- Email: [email protected]
Which patient do you prefer in the office? Younger with elevated FSH or elderly with normal FSH
A-308 IN-VITRO MATURATION AFFECTS THE HISTONE ACETHYLATION MODIFICATION OF MOUSE OOCYTES AND EARLY CLEAVAGE EMBRYOS. N. Wang, M.-y. Dong, H.-f. Huang, F. Jin. Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. OBJECTIVE: In-vitro fertilization and embryo transfer (IVF-ET) is a very successful treatment for infertile couples. However, the high costs for gonadotropin injections, the risk of ovarian hyperstimulation syndrome (OHSS) and the possible association between repeated ovarian stimulation and hormone-related cancers are the main drawbacks. In-vitro maturation (IVM) offers an alternative to conventional IVF treatment that minimizes drug administration and avoids ovarian hyperstimulation. However, the safety of IVM was questioned. Considering oocyte maturation is one of the most important periods of epigenetic reprogramming, the changes of epigenetic modification resulted from altered environments in IVM might be involved in. To investigate the influences of IVM on epigenetic reprogramming and the possible mechanisms, the expression of two regulatory enzymes for histone acetylation, histone acetyltransferase GCN5 (GCN5) and histone deacetylase 1 (HDAC1) in mouse metaphase II (MII) oocytes and the preimplantation embryos were analyzed. DESIGN: Experimental animal study. MATERIALS AND METHODS: Six-to-8-week-old ICR female mice were divided into two groups, IVM and control group. In IVM group, immature oocytes were collected from the ovaries of female mice without stimulation. MII oocytes were retrieved after 16-18h IVM of GV oocytes. In control group, in-vivo matured MII oocytes were retrieved directly from oviducts at post administration of HCG 7.5IU 13-15h after 7.5IU PMSG stimulation. Embryos in the two groups were recovered after 24-28h of IVF. RTPCR was used to determine the gene expression of GCN5 and HDAC1 in mouse MII oocytes and 2-cell stage embryos. RESULTS: The rates of fertilization and cleavage in IVM are lower than that in the control group (36.8%vs77.1%, p<0.01; 84.2%vs90.9%, p<0.01). The mRNA of GCN5 in MII oocytes and the two-cell embryos in IVM group are similar to that in the control group (p >0.05).However, HDAC1 mRNA was significantly decreased in both oocytes and embryos in IVM compared with the control group (P<0.05). CONCLUSIONS: IVM environments could down-regulate the gene expression of HDAC1 in MII oocytes and two-cell embryos. The culture conditions were inadequate to support the developmental capacity of some oocytes. The accurate mechanisms of those changes induced by IVM need further investigate. Supported by: National Basic Research Program of China (2007CB948104).
A-309 ABNORMAL DISTRIBUTION OF CORTICAL GRANULES IN CYNOMOLGUS MONKEY ONE-DAY OLD MII OOCYTES WHICH WERE IMMATURE AT OOCYTE RETRIVAL AFTER CONTROLLED OVARIAN HYPERSTIMULATION. M. Yamanaka, S. Hashimoto, J. Okahara-Narita, J. Yamasaki, R. Torii, Y. Morimoto. IVF Namba Clinic, Osaka, Japan; Shiga University of Medical Science, Shiga, Japan. OBJECTIVE: Developmental competence of cynomolgus monkey (macaca fascicularis) oocytes, which were immature at oocyte retrieval after controlled ovarian hyperstimulation (COH) and reached to metaphase II stage (MII, 1-day old MII oocytes) after overnight culture, were low compared with mature oocytes at oocyte retrieval (fresh MII oocytes). In this study, ultrastructures of 1-day old and fresh MII oocytes were assessed. DESIGN: An experimental study using a monkey model was performed. MATERIALS AND METHODS: Female cynomolgus monkey (5 years old) was used for COH and oocyte retrieval was carried out using a laparoscope. Cumulus cells were removed from oocyte using hyaluronidase. Some of immature (germinal vesicle (GV) and metaphase I (MI)) and mature (fresh MII) oocytes were fixed for control as below. Immature oocytes were cultured in TCM199 supplemented with 5% fetal calf serum for 24h. Control and 1-day old MII oocytes were prefixed by glutaraldehyde, postfixed by osmium, dehydrated and embedded in EPON blocks. Ultrathin sections were observed by transmission electron microscope (TEM) after staining. RESULTS: Fifty oocytes (14 GV, 21 MI, 9 MII and 6 degenerated oocytes, respectively) were retrieved. Immature oocytes (12 GV and 19 MI) were cul-
