- Email: [email protected]
The effect of oocyte reserve on pregnancy rates (PRs) per oocyte harvest in women aged≤35
immersed into the water at 37 C after 5min at RT. 1.0M, 0.5M, and 0.25M, 0.125M sucrose or trehalose in sequentially according to our lab protocol. Group 1 and 3 was used sucrose as cryoprotectant, instead group 2 and 4 was used trehalose. We observed histology, viability, growing and apoptosis of follicle, using H&E, PCNA, VEGF, and Caspase-3 within 30 minutes. RESULTS: No difference was found between sucrose and trehalose as cryoprotectant among groups. But the group 1 and 2 which has the more soaking time (30 min.) showed the better histological intactness and viability of follicle than group 3, 4. The expression of caspase-3 has no difference in each group. CONCLUSION: Enough exposure time to freeze will give better condition after thawing in vitrification of ovary tissue. Therefore, vitrification method is more reliable way to freeze compared to the previous freezing methods for ovary tissue. Supported by: The grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare abd Family Affairs.
P-12 Tuesday, October 23, 2012 € ANTI-MULLERIAN HORMONE (AMH): A RELIABLE BIOMARKER OF OOCYTES QUALITY IN STIMULATED IN VITRO FERTILIZATION (IVF). P. Lehmann, M. Del P. Velez, J. Saumet, L. Lapensee, F. Bissonnette, J. Kadoch. Obstetric and Gynecology, Clinic OVO and University of Montreal, Montreal, QC, Canada. OBJECTIVE: To evaluate the impact of serum AMH levels on stimulated IVF implantation and pregnancy rates. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 637 patients undergoing stimulated IVF protocols between January 2009 and December 2011 were included. Only non-polycystic ovary first IVF attempt patients were considered for the analysis. Cycle outcomes were analysed according to AMH percentiles per patient’s age category (<35, 35-39 and 40-43 years old) based on the AMH normogram of our infertile population. Univariate and multivariate analysis adjusted for patient’s age, total exogenous FSH dosage and number of eggs retrieved were performed. RESULTS: The multivariate analysis demonstrated that women under 35 years old with AMH levels<25th percentile (<1 ng/ml) had a significant lower implantation rate (0.26 vs. 0.45 P 0.04), compared to the reference population (R25th percentile - AMH%75th percentile). Similar results were obtained with the ongoing pregnancy rate per cycle (OR 0.46 95% CI 0.22-0.96). Additionally, in all age categories, patients with AMH levels<25th percentile, had a lower embryo freezing rate (OR 0.41 95% CI 0.21-0.80, OR 0.45 95% CI 0.23-0.86, OR 0.18 95% CI 0.04-0.82) and a lower number of mature oocytes per cycle (6(SD 3.5) Vs 8.5(SD 4.2), 4.2 (SD 2.7) Vs 7 (SD 4.1), 3.6 (SD 1.8) Vs 5.8 (SD 3.9)), respectively (P<0,001). For all ages combined, the multivariate analyses showed that patients with AMH levels<25th perc (<0.47 ng/ml) were two time less likely to obtain an ongoing pregnancy per cycle started (OR 0.56 95% CI 0.31-0.99), compared to the reference population. CONCLUSION: AMH plays a major role in assisted reproductive technology (ART). It allows not only the quantification of the ovarian reserve, but also the prediction to an eventual ovarian response to the stimulation. Our results suggest that AMH is a reliable biomarker of oocyte quality. Furthermore, it could enable a better patient protocol allocation along with a more comprehensive embryo transfer policy.
