Assessing the impact of delayed blastulation using time lapse morphokinetics and preimplantation genetic testing in an IVF patient population

Kimelman, Dana; Confino, Rafael; Okeigwe, Ijeoma; Lambe-Steinmiller, J.; Confino, Edmond; Shulman, L.P.; Zhang, Junyi; Pavone, Mary Ellen

doi:10.1007/s10815-019-01501-1

Cited by 26 publications

(17 citation statements)

References 46 publications

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“…The importance of the day of blastocyst development has extensively been studied in relation to ploidy outcomes and implantation potential. Embryos that start to blastulate on day 5 have higher euploid rates compared to embryos that start to blastulate on day 6 [ 37 ], though similar euploid rates have also been described between day 5 and day 6 blastocysts [ 38 ]. In fresh embryo transfer cycles, the stimulation induced endometrial advancement causes a superiority of day 5 blastocysts compared to day 6 in terms of pregnancy and implantation potential [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Though a recent meta-analysis indicated the benefit of day 5 blastocysts in both fresh and frozen embryo transfer cycles [ 40 ], the available low quality of clinical evidence still questions the superiority of day 5 blastocysts [ 41 ]. More specifically, in case of euploid frozen embryo transfer cycles, day 5 and day 6 blastocysts have shown a similar pregnancy potential [ 38 ]. Most studies that use TLM parameters to predict blastocyst development, analyze top or good quality development on day 5 [ 29 – 35 ], and only very limited data is available on blastocyst development between day 5 and day 6 [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, in case of euploid frozen embryo transfer cycles, day 5 and day 6 blastocysts have shown a similar pregnancy potential [ 38 ]. Most studies that use TLM parameters to predict blastocyst development, analyze top or good quality development on day 5 [ 29 – 35 ], and only very limited data is available on blastocyst development between day 5 and day 6 [ 38 ]. In the latter study, only early TLM parameters (tPNf to t8) were analyzed and all of them were significantly different between day 5 and day 6 blastocysts [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

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Marginal differences in preimplantation morphokinetics between conventional IVF and ICSI in patients with preimplantation genetic testing for aneuploidy (PGT-A): A sibling oocyte study

et al. 2022

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Objective This study aimed to analyze the morphokinetic behaviour between conventional IVF and ICSI, in cycles with preimplantation genetic testing for aneuploidies (PGT-A). Materials A randomized controlled trial (NCT03708991) was conducted in a private fertility center. Thirty couples with non-male factor infertility were recruited between November 2018 and April 2019. A total of 568 sibling cumulus oocyte complexes were randomly inseminated with conventional IVF and ICSI and cultured in an Embryoscope time-lapse system. The morphokinetic behaviour of IVF/ICSI sibling oocytes was analysed as primary endpoint. As secondary endpoints, morphokinetic parameters that predict blastocysts that will be biopsied, the day of biopsy, gender and euploid outcome was assessed. Results When comparing IVF to ICSI, only the time to reach the 2-cell stage (t2) was significantly delayed for IVF embryos: OR: 1.282 [1.020–1.612], p = 0.033. After standardizing for tPNf (ct parameters), only Blast(tStartBlastulation-t2) remained significant: OR: 0.803 [0.648–0.994], p = 0.044. For the analysis of zygotes that will be biopsied on day 5/6 versus zygotes without biopsy, only early morphokinetic parameters were considered. All parameters were different in the multivariate model: ct2: OR: 0.840 [0.709–0.996], p = 0.045; ct6: OR: 0.943 [0.890–0.998], p = 0.043; cc2(t3-t2): OR: 1.148 [1.044–1.263], p = 0.004; cc3(t5-t3): OR: 1.177 [1.107–1.251], p<0.0001. When comparing the development between blastocysts biopsied on day 5 versus day 6, only three morphokinetic parameters were significant: cc2(t3-t2): OR: 1.394 [1.010–1.926], p = 0.044; ctBlastocyst: OR: 0.613 [0.489–0.768], p<0.0001 and ctExpandedBlastocyst: OR: 0.913 [0.868–0.960], p = 0.0004. Multivariate analysis of gender and ploidy did not reveal differences in morphokinetic behaviour. Conclusion Minor morphokinetic differences are observed between IVF and ICSI. Early in the development, distinct cleavage patterns are observed between embryos that will be biopsied or not.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Marginal differences in preimplantation morphokinetics between conventional IVF and ICSI in patients with preimplantation genetic testing for aneuploidy (PGT-A): A sibling oocyte study

et al. 2022

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“… 50 In contrast, a logistic regression analysis performed on 485 biopsied embryos identified t3 and t5–t2 as the best predictors of chromosomal normality. 51 Kimelman and colleagues 52 analyzed 2292 embryos from 524 patients and observed significantly longer timings for each morphokinetic variable for blastocysts obtained on day 6 compared to day 5 of culture. Importantly, there were no statistical differences in aneuploidy rates between the two groups.…”

