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Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review.

ABSTRACT:

Background

Sequential 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.

Methods

A 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.

Results

Ten 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.

Conclusion

The 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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8439041 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF.MethodsWe searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate.ResultsNo differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2 = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2 = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2 = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2 = 93 %). The overall quality of the evidence was very low for all these four outcomes.ConclusionsAlthough using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

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Project description:BackgroundTime-lapse imaging combined with embryo morphokinetics may offer a non-invasive means for improving embryo selection. Data from clinics worldwide are necessary to compare and ultimately develop embryo classifications models using kinetic data. The primary objective of this study was to determine if there were kinetic differences between embryos with limited potential and those more often associated with in vitro blastocyst formation and/or implantation. We also wanted to compare putative kinetic markers for embryo selection as proposed by other laboratories to what we were observing in our own laboratory setting.MethodsKinetic data and cycle outcomes were retrospectively analyzed in patients age 39 and younger with 7 or more zygotes cultured in the Embryoscope. Timing of specific events from the point of insemination were determined using time-lapse (TL) imaging. The following kinetic markers were assessed: time to syngamy (tPNf), t2, time to two cells (c), 3c (t3), 4c ( t4), 5c (t5), 8c (t8), morula (tMor), start of blastulation (tSB); tBL, blastocyst (tBL); expanded blastocyst (tEBL). Durations of the second (cc2) and third (cc3) cell cycles, the t5-t2 interval as well as time to complete synchronous divisions s1, s2 and s3 were calculated. Incidence and impact on development of nuclear and cleavage anomalies were also assessed.ResultsA total of 648 embryos transferred on day 5 were analyzed. The clinical pregnancy and implantation rate were 72% and 50%, respectively. Morphokinetic data showed that tPNf, t2,t4, t8, s1, s2,s3 and cc2 were significantly different in embryos forming blastocysts (ET or frozen) versus those with limited potential either failing to blastulate or else forming poor quality blastocysts ,ultimately discarded. Comparison of embryo kinetics in cycles with all embryos implanting (KID+) versus no implantation (KID-) suggested that markers of embryo competence to implant may be different from ability to form a blastocyst. The incidence of multinucleation and reverse cleavage amongst the embryos observed was 25% and 7%, respectively. Over 40% of embryos exhibiting these characteristics did however form blastocysts meeting our criteria for freezing.ConclusionsThese data provide us with a platform with which to potentially enhance embryo selection for transfer.

Project description:ObjectiveTo study the impact of congenital uterine anomalies on reproductive outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET).MethodsA retrospective study including a total of 865women with congenital uterine anomalies and 865 age and admission time matched controls who underwent the first IVF/ICSI-ET cycle between January 2010 and December 2019 was conducted. Women with uterine anomalies were classified into canalization defect (complete septate uterus and subseptate uterus) and unification defect (unicornuate uterus, bicornuate uterus, and didelphus uterus) according to the processes of abnormal embryological development. Control women were selected by age (± 1.0 year) and admission time (± 6 months) matched with a 1:1 ratio. The reproductive outcomes were compared between women with uterine anomalies and the controls. The primary outcome was live birth; secondary outcomes were clinical pregnancy, ectopic pregnancy, preterm delivery, and spontaneous pregnancy loss.ResultsCompared with women with a normal uterus, women with canalization defects were less likely to experience live birth [84/332 (25.3%) vs 128/332 (38.6%), RR: 0.647, 95% CI 0.513-0.815, P < 0.001]. They also had a lower clinical pregnancy rate [126/332 (38.0%) vs 206/332 (62.0%), RR: 0.829, 95% CI 0.690-0.997, P = 0.046] and experienced a higher first-trimester pregnancy loss rate [25/126 (19.8%) vs 11/206 (5.3%), RR: 2.716, 95% CI 1.393-5.295, P = 0.003]. Compared with women with a normal uterus, women with a unification defect were also less likely to experience live birth [132/533 (24.8%) vs 219/533 (41.1%), RR: 0.713, 95% CI 0.586-0.868, P = 0.001]. Women with a unification defect had lower clinical pregnancy rates [182/533 (34.1%) vs 263/533 (49.1%), RR: 0.813, 95% CI 0.695-0.952, P = 0.010] and increased first-trimester pregnancy loss [36/182 (19.8%) vs 20/263 (7.6%), RR: 3.288, 95% CI 1.776-6.085, P < 0.001]. While uterine anomaly seemed not increase the risk of preterm birth, ectopic pregnancy and second-trimester pregnancy loss.ConclusionsBoth canalization defects and unification defects were associated with lower fertility outcomes, including lower live birth rates, lower clinical pregnancy rates, and higher early miscarriage rates.