Once-a-day injection dosing for a mixed (FSH:hMG) stimulation protocol showed superior clinical outcomes compared to a twice-a-day dosing schedule

Abstract

OBJECTIVE: To analyze prospective clinical data to determine the efficacy of once-a-day versus twice-a-day dosing of a mixture of FSH:hMG (mixed protocol, Bravelle: Menopur). Both dosing injection frequencies have been used clinically with success, but a side-by-side prospective study of once-a-day compared to twice-a-day injections was needed.DESIGN: This is a prospective randomized, comparative two arm, open-label, IRB approved study conducted at one medical practice, located at two sites.MATERIALS AND METHODS: Patients (age 24-42) receiving ovulation induction for in-vitro fertilization were enrolled in the study. At baseline ultrasound, patients were randomly assigned to either the once-a-day (n=27) or the twice-a-day (n=16) injection protocol. Outcome measures examined included: oocytes retrieved, fertilization rate, embryo progression to blastocyst, peak estradiol levels, total dose of FSH used, dose and duration of stimulation, implantation rates, cancelled cycles and clinical pregnancy rates. Means for each group were compared and two-tailed p-values determined using the Student's t-test. If the normality assumption was not met, non-parametric tests were used.RESULTS: Percentage of pregnancies with cardiac activity at six weeks was significantly higher (85%, p=0.0077) in patients enrolled in the once-a-day protocol compared to the twice-a-day injection protocol (38%). Patient clinical parameters including maternal age, total FSH ordered, peak estradiol, and number of days stimulation were not significantly different. However, the final number of follicles recruited (p=0.0348), number of oocytes retrieved (p=0.0397), number of fertilized oocytes (p=0.0054) and number of blastocyst stage embryos produced (p=0.02) were significantly greater in the once-a-day group. Interestingly, the cancellation rate was higher in the twice-a-day (20%) vs. the once-a-day group (7%).CONCLUSIONS: The once-a-day injection protocol was superior to the twice-a-day injection protocol in the number of follicles produced, oocytes retrieved, fertilized oocytes obtained, blastocysts produced on day 5 of culture and number of clinical pregnancies achieved. Since maternal age, days of stimulation and total FSH units ordered were not different between the groups, difficulty in adhering to the twice-a-day injection protocol (three times higher cancellation rate) may have contributed to the inferior outcomes in the twice-a-day injection protocol group. OBJECTIVE: To analyze prospective clinical data to determine the efficacy of once-a-day versus twice-a-day dosing of a mixture of FSH:hMG (mixed protocol, Bravelle: Menopur). Both dosing injection frequencies have been used clinically with success, but a side-by-side prospective study of once-a-day compared to twice-a-day injections was needed. DESIGN: This is a prospective randomized, comparative two arm, open-label, IRB approved study conducted at one medical practice, located at two sites. MATERIALS AND METHODS: Patients (age 24-42) receiving ovulation induction for in-vitro fertilization were enrolled in the study. At baseline ultrasound, patients were randomly assigned to either the once-a-day (n=27) or the twice-a-day (n=16) injection protocol. Outcome measures examined included: oocytes retrieved, fertilization rate, embryo progression to blastocyst, peak estradiol levels, total dose of FSH used, dose and duration of stimulation, implantation rates, cancelled cycles and clinical pregnancy rates. Means for each group were compared and two-tailed p-values determined using the Student's t-test. If the normality assumption was not met, non-parametric tests were used. RESULTS: Percentage of pregnancies with cardiac activity at six weeks was significantly higher (85%, p=0.0077) in patients enrolled in the once-a-day protocol compared to the twice-a-day injection protocol (38%). Patient clinical parameters including maternal age, total FSH ordered, peak estradiol, and number of days stimulation were not significantly different. However, the final number of follicles recruited (p=0.0348), number of oocytes retrieved (p=0.0397), number of fertilized oocytes (p=0.0054) and number of blastocyst stage embryos produced (p=0.02) were significantly greater in the once-a-day group. Interestingly, the cancellation rate was higher in the twice-a-day (20%) vs. the once-a-day group (7%). CONCLUSIONS: The once-a-day injection protocol was superior to the twice-a-day injection protocol in the number of follicles produced, oocytes retrieved, fertilized oocytes obtained, blastocysts produced on day 5 of culture and number of clinical pregnancies achieved. Since maternal age, days of stimulation and total FSH units ordered were not different between the groups, difficulty in adhering to the twice-a-day injection protocol (three times higher cancellation rate) may have contributed to the inferior outcomes in the twice-a-day injection protocol group.