOR: 1.09; 95% CI: 1.06-1.12, p < 0.0001). The numerical value of the cut-off point for the endometrial thickness was 8.7 mm. When the endometrial thickness was less than 8.7 mm, with each additional 1 mm of endometrial thickness, the implantation rate increased by 32%, the clinical pregnancy rate increased by 36%, and the live birth rate increased by 45%.ConclusionsIn the HRT-FET cycles, the optimal live birth rate would be obtained when the endometrial thickness remains within the range of 8.7-14.5 mm. If the endometrium is too thin or too thick, the live birth rate will be reduced.
Project description:BackgroundA thin endometrium affects embryo implantation. We designed a retrospective cohort study to analyze the differences of in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) outcomes between fresh embryo transfer (ET) and frozen ET in patients with a thin endometrium.MethodsThe present study comprised of 1,110 patients with a thin endometrium undergoing IVF-ICSI between January 2013 and December 2017 in our unit. Propensity score matching (PSM) was used to balance the influence of intergroup confounding factors and to compare the pregnancy outcomes of the matched patients in the two groups. The fresh embryo group and frozen embryo group consisted of 632 and 478 women, respectively. After PSM, 173 patients were included in the two groups, respectively.ResultsThe frozen embryo group showed a higher live birth rate (31% vs. 18.4%, P<0.001; 30.6% vs. 19.7%, P=0.019), clinical pregnancy rate (40% vs. 26.4%, P<0.001; 38.7% vs. 25.4%, P=0.008), and biochemical pregnancy rate (46.2% vs. 32.9%, P<0.001; 44.5% vs. 31.8%, P=0.020) than the fresh embryo group before and after PSM.ConclusionsOur results demonstrated that for women with a thin endometrium who were undergoing IVF, the live birth rate, clinical pregnancy rate, and biochemical pregnancy rate after frozen ET were significantly higher than in the fresh ET group.
Project description:BackgroundRecurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) during in vitro fertilization (IVF) treatment are still tough problems without effective treatments; thus, they are important research topics. There is controversy on whether low molecular weight heparin (LMWH) improves pregnancy outcomes in women with unexplained RPL and RIF. Moreover, currently, there is a paucity of reports on the role of LMWH in the entire population undergoing frozen-thawed embryo transfer (FET) cycles. This study aimed to estimate the effects of LMWH on pregnancy outcomes in women undergoing FET cycles.MethodsThere were 1881 female patients included in the study. Of the 1881 patients, 107 underwent preimplantation genetic diagnosis cycles, which were analyzed individually. The patients were divided into two groups: the LMWH group received injections of 4100 IU/d LMWH from the day of transfer until 14 ± 2 days posttransplant, the control group was the comparison group (without LMWH use). The baseline characteristics and reproductive outcomes of the patients were reviewed.ResultsOf the 1774 women with normal FET cycles, no significant differences were found in the number of embryos implanted (1.31 ± 0.02 vs. 1.28 ± 0.02), embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, late abortion rate, and ectopic pregnancy rate between the two groups. The LMWH group had a higher early abortion (17.8% [76/427] vs. 12.5% [55/439], p = 0.030). In the sub-group analysis, among the patients who underwent more than four transfers, the LMWH group had a lower late abortion rate (1.7% [1/60] vs. 13.2% [7/53], p = 0.043). Similarly, of the 107 women who underwent preimplantation genetic diagnosis cycles, the reproductive outcomes were comparable between the two groups.ConclusionIn the general population and PGD patients, LMWH did not improve pregnancy outcomes. Therefore, the routine use of LMWH is not recommended for early treatment.
Project description:ObjectiveA beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP.MethodThis study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient's whole blood (WB) and PRP by utilizing a commercial screening kit.ResultsThe live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB.ConclusionIntrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement.
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.
