What is the risk of metabolic syndrome in adolescents with normal BMI who have polycystic ovary syndrome?

P-363 Wednesday, October 22, 2014 MCP-1, A CENTRAL MEDIATOR OF OBESITY AND DIETINDUCED OVARIAN DYSFUNCTION. O. A. Asemota,a a b a a,b,c D. S. Berger, Y. Seki, S. K. Jindal, M. J. Charron, E. Buyuk.a aReproductive Endocrinology and Infertility, Montefiore Institute of Reproductive Medicine and Health, Bronx, NY; bBiochemistry, Albert Einstein College of Medicine, Bronx, NY; cEndocrinology, Albert Einstein College of Medicine, Bronx, NY. OBJECTIVE: To investigate the role of obesity, diet and MCP-1 in ovarian function using a rodent model. DESIGN: Prospective controlled study. MATERIALS AND METHODS: Four groups of 6 week-old female mice were studied. Group 1 (Control): C57Bl6/J mice (N¼24) fed normal chow (NC). Group 2: C57Bl6/J mice (N¼24) fed high-fat (HF) diet to induce obesity. Group 3: MCP-1 knockout (KO) mice (N ¼ 12) fed HF diet. Group 4: Agouti (B6. Cg-Ay/J) mice (N ¼ 12) fed NC. All groups were fed from 6-18 weeks old. At 18-20 weeks, glucose tolerance test (GTT), insulin tolerance test (ITT) and Echo MRI for adiposity were performed. 6 mice from each group underwent ovarian hyperstimulation (OH), were sacrificed and their oocytes collected. The other 6 non-stimulated mice were sacrificed and their ovaries harvested. The remaining 12 in group 1 were continued on NC; while in Group 2, the remaining 12 were switched to NC. Both groups had GTT, ITT and Echo MRI at 30-32 weeks. In each group 6 mice underwent OH with oocyte collection; the other 6 were sacrificed and their ovaries harvested. Outcome measures were body weight (BW), adiposity, GTT, ITT, and number of oocytes collected after OH. Student T- test, Mann Whitney U, and ANOVA were used, P<0.05. RESULTS: Compared to control group, mice in Groups 2, 3, 4 gained more BW, had increased adiposity (P<0.0001) and fasting hyperglycemia (P<0.001). None of the groups had insulin resistance, while Group 2 had a modest improvement in glucose excursion. After OH, significantly fewer oocytes were collected from Group 2 compared to Group 1 (6.71.8 vs 1.80.5, P¼0.04). Interestingly, despite gaining the most BW and adiposity on HF diet, MCP-1 KO mice had similar number of oocytes collected when compared to control group (6.20.9 vs 6.71.8, P¼0.9). Group 4 had fewer eggs collected compared to control group, but the difference was not statistically significant (3.30.8 vs 6.71.8, P¼0.3). After switching to NC, at 32 weeks, Group 2 had a similar number of oocytes collected compared to control group (6.71.8 vs. 7.31.5, P¼0.8). CONCLUSION: Obesity and high fat diet adversely alter ovarian function. This alteration can be reversed by change in diet and weight loss, or by inhibition of MCP-1. MCP-1 may be a therapeutic target in treating obesity induced ovarian dysfunction. Supported by: Ferring Pharmaceuticals Inc. P-364 Wednesday, October 22, 2014 INVESTIGATING THE IMPACT OF BODY MASS INDEX (BMI) ON EMBRYO MORPHOKINETICS USING TIME-LAPSE EMBRYO IMAGING. K. N. Goldman,a Y. G. Kramer,a K. Melzer-Ross,b J. A. Grifo.a aObstetrics and Gynecology, New York University Langone Medical Center, New York, NY; bGenesis Fertility and Reproductive Medicine, Brooklyn, NY. OBJECTIVE: To determine if a relationship exists between BMI and timing of early embryonic events using Embryoscope time-lapse imaging. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Included were patients (pts) ages 33-43 with embryos that underwent Embryoscope morphokinetic evaluation following routine in vitro fertilization (IVF) followed by trophectoderm biopsy between July 2012 and May 2013. Pt BMI was calculated from height and weight on the day of oocyte retrieval (OR). Pts were excluded if donor oocytes or cryopreserved oocytes were utilized, or if BMI was unavailable. All morphokinetic parameters were calculated from the time of syngamy. Pts were divided into normal BMI (BMI 18-23) and high BMI (range BMI >23) for analysis. The primary outcome was time to full blastocyst after syngamy (t-blast). Secondary outcomes included: 2-cell furrow (t-2 furrow), 2-cell stage (t-2), 3-cell (t-3), 4-cell (t-4), 5-cell (t-5), 8-cell (t-8), start of compaction (t-comp1), completion of compaction (t-comp2), and start of cavitation (t-cav). Student’s T-test was used for statistical analysis with significance set at p<0.05. RESULTS: 106 embryos underwent morphokinetic evaluation in the Embryoscope including 62 embryos in the BMI 18-23 group (n¼13 pts), and 44 embryos in the BMI >23 group (n¼8 pts). There were no differences between the two groups when comparing age at OR (38.6  2 vs 37.2  2), day 2 estradiol (E2) and FSH, units of gonadotropin, peak E2, total oocytes

