Sitagliptin and metformin alone or in combination in patients with polycystic ovarian syndrome (PCOS): a pilot study

P-385 Wednesday, October 22, 2014 ELEVATED LEVELS OF DIABETES ASSOCIATED PEPTIDE HORMONES ARE FOUND IN FOLLICULAR FLUID AND SERUM OF OBESE POLYCYSTIC OVARY SYNDROME PATIENTS. A. E. Batcheller,a A. M. Martinez,a S. R. Lindheim,b D. Cool,b W. Grunwald, Jr.,b K. B. DiPaola,a J. M. Sroga.a aUC Center for Reproductive Health, University of Cincinnati, West Chester, OH; bObstetrics and Gynecology, Wright State University, Dayton, OH. OBJECTIVE: To identify the relationship between diabetes associated peptide hormones (DAPH) and inflammatory markers in follicular fluid and serum of obese and lean polycystic ovary syndrome (PCOS) patients with in vitro fertilization (IVF) cycle parameters and pregnancy outcomes. DESIGN: Prospective Descriptive Study. MATERIALS AND METHODS: An IRB approved study of three groups of IVF patients <35 yrs old: obese PCOS (BMI>30 kg/m2; n¼8), lean PCOS (BMI<25 kg/m2; n¼12), and donor or tubal factor controls (n¼11). PCOS was diagnosed by Rotterdam criteria. Serum was collected prior to IVF cycle initiation. Follicular fluid was collected at retrieval. A Human Diabetes 10plex Assay was used to quantify DAPH. A Human Cytokine 27-plex Assay was used to quantify inflammatory markers. Results were analyzed using one-way ANOVA with Tukey post hoc analysis using SPSS v 21. Significance was defined as p<0.05. RESULTS: Of the 10 DAPH assessed, C-peptide, insulin, and leptin had significant associations. Obese PCOS patients had higher levels of C-peptide (194.4163.5 pg/mL), insulin (172.6113.6 pg/mL), and leptin (10,046.14920.2pg/mL) in follicular fluid compared to lean PCOS and controls. A difference in C-peptide (p<0.03), insulin (p<0.01), and leptin (p¼0.04) was noted between obese and lean PCOS follicular fluid. A difference in C-peptide (p<0.03) and insulin (p<0.01) was noted between obese PCOS and control follicular fluid. Obese PCOS had higher levels of serum leptin (5575.51650.2pg/mL), with a difference in leptin concentrations noted between obese PCOS and controls (p¼0.01), and obese and lean PCOS (p<0.01). Higher levels of C-peptide (p<0.04) and leptin (p¼0.01) in the follicular fluid were associated with increased gonadotropin usage. A trend toward fewer oocytes retrieved (p¼0.06), and significantly lower number of normally fertilized zygotes (p<0.04) was seen with higher C-peptide levels. A trend toward an increased clinical pregnancy rate was noted with lower serum leptin levels (p¼0.08). There was no significant difference in inflammatory marker concentration or pregnancy outcomes between the groups. CONCLUSION: Elevated levels DAPH, which are highly correlated with adverse long-term health outcomes, are present in young obese PCOS patients undergoing IVF. DAPHs may play a role in the need for higher gonadotropin dosing in IVF cycles and suboptimal oocyte fertilization in this patient population. Supported by: Funding provided through a Merck Investigator Studies Program Grant. P-386 Wednesday, October 22, 2014 SITAGLIPTIN AND METFORMIN ALONE OR IN COMBINATION IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS): A PILOT STUDY. J. C. Paredes-Palmab,c E. Lopez-Bayghen.a,c a Departamento de Toxicologia, Cinvestav-IPN, Mexico, DF, Mexico; bHospital General Darıo Fernandez, ISSSTE, Mexico, DF, Mexico; cMaestrıa en Endocrinologıa Ginecol ogica e Infertilidad, Instituto de Infertilidad y Genetica, Ingenes, Mexico, DF, Mexico. OBJECTIVE: To evaluate the effect of treatment with sitagliptin and metformin alone and in combination on menstrual frequency, hormonal and metabolic profiles in obese and non-obese women with PCOS. DESIGN: Open-randomized controlled clinical trial. MATERIALS AND METHODS: IC: age 18-37 y, PCOS (Rotterdam criteria); no history of ART (previous 6 mo). EC: diabetes mellitus, smokers, or those under hormone therapy or treatment with drugs affecting intestinal motility, lipid levels, weight, or metformin intake (6 mo prior to study entry). Candidates were cited every Friday and explained the reason for the study, advantages and disadvantages (transvaginal USG and quantification of LH, FSH, testosterone, androstenedione, dehydroepiandrosterone, prolactin, cortisol, ACTH, TSH, T4, T3). Patients were quoted in follicular phase of menstrual cycle (days 1 to 5 of menstruation); at this time randomization was performed: G1, metformin 850 mg/24 h); G2, Sitagliptin 100 mg/24 h; G3, Sitagliptin plus metformin same doses. Before first dose, a glucose tolerance curve (5 h/75g of glucose); glucose, lipid pro-