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Abstracts
tured. Seven mature oocytes were obtained. By observation using TEM, the morphological change of mitochondria during meiotic maturation was assessed. Mitochondria were oval at GV stage and some of them extended at MI stage. Flattened and crescent-shaped mitochondria which encircled smooth endoplasmic reticulum were observed in both fresh and 1-day old MII oocytes. However, in 1-day old MII oocytes, cortical granules were observed not only in the surface but also inside of oocyte. In addition, large fragments were observed in the perivitelline space. Microvilli were observed in all oocytes. CONCLUSIONS: These results suggest that cytoplasmic maturation is incomplete in 1-day old MII oocyte because of improper localization of cortical granules. The unbalance of maturation between nucleus and cytoplasm may impair the developmental competence of 1-day old MII oocyte. Supported by: None. A-310 ANALYSIS OF MEIOTIC ABNORMALITIES OF IN VITRO MATURED OOCYTES FROM STIMULATED CYCLES OF NON-OBESE ENDOMETRIOTIC AND PCOS PATIENTS: A PILOT STUDY. P. A. A. S Navarro, R. A. Ferriani, R. C. Vieira, E. M. Ferreira, A. C. J. S Rosa e Silva, I. D. E. S Barcelos. Department of Obstetrics and Gynecology, Ribeira˜o Preto Medical School-USP, Ribeira˜o Preto, Brazil; Ribeira˜o Preto Medical School-USP, Ribeira˜o Preto, Brazil. OBJECTIVE: Endometriosis and Polycystic Ovarian Syndrome (PCOS) are major causes of human infertility. According to controversial data, both may be associated with worse outcomes of assisted reproduction techniques, which could be caused by an impairment of oocyte quality. Thus, we compared meiotic spindle morphology and chromosomal distribution of in vitro matured human oocytes from non-obese patients with endometriosis and PCOS submitted to ovarian stimulation for ICSI. DESIGN: A prospective, controlled study. MATERIALS AND METHODS: Infertile patients aged up to 38 years undergoing stimulated cycles for oocyte retrieval for ICSI were selected prospectively and consecutively and divided into endometriosis (20 patients) and PCOS (13 patients) groups. Immature oocytes (74 and 34 from endometriosis and PCOS patients, respectively) were submitted to in vitro maturation (IVM) for 19 hours 1 hour (GV) or 4 hours 30 minutes (MI) according to a maturation time curve determined before the beginning of the present study. Using immunostaining and fluorescence microscopy, we imaged spindle and chromosomal distribution of oocytes that extruded the first polar body after IVM. RESULTS: IVM rates were similar for both groups (53.1% and 50%, respectively, for the PCOS and control groups). Spindle and chromosome organization were observed in 35 and 17 oocytes from the endometriosis and PCOS groups, respectively. In the endometriosis group, 13 were normal MII oocytes (37.2%), 9 abnormal MII (25.7%), 11 normal telophase I (31.4%), and 2 normal telophase II (5.7%). In the PCOS group, 6 oocytes were normal MII (35.3%), 8 abnormal MII (47.1%), and 3 normal telophase I (17.6%). The proportions of normal MII oocytes were similar for the two groups (37.2% and 35.3% in endometriosis and PCOS groups, respectively). CONCLUSIONS: Our preliminary data demonstrate that in vitro maturation rates of immature oocytes obtained from stimulated cycles are similar in non-obese infertile women with endometriosis and with PCOS. In vitro matured oocytes from endometriotic patients have a higher percentage of TI when compared to PCOS patients. Our preliminary results also suggest that the incidence of meiotic anomalies, characterized by spindle rupture and/or chromosome misalignment, is similar in in vitro matured oocytes from non-obese PCOS and endometriotic patients. Both results will be better evaluated by increasing the present patient series. Supported by: CAPES, CNPq, and FAEPA/HC-FMRP/USP, Brazil.