P-13 Tuesday, October 23, 2012 CYCLOPHOSPHAMIDE (CYC) EXPOSURE IN PEDIATRIC PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (pSLE) IS ASSOCIATED WITH REDUCED SERUM ANTI-MULLERIAN HORMONE (AMH) LEVELS. L. C. Grossman,a J. Isgro,b S. K. Nurudeen,a M. V. Sauer,a R. Lobo,a N. C. Douglas.a aObstetrics and Gynecology, Columbia University College of Physicians & Surgeons, New York, NY; bPediatric Rheumatology, Columbia University College of Physicians & Surgeons, New York, NY. OBJECTIVE: The reproductive risk of young girls and women suffering from pSLE of varying disease severity and medication exposure is not well established. This pilot study aimed to compare serum AMH levels between pSLE patients and healthy controls. DESIGN: Retrospective cohort study MATERIALS AND METHODS: pSLE patients (n¼20, median age 19.0 years) and controls (n¼20, median age 18.5 years), all>3 months after menarche, were studied. Demographic data, menstrual history, and serum levels of
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ASRM Abstracts
AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were obtained. For pSLE patients, SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics (SLICC) damage index scores, and medications were also recorded. The median disease duration was 4.8 years. Current medication use by pSLE patients included hydroxychloroquine (90%) and prednisone (70%); 30% had prior exposure to CYC. RESULTS: There was no significant difference in BMI, age since menarche, reported irregular menses, or median levels of FSH, LH, E2 between pSLE patients and controls. Although median AMH levels in pSLE patients and controls were similar (1.7 (IQR 0.1-2.4) and 1.9 (IQR 1.1-2.8) ng/ml), AMH levels in pSLE patients with a history of CYC exposure (pSLE+CYC) were significantly lower than in pSLE patients who had never received CYC (pSLE-CYC) (0.8 (IQR 0.2-1.7) and 1.9 (IQR 1.5-2.5) ng/ml) with P¼0.03. SLEDAI scores were similar, however SLICC damage scores were significantly higher in pSLE+CYC with P¼0.04. There was no correlation between AMH level and SLEDAI or SLICC damage scores. CONCLUSION: The disease severity of pSLE does not appear to be correlated with serum AMH levels. However, exposure to CYC is associated with a significant reduction in AMH levels, which implies a risk of diminished ovarian reserve and impaired future fertility in these patients. Following pSLE patients prospectively is necessary to observe further changes in AMH levels over time and determine the meaning of this relationship.
P-14 Tuesday, October 23, 2012 WOMEN WITH POLYCYSTIC OVARY SYNDROME EXPERIENCE MORE RAPID DECLINE IN ANTI-MULLERIAN HORMONE LEVELS. F. J. Roca,a A. K. Schutt,b E. C. Mazur,a W. E. Gibbons,a E. Kovanci.a aOb&Gyn, Baylor College of Medicine, Houston, TX; bOb&Gyn, University of Virginia, Charlottesville, VA. OBJECTIVE: It is not clear how higher antimullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) change with age compared to normal cycling women. Our objective was to investigate the change in AMH levels with age in women with PCOS and to determine the predictive value of AMH in these women if they undergo IVF. DESIGN: Retrospective case-control. MATERIALS AND METHODS: Our study included 366 women with an AMH level from March 2009 to April 2012. Patient charts were reviewed for peak estradiol, number of total eggs retrieved, fertilization rate and pregnancy rate. The Rotterdam Criteria were used to confirm the diagnosis of PCOS. Pregnancy was defined as a positive serum beta HCG. The data were analyzed using Wilcoxon rank sum test and Fisher exact test. The ANCOVA was used to compare regression lines. RESULTS: Women with PCOS were younger than women without PCOS (33.4 vs 35.7 P<0.01). The average AMH level was higher in women with PCOS (6.1 vs 1.8 ng/mL, P<0.01). The rate of decline in AMH was more rapid among women with PCOS than in women without PCOS (P<0.05). Of 84 women who underwent IVF, 25 had PCOS and 59 did not. Overall IVF pregnancy rate was not different between women with PCOS vs. without PCOS (40% in both). Women with PCOS had a higher average peak estradiol, higher average number of total oocytes retrieved, but similar average fertilization rate. When the AMH level was%5, women with PCOS had a higher likelihood of pregnancy compared to women without PCOS (53% vs. 38% P>0.05). Women with PCOS had a lower likelihood of pregnancy when the AMH levels were>5 (13% and 67%, P>0.05). Women with PCOS and AMH>5 had lower BMI and higher peak E2 than women with PCOS and AMH%5. CONCLUSION: Our data suggests that AMH declines more rapidly in women with PCOS. AMH levels>5 may have a negative impact on IVF success in women with PCOS. A normal or high AMH level in women with PCOS should be cautiously interpreted as it may decline rapidly, and very high levels may be detrimental for IVF success.
