P-355 Effect of biphasic CAPA-IVM on ovarian tissue oocytes of transgender men
Authors: Fakhar I Adil M , Christodoulaki A , Chuva de Sousa Lopes S  M , Weyers S , Menten B , Van Soom A , Stoop D , De Roo C , Heindryckx B 
Published: July 2024

Abstract

Study question
Can CAPA-IVM (Biphasic in-vitro maturation) with C-type natriuretic peptide (CNP), followed by in vitro maturation (IVM) improve ovarian tissue oocyte (OTO) maturation in transgender patients?

Summary answer
CAPA-IVM did not show any significant difference in maturation competence and frequency of chromosomal aberrations when compared with standard and in-house IVM.

What is known already
OTO-IVM is a method of fertility preservation in patients where prior ovarian stimulation is undesired. It has resulted in live births in cancer and polycystic ovarian syndrome (PCOS) patients. CAPA-IVM has further improved oocyte competency in these patients by synchronizing nuclear and cytoplasmic maturity. Similarly, OTO can be collected from transgender men without ovarian stimulation during gender reassignment surgery. While oocytes do survive and mature, OTO-IVM in transgender men is characterized by decreased fertilization rate and severely compromised developmental competency. We investigated whether CAPA-IVM can improve cytoplasmic immaturity for transgender OTO.

Study design, size, duration
Patients were recruited from July 2022 to July 2023. Both ovaries were collected from 9 transgender patients (age= 20-24 years, mean age=22 years) who underwent gender reassignment surgery after testosterone treatment (mean length= 34 months). All ovaries were collected in cold medium (4oC) and manipulation was performed within 30 minutes of the collection for the retrieval of cumulus oocyte complexes (COCs).

Participants/materials, setting, methods
Collected COCs were cultured either in in-house IVM and Standard (Medicult) IVM medium for 48 hours or in biphasic CAPA-IVM for 54 hours (24 hours pre-maturation culture and 30 hours IVM). Following maturation, oocytes were analyzed for calcium (Ca2+)-releasing potential and developmental competency after ICSI. In vitro matured MI (metaphase I) oocytes from stimulated IVF patients served as controls. Genetic analysis was performed on subsequent embryos to detect chromosomal abnormalities in all groups.

Main results and the role of chance
After culturing 330 COCs, the survival rate following maturation was similar in the in-house IVM (79%) compared to Medicult (72%, p = 0.221) and CAPA-IVM (73%, p = 0.251). A similar maturation rate (i.e. 55-57%) was observed in the different groups. Following ICSI, 15/25 (60%) CAPA-IVM, 13/19 (68.5%) Medicult IVM, and 17/28 (61%) in-house IVM oocytes were normally fertilized, which was lower than controls (24/29, 83%). Blastocyst rate was inferior in all OTO groups and significantly lower (p = 0.031) in Medicult-IVM (0/13) compared to controls (7/24). Ca2+-releasing potential of oocytes was determined as a product of amplitude and frequency, in arbitrary units (AU). The average values for CAPA-IVM (1.74AU), Medicult IVM (1.24AU), and in-house IVM (1.54AU) were significantly lower (p = 0.022, p = 0.008 and p = 0.017 respectively) compared to controls (4.76AU). Shallow whole genome sequencing of developed embryos (Day 2- Day 5) showed that 8/13 (61.5%) in CAPA-IVM, 4/8 (50%) in In-house IVM, 1/6 (17%) in Medicult, and 4/12 (33%) in the Control group were chromosomally normal.

Limitations, reasons for caution
The limited inclusion of patients warrants caution in the interpretation of the results. Moreover, the lack of a better control group might mask the properties of OTO-IVM.

Wider implications of the findings
Our preliminary results do not demonstrate an improvement in oocyte maturation and embryo development with the implementation of CAPA-IVM. However, future proteomics and transcriptomic studies would shed more light on the advantages of the current IVM systems and decipher the true potential of OTO-IVM from transgender men.

Trial registration number
not applicable