Cleavage-stage versus blastocyst-stage embryo transfer in assisted reproductive technology.
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ABSTRACT:
SUBMITTER: Glujovsky D
PROVIDER: S-EPMC9119424 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
Cleavage-stage versus blastocyst-stage embryo transfer in assisted reproductive technology.
Glujovsky Demián D Quinteiro Retamar Andrea Marta AM Alvarez Sedo Cristian Roberto CR Ciapponi Agustín A Cornelisse Simone S Blake Deborah D
The Cochrane database of systematic reviews 20220519
<h4>Background</h4>Advances in embryo culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage-stage embryo transfer to blastocyst-stage embryo transfer. The rationale for blastocyst-stage transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates.<h4>Objectives</h4>To determine whether blastocyst-stage (day 5 to 6) embryo transfer improves the live birth rate (LBR) per fre ...[more]
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Project description:PURPOSE:Is there a difference in implantation and pregnancy rates between embryos transferred electively at cleavage or blastocyst stage in infertile women ≤ 38 years with at least four zygotes on day 1 post retrieval? METHODS:A randomized clinical trial was conducted in a single tertiary care hospital with a sample size of 194 patients in each arm for a total population of 388 women. Patients less than 39 years of age with more than three fertilized oocytes and less than four previous assisted reproductive technology (ART) attempts were inclusion criteria. RESULTS:The two groups were similar for age, years of infertility, indication to treatment, basal antimüllerian hormone and FSH, number of previous ART cycles, primary or secondary infertility, type of induction protocol, days of stimulation, total gonadotrophin dose, and estradiol (E2) and progesterone (P) levels at trigger. No statistically significant differences were found in terms of number of retrieved oocytes, inseminated oocytes, fertilization rate, canceled transfers (7.73% in blastocyst and 3.61% in cleavage stage group), and cycles with frozen embryos and/or oocytes. Although a higher number of fertilized oocytes were in the blastocyst stage group (6.18 ± 1.46 vs 5.89 ± 1.54, p = 0.052), a statistically greater number of embryos/randomized cycle were transferred at cleavage stage (1.93 ± 0.371) compared with the number of transferred blastocysts (1.80 ± 0.56), probably due to the number of embryos not reaching blastocyst stage (3.09%). The implantation rate (28.37 vs 25.67%), pregnancy rate per cycle (36.06 vs38.66%), transfer (39.66 vs 40.11%), spontaneous abortions (19.72% vs 12.00%), delivery rate per cycle (27.84 vs 32.99%), and transfer (30.17 vs 34.22%) were not significantly different between the blastocyst and cleavage stage groups. The twin delivery rate was higher in the blastocyst stage group, although not significant (42.59 vs 28.12%). The mean numbers of frozen blastocyst (2.30 ± 1.40 vs 2.02 ± 1.00) and frozen oocytes (7.09 ± 3.55vs 6.79 ± 3.26) were not significantly different between the two groups. CONCLUSIONS:Fresh blastocyst-stage transfer versus cleavage-stage transfer did not show any significant difference in terms of implantation and pregnancy rate in this selected group of patients. A high twin delivery rate in both groups (35.59%) was registered, and although not significant, they were higher in the blastocyst transfer group (42.59 vs 28.12%). Our conclusion supports considering single embryo transfer (SET) policy, even in cleavage stage in patients younger than 39 years with at least four zygotes. TRIAL REGISTRATION:ClinicalTrials.gov registration number NCT02639000.
| S-EPMC5904063 | biostudies-literature
Project description:BACKGROUND:With improvements in in vitro culture techniques there has been a steady shift in practice to transfer embryos at the blastocyst stage (post fertilization day (p.f.d.) 5-7), when embryos reach the endometrial cavity during natural conception. For patients with > 5 zygotes on day 1 of embryo development, fresh blastocyst embryo transfer (ET) increases live birth rates when compared to cleavage stage (p.f.d. 3) transfer. In poorer prognosis patients (≤ 5 zygotes) cleavage stage ET is commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst stage. However, there is a dearth of randomized controlled trial (RCT) data demonstrating improved live birth rates per cycle for cleavage vs blastocyst stage ET in this subgroup of patients. The hypothesis of the PRECiSE (PooR Embryo Yield Cleavage Stage Versus blaStocyst Embryo Transfer) trial is that blastocyst ET is not inferior to cleavage stage ET with regard to live birth rates per retrieval in poorer prognosis patients. The adoption of routine blastocyst culture for all patients would result in higher rates of single embryo transfers (SET), reduced incidence of multiple pregnancies and simplified laboratory protocols, thereby reducing costs. METHODS/DESIGN:Multicenter, non-inferiority randomized controlled trial (RCT) comparing blastocyst to cleavage stage embryo transfer in poorer prognosis patients with ≤5 zygotes on day 1 after fertilization. The primary outcome is live birth per retrieval. Secondary outcomes include: time to pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and multiple pregnancy rate (per retrieval). This trial will enroll 658 women with ≤5 zygotes on day 1 at 6 IVF centers over the course of 22 months. DISCUSSION:If the hypothesis is proven true, the data from this trial may facilitate the adoption of uniform blastocyst culture in all IVF patients. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03764865. Registered 5 December 2019, Protocol issue date: 4 December 2018, Original.