P-15 Tuesday, October 23, 2012 THE EFFECT OF OOCYTE RESERVE ON PREGNANCY RATES (PRs) PER OOCYTE HARVEST IN WOMEN AGED%35. J. H. Check,a,b A. Whetstone,c C. Wilson,a J. K. Choe.a aDept. OB/GYN, Division of Repro. Endo. & Infertility, UMDNJ, Robert Wood Johnson Med. School at Camden, Camden, NJ; bDept. OB/GYN, Division of Repro. Endo. & Infertility, Cooper Medical School of Rowan University, Camden, NJ; cDept. OB/GYN, UMDNJSchool of Osteopathic Medicine, Stratford, NJ.
Vol. 98, No. 3, Supplement, September 2012
OBJECTIVE: Using mild stimulation for controlled ovarian hyperstimulation (COH) some claim to achieve almost comparable PRs following in vitro fertilization-embryo transfer (IVF-ET) in women with diminished oocyte reserve vs. normal oocyte reserve receiving conventional COH. The objective was to compare the impact of diminished oocyte reserve on PR per oocyte harvest which includes not only the PR per fresh transfer but also the frozen embryos derived from that retrieval. DESIGN: Retrospective cohort analysis. MATERIALS AND METHODS: The PRs per ET and PR per oocyte harvest were compared by chi-square analysis in women with normal oocyte reserve (day 3 serum follicle stimulating hormone (FSH)%11 mIU/mL) vs. diminished (FSHR12 mIU/mL) over a 10 year period. Clinical (ultrasound evidence of pregnancy at 8 weeks) viable (live fetus at 12 weeks) and live delivered PRs were compared between the group with normal vs. diminished oocyte reserve. RESULTS: For women with normal oocyte reserve there were a total of 1719 fresh ETs and 1498 frozen ETs (total of 3217 ETs). For diminished oocyte reserve there were 380 fresh ETs and 59 frozen ETs (total of 449 ETs). For the normal reserve group the clinical, viable and live delivered PRs per fresh ET were 47.1% (811/1719), 43.5% and 40.4%. For low egg reserve these PRs were 39.4% (150/380), 35.2% and 33.9%. For frozen ETs for normal reserve the PRs were 43.6% (654/1498), 38.3% and 35.5%. For frozen ETs with low reserve the PRs were 27.1% (16/59), 25.4% and 25.4%. The live delivered PR per oocyte harvest was 74.9% (1228/1719) for normal reserve vs. 37.8% (140/380) for diminished reserve (P<0.001). CONCLUSION: Whereas the use of mild COH protocols allows a live PR per transfer only 20% less for women with diminished oocyte reserve vs. normal reserve following IVF-ET, the PR per oocyte harvest is 50% less. This may be due to fewer embryos available for freezing and subsequent frozen ET.
CANCER P-16 Tuesday, October 23, 2012 THE PROTECTIVE EFFECT OF FIBRATE AGAINST ENDOTHELIAL DYSFUNCTION INDUCED BY PLATINUM-BASED CHEMOTHERAPY IN GYNECOLOGICAL CANCER PATIENTS. A. Watanabe, A. Tanabe, Y. Tanaka, S. Tsunetoh, Y. Terai, M. Ohmichi. Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka, Japan. OBJECTIVE: Patients with ovarian cancer and uterine endometrial cancer generally undergo surgery followed by the administration of platinum-based chemotherapy(PtChem). Although, previous reports suggested that PtChem are associated with vascular toxicity, the mechanisms were still unclear. Previous report demonstrated that cisplatin may directly inhibit peroxisome proliferator-activated receptor-alpha (PPARa) following by acute renal failure. Furthermore, it has been shown that PPARa ligands prevent the development of renal failure. Therefore, our aim was to evaluate the influence of PtChem on arteriosclerosis and whether fibrate prevents vascular dysfunction in cancer survivors. DESIGN: Retrospective case-controloed and prospective study. MATERIALS AND METHODS: Study 1: This study enrolled 47 women who underwent surgical treatment with or without PtChem according to established protocols. