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Continuous embryo culture elicits higher blastulation but similar cumulative delivery rates than sequential: a large prospective study

  • Assisted Reproduction Technologies
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Abstract

Purpose

To assess whether continuous embryo culture involves better embryological and/or clinical outcomes than sequential.

Methods

Prospective study at a private IVF center. All consecutive IVF cycles (September 2013–2015) fulfilling the inclusion criteria underwent embryo culture in either Continuous-Single-Culture-Media (CSCM, n = 972) or sequential media (Quinn’s Advantage, n = 514), respectively. ICSI, blastocyst culture in either standard (MINC) or undisturbed (Embryoscope) incubation, transfer (until September 2016), and pregnancy follow-up (until September 2017) were performed. When aneuploidy testing was required, trophectoderm biopsy and qPCR were performed. Sub-analyses and logistic regression corrected for confounders were performed. The primary outcomes were overall blastocyst rate per oocyte and mean blastocyst rate per cycle. The sample size was defined to reach 95 and 80% statistical power for the former and the latter outcome, respectively. Secondary outcomes were euploidy (if assessed), cumulative delivery rates, gestational age, and birthweight.

Results

Continuous embryo culture resulted into a higher overall blastocyst rate per inseminated oocyte than sequential (n = 2211/5841, 37.9% vs. 1073/3216, 33.4%; p < 0.01), confirmed also from a cycle-based analysis (mean blastocyst rate: 38.7% ± 29.7% vs. 34.3% ± 29.4%; p = 0.01). The continuous media (OR = 1.23), the undisturbed incubation system (OR = 1.22), the maternal age (OR = 0.92), and the sperm factor (OR = 0.85) were outlined as positive predictors of blastulation. However, the cumulative delivery rates per ended cycle (i.e., delivery achieved or no blastocyst produced or left; > 90%) were comparable in the two groups (n = 244/903, 27.0% vs. 129/475, 27.2%). The neonatal outcomes were similar.

Conclusions

Continuous culture involves better embryological but similar clinical outcomes than sequential. This large prospective study supports the absence of clinical disparity among the two approaches.

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Author’s role

LR, CS, and FMU designed the study. DC analyzed the data and drafted the manuscript. All the authors contributed to the data collection and provided an important contribution for their interpretation and discussion.

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Authors

Corresponding author

Correspondence to Danilo Cimadomo.

Ethics declarations

The Institutional Review Board of the clinic approved the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplemental Figure 1

A) Blastocysts’ morphological quality in the two arms of the study. Blastocyst morphology was assessed as described in [19, 20] (see materials and methods). A statistically-significant higher rate of excellent quality blastocysts, and lower rate of good and average quality ones derived from the culture with single step (Irvine CSCM) with respect to sequential media (Quinn’s Advantage); p = 0.01; B) Day of blastocyst’s full development in the two arms of the study. The embryos cultured with Irvine CSCM were faster in completing their development to blastocyst; p < 0.01. (GIF 34 kb)

High resolution image (TIF 10268 kb)

Supplemental Figure 2

A) Distribution of the deliveries in the two classes of gestational age (pre- or full-term) among the two study groups. p = NS; B) Box-plots showing the gestational age in the two arms of the study. p = NS; C) Distribution of the babies born in the three classes of birthweight (low, normal or large) among the two study groups. p = NS; D) Box-plots showing the birthweight in the two arms of the study. p = NS. (GIF 46 kb)

High resolution image (TIF 7211 kb)

Supplemental Table 1

(DOCX 30 kb)

Supplemental Table 2

(DOCX 28 kb)

Supplemental Table 3

(DOCX 25 kb)

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Cimadomo, D., Scarica, C., Maggiulli, R. et al. Continuous embryo culture elicits higher blastulation but similar cumulative delivery rates than sequential: a large prospective study. J Assist Reprod Genet 35, 1329–1338 (2018). https://doi.org/10.1007/s10815-018-1195-4

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  • DOI: https://doi.org/10.1007/s10815-018-1195-4

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