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Anti Mullerian hormone (AMH) levels predict cardiovascular risk assessment in young women with PCOS
of OHSS, especially in patients with PCO. IVM is a relatively new option for ART promising significant benefits, but still controversial. However, we have been using IVM as a first choice of ART mainly for PCO patients for more than 10 years. The present study was conducted to validate if IVM was clinically useful for infertility by analyzing all pregnant cases of the last 10 years. DESIGN: Retrospective clinical study at private setting fertility clinic. MATERIALS AND METHODS: Three hundred and thirty six cycles of IVM performed from January 2004 to December 2013 were analyzed retrospectively. Ultrasound monitoring was started from day 7 of menstrual cycle and oocyte retrieval was performed when the smallest follicle reached 7 mm in diameter. Regardless of the choice of priming, HCG 10,000 units was administered and followed by oocyte retrieval 38 hours later. When endometrium was thicker than 8mm at oocyte retrieval, fresh embryo transfer was performed. Otherwise, all embryos were vitrified for frozen transfer cycle. Frozen cycles were not included in the present study. Clinical outcomes such as number of oocytes retrieved, maturation rate, embryo transfer rate, and clinical pregnancy rate (GS positive) were analyzed. Moreover, appropriate timing for oocyte retrieval was evaluated. RESULTS: Average number of oocyte retrieved was 10.4 (3498 oocytes per 336 retrievals) and maturation rate was 47.8 % (1683 metaphase two/ 3498 retrieved oocytes). Fresh cycle embryo transfer rate was 47.8% (216 transfers per 336 retrievals). Oocyte retrievals on PCO patient rate was 66.9% (225 cycle per 336 cycles). Clinical pregnancy rate with gestational sac was 31.5% (68 pregnancies per 216 transfers) and 53 babies were born without any congenital abnormality. Appropriate cycle day for IVM oocyte retrieval was day 15.4 (between day 9 and 28) for fresh cycle. However, PCO patients have wide ranges of menstrual cycle days. Therefore, we determined appropriate timing of retrieval by the percentage of individual menstrual cycle length. Thirty three percent of cycle length is appropriate for retrievals in fresh cycle. Average estradiol value of pregnant patients on the day of HCG was 192 pg/ml. CONCLUSIONS: Average clinical pregnancy rate of IVM was 31.5% and it was considered acceptable for clinical validity not only because of less physical and financial burdens, but also absolute no risk of OHSS. Overall, IVM is a valid treatment of ART especially for PCO patients when appropriately performed. References: Validation of clinical IVM.
P-57 Tuesday, October 20, 2015 CLINICAL OUTCOME OF PCOS PATIENTS UNDERGOING ASSISTED REPRODUCTIVE TECHNOLOGY: THE ROLE OF IN VITRO MATURATION. T. Takeuchi,a N. Aono,a N. Oka,a R. Obata,a N. Okuyama,a S. Yanagihori,a T. Okuda,a K. Kyono.a,b aKyono ART Clinic Takanawa, Minatoku, Tokyo, Japan; bKyono ART Clinic, Sendai, Miyagi, Japan. OBJECTIVE: Assisted reproductive technology in PCOS patients is often associated with ovarian hyperstimulation syndrome (OHSS). The severe form of OHSS is an iatrogenic complication and possibly a life-threatening condition resulting from ovarian stimulation. In vitro maturation (IVM) techniques have been developed and employed in clinical settings to circumvent OHSS by minimizing or eliminating gonadotropin administration. The aim of this study was to assess the efficacy of IVM in PCOS patients by comparing its clinical outcome with that of conventional ovarian stimulation protocols. DESIGN: Retrospective review of clinical outcome in PCOS patients. MATERIALS AND METHODS: The average maternal age of the patients involved was 32.6 3 years. In IVM cycles, no gonadotropin was administered, but 10,000 IU of hCG 36 hours prior to oocyte retrieval. Oocytes were cultured in an IVM medium for 24 hours and were inseminated by ICSI. The endometrium was prepared by administering