Gonadotropin-releasing hormone (GnRH)-agonist versus GnRH-antagonist in ovarian stimulation for assisted reproductive techniques: Results of a prospective randomized trial

ObjectiveThis investigation aims to compare a depot formulation of leuprolide acetate versus a single-dose of cetrorelix acetate to prevent LH surge and premature luteinization in ovarian stimulation protocols for assisted reproductive technology (ART).DesignRandomized and prospective study in a tertiary care institutional hospital.Materials and methods47 women undergoing ovarian stimulation for ART were randomly allocated in two groups. In group A (n = 24), ovarian stimulation was commenced on day 3 of a spontaneous menstrual cycle, with daily subcutaneous administration of 150 IU of recombinant follicle-stimulating hormone (r-FSH, Gonal F®, Serono, Brazil). A single-dose of 3 mg cetrorelix (Cetrotide®, Serono, Brazil) was administered subcutaneously on day 7 of ovarian stimulation. When at least two follicles ≥ 17 mm were not obtained within 5 days, it was administered a complementation dose of 0.25 mg of cetrorelix daily, until the day of hCG. In group B (n = 23), we performed a long protocol with a depot formulation of GnRH-agonist. Patients in this group received 3.75 mg of leuprolide acetate (Lupron depot®, Abbott, Brazil), intramuscularly, in the mid luteal phase of the previous cycle. Ovarian stimulation was conducted with daily administration of 150 IU r-FSH (Gonal-F®, Serono, Brazil). In both groups, triggering of ovulation was performed with 10,000 IU of hCG (Profasi®, Serono, Brazil) administered when 2 follicles were ≥ 17 mm. Oocyte retrieval was performed 34–36 hours after hCG administration. The cancellation rates, the LH and progesterone concentrations at hCG administration time, the number of mature oocytes collected, the stimulation duration and the number of r-FSH ampoules administered were evaluated in the two groups. For the statistical analysis, chi square test and Student’s t test were utilized when appropriate.ResultsFour cycles were cancelled because of poor response to ovarian stimulation (3 in group A, 13.0%, and 1 in group B, 4.1%, P > 0.05). No LH surge was observed in both groups. LH and progesterone serum levels on hCG day were not statistically different in both groups (LH: 1.60 ± 0.48 mIU/mL in group A versus 4.00 ± 1.66 mIU/mL in group B; progesterone: 0.52 ± 0.22 ng/mL in group A versus 0.63 ± 0.22 ng/mL in group B, P > 0.05). The number of mature oocytes retrieved was similar between the groups (5.73 ± 2.52 in group A versus 6.00 ± 3.16 in group B, P > 0.05). The duration of ovarian stimulation was lower in the antagonist group (9.56 ± 0.66 days versus 10.45 ± 0.82 days, P < 0.05). In the same way, the number of r-FSH ampoules administered was lower in the antagonist group (17.91 ± 2.37 versus 20.30 ± 1.45, P < 0.05).ConclusionThe results of this investigation suggest that both a depot formulation of GnRH-agonist administered in the mid-luteal phase of the previous cycle and a single dose of antagonist administered in the late follicular phase, in ovarian stimulation for ART, are similar to prevent LH surge and produce a similar number of mature oocytes. Our data also showed that the number of r-FSH treatment days and the number of r-FSH ampoules used were significantly less in the antagonist group than in the GnRH-agonist group. Moreover, in both groups the progesterone levels were below the cut-off values for this hormone on the hCG day, showing the same efficiency of the two treatments in preventing premature luteinization. ObjectiveThis investigation aims to compare a depot formulation of leuprolide acetate versus a single-dose of cetrorelix acetate to prevent LH surge and premature luteinization in ovarian stimulation protocols for assisted reproductive technology (ART). This investigation aims to compare a depot formulation of leuprolide acetate versus a single-dose of cetrorelix acetate to prevent LH surge and premature luteinization in ovarian stimulation protocols for assisted reproductive technology (ART). DesignRandomized and prospective study in a tertiary care institutional hospital. Randomized and prospective study in a tertiary care institutional hospital. Materials and methods47 women undergoing ovarian stimulation for ART were randomly allocated in two groups. In group A (n = 24), ovarian stimulation was commenced on day 3 of a spontaneous menstrual cycle, with daily subcutaneous administration of 150 IU of recombinant follicle-stimulating hormone (r-FSH, Gonal F®, Serono, Brazil). A single-dose of 3 mg cetrorelix (Cetrotide®, Serono, Brazil) was administered subcutaneously on day 7 of ovarian stimulation. When at least two follicles ≥ 17 mm were not obtained within 5 days, it was administered a complementation dose of 0.25 mg of cetrorelix daily, until the day of hCG. In group B (n = 23), we performed a long protocol with a depot formulation of GnRH-agonist. Patients in this group received 3.75 mg of leuprolide acetate (Lupron depot®, Abbott, Brazil), intramuscularly, in the mid luteal phase of the previous cycle. Ovarian stimulation was conducted with daily administration of 150 IU r-FSH (Gonal-F®, Serono, Brazil). In both groups, triggering of ovulation was performed with 10,000 IU of hCG (Profasi®, Serono, Brazil) administered when 2 follicles were ≥ 17 mm. Oocyte retrieval was performed 34–36 hours after hCG administration. The cancellation rates, the LH and progesterone concentrations at hCG administration time, the number of mature oocytes collected, the stimulation duration and the number of r-FSH ampoules administered were evaluated in the two groups. For the statistical analysis, chi square test and Student’s t test were utilized when appropriate. 