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Bacterial vaginosis and infertility: Cause or association?

Authors:
  • Sohag faculty of medicin

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Objectives: To estimate the prevalence of bacterial vaginosis (BV) in infertile women and evaluate the effect of treatment of BV on the pregnancy rate in patients with polycystic ovarian disease (PCOD) and unexplained infertility. Study design: Cohort study conducted at the Department of Obstetrics and Gynecology in collaboration with the Microbiology Department of Sohag University Hospital, Egypt. All eligible women with female factor infertility (n=874) were enrolled and all asymptomatic fertile women (n=382) attending the family planning clinic of the study hospital were recruited as a control group. The study was in two phases: the first included screening all participants for BV after Gram-staining of the vaginal discharge. The second phase was concerned with evaluating the effect of treatment of BV on the cumulative pregnancy rate (CPP) in patients with PCOD (group I; n=278) and unexplained infertility (group II; n=170). Each group was divided into three sub-groups: groups Ia (n=129) and IIa (n=73) were BV positive and treated for BV; groups Ib (n=61) and IIb (n=49) were BV positive and did not receive treatment for BV, and groups Ic (n=88) and IIc (n=48) were BV negative. The prevalence of BV was compared using the Chi-square. The long rank test of Kaplan-Meier life table analysis was used to compare the CPR. A multivariate regression model was designed to define the most significant variable which affected the pregnancy rate in patients with PCOD. Results: The prevalence of BV was significantly higher in infertile than fertile women (45.5% vs 15.4%). The highest prevalence was found in patients with PCOD (60.1%) and unexplained infertility (37.4%). The CPR in both patients with PCOD and unexplained infertility were significantly higher in the patients who were treated for BV. Regression model showed that BV was one of the significant factors interfering with pregnancy. Conclusions: BV is strongly implicated in female infertility and is probably an underestimated cause of unexplained infertility. Screening and treatment of BV in patients with PCOD and unexplained infertility improved the pregnancy rate considerably.
Content may be subject to copyright.
Bacterial
vaginosis
and
infertility:
cause
or
association?
Rasheed
M.
Salah
a,
*,
Abdelmonem
M.
Allam
a
,
Amin
M.
Magdy
a
,
Abeer
Sh.
Mohamed
b
a
Department
of
Obstetrics
and
Gynecology,
Sohag
Faculty
of
Medicine,
Sohag
University
Hospital,
Egypt
b
Department
of
Microbiology
and
Immunology,
Sohag
Faculty
of
Medicine,
Sohag
University
Hospital,
Egypt
1.
Introduction
Bacterial
vaginosis
(BV)
is
considered
the
most
common
cause
of
vaginitis
in
sexually
active
women
during
the
reproductive
years
[1].
The
infection
is
characterized
primarily
by
paucity
or
depletion
of
the
vaginal
lacto-bacilli
and
their
replacement
by
an
outgrowth
of
different
micro-organisms
including
Gardnerella
vaginalis
(GV),
anaerobic
rods,
pepto-streptococci,
and
mycoplasma
species
[2].
Although
the
exact
cause
of
this
disruption
of
the
normal
vaginal
milieu
is
still
not
fully
elucidated,
previous
studies
pointed
to
a
role
of
hormonal
disturbances
[3–5].
From
the
obstetric
point
of
view,
BV
is
associated
with
many
complications
including
abortion
[6],
premature
rupture
of
membranes
and
preterm
delivery
[7].
The
implication
of
BV
in
infertility,
on
the
contrary,
is
still
controversial
and
precarious.
While
some
studies
linked
bacterial
vaginosis
to
pelvic
inflamma-
tory
disease
(PID)
and
hence
tubal
infertility
[5,8–10],
others
disputed
any
relationship
[11,12].
Moreover,
previous
studies
reported
a
high
prevalence
of
BV
in
both
non-tubal
and
unexplained
infertility
[5,13,14].
All
studies
concerned
with
the
issue
of
BV
and
infertility,
however,
addressed
mainly
the
prevalence
of
BV
amongst
infertile
women
and
none
tested
the
effect
of
treatment
of
BV
on
the
pregnancy
rate
in
infertile
women.
Moreover,
to
our
knowledge,
the
prevalence
of
BV
in
patients
with
polycystic
ovarian
disease
European
Journal
of
Obstetrics
&
Gynecology
and
Reproductive
Biology
167
(2013)
59–63
A
R
T
I
C
L
E
I
N
F
O
Article
history:
Received
12
February
2012
Received
in
revised
form
16
September
2012
Accepted
25
October
2012
A
B
S
T
R
A
C
T
Objectives:
To
estimate
the
prevalence
of
bacterial
vaginosis
(BV)
in
infertile
women
and
evaluate
the
effect
of
treatment
of
BV
on
the
pregnancy
rate
in
patients
with
polycystic
ovarian
disease
(PCOD)
and
unexplained
infertility.
Study
design:
Cohort
study
conducted
at
the
Department
of
Obstetrics
and
Gynecology
in
collaboration
with
the
Microbiology
Department
of
Sohag
University
Hospital,
Egypt.
All
eligible
women
with
female
factor
infertility
(n
=
874)
were
enrolled
and
all
asymptomatic
fertile
women
(n
=
382)
attending
the
family
planning
clinic
of
the
study
hospital
were
recruited
as
a
control
group.
The
study
was
in
two
phases:
the
first
included
screening
all
participants
for
BV
after
Gram-staining
of
the
vaginal
discharge.
The
second
phase
was
concerned
with
evaluating
the
effect
of
treatment
of
BV
on
the
cumulative
pregnancy
rate
(CPP)
in
patients
with
PCOD
(group
I;
n
=
278)
and
unexplained
infertility
(group
II;
n
=
170).
Each
group
was
divided
into
three
sub-groups:
groups
Ia
(n
=
129)
and
IIa
(n
=
73)
were
BV
positive
and
treated
for
BV;
groups
Ib
(n
=
61)
and
IIb
(n
=
49)
were
BV
positive
and
did
not
receive
treatment
for
BV,
and
groups
Ic
(n
=
88)
and
IIc
(n
=
48)
were
BV
negative.
The
prevalence
of
BV
was
compared
using
the
Chi-square.
The
long
rank
test
of
Kaplan-Meier
life
table
analysis
was
used
to
compare
the
CPR.
A
multivariate
regression
model
was
designed
to
define
the
most
significant
variable
which
affected
the
pregnancy
rate
in
patients
with
PCOD.
Results:
The
prevalence
of
BV
was
significantly
higher
in
infertile
than
fertile
women
(45.5%
vs
15.4%).
The
highest
prevalence
was
found
in
patients
with
PCOD
(60.1%)
and
unexplained
infertility
(37.4%).
The
CPR
in
both
patients
with
PCOD
and
unexplained
infertility
were
significantly
higher
in
the
patients
who
were
treated
for
BV.
Regression
model
showed
that
BV
was
one
of
the
significant
factors
interfering
with
pregnancy.
