Interim analysis of patients undergoing minimal stimulation with ovarian support cell in vitro maturation (OSC-IVM) treatment for infertility as part of an observational clinical study

Study Question: What are the embryological and clinical pregnancy outcomes of normal
ovulatory, subfertile women who undergo minimal stimulation with ovarian support cell in vitro
maturation treatment?
Summary answer: Clinically acceptable rates of oocyte maturation and euploid day 5/6
blastocyst formation were achieved after OSC-IVM treatment.
What is known already: Historically, the clinical efficacy of in vitro maturation (IVM) has been
low due to a combination of poor maturation rates and developmental competence, while
displaying a safe tolerability profile. We previously showed that IVM using stem cell
derived-ovarian support cells (OSC) improves the maturation of immature cumulus oocyte
complexes (COCs) retrieved from abbreviated hormonal stimulations. Mature oocytes from
OSC-IVM are capable of generating euploid embryos at a superior rate to conventional IVM
treatments.
Study design, size, duration: This interim analysis spans the first seven of a projected twenty
patients undergoing treatment at a prospectively registered single center, single arm,
longitudinal observational study in Lima, Peru. Treatment began October of 2023 and is
expected to last until December of 2024.
Participants/materials, setting, methods: Participants are subfertile with no ovarian or uterine
abnormalities, under the age of 35. Patients undergo 2-4 days of FSH stimulation with a
reduced hCG trigger. COCs are cultured in the OSC-IVM condition (IVM medium supplemented
with FSH, hCG, A4 and OSCs) for 30h. Matured oocytes are fertilized via ICSI, grown to the
blastocyst stage under timelapse incubation and tested for euploidy. Single euploid blastocysts
are transferred and patients are monitored for pregnancy outcomes.
Main results and the role of chance: In this study, the mean antral follicle count (AFC) at
puncture was 9.86 ± 1.68 (standard deviation) with a mean number of COCs retrieved of 5.70 ±
2.14. For incremental embryological outcomes on a per patient basis, the maturation rate was
63.65% ± 31.6%, the fertilization rate was 70.83% ± 16.5%, the cleavage rate was 100% ± 0%,
the blastocyst rate was 33.9% ± 31.3%, the high quality blastocyst rate was 87.50% ± 25.0%,
and the euploidy rate was 75% ± 28.9%. Embryo transfers are ongoing. No study related
adverse events have been reported. 4 of 7 patients are proceeding to embryo transfer, with 3 patients failing to obtain euploid day 5 or 6 embryos. All 3 patients who failed to obtain
transferrable blastocysts had 5 or less oocytes retrieved.
Limitations, reasons for caution: This study is ongoing with preliminary results. Recruitment
for this prospective study is below 50% and clinical pregnancy endpoints are still being collected
for all patients. Additionally, the single arm, single center nature of this observational study limits
the generalizability of the findings.
Wider implications of the findings: OSC-IVM is an effective method for obtaining high-quality,
euploid embryos. OSC-IVM has the potential to improve fertility care for patients by reducing the
hormonal load. As is known, due to the lower number of oocytes obtained after minimal
stimulation, IVM is recommended for high ovarian reserve patients.
Study funding/competing interest(s): This study is funded by Gameto Inc.
Trial registration number: ISRCTN36032472