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) performed before surgery, and subsequently at 12 months after treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured before and immediately following PtChem. Study 2: This study enrolled 35 patients who were administrated with (n¼4) or without (n¼31) bezafibrate. %FMD and serum PTX3 levels were measured before and immediately following PtChem. RESULTS: Study 1. PtChem was associated with an increased baPWV. Significant decreases of %FMD were observed immediately following PtChem. Study 2. In fibrate group, the plasma levels of TG were reduced, the fold decrease of %FMD was improved, and the fold increases of the PTX3 levels were decreased. CONCLUSION: This research suggests that PtChem induces vascular endothelial dysfunction, and PPARa ligands may prevent the development of atherosclerosis induced by PtChem. Supported by: Partially supported by Grant in Aid for Scientific Research No. 24592535 (to AT) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
FERTILITY & STERILITYÒ
P-17 Tuesday, October 23, 2012 A RANDOMIZED OPEN LABEL CLINICAL TRIAL OF FIXED VS.TITRATED DOSE LETROZOLE FOR OVARIAN STIMULATION IN BREAST CANCER PATIENTS: AN INTERIM ANALYSIS. E. R. Rauch,a,b R. Stubbs,a P. Christos,a M. CostantiniFerrando,a,c G. Schattman.a aThe Center for Reproductive Medicine and Infertility, New York Presbyterian- Joan and Sanford Weill Medical College, New York, NY; bIVFNJ, Somerset, NJ; cRMANJ, Morristown, NJ. OBJECTIVE: Chemotherapy has detrimental effects on ovarian function and future fertility. Ovarian stimulation for oocyte cryopreservation results in supra-physiologic estrogen levels which concerns patients with hormonally sensitive disease. DESIGN: Prospective, randomized, open label, clinical trial of fixed v. titrated dose letrozole with cryopreservation of oocytes and embryos in breast cancer patients. Interim analysis is presented. MATERIALS AND METHODS: Patients were randomized by age to one of 2 treatment arms: Fixed dose letrozole with ovarian stimulation starting on day 3 or ovarian stimulation with letrozole initiated and titrated based on estradiol level. Primary outcome was number of mature oocytes and secondary outcomes are shown below. Comparison between groups was performed by the two-sample t-test, Wilcoxon rank-sum or Fisher’s exact test as appropriate. RESULTS: Results are shown in Table 1. Interim analysis Fixed Letrozole (n¼10) Age BMI D3 FSH AMH Total gonadotropin dose Days of stimulation Peak estradiol Estradiol post HCG Ooctyes harvested Oocytes mature Adverse events
342.5 21.92.8 5.91.6 2.31.1 2463.01528.7
Titrated Letrozole (n¼10)
P-value
345.2 21.51.8 6.42.0 1.81.6 2625.01168.3
0.96 0.70 0.57 0.47 0.79
9.3 1.3 662.3262.2 1001.6422.8 17.012.9 13.610.7 (median¼11.0) 2 (20%): 3 (30%): abdominal abdominal pain, OHSS pain, OHSS, epigastric pain 10.62.6 670.1188.7 1072.6409.6 20.58.6 19.08.2 (median¼20)
0.18 0.94 0.71 0.49 0.12 1.00
Results reported as meanstandard deviation or frequency (percent). CONCLUSION: Both fixed or titrated letrozole protocols offer similar efficacy with regard to number of oocytes retrieved for cryopreservation in cancer patients pre-chemotherapy. Safety profiles are comparable between arms and consistent with typical IVF regimens. There have been no breast cancer recurrences noted for the first 11 subjects with 1-year follow-up. Supported by: Institutional.
