The Cardinal protocol: investigating a simplified, cost-conscious option for oocyte cryopreservation in a prospective noninferiority cohort study.

OBJECTIVE: To determine if the novel cost-conscious and simplified Cardinal protocol could achieve noninferior clinical outcomes in planned oocyte cryopreservation (OC) cycles, compared with routine protocols. DESIGN: Prospective noninferiority cohort study, nonrandomized. SUBJECTS: Patients undergoing planned OC were prospectively recruited at a single academic institution between July 2023 and August 2024. EXPOSURE: Participants self-selected between the routine protocols vs. the Cardinal protocol. All participants paid for their cycles out-of-pocket or using insurance. The Cardinal protocol is limited to 2 ultrasounds (baseline and stimulation day [SD] 9, no bloodwork, standardized follicle-stimulating hormone (FSH) dosing (antimüllerian hormone ≤ 4: 300 IU, antimüllerian hormone > 4: 225 IU), scheduled progestin start on SD6 in place of an antagonist, and autotrigger when ≥3 follicles are projected to be ≥18 mm. Routine protocols (antagonist, microdose flare) include up to maximum-dose gonadotropins, 5-6 ultrasounds, and 3-5 blood draws. MAIN OUTCOME MEASURES: The primary outcome was the number of mature metaphase II oocytes (MIIs) retrieved. Secondary outcomes included the total number of oocytes retrieved and cryopreserved, premature ovulation, ovarian hyperstimulation syndrome (OHSS), cycle cancellation, and postretrieval surgical complications. Total charges including the cost of medications were noted. A postcycle survey compared satisfaction and sociodemographic factors influencing patient choice between the Cardinal vs. routine protocols. RESULTS: Of 118 total participants, 60 enrolled in Cardinal and 58 opted for routine. No significant differences (i.e., in age, body mass index, race/ethnicity) existed between groups. A total of 137 cycles (70 Cardinal and 67 routine) were compared. The mean difference in MIIs between groups was +1.08 (95% CI -1.1 to 3.27), demonstrating noninferiority of the Cardinal protocol. Premature ovulation did not occur in either group. The OHSS rates were lower in Cardinal (2.9% vs. 23%); no other significant differences in adverse events were noted. The median charge for a Cardinal cycle was $5,004 lower than that of routine protocols. Postcycle surveys (73% response rate) demonstrated higher satisfaction with Cardinal at 85% vs. 65%, driven by cost and convenience. CONCLUSIONS: The Cardinal protocol appears to be a noninferior option to routine protocols. It considerably reduced charges by $5,000 without a decrease in MIIs retrieved, making it a cost-conscious protocol that should be seriously considered for OC cycles. The Cardinal protocol was overall satisfactory for patients who selected this over the routine protocols, notably across diverse sociodemographic groups. TRIAL REGISTRATION: NCT05842070; https://clinicaltrials.gov/study/NCT05842070.