Conclusions:
BV
is
strongly
implicated
in
female
infertility
and
is
probably
an
underestimated
cause
of
unexplained
infertility.
Screening
and
treatment
of
BV
in
patients
with
PCOD
and
unexplained
infertility
improved
the
pregnancy
rate
considerably.
ß
2012
Elsevier
Ireland
Ltd.
All
rights
reserved.
*
Corresponding
author
at:
Department
of
Obstetrics
and
Gynecology,
Faculty
of
Medicine,
Sohag
University,
University
Street
1,
2334
Sohag,
Egypt.
Tel.:
+2
0932320071;
fax:
+2
0394602963.
E-mail
address:
salahrasheed67@yahoo.com
(R.M.
Salah).
Contents
lists
available
at
SciVerse
ScienceDirect
European
Journal
of
Obstetrics
&
Gynecology
and
Reproductive
Biology
jou
r
nal
h
o
mep
ag
e:
w
ww
.elsevier
.co
m
/loc
ate/ejo
g
rb
0301-2115/$
see
front
matter
ß
2012
Elsevier
Ireland
Ltd.
All
rights
reserved.
http://dx.doi.org/10.1016/j.ejogrb.2012.10.031
TM
PDF Editor
(PCOD),
with
its
associated
hormonal
disturbances,
has
not
previously
been
addressed.
Accordingly,
the
aim
of
the
present
study
was
to
assess
the
prevalence
of
BV
and
evaluate
the
effect
of
treatment
of
BV
on
the
pregnancy
rate
in
infertile
women.
2.
Materials
and
methods
The
present
prospective
cohort
study
was
conducted
from
1st
March
2009
till
1st
September
2011
at
the
Obstetrics
and
Gynecology
Department
in
collaboration
with
the
Department
of
Microbiology
and
Immunology
of
Sohag
University
Hospital,
Egypt.
During
the
study
period,
all
women
with
female
factor
infertility
were
invited
to
participate
in
the
study
and
were
assigned
as
a
study
group
(n
=
979).
All
asymptomatic
fertile
women
(n
=
382)
attending
the
family
planning
clinic
of
the
study
hospital
who
agreed
to
participate
in
the
study
were
recruited
as
a
control
group.
Local
institutional
ethical
commit-
tee
provided
approval
and
written
consent
was
obtained
from
all
participants.
Thorough
clinical
and
sonographic
assessments
of
the
partici-
pants
were
undertaken.
Blood
samples
were
drawn
from
the
study
group
for
assay
of
the
basal
hormonal
profile
(FSH,
LH,
free
androgen
index
[FAI],
T3,
T4,
and
prolactin).
The
study
group
was
categorized
according
to
the
cause
of
infertility
into
those
with
PCOD
(n
=
371),
unexplained
infertility
(n
=
289),
tubal
infertility
(n
=
126),
and
endometriosis
(n
=
88).
PCOD
was
diagnosed
according
to
the
Rotterdam
criteria
[15]
while
tubal
infertility
and
endometriosis
were
diagnosed
after
conducting
laparoscopy
(Olympus,
Germany).
According
to
our
protocol,
unexplained
infertility
entailed
infertility
for
more
than
one
year
despite
regular
marital
life,
regular
cycles,
uneventful
clinical
examination,
normal
husband
semen
analysis
according
to
the
WHO
criteria
[16],
normal
basal
hormonal
level
(FSH,
LH,
T3,
T4,
and
prolactin),
regular
ovulation
for
at
least
three
consecutive
cycles
(documented
by
serial
folliculometry
and
midluteal
serum
progesterone
>10
ng/
dl),
normal
hysterosalpingography,
and
normal
laparoscopic
findings.
The
study
was
in
two
phases.
The
first
phase
aimed
at
evaluating
the
prevalence
of
BV.
This
was
done
through
screening
all
eligible
participants
(those
with
PCOD,
unexplained
infertility,
tubal
infertility,
and
endometriosis)
for
BV.
Exclusion
criteria
of
participants
during
this
stage
were
refusal
to
participate
in
the
study
and
abnormal
husband
semen
analysis.
The
second
phase
was
concerned
with
evaluating
the
effect
of
treatment
of
BV
on
the
pregnancy
rate
in
infertile
women.
In
order
to
accomplish
this,
patients
with
tubal
infertility
and
endometriosis
were
excluded
during
this
stage
and
only
those
with
PCOD
and
unexplained
infertility
were
followed
up
for
six
months
to
calculate
the
cumulative
pregnancy
rate
(CPR).
Exclusion
criteria
during
this
stage
were
refusal
to
participate
in
the
study,
presence
of
uterine
or
adnexal
pathology,
previous
PID,
previous
pelvic
surgery,
referral
to
assisted
reproduction,
previous
laparoscopic
ovarian
drilling
(LOD)
in
patients
with
PCOD,
and
obesity
(BMI
>
30
kg/m
2
)
in
patients
with
unexplained
infertility.
During
the
second
phase,
patients
with
PCOD
and
unexplained
infertility
were
assigned
as
groups
I
and
II
respectively.
Without
randomization,
some
of
the
BV-positive
patients
in
the
two
aforementioned
groups
were
treated
for
BV
while
the
rest
of
the
patients
were
not
treated.
Each
group
was
divided
into
three
subgroups:
groups
Ia
(n
=
129)
and
IIa
(n
=
73)
were
BV
positive
and
received
treatment
for
BV;
groups
Ib
(n
=
61)
and
IIb
(n
=
49)
were
BV
positive
and
did
not
receive
treatment
for
BV,
and
groups
Ic
(n
=
88)
and
IIc
(n
=
48)
were
BV
negative
and
considered
as
a
control
subgroup.
Both
partners
were
treated
for
BV
using
a
single
dose
of
2
g
secnidazole
(Secnidazole,
IEPICO,
Egypt)
which
was
repeated
every
month
in
the
patients
who
did
not
conceive.
Patients
with
PCOD
were
treated
with
clomiphene
citrate
(Clomid,
Sanafi
Aventis,
France)
50
mg
twice
daily
for
five
consecutive
days
starting
from
the
second
day
of
a
spontaneous
or
induced
cycle.
Trans-vaginal
folliculometry
(Acuson
XP,
USA)
was
conducted
and
when
al
least
one
follicle
measured
18
mm,
10,000
IU
of
human
chorionic
gonadotropin
was
given.
Midluteal
serum
progesterone
level
was
assayed
and
a
value
of
>10
ng/dl
was
indicative
of
ovulation.
If
the
patient
failed
to
ovulate,
the
dose
of
clomiphene
citrate
was
increased
during
the
subsequent
cycles
to
a
maximum
of
200
mg/day.
The
patients
who
failed
to
ovulate
were
excluded
from
the
statistical
analysis
only
during
the
same
cycle.
Patients
with
unexplained
infertility
were
treated
with
gonadotropins
using
the
standardized
step-up
protocol
described
elsewhere
[17]
or
referred
to
assisted
reproduction.