estradiol from the day of oocyte retrieval, followed by luteal support. When IVM cycles were not successful, same patients underwent controlled ovarian stimulation (COS) for harvesting mature oocytes. Embryological parameters, clinical outcome and complications were compared between IVM and COS cycles. RESULTS: A total of 20 consenting PCOS patients underwent 22 IVM treatment cycles. Following unsuccessful IVM treatment 14 patients underwent 24 COS cycles. The average number of retrieved oocytes in IVM cycles was 16.9 7, with the maturation and fertilization rate being 41.7% and 49.0%, respectively, while these were 10.4 3, 80.8% and 52.7%, respectively in COS cycles. IVM yielded more oocytes; however, the number of fertilized oocytes was similar between the two. Only mild or moderate form of OHSS was observed in 15 out of 24 (62.5%) COS cycles, while none developed in IVM cycles. Following fresh and frozen transfers, 8 out
FERTILITY & STERILITYÒ
of 20 (40.0%) became pregnant in IVM; similarly, 26 transfers resulted in 10 (41.7%) pregnancies in COS. Pregnancy rate per patient was 33.3% (6/ 20) in IVM, and 57.1% (8/14) in COS, cumulatively 70% (14/20). CONCLUSIONS: Overall clinical pregnancy rate of PCOS patients following ART was 70%. IVM completely eliminated OHSS and reduced costs while maintaining a satisfactory pregnancy rate. Thus, IVM can be offered to PCOS patients undergoing ART as a first line treatment. P-58 Tuesday, October 20, 2015 ANTI MULLERIAN HORMONE (AMH) LEVELS PREDICT CARDIOVASCULAR RISK ASSESSMENT IN YOUNG WOMEN WITH PCOS. R. Feldman,a,b S. Butts,c A. Dokras.a,b aUniversity of Pennsylvania, Philadelphia, PA; bObstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA; cPerelman School of Medicine, Philadelphia, PA. OBJECTIVE: Serum levels of anti-mullerian hormone (AMH), a member of the TGFb family, are elevated in women with PCOS. There is conflicting information in women with and without PCOS regarding the association between low AMH levels and increased cardiometabolic risk. Young women with PCOS have an increased risk of metabolic syndrome and we hypothesized that serum AMH levels would predict risk of metabolic syndrome in this population. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Women seen at the Penn PCOS center from 2010-2014 with complete metabolic work up were included in this study (n¼469). Metabolic syndrome (Met Syn) was defined by modified NCEP-ATP III criteria (BMIR30, sBP/dBPR135/85mmHg or taking antihypertensives medications, fasting glucose R100mg/ml or taking medications for diabetes, TGR150mg/ml, HDL-C %50mg/ml). AMH was measured using the Gen II ELISA, lipids were measured by standard enzymatic methods and total testosterone was measured by radioimmunoassay. Spearman correlation coefficients were used to determine relationships between continuous variables. Linear regression was used to model associations between AMH and lipids adjusting for confounders. AMH was dichotomized based on tertiles and univariate tests and logistic regression modeling were used to evaluate associations of selected variables with tertiles of AMH. RESULTS: The median AMH level in the entire cohort was 5.06ng/ml (IQR 3.08-7.97) . The mean age of the group was 27.66years, 42.1% were non-white and 8.1% were smokers. The overall prevalence of Met Syn was 19%. AMH levels positively correlated with total testosterone (p<0.008). On examination of individual components of Met Syn, AMH levels positively correlated with HDL-C (p<0.001) and negatively correlated with fasting glucose (p<0.004), total insulin (p<0.001), BMI (p<0.001), systolic and diastolic BP (p<0.003, p<0.005 respectively). AMH did not have a significant correlation with smoking, LDL-C, TG, CRP, DHEAS and SHBG. Total testosterone did not correlate with individual components of Met Syn. For every unit increase in AMH the odds of Met Syn decreased by 10% (OR 0.9 (0.83-0.97) in the univariate model (p¼0.01) and in the multivariate model (p<0.02). The OR for Met Syn for women