SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 218A

218A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

F-109
Peripheral Basophil Count is Increased in Patients with Endometriosis.
Qian Feng†,1,3 Nilufer Rahmioglu,3 Kevin Paddon,2 Carol Hubbard,3 Krina
T Zondervan,3 Christian M Becker*,3 Karin Hellner*.3 1Guangzhou
University of TCM, Guangzhou, China; 2Oxford University Hospitals
NHS Foundation Trust, Oxford, United Kingdom; 3University of Oxford,
Oxford, United Kingdom.
INTRODUCTION: Endometriosis affects up to 10% of premenopausal
women causing pelvic pain and infertility. Whilst the pathogenesis remains
unclear, estrogen-dependence and inflammation play a key role. Currently,
laparoscopic surgery is the diagnostic gold standard. Thus, an urgent unmet
clinic need for a minimally invasive and widely available diagnostic tool
exists. Levels of circulating leukocytes have been suggested as potent
biomarkers for various conditions and can be extracted from routine full
blood count (FBC) tests. This study investigates the potential value of
leukocyte subtypes as biomarkers for endometriosis.
METHODS: We analysed prospective data and blood leukocyte subtype
counts from preoperative FBC samples in 517 women who underwent
surgery for suspected endometriosis recruited as part of the ENDOX study
(330 endometriosis cases and 187 controls with negative laparoscopy).
Clinical and intraoperative surgical data were collected according to
WERF EPHect standards. Differences in leukocyte subtypes were
evaluated using T-test between groups and comorbidity differences were
compared using Chi-square test. The association of leukocyte counts
with diagnosis of endometriosis and its subtypes was analysed using a
logistic regression model.
RESULTS: Basophils were the only leukocyte subtype found significantly
increased in endometriosis patients (P=0.005) in both ASRM Stage I/II
(P=0.023) and Stage III/IV disease (P=0.004). No significant difference
in the incidence of immunological disorders was seen between groups.
CONCLUSION: Our study is the first to analyze the potential diagnostic
propensities of peripheral leukocytes for endometriosis. We found a
positive association between the presence and severity of endometriosis
and basophil counts, regardless of the presence of immunological
disorders. This suggests that peripheral basophils may play a role in the
underlying pathophysiology of endometriosis, but further research is
necessary to understand their role in the context of comorbidities.

F-110
Regulation of Chloride Channel Proteins by Ovarian Hormones in
Rhesus Macaques with and without Endometriosis. Fangzhou Luo,
Corinne Wilcox, Ov Slayden. Oregon Health & Science University,
Beaverton, OR, United States.
INTRODUCTION: Cystic fibrosis transmembrane regulator protein
(CFTR) and Ca+-activated chloride channel 1 (CLCA1) are membrane
proteins that play integral roles in the secretion of fluids in many organs.
The primate endometrium undergoes cyclic changes in cell epithelial
proliferation and secretion that are driven by changes in circulating
estradiol (E2) and progesterone (P). Endometrial cycles are disrupted
in subjects with endometriosis. We hypothesized that cyclic expression
of CFTR and CLCA1 could be dysregulated in cases of endometriosis.
To test this hypothesis we evaluated CFTR and CLCA1 gene expression
and protein localization in the endometrium of rhesus macaques with and
without induced endometriosis.
METHODS: Rhesus macaques were treated to stimulate menstrual
cycles. These cycles were created by the sequential insertion and removal
of Silastic capsules releasing E2 and then E2 +P. Endometriosis was induced
(Slayden et al., Fertil. & Steril . Vol 100 Issue 3 S101.) in disease-free,
artificially cycled animals (n=5) by seeding of menstrual tissue 72 hours
following P withdrawal, concordant with day one of menstruation. Healthy
reproductive endometrial tissues were collected from artificially cycled
controls. Quantative real-time RT-PCR (Q-RT-PCR) was used to detect
CFTR and CLCA1 transcript. Immunohistochemistry was validated to
localize CFTR, CLCA1 and Von Willebrand Factor in tissue sections.
RESULTS: Q-RT-PCR detected a significant (P<0.05) increase of both
CFTR and CLCA1 in the endometrium during the artificial secretory
phase compared to the artificial proliferative phase. This is consistent
with other reports of endometriosis-stimulated progesterone resistance

