Inflammation: a link between endometriosis and preterm birth

doi:10.1016/j.fertnstert.2012.04.051

Fertility and Sterility

Volume 98, Issue 1, July 2012, Pages 36-40

https://doi.org/10.1016/j.fertnstert.2012.04.051 Get rights and content

Endometriosis is a chronic inflammatory disease affecting women's health. Pain and infertility are the major symptoms caused by a hormonal/immunological dysfunction, which causes an endometrial impairment. The same pathogenetic mechanisms are also associated with preterm birth: hormones, cytokines, neurohormones, and growth factors interact in modulating extracellular matrix and prostaglandin secretion, thus activating the inflammatory process in placental membranes and myometrium. An overlap of molecules and mechanisms may explain the evidence that preterm birth is a common outcome in pregnant patients with endometriosis.

Section snippets

Inflammation, Endometrium, and Endometriosis

Endometrium is the reproductive tissue richest in inflammatory mediators. Endometrial immune cells migrating from bone marrow induce changes that are critical for embryo implantation and positive pregnancy outcome. Immune cell trafficking into the endometrium has been known for decades, highlighted in the classical description of the histological changes of this tissue (5). The features of menstruation parallel an inflammatory response, with an accumulation of leukocytes in the endometrium

Acknowledgments

The authors thank Cinzia Orlandini for helping in the preparation of the manuscript.

