Project description:PurposeTo assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes.MethodsThis single-center retrospective cohort study included blastocyst single embryo transfers (SET) performed between 1/2012-2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality. Among cycles resulting in live birth, associations with preterm birth, small for gestational age (SGA) and large for gestational age (LGA), were evaluated using logistic regression.ResultsA total of 1023 fresh and 1222 CET cycles were included, of which 465 (45.1%) fresh and 600 (48.5%) CET cycles resulted in singleton live birth. Clinical pregnancy rates increased with increasing expansion among fresh transfers (p for trend = 0.001) but not CET (p = 0.221), and with TE quality for both fresh and CET cycles (p = 0.005 and < 0.0001, respectively). Live birth rates increased with increasing expansion (fresh p = 0.005, CET p = 0.018) and TE quality (fresh p = 0.028, CET p = 0.023). ICM grade was not associated with pregnancy outcomes; however, higher ICM quality among CET cycles was associated with increased chance of preterm birth (p = 0.005).ConclusionsIn blastocyst SET, blastocyst expansion and TE quality were each associated with clinical pregnancy and live birth. While higher ICM quality was associated with increased chance of preterm birth among CET, no other associations with perinatal outcomes were identified. Clinicians can be reassured that pregnancies from blastocysts with lower expansion, ICM, or TE qualities are not more likely to result in adverse perinatal outcomes.
Project description:BackgroundElevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles.MethodsThis study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001-3,000 pg/ml), set 3 (E2 = 3,001-4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses.ResultsThe multivariate regression model in the cleavage group showed that patients' CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P = 0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P = 0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72-0.96], P = 0.012).ConclusionsElevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.
Project description:PurposeSeveral studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single- and multiple-blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single-blastocyst frozen-embryo transfer (sbFET).MethodsPatients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns' associations with pregnancy outcomes in relation to blastocyst grade and pregnancy-related factors.ResultsOf the 1383 cycles, 483 were Lf, 840 were partial-Lf, and 60 were non-Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial-Lf: 58.1%; non-Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non-Lf: OR (95% CI): 6.07 (3.24-11.37), 7.43 (3.47-15.39), and 0.20 (0.07-0.57).ConclusionsNon-Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns.
Project description:IntroductionThe global adoption of the "freeze-all strategy" has led to a continuous increase in utilization of single vitrified-warmed blastocyst embryo transfer (SVBT) owing to its clinical effectiveness. Accurate prediction of clinical pregnancy is crucial from a patient-centered perspective. However, this remains challenging, with inherent limitations due to the absence of precise and user-friendly prediction tools. Thus, this study primarily aimed to develop and assess a nomogram based on quantitative clinical data to optimize the efficacy of personalized prognosis assessment.Materials and methodsWe conducted a retrospective cohort analysis of ongoing pregnancy data from 658 patients with infertility who underwent SVBT at our center between October 17, 2017, and December 18, 2021. Patients were randomly assigned to the training (n=461) or validation (n=197) cohort for nomogram development and testing, respectively. A nomogram was constructed using the results of the multivariable logistic regression (MLR), which included clinical covariates that were assessed for their association with ongoing pregnancy.ResultsThe MLR identified eight significant variables that independently predicted ongoing pregnancy outcomes in the study population. These predictors encompassed maternal physiology, including maternal age at oocyte retrieval and serum anti-Müllerian hormone levels; uterine factors, such as adenomyosis; and various embryo assessment parameters, including the number of fertilized embryos, blastocyst morphology, blastulation day, blastocyst re-expansion speed, and presence of embryo string. The area under the receiver operating characteristic curve in our prediction model was 0.675 (95% confidence interval [CI], 0.622-0.729) and 0.656 (95% CI, 0.573-0.739) in the training and validation cohorts, respectively, indicating good discrimination performance in both cohorts.ConclusionsOur individualized nomogram is a practical and user-friendly tool that can provide accurate and useful SVBT information for patients and clinicians. By offering this model to patients, clinical stakeholders can alleviate uncertainty and confusion about fertility treatment options and enhance patients' confidence in making informed decisions.