Scientific Abstracts

in the reproductive tract. CFTR staining was localized to the glandular
and luminal epithelium. CLCA1 staining was localized to the endometrial
stroma. Monkeys with endometriosis displayed a significant attenuation
of both CFTR and CLCA1 in the secretory phase. CLCA1 displayed an
exceptionally strong staining in endometriotic uterus, which co-localized
to staining with Von Willebrand Factor.
CONCLUSION: Our studies indicate that both CFTR and CLCA1
undergo cyclic regulation during the menstrual cycle and become
dysregulated due to progesterone resistance. Drugs targeting CLCA1
and CFTR may help with managing fluid secretion in patients with
endometriosis.

F-111
Effect of Pathologically Diagnosed and Clinically Staged Endometriosis
on Future Ovarian Cancer Development: A Retrospective PopulationBased Case Control Study. Emily Barnard†, Valentina Zanfagnin, Amy
Weaver, Tatnai Burnett, Gaurang Daftary, Andrea Mariani*. Mayo Clinic,
Rochester, MN, United States.
INTRODUCTION: Endometriosis is characterized by extra-uterine
endometrial glands and stroma and has historically been considered
benign. However, studies now suggest increased risk of ovarian carcinoma
in patients with endometriosis. Limitations in current literature include
a lack of knowledge of the progression of endometriosis from initial
pathologic diagnosis to subsequent ovarian cancer. Further, there is no
data on how the stage of endometriosis affects risk of future malignancy.
The objective of our study was to evaluate epidemiologic correlates in the
progression of endometriosis to ovarian cancer in women with a pathologic
diagnosis and clinical staging of endometriosis.
METHODS: We conducted a nested case control study using the
Rochester Epidemiology Project database. We identified 18 female
residents of Olmstead County with endometriosis on pathology report
from August 1979 - October 2008 who were either concurrently or
subsequently diagnosed with ovarian, primary peritoneal, or fallopian
tube carcinoma ("index date"). For each case, two age-matched controls
(±3 years) were randomly selected from a cohort of Olmsted County
residents with pathologically-confirmed endometriosis who resided in
the county at the index date and did not have a cancer diagnosis. Stage
of endometriosis was found in operative reports and where not reported
was assigned based on the American Society for Reproductive Medicine's
endometriosis scoring system.
RESULTS: Baseline risk factors between the cases and the controls did
not differ, including age at endometriosis diagnosis, oral contraceptive use,
infertility, tobacco use, or obesity (p > 0.05). However, a trend showed
cancer cases were less likely multiparous compared to controls (55.6%
vs 75.0%; p=0.11). Ovarian cancer was the most common malignancy
(83.3%) followed by fallopian tube (11.1%) and primary peritoneal (5.6%)
carcinoma. Endometrioid histology was dominant (50.0%), followed by
clear cell (11.1%). Cancer was most often diagnosed at stage I (55.5%)
and grade 3 (38.9%). Among the 18 cancer cases, 9 (50%) had stage I
endometriosis and 9 (50%) had stage III endometriosis. We did not identify
a significant association between stage III-IV endometriosis and cancer
(50% of cases vs. 44.4% of controls, p=0.67).
CONCLUSION: Women who develop ovarian, primary peritoneal or
tubal carcinoma do not have a higher risk for malignancy based on more
advanced stage of endometriosis. Patients who were diagnosed with cancer
tended to be discovered at early stage; the most common subtype was
endometrioid. The small number of cases reflect the rarity of this condition.
Future directions include histologic analysis of tissue from cases and
controls to evaluate molecular markers and delineate if differences exist
which could be used prognostically to predict progression to malignancy.

Table of Contents for the Digital Edition of SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018