FERTILITY & STERILITYÒ

and Metaphase-II (MII) oocytes retrieved, 2 pro-nuclear (2PN) zygotes, and number of blastocysts analyzed. There was no difference between groups when comparing t-blast after syngamy, t-2 furrow, t-2, t-3, t-4, t-5, t-8, tcomp1, t-comp2, and t-cav. Table 1. Embryo morphokinetic parameters

BMI 18-23 (n¼62 embryos)

BMI >23 (n¼44 embryos)

p-value

2.3  0.4 2.9  1.3 13.3  2.7 14.4  2.0 26.8  4.2 32.8  6.2 48.5  12.7 60.1  10.9 71.5  9.2 83.9  9.8

2.1  0.3 2.7  0.5 13.9  1.2 14.8  1.6 26.7  5.5 33.1  5.9 46.7  11.7 57.6  9.4 70.8  6.5 81.8  7.5

0.08 0.34 0.18 0.24 0.88 0.85 0.48 0.28 0.69 0.25

t-2 furrow t-2 t-3 t-4 t-5 t-8 t-comp 1 t-comp 2 t-cav t-blast

Data are presented in Mean  S.D. CONCLUSION: There was no relationship between BMI and embryo morphokinetic parameters in this otherwise homogeneous cohort of patients, suggesting that the negative impact of being overweight on IVF and reproductive outcomes may not be related to timing of early embryonic events. POLYCYSTIC OVARY SYNDROME P-365 Wednesday, October 22, 2014 WHAT IS THE RISK OF METABOLIC SYNDROME IN ADOLESCENTS WITH NORMAL BMI WHO HAVE POLYCYSTIC OVARY SYNDROME? H. Hassa,a Y. Aydin,a D. Burkankulu,a D. Arslantas,b D. Sayiner,c N. Ozerdogan.c aObstetrics and Gynecology Department, Eskisehir Osmangazi University-Medical Faculty, Eskisehir, Turkey; bDepartment of Public Health, Eskisehir Osmangazi University-Medical Faculty, Eskisehir, Turkey; cEskisehir Osmangazi University-Nursing College, Eskisehir, Turkey. OBJECTIVE: The purpose of this study was to evaluate the effects of polycystic ovary syndrome (PCOS) on the prevalence of metabolic syndrome (MBS) in adolescents with normal body mass index (BMI). DESIGN: Cross-sectional study conducted in a university hospital adolescent clinic. MATERIALS AND METHODS: We studied with 63 adolescent girls with PCOS and 159 matched controls. The diagnosis of PCOS was based on the recent ESHRE/ASRM proposal and required that all three of the Rotterdam criteria for diagnosing PCOS in adolescents be met (1). In all of the participants BMI was less than 25 kg/m2. Indices of insulin sensitivity, metabolic variables, circulating androgen levels, lipidemic markers were measured and blood pressures (BP) were assessed. To diagnose the cases with MBS, Cook modified criteria were used and patients who had at least 3 of the 5 criteria were diagnosed with MBS (2). RESULTS: Adolescent girls with PCOS had higher blood pressure parameters (P<0.01), insulin (P¼0.007), LDL (P¼0.017), triglycerides (P¼0.045) and total (P<0.001) and free testosterone (P¼0.001) levels compared to the control group. More cases with at least one of Cook’s criteria were found among girls with PCOS compared to the control group (P¼0.05). The prevalence of MBS was significantly higher in girls with PCOS compared to control group (P¼0.02). Prevalence of metabolic risk factors and metabolic syndrome in adolescents with and without PCOS

