Keywords: Ovarian support cells, in vitro maturation, stem cells, pregnancy, abbreviated hormonal stimulation
OBJECTIVE: We have previously demonstrated the effectiveness of a novel in vitro maturation (IVM) approach using human induced pluripotent stem cell (hiPSC)-derived ovarian support cells (OSC) for improving the maturation rate of immature cumulus oocyte complexes (COCs) retrieved from truncated hormonal stimulations. Notably, mature oocytes from OSC-IVM are capable of generating euploid embryos at a superior rate to conventional IVM treatments. Here, we present a case report detailing the first clinical translation of this IVM approach.
MATERIALS AND METHODS: This case report is from a First In Human clinical observational study (ISRCTN36032472) aimed at investigating the efficacy and safety of OSC-IVM treatment. Human immature COCs were obtained from a subfertile patient under an abbreviated stimulation protocol, which consisted of a total of 600 IU of rFSH and a 2500 IU of hCG trigger when the leading follicle reached 10mm. Retrieved COCs were co-cultured with OSCs in supplemented MediCult IVM media (CooperSurgical) for 30 hours. After IVM, maturation rate was assessed and matured oocytes underwent ICSI. A time-lapse system was employed for embryo culture (Esco, Lifesciences), and high-quality blastocysts underwent PGT-A analysis for single euploid blastocyst transfer.
RESULTS: A normo-ovulatory 31-year-old subject without hormonal/anatomical abnormalities, exhibited an AMH of 3.98 ng/ml and a basal antral follicle count (AFC) of 12. On the trigger day, estradiol measured 145.53 pg/ml and progesterone 0.22 ng/ml. 8 immature compact COCs were retrieved out of 9 punctured follicles, with 75% (6/8) maturing post OSC-IVM treatment. Fertilization rate was 66.7% (4/6), resulting in 100% (4/4) cleavage embryo formation by day 4. Blastocyst formation rate was 50% (2/4), with one high quality (5AB) euploid blastocyst vitrified on day 5. Time-lapse imaging showed the embryo reached pronuclei fading at 21.26h, 7-cells at 44.87h, blastocyst stage at 85.99h, and blastocyst hatching at 117.73h. Upon thawing, blastocyst showed 100% expansion before proceeding with embryo transfer. 14 days post-transfer, the bHCG level was 1,347 mIU/mL, which increased to 3,803 mIU/mL by day 16, indicating an exponential rise and confirming sustained pregnancy. Continued monitoring will be maintained through the pregnancy until live birth.
CONCLUSION: We have demonstrated that OSCs are able to mature COCs from truncated stimulation cycles, yielding healthy euploid Day 5 blastocysts and ultimately resulting in a successful pregnancy.
IMPACT STATEMENT: Ovarian support cell-assisted in vitro matured immature oocytes from truncated hormonal stimulation can produce healthy clinical pregnancy in subfertile subjects.