P-18 Tuesday, October 23, 2012 THE INFLUENCE OF THE ANTICANCER DRUG CYCLOPHOSPHAMIDE ON FERTILIZATION AND EMBRYO GROWTH IN A MOUSE MODEL. M. Koike,a Y. Kumasako,a E. Otsu,a Y. Araki,b Y. Araki,b T. Utsunomiya.a aSt. Luke Clinic, Oita City, Oita, Japan; bThe Institute for Advanced Reproductive Medical Technology, Maebashi, Gunma, Japan. OBJECTIVE: Currently, unfertilized oocytes from patients undergoing chemotherapy are frozen for future use. Therefore, the object of this study was to evaluate the influence of an anticancer drug on fertilization and embryo growth in mice. DESIGN: Experimental Study. MATERIALS AND METHODS: We evaluated the relationship between various drug concentrations and fertilization ability, potential oocyte growth, activation time of the drug, and blastocyst quality in a mouse model. Cyclophosphamide (CPA) at doses of 0, 50, 100, 200, 400, and 800 mg/kg were intraperitoneally injected into adult female closed colony strain (ICR)
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P-12 Tuesday, October 23, 2012 € ANTI-MULLERIAN HORMONE (AMH): A RELIABLE BIOMARKER OF OOCYTES QUALITY IN STIMULATED IN VITRO FERTILIZATION (IVF). P. Lehmann, M. Del P. Velez, J. Saumet, L. Lapensee, F. Bissonnette, J. Kadoch. Obstetric and Gynecology, Clinic OVO and University of Montreal, Montreal, QC, Canada. OBJECTIVE: To evaluate the impact of serum AMH levels on stimulated IVF implantation and pregnancy rates. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: 637 patients undergoing stimulated IVF protocols between January 2009 and December 2011 were included. Only non-polycystic ovary first IVF attempt patients were considered for the analysis. Cycle outcomes were analysed according to AMH percentiles per patient’s age category (<35, 35-39 and 40-43 years old) based on the AMH normogram of our infertile population. Univariate and multivariate analysis adjusted for patient’s age, total exogenous FSH dosage and number of eggs retrieved were performed. RESULTS: The multivariate analysis demonstrated that women under 35 years old with AMH levels<25th percentile (<1 ng/ml) had a significant lower implantation rate (0.26 vs. 0.45 P 0.04), compared to the reference population (R25th percentile - AMH%75th percentile). Similar results were obtained with the ongoing pregnancy rate per cycle (OR 0.46 95% CI 0.22-0.96). Additionally, in all age categories, patients with AMH levels<25th percentile, had a lower embryo freezing rate (OR 0.41 95% CI 0.21-0.80, OR 0.45 95% CI 0.23-0.86, OR 0.18 95% CI 0.04-0.82) and a lower number of mature oocytes per cycle (6(SD 3.5) Vs 8.5(SD 4.2), 4.2 (SD 2.7) Vs 7 (SD 4.1), 3.6 (SD 1.8) Vs 5.8 (SD 3.9)), respectively (P<0,001). For all ages combined, the multivariate analyses showed that patients with AMH levels<25th perc (<0.47 ng/ml) were two time less likely to obtain an ongoing pregnancy per cycle started (OR 0.56 95% CI 0.31-0.99), compared to the reference population. CONCLUSION: AMH plays a major role in assisted reproductive technology (ART). It allows not only the quantification of the ovarian reserve, but also the prediction to an eventual ovarian response to the stimulation. Our results suggest that AMH is a reliable biomarker of oocyte quality. Furthermore, it could enable a better patient protocol allocation along with a more comprehensive embryo transfer policy.
