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Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

ABSTRACT: PURPOSE:To determine the developmental competence of fast-cleaving D3 embryos. METHODS:Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ?13 -cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the chance to give rise to an euploid blastocyst in each group compared with the chance of 8-cell embryos. Implantation and live birth rates were also analyzed. RESULTS:The statistical analysis showed that embryos with 9 to 11 cells had a slightly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.77 (0.61-0.96)) while embryos with more than 11 cells were found to be just as likely to give rise to an euploid blastocyst as the 8-cell embryos (OR (95% CI) 1.20 (0.92-1.56)). Conversely, slow-cleaving embryos had a significantly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.31 (0.24-0.39)). Moreover, euploid blastocysts derived from fast-cleaving embryos and from 8-cell embryos exhibit similar live birth rates. No significant differences were found in the chance to give rise a live birth between 8-cell and 9- to 11-cell embryos (OR (95% CI) 1.23 (0.70-2.15)) and >?11-cell embryos (OR (95% CI) 1.09 (0.57-2.09)). CONCLUSIONS:Embryos with more than 11 cells exhibit similar developmental competence to 8-cell embryos. Their poor prognosis should be reconsidered.

SUBMITTER: Pons MC

PROVIDER: S-EPMC6885468 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

Pons Maria Carme MC Carrasco Beatriz B Parriego Mònica M Boada Montserrat M González-Foruria Iñaki I Garcia Sandra S Coroleu Buenaventura B Barri Pedro N PN Veiga Anna A

Journal of assisted reproduction and genetics 20190902 11

<h4>Purpose</h4>To determine the developmental competence of fast-cleaving D3 embryos.<h4>Methods</h4>Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ≥13 -cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the ...[more]

PMID: 31478159

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Project description:ObjectiveTo investigate whether the mitochondrial DNA (mtDNA) content of a single biopsy at trophoblast correlates with the developmental potential and reproductive outcomes of blastocyst.MethodsA retrospective analysis applied the dataset of 1,675 embryos with preimplantation genetic testing for aneuploidy (PGT-A) from 1,305 individuals, and 1,383 embryos involved cryotransfers of single euploid embryo between January 2015 and December 2019. The studied cohort was divided for algorithm establishment on the NGS platform (n=40), correlation of biological features (n=1,635), and correlation of reproductive outcomes (n=1,340). Of the algorithm derived from the NGS platform, the reliability and repeatability were validated via qPCR assay and inter-run controls, respectively. Of the correlation across biological features, stratification analyses were applied to evaluate the effect from a single contributor. Eventually, the correlation between the mtDNA ratios and reproductive outcomes was adjusted according to the significant effector(s).ResultsThe mtDNA ratios showed statistically different between embryos with different days of blastocyst formation ([Day 5]: 1.06 vs. [Day 6]: 0.66, p=0.021), and between embryos with different expansion stages ([Expansion 5]: 1.05 vs. [Expansion 6]: 0.49, p=0.012). None or weakly correlated with the maternal age, morphology, ploidy, and gender. Analyzed by the different days of blastocyst formation with fixed expansion score as 5 in the euploid single embryo transfers (eSET), the day 6 eSET showed significantly lower reduced mtDNA ratio (n=139) in failure groups of fetal heartbeat (p=0.004), ongoing pregnancy (p=0.007), and live birth (p=0.01); however, no correlation between mtDNA ratios and pregnancy outcomes was observed in the day 5 eSET (n=1,201).ConclusionsThe study first demonstrated that mtDNA ratio was dependent on the days of blastocyst formation while expansion stage was fixed. Lower mtDNA ratios were observed in the day 6 eSET with adverse outcomes. The present stratification analyses reveal that the timeline of embryo is an important covariate to the mtDNA content.

Project description:Background:To evaluate if it is safe and effective to transfer poor quality embryos. Methods:It was a retrospective analysis using individual patient data with positive controls. All patients undergoing embryo transfers of poor quality embryos on day 3 or on day 5 as part of fresh In Vitro Fertilization (IVF) cycles performed between 2012 and 2016. This study assessed a total of 738 poor quality embryos from 488 IVF programs. 261 embryo transfers were performed on day 3 (402 embryos were transferred) and 227 on day 5 (336 embryos were transferred). Control group consisted of 9893 fair and good quality embryos from 5994 IVF programs. Outcome rates were compared with two-tailed Fisher exact test using fisher.test function in R software. 95% confidence intervals for proportions were calculated using the Clopper-Pearson method with binom.test function in R. The groups of patients with poor vs. good and fair quality embryos were compared by age, body mass index(BMI), number of oocytes, female and male main diagnosis, cycle type, controlled ovarian stimulation (COS) protocol, the starting day of gonadotropin administration, the starting dose of gonadotropins, the total dose of gonadotropins, the total number of days of gonadotropins administration, the starting day of gonadotropin-releasing hormone (GnRH) agonist administration, the total number of ampoules of GnRH-agonist used, day of the trigger of ovulation administration and the type of the trigger of ovulation using the Student's t-test for interval variables and with the chi-square test for nominal variables. Results:No significant differences in the implantation rate, clinical pregnancy rate, miscarriage rate, live births, and the number of children born were found between the groups of poor quality embryos transferred on day 3 and day 5. Though the implantation rate was lower for the group of poor quality embryos, than for the control (13.9% vs 37.2%), statistically significant differences between the proportion of implanted embryos which resulted in clinical pregnancies and live births in both groups were not observed (72% vs 78.2 and 55.8% vs 62.0% respectively). Conclusion:Transfer of poor quality embryos at either day 3 or day 5 have a low potential for implantation, though those embryos which successfully implanted have the same potential for live birth as the embryos of fair and good quality. This study supports that it is safe to transfer poor quality embryos when they are the only option for fresh embryo transfer (ET).

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Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

Publications

Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

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