Project description:BackgroundThin endometrial thickness (EMT) has been suggested to be associated with reduced incidence of pregnancy rate after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment, but the effect of thin endometrium on obstetric outcome is less investigated. This study aims to determine whether EMT affects the incidence of obstetric complications in fresh IVF/ICSI-embryo transfer (ET) cycles.MethodsWe conducted a retrospective cohort study collecting a total of 9266 women who had singleton livebirths after fresh IVF/ICSI-ET treatment cycles at the Center for Reproductive Medicine Affiliated to Shandong University between January 2014 and December 2018. The women were divided into three groups according to the EMT: 544 women with an EMT ≤8 mm, 6234 with an EMT > 8-12 mm, and 2488 with an EMT > 12 mm. The primary outcomes were the incidence of obstetric complications including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), placental abruption, placenta previa, postpartum hemorrhage (PPH) and cesarean section. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for associations between the EMT measured on the day of human chorionic gonadotropin (HCG) trigger and the risk of the outcomes of interest.ResultsThe HDP incidence rate of pregnant women was highest in EMT ≤ 8 mm group and significantly higher than those in EMT from > 8-12 mm and EMT > 12 mm group, respectively (6.8% versus 3.6 and 3.5%, respectively; P = 0.001). After adjustment for confounding variables by multivariate logistic regression analysis, a thin EMT was still statistically significant associated with an increased risk of HDP. Compared with women with an EMT > 8-12 mm, women with an EMT ≤8 mm had an increased risk of HDP (aOR = 1.853, 95% CI 1.281-2.679, P = 0.001).ConclusionA thin endometrium (≤8 mm) was found to be associated with an increased risk of HDP after adjustment for confounding variables, indicating that the thin endometrium itself is a risk factor for HDP. Obstetricians should remain aware of the possibility of HDP when women with a thin EMT achieve pregnancy through fresh IVF/ICSI-ET treatment cycles.
Project description:Study questionAre there any differences in live birth rates (LBR) following fresh blastocyst transfer in natural or clomiphene-stimulated cycles, or after elective blastocyst freezing in clomiphene-stimulated cycles followed by thawing and transfer at different time-points?Summary answerClomiphene citrate (CC) administration adversely affected the LBR after single fresh blastocyst transfer (SBT) in CC cycles compared with that in natural cycles, while this adverse effect of CC is not present when a single vitrified-warmed blastocyst transfer (SVBT) is performed in subsequent natural ovulatory cycles, regardless of the duration between CC administration and the day of SVBT.What is known alreadyCC affects uterine receptivity associated with a thinning of the uterine endometrium through an antioestrogenic effect. However, the duration that this adverse effect of CC on uterine endometrium persists after initial use is still unknown.Study design size durationA retrospective cohort study of 157 natural cycle IVFs followed by SBT and 1496 minimal ovarian stimulation with CC IVF cycles followed by SBT (n = 24) or SVBT (n = 1472) from January 2010 to December 2014 was conducted. SVBT cycles were classified into two groups according to the period between the last day of CC administration and the day of SVBT (A: ≤60 d and B: ≥61 d). All groups were then compared based on pregnancy outcomes (natural-SBT group: n = 157, CC-SBT group: n = 24, SVBT-A: n = 1143, SVBT-B: n = 329).Participants/materials setting methodsWomen were aged 30-39 years at oocyte retrieval. In SVBT cycles, blastocysts were vitrified and warmed using a Cryotop safety kit. SVBT was performed in subsequent natural ovulatory cycles. The main outcomes were LBR and neonatal outcome, and both were compared among the groups.Main results and the role of chanceThe LBR in the CC-SBT group (29.2%, 7/24) was significantly lower compared with the natural-SBT (56.1%, 88/157) (P = 0.01) and SVBT-A (50.0%, 572/1143) (P = 0.04), but not SVBT-B (47.4%, 156/329), groups. Furthermore, multivariate logistic regression analysis revealed that the LBR was comparable among the natural-SBT and SVBT groups, but was significantly lower in the CC-SBT group (adjusted odds ratio: 0.324, 95% CI: 0.119-0.800, P = 0.01). No significant differences among all groups were observed for gestational age (P = 0.19), birthweight (P = 0.41) and incidence of malformation (P = 0.53).Limitations reasons for cautionIn this study we analysed a biased sample, based on clinical judgement regarding endometrial thickness, and the study was limited by its retrospective nature. The low statistical power caused by the group size disparity was also a limitation, especially in the CC-SBT group. Although the outcome showing inferiority of CC-SBT compared to natural-SBT is consistent with general findings in the literature, further large-scale clinical studies, ideally RCTs, are necessary to validate our results and clarify the prolonged effect of CC in SVBT cycles on pregnancy and neonatal outcomes.Wider implications of the findingsOur observation suggests that CC administered in minimal ovarian stimulation cycles affects adversely the pregnancy outcomes when SBT is performed. Therefore, for a CC-based minimal stimulation IVF cycle, we suggest that frozen embryo transfer should be performed in a subsequent natural ovulatory cycle to avoid the possibility of implantation failure associated with CC administration.Study funding/competing interestsThe authors have no conflicts of interest to declare. No external funding was either sought or obtained.