Screening
for
BV
was
undertaken
during
the
initial
clinical
evaluation
of
the
participants.
A
sterile
non-lubricated
Cusco’s
speculum
was
introduced
into
the
vagina
and
a
swab
from
the
discharge
of
the
posterior
fornix
was
taken
using
a
sterile
cotton
swab.
The
swab
was
immediately
smeared
onto
a
glass
slide,
left
to
dry
then
Gram-stained
and
examined
under
the
microscope
(1000
magnification).
BV
was
diagnosed
according
to
the
modified
Spiegel’s
criteria
[18]
which
categorize
the
vaginal
flora
into
three
grades:
normal
(mainly
lacto-bacilli),
intermediate
(reduced
lacto-bacilli
with
increased
number
of
other
morpho-
types),
and
BV
(depleted
or
absent
lacto-bacilli
with
predominance
of
other
morphotypes;
mainly
GV).
The
sample
size
of
the
study
was
calculated
so
as
to
achieve
80%
power
and
5%
confidence
of
significance.
Depending
upon
the
results
of
published
studies,
we
assumed
12%
and
24%
prevalence
of
BV
in
the
fertile
and
infertile
women
respectively.
According
to
these
proportions,
the
calculated
sample
size
needed
for
the
study
was
246
patients.
Owing
to
the
expected
high
drop-out
rate
and
the
design
of
the
study
which
required
multiple
sub-groupings
of
the
participants,
more
than
three
times
the
calculated
sample
size
was
enrolled
into
the
study.
The
prevalence
of
BV
in
the
different
causes
of
infertility
was
compared
using
the
Chi-square
and
the
real
variables
were
compared
using
Student’s
t-test
(p
value
<0.05
was
considered
significant).
Kaplan-Meier
life
table
analysis
was
used
to
calculate
the
CPR
during
the
6-month
follow-up
period
and
the
log
rank
test
was
used
to
compare
the
statistical
difference.
Cox
regression
was
used
to
perform
a
univariate
analysis
of
the
possible
variables
which
may
affect
the
pregnancy
rate
in
patients
with
PCOD.
A
forwards
multivariate
step-wise
regression
model
was
then
designed
to
define
the
most
significant
variable
which
affected
the
pregnancy
rate
in
patients
with
PCOD.
The
statistical
analysis
was
done
according
to
the
per
protocol
rule.
3.
Results
During
the
study
period,
a
total
of
979
infertile
women
were
recruited
for
the
study.
A
total
of
874
infertile
women
fulfilled
the
inclusion
criteria
and
were
assigned
as
a
study
group
while
382
asymptomatic
fertile
women
agreed
to
participate
as
controls.
The
study
group
included
371
(42.4%)
patients
with
PCOD,
289
(33.1%)
with
unexplained
infertility,
126
(14.4%)
with
tubal
infertility,
and
88
(10.1%)
with
endometriosis.
During
the
second
phase
of
the
study,
a
total
of
212
(32.1%)
patients
(93
with
PCOD
and
119
with
unexplained
infertility)
were
excluded
while
the
remaining
448
patients
(278
with
PCOD
and
170
with
unexplained
infertility)
were
enrolled
into
the
study
(Fig.
1).
The
average
ages
(25.8
3.1
years
vs
27.1
2.2
years)
and
BMI
(26.3
2.1
vs
26.9
1.8)
were
comparable
in
the
fertile
and
infertile
women.
The
prevalence
of
BV
in
the
control
women
was
15.4%
(59/
382)
compared
to
45.5%
(398/874)
in
infertile
women
(p
<
0.001).
The
highest
prevalence
of
BV
(60.1%)
was
found
in
patients
with
PCOD
R.M.
Salah
et
al.
/
European
Journal
of
Obstetrics
&
Gynecology
and
Reproductive
Biology
167
(2013)
59–63
60
TM
PDF Editor
(OR
=
7.11;
p
<
0.001)
followed
by
those
with
unexplained
infertility
(OR
=
3.24;
p
=
0.001)
(Table
1).
During
the
second
phase
of
the
study,
the
average
age,
BMI,
duration
of
infertility,
ovarian
volume,
LH,
FAI,
and
the
ovulation
rates
in
patients
with
PCOD
were
comparable
in
the
three
sub-
groups
(data
not
shown).
The
pregnancy
rate
during
the
first
cycle
was
significantly
higher
in
group
Ic
(14.2%)
than
groups
Ia
(6.3%;
p
=
0.03)
and
Ib
(5.9%;
p
=
0.03).
The
CPR
was
significantly
higher
in
group
Ia
than
Ib
(49.1%
vs
23.5%;
p
=
0.001)
and
comparable
to
group
Ic
(51.3%)
(Fig.
2).
The
same
trend
was
found
in
patients
with
unexplained
infertility,
where
the
CPR
was
higher
in
group
IIa
than
IIb
(24.5%
vs
14.3%;
p
=
0.04)
and
comparable
to
group
IIc
(26.1%)
(Fig.
3).
A
bbreviati
ons
, BV; Bacterial vaginos
is,
PCOD;
po
lycystic ovarian disease,
A
RT; Assi
sted reproductive techniques,
OHSS;
Ovarian
hyp
ers
timula
tion
syndrome, LOD; Laparoscopic ovarian dri
lling,
UI
; Unex
plaine
d inf
ertility
,
CPR; Cumul
ative pr
egn
ancy rate.
1st phase
;
Infer
tile patie
nts
assesse
d for
eligibility
(study g
rou
p,
n=97
9)
Enrol
lment (n=87
4)Excluded (n=
105)
Screening
for BV
Fertile women
(control gr
oup,
n = 382)
2nd ph
ase
;pati
ents
with
PCOD
and un
explai
ned
infer
tility
Enrol
lment (n
= 660)
Allocation (n = 448)
Excluded
(n = 212)
-
Drop-ou
t
(n = 91)
-Fa
ilure
to afford
for
gonad
otropin (n= 45)
-
Referral to A
RT
(n=
24)
-
OHSS (n = 18)
-
LOD
(n =
14)
-
Obesity (n
=
13)
-
Pelv
ic surge
ry
(n
= 5)
-
Divorce
(n = 2)
Group I:
PCOD (n=278) Grou
p II:
UI (n = 170)
No
randomization
IIa
: Treated
for
BV
(n=73)
IIb:
Un
-treated
for
BV (n=49)
IIc:
BV ne
gative
(n=48)
Ia: T
reated for BV
(n=129)
Ib: Un
-tre
ated
for BV
(n=61)
Ic: BV ne
gative (n=88)
-
Refusal to participate
(n=34)
-
Abnormal semen
(n= 71
)
Ia:
49.1%
Ib: 23.5%
Ic: 51.3%
6-month
CPR
IIa: 2
4.5%
IIb: 1
4.3%
IIC: 26.1%
Fig.
1.
Flowchart
of
the
study.
Table
1
The
prevalence
of
bacterial
vaginosis
in
infertile
women
with
different
causes
of
infertility.
