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  See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/269983091 Sitagliptin and metformin alone or incombination in patients with polycystic ovariansyndrome (PCOS): a pilot study   Article   in  Fertility and Sterility · September 2014 DOI: 10.1016/j.fertnstert.2014.07.905 CITATIONS 0 READS 135 2 authors , including:Esther López-BayghenCenter for Research and Advanced Studies of the National Polytechnic Institute 72   PUBLICATIONS   1,193   CITATIONS   SEE PROFILE All content following this page was uploaded by Esther López-Bayghen on 07 May 2015. The user has requested enhancement of the downloaded file.  P-385  Wednesday, October 22, 2014 ELEVATED LEVELS OF DIABETES ASSOCIATED PEPTIDEHORMONES ARE FOUND IN FOLLICULAR FLUID ANDSERUM OF OBESE POLYCYSTIC OVARY SYNDROMEPATIENTS.  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 a UC Centerfor Reproductive Health, University of Cincinnati, West Chester, OH;  b Ob-stetrics and Gynecology, Wright State University, Dayton, OH.OBJECTIVE: To identify the relationship between diabetes associatedpeptide hormones (DAPH) and inflammatory markers in follicular fluidand serum of obese and lean polycystic ovary syndrome (PCOS) patientswith in vitro fertilization (IVF) cycle parameters and pregnancy outcomes.DESIGN: Prospective Descriptive Study.MATERIALS AND METHODS: An IRB approved study of three groupsofIVFpatients < 35yrsold:obesePCOS(BMI > 30kg/m2;n ¼ 8),leanPCOS(BMI < 25 kg/m2; n ¼ 12), and donor or tubal factor controls (n ¼ 11). PCOSwas diagnosedby Rotterdam criteria. Serumwascollectedprior to IVF cycleinitiation. Follicular fluid was collected at retrieval. A Human Diabetes 10-plex Assay was used to quantify DAPH. A Human Cytokine 27-plex Assaywas used to quantify inflammatory markers. Results were analyzed usingone-way ANOVA with Tukey post hoc analysis using SPSS v 21. Signifi-cance was defined as p < 0.05.RESULTS: Of the 10 DAPH assessed, C-peptide, insulin, and leptin hadsignificant associations. Obese PCOS patients had higher levels of C-peptide(194.4  163.5 pg/mL), insulin (172.6  113.6 pg/mL), and leptin(10,046.1  4920.2pg/mL)infollicularfluidcomparedtoleanPCOSandcon-trols. A difference in C-peptide (p < 0.03), insulin (p < 0.01), and leptin(p ¼ 0.04) was noted between obese and lean PCOS follicular fluid. A differ-ence in C-peptide (p < 0.03) and insulin (p < 0.01) was noted between obesePCOS and control follicular fluid. Obese PCOS had higher levels of serumleptin (5575.5  1650.2pg/mL), with a difference in leptin concentrationsnoted between obese PCOS and controls (p ¼ 0.01), and obese and leanPCOS (p < 0.01). Higher levels of C-peptide (p < 0.04) and leptin (p ¼ 0.01)in the follicular fluid were associated with increased gonadotropin usage.A trend toward fewer oocytes retrieved (p ¼ 0.06), and significantly lowernumber of normally fertilized zygotes(p < 0.04) was seen with higher C-pep-tide levels. A trend toward an increased clinical pregnancy rate was notedwith lower serum leptin levels (p ¼ 0.08). There was no significant differencein inflammatory marker concentration or pregnancy outcomes between thegroups.CONCLUSION: Elevated levels DAPH, which are highly correlated withadverse long-term health outcomes, are present in young obese PCOS pa-tients undergoing IVF. DAPHs may play a role in the need for higher gonad-otropin dosing in IVF cycles and suboptimal oocyte fertilization in thispatient population. Supported by:  Funding provided through a Merck Investigator StudiesProgram Grant. P-386  Wednesday, October 22, 2014 SITAGLIPTIN AND METFORMIN ALONE OR IN COMBINATIONIN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME(PCOS):APILOTSTUDY.  J. C. Paredes-Palma b,c E. L  opez-Bayghen. a,ca Departamento de Toxicologia, Cinvestav-IPN, M  exico, DF, Mexico;  b Ho-spital General Dar  ı o Fern  andez, ISSSTE, M  exico, DF, Mexico;  c Maestr  ı aen Endocrinolog  ı a Ginecol  ogica e Infertilidad, Instituto de Infertilidad yGen  etica, Ingenes, M  exico, DF, Mexico.OBJECTIVE: To evaluate the effect of treatment with sitagliptin and met-formin alone and in combination on menstrual frequency, hormonal andmetabolic profiles in obese and non-obese women with PCOS.DESIGN: Open-randomized controlled clinical trial.MATERIALS AND METHODS: IC: age 18-37 y, PCOS (Rotterdamcriteria); no history of ART (previous 6 mo). EC: diabetes mellitus,smokers, or those under hormone therapy or treatment with drugs affectingintestinal motility, lipid levels, weight, or metformin intake (6 mo prior tostudy entry). Candidates were cited every Friday and explained the reasonfor the study, advantages and disadvantages (transvaginal USG and quanti-fication of