Project description:Objective To compare the pregnancy outcome after fresh embryo transfer between GnRH antagonist and GnRH agonist regimens in patients with thin endometrium. Methods This retrospective study included all fresh embryo transfers following GnRH agonist or GnRH antagonist protocols in patients with thin endometrium from 2016 to 2021. The thin endometrium was defined as an endometrial thickness of 7.5 mm or less on the triggering day. Multivariant regression analysis was applied to assess the association of GnRH agonist or GnRH antagonist regimen with live birth following fresh embryo transfer in patients with thin endometrium. Results A total of 69 and 192 cases were, respectively, included in the GnRH antagonist or GnRH agonist group. The stimulation duration was significantly longer by the GnRH agonist protocol than the GnRH antagonist protocol (11.2 ± 2.1 vs. 9.1 ± 1.9 days, P = 0.002). The rates of clinical pregnancy or live birth were significantly lower in the GnRH antagonist group compared to the GnRH agonist group (26.1 vs. 47.9%, P = 0.027; 17.4 vs. 40.1%, P = 0.01, respectively). Multivariable regression analysis demonstrated that GnRH agonist regimen was related to higher live birth rate compared with GnRH agonist protocol [adjusted OR: 2.6, 95% confidence intervals (CI): 1.3–5.3]. No significant difference in miscarriage rate and the neonatal outcome was present between the two protocols. Conclusion Our findings suggest that GnRH agonist protocol results in a higher rate of live birth after fresh embryo transfer than GnRH antagonist protocol in patients with thin endometrium.
Project description:PurposeClinical pregnancy rate after IVF with eSET stagnates between 30 and 40%. In order to increase pregnancy and live birth rates, multiple embryo transfer is still common practice. Providing additional non-invasive tools to choose the competent embryo for transfer could avoid multiple pregnancy and improve time to pregnancy. Cumulus mRNA analysis with quantitative PCR (QPCR) is a non-invasive approach. However, so far, no gene sets have been validated in prospective interventional studies.MethodsA prospective interventional single-center pilot study with two matched controls (day-3 and day-5 eSET) was performed in 96 patients consenting to the analysis of the cumulus-corona of their oocytes. All patients were super-ovulated for ICSI and eSET at day 3. All oocytes were denuded individually and cumulus was analyzed by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D) and two housekeeping genes (UBC and β2M). Patients (n = 62) with 2 or more day-3 embryos (good or excellent morphology) had their embryo chosen following the normalized expression of the genes.ResultsCorona testing significantly increased the clinical pregnancy and live births rates (63% and 55%) compared to single embryo transfer (eSET) on day 3 (27% and 23%: p < 0.001) and day 5 (43% and 39%: p = 0.022 and p = 0.050) fresh transfer cycle controls with morphology-only selection. Time-to-pregnancy was significantly reduced, regardless of the number of good-quality embryos available on day 3.ConclusionCombining standard morphology scoring and cumulus/corona gene expression analysis increases day-3 eSET results and significantly reduces the time to pregnancy.Trial registration numberThis is not an RCT study and was only registered by the ethical committee of the University Hospital UZBRUSSEL of the Vrije Universiteit Brussel VUB (BUN: 143201318000).
Project description:ObjectivesTo evaluate the association of fresh and frozen embryo transfer with the development of ischemic placental disease (IPD), hypothesizing that differences in implantation environment affect placentation and thus pregnancy outcomes.DesignWe performed a secondary analysis of a retrospective cohort study of deliveries linked to IVF cycles.SettingTertiary hospital and infertility treatment center.Patient(s)We included all women who underwent an autologous IVF cycle and had a live-born infant or an intrauterine fetal demise (IUFD). We excluded women less than 18 years of age.Intervention(s)We compared pregnancies resulting from frozen embryo transfer (frozen) cycles with those resulting from fresh embryo transfer (fresh) cycles.Main outcome measure(s)The primary outcome was a composite outcome of IPD or IUFD due to placental insufficiency. Ischemic placental disease included pre-eclampsia, placental abruption, and small for gestational age (SGA). We calculated risk ratios (RRs) and 95% confidence intervals (CIs).Result(s)Compared with fresh cycles, frozen cycles had a lower risk of IPD or IUFD from placental insufficiency (RR 0.75, 95% CI 0.59-0.97). Frozen cycles also conferred a lower risk of SGA than fresh cycles (RR 0.58, 95% CI 0.41-0.81). Risks of pre-eclampsia (RR 1.3, 95% CI 0.84-1.9) and abruption (RR 1.2, 95% CI 0.56-2.4) were similar.Conclusion(s)There was a lower risk of IPD among frozen cycles compared with fresh cycles. This association was largely driven by lower risk of SGA among frozen cycles.
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.