in the lowest AMH tertile compared to those in the highest AMH tertile was 2.3 (95% CI 1.1-4.6, p¼0.02). Adjusted for age, race and testosterone the OR for Met Syn in the lowest AMH tertile was 2.1 (95% CI 1.01-4.3, p¼0.04). Total testosterone did not predict risk of Met Syn (p¼0.5). CONCLUSIONS: Our findings indicate that AMH levels, independent of age, race and testosterone are a strong predictor of Met Syn risk in young women with PCOS. Although the causal or temporal relationship for our findings is unclear, our study suggests that metabolic risk in young women with PCOS is influenced by the ovarian hormone AMH but not testosterone. P-59 Tuesday, October 20, 2015 ESTIMATION OF SERUM AMH LEVEL ON DAY 7 OF CONTROLLED OVARIAN STIMULATION WITH ANTAGONIST IS AN EARLY PREDICTOR OF OHSS IN HIGH RESPONDER WOMEN WITH PCOS. N. M. Chimotea B. N. Chimote.b aEmbryology/Endocrinology, Vaunshdhara Clinic and Assisted Conception Centre, Nagpur, India; bVaunshdhara Clinic and Assisted Conception Centre, Nagpur, India. OBJECTIVE: Controlled Ovarian Hyperstimulation (COH) in IVF cycles exposes PCOS women to a higher chance of going into ovarian hyperstimulation syndrome (OHSS) due to recruitment of higher number of follicles. Baseline serum AMH level although being routinely used as a marker for
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P-57 Tuesday, October 20, 2015 CLINICAL OUTCOME OF PCOS PATIENTS UNDERGOING ASSISTED REPRODUCTIVE TECHNOLOGY: THE ROLE OF IN VITRO MATURATION. T. Takeuchi,a N. Aono,a N. Oka,a R. Obata,a N. Okuyama,a S. Yanagihori,a T. Okuda,a K. Kyono.a,b aKyono ART Clinic Takanawa, Minatoku, Tokyo, Japan; bKyono ART Clinic, Sendai, Miyagi, Japan. OBJECTIVE: Assisted reproductive technology in PCOS patients is often associated with ovarian hyperstimulation syndrome (OHSS). The severe form of OHSS is an iatrogenic complication and possibly a life-threatening condition resulting from ovarian stimulation. In vitro maturation (IVM) techniques have been developed and employed in clinical settings to circumvent OHSS by minimizing or eliminating gonadotropin administration. The aim of this study was to assess the efficacy of IVM in PCOS patients by comparing its clinical outcome with that of conventional ovarian stimulation protocols. DESIGN: Retrospective review of clinical outcome in PCOS patients. MATERIALS AND METHODS: The average maternal age of the patients involved was 32.6 3 years. In IVM cycles, no gonadotropin was administered, but 10,000 IU of hCG 36 hours prior to oocyte retrieval. Oocytes were cultured in an IVM medium for 24 hours and were inseminated by ICSI. The endometrium was prepared by administering estradiol from the day of oocyte retrieval, followed by luteal support. When IVM cycles were not successful, same patients underwent controlled ovarian stimulation (COS) for harvesting mature oocytes. Embryological parameters, clinical outcome and complications were compared between IVM and COS cycles. RESULTS: A total of 20 consenting PCOS patients underwent 22 IVM treatment cycles. Following unsuccessful IVM treatment 14 patients underwent 24 COS cycles. The average number of retrieved oocytes in IVM cycles was 16.9 7, with the maturation and fertilization rate being 41.7% and 49.0%, respectively, while these were 10.4 3, 80.8% and 52.7%, respectively in COS cycles. IVM yielded more oocytes; however, the number of fertilized oocytes was similar between the two. Only mild or moderate form of OHSS was observed in 15 out of 24 (62.5%) COS cycles, while none developed in IVM cycles. Following fresh and frozen transfers, 8 out
FERTILITY & STERILITYÒ
