- Email: [email protected]
Evaluation of sonographic and biochemical markers of clomiphene citrate resistance in polycystic ovary syndrome
qRT-PCR. Spearman correlation compared FF cortisol/cortisone levels with CC lipid content and patient/IVF cycle parameters. Wilcoxon rank sum test compared FF cortisol:cortisone ratios in clinically pregnant (fetal heartbeat) vs. non-pregnant cycles. RESULTS: FF cortisol levels (5.82.0 mg/dL) inversely correlated with CC lipid content (6340 fluorescent units; R¼-0.4, P<0.025) and maternal age (R¼-0.3, P<0.05); FF cortisol and CC lipid remained correlated adjusting for age (R¼-0.45, P<0.01). Age-adjusted FF cortisol levels positively correlated with numbers of total and mature oocytes retrieved (R¼0.4, P<0.025) but not with amounts of FSH/HMG given (P¼0.2). The FF cortisol/cortisone ratio was higher in pregnancy cycles (4.7 [4.0-5.4]) than non-pregnancy cycles (3.7 [3.5-4.4], P<0.025), and tended to remain higher adjusting for age (P¼0.07). CCs expressed mRNA for NR3C1 (0.077 0.147), 11-bHSD1 as a major isoform (11-bHSD1 [1.647 1.581]; 11bHSD2 [0.009 0.017]: 183 fold-increase, p<0.001) and LPL as a major lipolytic enzyme (LPL [0.033 0.029]; HSL [0.00006 0.00018]: 577fold increase, p<0.001). CONCLUSION: Cortisol production by the periovulatory follicle may promote CC lipid metabolism during human oocyte development. Supported by: Stein/Oppenheimer Endowment; UCLA OB/GYN Dept. P-353 Wednesday, October 22, 2014 VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND PLACENTAL GROWTH FACTOR (PLGF) DIRECTLY CORRELATE WITH OVARIAN FOLLICLE SIZE IN WOMEN UNDERGOING IN VITRO FERTILIZATION (IVF). L. Hou, R. N. Taylor, Y. Shu, E. B. Johnston-MacAnanny, T. M. Yalcinkaya. Section of Reproductive Endocrinology-Infertility, Wake Forest School of Medicine, Winston-Salem, NC. OBJECTIVE: To assess VEGF and PlGF concentrations in FF from women undergoing IVF, stratified according to follicle size, and to correlate these with VEGF and PlGF mRNA expression in corresponding luteinized granulosa cells (GC), as a follow-up of our previous demonstration that these genes are expressed in GC(1). DESIGN: Prospective sample collection for in vitro studies. MATERIALS AND METHODS: 18 consenting subjects with normal ovarian function (IVF being undertaken due to male factor) were recruited prior to oocyte retrieval (mean age of the women ¼ 31 years). Only bloodfree FF obtained with the first puncture of each ovary was collected, without the use of flushing media to avoid dilution of the FF contents. All specimens were categorized and analyzed as FF derived from small follicles (8-14 mm diameter) or large follicles (>14 mm diameter). VEGF and PlGF concentrations in the FF were measured using validated commercial ELISAs (RayBioÒ). Levels of FF estradiol (E2) and progesterone (P4) were determined by RIA. VEGF and PlGF mRNA expression was evaluated by real time RT-PCR, using cultured GC derived from the small and large follicles as indicated above. We also evaluated the expression of other relevant ovarian genes. RESULTS: FF VEGF concentrations from large follicles were markedly higher (6788 2863 pg/ml) compared to those in small follicles (1942 879 pg/ml, p ¼ 0.0003). PlGF concentrations in FF from large follicles also was higher (2004 816 pg/ml) than in small follicles (1144 898 pg/ml, p ¼0.002). By RT-PCR, the expression of VEGF mRNA was 2.5 fold greater in GC from large follicles than from small follicles. However, we observed no significant statistical differences in PlGF mRNA expression relative to follicle size. As expected, expression of mRNAs encoding steroidogenic acute regulatory protein (StAR), anti-mullerian hormone (AMH) and aromatase P450 (CYP19) were all increased in cells from large follicles as compared with those from small follicles. CONCLUSION: VEGF and PlGF protein concentrations in FF are correlated with follicle size; this relationship also applied to E2 concentration and StAR, AMH and CYP19 expression. Moreover, VEGF and PlGF levels were significantly higher in FF than in matched serum. Similar trends were noted for VEGF mRNA, but not PlGF mRNA expression from cultured GC. We conclude that local VEGF and PlGF gene expression are likely to mediate ovarian follicle angiogenesis and may contribute to oocyte development, maturation and selection of dominant follicle. Supported by: Ob/Gyn departmental research fund. P-354 Wednesday, October 22, 2014 THE FUNCTION OF MITOCHONDRIA IN CUMULUS CELLS OF PCOS PATIENTS. H.-C. Zhao, Y. Yu, J. Qiao. Peking University Third Hospital, Beijing, China.