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To assess obstetrical outcomes, perceptions of childbirth experience and emotional adjustment, in women with dyspareunia.
In this cross-sectional study, 440 women were recruited within 48 h postpartum in the maternity ward of a large medical center, during the period of April 2018- August 2020. Self-report questionnaires were administered which addressed demographic and reproductive background, dyspareunia, perceptions of control during labor (Labor Agentry Scale), perceived professional support (Intrapartum Care Scale), and maternal adjustment, implicated in perinatal dissociation (Peritraumatic Dissociative Experiences Questionnaire), acute stress disorder (ASD) symptoms (Stanford Acute Stress Reaction Questionnaire), bonding (Mother-to-Infant Bonding Scale), anticipated maternal self-efficacy (Maternal Self-Efficacy Scale) and well-being (Positive and Negative Affect Schedule, Edinburgh Postnatal Depression Scale). Obstetrical information was retrieved from clinical files and included pregnancy complications, week and mode of delivery, nature of labor onset, analgesia during delivery, birthweight, perineal tears.
The dyspareunia group included 71 women (18.3%) and the comparison group 317 (81.7%). Demographic data were similar among groups. No difference was observed in nature of labor onset, type of analgesia, route of delivery, perineal tears. More participants with dyspareunia had premature delivery versus comparisons (14.1% vs 5.6%, p = 0.02). Women with dyspareunia reported lower levels of control (p = 0.01) and perceived support during childbirth (p < 0.001), higher levels of perinatal dissociation (p < 0.001) ASD symptoms (p < 0.001), depression (p = 0.02), negative affect (p < 0.001), and reported lower levels of maternal bonding (p < 0.001) and anticipated maternal self-efficacy (p = 0.01).
Dyspareunia was associated with more premature deliveries, parameters of emotional distress during childbirth and poorer maternal adjustment following childbirth. Perinatal caregivers should be cognizant of such cognitive and emotional reactions in women with dyspareunia, so as to assess for a history of dyspareunia in pregnant women and provide adequate support during pregnancy and delivery.
Severe maternal morbidity associated with endometriosis: a population-based, retrospective cohort study
2023, Fertility and Sterility
To evaluate the association between endometriosis and the risk of severe maternal morbidity (SMM) as defined by the Centers for Disease Control and Prevention.
This was a population-based, retrospective cohort study using the California Office of Statewide Health Planning and Development Linked Birth File with hospital discharge International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnoses between 2007 and 2012.
Population-based.
A total of 3,098,578 pregnancies from 2007 to 2012.
Prior diagnosis of endometriosis identified using the ICD-9-CM codes 617.0–617.9.
The primary outcome of interest was SMM, which was defined as having been diagnosed with any of the ICD-9-CM codes corresponding to 25 peripartum conditions listed by the Centers for Disease Control and Prevention. The secondary outcomes of interest were each individual condition.
Of the 3,098,578 pregnancies analyzed, 2,910 pregnancies were among women with a prior diagnosis of endometriosis. There were 45,655 pregnancies complicated by at least 1 SMM; 158 pregnancies (54.3 per 1,000 pregnancies) were in women with endometriosis and 45,497 (14.7 per 1,000 pregnancies) were in women without endometriosis. Women with pregnancies complicated by endometriosis were 2.41 times more likely to develop SMM than women who did not have endometriosis (adjusted odds ratio [aOR], 2.41; 95% confidence interval [CI], 2.03–2.87). There was an increased risk of disseminated intravascular coagulation (aOR, 2.46; 95% CI, 1.65–3.66), heart failure during a procedure or surgery (aOR, 2.58; 95% CI, 1.69–3.94), pulmonary edema (aOR, 3.02; 95% CI, 1.11–8.17), blood transfusion (aOR, 2.17; 95% CI, 1.75–2.68), and hysterectomy (aOR, 2.46; 95% CI, 1.58–3.85). When the association was stratified by delivery mode, the risk of SMM was higher for vaginal delivery (aOR, 4.59; 95% CI, 2.73–7.71) than for cesarean delivery (aOR, 1.64; 95% CI, 1.37–1.97) (P-interaction<.0001).
This study demonstrated that endometriosis is a major risk factor for SMM, especially among those who deliver vaginally. Furthermore, precautions should be taken before delivery in anticipation of potential complications.
Morbilidad materna grave asociada a endometriosis: un estudio de cohorte retrospectivo basado en una población.
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Este fue un estudio de cohorte retrospectivo basado en una población, utilizando el archivo de nacimiento vinculado de la Oficina de Planificación y Desarrollo de la Salud Estatal de California con diagnósticos de alta hospitalaria Clasificación Internacional de Enfermedades, 9^a Revisión, Modificación Clínica (ICD-9-CM) entre 2007 y 2012.
Basado en una población.
Un total de 3.098.578 embarazos de 2007 a 2012.
Diagnóstico previo de endometriosis identificado usando los códigos ICD-9-CM 617.0-617.9.
El principal resultado de interés fue la MMG, que se definió como haber sido diagnosticado con cualquiera de los códigos ICD-9-CM correspondientes a 25 afecciones periparto enumeradas por los Centros para el Control y la Prevención de Enfermedades. Los resultados secundarios de interés fueron cada condición individual.
De los 3.098.578 embarazos analizados, 2.910 embarazos fueron de mujeres con diagnóstico previo de endometriosis. Hubo 45.655 embarazos complicados por al menos 1 MMG; 158 embarazos (54,3 por 1000 embarazos) fueron de mujeres con endometriosis y 45.497 (14,7 por 1000 embarazos) fueron de mujeres sin endometriosis. Las mujeres con embarazos complicados por endometriosis tenían 2,41 veces más probabilidades de desarrollar MMG que las mujeres que no tenían endometriosis (odds ratio ajustado [aOR], 2,41; intervalo de confianza [IC] del 95%, 2,03–2,87). Hubo un mayor riesgo de coagulación intravascular diseminada (aOR, 2,46; IC 95 %, 1,65-3,66), insuficiencia cardíaca durante un procedimiento o cirugía (aOR, 2,58; IC 95 %, 1,69-3,94), edema pulmonar (aOR, 3,02; IC 95 %, 1,11–8,17), transfusión de sangre (aOR, 2,17; IC 95 %, 1,75-2,68) e histerectomía (aOR, 2,46; IC 95 %, 1,58-3,85). Cuando la asociación se estratificó por modalidad de parto, el riesgo de MMG fue mayor para el parto vaginal (aOR, 4,59; IC 95 %, 2,73-7,71) que para el parto por cesárea (aOR, 1,64; IC 95 %, 1,37-1,97) (interacción P< 0,0001).
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Retrospective cohort study evaluating the data on all live births following IVF treatment between 2009 and 2017 at one university-affiliated tertiary hospital. All patients had placentas sent for full gross and histopathology assessment, irrespective of complication status or delivery mode. The primary outcomes of the study included anatomical, inflammation, vascular malperfusion and villous maturation placental disorders. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate logistic model was used to adjust the results for confounding factors potentially associated with significant placental characteristics.