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OVARIAN RESERVE
WHICH PATIENT DO YOU PREFER IN THE OFFICE? YOUNGER WITH ELEVATED FSH OR ELDERLY WITH NORMAL FSH. E. Young, Jr, L. Sabatini, M. I. Viola, F. Lorenzo, L. M. Auge, H. Beraja. Gynecology, IFER, Buenos Aires, Capital Federal, Argentina. OBJECTIVE: Analyze which factor has more impact as a predictor of response in IVF outcomes: age or basal FSH. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Of the 268 patients who carried out an IVF treatment with antagonist GnRh cycles from February to August 2005, 128 met the inclusion criteria (% 35 years and FSH R 7.71 and > 35 years and FSH < 7.71).Main outcome measure were: Cause of infertility,
Vol. 90, Suppl 1, September 2008
number of follicles, number of oocytes, MII oocytes, embryo quality, pregnancy rate, miscarriage rate, ectopic pregnancy rate, live birth rate. RESULTS: A hundred and twenty eight (128) patients were selected and divided into two groups: Group A: % 35 years and FSH R 7.71 (56) and Group B: > 35 years and FSH < 7.71 (72), comparing the reproductive outcome. Patients in group B showed a significantly greater number of follicles, gathered number of oocytes and MII oocytes (p ¼ <0.005). But group A showed a greater trend on pregnancy rates and live birth, although this was not statistically significant (p¼ NS). TABLE 1.
No. of follicles No. of oocytes retrieved No. of MII Clinical pregnancy rate Miscarriage rate Live birth Rate
< 35 years and FSH > 7.71 (56)
>35 years and FSH <7.71 (72)
6.80 3.33 6.29 3.70
8.74 4.29 9.17 5.22
<0.05 <0.05
4.71 2.72 17/56 (30%)
7.06 4.12 18/72 (25%)
<0.05 NS
1/17 (1.7%) 22/56 (39%)
3/18 (4.61%) 19/72 (26%)
<0.05 NS
p
CONCLUSIONS: Both basal FSH and age contributed to the prediction of the quantitative ovarian reserve as reflected by the number of oocytes collected. However, age is a better predictor of pregnancy potential for women undergoing IVF. Supported by: None.
A-316 MYOMECTOMY MAY DECREASE AMH LEVELS: A PILOT STUDY. H. N. Browne, L. Nieman, T. Williams, Q. Wei, J. Spies, A. Armstrong. Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda; Howard University College of Medicine, Washington, DC; Interventional Radiology/Department of Radiology, Georgetown University Hospital, Washington, DC. OBJECTIVE: The impact of myomectomy on ovarian reserve is unknown. However, it is considered to be the preferred treatment in patients desiring future fertility. It has not been shown to adversely impact ovarian reserve as measured by FSH. However, recent studies have suggested that AMH is a more sensitive and accurate predictor of ovarian reserve compared to FSH. Our objective was to examine the impact of myomectomy on ovarian reserve as measured by AMH. DESIGN: A prospective, observational study. MATERIALS AND METHODS: Pre and post-operative AMH levels were obtained from six women with symptomatic uterine fibroids to assess the effect of myomectomy on ovarian reserve. These women were enrolled in a Phase II clinical trial, at the NIH, that used the selective progesterone receptor modulator (CDB-2914). Patients with a FSH > 20 mIU/L were excluded from the study. Post-operative AMH levels were drawn between 2 to 18 months after surgery. Statistical analysis was performed with a paired t-test, and the results are presented as the mean SD. A p value of < 0.05 was considered to be statistically significant. RESULTS: The mean age was 37 3.2 and 38 2.9 years before and after surgery, respectively. Mean pre and post-myomectomy serum AMH levels were 1.27 1.21 and 0.72 0.83, respectively (p¼ 0.059). A notable decrease was seen in AMH levels before and after surgery; however, this difference was not statistically significant (Table 1). TABLE 1.
