Gonadotropin Dose Step-up in Women With an Initial Low Response to Ovarian Stimulation for In Vitro Fertilization (IVF)

ObjectiveTo evaluate the impact of gonadotropin dose increase on day 4 of stimulation (step-up protocol) on the outcome of In Vitro Fertilization (IVF) cycle with or without Intracytoplasmic Sperm Injection (ICSI).DesignRetrospective Case control Study.Materials and methodsFrom the period April 2000 to February 2005 at a university affiliated infertility clinic 128 consecutive patients who underwent IVF ± ICSI cycles using the long GnRH agonist protocol and required an increase in the gonadotropin dosage during the stimulation phase were identified (Group 1). This increase was secondary to an inadequate serum estradiol (E2) level (<250 pmol/L) on day 4 of gonadotropin stimulation. The control group consisted of 303 consecutive patients who had IVF ± ICSI cycles using the long GnRH agonist protocol and in whom the dose did not require adjustment (Group 2). Cancellations in both groups were excluded. Main outcomes include number of oocytes retrieved, fertilization rate and pregnancy rate. Student’s t-test and chi-square test were used where appropriate.ResultsThe average age (± SD) for group 1 and 2 was 32.1 ±3.9 and 33 ±4 years respectively (p=0.037). No statistical difference was found between group 1 and 2 with regards to parity or BMI. The mean day 3 FSH (± SD) was 7.8 ±2 for group 1 & 7.25 ±2 for group 2 (p=0.009). A longer stimulation cycle (p=0.0001) was seen in group 1 when compared group 2. Mean (± SD) number of oocytes retrieved was 13.6 ±6.5 & 12.4 ±5.6 for groups 1 &2 consecutively (p=0.04), Mean (± SD) number of fertilized oocytes was 8.7 ±5 for group 1 & 7.4 ±4.5 for group 2 (p=0.008). No difference was observed in the clinical pregnancy rate, 24% in group1 and 26% in group 2 (p=0.68).ConclusionThe step-up protocol in slow responding patients is effective in achieving outcomes comparable to the normal responders receiving routine stimulation protocol. However, a longer duration and an increased medication cost are to be expected in the step-up protocol. ObjectiveTo evaluate the impact of gonadotropin dose increase on day 4 of stimulation (step-up protocol) on the outcome of In Vitro Fertilization (IVF) cycle with or without Intracytoplasmic Sperm Injection (ICSI). To evaluate the impact of gonadotropin dose increase on day 4 of stimulation (step-up protocol) on the outcome of In Vitro Fertilization (IVF) cycle with or without Intracytoplasmic Sperm Injection (ICSI). DesignRetrospective Case control Study. Retrospective Case control Study. Materials and methodsFrom the period April 2000 to February 2005 at a university affiliated infertility clinic 128 consecutive patients who underwent IVF ± ICSI cycles using the long GnRH agonist protocol and required an increase in the gonadotropin dosage during the stimulation phase were identified (Group 1). This increase was secondary to an inadequate serum estradiol (E2) level (<250 pmol/L) on day 4 of gonadotropin stimulation. The control group consisted of 303 consecutive patients who had IVF ± ICSI cycles using the long GnRH agonist protocol and in whom the dose did not require adjustment (Group 2). Cancellations in both groups were excluded. Main outcomes include number of oocytes retrieved, fertilization rate and pregnancy rate. Student’s t-test and chi-square test were used where appropriate. From the period April 2000 to February 2005 at a university affiliated infertility clinic 128 consecutive patients who underwent IVF ± ICSI cycles using the long GnRH agonist protocol and required an increase in the gonadotropin dosage during the stimulation phase were identified (Group 1). This increase was secondary to an inadequate serum estradiol (E2) level (<250 pmol/L) on day 4 of gonadotropin stimulation. The control group consisted of 303 consecutive patients who had IVF ± ICSI cycles using the long GnRH agonist protocol and in whom the dose did not require adjustment (Group 2). Cancellations in both groups were excluded. Main outcomes include number of oocytes retrieved, fertilization rate and pregnancy rate. Student’s t-test and chi-square test were used where appropriate. ResultsThe average age (± SD) for group 1 and 2 was 32.1 ±3.9 and 33 ±4 years respectively (p=0.037). No statistical difference was found between group 1 and 2 with regards to parity or BMI. The mean day 3 FSH (± SD) was 7.8 ±2 for group 1 & 7.25 ±2 for group 2 (p=0.009). A longer stimulation cycle (p=0.0001) was seen in group 1 when compared group 2. Mean (± SD) number of oocytes retrieved was 13.6 ±6.5 & 12.4 ±5.6 for groups 1 &2 consecutively (p=0.04), Mean (± SD) number of fertilized oocytes was 8.7 ±5 for group 1 & 7.4 ±4.5 for group 2 (p=0.008). No difference was observed in the clinical pregnancy rate, 24% in group1 and 26% in group 2 (p=0.68). The average age (± SD) for group 1 and 2 was 32.1 ±3.9 and 33 ±4 years respectively (p=0.037). No statistical difference was found between group 1 and 2 with regards to parity or BMI. The mean day 3 FSH (± SD) was 7.8 ±2 for group 1 & 7.25 ±2 for group 2 (p=0.009). A longer stimulation cycle (p=0.0001) was seen in group 1 when compared group 2. Mean (± SD) number of oocytes retrieved was 13.6 ±6.5 & 12.4 ±5.6 for groups 1 &2 consecutively (p=0.04), Mean (± SD) number of fertilized oocytes was 8.7 ±5 for group 1 & 7.4 ±4.5 for group 2 (p=0.008). No difference was observed in the clinical pregnancy rate, 24% in group1 and 26% in group 2 (p=0.68). ConclusionThe step-up protocol in slow responding patients is effective in achieving outcomes comparable to the normal responders receiving routine stimulation protocol. However, a longer duration and an increased medication cost are to be expected in the step-up protocol. The step-up protocol in slow responding patients is effective in achieving outcomes comparable to the normal responders receiving routine stimulation protocol. However, a longer duration and an increased medication cost are to be expected in the step-up protocol.