Cases with R1 metabolic risk factor, n (%) Cases with R2 metabolic risk factor, n (%) Cases with R3 metabolic risk factor (metabolic syndrome), n (%)

Cases with PCOS (n¼63)

Cases without PCOS (n¼159)

31 (50.1)

34 (21.3)

0.05

7 (11.1)

10 (6.2)

NS

5 (7.9)

1 (0.6)

0.02

P value

NS: non-significant

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CONCLUSION: The prevalence of MBS was higher in adolescent girls with normal BMI and PCOS, compared to an age- and BMI-matched control group. Thus, as clinicians, we must determine the criteria for MBS in girls with PCOS, even if they have a normal BMI. In addition to the most important complaints of adolescent girls with PCOS, such as hirsutism, acne and oligomenorrhea, we must consider the criteria for MBS, which can determine long-term quality of life. Supported by: This study was funded by the Scientific Investigations Department of our University with the number of 201211008. P-366 Wednesday, October 22, 2014 SUBJECTIVE PERCEPTION OF HAIR EXCESS RELIABLY PREDICTS OBJECTIVE HIRSUTISM IN WOMEN WITH PCOS. K. W. Keefe,a M. A. Khan,b S. Alaparth,c V. Snegovskikh,d J. Williams,a L. Pal.a aObstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT; bZiauddin Medical College, Karachi, Sindh, Pakistan; cLehigh University, Bethlehem, PA; dObstetrics and Gynecology, Brown University School of Medicine, Providence, RI. OBJECTIVE: To ascertain how closely subjective perception of hirsutism correlates with objective assessment utilizing Ferriman Galway (FG) pictorial scoring system, and to determine if this relationship varies by race. DESIGN: Cross sectional study of women who were evaluated at an academic reproductive endocrine practice by a single reproductive endocrinologist for complaints relating to polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: At initial evaluation, patients were asked to identify subjective perception of hirsutism severity utilizing a modified 11 site FG pictorial scoring system. An objective evaluation of the hair excess severity was then performed by a trained reproductive endocrinologist who was blinded to the subjective scoring at the time of physical examination. Degree of congruence between subjective and objective FG scores was assessed in the context of age and self identified race (White, African American, South Asian, Other). RESULTS: Of the 101 women diagnosed with PCOS (Rotterdam criteria), subjective assessment of degree and distribution of hair excess highly correlated with objective evaluation by a trained reproductive endocrinologist (r¼0.79, p<0.001). The magnitude of correlation between subjective and objective FG scores was highest for AA race (n¼14, r¼0.82, p<0.01), intermediate for Whites (n¼66, r¼0.78, p<0.01), and South Asians (n¼9, r¼0.76, p¼0.01) and lowest for women of ‘‘other race’’ (n¼12, r¼0.62, p¼0.03). Logistic regression analysis adjusting for patient age and race identified a 33% increased likelihood for hirsutism (FG score R8) for each unit increase in subjective FG score (OR 1.33, 95% CI 1.17-1.50). CONCLUSION: In women with PCOS, patient self-scoring of hair excess intensity and distribution by utilizing FG pictorial chart allows reliable assessment of hirsutism severity. P-367 Wednesday, October 22, 2014 WOMEN WITH MALE-ASSOCIATED HIP ABNORMALITIES (CAM FEMOROACETABULAR IMPINGEMENT) HAVE HIGHER A. Napoli,b ANTRAL FOLLICLE COUNTS. T. C. Plowden,a A. H. DeCherney,a A. B. Wolff,b E. F. Wolff.a aPRAE, NICHD, NIH, Bethesda, MD; bWashington Orthopaedics & Sports Medicine, Washington, DC. OBJECTIVE: Hip pain in young people is often the result of Cam type femoroacetabular impingement (FAI), which is known to develop during puberty at the time of proximal femoral physeal closure. There is no way to prevent this abnormal hip development, and patients must undergo complex surgery to correct severe hip damage. Interestingly, Cam FAI is typically seen in men. The objective of this study was to determine if androgenic hip morphology (defined as cam FAI) was associated with androgenic gynecologic features such as polycystic ovaries, menstrual irregularity and hyperandrogenism. DESIGN: Prospective cohort of reproductive aged women with hip pain requiring arthroscopic hip surgery. MATERIALS AND METHODS: Reproductive aged women with indication for arthroscopic hip surgery were assessed. Measurements of alpha angles on 45 degree Dunn lateral radiographs were done. Cam FAI was defined as an alpha angle of >55 degrees. MRI was used to asses antral follicles and the average number per ovary was recorded. In a subset of patients, menstrual irregularity and clinical hyperandrogenism were assessed by history and