Prevalence
(%)
OR
(CI)
p
Value
a
Total
infertility
45.5
5.23
(3.06
8.12)
0.0001
PCOD
60.1
7.11
(4.56
12.3)
0.0001
Unexplained
infertility
37.4
3.24
(2.15
5.16)
0.001
Tubal
infertility
24.6
1.83
(0.90
3.71)
0.09
Endometriosis
19.3
0.70
(0.83
3.47)
0.32
Control
15.4
All
data
were
expressed
as
mean
SD,
unless
otherwise
indicated.
Abbreviations:
OR:
odd
ratio;
CI:
confidence
interval;
PCOD:
polycystic
ovarian
disease.
a
Compared
to
the
control
group.
R.M.
Salah
et
al.
/
European
Journal
of
Obstetrics
&
Gynecology
and
Reproductive
Biology
167
(2013)
59–63
61
TM
PDF Editor
Univariate
analysis
showed
that
the
age,
duration
of
infertility,
BMI,
FAI,
LH,
and
BV
were
the
most
significant
variables
which
affected
the
pregnancy
rate
in
patients
with
PCOD
(Table
2).
After
adjustment
for
age,
BMI,
and
LH
using
a
multivariate
analysis,
BV
still
showed
significant
difference
between
the
pregnant
and
non-
pregnant
patients.
This
difference
became
abolished
only
after
adjustment
for
FAI
(Table
3).
4.
Comment
The
present
study
reported
a
high
prevalence
of
BV
in
infertile
women,
particularly
those
with
PCOD
and
unexplained
infertility,
and
to
a
lesser
extent
in
those
with
tubal
infertility.
These
results
disagreed
with
those
reported
by
Wilson
et
al.
[5]
who
reported
a
higher
prevalence
of
BV
in
patients
with
tubal
infertility
than
those
with
unexplained
and
ovulatory
infertility.
Among
our
partici-
pants,
however,
the
largest
group
had
PCOD
(42.5%)
with
its
consequences
of
anovulation
and
hormonal
disturbances.
Many
studies
have
suggested
a
possible
role
of
hormonal
imbalance
in
the
acquisition
of
BV
[3–5].
By
contrast,
in
the
study
of
Wilson
et
al.,
a
large
proportion
of
the
patients
had
tubal
infertility
while
a
minority
had
anovulation.
This
difference
in
the
proportions
of
the
causes
of
infertility
could
explain
the
contradiction
between
the
two
studies.
The
high
prevalence
of
BV
in
infertile
women
may
suggest
either
a
possible
role
of
BV
on
fertility
or
just
an
association
between
BV
and
infertility.
Although
some
studies
concluded
that
infertile
patients
were
inherently
predisposed
to
BV
and
disputed
any
role
of
BV
in
fertility
[11,12,19,20],
the
results
of
the
current
study
not
only
contradict
this
conclusion
but
also
provide
evidences
for
a
possible
role
of
BV
in
infertility.
The
high
prevalence
of
BV
in
the
different
causes
of
infertility,
even
including
those
with
endometriosis,
is
one
piece
of
evidence.
The
results
of
the
univariate
analysis
of
the
variables
which
affected
the
pregnancy
rate
in
patients
with
PCOD
provide
another.
These
findings
are
further
reinforced
by
the
results
of
the
regression
model.
Even
after
controlling
for
the
different
variables
which
influenced
the
pregnancy
rate
in
patients
with
PCOD,
BV
still
remained
a
significant
factor
impairing
the
pregnancy
rate.
Moreover
the
deleterious
effect
of
BV
on
fertility
was
abolished
only
after
adjustment
for
the
FAI;
a
finding
which
may
suggest
a
possible
link
between
BV
and
high
androgen
levels.
Similar
to
our
results,
some
studies
have
suggested
a
possible
role
of
BV
on
female
fertility
[5,8–10,13].
None
of
these
studies,
however,
evaluated
the
influence
of
treatment
of
BV
on
the
pregnancy
rate.
To
the
best
of
our
knowledge,
the
present
study
was
the
first
to
test
the
effect
of
treatment
of
BV
on
the
pregnancy
rate
in
infertile
women.
The
present
study
showed
that
a
single-
dose
treatment
of
BV
was
associated
with
a
high
CPR
in
patients
with
PCOD
and
unexplained
infertility.
These
high
pregnancy
rates
not
only
provide
a
clear
evidence
implicating
BV
in
infertility,
but
also
suggest
BV
as
a
new
cause
of
unexplained
infertility
which
has
probably
been
underestimated.
One
of
the
most
interesting
findings
of
the
current
study
was
the
very
high
proportion
of
BV
in
patients
with
PCOD.
This
may
seem
illogical
as
it
is
well
known
that
a
high
estrogen
milieu,
which
Table
2
Univariate
analysis
of
the
variables
which
affected
the
pregnancy
rate
in
patients
with
PCOD.
Pregnant
(n
=
143)
Not
pregnant
(n
=
(135)
p
Value
Age
(years)
22.5
1.2
28.7
0.9
0.02
Infertility
(years)
1.7
0.8
4.1
1.1
0.02
BMI
(kg/m
2
)
28.3
1.4
33.6
1.4
0.01
LH
(mIU/dl)
9.4
0.6
16.1
2.4
0.01
FIA
3.6
0.99
7.5
2.8
0.001
Ovarian
volume
(cm
3
)
9.9
2.2
11.6
0.9
0.37
LH/FSH
ratio
4.4
0.9
6.2
1.2
0.03
BV
(%)
23.2
4.1
44.7
2.5
0.001
All
data
were
expressed
as
mean
SD,
unless
otherwise
indicated.
Abbreviations:
BMI:
body
mass
index;
LH:
luteinizing
hormone;
FAI:
free
androgen
index
(serum
testosterone
100/sex
hormone
binding
globulin);
FSH:
follicle
stimulating
hormone;
BV:
bacterial
vaginosis.
Table
3
Step-wise
multivariate
logistic
regression
analysis
of
the
variables
which
affected
the
pregnancy
rate
in
patients
with
PCOD.
Univariate
analysis
a
Multivariate
analysis
Step
1
Step
2
Step
3
Step
4
Age
(years)
0.02
In
model
In
model
In
model
In
model
Infertility
(years)
0.02
0.03
In
model
In
model
In
model
BMI
(kg/m
2
)
0.01
0.08
0.13
0.64
0.98
LH
(mIu/dl)
0.01
0.01
0.04
In
model
In
model
FAI
0.001
0.001
0.01
0.02
In
model
FSH/LH
0.03
0.04
0.08
0.15
0.23
BV
0.001
0.01
0.03
0.03
0.14
All
data
were
expressed
as
mean
SD,
unless
otherwise
indicated.
Abbreviations:
BMI:
body
mass
index;
LH:
luteinizing
hormone;
FAI:
free
androgen
index
(serum
testosterone
100/sex
hormone
binding
globulin);
FSH:
follicle
stimulating
hormone;
BV:
bacterial
vaginosis.
a
Only
variables
with
statistical
significance
were
included.
