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Pituitary-ovarian recovery after oral contraceptive use before in vitro fertilization (IVF)
Gant on mean cycle day 8 (lead follicle of 12–14 mm in diameter). Both Gag and Gant were continued until the day of hCG injection (hCG). Androgen assays were run on serum collected on cycle day 3, mid-follicular day (days 7–12), and the day of hCG. Values for testosterone (T, total and free), estradiol, DHEAS, androstenedione (A) and sex hormone binding globulin (SHBG) were analyzed. Significance was assessed using repeated measures ANOVA. Results: All Rec⫹Gag cycles were associated with a late-follicular rise in circulating androgens relative to that on day 3. In contrast, serum T did not increase in the Gant cycles and free T levels actually fell most likely because of a rise in SHBG. Serum DHEAS levels failed to show a consistent pattern in the Gant cycles. However, serum A levels did show a consistent rise with Gant treatment. Serum androgen profiles Rec ⫹ Gag day 3
mid
Any hMG ⫹ Gant hCG
day 3
mid
hCG
Rec ⫹ Gant day 3
mid
hCG
A 13⫾1 21⫾2* 28⫾2* 17⫾1 21⫾1* 22⫾2* 15⫾1 21⫾1* 22⫾2* (ng/dl) Total T 32⫾3 46⫾4* 63⫾5* 32⫾7 24⫾4 30⫾4 33.7⫾6 39⫾6 38⫾6 (ng/dl) Free T 0.8⫾0.1 1.1⫾0.1 1.5⫾0.1* 1.4⫾0.1 1.4⫾0.1 1.3⫾0.1* 1.1⫾0.1 1.1⫾0.1 0.9⫾0.1* (ng/dl) SHBG 73⫾6 67⫾5 93⫾8* 66⫾10 61⫾9 71⫾11* 66⫾9 66⫾7 77⫾9* (nMol/l) E2 23⫾1 870⫾66* 1863⫾137* 35⫾2 517⫾51* 863⫾72* 34⫾2 682⫾85* 1125⫾136* (pg/ml) Mid: mid-follicular. * ⫽ significance relative to day 3: p ⬍ 0.5
Conclusions: Gag and Gant cycles produce different androgen patterns unrelated to whether HMG or Rec is used. Since Gant cycles in the study consisted primarily of poorly responding patients with diminished ovarian reserve, the possibility remains that the difference is a function of follicle number rather than a reflection of a more effective suppression of endogenous GnRH. Future studies testing Gant in good responding patients will provide an answer to this question. Supported by: Orgenon.
P-175 Role of FSH hormone gene (FSRH) mutations in young poor responders undergoing ART. Omur Taskin, Mualla Ozcan, Mehmet Simsek, Ozgul Alpek, Guven Luleci, Sinan Kursun. Akdeniz Univ, Antalya, Turkey. Objective: It has been known that defects in FSHR gene has been associated with altered ovarian response and/or premature ovarian failure. We tried to evaluate the incidence and possible role of FSRH mutations on follicular response in young poor responders with normal menstrual and hormonal parameters. Design: Prospective cohort clinical trial Materials/Methods: Twelve infertile woman aged 24 –31 yrs who were grouped as poor responders and age matched infertile normal responders (n:12) during controlled ovarian stimulation (COH) 3.normal day 3 FSH and estradiol levels with normal CC test were included. Bad response was based on the criterias 1.inadequate estradiol response 2.less than 4 leading follicles in 2 consecutive COH cycles for ART.All DNA analysisi were performed after completition of ovarian stimulation and genomic DNA was extracted. Single Stranded Conformational Chain Polymorphism (SSCP) was employed for the characterization of the polymorphism. Results: The demographic and ovarian stimulation characteristics were similar between the control and poor response groups. No shifts were observed on the 7th exon of FSHR gene in both poor responders and control patients. Conclusions: Inherent defects in ovulation may cause bad response in the above young patients with otherwise normal hormonal parameters. Since FSHR genotype determines ovarian response to FSH, it should have impact on the delineation of stimulation protocols thus reducing the cost and increasing the success in poor responders. Although the sample size is limited, no defects has been shown in the FSHR gene in our patients and control groups. Further detailed studies may be needed to outline the exact
S174
Abstracts