Section: Algorithmsmentioning

confidence: 99%

The clinical use of time-lapse in human-assisted reproduction

Minasi

Greco

Varricchio

et al. 2020

Clin Med�Insights�Reprod�Health

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A major challenge in the assisted reproduction laboratory is to set up reproducible and efficient criteria to identify the embryo with the highest developmental potential. Over the years, several methods have been used worldwide with this purpose. Initially, standard morphology assessment was the only available strategy. It is now universally recognized that besides being a very subjective embryo selection strategy, morphology evaluation alone has a very poor prognostic value. More recently, the availability of time-lapse incubators allowed a continuous monitoring of human embryo development. This technology has spread quickly and many fertility clinics over the world produced a remarkable amount of data. To date, however, a general consensus on which variables, or combination of variables, should play a central role in embryo selection is still lacking. Many confounding factors, concerning both patient features and clinical and biological procedures, have been observed to influence embryo development. In addition, several studies have reported unexpected positive outcomes, even in the presence of abnormal developmental criteria. While it does not seem that time-lapse technology is ready to entirely replace the more invasive preimplantation genetic testing in identifying the embryo with the highest implantation potential, it is certainly true that its application is rapidly growing, becoming progressively more accurate. Studies involving artificial intelligence and deep-learning models as well as combining morphokinetic with other non-invasive markers of embryo development, are currently ongoing, raising hopes for its successful applicability for clinical purpose in the near future. The present review mainly focuses on data published starting from the first decade of 2000, when time-lapse technology was introduced as a routine clinical practice in the infertility centers.

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“…Kirillova et al (13) reported similar clinical factors in women achieving pregnancy after the transfer of poor-quality compared with good-and fair-quality embryos, such as female age or ovarian stimulation protocols, whereas the number of mature oocytes retrieved was significantly different according to the embryo quality. Regarding ploidy, Kimelman et al showed similar rates of euploidy in D5 and D6 embryos that underwent preimplantation genetic testing for aneuploidy, suggesting that the speed of embryo development can be due to other factors than aneuploidy (14). Factors that affect embryo quality between D5 and D6 is deserving of further study.…”

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confidence: 99%

Tobacco consumption is associated with slow-growing day-6 blastocysts

et al. 2020

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Objective: To investigate if there are any obvious clinical factors associated with delayed blastulation at day 6 (D6) compared with day 5 (D5). Design: Monocentric observational cohort study from November 2012 to December 2018. Setting: Tertiary-care academic medical center. Patient(s): A total of 941 women with an entire cohort of exclusively D5 blastocysts compared with 162 patients with a cohort of exclusively D6 blastocysts. Intervention(s): None. Main Outcome Measure(s): Clinical characteristics and data related to the ovarian stimulation protocols. Result(s): After univariate analysis, a significantly higher proportion of women who were active smokers was found in the D6 group compared with the D5 group (n ¼ 22/162 [13.6%] vs. n ¼ 82/941 [8.7%]). In addition, the women in the D6 group had a higher rank number of assisted reproductive technology (ART; total no. of ART cycles performed: 2.1 AE 1.4 vs. 1.6 AE 1.1) and a lower antral follicle count (AFC; 18.7 AE 11.3 vs. 22.2 AE 12.8). Moreover, fertilization with the use of intracytoplasmic sperm injection was used more frequently in the D6 group compared with the D5 group. Logistic regression analysis adjusted for confounders highlighted several independent predictors for reaching blastocyst stage at D6 rather than D5: being an active smoker, previous ART cycles, and a lower AFC. Conclusion(s):Obtaining an exclusively D6 blastocyst cohort is independently associated with women who are active smokers, previous ART cycles, and a lower AFC. These findings provide evidence, to be confirmed by further studies, that women who are active smokers could greatly benefit from smoking cessation before undergoing ART.

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Assessing the impact of delayed blastulation using time lapse morphokinetics and preimplantation genetic testing in an IVF patient population

Cited by 26 publications

References 46 publications

Marginal differences in preimplantation morphokinetics between conventional IVF and ICSI in patients with preimplantation genetic testing for aneuploidy (PGT-A): A sibling oocyte study

Marginal differences in preimplantation morphokinetics between conventional IVF and ICSI in patients with preimplantation genetic testing for aneuploidy (PGT-A): A sibling oocyte study

The clinical use of time-lapse in human-assisted reproduction

Tobacco consumption is associated with slow-growing day-6 blastocysts

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