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

Sanchez F^1,², Le AH^3,⁴, Ho VNA^3,⁴, Romero S^1,², Van Ranst H¹, De Vos M¹, Gilchrist RB⁵, Ho TM^3,⁴, Vuong LN^3,^4,⁶, Smitz J¹

Follicle Biology Laboratory, UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090, Brussel, Belgium.
Laboratory of Reproductive Biology and Fertility Preservation, Cayetano Heredia University (UPCH), Lima, Peru.
IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam.
HOPE Research Center, Ho Chi Minh City, Vietnam.
Fertility and Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
Department of Obstetrics and Gynecology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam

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.

KEYWORDS:

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

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