Endometriosis and pregnancy outcome : women with previously excised posterior DIE

Obstetric complications after laparoscopic excision of posterior deep infiltrating endometriosis: a case–control study

2018 Study Abstract

In this issue, Nirgianakis et al. present a retrospective analysis of the complications of pregnancy after laparoscopic excision of deep infiltrating endometriosis (DIE). Most important is that excision of DIE does not affect the increased risk of placenta previa, gestational hypertension, and intrauterine growth retardation (IUGR) associated with endometriosis. In addition, the risk of a vaginal delivery was not increased in the entire group or in the 26 women with a vaginal excision of endometriosis.

Read the full text (free access).
Fertility and Sterility, Volume 110, Issue 3, Pages 406–407, August 2018.

DES Exposure and Endometriosis

Prevalence of migraines in adolescents with endometriosis

Cross-sectional study conducted within The Women’s Health Study: From Adolescence to Adulthood—an ongoing longitudinal cohort

Prenatal exposure to estrogenic substances (such as DES) and environmental toxins (such as bisphenols) may increase the incidence of endometriosis in female offspring

2018 Study Abstract

Objective
To determine the prevalence and experience of migraines in adolescents with surgically confirmed endometriosis compared with those without endometriosis.

Design
Cross-sectional study conducted within The Women’s Health Study: From Adolescence to Adulthood—an ongoing longitudinal cohort.

Setting
Boston Center for Endometriosis.

Patient(s)
Adolescent females enrolled November 2012 through November 2016. The case group included adolescents surgically diagnosed with endometriosis. The control group included adolescents without endometriosis, recruited from the local community and clinics.

Intervention(s)
Not available.

Main Outcome Measure(s)
An extensive online health questionnaire regarding medical history, lifestyle, medication use, anthropometrics, and symptom experience and treatments. Migraine diagnosis was self-reported. Migraine pain and noncyclic pelvic pain severity were rated using an 11-point numerical rating scale. Cyclic pelvic pain was categorized.

Result(s)
Adolescents with endometriosis were more likely to experience migraines (69.3%) than those without endometriosis (30.7%) (multivariable odds ratio = 4.77, 95% confidence interval 2.53, 9.02). For each 1-point increase in the migraine numerical rating scale, the odds of endometriosis increased by 22% (multivariable odds ratio = 1.22, 95% confidence interval 1.03, 1.44; Ptrend = .02). Among those with endometriosis, age of menarche was associated inversely with the odds of migraines. Participants with endometriosis and migraines have more dysmenorrhea than those without migraines.

Conclusion(s)
Adolescents with endometriosis are more likely to experience migraines than adolescents without endometriosis. A linear relationship exists between migraine pain severity and the odds of endometriosis, suggesting heightened pain sensitivity for adolescents with endometriosis. Due to the strong correlation, patients who present with either condition should be screened for comorbidity to maximize the benefits of care.

Controversial pregnancy test drug shows deformities in zebrafish embryos within hours of exposure

Primodos drug components can cause embryonic damage in a dose and time responsive manner

“This is a great stepping stone. It doesn’t give definitive answers, but it’s a start, so we can finally put to rest whether or not Primodos caused birth defects

Dr Vargesson says.

The components of a controversial drug, allegedly linked to birth defects in the 1960s and ’70s, caused deformations to fish embryos just hours after they received a dose in new studies by researchers at the University of Aberdeen.

Primodos was a hormone pregnancy test used by thousands of women in the UK between 1958 and 1978.

“The first step was to show the drug has caused problems in fish and hopefully that will lead to some funding for tests on mammals and other tissues to show exactly what is going on.”

Dr Vargesson says.

Research at the time suggested the drug could be linked to a higher risk of women giving birth to babies with abnormalities – a claim denied by Primodos’ manufacturer.

Although Primodos is no longer in use, its components (Norethisterone acetate and Ethinyl estradiol) are used in other medications today including treatments for endometriosis and contraceptives.

“This research helps the campaigners because they can see there has been some up-to-date science being done with modern techniques.”

Dr Vargesson says.

In November last year a UK Government expert working group (EWG) study found no ‘causal association’ between the drug and the abnormalities, stating that outdated methods used by scientists in the 1970s was partly responsible for a failure to find a connection.

Now a new study at the University of Aberdeen, published today in the Scientific Reports journal, has revealed more about the effects of Primodos’ components on the embryos of zebrafish

The paper outlines how after the components of Primodos were added to water around zebrafish embryos, their movement slowed down rapidly; developed changes to the heart within four hours; and within 24 hours displayed damage to tissues such as the fins, eyes and spinal cords.

“I would like to think the PM will take this on board and consider there might be an alternative decision to the one the Commission On Human Medicines made in the Westminster report.”

Dr Vargesson says.