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ASRM Abstracts

physical exam. Means were compared using students t test and correlations using Pearson’s. All continuous data was expressed as Mean+SD. RESULTS: 15 women with cam FAI and 13 without were found to have median alpha angle of 62 and 46 respectively (P<0.0001). Average ages were similar between groups, but antral follicle counts per ovary were significantly higher in women with cam FAI than controls, respectively (13.7+5.3 vs 8.5+2.9, P¼0.004). Univariate analysis revealed a statistically significant correlation between alpha angle measurements and antral follicle counts per ovary (R¼0.30, P¼0.03), indicating that Cam FAI appears to be more consistent with a continuum rather than cut-point with respect to antral follicle counts. Clinical symptoms of PCOS were assessed in a subset of women (n¼10), but no association of Cam FAI was detected with a history of clinical hyperandrogenism or menstrual irregularity. CONCLUSION: Androgenic hip morphology (cam FAI) was found to be strongly associated with antral follicle numbers, but not menstrual irregularity or clinical hyperadrogenism. Further study is needed to characterize biochemical evidence of hyperandrogenism related to this disorder as well as assess hormonal influence such as PCOS on hip development during puberty. Abnormal female hip development during puberty may be amenable to anti-androgenic treatments to prevent the development of Cam FAI. Supported by: Program in Reproductive and Adult Endocrinology, NICHD, NIH. P-368 Wednesday, October 22, 2014 PREDICTIVE VALUE OF SERUM ANTI-MULLERIAN HORMONE IN OBESE AND NON-OBESE WOME WITH POLYCYSTIC OVARY SYNDROME (PCOS) RECEIVING ORAL OVULATION INDUCTION (OI) AGENTS. J. Uyenishi, W. Vitek, J. Queenan, B. Bhagavath, K. Hoeger. Reproductive Endocrinology and Infertility, URMC, Rochester, NY. OBJECTIVE: To determine if serum anti-M€ullerian hormone (AMH) concentration in obese and non-obese women with PCOS is predictive of ovulation with oral agents. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Retrospective review of women with anovulatroy infertility, PCOS, and an AMH concentration drawn prior to receiving either clomiphene citrate (CC) or letrozole (LET) between 9/2012 to 12/2013. Women were stratified into obese (BMI R 30 kg/m2) and nonobese (BMI < 30 kg/m2) categories. AMH and ovulatory status was compared in obese and non-obese women using a Wilcoxon rank test. AMH concentration and ovulatory status from the first induced cycle with oral agents was compared using bivariate and multivariate logistic regression analysis adjusting for age, use of metformin, type of infertility, ethnicity, and drug dose. AMH as a predictor of number of follicles measuring >14mm by transvaginal ultrasound was analyzed as a secondary outcome using a similar multivariate analysis. RESULTS: 95 cycles of CC and 23 cycles of LET among 118 women with PCOS included; 68 obese and 50 non-obese. AMH was elevated in non-obese women (non-obese 6.76 vs. obese 4.20 p <0.001) and also higher in nonobese ovulators (non-obese 6.21 vs obese 4.02, p<0.01). In a multivariate analysis, AMH was not predictive of ovulation in patients receiving oral OI agents. Higher levels of AMH were associated with a decrease in the relative odds of ovulating (p ¼ 0.085) in non-obese women. In obese patients, every 1.13 ng/mL decrease in AMH was associated with one additional mature follicle (p<0.05); likewise, in non-obese patients, every 1.12 ng/mL decrease in AMH was associated with one additional mature follicle (p<0.01). Baseline characteristics of study population

Characteristic

Non-obese

Obese

p-value

Age, years BMI, kg/m2 Race Caucasian Non-Caucasian Infertility primary secondary Meformin Yes No AMH, ng/mL

30.3 24.3

31.3 39.1

0.1521 <0.0001 0.028

41 9

65 3

41 9

45 23

4 46 6.76

17 51 4.2

0.056 0.027 <0.001

Vol. 102, No. 3, Supplement, September 2014