Endometriosis increases your risk for pregnancy complications

Posted By Braverman IVF & Reproductive Immunology || 3-Feb-2017

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
  1. 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.

  1. Obstetrical complications associated with Endometriosis
  1. 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).

  1. 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).

  1. Obstetrical bleeding

Among women with endometriosis the risk of antepartum bleeding was increased by 80% to 100% depending on the studies (8, 12).

  1. 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).

  1. 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.


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