P-13 Tuesday, October 23, 2012 CYCLOPHOSPHAMIDE (CYC) EXPOSURE IN PEDIATRIC PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (pSLE) IS ASSOCIATED WITH REDUCED SERUM ANTI-MULLERIAN HORMONE (AMH) LEVELS. L. C. Grossman,a J. Isgro,b S. K. Nurudeen,a M. V. Sauer,a R. Lobo,a N. C. Douglas.a aObstetrics and Gynecology, Columbia University College of Physicians & Surgeons, New York, NY; bPediatric Rheumatology, Columbia University College of Physicians & Surgeons, New York, NY. OBJECTIVE: The reproductive risk of young girls and women suffering from pSLE of varying disease severity and medication exposure is not well established. This pilot study aimed to compare serum AMH levels between pSLE patients and healthy controls. DESIGN: Retrospective cohort study MATERIALS AND METHODS: pSLE patients (n¼20, median age 19.0 years) and controls (n¼20, median age 18.5 years), all>3 months after menarche, were studied. Demographic data, menstrual history, and serum levels of
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ASRM Abstracts
AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were obtained. For pSLE patients, SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics (SLICC) damage index scores, and medications were also recorded. The median disease duration was 4.8 years. Current medication use by pSLE patients included hydroxychloroquine (90%) and prednisone (70%); 30% had prior exposure to CYC. RESULTS: There was no significant difference in BMI, age since menarche, reported irregular menses, or median levels of FSH, LH, E2 between pSLE patients and controls. Although median AMH levels in pSLE patients and controls were similar (1.7 (IQR 0.1-2.4) and 1.9 (IQR 1.1-2.8) ng/ml), AMH levels in pSLE patients with a history of CYC exposure (pSLE+CYC) were significantly lower than in pSLE patients who had never received CYC (pSLE-CYC) (0.8 (IQR 0.2-1.7) and 1.9 (IQR 1.5-2.5) ng/ml) with P¼0.03. SLEDAI scores were similar, however SLICC damage scores were significantly higher in pSLE+CYC with P¼0.04. There was no correlation between AMH level and SLEDAI or SLICC damage scores. CONCLUSION: The disease severity of pSLE does not appear to be correlated with serum AMH levels. However, exposure to CYC is associated with a significant reduction in AMH levels, which implies a risk of diminished ovarian reserve and impaired future fertility in these patients. Following pSLE patients prospectively is necessary to observe further changes in AMH levels over time and determine the meaning of this relationship.
P-14 Tuesday, October 23, 2012 WOMEN WITH POLYCYSTIC OVARY SYNDROME EXPERIENCE MORE RAPID DECLINE IN ANTI-MULLERIAN HORMONE LEVELS. F. J. Roca,a A. K. Schutt,b E. C. Mazur,a W. E. Gibbons,a E. Kovanci.a aOb&Gyn, Baylor College of Medicine, Houston, TX; bOb&Gyn, University of Virginia, Charlottesville, VA. OBJECTIVE: It is not clear how higher antimullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) change with age compared to normal cycling women. Our objective was to investigate the change in AMH levels with age in women with PCOS and to determine the predictive value of AMH in these women if they undergo IVF. DESIGN: Retrospective case-control. MATERIALS AND METHODS: Our study included 366 women with an AMH level from March 2009 to April 2012. Patient charts were reviewed for peak estradiol, number of total eggs retrieved, fertilization rate and pregnancy rate. The Rotterdam Criteria were used to confirm the diagnosis of PCOS. Pregnancy was defined as a positive serum beta HCG. The data were analyzed using Wilcoxon rank sum test and Fisher exact test. The ANCOVA was used to compare regression lines. RESULTS: Women with PCOS were younger than women without PCOS (33.4 vs 35.7 P<0.01). The average AMH level was higher in women with PCOS (6.1 vs 1.8 ng/mL, P<0.01). The rate of decline in AMH was more rapid among women with PCOS than in women without PCOS (P<0.05). Of 84 women who underwent IVF, 25 had PCOS and 59 did not. Overall IVF pregnancy rate was not different between women with PCOS vs. without PCOS (40% in both). Women with PCOS had a higher average peak estradiol, higher average number of total oocytes retrieved, but similar average fertilization rate. When the AMH level was%5, women with PCOS had a higher likelihood of pregnancy compared to women without PCOS (53% vs. 38% P>0.05). Women with PCOS had a lower likelihood of pregnancy when the AMH levels were>5 (13% and 67%, P>0.05). Women with PCOS and AMH>5 had lower BMI and higher peak E2 than women with PCOS and AMH%5. CONCLUSION: Our data suggests that AMH declines more rapidly in women with PCOS. AMH levels>5 may have a negative impact on IVF success in women with PCOS. A normal or high AMH level in women with PCOS should be cautiously interpreted as it may decline rapidly, and very high levels may be detrimental for IVF success.
P-15 Tuesday, October 23, 2012 THE EFFECT OF OOCYTE RESERVE ON PREGNANCY RATES (PRs) PER OOCYTE HARVEST IN WOMEN AGED%35. J. H. Check,a,b A. Whetstone,c C. Wilson,a J. K. Choe.a aDept. OB/GYN, Division of Repro. Endo. & Infertility, UMDNJ, Robert Wood Johnson Med. School at Camden, Camden, NJ; bDept. OB/GYN, Division of Repro. Endo. & Infertility, Cooper Medical School of Rowan University, Camden, NJ; cDept. OB/GYN, UMDNJSchool of Osteopathic Medicine, Stratford, NJ.
