Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis

Abstract

Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum in pregnancy, and spontaneous bowel perforation in pregnancy.

Methods: We performed the literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), by searches in PubMed and EMBASE, until 1 November 2020 (PROSPERO ID CRD42020213999). We included peer-reviewed observational cohort studies and case-control studies and scored them according to the Newcastle-Ottawa Scale, to assess the risk of bias and confounding.

Results: 39 studies were included. Women with endometriosis had an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth, compared to women without endometriosis. These results remained unchanged in sub-analyses, including studies on spontaneous pregnancies only. Spontaneous hemoperitoneum in pregnancy and bowel perforation seemed to be associated with endometriosis; however, the studies were few and did not meet the inclusion criteria.

Conclusions: The literature shows that endometriosis is associated with an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth.

Keywords: cesarean section; endometriosis; hemorrhage; pre-eclampsia; preterm birth; small for gestational age; stillbirth.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart identifying the inclusion of studies. Note: n, number.

Figure 2

Forest plot for endometriosis and hypertensive disorders in pregnancy overall including studies with NOS ≥7. Chen et al., (2018) [30] and Farland et al., (2019) [34] used adjusted relative risks; Hadfield et al., (2009) [38], Pan et al., (2017) [51], and Saraswat et al., (2017) [53] used adjusted odds ratios.

Figure 3

Forest plot for endometriosis and gestational hypertension, including studies with NOS ≥7. Aris et al., (2014) [24] and Benaglia et al., (2016) [27] used crude odds ratios; Berlac et al., (2017) [28] and Stern et al. (2015) [57] used adjusted odds ratios.

Figure 4

Forest plots for endometriosis and pre-eclampsia including studies with NOS ≥7. Aris et al., (2014) [24], Benaglia et al., (2016) [27], Hadfield et al., (2009) [38], and Harada et al., (2019) [40] used crude odds ratios; Berlac et al., (2017) [28], Epelboin et al., (2020) [32], Glavind et al., (2017) [37], Harada et al., (2016) [39], Stephansson et al., (2009) [56], and Yi et al., (2020) [62] used adjusted odds ratios.

Figure 5

Forest plot for endometriosis and low birth weight, including studies with NOS ≥7. Chen et al., 2018 [30] and Farland et al., 2019 [34] used adjusted relative risks; Aris et al., (2014) [24] and Benaglia et al., (2016) [27] used crude odds ratios; Saraswat et al., (2017) [53], Stern et al., (2015) [57], and Yi et al., (2020) [62] used adjusted odds ratios.

Figure 6

Forest plot for endometriosis and SGA, including studies with NOS ≥7. Chen et al., 2018 [30] used adjusted relative risk; Aris et al., 2014 [24] and Benaglia et al., 2016 [27] used crude odds ratios; Berlac et al., 2017 [28], Epelboin et al., 2020 [32], Glavind et al., 2017 [37], Stephansson et al., 2009 [56], and Stern et al., 2015 [57] used adjusted odds ratios.

Figure 7

Forest plot for endometriosis and preterm birth including studies with NOS ≥7. Chen et al., 2018 [30] and Farland et al., 2019 [34] used adjusted relative risks; Aris et al., 2014 [24] and Harada et al., 2016 [39] used crude odds ratios; Benaglia et al., 2016 [27], Berlac et al., 2017 [28], Epelboin et al., 2020 [32], Glavind et al., 2017 [37], Harada et al., 2019 [40], Saraswat et al., 2017 [53], Stephansson et al., 2009 [56], Stern et al., 2015 [57], and Yi et al., 2020 [62] used adjusted odds ratios.

Figure 8

Forest plot for endometriosis and placenta previa including studies with NOS ≥7. Chen et al., 2018 [30] used adjusted relative risk; Benaglia et al., 2016 [27], Berlac et al., 2017 [28], Epelboin et al., 2020 [32], Harada et al., 2016 [39], Harada et al., 2019 [40], Saraswat et al., 2017 [53], and Yi et al., 2020 [62] used adjusted odds ratios.

Figure 9

Forest plot for endometriosis and placental abruption including studies with NOS ≥7. Chen et al., 2018 [30] used adjusted relative risk; Benaglia et al., 2016 [27] and Harada et al., 2019 [40] used crude odds ratios; Berlac et al., 2017 [28], Epelboin et al., 2020 [32], Harada et al., 2016 [39], Saraswat et al., 2017 [53], and Yi et al., 2020 [62] used adjusted odds ratios.

Figure 10

Forest plot for endometriosis and cesarean section including studies with NOS ≥7. Chen et al., 2018 [30] used adjusted relative risk; Benaglia et al., 2016 [27], Harada et al., 2016 [39], and Harada et al., 2019 [40] used crude odds ratios; Berlac et al., 2017 [28], Glavind et al., 2017 [37], Saraswat et al., 2017 [53], Stephansson et al., 2009 [56], Stern et al., 2015 [57], and Yi et al., 2020 [62] used adjusted odds ratios.

Figure 11

Forest plot for endometriosis and stillbirth including studies with NOS ≥7. Farland et al., 2019 [34] used adjusted relative risk; Aris et al., 2014 [24], Harada et al., 2016 [39], and Harada et al., 2019 [40] used crude odds ratios; Berlac et al., 2017 [28], Saraswat et al., 2017 [53], Stephansson et al., 2009 [56], and Yi et al., 2020 [62] used adjusted odds ratios.

Figure 12

Forest plot for endometriosis and postpartum hemorrhage, including studies with NOS ≥7. Chen et al., 2018 [30] used adjusted relative risk; Berlac et al., 2017 [28], Glavind et al., 2017 [37], Saraswat et al., 2017 [53], and Yi et al., 2020 [62] used adjusted odds ratios.