0
10
20
30
40
50
60
1
2
3
4
5
6
Months
Pregnancy rate (%)
Treated for BV
Un-treated for VB
BV-negative
p (long rank test) = 0.001
Fig.
2.
Cumulative
pregnancy
rates
in
patients
with
PCOD.
0
5
10
15
20
25
30
1
2
3
4
5
6
Months
Pregnancy rate (%)
Treated for BV
Un-treated for BV
BV-negative
p (lo
ng r
ank t
est
) = 0.04
Fig.
3.
Cumulative
pregnancy
rates
in
patients
with
unexplained
infertility.
R.M.
Salah
et
al.
/
European
Journal
of
Obstetrics
&
Gynecology
and
Reproductive
Biology
167
(2013)
59–63
62
TM
PDF Editor
is
the
case
in
PCOD,
increases
the
number
of
the
lactobacilli
and
decreases
the
risk
of
BV
[21].
PCOD
is
also
associated
with
other
hormonal
disturbances,
however,
particularly
elevated
androgen
levels
and
insulin
resistance.
Whether
these
hormonal
distur-
bances
were
responsible
for
the
high
prevalence
of
BV
in
patients
with
PCOD
is
a
question
that
remains
unanswered.
Nevertheless,
the
dramatic
increase
in
the
pregnancy
rate
after
treatment
of
BV
in
patients
with
PCOD
might
suggest
a
hypothetical
vicious
circuit
of
hormonal
disruption
leading
to
increased
risk
of
BV
which
may
participate
in
perpetuating
the
problem
of
infertility.
Another
interesting
finding
was
the
surprisingly
low
pregnancy
rates
during
the
first
cycle
after
treatment
of
BV
which
was
even
lower
than
that
of
the
control
subgroups.
This
finding
was
consistent
in
patients
with
PCOD
and
unexplained
infertility.
Although
the
exact
means
by
which
BV
may
cause
infertility
is
still
unsettled,
many
mechanisms
including
plasma
cell
endometritis
[10,22],
tubal
motility
disorders
[1],
and
auto-immune
infertility
[13,23]
have
been
proposed.
It
is
possible
that
one
or
more
of
the
effects
of
these
factors
may
still
persist
for
some
time
after
treatment
of
BV
and
may
be
responsible
for
the
low
pregnancy
rate
during
the
first
cycle
of
treatment.
Another
possible
explanation
is
resistance
of
BV
to
treatment,
but
the
high
pregnancy
rate
during
the
subsequent
cycles
precluded
this
explanation.
The
most
evident
limitation
of
the
present
study
was
the
lack
of
follow-up
of
the
patients
to
detect
resistance
or
recurrence
of
BV
following
treatment.
Previous
studies,
however,
reported
high
cure
and
low
recurrence
rates
after
treatment
of
BV
with
secnidazole
[24].
Moreover,
administering
the
drug
every
cycle
might
further
decrease
the
recurrence
rate.
Another
point
of
concern
was
the
non-randomization
of
the
participants.
Although
at
the
beginning
of
the
study
the
authors
designed
it
as
a
randomized
one,
but
this
randomization
was
not
possible
because
a
large
number
of
participants
refused
to
be
included
in
the
control
sub-groups.
A
third
shortcoming
was
lack
of
information
about
the
methods
of
contraception
(which
may
influence
the
prevalence
of
BV)
used
by
the
control
group.
In
conclusion,
the
prevalence
of
BV
was
very
high
in
infertile
women,
particularly
those
with
PCOD
and
unexplained
infertility.
BV
is
strongly
implicated
in
female
infertility
and
it
is
probably
an
underestimated
cause
of
unexplained
infertility.
Screening
and
treatment
of
BV
during
the
course
of
infertility
treatment
increased
the
pregnancy
rate
considerably.
Randomized
studies
including
larger
number
of
participants
are
needed,
however,
to
reach
more
validated
conclusions.
Moreover,
research
is
strongly
recom-
mended
on
the
mechanisms
by
which
BV
impairs
fertility
and
on
the
link
between
BV
and
elevated
androgen
levels.
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... It can be cured by restoring the representative vaginal components of the microbiota with probiotic formula, usually species of the genus Lactobacillus [15,16]. Salah et al. [17] postulated that BV is strongly implicated in underestimated causes of unexplained infertility. They found that BV detection and treatment improves the pregnancy rate in women [17]. ...
... Salah et al. [17] postulated that BV is strongly implicated in underestimated causes of unexplained infertility. They found that BV detection and treatment improves the pregnancy rate in women [17]. Furthermore, van Oostrum et al. [18] claim that BV is meaningfully linked with preclinical pregnancy loss. ...
Article
Full-text available
The use of probiotics in reproductive-related dysbiosis is an area of continuous progress due to the growing interest from clinicians and patients suffering from recurrent reproductive microbiota disorders. An imbalance in the natural colonization sites related to reproductive health—vaginal, cervicovaginal, endometrial, and pregnancy-related altered microbiota—could play a decisive role in reproductive outcomes. Oral and vaginal administrations are in continuous discussion regarding the clinical effects pursued, but the oral route is used and studied more often despite the need for further transference to the colonization site. The aim of the present review was to retrieve the standardized protocols of vaginal probiotics commonly used for investigating their microbiota modulation capacities. Most of the studies selected focused on treating bacterial vaginosis (BV) as the most common dysbiosis; a few studies focused on vulvovaginal candidiasis (VVC) and on pretreatment during in vitro fertilization (IVF). Vaginal probiotic doses administered were similar to oral probiotics protocols, ranging from ≥107 CFU/day to 2.5 × 1010 CFU/day, but were highly variable regarding the treatment duration timing. Moderate vaginal microbiota modulation was achieved; the relative abundance of abnormal microbiota decreased and Lactobacillus species increased.
... Bacterial vaginosis (BV) is the worldwide leading vaginal bacterial infection identified in women of childbearing age, with a high prevalence in the general population, ranging from 23% to 29% across regions (Peebles et al., 2019). If left untreated, BV may cause serious obstetric and gynaecologic complications, including preterm delivery (Romero et al., 2004;Shimaoka et al., 2019), spontaneous abortion (Leitich and Kiss, 2007;Isik et al., 2016), low birth weight (Goldenberg and Culhane, 2003;Dingens et al., 2016), pelvic inflammatory disease (Ness et al., 2005;Gondwe et al., 2020), infertility (Salah et al., 2013), and may also lead to an increased risk of acquisition and transmission of several sexually transmitted infectious agents (Gillet et al., 2011;Haddad et al., 2018). Although the understanding of BV etiology is still limited, it is known that BV is characterized by a decrease of beneficial vaginal bacteria and by an increase of strict and facultative anaerobic bacteria (Chen et al., 2021) leading to the development of a polymicrobial biofilm (Swidsinski et al., 2005). ...