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OBJECTIVE: To assess the the changes of mitochondrial function in cumulus cells of PCOS patients; to explore the potential impact of PCOS on follicular microenvironment; to improve the growth and development of PCOS patients’ follicle and oocyte. DESIGN: Cumulus cell was taken on oocyte retrieval day from 80 PCOS women and 91 controls underwent intracytoplasmic sperm injection (ICSI) treatment. The function of mitochondrial in cumulus cells was assessed. MATERIALS AND METHODS: The ultrastructure of mitochondria was observed by transmission electron microscopy (TEM). The mitochondrial membrane potential was assessed using MitoPT-JC1 assay kit by flow cytometer. The localization of mitochondrial was assessed by immunofluorescence with Mito Tracker Green. MtDNA content and expression of PGC-1a were detected by real-time PCR. The methylation of PGC-1a promoter was detected by methylation-specific real-time PCR. The levels of ATP were detected by chemiluminescence. RESULTS: The mitochondria in cumulus from PCOS patients showed an increased frequency of fragmented mitochondria, a decreased transmembrane potential, an aggregated distribution of mitochondria and a decreased mtDNA content with a decrease PGC-1a mRNA expression and hypermethylation of PGC-1a promoter. However, the level of ATP in cumulus from PCOS patients showed no change. CONCLUSION: The dysfunction of mitochondria in cumulus cells from PCOS patients may play a role in the pathogenesis of PCOS and may affect the follicle growth and oocyte development. Supported by: This work was Supported in part by the Ministry of Science and Technology of China Grants (973 program; 2011CB944504) to J.Q., and by the National Natural Science Funds for Young Scholars (31000661) to Y.Y., and by the National Natural Science Foundation of China (General Program) (81070534 to P.L.; 31371521 to Y.Y.).
OBESITY AND METABOLISM P-355 Wednesday, October 22, 2014 EVALUATION OF SONOGRAPHIC AND BIOCHEMICAL MARKERS OF CLOMIPHENE CITRATE RESISTANCE IN POLYM. Salah,a CYSTIC OVARY SYNDROME. A. F. Amen,a b c a a H. Abozeid, M. Elbaz, E. Badran. OB/Gyn, Assiut University, Assiut, Egypt; bRadiodiagnostics, Assiut University, Assiut, Egypt; cBiochemistery, Assiut University, Assiut, Egypt. OBJECTIVE: To investigate potential hormonal, metabolic and vascular markers implicated in resistance of polycystic ovary syndrome (PCOS) patients to clomiphene citrate. DESIGN: Cross sectional observational study. MATERIALS AND METHODS: 90 PCOS patients diagnosed by the Rotterdam criteria were recruited in a university affiliated fertility clinic . 49 patients were clomiphene citrate( CC) resistant ( failed to ovulate in response to CC 150 mg /day for 5 days for 3 successive cycles) and 41 patients were CC responders. History was taken and body mass index (BMI) was calculated, Hormonal and metabolic markers including serum luteinizing hormone (LH,), follicle stimulating hormone( FSH),total testosterone, fasting insulin, fasting glucose and homeostatic model assessment-insulin resistance (HOMA-IR) and 25 hydroxy vitamin D were evaluated in both groups. Sonographic evaluation of ovarian and uterine blood flow and carotid intima-media thickness (CIMT) were compared between the groups. RESULTS: The mean age was comparable while the BMI was significantly higher in the CC resistant group. Total testosterone, serum LH, fasting serum insulin, and HOMA-RI were significantly higher in the CC resistant group ( P values were 0.000) ,while serum 25 hydroxy vitamin D was significantly lower in CC resistant patients (16.25 9.95 ng/ml)than in the CC responders(31.88 7.24 ng/ml). Relevant sonoraphic vascular markers were examined. Ovarian artery RI( resistive index),and PI (pulsitility index) were significantly lower in CC resistant patients,RI (2.30 0.48) compared to ( 2.00 0.58 ), PI (0.45 0.50) compared to (2.17 0.61). Uterine artery PI in CC resistant patients were significantly higher(2.30 0.48) compared to(2.00 0.58)( P values were 0.0001 ) . CIMT as a marker for early atherosclerosis, was significantly higher in the CC resistant group (P value 0.0001) . Four patients of the CC resistant group had evidence of atheromatous plaques. There was no significant difference between both groups in the following (FSH, fasting glucose, uterine artery RI , and ovarian volume). CONCLUSION: The resistance of PCOS patients to CC may be affected by multiple metabolic and vascular factors. Lower levels of vitamin D may influence the potency of CC in ovulation induction in PCOS patients. The
