Keywords: Ovarian support cells, in vitro maturation, abbreviated hormonal stimulation, egg donors, egg freezers
OBJECTIVE: We have previously shown that in vitro maturation (IVM) using human induced pluripotent stem cell (hiPSC)-derived ovarian support cells (OSC) improves the maturation rates of immature cumulus oocyte complexes (COCs) from abbreviated hormonal stimulations, outperforming commercially available IVM solutions and yielding healthy euploid blastocysts. In the current case series, we show the successful application of OSC-IVM coupled with abbreviated hormonal stimulation as an alternative protocol to conventional stimulation for donor egg cycles.
MATERIALS AND METHODS: Human cumulus oocyte complexes (COCs) were obtained from normo-ovulatory oocyte donors (n=4) following an abbreviated stimulation gonadotropin regimen, consisting of three to four 200 IU doses of rFSH starting day 2 of the menstrual cycle, with a 2,500 or 5,000 IU hCG trigger when the leading follicle reached 10mm in diameter. Compact COCs were retrieved from the subject, washed and placed directly into OSC-IVM co-culture (IVM medium supplemented with 75 mIU/ml FSH, 100 mIU/ml hCG, 500 ng/ml A4, and OSCs) for 30 hours. After culture, COCs were stripped and matured (MII) oocytes were vitrified using Kitazato´s protocol for future use for embryo formation with eligible recipients. This case report is part of an ongoing pilot study for the commercial use of the OSCs.
RESULTS: Subjects of this case series were between the ages 24 to 30 years old, had a body mass index of 23.5 ± 1.9 kg/m2, anti-müllerian hormone (AMH) of 7.2 ± 3.7 ng/ml, and an average basal antral follicle count (AFC) of 25 ± 6. The AFC on the first day of stimulation and day of retrieval were 18 ± 9 and 19 ± 4, respectively. The average number of compact COCs retrieved was 9 ± 3 with a retrieval efficiency of 49.2 ± 14.9% (based on the retrieval AFC). After OSC-IVM, the maturation rate was 69.6 ± 20.52% (n=25) with an average of 6 MII oocytes to cryopreserve per donor. There was no incidence of ovarian hyperstimulation syndrome (OHSS) in any of the donors.
CONCLUSION: This case report demonstrates that OSC-IVM can be applied in cycles requiring oocyte donation. Though the average number of oocytes retrieved in truncated stimulation cycles is often lower in comparison to conventional cycles, the efficacy and lowered cost of minimal stimulation in conjunction with OSC-IVM indicates this protocol could be an alternative to patients requiring donor oocytes. Significantly, this case report is part of the first in donor cycle clinical application of the OSC-IVM approach.
IMPACT STATEMENT: Ovarian support cell-assisted in vitro matured immature oocytes from abbreviated hormonal stimulation can be used as alternative protocol for donor oocyte cycles.