A-315 COMPARISON OF PREDICTIVE VALUE OF ANTI-MULLERIAN HORMONE (AMH) AND DAY 3 FOLLICLE STIMULATING HORMONE FOR PREGNANCY AND OOCYTE RETRIEVAL. D. H. Barad, K. Oktay, A. Weghofer, N. Gleicher. Center for Human Reproduction, New York, NY; New York Medical College, Valhalla, NY; Vienna University School of Medicine, Vienna, Austria. OBJECTIVE: Follicle stimulating hormone (FSH) and anti-Mu¨llerian hormone (AMH) have both been widely reported to correlate to ovarian reserve and in vitro fertilization (IVF) outcomes. A study, comparing FSH and AMH as predictors of pregnancy in IVF, has, however, not been reported before. DESIGN: Cross-sectional survey of existing clinical data. MATERIALS AND METHODS: We investigated in a convenience sample of 90 consecutive IVF patients whether FSH and AMH levels correlated to clinical pregnancy rates after in-vitro fertilization and embryo transfer. FSH levels were obtained on cycle days 2-3, while AMH was drawn at random. Both hormones were measured by standard commercial assay systems. Clinical pregnancy was defined as an ongoing intrauterine pregnancy of greater than 8 weeks with active fetal heart beat. Sensitivity of each predictor was evaluated using ROC curves. Continuous variables are reported as mean and standard deviation. Statistical analysis was performed using SPSS 15.0. RESULTS: 30 % of the patients had male factor or tubal factor infertility; over 50% had evidence of diminished ovarian reserve. The remainder had various other etiologies of infertility. The average patient age was 36.6 5.5 years. The average day 3 FSH level was 12.9 8.9 mIU/mL. The average AMH level was 1.2 1.5 ng/ml. Clinical pregnancy was achieved by 24 of the 81 patients. The ROC curves for AMH and FSH as predictors of Clinical Pregnancy are shown above in the figure. For AMH the area under the ROC curve was 0.68; 95% CI 0.53 to 0.80; p ¼ 0.018. The inflection point for AMH with maximal sensitivity and specificity for prediction of clinical pregnancy was between 0.8 and 1.1 ng/ mL. For FSH the area under the ROC curve did not significantly deviate from the diagonal (p¼ 0.74). Pregnancy occurred among 44% of patients with AMH > 0.8 ng/mL (15/34) and only 19% (9/47) of those with AMH <¼ 0.8 ng/mL (Chi Square 5.9; p ¼ 0.015). CONCLUSIONS: Among patients preparing to undergo an IVF cycle, AMH is a better predictor of pregnancy than is day 3 FSH. If confirmed by larger scale studies, AMH levels should replace FSH evaluations as routine assessments of ovarian reserve prior to IVF. Supported by: Foundation for Reproductive Medicine.
FERTILITY & STERILITYÒ
Time Interval Between Pre and PostAMH Blood Samples Pre AMH Post AMH Subjects (months) Levels (ng/dl) Levels (ng/dl) P Value 1 2 3 4 5 6 Mean
18 16 16 5 4 2
1.1 0.7 1.4 0.4 0.4 3.6 1.27 + 1.21
0.2 0.3 1.4 0.2 0.1 2.1 0.72 + 0.83
0.059
CONCLUSIONS: The results from this small pilot study show a decrease in AMH levels following myomectomy. Larger, prospective studies that exam ovarian reserve after operative and non-operative treatment of uterine fibroids will be necessary to identify the treatment that has the least impact on ovarian reserve. Supported by: In part, by the Intramural Research Program of the Reproductive Biology and Medicine Branch, NICHD, NIH.
