Effect of biphasic CAPA-IVM on ovarian tissue oocytes of transgender men

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 Biphasic CAPA-IVM did not show any significant difference in maturation competence and genetic variations when compared with 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 the OTO competency in these patients. Similarly, OTO could be collected from transgender men without ovarian stimulation during gender reassignment surgery. Even having adequate survival and maturation, OTO-IVM in transgender men has exhibited decreased fertilization rate and severely compromised developmental competency probably due to long testosterone treatment before surgery. For this reason, we sought to investigate whether this compromised potential can be rescued through biphasic CAPA-IVM. Study design, size, duration Patients were recruited from July 2022 to December 2022. Ovaries were collected from 4 transgender patients (age= 18-26 years, mean age=21 years) who underwent gender reassignment surgery after testosterone treatment (mean length= 32 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 COCs collected during ovarian manipulation were cultured either in in-house IVM medium for 48 hours or in biphasic CAPA-IVM for 54 hours. Following maturation, these oocytes were analyzed for Calcium (Ca2+)-releasing potential and developmental competency after ICSI. In vitro matured GV (germinal vesicle), MI (metaphase I) and in vivo matured oocytes with clusters of smooth endoplasmic reticulum (SERa) served as controls. Genetic analysis was performed on subsequent embryos to detect chromosomal abnormalities in all groups. Main results and the role of chance A Total of 133 COCs were collected (44 in CAPA-IVM and 53 in in-house IVM) and both showed a similar maturation rate i.e. 55%. After culture period, the survival rate tended to be higher in the in-house IVM compared to CAPA-IVM (78% vs. 68%, p = 0.184). Following ICSI, 8/11 CAPA-IVM and 8/13 in-house IVM oocytes were normally fertilized, comparable to controls (5/5) (p = 0.195 and p = 0.103 respectively). Blastocyst rates were lower in both CAPA-IVM (1/8) and in house IVM (2/8) compared to controls (3/5), however not significant (p = 0.071 and p = 0.207 respectively). Ca2+-releasing potential of oocytes was determined as a product of amplitude and frequency, in arbitrary units (AU). The average values for CAPA-IVM (1.61) and in-house IVM (1.58) were similar (p = 0.97). Shallow whole genome sequencing (Shallow WGS) of developed embryos showed that 3/5 in PMC group, 3/7 in in-house IVM group were chromosomally abnormal. Limitations, reasons for caution The number of included patients is low, so obtained results should be interpreted with caution. Wider implications of the findings To the best of our knowledge, this is the first study on the use of biphasic CAPA-IVM for transgender OTO-IVM oocytes. Further investigation on the added value of CAPA-IVM together with the effect of testosterone treatment length might help shape more accurate guidelines for the fertility preservation of transgender men. Trial registration number not applicable