More surprisingly, according to the researchers, the study showed that the drug accumulates in the zebrafish embryo over time. They suggest that if this also occurs in a mammalian species that even a seemingly low dose of the drug for the mother could result in much higher levels for the embryo.

This latest study was led by Dr Neil Vargesson from the University of Aberdeen, who has also published extensive research into thalidomide – a drug used in Germany in the 1950s to treat morning sickness but which caused thousands of babies worldwide to be born with malformed limbs.

“At the moment the scientific research into whether or not Primodos caused these birth defects is inconclusive.”

“What this study highlights is that there is a lot still to be learned about Primodos and more widely its components effects on mammals.”

“Our experiments with the zebrafish embryos shows quite clearly the effects the Primodos components have. This does not mean it would do the same in humans of course, we are a long way from saying that but we need to carry out more research into these components because they are still in drugs today and in some cases in much higher doses than those found in Primodos.”

“The assumption by some previously has been that the doses given to mothers was too low to cause any damage but our study shows that the levels of Primodos’ components accumulate in the embryos over time because they don’t have a fully functional liver that can break down the drug. This too is new information and if the same thing happens in mammals, these drugs could build up in the embryo to much higher levels than shown in the mother’s blood.”

Dr Vargesson explains.

More About Primodos

Endometriosis linked to elevated risk of placenta previa in pregnancy

Association between surgically diagnosed endometriosis and adverse pregnancy outcomes

2018 Study Abstract

Objective
To examine the association between surgically diagnosed endometriosis and pregnancy outcomes in subsequent pregnancies.

Design
Retrospective cohort study of women who delivered a singleton live birth from 2003 to 2013 in Ottawa, Ontario, Canada.

Setting
Tertiary level academic center.

Patient(s)
Pregnant women with surgically diagnosed endometriosis were identified using International Classification of Diseases-10 codes from previous hospital admissions and were compared with pregnant women with no prior admission for endometriosis for the occurrences of adverse pregnancy outcomes.

Intervention(s)
Observational study.

Main Outcome Measure(s)
Gestational hypertension, preeclampsia, placenta previa, placental abruption, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and neonatal intensive care unit admission.

Results
Among the 52,202 eligible mother-infant pairs, we identified 469 mothers with surgically diagnosed endometriosis from a previous hospital encounter. Compared with women without endometriosis, women with endometriosis were on average older and were more likely to be primiparous, have lower gravidity, have a history spontaneous abortion, conceive with assisted reproductive technology, and reside in areas with higher neighborhood income and lower proportion of immigrants. Women with endometriosis were found to have an elevated risk of placenta previa (relative risk [RR], 3.30; 95% confidence interval [CI], 1.65–5.40) and cesarean delivery (RR, 1.24; 95% CI, 1.10–1.40). After adjustment for potential confounding factors, women with endometriosis were found to have a significantly elevated risk of placenta previa compared with women without endometriosis (adjusted RR, 2.54; 95% CI, 1.39–4.64).

Conclusion(s)
This study identifies baseline demographic differences between women with and without endometriosis and suggests that women affected by endometriosis have an independently elevated risk of placenta previa in pregnancy.

Pregnancy complications in patients with endometriosis

Prenatal exposure to estrogenic substances (such as DES) and environmental toxins (such as bisphenols) may increase the incidence of endometriosis in female offspring

Zullo et al. have done an extensive and thorough meta-analysis of the literature concerning endometriosis and pregnancy complications, one of the largest and most comprehensive studies to date.

Their systematic review and meta-analysis : endometriosis and obstetrics complications, provides further insight into endometriosis and pregnancy by combining the many heterogeneous studies on this topic, and it raises awareness of the many implications of endometriosis.

2017 Study Abstract

Objective
To evaluate the effect of endometriosis on pregnancy outcomes.

Design
Systematic review and meta-analysis.

Setting
Not applicable.

Patient(s)
Women with or without endometriosis.

Intervention(s)
Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included.

Main Outcome Measure(s)
Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI).

Result(s)
Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia.

Conclusion(s)
Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.

Endometriosis, especially mild disease : a risk factor for miscarriages

Prenatal exposure to estrogenic substances (such as DES) and environmental toxins (such as bisphenols) may increase the incidence of endometriosis in female offspring

2017 Study Abstract

Objective
To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW).

Design
Cross-sectional analysis nested in a retrospective observational study (n = 940).

Setting
Hospitals and associated private practices.

Patient(s)
Previously pregnant women (n = 268) within reproductive age in matched pairs.

Intervention(s)
Retrospective analysis of surgical reports and self-administered questionnaires.

Main Outcome Measure(s)
Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months’ time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis).

