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Gonadotropin Dose Step-up in Women With an Initial Low Response to Ovarian Stimulation for In Vitro Fertilization (IVF)
after processing. Cycle stimulation: Continuous low dose (125 mcg) ganirelix acetate daily starting with onset of menses and continuing to day of hCG administration compared with leuprolide acetate, 0.5 mg daily, beginning 12 days prior to initiation of FSH for 5 days then decreasing to 0.25mg and continuing to day of hCG administration. Ovulation induction in both groups_start recombinant FSH 150 IU to 450 IU daily with a small amount of LH add-back via hMG. Adjust dose as necessary starting on CD 9. HCG when at least 2 follicles ⱖ 18mm. RESULTS: CONCLUSION: This preliminary data supports the conclusion that a stimulation protocol using low-dose ganirelix starting with the onset of menses appears to be as good as the traditional luteal leuprolide protocol for women with expected average response to stimulation. Supported by: some medication support from Organon
patient’s body mass index from cycle day 3 until hCG administration. HGC was given when a leading follicle reached 17 mm of mean diameter. Two IUIs were performed, 12 and 36 hours after hCG administration. Cancellation, pregnancy per IUI and per started cycle, multiple pregnancy, miscarriage and take home rates were compared between both groups. RESULTS: No significant differences were observed between both groups in terms of pregnancy rates per started cycle or per IUI, although slightly better outcome was obtained with letrozole. However, as cancellation and miscarriage rates were higher (although not significant) in the Letrozole group, the take home baby rate per started cycle was comparable between both groups.
P-410 Ovulation Induction in Women Resistant to Clomiphene With a Combination of Clomiphene and Letrozole. J. S. Martin. Southern Ontario Fertility Technologies (S.O.F.T.), London, ON, Canada. OBJECTIVE: To investigate the possibility of successful ovulation induction and pregnancy in women documented to be resistant to induction of ovulation with clomiphene citrate at 150 mg day 3 to 7 of their cycle using a combination of clomiphene and letrozol. DESIGN: Case series. MATERIALS AND METHODS: Forty-four consecutive women who had not been able to ovulate on 150 mg of clomiphene citrate 150 mg day 3 to 7 (non-elevated luteal progesterone and no spontaneous menstruation) were given informed consent and offered and accepted entry into this trial. Non-ovulation was then documented by prescribing 150 mg of clomiphene day 3 to 7 of cycle and monitoring the cycle with serial estradiols, LHs and vaginal ultrasounds. Monitoring began on day 12 of cycle and continued until ovulation occurred (tripling of baseline LH in presence of a follicle 16 mm or greater) or three monitoring days occurred without follicle growth and increased estradiol. The women were monitored to day 19.4 ⫾ 3.2 days into their cycle. Five women had late ovulations and were excluded from the study (19 to 44 days into their cycles). The results of the first cycle with clomiphene 100 mg day 3 to 7 of cycle and letrozole 7.5 mg (2.5 mg X 3) were recorded. RESULTS: Thirty-nine cycles were monitored. Ovulation occurred in 18 cycles (18/39 ⫽ 46%). In the women who ovulated, there were 2.3 ⫾ 1.8 follicles with a diameter ⱖ 16 mm and ovulation day occurred 16.6 ⫾ 7.8 days into their cycles. A positive pregnancy test occurred in 4 (4/18 ⫽ 22%) women 14 days after ovulation. Three of the four had appropriate increases in their pregnancy tests and went on to have early viability pregnancy ultrasounds. All three have ongoing or successful pregnancies. One patient has twins. CONCLUSION: Ovulation induction can sometimes be successful in women documented to be resistant to clomiphene using a combination of clomiphene citrate and letrozole. This is probably worth trying before proceeding to ovarian cautery or gonadotropins Supported by: S.O.F.T.
P-411 Letrozole Versus Recombinant FSH in Ovulation Induction for Intrauterine Insemination in Patients With Polycystic Ovarian Syndrome. C. E. Busso, E. Bosch, M. De Los Santos, N. Garrido, J. Remohi, A. Pellicer. Instituto Valenciano de Infertilidad, Valencia, Spain. OBJECTIVE: To compare the efficiency of the aromatase inhibitor Letrozole with follicle-stimulating hormone (FSH) , for ovulation induction in patients with polycystic ovarian syndrome (PCOS) undergoing intrauterine insemination (IUI). DESIGN: Monocentric comparative retrospective study. MATERIALS AND METHODS: Analysis of 106 cycles of IUI performed in our institution between January 1st, 2003 and December 31st, 2004 in patients with PCOS ( according to the Rotterdam consensus parameters). Of them, 31 cycles used Letrozole for ovulation induction and 75 cycles employed recombinant FSH. The Letrozole cycles were induced with 5 mg a day, starting on day 2 or day 3 of cycle for 5 days. Recombinant FSH cycles were induced with a daily dosis of 50 -150 IU/day according to
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Abstracts
CONCLUSION: The use of Letrozole for ovulation induction in PCOS women for IUI provides similar outcome in terms of take home baby rate per started cycle than the use of recombinant FSH. Supported by: None P-412 Gonadotropin Dose Step-up in Women With an Initial Low Response to Ovarian Stimulation for In Vitro Fertilization (IVF). B. Abu-Rafea, L. Hughes, F. Tekpetey, J. Hollett-Caines, M. Rebel, V. Feyles. University of Western Ontario, London, ON, Canada. OBJECTIVE: 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). DESIGN: Retrospective Case control Study. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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. Supported by: None
Vol. 84, Suppl 1, September 2005
patient’s body mass index from cycle day 3 until hCG administration. HGC was given when a leading follicle reached 17 mm of mean diameter. Two IUIs were performed, 12 and 36 hours after hCG administration. Cancellation, pregnancy per IUI and per started cycle, multiple pregnancy, miscarriage and take home rates were compared between both groups. RESULTS: No significant differences were observed between both groups in terms of pregnancy rates per started cycle or per IUI, although slightly better outcome was obtained with letrozole. However, as cancellation and miscarriage rates were higher (although not significant) in the Letrozole group, the take home baby rate per started cycle was comparable between both groups.