Vol. 98, No. 3, Supplement, September 2012
OBJECTIVE: Using mild stimulation for controlled ovarian hyperstimulation (COH) some claim to achieve almost comparable PRs following in vitro fertilization-embryo transfer (IVF-ET) in women with diminished oocyte reserve vs. normal oocyte reserve receiving conventional COH. The objective was to compare the impact of diminished oocyte reserve on PR per oocyte harvest which includes not only the PR per fresh transfer but also the frozen embryos derived from that retrieval. DESIGN: Retrospective cohort analysis. MATERIALS AND METHODS: The PRs per ET and PR per oocyte harvest were compared by chi-square analysis in women with normal oocyte reserve (day 3 serum follicle stimulating hormone (FSH)%11 mIU/mL) vs. diminished (FSHR12 mIU/mL) over a 10 year period. Clinical (ultrasound evidence of pregnancy at 8 weeks) viable (live fetus at 12 weeks) and live delivered PRs were compared between the group with normal vs. diminished oocyte reserve. RESULTS: For women with normal oocyte reserve there were a total of 1719 fresh ETs and 1498 frozen ETs (total of 3217 ETs). For diminished oocyte reserve there were 380 fresh ETs and 59 frozen ETs (total of 449 ETs). For the normal reserve group the clinical, viable and live delivered PRs per fresh ET were 47.1% (811/1719), 43.5% and 40.4%. For low egg reserve these PRs were 39.4% (150/380), 35.2% and 33.9%. For frozen ETs for normal reserve the PRs were 43.6% (654/1498), 38.3% and 35.5%. For frozen ETs with low reserve the PRs were 27.1% (16/59), 25.4% and 25.4%. The live delivered PR per oocyte harvest was 74.9% (1228/1719) for normal reserve vs. 37.8% (140/380) for diminished reserve (P<0.001). CONCLUSION: Whereas the use of mild COH protocols allows a live PR per transfer only 20% less for women with diminished oocyte reserve vs. normal reserve following IVF-ET, the PR per oocyte harvest is 50% less. This may be due to fewer embryos available for freezing and subsequent frozen ET.
CANCER P-16 Tuesday, October 23, 2012 THE PROTECTIVE EFFECT OF FIBRATE AGAINST ENDOTHELIAL DYSFUNCTION INDUCED BY PLATINUM-BASED CHEMOTHERAPY IN GYNECOLOGICAL CANCER PATIENTS. A. Watanabe, A. Tanabe, Y. Tanaka, S. Tsunetoh, Y. Terai, M. Ohmichi. Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka, Japan. OBJECTIVE: Patients with ovarian cancer and uterine endometrial cancer generally undergo surgery followed by the administration of platinum-based chemotherapy(PtChem). Although, previous reports suggested that PtChem are associated with vascular toxicity, the mechanisms were still unclear. Previous report demonstrated that cisplatin may directly inhibit peroxisome proliferator-activated receptor-alpha (PPARa) following by acute renal failure. Furthermore, it has been shown that PPARa ligands prevent the development of renal failure. Therefore, our aim was to evaluate the influence of PtChem on arteriosclerosis and whether fibrate prevents vascular dysfunction in cancer survivors. DESIGN: Retrospective case-controloed and prospective study. MATERIALS AND METHODS: Study 1: This study enrolled 47 women who underwent surgical treatment with or without PtChem according to established protocols. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) performed before surgery, and subsequently at 12 months after treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured before and immediately following PtChem. Study 2: This study enrolled 35 patients who were administrated with (n¼4) or without (n¼31) bezafibrate. %FMD and serum PTX3 levels were measured before and immediately following PtChem. RESULTS: Study 1. PtChem was associated with an increased baPWV. Significant decreases of %FMD were observed immediately following PtChem. Study 2. In fibrate group, the plasma levels of TG were reduced, the fold decrease of %FMD was improved, and the fold increases of the PTX3 levels were decreased. CONCLUSION: This research suggests that PtChem induces vascular endothelial dysfunction, and PPARa ligands may prevent the development of atherosclerosis induced by PtChem. Supported by: Partially supported by Grant in Aid for Scientific Research No. 24592535 (to AT) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
