A serie of articles have been recently published highlighting an increased
risk of obstetrical complications associated with pregnancies in patient
with endometriosis.
Endometriosis is a benign gynecologic disorder, described as chronic, inflammatory
and estrogen-dependent (1).
It affects 11% of women of reproductive age worldwide (2) and is characterized
by the presence of endometrial cells outside the endometrium (3).
It is the most common gynecological disorder that may be present in up
to 44% of asymptomatic women (4).
For more information,
read our blog and
watch our videos on
silent endometriosis.
A large proportion of women with endometriosis (up to 50%) experiences
some degree of infertility (5) that can be trigger by:
- anatomic distortion
- diminished ovarian reserve
-
alteration of oocyte quality by inflammatory factors or disruption of the
oocyte mitochondrial activity (for more information,
read our blog on the topic)
- peritoneal inflammation that can disrupt the endometrial receptivity
- Endometriosis increases the risk for miscarriages
Many women with endometriosis undergo infertility treatment including the
use of assisted reproductive technologies (ART) such as In Vitro fertilization.
Several retrospective studies have put into light an
increased rate of miscarriages for women with endometriosis.
In a recent retrospective study (6) comparing the pregnancy outcome in
patient with laparoscopy proven endometriosis versus endometriosis-free
patient (who had a laparoscopic surgery for benign gynaecological conditions),
the authors found that 29% of ENDO patients miscarried versus 19% for
the control group (endo-free patients).
Another analysis showed that this difference is even more accentuated
when considering patients with a history of infertility (miscarriage rate
of 53% for ENDO patients versus 30% for endo-free patients).
However, it is important to note that asymptomatic women are less likely
to be referred for surgery and might be underrepresented.
In a large and systematic review (7) including 92 studies and 78 meta-analysis
with a total of over 20 000 women with endometriosis and 122 000 endo-free
patients (controls) undergoing ART, the authors found
a 31% increase in miscarriage rate in women with endometriosis.
Unfortunately, the studies don’t give any details on surgical treatment
of the disease before pregnancy that could modify the occurrence of miscarriages.
- Obstetrical complications associated with Endometriosis
- Preterm Birth
In a nationwide Swedish cohort of 1,442,675 singleton pregnancies (8) including
13,090 women with endometriosis (confirmed by laparoscopy), a significant
increase of preterm birth (<37 weeks) has been found (+33%) irrespective
of the use for ART.
Another Nationwide Danish study (9) showed similar results with an incidence
in preterm births that almost doubled in ENDO patients (n=1719 pregnancies,
7.3%) when compared to control endo-free patients (n=81074 pregnancies,
4.33%), regardless of ART use.
A recent cohort study led in Japan (10) showed that women with endometriosis
were 2 times more likely to have a preterm premature rupture of the membrane
(PPROM) than endo-free women when conceiving naturally. This rate increased
to 3 times when using infertility treatment.
Interestingly, in this study 80.6% of ENDO patients conceived naturally
(least severe cases of endometriosis) and were still prone to develop
PPROM and other obstetrical complications, showing that these complications
are most likely associated with ENDO and not the use of ART. Nevertheless,
these results should be taken with caution as the endometriosis diagnostic
was self-reported (patient questionnaire with no other supporting evidences).
Another study (12) supports the fact that obstetrical complications are
triggered by endometriosis. Preterm birth rate was twice as high in ENDO
patients undergoing ART when compared to their control matched ART (similar
characteristics: age, BMI, obstetrical history but endo-free patients
undergoing ART for male infertility etc…). Newborns of women with
endometriosis were born a week earlier on average.
Lastly, a retrospective cohort study showed an increased rate of premature
births (that doubles) associated with women having ovarian endometrioma
and undergoing ART when compared to endo-free patients (11).
- Pre-eclampsia
There is conflicting result on the relationship between endometriosis and
pre-eclampsia. Some studies cited above showed an increased risk associated
with endometriosis ranging from +17% to +37% when compared with unaffected
women (8-9) while lower and unchanged risks were also reported (10, 13-15).
- Obstetrical bleeding
Among women with endometriosis the risk of antepartum bleeding was increased
by 80% to 100% depending on the studies (8, 12).
- C-section
Many studies have found an association between endometriosis and an increased
risk for C-section that double in most of the studies (8-9, 11-12, 15).
- How can endometriosis trigger obstetrical complications? The link is Inflammation
The two most prevalent obstetrical complications in relation to endometriosis
are preterm birth and pre-eclampsia.
Preterm births are a leading cause of neonatal mortality and morbidity worldwide and
has been strongly linked to
inflammation. Pro-inflammatory cytokine production can trigger uterine contraction,
facilitates cervical ripening thus leading to preterm labor (17).
Pre-eclampsia (PE) affects up to 7% of pregnancies in the United States. Characterized by
hypertension and proteinuria during pregnancy, PE is associated with an
immune imbalance where pro-inflammatory CD4+T cells are increased while Treg cells expression is repressed. This disorder
is characterized by
inflammation with an increased secretion of
pro-inflammatory cytokines and oxidative stress that injures the placenta leading to
placental ischemia during pregnancy.
Just like PE and pre-term births, endometriosis is an inflammatory condition.
The peritoneal fluid of women with endometriosis is characterized by proinflammatory
changes, with increased levels of cytokines such as IL-6 and angiogenic
factors (18), which could be a possible explanation for the higher risk
of preterm birth (19). Further, in ENDO patients, there is an overexpression
of two prostaglandins in the endometrium namely PGE2 and PGF2α that
could trigger uterine contraction thus leading to premature labor (20).
During pregnancy, spiral arteries undergo a deep transformation in a specific
zone of the uterus, named the junctional zone which is the site of placentation.
Pre-eclampsia has been characterized by a defective transformation of
the spiral arteries at this specific zone (21) and imaging studies have
found an association between endometriosis and a thickening of this zone
(22) that could explain its disrupted activity.
In addition to a Scottish study released last week (23), these recent data
strongly suggest that endometriosis could have dramatic consequences on
a pregnancy from miscarriage or unexplained haemorrhage to preterm delivery
or pre-eclampsia depending on the severity of the defective placentation.
At Braverman Reproductive Immunology, we have considered for years, that endometriosis
predisposes women to miscarriages and later pregnancy complications.
Even when patients can conceive, endometriosis
should not be left untreated or
unmonitored as it can induce dramatic effects on the pregnancy.
We have developed a full program to
counteract the deleterious effects of endometriosis in our patients
with adequate care ranging from laparoscopic surgery with endometriotic lesions resection
to immune therapy to
minimize and control the inflammation during pregnancy. In addition, we have elaborated two supplements
Endo-Optimize supplement and
Endo-Optimize probiotic that could help restoring your egg mitochondrial function leading to better
egg and embryo quality.
References