| S-EPMC6993366 | biostudies-literature
Project description:OBJECTIVE:To compare the pregnancy and obstetric outcomes in elective single versus two cleavage-stage embryo transfer. METHODS:Fresh cleavage-stage embryo transfer cycles between January, 2014 and October, 2015 were reviewed, including 39 single embryo transfer (eSET) cycles and 200 double embryo transfer (DET) cycles. The clinical pregnancy rates, implantation rates, multiple pregnancy rates, live birth rate, and obstetric outcomes (gestational age, preterm delivery rate and mean birth weight) were compared between the two groups. RESULTS:The baseline characteristics were comparable between the two groups. The estradiol level on the day of trigger and the oocyte number were significantly higher in eSET group than in DET group (10654.4 pmol/L vs 8284.2 pmol/L and 8.4 vs 7.0, respectively). No significant difference was found in the pregnancy rate (56.4% vs 66.0%) or live birth rate (48.7% vs 51.5%) between the two groups, and their implantation rates differed significantly (56.4% vs 37.8%). No multiple pregnancies occurred in eSET group while the rate of multiple pregnancies was 22.7% in DET group. The gestational age and mean birth weight were significantly higher in eSET group (P<0.05), and the preterm delivery rate after DET was nearly three times of that after eSET, although this difference was not statistically significant. CONCLUSIONS:Elective single embryo transfer can be performed without compromising the live birth rates. Multiple pregnancy rates can be significantly reduced with eSET, which also results in a higher chance of delivering a term singleton live birth compared with DET.
| S-EPMC6744098 | biostudies-literature
Project description: Not available
| S-EPMC10107888 | biostudies-literature
Project description:PurposeStudies on rodents have shown that assisted reproductive technologies (ARTs) are associated with perturbation of genomic imprinting in blastocyst-stage embryos. However, the vulnerable developmental window for ART influence on the genomic imprinting of embryos is still undetermined. The purpose of this study was to establish the specific embryonic development stage at which the loss of methylation of H19 imprinting control regions (ICRs) was caused by ART occurrence. Additionally, we explored protocols to safeguard against possible negative impacts of ART on embryo H19 imprinting.MethodsMouse embryos were generated under four different experimental conditions, divided into four groups: control, in vitro culture (IVC), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). The methylation levels of H19 ICR of the grouped or individual embryos were analyzed by bisulfite-sequencing PCR.ResultsOur data showed that the loss of methylation of H19 ICR in mouse blastocysts was inflicted to a similar extent by IVC, IVF, and ICSI. Specifically, we observed a significant loss of methylation of H19 ICR between the mouse 8-cell and morula stages. In addition, we revealed that the transfer of mouse embryos generated by ARTs in the uterus at the 8-cell stage induced the occurrence of methylation patterns in the blastocysts closer to the in vivo ones.ConclusionsOur findings indicate that the loss of methylation of H19 ICR caused by ARTs occurs between the 8-cell and the morula stages, and the transfer of cleavage embryos to the uterus mitigates the loss methylation of H19 derived by mice ARTs.
| S-EPMC6885496 | biostudies-literature
Project description:BackgroundSequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes.MethodsA literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I2 statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019.ResultsTen eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26-1.60, P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17-2.13, P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20-1.66, P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer.ConclusionThe current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.
| S-EPMC8439041 | biostudies-literature
Project description:In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).