of 20 (40.0%) became pregnant in IVM; similarly, 26 transfers resulted in 10 (41.7%) pregnancies in COS. Pregnancy rate per patient was 33.3% (6/ 20) in IVM, and 57.1% (8/14) in COS, cumulatively 70% (14/20). CONCLUSIONS: Overall clinical pregnancy rate of PCOS patients following ART was 70%. IVM completely eliminated OHSS and reduced costs while maintaining a satisfactory pregnancy rate. Thus, IVM can be offered to PCOS patients undergoing ART as a first line treatment. P-58 Tuesday, October 20, 2015 ANTI MULLERIAN HORMONE (AMH) LEVELS PREDICT CARDIOVASCULAR RISK ASSESSMENT IN YOUNG WOMEN WITH PCOS. R. Feldman,a,b S. Butts,c A. Dokras.a,b aUniversity of Pennsylvania, Philadelphia, PA; bObstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA; cPerelman School of Medicine, Philadelphia, PA. OBJECTIVE: Serum levels of anti-mullerian hormone (AMH), a member of the TGFb family, are elevated in women with PCOS. There is conflicting information in women with and without PCOS regarding the association between low AMH levels and increased cardiometabolic risk. Young women with PCOS have an increased risk of metabolic syndrome and we hypothesized that serum AMH levels would predict risk of metabolic syndrome in this population. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Women seen at the Penn PCOS center from 2010-2014 with complete metabolic work up were included in this study (n¼469). Metabolic syndrome (Met Syn) was defined by modified NCEP-ATP III criteria (BMIR30, sBP/dBPR135/85mmHg or taking antihypertensives medications, fasting glucose R100mg/ml or taking medications for diabetes, TGR150mg/ml, HDL-C %50mg/ml). AMH was measured using the Gen II ELISA, lipids were measured by standard enzymatic methods and total testosterone was measured by radioimmunoassay. Spearman correlation coefficients were used to determine relationships between continuous variables. Linear regression was used to model associations between AMH and lipids adjusting for confounders. AMH was dichotomized based on tertiles and univariate tests and logistic regression modeling were used to evaluate associations of selected variables with tertiles of AMH. RESULTS: The median AMH level in the entire cohort was 5.06ng/ml (IQR 3.08-7.97) . The mean age of the group was 27.66years, 42.1% were non-white and 8.1% were smokers. The overall prevalence of Met Syn was 19%. AMH levels positively correlated with total testosterone (p<0.008). On examination of individual components of Met Syn, AMH levels positively correlated with HDL-C (p<0.001) and negatively correlated with fasting glucose (p<0.004), total insulin (p<0.001), BMI (p<0.001), systolic and diastolic BP (p<0.003, p<0.005 respectively). AMH did not have a significant correlation with smoking, LDL-C, TG, CRP, DHEAS and SHBG. Total testosterone did not correlate with individual components of Met Syn. For every unit increase in AMH the odds of Met Syn decreased by 10% (OR 0.9 (0.83-0.97) in the univariate model (p¼0.01) and in the multivariate model (p<0.02). The OR for Met Syn for women in the lowest AMH tertile compared to those in the highest AMH tertile was 2.3 (95% CI 1.1-4.6, p¼0.02). Adjusted for age, race and testosterone the OR for Met Syn in the lowest AMH tertile was 2.1 (95% CI 1.01-4.3, p¼0.04). Total testosterone did not predict risk of Met Syn (p¼0.5). CONCLUSIONS: Our findings indicate that AMH levels, independent of age, race and testosterone are a strong predictor of Met Syn risk in young women with PCOS. Although the causal or temporal relationship for our findings is unclear, our study suggests that metabolic risk in young women with PCOS is influenced by the ovarian hormone AMH but not testosterone. P-59 Tuesday, October 20, 2015 ESTIMATION OF SERUM AMH LEVEL ON DAY 7 OF CONTROLLED OVARIAN STIMULATION WITH ANTAGONIST IS AN EARLY PREDICTOR OF OHSS IN HIGH RESPONDER WOMEN WITH PCOS. N. M. Chimotea B. N. Chimote.b aEmbryology/Endocrinology, Vaunshdhara Clinic and Assisted Conception Centre, Nagpur, India; bVaunshdhara Clinic and Assisted Conception Centre, Nagpur, India. OBJECTIVE: Controlled Ovarian Hyperstimulation (COH) in IVF cycles exposes PCOS women to a higher chance of going into ovarian hyperstimulation syndrome (OHSS) due to recruitment of higher number of follicles. Baseline serum AMH level although being routinely used as a marker for
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