Clinical validation of embryo culture and selection by morphokinetic analysis A randomized controlled trial of the EmbryoScope

Capsule:
An alternative strategy for embryo selection based on a multivariable morphokinetic model combined with continuous incubation in an integrated timelapse monitoring system improves the clinical results.

Authors:
Irene Rubio, Ph.D., Arancha Galan, Ph.D., Zaloa Larreategui, Ph.D., Jose Bellver, M.D., Fernando Ayerdi, Ph.D., Javier Herrero, Ph.D., Marcos Meseguer, Ph.D.

Volume 102, Issue 5, Pages 1287-1294

Abstract:

Objective:
To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system (TMS) and selection supported by the use of a multivariable morphokinetic model improve reproductive outcomes in comparison with incubation in a standard incubator (SI) embryo culture and selection based exclusively on morphology.

Design:
Prospective, randomized, double-blinded, controlled study.

Setting:
University-affiliated private in vitro fertilization (IVF) setting.

Patient(s):
843 infertile couples undergoing intracytoplasmic sperm injection (ICSI).

Intervention(s):
No patient intervention; embryos cultured in SI with development evaluated only by morphology (control group) and embryos cultured in TMS with embryo selection was based on a multivariable model (study group).

Main Outcome Measure(s):
Rates of embryo implantation, pregnancy, ongoing pregnancy (OPR), and early pregnancy loss.

Result(s):
Analyzing per treated cycle, the ongoing pregnancy rate was statistically significantly increased 51.4% (95% CI, 46.7–56.0) for the TMS group compared with 41.7% (95% CI, 36.9–46.5) for the SI group. For pregnancy rate, differences were not statistically significant at 61.6% (95% CI, 56.9–66.0) versus 56.3% (95% CI, 51.4–61.0). The results per transfer were similar: statistically significant differences in ongoing pregnancy rate of 54.5% (95% CI, 49.6–59.2) versus 45.3% (95% CI, 40.3–50.4) and not statistically significant for pregnancy rate at 65.2% (95% CI, 60.6–69.8) versus 61.1% (95% CI, 56.2–66.1). Early pregnancy loss was statistically significantly decreased for the TMS group with 16.6% (95% CI, 12.6–21.4) versus 25.8% (95% CI, 20.6–31.9). The implantation rate was statistically significantly increased at 44.9% (95% CI, 41.4–48.4) versus 37.1% (95% CI, 33.6–40.7).

Conclusion(s):
The strategy of culturing and selecting embryos in the integrated EmbryoScope time-lapse monitoring system improves reproductive outcomes.

Clinical Trial Registration Number:
NCT01549262.

  • Shvetha Zarek

    This was a triple blind randomized controlled trial of 843 couples undergoing ART in two centers in Spain. Subjects were 20-38 years old undergoing their first or second ICSI cycle and were randomized to a standard incubator or an incubator with a built in time monitoring system (EmbryoScope). This study included both cleavage stage and blastocyst stage embryo transfers. The authors states that the day of transfer was decided on day of oocyte retrieval based on previous medical criteria. The primary outcome was ongoing pregnancy at 12 weeks. The authors report an improved ongoing pregnancy rate in the EmbryoScope arm (51.4% (95% CI, 46.7–56.0) versus 41.7% (95% CI, 36.9–46.5, p=.005) for the SI/control group, as well as decreased pregnancy loss and increased implantation rate. The EmbryoScope group had a higher percentage of optimal Day 3 and Day 5 embryos transferred.

    This study aims to assess the utility of the EmbryoScope both in cleavage stage and blastocyst transfer with a commendable RCT study design! There were a number of questions specifically on deviation from randomization for patient requests for the EmbryoScope and how this was incorporated into the analyses given that these patients were not truly randomized. In addition, is there further information available about how previous medical criteria (especially in a first ART cycle) was used to determine day of embryo transfer? Thank you, kindly.

    • Marcos Meseguer

      Thank you for
      your comments.

      Yes initially the study were triple blinded but
      we detected a failure in the randomization as some of our patients after being
      randomized asked personally if they were included in the embryoscope group and
      asked for a change, that happened in a very reduced proportion of patients but
      forced us to not consider that randomization were fully achieved in that step. Nevertheless,
      randomization was achieved at the gynecologist level (evaluating the primary
      effect) did not know to which group the patients had been assigned, and [2] the
      statistician evaluating the results only knew the incubators by a binary code
      and not by type. This small deviation from the original plan was not
      compensated or controlled by any special and subsequent analysis in the final
      outcome and we strongly believe that did not affect the final outcome of the
      study.

      Regarding your second question, it was
      almost impossible to determine any specific criteria to determine the day of
      the transfer. In the study more than 8 doctors participated collecting
      patients, some of them do Day 5 transfer routinely, some of them only Day 3.
      Some patients come to our clinic asking directly for Day 5 transfer. Some of
      them have already a baby naturally conceived and asked for blastocyst and
      SET…….this is why we were unable to find any medical predefined mediacal criteria.

      Hope those answers will be valuable for
      you.

      Best

      Marcos

      • Shvetha Zarek

        Thank you very much for the reply. It was very helpful in confirming that the number of subjects that were not randomized was small. We very much enjoyed reviewing this study in our group and send our best regards to you and the co-authors. Thank you very much.

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