See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/269983091

Sitagliptin and metformin alone or in

combination in patients with polycystic ovarian
syndrome (PCOS): a pilot study

Article in Fertility and Sterility · September 2014

DOI: 10.1016/j.fertnstert.2014.07.905

CITATIONS READS

0 135

2 authors, including:

Esther López-Bayghen
Center 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 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; bOb-
stetrics 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 10-
plex 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. Signifi-
cance 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 con-
trols. 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 differ-
ence 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-pep-
tide 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 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 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; bHo-
spital 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 met-
formin 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 quanti-
fication of LH, FSH, testosterone, androstenedione, dehydroepiandroster-
one, 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, Si-
tagliptin 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-
e266 ASRM Abstracts
View publication stats
file and insulin were recorded Same measurements: 24 weeks after comple-
tion 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 pro-
gesterone 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 men-
strual 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 PU-
BERTAL 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 Uni-
versity, 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, character-
ized by a rapid LH pulse frequency. The early mechanism underlying the pu-
bertal regulation of the GnRH/LH pulsatile release in adolescents with PCOS
remains 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 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 cere-
bral 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 stim-
ulatory 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 Hos-
pital, Boston, MA; cReproductive Endocrine, Massachusetts General Hospi-
tal, Boston, MA.
Vol. 102, No. 3, Supplement, September 2014