Project description:The well-prepared endometrium with appropriate thickness plays a critical role in successful embryo implantation. The thin endometrium is the main factor of frozen-embryo transfer (FET), resulting in the failure of implantation undergoing FET. Hormone treatment is suggested to improve endometrium thickness; however, among the larger numbers of cases, it cannot reach the sufficient thickness, which leads to a high cancelation rate of embryo transfer as well as waste high-quality embryos. Thus, it increases the burden to patients in both economic and psychological perspectives. We performed a retrospective observational study, which was composed with 2 cohorts, either with the conventional hormone replacement therapy (HRT) protocol or HRT with gonadotrophin-releasing hormone agonist (GnRHa) pretreatment to prepare the endometrium before FET. The measurements of endometrium thickness, hormone level, transfer cycle cancelation rate, pregnancy rate, and implantation rate were retrieved from the medical records during the routine clinic visits until 1 month after embryo transfer. The comparisons between 2 cohorts were performed by t-test or Mann-Whitney U test depending on the different attributions of data. In total, 49 cycles were under HRT with GnRHa pretreatment and 84 cycles were under the conventional HRT protocol. HRT with GnRHa pretreatment group improved the endometrial thickness (8.13 ± 1.79 vs 7.51 ± 1.45, P = .031), decreased the transfer cancelation rate (P = .003), and increased clinical pregnancy rate and implantation rate significantly (both P = .001). Additionally, luteinizing hormone level in pretreatment group was consistently lower than conventional HRT group (P < .05). Our study revealed HRT with GnRHa pretreatment efficiently improved the endometrial thickness, therefore, decreased the FET cycle cancelation. It also elevated the embryo implantation rate and clinical pregnancy rate by improving endometrial receptivity.
Project description:The application of anticoagulants and immune agents in assisted reproduction technology has been in a chaotic state, and no clear conclusion has been reached regarding the effectiveness and safety of this treatment. We aimed to explore the potential association between adjuvant medication and pregnancy outcomes and offspring safety in a retrospective cohort study including 8,873 frozen-thawed embryo transfer cycles. The included cycles were divided into three groups according to the drugs used, namely, the routine treatment group (without anticoagulant agents and immune agents), the anticoagulant agent group, and the immunotherapy group. Among normal ovulatory patients, those who used immune agents had a 1.4-fold increased risk of miscarriage (≤13 weeks), but a 0.8-fold decreased chance of birth (≥28 weeks) compared with the routine treatment group. Among patients with more than 1 embryo transferred, those who used anticoagulant agents showed a 1.2-fold higher risk of multiple birth than those undergoing routine treatment. Among patients without pregnancy complications, anticoagulant treatment was associated with a 2.1-fold increased risk of congenital anomalies. Among young patients (<26 years) with a singleton pregnancy, the neonatal birth weight of the immunotherapy group and the anticoagulant treatment group was 305.4 g and 175.9 g heavier than the routine treatment group, respectively. In conclusion, adjuvant anticoagulants or immune agent treatment in assisted reproductive technology should be used under strict supervision, and the principle of individualized treatment should be followed.
Project description:This study aims to develop physician support software for determining ovulation time and assess its impact on pregnancy outcomes in natural cycle frozen embryo transfers (NC-FET). To develop, assess, and validate an ovulation prediction model, three datasets were used: REI Ovulation Determination dataset (500 cycles) split into training (309), validation (90), and test (101) sets; the Documented Ovulation dataset (101 cycles) with confirmed ovulation (documented follicular rupture and LH surge); and the Clinical Pregnancy Rates dataset (515 NC-FET cycles), categorized into "Matched" and "Mismatched" based on alignment with the model's ovulation determination. Pregnancy outcomes were compared between the groups. The ovulation prediction model exhibited 93.85% and 92.89% matching rates with the REI Ovulation Determination and Documented Ovulation datasets, respectively. In the Clinical Pregnancy Rates dataset, the Matched group (282 cycles) showed significantly higher clinical pregnancy rates than the Mismatched group (34.6% vs. 25.9%, p = 0.04) and similar results for patients under 37 (41.1% vs. 30.7%, p = 0.04). Logistic regression indicated lower pregnancy rates in Mismatched cases (odds ratio 0.67 for the general population, 0.63 for patients under 37). In conclusion, we introduce a highly accurate AI ovulation prediction model. Treatment cycles aligning with the model's recommendations had significantly increased clinical pregnancy rates.
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.
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.