SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 136A

136A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

Scientific Abstracts

Fibroid characteristics and gestational age adjusting for 1 Age, BMI 2 Age,
BMI, race/ethnicity
Gestational age (days)
Coeff.1
No fibroids

Referent

Presence

-0.3

95% CI1

Coeff.2

95% CI2

(-1.7, 1.2)

0.4

(-1.1, 1.9)

Number
1

0.6

(-1.0, 2.3)

1.1

(-0.6, 2.7)

2+

-2.7

(-5.3, -0.1)

-1.4

(-4.0, 1.2)

Any subserous

-0.7

(-3.1, 1.7)

-0.3

(-2.7, 2.1)

Any intramural

-0.2

(-2.4, 1.9)

0.5

(-1.6, 2.7)

Any submucous

0.0

(-3.1, 3.1)

1.1

(-2.0, 4.1)

Lowest quartile

1.8

(-0.9, 4.6)

2.2

(-0.6, 4.9)

2nd quartile

-1.2

(-3.9, 1.6)

-0.7

(-3.4, 2.1)

3rd quartile

0.1

(-2.7, 2.8)

0.8

(-1.9, 3.5)

Top quartile

-1.8

(-4.6, 0.9)

-0.6

(-3.4, 2.1)

Type

Relationship between fibroid status and risk of preterm birth by indication
(n=4,459)
Outcome

Preterm1

Unadjusted
RR

95% CI

Adjusted
RR2

95% CI

All preterm birth

191

1.18

(0.771.81)

1.14

(0.731.77)

Spontaneous
preterm birth

125

1.36

(0.822.25)

1.29

(0.762.19)

Iatrogenic preterm
birth

66

0.87

(0.382.01)

0.86

(0.362.03)

Analysis compares preterm births to 4,268 term births 2Adjusted for maternal
age and race
1

Total Volume, cm3

T-079
Uterine Fibroids and Risk of Preterm Birth by Indication in a
Prospective Cohort. Alexandra C Sundermann†,1 Tiara D Aldridge,2
Katherine E Hartmann,2 Sarah H Jones,1 Eric S Torstenson,1 Digna R
Velez Edwards*.2 1Vanderbilt Institute for Medicine and Public Health,
Nasvhille, TN, United States; 2Vanderbilt University Medical Center,
Nasvhille, TN, United States.
INTRODUCTION: Uterine fibroids are present in approximately
11% of pregnancies, yet their impact on risk of preterm birth is poorly
characterized. Indication for preterm birth is critical to consider since the
mechanisms for spontaneous preterm birth are distinct from the sequence
of events leading to preterm iatrogenic birth. We sought to determine
the relationship between fibroid presence and risk of preterm birth in a
prospective pregnancy cohort that systematically assessed fibroid status
in the first trimester.
METHODS: Women in the Right from the Start community-based,
prospective pregnancy cohort (2000-2012) received standardized
transvaginal ultrasounds to determine fibroid status, number, size, and
location at a median gestational age of seven weeks, six days. Preterm
birth was defined as live birth prior to 37 weeks' gestation and was
categorized as spontaneous (preterm labor or preterm premature rupture
of membranes) or iatrogenic (delivery for maternal or fetal indications).
We excluded participants without indication for preterm birth (n=162).
We used log-binomial regression to estimate crude and adjusted risk ratios
(RR) and 95% confidence intervals (CI) for the association between fibroid
status and risk of preterm birth by indication.
RESULTS: Among the 4,459 participants with singleton pregnancies,
462 participants had at least one fibroid (10.4%) and 191 pregnancies
resulted in preterm birth (4.3%). The prevalence of fibroids for women
with preterm and term births were comparable (12.0% v. 10.3%). The
overall magnitude of effect for the association between fibroids and
preterm birth is modest and imprecise (see Table). If fibroids increase
risk of preterm birth, the effect is likely driven by the relationship with
spontaneous preterm birth. No fibroid characteristic was associated with
an increased risk of preterm birth.

CONCLUSION: Fibroids are thought to increase risk of preterm birth,
but findings are inconsistent. Studies that do not specify preterm birth
indication may dilute estimates of a true association between fibroid
presence and spontaneous preterm birth. A study that prospectively
differentiates preterm birth outcomes by indication could more clearly
characterize attributable risk.

T-080
Potential of Wharton's Jelly Mesenchymal Stem Cell Exosomes for
the Treatment of Hypoxic-Ischemic Encephalopathy of Prematurity.
Gierin Thomi†,1,2 Marianne Joerger-Messerli,1,2 Valérie Haesler,1,2 Daniel
V Surbek*,1,2 Andreina Schoeberlein*.1,2 1Department of BioMedical
Research, University of Bern, Bern, Switzerland; 2Department of
Obstetrics and Gynecology, Inselspital, Bern University Hospital, Bern,
Switzerland.
INTRODUCTION: Hypoxic-ischemic encephalopathy (HIE) of
prematurity is often accompanied by infection and inflammation. In animal
models of HIE, Wharton's jelly mesenchymal stem cells (WJ-MSC) have
the capacity to induce neuroregeneration and reduce inflammation, mainly
due to their paracrine effects involving the release of exosomes. Our aim
was to evaluate the feasibility of an intranasal administration of WJ-MSCderived exosomes in vivo and their anti-inflammatory potential in vitro.
METHODS: We isolated the exosomes from WJ-MSC supernatants
by serial centrifugations. We evaluated the feasibility of an intranasal
exosome administration using an in vivo model of HIE. Brain damage
was introduced in 3-day old rat pups by lipopolysaccharides (LPS, i.p.)
and unilateral carotid artery cautherization followed by hypoxia (8%
O2). Exosomes were labeled with an infrared dye, delivered intranasally
and traced in the bodies 30 min, 3 h and 24 h later. Microglial activation
was studied using the cell line BV-2. To study anti-inflammatory effects,
BV-cells were stimulated with LPS in presence or absence of exosomes.
Toll like receptor 4 (TLR-4) signaling pathways activation and proinflammatory gene expression were evaluated after 15 min, 30 min, 60
min and 6 h.
RESULTS: Intranasally administered exosomes rapidly translocated to
the brain and diffused locally within 30 min. No exosomes were found in
the spleen, likely excluding systemic absorption. Exosomes suppressed
TLR-4 signaling activation in LPS-stimulated BV-2 cells by preventing
the suppression of NF-κB inhibitor alpha (IκBα) and the phosphorylation
of extracellular signal-regulated kinases (ERK) (P<0.005). This led to a
dampened upregulation of the pro-inflammatory genes tumor necrosis
factor (TNF)-α and interleukin (IL)-6 and suppressed the TLR-4
responsive gene IκBα (P<0.05).
CONCLUSION: In conclusion, we demonstrate that WJ-MSC-derived
exosomes have strong anti-inflammatory effects on microglia cells via
the TLR-4 receptor. Intranasal WJ-MSC exosome delivery bypasses the
systemic circulation and represents a novel cell-free approach to treat
neuroinflammation after HIE. Financial support by Gottfried and Julia
Bangerter-Rhyner Foundation.
Table of Contents for the Digital Edition of SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018