FERTILITY & STERILITYÒ
P-17 Tuesday, October 23, 2012 A RANDOMIZED OPEN LABEL CLINICAL TRIAL OF FIXED VS.TITRATED DOSE LETROZOLE FOR OVARIAN STIMULATION IN BREAST CANCER PATIENTS: AN INTERIM ANALYSIS. E. R. Rauch,a,b R. Stubbs,a P. Christos,a M. CostantiniFerrando,a,c G. Schattman.a aThe Center for Reproductive Medicine and Infertility, New York Presbyterian- Joan and Sanford Weill Medical College, New York, NY; bIVFNJ, Somerset, NJ; cRMANJ, Morristown, NJ. OBJECTIVE: Chemotherapy has detrimental effects on ovarian function and future fertility. Ovarian stimulation for oocyte cryopreservation results in supra-physiologic estrogen levels which concerns patients with hormonally sensitive disease. DESIGN: Prospective, randomized, open label, clinical trial of fixed v. titrated dose letrozole with cryopreservation of oocytes and embryos in breast cancer patients. Interim analysis is presented. MATERIALS AND METHODS: Patients were randomized by age to one of 2 treatment arms: Fixed dose letrozole with ovarian stimulation starting on day 3 or ovarian stimulation with letrozole initiated and titrated based on estradiol level. Primary outcome was number of mature oocytes and secondary outcomes are shown below. Comparison between groups was performed by the two-sample t-test, Wilcoxon rank-sum or Fisher’s exact test as appropriate. RESULTS: Results are shown in Table 1. Interim analysis Fixed Letrozole (n¼10) Age BMI D3 FSH AMH Total gonadotropin dose Days of stimulation Peak estradiol Estradiol post HCG Ooctyes harvested Oocytes mature Adverse events
342.5 21.92.8 5.91.6 2.31.1 2463.01528.7
Titrated Letrozole (n¼10)
P-value
345.2 21.51.8 6.42.0 1.81.6 2625.01168.3
0.96 0.70 0.57 0.47 0.79
9.3 1.3 662.3262.2 1001.6422.8 17.012.9 13.610.7 (median¼11.0) 2 (20%): 3 (30%): abdominal abdominal pain, OHSS pain, OHSS, epigastric pain 10.62.6 670.1188.7 1072.6409.6 20.58.6 19.08.2 (median¼20)
0.18 0.94 0.71 0.49 0.12 1.00
Results reported as meanstandard deviation or frequency (percent). CONCLUSION: Both fixed or titrated letrozole protocols offer similar efficacy with regard to number of oocytes retrieved for cryopreservation in cancer patients pre-chemotherapy. Safety profiles are comparable between arms and consistent with typical IVF regimens. There have been no breast cancer recurrences noted for the first 11 subjects with 1-year follow-up. Supported by: Institutional.
P-18 Tuesday, October 23, 2012 THE INFLUENCE OF THE ANTICANCER DRUG CYCLOPHOSPHAMIDE ON FERTILIZATION AND EMBRYO GROWTH IN A MOUSE MODEL. M. Koike,a Y. Kumasako,a E. Otsu,a Y. Araki,b Y. Araki,b T. Utsunomiya.a aSt. Luke Clinic, Oita City, Oita, Japan; bThe Institute for Advanced Reproductive Medical Technology, Maebashi, Gunma, Japan. OBJECTIVE: Currently, unfertilized oocytes from patients undergoing chemotherapy are frozen for future use. Therefore, the object of this study was to evaluate the influence of an anticancer drug on fertilization and embryo growth in mice. DESIGN: Experimental Study. MATERIALS AND METHODS: We evaluated the relationship between various drug concentrations and fertilization ability, potential oocyte growth, activation time of the drug, and blastocyst quality in a mouse model. Cyclophosphamide (CPA) at doses of 0, 50, 100, 200, 400, and 800 mg/kg were intraperitoneally injected into adult female closed colony strain (ICR)
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