A-317 CORRELATION BETWEEN BASAL ANTI MULLERIAN HORMONE AND FOLLICLE STIMULATING HORMONE WITH NUMBERS OF MATURE OOCYTE DURING IN VITRO FERTILIZATION. T. Djuwantono, H. Harlianto, W. Permadi, D. Nataprawira, N. Astarto, R. Anwar. Obgyn, Medical Faculty University of Padjadjaran, ASTER Fertility Clinic, Hasan Sadikin Hospital, Bandung, Indonesia. OBJECTIVE: To determine whether there’s any correlation between level of Anti Mullerian Hormone (AMH) and basal Follicle Stimulating Hormone (FSH) on day-3 and number of mature oocytes at the time of ovum pick up procedure during in vitro fertilization program. DESIGN: Prospective cohort study. MATERIALS AND METHODS: A correlational analytic with prospective cohort study was conducted on 47 women who had undergone a controlled ovarian stimulation with long protocol during IVF program in Aster Fertility Clinic, Department of Obstetrics and Gynecology, Dr. Hasan Sadikin
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A-309 ABNORMAL DISTRIBUTION OF CORTICAL GRANULES IN CYNOMOLGUS MONKEY ONE-DAY OLD MII OOCYTES WHICH WERE IMMATURE AT OOCYTE RETRIVAL AFTER CONTROLLED OVARIAN HYPERSTIMULATION. M. Yamanaka, S. Hashimoto, J. Okahara-Narita, J. Yamasaki, R. Torii, Y. Morimoto. IVF Namba Clinic, Osaka, Japan; Shiga University of Medical Science, Shiga, Japan. OBJECTIVE: Developmental competence of cynomolgus monkey (macaca fascicularis) oocytes, which were immature at oocyte retrieval after controlled ovarian hyperstimulation (COH) and reached to metaphase II stage (MII, 1-day old MII oocytes) after overnight culture, were low compared with mature oocytes at oocyte retrieval (fresh MII oocytes). In this study, ultrastructures of 1-day old and fresh MII oocytes were assessed. DESIGN: An experimental study using a monkey model was performed. MATERIALS AND METHODS: Female cynomolgus monkey (5 years old) was used for COH and oocyte retrieval was carried out using a laparoscope. Cumulus cells were removed from oocyte using hyaluronidase. Some of immature (germinal vesicle (GV) and metaphase I (MI)) and mature (fresh MII) oocytes were fixed for control as below. Immature oocytes were cultured in TCM199 supplemented with 5% fetal calf serum for 24h. Control and 1-day old MII oocytes were prefixed by glutaraldehyde, postfixed by osmium, dehydrated and embedded in EPON blocks. Ultrathin sections were observed by transmission electron microscope (TEM) after staining. RESULTS: Fifty oocytes (14 GV, 21 MI, 9 MII and 6 degenerated oocytes, respectively) were retrieved. Immature oocytes (12 GV and 19 MI) were cul-
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Abstracts
tured. Seven mature oocytes were obtained. By observation using TEM, the morphological change of mitochondria during meiotic maturation was assessed. Mitochondria were oval at GV stage and some of them extended at MI stage. Flattened and crescent-shaped mitochondria which encircled smooth endoplasmic reticulum were observed in both fresh and 1-day old MII oocytes. However, in 1-day old MII oocytes, cortical granules were observed not only in the surface but also inside of oocyte. In addition, large fragments were observed in the perivitelline space. Microvilli were observed in all oocytes. CONCLUSIONS: These results suggest that cytoplasmic maturation is incomplete in 1-day old MII oocyte because of improper localization of cortical granules. The unbalance of maturation between nucleus and cytoplasm may impair the developmental competence of 1-day old MII oocyte. Supported by: None. A-310 ANALYSIS OF MEIOTIC ABNORMALITIES OF IN VITRO MATURED OOCYTES FROM STIMULATED CYCLES OF NON-OBESE ENDOMETRIOTIC AND PCOS PATIENTS: A PILOT STUDY. P. A. A. S Navarro, R. A. Ferriani, R. C. Vieira, E. M. Ferreira, A. C. J. S Rosa e Silva, I. D. E. S Barcelos. Department of Obstetrics and Gynecology, Ribeira˜o Preto Medical School-USP, Ribeira˜o