In vitro oocyte maturation (IVM) is a successful art option for PCOS patients

Abstract

In vitro maturation (IVM), while successful in domestic and laboratory species, has not been widely adopted in human ART. This is due in part to low oocyte maturation in vitro, as well as the widespread success of stimulation protocols that include administration of hCG to induce ovulation followed by retrieval of mature oocytes. However, some patients are susceptible to ovarian hyper-stimulation (OHSS) using this approach. Retrieval of immature oocytes after minimal ovarian stimulation without an ovulation trigger would alleviate this concern. The objective of this IRB approved clinical trial is to evaluate the efficacy of a newly developed IVM system as a clinical treatment for infertile patients. Prospective cohort study Beginning on D2 until D5 of the cycle, patients received 150 IU Menopure at 2 PM. Patients had an ultrasound and blood draw prior to oocyte retrieval on D7, 42-46 hr after the last injection. Oocytes were retrieved into medium containing meiotic inhibitors (Pre-IVM) and cultured in this medium for 20-24 hr, at which time oocytes were washed and moved into IVM medium for 27-30 hr. Following IVM, cumulus cells were removed and eggs assessed for maturity. Mature (MII) oocytes underwent ICSI; immature oocytes were returned to IVM medium for an additional 18 hr, when any mature oocytes underwent ICSI. Zygotes (2PN) were cultured in sequential culture medium and good quality blastocysts vitrified on days 5, 6, and 7. All blastocysts were biopsied for PGT-A. To date (January-April, 2019), 8 patients have participated in the clinical study. Four patients were diagnosed with PCOS, two patients with PCO and recurrent pregnancy loss, one patient with fibroids and unexplained infertility, and one patient with DOR and poor embryo quality. Average patient characteristics include: Age, 31.5 y; AMH 7.0 ng/mL; D3 FSH 6.3 mIU/mL; AFC, 45.1; and BMI 28.5. On the day of retrieval, average E2 was 248 pg/mL, and the average size of the largest follicle was 9.1 mm. In total, 234 immature oocytes were retrieved (average 29.3 oocytes per patient, range 5-55), of which 27 were atretic (11.5%). After pre-IVM and IVM, 114 (55.1%) oocytes matured; an additional 41 oocytes matured the following day for a total maturation percentage of 74.9% (155/207). After ICSI, 81/155 (52.3%) of eggs fertilized normally. Following culture, 6 good quality blastocysts (7.4%) were produced on D5, and 16 (19.8%) overall. Five of the eight patients (62.5%) produced at least 1 good quality blastocyst; all of these 5 were PCO/PCOS patients. Ten of the 16 blastocysts produced were euploid (62.5%). To date, 2 patients have undergone FET; one has an ongoing pregnancy. IVM is successful in a clinical setting, and is logistically feasible in the typical IVF laboratory work flow. This approach alleviates concerns of hyper-stimulation, and drastically reduces medication costs and injections. Thus, IVM is a realistic alternative ART approach for PCOS patients.