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.

Keywords: C-type natriuretic peptide; Embryo; IVF; IVM; Oocyte prematuration.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1

Representative scheme showing the clinical protocol applied and the key steps following oocyte retrieval. The stimulation protocol used was similar for the two different groups of IVM systems

Fig. 2

Representative images of cumulus-oocyte complexes immediately after oocyte retrieval (left panel) and after undergoing the CAPA-IVM system. The figure shows a group of COCs

Fig. 3

Representative example of a pool of COCs after retrieval (left panel), with an oocyte that is only partially surrounded by cumulus cells (arrow). In the middle panel are COCs after CAPA culture. In the right panel a fully expanded COC is shown and an oocyte that has become totally disconnected from cumulus cells (arrow) after incubation in CAPA-IVM