47 women undergoing ovarian stimulation for ART were randomly allocated in two groups. In group A (n = 24), ovarian stimulation was commenced on day 3 of a spontaneous menstrual cycle, with daily subcutaneous administration of 150 IU of recombinant follicle-stimulating hormone (r-FSH, Gonal F®, Serono, Brazil). A single-dose of 3 mg cetrorelix (Cetrotide®, Serono, Brazil) was administered subcutaneously on day 7 of ovarian stimulation. When at least two follicles ≥ 17 mm were not obtained within 5 days, it was administered a complementation dose of 0.25 mg of cetrorelix daily, until the day of hCG. In group B (n = 23), we performed a long protocol with a depot formulation of GnRH-agonist. Patients in this group received 3.75 mg of leuprolide acetate (Lupron depot®, Abbott, Brazil), intramuscularly, in the mid luteal phase of the previous cycle. Ovarian stimulation was conducted with daily administration of 150 IU r-FSH (Gonal-F®, Serono, Brazil). In both groups, triggering of ovulation was performed with 10,000 IU of hCG (Profasi®, Serono, Brazil) administered when 2 follicles were ≥ 17 mm. Oocyte retrieval was performed 34–36 hours after hCG administration. The cancellation rates, the LH and progesterone concentrations at hCG administration time, the number of mature oocytes collected, the stimulation duration and the number of r-FSH ampoules administered were evaluated in the two groups. For the statistical analysis, chi square test and Student’s t test were utilized when appropriate. ResultsFour cycles were cancelled because of poor response to ovarian stimulation (3 in group A, 13.0%, and 1 in group B, 4.1%, P > 0.05). No LH surge was observed in both groups. LH and progesterone serum levels on hCG day were not statistically different in both groups (LH: 1.60 ± 0.48 mIU/mL in group A versus 4.00 ± 1.66 mIU/mL in group B; progesterone: 0.52 ± 0.22 ng/mL in group A versus 0.63 ± 0.22 ng/mL in group B, P > 0.05). The number of mature oocytes retrieved was similar between the groups (5.73 ± 2.52 in group A versus 6.00 ± 3.16 in group B, P > 0.05). The duration of ovarian stimulation was lower in the antagonist group (9.56 ± 0.66 days versus 10.45 ± 0.82 days, P < 0.05). In the same way, the number of r-FSH ampoules administered was lower in the antagonist group (17.91 ± 2.37 versus 20.30 ± 1.45, P < 0.05). Four cycles were cancelled because of poor response to ovarian stimulation (3 in group A, 13.0%, and 1 in group B, 4.1%, P > 0.05). No LH surge was observed in both groups. LH and progesterone serum levels on hCG day were not statistically different in both groups (LH: 1.60 ± 0.48 mIU/mL in group A versus 4.00 ± 1.66 mIU/mL in group B; progesterone: 0.52 ± 0.22 ng/mL in group A versus 0.63 ± 0.22 ng/mL in group B, P > 0.05). The number of mature oocytes retrieved was similar between the groups (5.73 ± 2.52 in group A versus 6.00 ± 3.16 in group B, P > 0.05). The duration of ovarian stimulation was lower in the antagonist group (9.56 ± 0.66 days versus 10.45 ± 0.82 days, P < 0.05). In the same way, the number of r-FSH ampoules administered was lower in the antagonist group (17.91 ± 2.37 versus 20.30 ± 1.45, P < 0.05). ConclusionThe results of this investigation suggest that both a depot formulation of GnRH-agonist administered in the mid-luteal phase of the previous cycle and a single dose of antagonist administered in the late follicular phase, in ovarian stimulation for ART, are similar to prevent LH surge and produce a similar number of mature oocytes. Our data also showed that the number of r-FSH treatment days and the number of r-FSH ampoules used were significantly less in the antagonist group than in the GnRH-agonist group. Moreover, in both groups the progesterone levels were below the cut-off values for this hormone on the hCG day, showing the same efficiency of the two treatments in preventing premature luteinization. The results of this investigation suggest that both a depot formulation of GnRH-agonist administered in the mid-luteal phase of the previous cycle and a single dose of antagonist administered in the late follicular phase, in ovarian stimulation for ART, are similar to prevent LH surge and produce a similar number of mature oocytes. Our data also showed that the number of r-FSH treatment days and the number of r-FSH ampoules used were significantly less in the antagonist group than in the GnRH-agonist group. Moreover, in both groups the progesterone levels were below the cut-off values for this hormone on the hCG day, showing the same efficiency of the two treatments in preventing premature luteinization.