Vol. 102, No. 3, Supplement, September 2014
asociation between CC resistance and increased CIMT could be further evaluated as a prognostic indicator of the cardiovascular risk in women with PCOS. P-356 Wednesday, October 22, 2014 BODY MASS INDEX AND BREAST CANCER: A NATIONWIDE POPULATION-BASED PROSPECTIVE COHORT STUDY ON 1,393,985 TAIWANESE WOMEN. M.-J. Chen,a Y.-Y. W. Wu,b,c M.-F. A. Yen,d C.-Y. J. Fann,e L.-S. S. Chen,d Y.-H. S. Chiu,f Y.-S. Yang,a H.-N. Ho,a H.-H. Chen,b S.-T. Chiou.c,g aDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; bGraduate Institute of Epidemiology and Preventive Medicine, Taipei, Taiwan; cInstitute of Public Health, Taipei, Taiwan; dSchool of Oral Hygiene, College of Oral Medicine, Taipei, Taiwan; eDepartment of Health Industry Management, School of Healthcare Management, Tao-Yuan, Taiwan; fDepartment of Health Care Management, College of Management, Tao-Yuan, Taiwan; gHealth Promotion Administration, Taipei, Taiwan. OBJECTIVE: Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The linkage between obesity and the risk of breast cancer in Asian women remains elusive. This study aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women. DESIGN: This prospective cohort study enrolled women from the different phases of nationwide Taiwanese breast cancer screening program between 1999 and 2009. MATERIALS AND METHODS: A total of 1,393,985 women who were cancer-free before recruitment. Public health nurses or health care providers conducted in-person interviews at recruitment to collect data. The incidence of breast cancer during follow-up was assessed through the linkage of the entire cohort with the National Cancer Registry and the National Death Certification System. RESULTS: Though morbid obesity (BMI exceeding 35 kg/m2) at baseline appeared to be associated with a reduced risk of breast cancer in premenopausal women, especially among those diagnosed at younger ages, this association was not statistically significant. BMI was not significantly associated with the occurrence of incident breast cancer among women who were enrolled before menopause, but BMI was significantly associated with the risk of incident breast cancer among postmenopausal women after adjustment for extraneous risk factors. CONCLUSION: Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women. Supported by: This study is Supported by the Health Promotion Administration, Ministry of Health and Welfare in Taiwan. P-357 Wednesday, October 22, 2014 A SURVEY ASSESSING OBESITY POLICIES FOR ASSISTED REPRODUCTIVE TECHNOLOGY (ART) IN THE UNITED STATES. L. A. Kaye, C. Sueldo, L. Engmann, J. C. Nulsen, C. A. Benadiva. Center for Advanced Reproductive Services, University of Connecticut, Farmington, CT. OBJECTIVE: Given the uncertainties regarding safety and efficacy of ART in the obese patient, the purpose of this study was to survey the IVF centers across the United States to determine what policies, if any, have been instituted in response to an increasing overweight and obese population. DESIGN: Survey. MATERIALS AND METHODS: An anonymous survey was sent to Medical Directors at 395 IVF centers in the SART database regarding recommendations, policies, and restrictions for overweight/obese patients who desire infertility treatment. 77 surveys were received. RESULTS: Of the respondents, 58.4% perform 100-499 fresh ART cycles per year, and 19.7% practice in mandated states. 50 centers (64.9%) state they have a policy for obesity and offering ART, including in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), intrauterine insemination (IUI), and donor egg recipient cycles. Of those with policies, 64.0% depend specifically on BMI; 30.0% include BMI combined with other criteria. Other criteria included weight, neck/abdomen/waist circumference, waist-to-hip ratio, fat%, inadequate trial transfer, anesthesia clearance, and medical comorbidities such as hypertension, diabetes, and sleep apnea. 84% of programs with policies state they have a maximum BMI at which they will perform IVF, with 28.6% setting a limit at 40 and 9.5% setting a limit at
FERTILITY & STERILITYÒ
