Cumulus-corona gene expression analysis combined with morphological embryo scoring in single embryo transfer cycles increases live birth after fresh transfer and decreases time to pregnancy

Abstract

Purpose

Clinical pregnancy rate after IVF with eSET stagnates between 30 and 40%. In order to increase pregnancy and live birth rates, multiple embryo transfer is still common practice. Providing additional non-invasive tools to choose the competent embryo for transfer could avoid multiple pregnancy and improve time to pregnancy. Cumulus mRNA analysis with quantitative PCR (QPCR) is a non-invasive approach. However, so far, no gene sets have been validated in prospective interventional studies.

Methods

A prospective interventional single-center pilot study with two matched controls (day-3 and day-5 eSET) was performed in 96 patients consenting to the analysis of the cumulus-corona of their oocytes. All patients were super-ovulated for ICSI and eSET at day 3. All oocytes were denuded individually and cumulus was analyzed by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D) and two housekeeping genes (UBC and β2M). Patients (n = 62) with 2 or more day-3 embryos (good or excellent morphology) had their embryo chosen following the normalized expression of the genes.

Results

Corona testing significantly increased the clinical pregnancy and live births rates (63% and 55%) compared to single embryo transfer (eSET) on day 3 (27% and 23%: p < 0.001) and day 5 (43% and 39%: p = 0.022 and p = 0.050) fresh transfer cycle controls with morphology-only selection. Time-to-pregnancy was significantly reduced, regardless of the number of good-quality embryos available on day 3.

Conclusion

Combining standard morphology scoring and cumulus/corona gene expression analysis increases day-3 eSET results and significantly reduces the time to pregnancy.

Trial registration number

This is not an RCT study and was only registered by the ethical committee of the University Hospital UZBRUSSEL of the Vrije Universiteit Brussel VUB (BUN: 143201318000).

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Acknowledgments

The authors would like to thank their colleagues of the Centre for Reproductive Medicine, UZ Brussel, for their cooperation in this clinical study, the clinical data manager Walter Meul, and Prof. Dr. André Rosenthal for critical reading and suggestions.

Funding

This study was funded by IWT/VLAIO Innovation Mandate 130327 and 140568 and by the Vrije Universiteit Brussel IOFPOC26.

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Correspondence to J. Smitz.

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T. Adriaenssens and I. Van Vaerenbergh are joint first authors

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Adriaenssens, T., Van Vaerenbergh, I., Coucke, W. et al. Cumulus-corona gene expression analysis combined with morphological embryo scoring in single embryo transfer cycles increases live birth after fresh transfer and decreases time to pregnancy. J Assist Reprod Genet 36, 433–443 (2019). https://doi.org/10.1007/s10815-018-01398-2

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Keywords

  • Cumulus cells
  • Gene expression
  • Single embryo transfer
  • Clinical pregnancy
  • Non-invasive
  • Oocyte quality