Article
Full-text available
Bacterial vaginosis (BV) is associated with serious gynaecologic and obstetric complications. The hallmark of BV is the presence of a polymicrobial biofilm on the vaginal epithelium, but BV aetiology is still a matter of debate. We have previously developed an in vitro biofilm model that included three BV-associated species, but, up to now, no studies are available whereby more bacterial species are grown together to better mimic the in vivo situation. Herein, we characterized the first polymicrobial BV biofilm consisting of six cultivable BV-associated species by using both in vitro and ex vivo vaginal tissue models. Both models revealed that the six species were able to incorporate the polymicrobial biofilm, at different bacterial concentrations. As it has been thought that this polymicrobial biofilm may increase the survival of BV-associated species when exposed to antibiotics, we also assessed if the Thymbra capitata essential oil (EO), which has recently been shown to be highly bactericidal against several Gardnerella species, could maintain its anti-biofilm activity against this polymicrobial biofilm. Under our experimental conditions, T. capitata EO exhibited a high antibacterial effect against polymicrobial biofilms, in both tested models, with a significant reduction in the biofilm biomass and the number of culturable cells. Overall, this study shows that six BV-associated species can grow together and form a biofilm both in vitro and when using an ex vivo model. Moreover, the data obtained herein should be considered in further applications of T. capitata EO as an antimicrobial agent fighting BV.
... The human vaginal microbiome is generally characterised by the presence of five community state types based on the dominating species of bacteria (Verstraelen et al. 2009). Among these communities, four communities are dominated by Lactobacillus species (Verstraelen et al. 2009), while the fifth community lacks Lactobacillus dominance and shows overgrowth of pathogenic bacteria resulting in bacterial vaginosis and subsequent adverse pregnancy outcomes (Salah et al. 2013). Assessment of vaginal microbiota during induced cycles for embryo transfer after in vitro processes have found that microbiota composed solely of Lactobacillus (Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus gasseri or other Lactobacillus spp.) are associated with successful outcomes (Hyman et al. 2012;Koedooder et al. 2019). ...
Article
The role played by microbiota is attracting growing attention within the scientific and medical community, in both human and animal fields, in the last years. Most of the studies have been focused on the intestinal microbiome, whilst little attention has been paid to other systems, like the reproductive tract of both females and males. However, there is a growing body of information showing the interplay between reproductive tract dysbiosis, due to the action of pathogens and/or unhealthy lifestyle, and reproductive disease and disorders in many mammalian species. The present review aims to summarise current knowledge on the biodiversity of the microbiota of the reproductive tract, and the possible relationships between eubiosis or dysbiosis and reproductive health and function in both females and males.
... In addition to its ubiquity, BV is a urogenital condition that has been associated with adverse reproductive health outcomes including infertility 8 , increased risk for pre-term birth 9 , and low birth weights 10 . Moreover, an active state of BV is associated with an elevated risk for transmission of a variety of sexually transmitted infections (STIs) ranging from bacterial pathogens such as Chlamydia 11 and Mycoplasma 12 , to viral agents including HIV 13,14 and human papillomavirus (HPV) 15 . ...
Article
Full-text available
Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV , a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661.
... There is a high prevalence of BV among infertile patients compared to fertile women (45.5% vs. 15.4%). BV can also be found in 37.4% of patients with unexplained infertility and 60.1% of those with polycystic ovarian disease (PCOD) [48]. Moreover, BV treatment may also have positive effects to pregnancy rates in those infertile women [49]. ...
Article
Full-text available
In modern society, 75% of all women worldwide have had vaginitis at least once in their lives. The vagina has a dynamic microbial ecosystem with varying vaginal pH levels. An imbalance in that ecosystem can alter the vaginal pH and tip the scale to the point of causing issues, such as vaginitis, that require medical attention. Although vaginitis is not an incurable disease, it causes discomfort and pain that disrupt women’s daily lives. The most common causes of vaginitis include bacterial vaginosis, trichomoniasis, and vulvovaginal candidiasis. In this review, we discuss the causes, diagnostic methods, and symptoms of different types of vaginitis, the relationship of vaginitis to the prevalence of other diseases, issues associated with recurrent vaginitis and the immune system, and a variety of effective available treatments. In our article, we summarize the relationship of pH with the vaginal ecosystem, discuss the associated factors of vaginal pH, and finally introduce the different available vaginal pH self-test products.
Article
Objectives This study seeks to examine the association between predisposing risk factors and the prevalence of bacterial vaginosis (BV) as well as Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) infections in reproductive age women and investigate its relationship with infertility. Methods This cross-sectional, prospective study was carried out using sexually active females who presented at the Gynaecology Clinic with complaints of vaginal discharge. Two cervical smear samples were taken from the endocervical canal using sterile cotton swabs for each patient. The patients were questioned to obtain their demographic data and potential risk factors for lower genital tract infections, and their responses were recorded. Results Of 348 patients, BV was detected in 46.3%, UU in 26.7%, MH in 3.7% and UU and MH co-infection in 13.2%. The prevalence of BV concomitant with UU and/or MH was significantly high (p = .001). The most prominent risk factors for BV were UU and MH infection (AOR = 6.79, 95% confidence interval (CI): [2.63–17.56]), vaginal douche use (AOR = 6.80, 95% CI: [03.60–12.83]), abortion history (AOR = 2.82, 95% CI: [1.55–5.12]) and high body mass indexes (BMI) (AOR = .81, 95% CI: [.74–.89]). The prevalence of BV, UU and MH was significantly higher in infertile patients than fertile patients (p = .002). Conclusions Bacterial vaginosis, MH, and UU co-infection were common in patients with vaginal discharge, and it was detected considerably higher in infertile patients than in fertile patients.
Article
Background Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by the presence of a polymicrobial biofilm on the vaginal epithelium, formed primarily by Gardnerella spp., but also other anaerobic species. Interactions between bacteria in multi-species biofilms are likely to contribute to increased virulence and to enhanced antimicrobial tolerance observed in vivo. However, functional studies addressing this question are lacking. Objectives To gain insights into the role that interactions between BV-associated species in multi-species BV biofilms might have on antimicrobial tolerance, single- and triple-species biofilms formed by Gardnerella vaginalis, Fannyhessea (Atopobium) vaginae and Peptostreptococcus anaerobius were characterized, before and after metronidazole or clindamycin treatment. Methods Total biofilm biomass, total cells and cfu counts prior to and after antibiotic treatment were first determined. In addition, bacterial populations in the triple-species biofilms were also quantified by quantitative PCR (qPCR) and peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH). Results Despite the effect observed in single-species biofilms, neither metronidazole nor clindamycin was effective in reducing triple-species biofilm biomass. Similar results were obtained when evaluating the number of total or culturable cells. Interestingly, despite differences between strain susceptibilities to antibiotics, the composition of the triple-species biofilms was not strongly affected by antibiotics. Conclusions Taken together, these results strengthen the idea that, when co-incubated, bacteria can interact synergistically, leading to increased tolerance to antimicrobial therapy, which helps explain the observed clinically high BV recurrence rates.