Preto, Brazil; Ribeira˜o Preto Medical School-USP, Ribeira˜o Preto, Brazil. OBJECTIVE: Endometriosis and Polycystic Ovarian Syndrome (PCOS) are major causes of human infertility. According to controversial data, both may be associated with worse outcomes of assisted reproduction techniques, which could be caused by an impairment of oocyte quality. Thus, we compared meiotic spindle morphology and chromosomal distribution of in vitro matured human oocytes from non-obese patients with endometriosis and PCOS submitted to ovarian stimulation for ICSI. DESIGN: A prospective, controlled study. MATERIALS AND METHODS: Infertile patients aged up to 38 years undergoing stimulated cycles for oocyte retrieval for ICSI were selected prospectively and consecutively and divided into endometriosis (20 patients) and PCOS (13 patients) groups. Immature oocytes (74 and 34 from endometriosis and PCOS patients, respectively) were submitted to in vitro maturation (IVM) for 19 hours 1 hour (GV) or 4 hours 30 minutes (MI) according to a maturation time curve determined before the beginning of the present study. Using immunostaining and fluorescence microscopy, we imaged spindle and chromosomal distribution of oocytes that extruded the first polar body after IVM. RESULTS: IVM rates were similar for both groups (53.1% and 50%, respectively, for the PCOS and control groups). Spindle and chromosome organization were observed in 35 and 17 oocytes from the endometriosis and PCOS groups, respectively. In the endometriosis group, 13 were normal MII oocytes (37.2%), 9 abnormal MII (25.7%), 11 normal telophase I (31.4%), and 2 normal telophase II (5.7%). In the PCOS group, 6 oocytes were normal MII (35.3%), 8 abnormal MII (47.1%), and 3 normal telophase I (17.6%). The proportions of normal MII oocytes were similar for the two groups (37.2% and 35.3% in endometriosis and PCOS groups, respectively). CONCLUSIONS: Our preliminary data demonstrate that in vitro maturation rates of immature oocytes obtained from stimulated cycles are similar in non-obese infertile women with endometriosis and with PCOS. In vitro matured oocytes from endometriotic patients have a higher percentage of TI when compared to PCOS patients. Our preliminary results also suggest that the incidence of meiotic anomalies, characterized by spindle rupture and/or chromosome misalignment, is similar in in vitro matured oocytes from non-obese PCOS and endometriotic patients. Both results will be better evaluated by increasing the present patient series. Supported by: CAPES, CNPq, and FAEPA/HC-FMRP/USP, Brazil.
A-313
OVARIAN RESERVE
WHICH PATIENT DO YOU PREFER IN THE OFFICE? YOUNGER WITH ELEVATED FSH OR ELDERLY WITH NORMAL FSH. E. Young, Jr, L. Sabatini, M. I. Viola, F. Lorenzo, L. M. Auge, H. Beraja. Gynecology, IFER, Buenos Aires, Capital Federal, Argentina. OBJECTIVE: Analyze which factor has more impact as a predictor of response in IVF outcomes: age or basal FSH. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Of the 268 patients who carried out an IVF treatment with antagonist GnRh cycles from February to August 2005, 128 met the inclusion criteria (% 35 years and FSH R 7.71 and > 35 years and FSH < 7.71).Main outcome measure were: Cause of infertility,
Vol. 90, Suppl 1, September 2008
number of follicles, number of oocytes, MII oocytes, embryo quality, pregnancy rate, miscarriage rate, ectopic pregnancy rate, live birth rate. RESULTS: A hundred and twenty eight (128) patients were selected and divided into two groups: Group A: % 35 years and FSH R 7.71 (56) and Group B: > 35 years and FSH < 7.71 (72), comparing the reproductive outcome. Patients in group B showed a significantly greater number of follicles, gathered number of oocytes and MII oocytes (p ¼ <0.005). But group A showed a greater trend on pregnancy rates and live birth, although this was not statistically significant (p¼ NS). TABLE 1.