45. Similarly, 62.0% of programs reported a maximum BMI for donor egg recipients (mode BMI 40), but only 38% had a maximum BMI for IUI. When asked what criterion primarily dictates the exclusion of patients in ART, 62% reported anesthesia requirements. 14% selected safety during ongoing pregnancy and 14% selected IVF outcomes and success/miscarriage rates as their primary consideration. About half (50.6%) of centers have an affiliated outpatient anesthesia department with a policy regarding BMI, often setting a limit at 40 (35.9%); many require anesthesia consultation for ART. If weight loss is required before ART, 85.7% of respondents refer patients to a nutritionist/dietician, and 67.5% refer to another specialist such as bariatric surgery, endocrine, or psychology. When asked the highest BMI the center recalls treating, the maximum reported was 62, minimum 31, and mode 45. CONCLUSION: While some centers do not have policies regarding obesity and access to ART, those that do consider BMI and other criteria related to efficacy, procedural safety, safety in pregnancy, and overall health status. Policies vary widely and the topic requires continued discussion. P-358 Wednesday, October 22, 2014 ELEVATED MATERNAL BMI RESULTS IN SEVERELY DISRUPTED BLASTOCYST METABOLISM. R. L. Krisher,a A. F. Greene,a J. Stevens,b A. Heuberger,c W. B. Schoolcraft.d aNational Foundation for Fertility Research, Lone Tree, CO; bFertility Laboratories of Colorado, Lone Tree, CO; cColorado State University, Ft. Collins, CO; dColorado Center for Reproductive Medicine, Lone Tree, CO. OBJECTIVE: Compare the metabolism of blastocysts from patients with elevated BMI to those of women with normal BMI using metabolomic technology. DESIGN: Research study. MATERIALS AND METHODS: Media (Quinn’s AdvantageÒ; Cooper Surgical) samples were collected from wells of an EmbryoSlideÔ following culture (25 mL) of individual embryos that developed into good quality blastocysts on D5. Media samples from wells that did not contain an embryo were collected as controls. Three samples from each of three patients (n¼9 per treatment) were collected in both elevated (38.4; obese, OB) and normal (24.1, N) BMI groups. Patients were matched for age (OB and N, 35.7 yrs). Average blastocyst stage (OB and N, 3.6), ICM grade (A¼1, B¼2: OB 1.7; N 1.3) and TE grade (OB, 1.8; N, 1.9) were similar between treatments. Samples were analyzed using GC-MS. Metabolites were quantified using the mean peak area of selected ions against a 5-point standard curve. Values for each metabolite were analyzed using ANOVA with Tukey-Kramer multiple comparison test (p<0.05 considered significant). RESULTS: Of the 27 metabolites analyzed, 12 were metabolized differently (p<0.05) between N and OB blastocysts and 2 others tended (p<0.09) to be different. A majority of these metabolites (arginine, citrate, cysteine, glucose, isoleucine, lysine, methionine, phenylalanine, threonine, tyrosine) displayed a similar pattern, in which N blastocysts produced a small amount of the metabolite (not different than control) while OB blastocysts used the metabolite compared to control medium. Three nonessential amino acids (glycine, proline, serine) displayed a different pattern in which OB blastocysts produced a significant amount of the metabolite while N blastocysts did not alter the metabolite compared to control medium. Pyruvate was taken up from the medium (42 mM) by N embryos, but was not used by OB embryos. CONCLUSION: Although embryos from normal and elevated BMI patients both developed into good quality blastocysts on D5, a morphological assessment usually associated with high quality human blastocysts, they differed significantly in both amino acid and carbohydrate metabolism. The perturbed metabolism observed in blastocysts from women with elevated BMI may lead to impaired implantation, fetal development, or offspring health. P-359 Wednesday, October 22, 2014 IMPACT OF VARIOUS DOSES OF URINARY HCG ADMINISTERED TO TRIGGER FINAL OOCYTE MATURATION IN CONTROLLED OVARIAN STIMULATION FOR IVF ON THE CLINICAL PREGNANCY AND LIFE BIRTH RATES IN OBESE WOMEN. L. R. Hoyos, S. Khan, J. Bolnick, M. Singh, E. Puscheck, A. Awonuga. Obstetrics & Gynecology, Wayne State University, Detroit, MI. OBJECTIVE: To determine the impact of various doses of urinary human Chorionic Gonadotropin (u-hCG) administered to trigger final oocyte