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file and insulin were recorded Same measurements: 24 weeks after completion of treatment. Anthropometry was recorded. Normal menstrual pattern:five periods in 24 weeks. Statistical analysis: paired t tests and chi-square test; P<0.05). RESULTS: Sitagliptin or metformin improved menstruation index and progesterone levels in women with PCOS. The sitagliptin plus metformin combo was more effective improving the ovulation percentage and the progesterone levels than the other two treatments with no significant change in BMI. While the trend suggests that metformin would have a greater effect on increasing the frequency of menstrual periods, no statistical significant differences were found. Metformin alone produced weight and waist circumference losses but weight was not modified in the group treated with the combo. No statistically significant differences were observed in weight with the combo treatment, indicating that the observed increase in the frequency of menstruation and ovulation could be directly attributed to treatment. A significant decrease in insulin secretion was noticed in the combo and metformin groups with more changes in the metformin group. CONCLUSION: The sitagliptin plus metformin combo improved menstrual function in PCOS patients, independently of weight loss suggesting a direct effect over ovarian function. Supported by: Conacyt 212650. P-387 Wednesday, October 22, 2014 PRENATAL ANDROGEN EXCESS ENHANCES STIMULATION OF THE GNRH PULSE BY NEUROKININ B AND KISSPEPTIN IN PUBERTAL FEMALE RATS. X. Yan,a,b C. Yuan,a N. Zhao,a Y. Cui,a J. Liu.a aState Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; bClinical Center of Reproductive Medicine, First Affiliated Hospital, Xuzhou Medical College, Xuzhou, Jiangsu, China. OBJECTIVE: Adolescent girls with polycystic ovary syndrome (PCOS) manifest neuroendocrine derangements after the onset of puberty, characterized by a rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GnRH/LH pulsatile release in adolescents with PCOS remains uncertain. The aim of the study was to determine the effects of prenatal androgen exposure on the GnRH pulse and LH secretion at puberty. DESIGN: We administrated DHT to pregnant rats and observed serum LH levels and hypothalamic genes expression in female offspring from postnatal 4 to 8 weeks. MATERIALS AND METHODS: At the age of 4,6 and 8 weeks, we measured the level of serum LH and evaluated Kissl,NKB,ObRb mRNA levels in the hypothalamic arcuate nucleus of PCOS rats. Kisspeptin, NK3R agonist and Leptin were intracerebrally injected into the lateral cerebral ventricle of 6-week-old PCOS rats. The serum LH were measured 0,15,30 and 60 min after administration. RESULTS: The 6-week-old prenatally androgenized (PNA) female rats exhibited significantly elevated LH pulse frequency. The hypothalamic expression of NKB and ObRb mRNA in the PNA rats remarkably increased before puberty and remained high during puberty. However, increased Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous Kisspeptin, NK3R agonist and Leptin exerted tonic stimulation of GnRH neurons and increased LH secretion in pubertal PNA rats. Moreover, Leptin upregulated Kiss1 mRNA expression in the hypothalamus of pubertal PNA rats; however, pretreatment with a Kisspeptin antagonist failed to suppress the elevated serum LH levels stimulated by Leptin, indicating that the stimulatory effects of Leptin may be conveyed indirectly to GnRH neurons via other neural components, rather than through the Kisspeptin-GPR54 pathway. CONCLUSION: These findings showed that NKB and Leptin play an essential role in the activation of GnRH neurons and initiation of increased LH pulse frequency in pubertal PNA rats. Kisspeptin may coordinate their stimulatory effects on LH release. P-388 Wednesday, October 22, 2014 EVALUATING RISK VARIANTS FOR KOREAN WOMEN WITH POLYCYSTIC OVARY SYNDROME IN WOMEN OF EUROPEAN ETHNICITY. H.-J. Kim,a A. Bjonnes,b R. Saxena,b C. Welt.c aObstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Gyeongi, Korea; bAnesthesia and Critical Care, Massachusetts General Hospital, Boston, MA; cReproductive Endocrine, Massachusetts General Hospital, Boston, MA.

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