Article
Study question: To what extent is female preconception antibiotic use associated with fecundability? Summary answer: Preconception antibiotic use overall was not appreciably associated with fecundability. What is known already: Antibiotics are commonly used by women and are generally thought to be safe for use during pregnancy. However, little is known about possible effects of antibiotic use on fecundability, the per-cycle probability of conception. Previous research on this question has been limited to occupational rather than therapeutic exposure. Study design, size, duration: We analyzed data from an Internet-based preconception cohort study of 9524 female pregnancy planners aged 21-45 years residing in the USA and Canada who had been attempting to conceive for six or fewer cycles at study entry. Participants enrolled between June 2013 and September 2020 and completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. The questions pertaining to antibiotic type and indication were added to the PRESTO questionnaires in March 2016. Participants/materials, setting, methods: We assessed antibiotic use in the previous 4 weeks at baseline and on each follow-up questionnaire. Participants provided the name of the specific antibiotic and the indication for use. Antibiotics were classified based on active ingredient (penicillins, macrolides, nitrofurantoin, nitroimidazole, cephalosporins, sulfonamides, quinolones, tetracyclines, lincosamides), and indications were classified by type of infection (respiratory, urinary tract, skin, vaginal, pelvic, and surgical). Participants reported pregnancy status on follow-up questionnaires. We used proportional probabilities regression to estimate fecundability ratios (FR), the per-cycle probability of conception comparing exposed with unexposed individuals, and 95% CI, adjusting for sociodemographics, lifestyle factors, and reproductive history. Main results and the role of chance: Overall, women who used antibiotics in the past 4 weeks at baseline had similar fecundability to those who had not used antibiotics (FR: 0.98, 95% CI: 0.89-1.07). Sulfonamides and lincosamides were associated with slightly increased fecundability (FR: 1.39, 95% CI: 0.90-2.15, and FR: 1.58 95% CI: 0.96-2.60, respectively), while macrolides were associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47-1.04). Analyses of the indication for antibiotic use suggest that there is likely some confounding by indication. Limitations, reasons for caution: Findings were imprecise for some antibiotic classes and indications for use owing to small numbers of antibiotic users in these categories. There are likely heterogeneous effects of different combinations of indications and treatments, which may be obscured in the overall null results, but cannot be further elucidated in this analysis. Wider implications of the findings: There is little evidence that most antibiotics are associated with reduced fecundability. Antibiotics and the infections they treat are likely associated with fecundability through differing mechanisms, resulting in their association with increased fecundability in some circumstances and decreased fecundability in others. Study funding/competing interest(s): This study was supported through funds provided by the National Institute of Child Health and Human Development, National Institutes of Health (R01-HD086742, R21-HD072326). L.A.W. has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, Fertility Friend, and Kindara for primary data collection in PRESTO. The other authors have no conflicts of interest to disclose. Trial registration number: N/A.
Preprint
Full-text available
Bacterial vaginosis (BV) is a highly prevalent condition that is associated with acquisition of sexually transmitted infections and adverse reproductive outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced local inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. We demonstrate that 16S rRNA amplicon sequencing and a novel pipeline can be used to generate a molecular Nugent BV score (molBV) corresponding to the Nugent score 0 - 10. This algorithm is independent of the region of 16S rRNA amplified, the sequencing platform and source population. We further identify two local immune cytokine patterns associated with this molecular Nugent score (q-values<0.001). The main immune response is represented by an elevated IL-1β/IP-10 ratio, whereas a second pattern consists of an increased TNF-α/MIP-1β ratio. To evaluate the biological significance of molBV-BV and the local immune response, we show that clearance of high-risk HPV (HR-HPV) infections (HZ=1.86, 95% CI: 1.19-2.9) was associated with immune profiles, but not molBV-BV when both were considered in the model. In contrast, the TNF-α/MIP-1β signature was associated with progression of incident infections to CIN2+ (OR = 2.81, 95% CI: 1.62-5.42), but not HR-HPV clearance. Thus, BV is a heterogeneous condition that activates different arms of the local immune response, which in turn are independent risk factors for HR-HPV clearance and progression.
Article
Full-text available
Research question Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women suffering from infertility? Design The study was designed as a prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included in this randomized controlled trial. Patients were assigned to either probiotic treatment or control group. Subjects in the treatment group (n=40) took one sachet (2 g) a day of a defined probiotic supplement containing Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20 of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples were performed. Results After intervention phase, no effects on alpha diversity due to treatment could be observed. The between sample diversity of different women (beta diversity) at baseline exhibited no effects of age, treatment group or BMI. However, primary/secondary sterility showed significant impact on community. Three clusters (L. crispatus, L. iners and L. gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed contained growth of Ureaplasma parvum compared to the control group (p = 0.021). Conclusions In conclusion, the study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.
Article
Full-text available
Objective To determine the longitudinal changes in the incidence of bacterial vaginosis in pregnancy. Design A prospective study of women during pregnancy. Setting A District General Hospital in North-West London. Subject Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture. Results Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10 (59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P < 0.001). Conclusion Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.
Article
Background Genital infection is the most important cause of infertility worldwide, affecting not only Fallopian tubes but all anatomic urogenital sites, both male and female Methods We present a randomized, prospective and normalized study about sexually transmitted diseases (STD). We include 487 patients, 376 of whom were infertile and the remaining 111 were not and act as control group Results 47.3% of infertile patients showed at least one infection: 10.7% had Chlamydia trachomatis infection, whereas only 0.3% had gonococal infection. We found none syphilis. 12.9% of the patients showed yeast belonging to genus Candida, 5% bacterial vaginosis, 3.8% Escherichia coli and 0.3% Klebsiella pneumoniae. The percentage of isolation of Ureaplasma urealyticum and Mycoplasma hominis were 23.5% and 4.8%, respectively. We detected antibodies against Hepatitis B (any serological marker) in 7.8% of the cases. Chlamydial infection and the presence of U. urealyticum were related with infertility (÷ 1 2=6,070, p<0.005 and ÷ 1 2=8,782, p<0.005, respectively) Conclusions We think these results conclude that is necessary to perform routine tests to screen for C. trachomatis, N. gonorrhoeae, and for infections caused by micoplasma as well, among infertile patients. These patients must be considered of being at risk of acquiring STD, since the percentage of these diseases is higher than the percentage we found among the control group. It is important to insist on prevention and early diagnosis and treatment as a main goal to decrease the number of tubal occlusion and infertile couples
Article
This study aimed to establish the different prevalence of the microorganisms investigated in the two groups considered: fertile women with symptoms and asymptomatic women with infertility problems. The data from women (n= 952) investigated for two years for quality of genital discharge and the presence of Gardnerella vaginalis, Trichomonas vaginalis, Candida species, Streptococcus agalactiae, Mycoplasma hominis, Ureaplasma urealyiticum and Chlamydia trachomatis were retrospectively analyzed. In the population of fertile women with symptoms the microrganisms most frequently involved are Gardnerella vaginalis (26.6%), Candida species (12.1%) and Streptococcus agalactiae (9.2%). The genital discharges of asymptomatic women with infertility problems are characterized by a prevalence of Gardnerella vaginalis (19.7%), Enterobacteriaceae or Enterococci (12.1%) and Streptococcus agalactiae (8.6%). The reduction of vaginal lactobacilli flora and the presence of an elevated number of polymorphonucleates in the vaginal discharge are important parameters to consider for the evaluation of the health status of the human female urogenital tract. Our results indicate that is important to culture the vaginal discharge for Streptococcus agalactiae and for prevalence of Enterobacteriaceae and Enterococci. Lastly, the reasons for the prevalence of some microorganisms (Gardnerella vaginalis, Enterobacteriaceae and Enterococci, Streptococcus agalactiae) in the population of infertile asymptomatic women need to be better analyzed especially after the recent studies correlating idiopathic infertility with the presence of cervical cytokines in women with an abnormal vaginal flora.