No. of follicles No. of oocytes retrieved No. of MII Clinical pregnancy rate Miscarriage rate Live birth Rate
< 35 years and FSH > 7.71 (56)
>35 years and FSH <7.71 (72)
6.80 3.33 6.29 3.70
8.74 4.29 9.17 5.22
<0.05 <0.05
4.71 2.72 17/56 (30%)
7.06 4.12 18/72 (25%)
<0.05 NS
1/17 (1.7%) 22/56 (39%)
3/18 (4.61%) 19/72 (26%)
<0.05 NS
p
CONCLUSIONS: Both basal FSH and age contributed to the prediction of the quantitative ovarian reserve as reflected by the number of oocytes collected. However, age is a better predictor of pregnancy potential for women undergoing IVF. Supported by: None.
A-316 MYOMECTOMY MAY DECREASE AMH LEVELS: A PILOT STUDY. H. N. Browne, L. Nieman, T. Williams, Q. Wei, J. Spies, A. Armstrong. Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda; Howard University College of Medicine, Washington, DC; Interventional Radiology/Department of Radiology, Georgetown University Hospital, Washington, DC. OBJECTIVE: The impact of myomectomy on ovarian reserve is unknown. However, it is considered to be the preferred treatment in patients desiring future fertility. It has not been shown to adversely impact ovarian reserve as measured by FSH. However, recent studies have suggested that AMH is a more sensitive and accurate predictor of ovarian reserve compared to FSH. Our objective was to examine the impact of myomectomy on ovarian reserve as measured by AMH. DESIGN: A prospective, observational study. MATERIALS AND METHODS: Pre and post-operative AMH levels were obtained from six women with symptomatic uterine fibroids to assess the effect of myomectomy on ovarian reserve. These women were enrolled in a Phase II clinical trial, at the NIH, that used the selective progesterone receptor modulator (CDB-2914). Patients with a FSH > 20 mIU/L were excluded from the study. Post-operative AMH levels were drawn between 2 to 18 months after surgery. Statistical analysis was performed with a paired t-test, and the results are presented as the mean SD. A p value of < 0.05 was considered to be statistically significant. RESULTS: The mean age was 37 3.2 and 38 2.9 years before and after surgery, respectively. Mean pre and post-myomectomy serum AMH levels were 1.27 1.21 and 0.72 0.83, respectively (p¼ 0.059). A notable decrease was seen in AMH levels before and after surgery; however, this difference was not statistically significant (Table 1). TABLE 1.