A total of 1057 live births were included in the final analysis and were allocated to the group of women with endometriosis (n = 75) and those without (n = 982). After adjustment for confounding factors, endometriosis was found to be significantly associated with acute chorioamnionitis with moderate to severe maternal (odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.1–4.6) and fetal (OR 4.9, 95% CI 1.8–13.1) inflammatory response, placenta previa (OR 3.1, 95% CI 1.2–7.8), subchorionic fibrin deposition (OR 3.4, 95% CI 1.2–9.1), intervillous thrombosis (OR 3.4, 95% CI 1.5–8.1), and fetal vascular malperfusion (OR 5.1, 95% CI 1.4–18.1), as well as with preterm birth (OR 2.5, 95% CI 1.4–4.7).
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Pregnancy outcomes after in vitro fertilization for moderate and severe endometriosis. A case-control study
2022, Journal of Gynecology Obstetrics and Human Reproduction
Citation Excerpt :
In endometriosis, chronic inflammation leads to a rise of inflammatory cytokines like interleukins (IL) and tumor necrosis factor alpha (TNFα) in peritoneal tissue. IL1 and TNFα have an effect on myometrium receptors and could induce uterine contractions [6,7]. This situation may explain more threatened preterm labor in pregnant women with endometriosis [8].
Previous international studies showed that endometriosis could have a link with obstetrical complications, as an increased risk of preterm birth, gestational diabetes mellitus, and cesarean section. However, the results are difficult to interpret because biases are common, such as heterogeneity in the severity of the endometriosis cases included. That's why some complications as risk of miscarriage and post-partum hemorrhage are still debated. Our objective was to study pregnancy outcome after In Vitro Fertilization (IVF) in women suffering from rAFS stage III and IV endometriosis.
We conducted a case-control study between 2009 and 2019. We compared pregnancy outcomes after IVF in two groups of women matched by age, body mass index and smoking in two hospital centers. Group A was constituted by singleton pregnancies following ART for moderate and severe endometriosis (rAFS stage III and IV endometriosis). Group B was composed of singleton pregnancies in women with no endometriosis following ART for another reproductive disease. All women achieved pregnancy after 22 weeks.
A total of 240 pregnant women were included: 80 singleton IVF pregnancies (group A) were compared with 160 singleton IVF pregnancies (group B). We observed an increased risk of placenta previa (12.5% Vs 1.9%; p = 0,001), and cesarean section (49.4% (n = 39) Vs 29.6% (n = 47) p = 0,004). Rate of postpartum hemorrhage was not significantly different in endometriosis group (11.2% Vs 7.5% p = 0.47).
Despite conflicting results in literature due to a lot of confounding variables, the impact of endometriosis on pregnancy is still debated in women suffering from rAFS III and IV endometriosis. In our study, we observed statistically higher rates of placenta previa and cesarean section but not an increased risk of postpartum hemorrhage. Further larger series are needed to confirm our findings and a possible link with other obstetrical complications. However, we think that an ART pregnancy in a context of severe endometriosis should be considered at risk of adverse obstetrical outcomes.
Safety of transvaginal aspiration of cysts in pregnancies complicated with ovarian endometrioma
2021, Journal of Gynecology Obstetrics and Human Reproduction
Pregnancy complicated with ovarian endometrioma is a risk factor for preterm delivery and rupture or infection during pregnancy. This study aimed to clarify the effectiveness and safety of transvaginal aspiration during pregnancy for endometrioma diagnosed in the first trimester.
This retrospective observational study included 8 pregnant women with endometrioma who underwent transvaginal cyst aspiration at 12–14 weeks (aspiration group) between March 2011–March 2018 and 23 pregnant women with endometrioma who refused aspiration during the same period (observation group).
Characteristics of patients were compared in both groups. Safety, feasability and complications of transvaginal cyst aspiration were reported. Complications and obstetrical outcomes were reported and compared in both groups.
The maximum cyst diameter was 8.9 ± 1.5 cm (mean ± standard deviation) in the aspiration group, which was significantly larger than that in the observation group (4.7 ± 0.2 cm). Four preterm deliveries (17.3%) occurred in the observation group and none in the aspiration group. The emergency cesarean section rate during delivery was 14.2% in the aspiration group and 43.7% in the observation group.
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Perinatal outcomes associated with the positional relationship between the placenta and the adenomyosis lesion
2021, Journal of Gynecology Obstetrics and Human Reproduction
Although various perinatal complications have been reported to be increased in the pregnant patients with adenomyosis, it is not clear what type of patients with adenomyosis is more likely to cause obstetric complications. In this study, we focused on the positional relationship between the placenta and adenomyosis lesion in evaluating perinatal prognosis of pregnant patients with adenomyosis.
This retrospective cohort study was carried out between 1 January 2005 and 31 December 2019 in a single institution. Adenomyosis was diagnosed by magnetic resonance imaging (MRI) and/or transvaginal ultrasonography (TVUS). To evaluate the influence of adenomyosis on perinatal outcomes, we classified the positional relationship between the placenta and the adenomyosis lesion into two groups and examined the perinatal prognosis of the patients with adenomyosis by analyzing their clinical records. Group I (n = 9) was defined when the placenta was not overlaid on adenomyosis lesion. Group II (n = 11) was defined when a part of the placenta was overlaid on adenomyosis lesion.
Twenty pregnant patients with adenomyosis were analyzed. There were no differences in clinical backgrounds between group I and group II. There was a significant increase in the obstetric morbidity in group II than that of Group I(group I: 6.3%, 4/63 vs group II: 18.6%, 26/77; P < 0.001). In group II, fetal growth restriction (FGR) was more frequent (0%, 0/9 vs 45.5%, 5/11; P = 0.042) and the birth weight was significantly lower than that in group I (2951.1 g ± 326.5 g vs 2318.9 ± 656.1 g; P = 0.037). There was a trend of lighter weight of the placenta in group II (550.6 ± 66.5 g vs 437.5 ± 117.8 g; P = 0.063) and the volume of bleeding during delivery was a higher trend in group II than that in group I (845.1 ± 367.1 g vs 1356 ± 604.8 g; P = 0.083). Group II was furtherly subdivided into group IIa (less than half the major axis of the placenta overlaid on adenomyosis lesion) and group IIb (more than half the major axis of placenta overlaid on adenomyosis lesion). The obstetric morbidity tended to be higher in group IIb than in group IIa (group IIa: 22.9%, 8/35 vs group IIb: 42.9%, 18/42); P = 0.09). In group IIb, the frequency of FGR was significantly higher (group IIa: 0%, 0/5 vs IIb: 83.3%, 5/6; P = 0.020) and the birth weight was significantly lower than those in group IIa (2656.8 ± 231.9 g vs 2037 ± 780.1 g; P = 0.040). All cases of FGR, hypertensive disorder of pregnancy (HDP), and oligohydramnios were observed in group IIb.
Placental localization near adenomyosis may increase the risk of perinatal complications.