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OBJECTIVE: To assess the the changes of mitochondrial function in cumulus cells of PCOS patients; to explore the potential impact of PCOS on follicular microenvironment; to improve the growth and development of PCOS patients’ follicle and oocyte. DESIGN: Cumulus cell was taken on oocyte retrieval day from 80 PCOS women and 91 controls underwent intracytoplasmic sperm injection (ICSI) treatment. The function of mitochondrial in cumulus cells was assessed. MATERIALS AND METHODS: The ultrastructure of mitochondria was observed by transmission electron microscopy (TEM). The mitochondrial membrane potential was assessed using MitoPT-JC1 assay kit by flow cytometer. The localization of mitochondrial was assessed by immunofluorescence with Mito Tracker Green. MtDNA content and expression of PGC-1a were detected by real-time PCR. The methylation of PGC-1a promoter was detected by methylation-specific real-time PCR. The levels of ATP were detected by chemiluminescence. RESULTS: The mitochondria in cumulus from PCOS patients showed an increased frequency of fragmented mitochondria, a decreased transmembrane potential, an aggregated distribution of mitochondria and a decreased mtDNA content with a decrease PGC-1a mRNA expression and hypermethylation of PGC-1a promoter. However, the level of ATP in cumulus from PCOS patients showed no change. CONCLUSION: The dysfunction of mitochondria in cumulus cells from PCOS patients may play a role in the pathogenesis of PCOS and may affect the follicle growth and oocyte development. Supported by: This work was Supported in part by the Ministry of Science and Technology of China Grants (973 program; 2011CB944504) to J.Q., and by the National Natural Science Funds for Young Scholars (31000661) to Y.Y., and by the National Natural Science Foundation of China (General Program) (81070534 to P.L.; 31371521 to Y.Y.).
OBESITY AND METABOLISM P-355 Wednesday, October 22, 2014 EVALUATION OF SONOGRAPHIC AND BIOCHEMICAL MARKERS OF CLOMIPHENE CITRATE RESISTANCE IN POLYM. Salah,a CYSTIC OVARY SYNDROME. A. F. Amen,a b c a a H. Abozeid, M. Elbaz, E. Badran. OB/Gyn, Assiut University, Assiut, Egypt; bRadiodiagnostics, Assiut University, Assiut, Egypt; cBiochemistery, Assiut University, Assiut, Egypt. OBJECTIVE: To investigate potential hormonal, metabolic and vascular markers implicated in resistance of polycystic ovary syndrome (PCOS) patients to clomiphene citrate. DESIGN: Cross sectional observational study. MATERIALS AND METHODS: 90 PCOS patients diagnosed by the Rotterdam criteria were recruited in a university affiliated fertility clinic . 49 patients were clomiphene citrate( CC) resistant ( failed to ovulate in response to CC 150 mg /day for 5 days for 3 successive cycles) and 41 patients were CC responders. History was taken and body mass index (BMI) was calculated, Hormonal and metabolic markers including serum luteinizing hormone (LH,), follicle stimulating hormone( FSH),total testosterone, fasting insulin, fasting glucose and homeostatic model assessment-insulin resistance (HOMA-IR) and 25 hydroxy vitamin D were evaluated in both groups. Sonographic evaluation of ovarian and uterine blood flow and carotid intima-media thickness (CIMT) were compared between the groups. RESULTS: The mean age was comparable while the BMI was significantly higher in the CC resistant group. Total testosterone, serum LH, fasting serum insulin, and HOMA-RI were significantly higher in the CC resistant group ( P values were 0.000) ,while serum 25 hydroxy vitamin D was significantly lower in CC resistant patients (16.25 9.95 ng/ml)than in the CC responders(31.88 7.24 ng/ml). Relevant sonoraphic vascular markers were examined. Ovarian artery RI( resistive index),and PI (pulsitility index) were significantly lower in CC resistant patients,RI (2.30 0.48) compared to ( 2.00 0.58 ), PI (0.45 0.50) compared to (2.17 0.61). Uterine artery PI in CC resistant patients were significantly higher(2.30 0.48) compared to(2.00 0.58)( P values were 0.0001 ) . CIMT as a marker for early atherosclerosis, was significantly higher in the CC resistant group (P value 0.0001) . Four patients of the CC resistant group had evidence of atheromatous plaques. There was no significant difference between both groups in the following (FSH, fasting glucose, uterine artery RI , and ovarian volume). CONCLUSION: The resistance of PCOS patients to CC may be affected by multiple metabolic and vascular factors. Lower levels of vitamin D may influence the potency of CC in ovulation induction in PCOS patients. The