Result(s)
The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%–42.0%]) compared with CW (22.0% [16.7%–27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41–2.75). This remained significant in subfertile WwE (50.0% [40.7%–59.4%]) vs. CW (25.8% [8.5%–41.2%]) but not in fertile WwE (24.5% [16.3%–31.6%]) vs. CW (21.5% [15.9%–26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%–51.4%] vs. rASRM III/IV 30.8% [22.6%–38.7%], compared with 22.0% [16.7%–27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%–53.9%]) compared with ovarian endometriosis (28.6% [17.7%–38.7%]) and deep infiltrating endometriosis (33.9% [21.2%–46.0%]) compared with CW (22.0% [16.7%–27.0%]).

Conclusion(s)
Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage.

Breast feeding associated with a lower risk of endometriosis

History of breast feeding and risk of incident endometriosis: prospective cohort study

2017 Study Abstract

Objective
To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women.

Design
Prospective cohort study.

Setting
Nurses’ Health Study II, 1989-2011.

Participants
72 394women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea.

Main outcome measures
Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis.

Results
Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100 000 person years compared with 184 cases/100 000 person years in women who reported a lifetime total of ≥36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P<0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P<0.001 for trend). Women who breastfed for ≥36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced by postpartum amenorrhea (% mediated was 34% (95% confidence interval 15% to 59%) for total breast feeding and 57% (27% to 82%) for exclusive breast feeding).

Conclusion
Among women who experienced at least one pregnancy that lasted at least six months, breast feeding was inversely associated with risk of incident endometriosis. This association was partially, but not fully, influenced by postpartum amenorrhea, suggesting that breast feeding could influence the risk of endometriosis both through amenorrhea and other mechanisms. Given the chronic and incurable nature of endometriosis, breast feeding should be further investigated as an important modifiable behavior to mitigate risk for pregnant women.

  • History of breast feeding and risk of incident endometriosis: prospective cohort study, BMJ 2017;358:j3778, 29 August 2017.
  • Featured image credit @bmj_latest, 2 sept. 2017.

Environmental dioxins and endometriosis

Period activists want pads and tampon makers to disclose ingredients

Who knows what chemicals and other ingredients are in (your) tampons? Many sanitary pads don’t list any ingredients at all on the package…

One longtime concern about menstrual products has been whether the process of purifying or bleaching cotton and rayon with chlorine compounds may leave worrisome traces of toxic dioxins behind. Some research in nonhuman primates has linked exposure to dioxins to endometriosis.

Abstract

Endometriosis is a common gynecologic problem of unknown etiology. Estrogen dependence and immune modulation are established features of this disease, and environmental contaminants have been suggested to play a role in the pathobiology of this disease as well.

Previous work in nonhuman primates has shown that exposure to the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with an increased prevalence and severity of endometriosis. Further animal experiments have implicated dioxin and dioxin-like compounds in this disease. Rodent studies support the plausibility of a role of environmental contaminants in the pathophysiology of endometriosis, although a convincing mechanistic hypothesis has yet to be advanced.

Small hospital-based case-control studies have failed to provide compelling evidence for or against an association of environmental contaminants and endometriosis. Herein we review evidence that dioxin and dioxin-like compounds are potent modulators of immune and endocrine function critical to the pathobiology of endometriosis.

Furthermore, perspectives on the potential mechanism(s) of dioxin and dioxin-like compound-induced toxicity in endometriosis, important knowledge needs, potential animal models for endometriosis studies, and considerations integral to future human case-control studies are discussed.

Sources and Press Release
  • Environmental dioxins and endometriosis, Semin Reprod Med 2003; 21(2): 145-154, DOI: 10.1055/s-2003-41321.
  • Period Activists Want Tampon Makers to Disclose Ingredients, nytimes, MAY 24, 2017.
  • Image credit Al Drago/The New York Times – Representative Grace Meng, Democrat of New York, spoke Tuesday at a rally in Washington calling for makers of feminine hygiene products to disclose the ingredients used to make tampons and pads.

Health Effects from Endocrine Disrupting Chemicals Cost The U.S.

Yearly Exposure to Chemicals Dangerous to Hormone Function Burdens Americans with Hundreds of Billions in Disease Costs

Reducing chemical exposure could save Americans hundreds of billions of dollars in healthcare costs.

Endocrine disrupting chemicals and endometriosis

Endocrine disruptors and reproductive disorders

Abstract

Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women’s fertility, somatic health, and overall quality of life.

Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease.

We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques.

Endocrine disrupting chemicals and endometriosis, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 959–966, September 15, 2016.

laparoscopic surgery for endometriosis: fuschia_foot.

Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates.

To address the equivocal findings for various EDCs, future research directions for filling data gaps include

  1. use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities;
  2. the collection of various biologic media, including target tissues for quantifying exposures;
  3. study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders;
  4. and novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs, and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis.