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Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles

Abstract

Purpose

To investigate the effectiveness of a biphasic IVM culture strategy at improving IVM outcomes in oocytes from small follicles (< 6 mm) compared with routine Standard IVM in patients with polycystic ovaries.

Methods

This prospective pilot study was performed in 40 women with polycystic ovaries whose oocytes were randomized to two IVM culture methods. Patients received a total stimulation dose of 450 IU rFSH. Cumulus-oocyte complexes (COCs) from follicles < 6 mm and ≥ 6 mm were retrieved and cultured separately in either a prematuration medium with c-type natriuretic peptide followed by IVM (CAPA-IVM), or STD-IVM. Primary outcomes were maturation rate, embryo quality, and the number of vitrified day 3 embryos per patient.

Results

Use of the CAPA-IVM system led to a significant improvement in oocyte maturation (p < 0.05), to a doubling in percentage of good and top-quality day 3 embryos per COC, and to an increased number of vitrified day 3 embryos (p < 0.001), compared to STD IVM. Oocytes from follicles < 6 mm benefited most from CAPA-IVM, showing a significant increase in the amount of good and top-quality embryos compared to STD IVM. CAPA-IVM yielded significantly (p < 0.0001) less GV-arrested oocytes and larger oocyte diameters (p < 0.05) than STD IVM.

Conclusions

CAPA-IVM brings significant improvements in maturation and embryological outcomes, most notably to oocytes from small antral follicles (< 6 mm), which can be easily retrieved from patients with a minimal ovarian stimulation. The study demonstrates the robustness and transferability of the CAPA-IVM method across laboratories and populations.

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Acknowledgments

The authors acknowledge Francesca Lolicato PhD for logistic support and advice during the study. The authors acknowledge Wim Coucke from Scientific Institute of Public Health (Brussels) for performing the statistical analysis.

Funding

The authors acknowledge the support of the Fund for Research Flanders (Fonds Wetenschappelijk Onderzoek-Vlaanderen-FWO, Project nr AL895) and of the Industrial Research Fund of the Vrije Universiteit Brussel (Industrieel onderzoeksfonds, IOF 2042) to the Project 4R-ART.

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Correspondence to Johan Smitz.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study was performed in accordance with the ICH Harmonized Tripartite Guideline for GCP and the ethical principles of the Declaration of Helsinki. Ethics approval was obtained from the Review Board of the Research Center for Genetics and Reproductive Health and the Ethical Board of MyDuc Hospital (approval number 04/17/ĐĐ-BVMĐ, dated 28 March 2017).

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Informed consent was obtained from all individual participants included in the study.

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Sanchez, F., Le, A.H., Ho, V.N.A. et al. Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles. J Assist Reprod Genet 36, 2135–2144 (2019). https://doi.org/10.1007/s10815-019-01551-5

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Keywords

  • IVF
  • IVM
  • Embryo
  • Oocyte prematuration
  • C-type natriuretic peptide