Vol. 102, No. 3, Supplement, September 2014
asociation between CC resistance and increased CIMT could be further evaluated as a prognostic indicator of the cardiovascular risk in women with PCOS. P-356 Wednesday, October 22, 2014 BODY MASS INDEX AND BREAST CANCER: A NATIONWIDE POPULATION-BASED PROSPECTIVE COHORT STUDY ON 1,393,985 TAIWANESE WOMEN. M.-J. Chen,a Y.-Y. W. Wu,b,c M.-F. A. Yen,d C.-Y. J. Fann,e L.-S. S. Chen,d Y.-H. S. Chiu,f Y.-S. Yang,a H.-N. Ho,a H.-H. Chen,b S.-T. Chiou.c,g aDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; bGraduate Institute of Epidemiology and Preventive Medicine, Taipei, Taiwan; cInstitute of Public Health, Taipei, Taiwan; dSchool of Oral Hygiene, College of Oral Medicine, Taipei, Taiwan; eDepartment of Health Industry Management, School of Healthcare Management, Tao-Yuan, Taiwan; fDepartment of Health Care Management, College of Management, Tao-Yuan, Taiwan; gHealth Promotion Administration, Taipei, Taiwan. OBJECTIVE: Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The linkage between obesity and the risk of breast cancer in Asian women remains elusive. This study aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women. DESIGN: This prospective cohort study enrolled women from the different phases of nationwide Taiwanese breast cancer screening program between 1999 and 2009. MATERIALS AND METHODS: A total of 1,393,985 women who were cancer-free before recruitment. Public health nurses or health care providers conducted in-person interviews at recruitment to collect data. The incidence of breast cancer during follow-up was assessed through the linkage of the entire cohort with the National Cancer Registry and the National Death Certification System. RESULTS: Though morbid obesity (BMI exceeding 35 kg/m2) at baseline appeared to be associated with a reduced risk of breast cancer in premenopausal women, especially among those diagnosed at younger ages, this association was not statistically significant. BMI was not significantly associated with the occurrence of incident breast cancer among women who were enrolled before menopause, but BMI was significantly associated with the risk of incident breast cancer among postmenopausal women after adjustment for extraneous risk factors. CONCLUSION: Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women. Supported by: This study is Supported by the Health Promotion Administration, Ministry of Health and Welfare in Taiwan. P-357 Wednesday, October 22, 2014 A SURVEY ASSESSING OBESITY POLICIES FOR ASSISTED REPRODUCTIVE TECHNOLOGY (ART) IN THE UNITED STATES. L. A. Kaye, C. Sueldo, L. Engmann, J. C. Nulsen, C. A. Benadiva. Center for Advanced Reproductive Services, University of Connecticut, Farmington, CT. OBJECTIVE: Given the uncertainties regarding safety and efficacy of ART in the obese patient, the purpose of this study was to survey the IVF centers across the United States to determine what policies, if any, have been instituted in response to an increasing overweight and obese population. DESIGN: Survey. MATERIALS AND METHODS: An anonymous survey was sent to Medical Directors at 395 IVF centers in the SART database regarding recommendations, policies, and restrictions for overweight/obese patients who desire infertility treatment. 77 surveys were received. RESULTS: Of the respondents, 58.4% perform 100-499 fresh ART cycles per year, and 19.7% practice in mandated states. 50 centers (64.9%) state they have a policy for obesity and offering ART, including in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), intrauterine insemination (IUI), and donor egg recipient cycles. Of those with policies, 64.0% depend specifically on BMI; 30.0% include BMI combined with other criteria. Other criteria included weight, neck/abdomen/waist circumference, waist-to-hip ratio, fat%, inadequate trial transfer, anesthesia clearance, and medical comorbidities such as hypertension, diabetes, and sleep apnea. 84% of programs with policies state they have a maximum BMI at which they will perform IVF, with 28.6% setting a limit at 40 and 9.5% setting a limit at
FERTILITY & STERILITYÒ