P-410 Ovulation Induction in Women Resistant to Clomiphene With a Combination of Clomiphene and Letrozole. J. S. Martin. Southern Ontario Fertility Technologies (S.O.F.T.), London, ON, Canada. OBJECTIVE: To investigate the possibility of successful ovulation induction and pregnancy in women documented to be resistant to induction of ovulation with clomiphene citrate at 150 mg day 3 to 7 of their cycle using a combination of clomiphene and letrozol. DESIGN: Case series. MATERIALS AND METHODS: Forty-four consecutive women who had not been able to ovulate on 150 mg of clomiphene citrate 150 mg day 3 to 7 (non-elevated luteal progesterone and no spontaneous menstruation) were given informed consent and offered and accepted entry into this trial. Non-ovulation was then documented by prescribing 150 mg of clomiphene day 3 to 7 of cycle and monitoring the cycle with serial estradiols, LHs and vaginal ultrasounds. Monitoring began on day 12 of cycle and continued until ovulation occurred (tripling of baseline LH in presence of a follicle 16 mm or greater) or three monitoring days occurred without follicle growth and increased estradiol. The women were monitored to day 19.4 ⫾ 3.2 days into their cycle. Five women had late ovulations and were excluded from the study (19 to 44 days into their cycles). The results of the first cycle with clomiphene 100 mg day 3 to 7 of cycle and letrozole 7.5 mg (2.5 mg X 3) were recorded. RESULTS: Thirty-nine cycles were monitored. Ovulation occurred in 18 cycles (18/39 ⫽ 46%). In the women who ovulated, there were 2.3 ⫾ 1.8 follicles with a diameter ⱖ 16 mm and ovulation day occurred 16.6 ⫾ 7.8 days into their cycles. A positive pregnancy test occurred in 4 (4/18 ⫽ 22%) women 14 days after ovulation. Three of the four had appropriate increases in their pregnancy tests and went on to have early viability pregnancy ultrasounds. All three have ongoing or successful pregnancies. One patient has twins. CONCLUSION: Ovulation induction can sometimes be successful in women documented to be resistant to clomiphene using a combination of clomiphene citrate and letrozole. This is probably worth trying before proceeding to ovarian cautery or gonadotropins Supported by: S.O.F.T.
P-411 Letrozole Versus Recombinant FSH in Ovulation Induction for Intrauterine Insemination in Patients With Polycystic Ovarian Syndrome. C. E. Busso, E. Bosch, M. De Los Santos, N. Garrido, J. Remohi, A. Pellicer. Instituto Valenciano de Infertilidad, Valencia, Spain. OBJECTIVE: To compare the efficiency of the aromatase inhibitor Letrozole with follicle-stimulating hormone (FSH) , for ovulation induction in patients with polycystic ovarian syndrome (PCOS) undergoing intrauterine insemination (IUI). DESIGN: Monocentric comparative retrospective study. MATERIALS AND METHODS: Analysis of 106 cycles of IUI performed in our institution between January 1st, 2003 and December 31st, 2004 in patients with PCOS ( according to the Rotterdam consensus parameters). Of them, 31 cycles used Letrozole for ovulation induction and 75 cycles employed recombinant FSH. The Letrozole cycles were induced with 5 mg a day, starting on day 2 or day 3 of cycle for 5 days. Recombinant FSH cycles were induced with a daily dosis of 50 -150 IU/day according to
S298
Abstracts
CONCLUSION: The use of Letrozole for ovulation induction in PCOS women for IUI provides similar outcome in terms of take home baby rate per started cycle than the use of recombinant FSH. Supported by: None P-412 Gonadotropin Dose Step-up in Women With an Initial Low Response to Ovarian Stimulation for In Vitro Fertilization (IVF). B. Abu-Rafea, L. Hughes, F. Tekpetey, J. Hollett-Caines, M. Rebel, V. Feyles. University of Western Ontario, London, ON, Canada. OBJECTIVE: 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). DESIGN: Retrospective Case control Study. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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. Supported by: None
Vol. 84, Suppl 1, September 2005