| S-EPMC11377718 | biostudies-literature
Project description:PURPOSE:In vitro fertilization (IVF) infants have lower birthweights than their peers, predisposing them to long-term health consequences. Blastocyst transfer (BT), at day 5-6 post-fertilization, is increasing in usage, partially due to improved pregnancy outcomes over cleavage-stage transfer (CT, day 2-3). Data to date, however, have been inconclusive regarding BT's effects on birthweight. METHODS:Participants included all US autologous, single-gestation, fresh embryo transfer cycles initiated from 2007 to 2014 that resulted in a term infant (N = 124,154) from the National Assisted Reproductive Technology Surveillance System. Generalized linear models including obstetric history, maternal demographics, and infant sex and gestational age were used to compare birthweight outcomes for infants born following BT (N = 67,169) with infants born following CT (N = 56,985) and to test for an interaction between transfer stage and single embryo transfer (SET). RESULTS:Infants born following BT were 6 g larger than those born following CT (p = 0.04), but rates of macrosomia (RR 1.00, 95% CI 0.96-1.04) and low birthweight (LBW, RR 1.00, 95% CI 0.93-1.06) were not different between the groups. The interaction between SET and transfer stage was significant (p = 0.02). Among SET infants, BT was associated with 19.26 g increased birthweight compared to CT (p = 0.008). CONCLUSIONS:The increase in birthweights identified following BT is unlikely to be clinically relevant, as there were no differences in rates of macrosomia or LBW. These findings are clinically reassuring and indicate that the increasing use of BT is unlikely to further decrease the on average lower birthweights seen in IVF infants compared to their naturally conceived peers.
| S-EPMC6030018 | biostudies-literature
Project description:PurposeEmerging data suggests improved obstetric outcomes with frozen embryo transfer (FET) in an ovulatory or natural cycle (NC-FETs), as compared to programmed endometrial preparation. The objective of this study is to better understand practice patterns and provider attitudes regarding the use of NC-FETs in the United States (U.S.).MethodsIn this cross-sectional study, an anonymous 22-question survey was emailed to 441 U.S. Assisted Reproductive Technology (ART) clinics to assess the utilization of NC endometrial preparation for FET, protocols used, restrictions to offering NC-FET, and providers' perspectives on advantages and disadvantages of NC-FET. Descriptive statistics were used to analyze survey responses.Result(s)The survey response rate was 49% (216/441). Seventeen percent of responding clinics did not offer NC-FET. Of the clinics that did not offer NC-FET, 65% had only 1-2 physicians in their practice. Common reasons for not offering NC-FET included "lack of timing predictability for transfer" (81%) and "increased burden on staff/laboratory personnel on holidays and weekends" (54%). Of clinics offering NC-FET, 76% reported < 25% of cycles used the NC for endometrial preparation. Over half (52%) of clinics that offered NC-FET reported having eligibility restrictions for NC-FET. Reported benefits of NC-FET were "patient satisfaction" (18%), "decreased cost of medications" (18%), and "avoidance of intramuscular progesterone" (17%). The attitude towards NC-FET in their clinics was reported as positive by 65% of respondents.ConclusionNC-FETs are offered by most U.S. ART clinics but are used only in the minority of FET cycles for endometrial preparation, and use is often restricted.
| S-EPMC10224901 | biostudies-literature
Project description:ObjectivesTo evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and perinatal complications is increased compared with cleavage stage embryo transfers during in vitro fertilisation (IVF) treatment.DesignMulticentre randomised controlled trial.Setting21 hospitals and clinics in the Netherlands, 18 August 2018 to 17 December 2021.Participants1202 women with at least four embryos available on day 2 after oocyte retrieval were randomly assigned to either blastocyst stage embryo transfer (n=603) or cleavage stage embryo transfer (n=599).InterventionsIn the blastocyst group and cleavage group, embryo transfers were performed on day 5 and day 3, respectively, after oocyte retrieval, followed by cryopreservation of surplus embryos. Analysis was on an intention-to-treat basis, with secondary analyses as per protocol.Main outcome measuresThe primary outcome was the cumulative live birth rate per oocyte retrieval, including results of all frozen-thawed embryo transfers within a year after randomisation. Secondary outcomes included cumulative rates of pregnancy, pregnancy loss, and live birth after fresh embryo transfer, number of embryo transfers needed, number of frozen embryos, and obstetric and perinatal outcomes.ResultsThe cumulative live birth rate did not differ between the blastocyst group and cleavage group (58.9% (355 of 603) v 58.4% (350 of 599; risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). The blastocyst group showed a higher live birth rate after fresh embryo transfer (1.26, 1.00 to 1.58), lower cumulative pregnancy loss rate (0.68, 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55 v 1.82; P<0.001). The incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher in the blastocyst group (1.87, 1.05 to 3.34).ConclusionBlastocyst stage embryo transfers resulted in a similar cumulative live birth rate to cleavage stage embryo transfers in women with at least four embryos available during IVF treatment.Trial registrationInternational Clinical Trial Registry Platform NTR7034.
| S-EPMC11403767 | biostudies-literature