Article
Bacterial vaginosis (BV) is a common disorder of the genital tract in women characterized by an alteration of the normal acidic lactobacilli-predominant vaginal ecosystem to a vaginal environment dominated by Gardnerella vaginalis, mycoplasma species and anaerobes, with an increase in pH. The present study evaluated whether BV is associated with reproductive complications in women. BV was screened with a Gram stain of vaginal smear and interpretation was done using the Nugent score. Wet mount and polymerase chain reaction were used to screen other infections. Among 510 enrolled women, 72 (14.1%) had BV. Statistical analysis between the BV negative and positive population revealed a significant association (P = 0.0001) with infertility. In pregnant women, the infection rate was low (P = 0.01). Multiple infections such as Candida, Chlamydia and human papilloma virus were observed in 4.2%, 15.3% and 8.3% of BV-infected women, respectively. Results suggest that BV infection is associated with infertility and its absence leads to pregnancy, emphasizing its screening and treatment.
Article
There has been a recent recognition on the influence of local vaginal immunity on the acquisition of vulvovaginal disorders and their adverse consequences. Variations in local immune responses seem to play an important role in susceptibility to different vaginal infections as well as to the likelihood of recurrences. Bacterial vaginosis (BV), the most frequent vaginal disorder in most populations, is enigmatic in that the etiology is unknown, recurrences are common and vaginal inflammation is absent. We investigated the influence of BV on the vaginal concentration of the pro-inflammatory cytokine interleukin (IL)-12, the pleiotropic cytokine IL-6 and the anti-inflammatory cytokine IL-10 in non-pregnant women. Vaginal lavage samples were obtained from 45 patients with BV and from 46 asymptomatic controls. The supernatant fractions were examined for IL-6, IL-10 and IL-12 by commercial ELISAs. Analysis of the cytokine levels in the two groups was by the Mann-Whitney test. IL-6 concentrations varied considerably among women in the BV and control groups but the median levels were almost identical. The median concentrations of IL-10 and IL-12 were uniformly low in both groups but median levels were not statistically different. The marked alteration in the vaginal bacterial flora that is characteristic of BV does not result in enhancement or inhibition of the vaginal levels of IL-6, IL-10 and IL-12. Mechanisms to explain this striking lack of immune system variation remain to be determined.
Article
Pelvic inflammatory disease (PID) is a frequent infection in sexually active young women and results in adverse sequelae, including tubal-factor infertility and ectopic pregnancy. In the 1970s investigations using culdocentesis demonstrated that anaerobic bacteria played an important role in the etiology of PID. This finding has subsequently been confirmed by studies utilizing laparoscopy and/or endometrial biopsy to obtain specimens directly from the upper genital tract (uterine cavity and fallopian tube) of patients with acute PID. Recently, several investigations have shown an association between bacterial vaginosis and the development of acute PID. The microorganisms associated with bacterial vaginosis include anaerobes such as Prevotella bivia, other Prevotella species, and Peptostreptococcus species. These studies that have demonstrated the presence of bacterial vaginosis-associated bacteria in addition to the sexually transmitted organisms Neisseria gonorrhoeae and Chlamydia trachomatis suggest that treatment of acute PID must be broad spectrum in nature and effective against anaerobic bacteria as well as N. gonorrhoeae and C. trachomatis.
Article
Our purpose was to analyze (1) the effects of prevalent lower reproductive tract infections and (2) the effect of systematic diagnosis and treatment to reduce risks of early pregnancy loss (< 22 weeks), preterm premature rupture of membrances, and overall preterm birth. A prospective, controlled treatment trial was conducted on 1260 women. During the first 7 months of the program (observation, phase I), women were examined at initiation of prenatal care for a panel of lower genital tract microorganisms and bacterial vaginosis. Women were followed up with reexaminations at 22 to 29 weeks and after 32 weeks' gestation. The recommended treatments of the Centers for Disease Control (i.e., 300 mg of clindamycin orally twice daily for 7 days for bacterial vaginosis) were used for infected women during the second 8 months of the study (treatment, phase II). Data were analyzed according to intent to treat by means of univariate and multivariate methods. Overall, presence of bacterial vaginosis (32.5%) at enrollment was associated with pregnancy loss at < 22 weeks' gestation (relative risk 3.1, 95% confidence interval 1.4 to 6.9). Among women in the observation phase bacterial vaginosis was associated with increased risk of both preterm birth (relative risk 1.9, 95% confidence interval 1.2 to 3.0) and preterm premature rupture of membranes (relative risk 3.5, 95% confidence interval 1.4 to 8.9). Within this population (phase I) 21.9% of preterm birth overall (43.8% premature rupture of membranes) is estimated as attributable to bacterial vaginosis. Among women with bacterial vaginosis phase II (treatment) was associated with reduced preterm birth (relative risk 0.5, 95% confidence interval 0.3 to 0.9); there was a similar reduction for women with preterm premature rupture of membranes (relative risk 0.5, 95% confidence interval 0.2 to 1.4). Women with both bacterial vaginosis and trichomoniasis were at highest risk of preterm birth (28%); treatment of both conditions (phase II) reduced preterm birth (17%) but did not eliminate this risk. Earlier patient enrollment and oral antibiotic treatment were associated with reduced preterm birth. This prospective, controlled trial confirms that the presence of bacterial vaginosis is associated with increased risks of pregnancy loss at < 22 weeks, preterm premature rupture of membranes, and preterm birth. Orally administered clindamycin treatment is associated with a 50% reduction of bacterial vaginosis-linked preterm birth and preterm premature rupture of membranes. Women at risk for preterm birth or preterm premature rupture of membranes because of bacterial vaginosis or common genital tract infections should be screened, treated, reevaluated for cure, and re-treated if necessary.
Article
To determine the longitudinal changes in the incidence of vaginosis in pregnancy. A prospective study of women during pregnancy. A District General Hospital in North-West London. Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture. Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10(59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P < 0.001). Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.