role functional integrity of the FSH gene in young poor responders or in follicular dynamics. Supported by: None. P-176 Pituitary-ovarian recovery after oral contraceptive use before in vitro fertilization (IVF). Richard P. Dickey, Roman Pyrzak, Peter Y. Lu, Belinda M. Sartor, Steven N. Taylor, John M. Storment. Fertility Institute of New Orleans, New Orleans, LA. Objective: Our objective was to determine how rapidly the pituitary and ovary recovered following oral contraceptives (OC) the cycle before IVF. An additional objective was to compare ovarian and pituitary hormone levels in IVF patients randomized to receive OC⫹gonadotropin releasing hormone (GnRH) agonist or OC⫹GnRH antagonist for suppression of LH. Design: A prospective study of 20 patients randomized to OC⫹GnRH agonist or OC⫹GnRH antagonist before IVF. Materials/Methods: All patients received an OC (Desogen威) containing desogestrel 150 mcg and ethinyl estradiol 30 mcg for 14 to 28 days beginning the 3rd menstrual day of the cycle preceding IVF. Patients were randomized to OC⫹GnRH agonist (OCAg group) or OC⫹GnRH antagonist (OCAnt group) before beginning OCs. The last OC was taken on Sunday. Stimulation with 300 IU rFSH (Follistim威) was started on Friday, the 5th post OC day. The OCAg group started leuprolide acetate (Lupron威) 0.5 mg/day S.C. when 5 OC were left. The OCAnt group started ganirelix acetate (AntagonTM), 250 ug, when 2 follicles were 12 to 14 mm. HCG, 10,000, was administered when 2 or more follicles were 16 to 18 mm. Progesterone 50 mg IM was started the day of egg retrieval. FSH, LH, estradiol (E), and progesterone (P) were measured before OC start, the day of rFSH start, and every 1 to 2 days until HCG administration. Additionally, FSH, LH, and E were measured daily after the last OC until rFSH start in the OCAnt group. Results: The two groups did not differ in age, weight, or pre-OC hormone levels. On the day of rFSH stimulation start (post OC day 5), E, FSH, and LH, but not P, were significantly higher in the OC Ant group than in the OC Ag group: E (25.4 ⫹ 3.9 pg/mL vs 10.2 ⫹ 3.6 pg/mL, p ⫽ .009), FSH (9.2 ⫹ 1.2 mIU/mL vs 3.9 ⫹ 0.4 mIU/mL, p ⬍.000), LH (5.7 ⫹ 1.0 mIU/mL vs 2.6 ⫹ 0.5 mIU/mL, p ⫽ .012), P (63 ⫹ 10 ng/dL vs 63 ⫹ 20 ng/mL). There was no difference in the days of rFSH (8.5 ⫹ 0.8 vs 8.1 ⫹ 0.6) or total amount of rFSH used. The day of hCG administration, E and follicles ⬎12 mm, but not LH, P, or follicles ⬎16 mm, were significantly decreased in the OCAnt group: E (980 ⫹ 73 vs 1756 ⫹ 240 pg/mL, p ⫽ .019) LH (1.7 ⫹ 0.6 vs 4.0 ⫹ 1.6) P (121 ⫹ 26 vs 122 ⫹ 16) (⬎12mm 7.5 ⫹ 1.0 vs 13.0 ⫹ 1.7, p ⫽ .028) (⬎16mm 2.8 ⫹ 1.5 vs 4.5 ⫹ 1.1). Daily measurements in the OC Ant group established that the increase in E, FSH, and LH began on the 4th post OC day. Conclusions: We conclude that high E, FSH, and LH levels on post OC day 5, in patients not receiving GnRH agonist, may be the result of premature follicle development before rFSH is started and may be the cause of lower follicle numbers on HCG day. Starting rFSH before the 4th post OC day may result in recruitment of additional follicles in patients receiving GnRH antagonist. Supported by: A grant from Organon, Inc. P-177 Combined use of GnRH analog and antagonist: Redundancy vs. complementary action. Dov B. Goldstein, Florenta Bedernicianu, Jane Zhang, Marina Bulavina, Mihaela Voicu, Helen Fong. Cent Park West Fertility/ Brooklyn Fertility Ctr, New York, NY; Cent Park West Fertility/Brooklyn Fertility Ctr, New York, NY. Objective: It was found that GnRH has receptors in the whole male and female reproductive tract: testis, cumulus complex, oocytes, fallopian tubes, endometrium, etc. The GnRH Analogue (GnRHA) has a beneficial effect at all levels while the GnRH Antagonist opposes it with an apparent trend toward lower pregnancy rates. However, the GnRH Antagonist is becoming more accepted because of a lesser incidence of O.H.S.S. and less cycle cancellations especially, in the challenging P.C.O.S. cases (multiple smaller than 12mm follicles with high Estradiol (E2)). Our pilot study attempts to determine if the beneficial effects of the GnRHA can be maintained and further enhanced by the timely addition of the GnRH Antagonist.