45. Similarly, 62.0% of programs reported a maximum BMI for donor egg recipients (mode BMI 40), but only 38% had a maximum BMI for IUI. When asked what criterion primarily dictates the exclusion of patients in ART, 62% reported anesthesia requirements. 14% selected safety during ongoing pregnancy and 14% selected IVF outcomes and success/miscarriage rates as their primary consideration. About half (50.6%) of centers have an affiliated outpatient anesthesia department with a policy regarding BMI, often setting a limit at 40 (35.9%); many require anesthesia consultation for ART. If weight loss is required before ART, 85.7% of respondents refer patients to a nutritionist/dietician, and 67.5% refer to another specialist such as bariatric surgery, endocrine, or psychology. When asked the highest BMI the center recalls treating, the maximum reported was 62, minimum 31, and mode 45. CONCLUSION: While some centers do not have policies regarding obesity and access to ART, those that do consider BMI and other criteria related to efficacy, procedural safety, safety in pregnancy, and overall health status. Policies vary widely and the topic requires continued discussion. P-358 Wednesday, October 22, 2014 ELEVATED MATERNAL BMI RESULTS IN SEVERELY DISRUPTED BLASTOCYST METABOLISM. R. L. Krisher,a A. F. Greene,a J. Stevens,b A. Heuberger,c W. B. Schoolcraft.d aNational Foundation for Fertility Research, Lone Tree, CO; bFertility Laboratories of Colorado, Lone Tree, CO; cColorado State University, Ft. Collins, CO; dColorado Center for Reproductive Medicine, Lone Tree, CO. OBJECTIVE: Compare the metabolism of blastocysts from patients with elevated BMI to those of women with normal BMI using metabolomic technology. DESIGN: Research study. MATERIALS AND METHODS: Media (Quinn’s AdvantageÒ; Cooper Surgical) samples were collected from wells of an EmbryoSlideÔ following culture (25 mL) of individual embryos that developed into good quality blastocysts on D5. Media samples from wells that did not contain an embryo were collected as controls. Three samples from each of three patients (n¼9 per treatment) were collected in both elevated (38.4; obese, OB) and normal (24.1, N) BMI groups. Patients were matched for age (OB and N, 35.7 yrs). Average blastocyst stage (OB and N, 3.6), ICM grade (A¼1, B¼2: OB 1.7; N 1.3) and TE grade (OB, 1.8; N, 1.9) were similar between treatments. Samples were analyzed using GC-MS. Metabolites were quantified using the mean peak area of selected ions against a 5-point standard curve. Values for each metabolite were analyzed using ANOVA with Tukey-Kramer multiple comparison test (p<0.05 considered significant). RESULTS: Of the 27 metabolites analyzed, 12 were metabolized differently (p<0.05) between N and OB blastocysts and 2 others tended (p<0.09) to be different. A majority of these metabolites (arginine, citrate, cysteine, glucose, isoleucine, lysine, methionine, phenylalanine, threonine, tyrosine) displayed a similar pattern, in which N blastocysts produced a small amount of the metabolite (not different than control) while OB blastocysts used the metabolite compared to control medium. Three nonessential amino acids (glycine, proline, serine) displayed a different pattern in which OB blastocysts produced a significant amount of the metabolite while N blastocysts did not alter the metabolite compared to control medium. Pyruvate was taken up from the medium (42 mM) by N embryos, but was not used by OB embryos. CONCLUSION: Although embryos from normal and elevated BMI patients both developed into good quality blastocysts on D5, a morphological assessment usually associated with high quality human blastocysts, they differed significantly in both amino acid and carbohydrate metabolism. The perturbed metabolism observed in blastocysts from women with elevated BMI may lead to impaired implantation, fetal development, or offspring health. P-359 Wednesday, October 22, 2014 IMPACT OF VARIOUS DOSES OF URINARY HCG ADMINISTERED TO TRIGGER FINAL OOCYTE MATURATION IN CONTROLLED OVARIAN STIMULATION FOR IVF ON THE CLINICAL PREGNANCY AND LIFE BIRTH RATES IN OBESE WOMEN. L. R. Hoyos, S. Khan, J. Bolnick, M. Singh, E. Puscheck, A. Awonuga. Obstetrics & Gynecology, Wayne State University, Detroit, MI. OBJECTIVE: To determine the impact of various doses of urinary human Chorionic Gonadotropin (u-hCG) administered to trigger final oocyte
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