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: F.P. has nothing to disclose. F.A. has nothing to disclose. D.d.Z. has nothing to disclose. C.C. has nothing to disclose.

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ConceptionsInflammation: a link between endometriosis and preterm birth

Section snippets

Inflammation, Endometrium, and Endometriosis

Acknowledgments

Fertil Steril

J Reprod Immunol

Steroids

J Steroid Biochem Mol Biol

Lancet

Reprod Biomed Online

Placenta

Semin Fetal Neonatal Med

Fertil Steril

Fertil Steril

Inflammatory pathways in female reproductive health and disease

Reproduction

Inflammation in reproductive disorders

Reprod Sci

Inflammation and pregnancy

Reprod Sci

Cytokine networks and the regulation of uterine function in pregnancy and parturition

J Neuroendocrinol

Endocrine regulation of menstruation

Endocr Rev

Programming of human monocytes by the uteroplacental environment

Reprod Sci

Hormone-dependent gynaecological disorders: a pathophysiological perspective for appropriate treatment

Best Pract Res Cl Ob

TGF-beta superfamily expression and actions in the endometrium and placenta

Reproduction

Stress neuropeptides in the human endometrium: paracrine effects on cell differentiation and apoptosis

Hormones

Back to the original question in endometriosis: implantation or metaplasia?

J Endometriosis

Clinical practice. Endometriosis

N Engl J Med

Expression and role of peptides, proteins and growth factors in the pathogenesis of endometriosis

J Endometriosis

Impaired CRH and urocortin expression and function in eutopic endometrium of women with endometriosis

J Clin Endocrinol Metab

Ciclooxygenase enzymes and prostaglandins in pathology of the endometrium

Reproduction

Involvement of iron, nuclear factor-kappa B (NF-κB) and prostaglandins in the pathogenesis of peritoneal endometriosis-associated inflammation: a review

J Endometriosis

Endometriosis

N Engl J Med

Activin A increases invasiveness of endometrial cells in an in vitro model of human peritoneum

Mol Hum Reprod

Conceptions
Inflammation: a link between endometriosis and preterm birth