A-315 COMPARISON OF PREDICTIVE VALUE OF ANTI-MULLERIAN HORMONE (AMH) AND DAY 3 FOLLICLE STIMULATING HORMONE FOR PREGNANCY AND OOCYTE RETRIEVAL. D. H. Barad, K. Oktay, A. Weghofer, N. Gleicher. Center for Human Reproduction, New York, NY; New York Medical College, Valhalla, NY; Vienna University School of Medicine, Vienna, Austria. OBJECTIVE: Follicle stimulating hormone (FSH) and anti-Mu¨llerian hormone (AMH) have both been widely reported to correlate to ovarian reserve and in vitro fertilization (IVF) outcomes. A study, comparing FSH and AMH as predictors of pregnancy in IVF, has, however, not been reported before. DESIGN: Cross-sectional survey of existing clinical data. MATERIALS AND METHODS: We investigated in a convenience sample of 90 consecutive IVF patients whether FSH and AMH levels correlated to clinical pregnancy rates after in-vitro fertilization and embryo transfer. FSH levels were obtained on cycle days 2-3, while AMH was drawn at random. Both hormones were measured by standard commercial assay systems. Clinical pregnancy was defined as an ongoing intrauterine pregnancy of greater than 8 weeks with active fetal heart beat. Sensitivity of each predictor was evaluated using ROC curves. Continuous variables are reported as mean and standard deviation. Statistical analysis was performed using SPSS 15.0. RESULTS: 30 % of the patients had male factor or tubal factor infertility; over 50% had evidence of diminished ovarian reserve. The remainder had various other etiologies of infertility. The average patient age was 36.6 5.5 years. The average day 3 FSH level was 12.9 8.9 mIU/mL. The average AMH level was 1.2 1.5 ng/ml. Clinical pregnancy was achieved by 24 of the 81 patients. The ROC curves for AMH and FSH as predictors of Clinical Pregnancy are shown above in the figure. For AMH the area under the ROC curve was 0.68; 95% CI 0.53 to 0.80; p ¼ 0.018. The inflection point for AMH with maximal sensitivity and specificity for prediction of clinical pregnancy was between 0.8 and 1.1 ng/ mL. For FSH the area under the ROC curve did not significantly deviate from the diagonal (p¼ 0.74). Pregnancy occurred among 44% of patients with AMH > 0.8 ng/mL (15/34) and only 19% (9/47) of those with AMH <¼ 0.8 ng/mL (Chi Square 5.9; p ¼ 0.015). CONCLUSIONS: Among patients preparing to undergo an IVF cycle, AMH is a better predictor of pregnancy than is day 3 FSH. If confirmed by larger scale studies, AMH levels should replace FSH evaluations as routine assessments of ovarian reserve prior to IVF. Supported by: Foundation for Reproductive Medicine.
FERTILITY & STERILITYÒ
Time Interval Between Pre and PostAMH Blood Samples Pre AMH Post AMH Subjects (months) Levels (ng/dl) Levels (ng/dl) P Value 1 2 3 4 5 6 Mean
18 16 16 5 4 2
1.1 0.7 1.4 0.4 0.4 3.6 1.27 + 1.21
0.2 0.3 1.4 0.2 0.1 2.1 0.72 + 0.83
0.059
CONCLUSIONS: The results from this small pilot study show a decrease in AMH levels following myomectomy. Larger, prospective studies that exam ovarian reserve after operative and non-operative treatment of uterine fibroids will be necessary to identify the treatment that has the least impact on ovarian reserve. Supported by: In part, by the Intramural Research Program of the Reproductive Biology and Medicine Branch, NICHD, NIH.
A-317 CORRELATION BETWEEN BASAL ANTI MULLERIAN HORMONE AND FOLLICLE STIMULATING HORMONE WITH NUMBERS OF MATURE OOCYTE DURING IN VITRO FERTILIZATION. T. Djuwantono, H. Harlianto, W. Permadi, D. Nataprawira, N. Astarto, R. Anwar. Obgyn, Medical Faculty University of Padjadjaran, ASTER Fertility Clinic, Hasan Sadikin Hospital, Bandung, Indonesia. OBJECTIVE: To determine whether there’s any correlation between level of Anti Mullerian Hormone (AMH) and basal Follicle Stimulating Hormone (FSH) on day-3 and number of mature oocytes at the time of ovum pick up procedure during in vitro fertilization program. DESIGN: Prospective cohort study. MATERIALS AND METHODS: A correlational analytic with prospective cohort study was conducted on 47 women who had undergone a controlled ovarian stimulation with long protocol during IVF program in Aster Fertility Clinic, Department of Obstetrics and Gynecology, Dr. Hasan Sadikin
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