LH, FSH, testosterone, androstenedione, dehydroepiandroster-one, prolactin, cortisol, ACTH, TSH, T4, T3). Patients were quoted infollicular phase of menstrual cycle (days 1 to 5 of menstruation); at thistime randomization was performed: G1, metformin 850 mg/24 h); G2, Si-tagliptin 100 mg/24 h; G3, Sitagliptin plus metformin same doses. Beforefirst dose, a glucose tolerance curve (5 h/75g of glucose); glucose, lipid pro-file and insulin were recorded Same measurements: 24 weeks after comple-tion of treatment. Anthropometry was recorded. Normal menstrualpattern:five periods in 24 weeks. Statistical analysis: paired t tests andchi-square test; P < 0.05).RESULTS: Sitagliptin or metformin improved menstruation index andprogesterone levels in women with PCOS. The sitagliptin plus metformincombo was more effective improving the ovulation percentage and the pro-gesterone levels than the other two treatments with no significant change inBMI. While the trend suggests that metformin would have a greater effecton increasing the frequency of menstrual periods, no statistical significantdifferences were found. Metformin alone produced weight and waistcircumference losses but weight was not modified in the group treatedwith the combo. No statistically significant differences were observed inweight with the combo treatment, indicating that the observed increase inthe frequency of menstruation and ovulation could be directly attributedto treatment. A significant decrease in insulin secretion was noticed inthe combo and metformin groups with more changes in the metformingroup.CONCLUSION: The sitagliptin plus metformin combo improved men-strual function in PCOS patients, independently of weight loss suggestinga direct effect over ovarian function. Supported by:  Conacyt 212650. P-387  Wednesday, October 22, 2014 PRENATAL ANDROGEN EXCESS ENHANCES STIMULATION OFTHE GNRH PULSE BY NEUROKININ B AND KISSPEPTIN IN PU-BERTAL FEMALE RATS.  X. Yan, a,b C. Yuan, a N. Zhao, a Y. Cui, a J. Liu. a a State Key Laboratory of Reproductive Medicine, Clinical Centerof Reproductive Medicine, First Affiliated Hospital, Nanjing Medical Uni-versity, Nanjing, Jiangsu, China; b Clinical Centerof ReproductiveMedicine,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, character-ized by a rapid LH pulse frequency. The early mechanism underlying the pu-bertalregulationoftheGnRH/LHpulsatilereleaseinadolescentswithPCOSremains uncertain. The aim of the study was to determine the effects of pre-natal androgen exposure on the GnRH pulse and LH secretion at puberty.DESIGN: We administrated DHT to pregnant rats and observedserum LHlevels and hypothalamic genes expression in female offspring from postnatal4 to 8 weeks.MATERIALS AND METHODS: At the age of 4,6 and 8 weeks, wemeasured the level of serum LH and evaluated  Kissl,NKB,ObRb  mRNAlevels in the hypothalamic arcuate nucleus of PCOS rats. Kisspeptin,NK3R agonist and Leptin were intracerebrally injected into the lateral cere-bral ventricle of 6-week-old PCOS rats. The serum LH were measured0,15,30 and 60 min after administration.RESULTS: The 6-week-old prenatally androgenized (PNA) female ratsexhibited significantly elevated LH pulse frequency. The hypothalamicexpression of   NKB  and  ObRb  mRNA in the PNA rats remarkably increasedbefore puberty and remained high during puberty. However, increased  Kiss1 mRNA levels were detected only after the onset of puberty. ExogenousKisspeptin, NK3R agonist and Leptin exerted tonic stimulation of GnRHneurons and increased LH secretion in pubertal PNA rats. Moreover, Leptinupregulated  Kiss1  mRNA expression in the hypothalamus of pubertal PNArats; however, pretreatment with a Kisspeptin antagonist failed to suppressthe elevated serum LH levels stimulated by Leptin, indicating that the stim-ulatory effects of Leptin may be conveyed indirectly to GnRH neurons viaother neural components, rather than through the Kisspeptin-GPR54pathway.CONCLUSION: These findings showed that NKB and Leptin play anessential role in the activation of GnRH neurons and initiation of increasedLH pulse frequency in pubertal PNA rats. Kisspeptin may coordinate theirstimulatory effects on LH release. P-388  Wednesday, October 22, 2014 EVALUATING RISK VARIANTS FOR KOREAN WOMEN WITHPOLYCYSTIC OVARY SYNDROME IN WOMEN OF EUROPEANETHNICITY.  H.-J.Kim, a A.Bjonnes, b R.Saxena, b C.Welt. c a Obstetricsand Gynecology, Seoul National University Bundang Hospital, Seongnam,Gyeongi, Korea;  b Anesthesia and Critical Care, Massachusetts General Hos-pital, Boston, MA;  c Reproductive Endocrine, Massachusetts General Hospi-tal, Boston, MA. e266  ASRM Abstracts  Vol. 102, No. 3, Supplement, September 2014 View publication statsView publication stats
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