Vol. 78, No. 3, Suppl. 1, September 2002
mid
Any hMG ⫹ Gant hCG
day 3
mid
hCG
Rec ⫹ Gant day 3
mid
hCG
A 13⫾1 21⫾2* 28⫾2* 17⫾1 21⫾1* 22⫾2* 15⫾1 21⫾1* 22⫾2* (ng/dl) Total T 32⫾3 46⫾4* 63⫾5* 32⫾7 24⫾4 30⫾4 33.7⫾6 39⫾6 38⫾6 (ng/dl) Free T 0.8⫾0.1 1.1⫾0.1 1.5⫾0.1* 1.4⫾0.1 1.4⫾0.1 1.3⫾0.1* 1.1⫾0.1 1.1⫾0.1 0.9⫾0.1* (ng/dl) SHBG 73⫾6 67⫾5 93⫾8* 66⫾10 61⫾9 71⫾11* 66⫾9 66⫾7 77⫾9* (nMol/l) E2 23⫾1 870⫾66* 1863⫾137* 35⫾2 517⫾51* 863⫾72* 34⫾2 682⫾85* 1125⫾136* (pg/ml) Mid: mid-follicular. * ⫽ significance relative to day 3: p ⬍ 0.5
Conclusions: Gag and Gant cycles produce different androgen patterns unrelated to whether HMG or Rec is used. Since Gant cycles in the study consisted primarily of poorly responding patients with diminished ovarian reserve, the possibility remains that the difference is a function of follicle number rather than a reflection of a more effective suppression of endogenous GnRH. Future studies testing Gant in good responding patients will provide an answer to this question. Supported by: Orgenon.
P-175 Role of FSH hormone gene (FSRH) mutations in young poor responders undergoing ART. Omur Taskin, Mualla Ozcan, Mehmet Simsek, Ozgul Alpek, Guven Luleci, Sinan Kursun. Akdeniz Univ, Antalya, Turkey. Objective: It has been known that defects in FSHR gene has been associated with altered ovarian response and/or premature ovarian failure. We tried to evaluate the incidence and possible role of FSRH mutations on follicular response in young poor responders with normal menstrual and hormonal parameters. Design: Prospective cohort clinical trial Materials/Methods: Twelve infertile woman aged 24 –31 yrs who were grouped as poor responders and age matched infertile normal responders (n:12) during controlled ovarian stimulation (COH) 3.normal day 3 FSH and estradiol levels with normal CC test were included. Bad response was based on the criterias 1.inadequate estradiol response 2.less than 4 leading follicles in 2 consecutive COH cycles for ART.All DNA analysisi were performed after completition of ovarian stimulation and genomic DNA was extracted. Single Stranded Conformational Chain Polymorphism (SSCP) was employed for the characterization of the polymorphism. Results: The demographic and ovarian stimulation characteristics were similar between the control and poor response groups. No shifts were observed on the 7th exon of FSHR gene in both poor responders and control patients. Conclusions: Inherent defects in ovulation may cause bad response in the above young patients with otherwise normal hormonal parameters. Since FSHR genotype determines ovarian response to FSH, it should have impact on the delineation of stimulation protocols thus reducing the cost and increasing the success in poor responders. Although the sample size is limited, no defects has been shown in the FSHR gene in our patients and control groups. Further detailed studies may be needed to outline the exact
S174
Abstracts
role functional integrity of the FSH gene in young poor responders or in follicular dynamics. Supported by: None. P-176 Pituitary-ovarian recovery after oral contraceptive use before in vitro fertilization (IVF). Richard P. Dickey, Roman Pyrzak, Peter Y. Lu, Belinda M. Sartor, Steven N. Taylor, John M. Storment. Fertility Institute of New Orleans, New Orleans, LA. Objective: Our objective was to determine how rapidly the pituitary and ovary recovered following oral contraceptives (OC) the cycle before IVF. An additional objective was to compare ovarian and pituitary hormone levels in IVF patients randomized to receive OC⫹gonadotropin releasing hormone (GnRH) agonist or OC⫹GnRH antagonist for suppression of LH. Design: A prospective study of 20 patients randomized to OC⫹GnRH agonist or OC⫹GnRH antagonist before IVF. Materials/Methods: All patients received an OC (Desogen威) containing desogestrel 150 mcg and ethinyl estradiol 30 mcg for 14 to 28 days beginning the 3rd menstrual day of the cycle preceding IVF. Patients were randomized to OC⫹GnRH agonist (OCAg group) or OC⫹GnRH antagonist (OCAnt group) before beginning OCs. The last OC was taken on Sunday. Stimulation with 300 IU rFSH (Follistim威) was started on Friday, the 5th post OC day. The OCAg group started leuprolide acetate (Lupron威) 0.5 mg/day S.C. when 5 OC were left. The OCAnt group started ganirelix acetate (AntagonTM), 250 ug, when 2 follicles were 12 to 14 mm. HCG, 10,000, was administered when 2 or more follicles were 16 to 18 mm. Progesterone 50 mg IM was started the day of egg retrieval. FSH, LH, estradiol (E), and progesterone (P) were measured before OC start, the day of rFSH start, and every 1 to 2 days until HCG administration. Additionally, FSH, LH, and E were measured daily after the last OC until rFSH start in the OCAnt group. Results: The two groups did not differ in age, weight, or pre-OC hormone levels. On the day of rFSH stimulation start (post OC day 5), E, FSH, and LH, but not P, were significantly higher in the OC Ant group than in the OC Ag group: E (25.4 ⫹ 3.9 pg/mL vs 10.2 ⫹ 3.6 pg/mL, p ⫽ .009), FSH (9.2 ⫹ 1.2 mIU/mL vs 3.9 ⫹ 0.4 mIU/mL, p ⬍.000), LH (5.7 ⫹ 1.0 mIU/mL vs 2.6 ⫹ 0.5 mIU/mL, p ⫽ .012), P (63 ⫹ 10 ng/dL vs 63 ⫹ 20 ng/mL). There was no difference in the days of rFSH (8.5 ⫹ 0.8 vs 8.1 ⫹ 0.6) or total amount of rFSH used. The day of hCG administration, E and follicles ⬎12 mm, but not LH, P, or follicles ⬎16 mm, were significantly decreased in the OCAnt group: E (980 ⫹ 73 vs 1756 ⫹ 240 pg/mL, p ⫽ .019) LH (1.7 ⫹ 0.6 vs 4.0 ⫹ 1.6) P (121 ⫹ 26 vs 122 ⫹ 16) (⬎12mm 7.5 ⫹ 1.0 vs 13.0 ⫹ 1.7, p ⫽ .028) (⬎16mm 2.8 ⫹ 1.5 vs 4.5 ⫹ 1.1). Daily measurements in the OC Ant group established that the increase in E, FSH, and LH began on the 4th post OC day. Conclusions: We conclude that high E, FSH, and LH levels on post OC day 5, in patients not receiving GnRH agonist, may be the result of premature follicle development before rFSH is started and may be the cause of lower follicle numbers on HCG day. Starting rFSH before the 4th post OC day may result in recruitment of additional follicles in patients receiving GnRH antagonist. Supported by: A grant from Organon, Inc. P-177 Combined use of GnRH analog and antagonist: Redundancy vs. complementary action. Dov B. Goldstein, Florenta Bedernicianu, Jane Zhang, Marina Bulavina, Mihaela Voicu, Helen Fong. Cent Park West Fertility/ Brooklyn Fertility Ctr, New York, NY; Cent Park West Fertility/Brooklyn Fertility Ctr, New York, NY. Objective: It was found that GnRH has receptors in the whole male and female reproductive tract: testis, cumulus complex, oocytes, fallopian tubes, endometrium, etc. The GnRH Analogue (GnRHA) has a beneficial effect at all levels while the GnRH Antagonist opposes it with an apparent trend toward lower pregnancy rates. However, the GnRH Antagonist is becoming more accepted because of a lesser incidence of O.H.S.S. and less cycle cancellations especially, in the challenging P.C.O.S. cases (multiple smaller than 12mm follicles with high Estradiol (E2)). Our pilot study attempts to determine if the beneficial effects of the GnRHA can be maintained and further enhanced by the timely addition of the GnRH Antagonist.
Vol. 78, No. 3, Suppl. 1, September 2002