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Pathogenesis of deep endometriosis
Open accessAbstract
The pathophysiology of (deep) endometriosis is still unclear. As originally suggested by Cullen, change the definition "deeper than 5 mm" to "adenomyosis externa." With the discovery of the old European literature on uterine bleeding in 5%-10% of the neonates and histologic evidence that the bleeding represents decidual shedding, it is postulated/hypothesized that endometrial stem/progenitor cells, implanted in the pelvic cavity after birth, may be at the origin of adolescent and even the occasionally premenarcheal pelvic endometriosis. Endometriosis in the adolescent is characterized by angiogenic and hemorrhagic peritoneal and ovarian lesions. The development of deep endometriosis at a later age suggests that deep infiltrating endometriosis is a delayed stage of endometriosis. Another hypothesis is that the endometriotic cell has undergone genetic or epigenetic changes and those specific changes determine the development into deep endometriosis. This is compatible with the hereditary aspects, and with the clonality of deep and cystic ovarian endometriosis. It explains the predisposition and an eventual causal effect by dioxin or radiation. Specific genetic/epigenetic changes could explain the various expressions and thus typical, cystic, and deep endometriosis become three different diseases. Subtle lesions are not a disease until epi(genetic) changes occur. A classification should reflect that deep endometriosis is a specific disease. In conclusion the pathophysiology of deep endometriosis remains debated and the mechanisms of disease progression, as well as the role of genetics and epigenetics in the process, still needs to be unraveled.
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TL;DR
This review argues that the pathophysiology of deep endometriosis remains debated and proposes two complementary hypotheses: early-onset disease arising from neonatal uterine bleeding and endometrial stem/progenitor cells, and deep endometriosis as a specific benign tumor-like disease driven by genetic/epigenetic changes and recurrent tissue injury and repair (ReTIAR). It recommends abandoning the “deeper than 5 mm” definition in favor of “adenomyosis externa” and suggests that typical, cystic, and deep endometriosis may be three different diseases.
Key findings
- Deep endometriosis as the only form of disease, without other endometriotic lesions, was present in only 6.5%; under an adenomyosis externa definition, most deep lesions are unique (occasionally 2, rarely 3) and big (mostly >1 cm in diameter).
- Neonatal uterine bleeding occurs in approximately 5% of neonates, and low birth weight (<2,500 g) was associated with a higher risk of endometriosis, especially deep infiltrating endometriosis; a 743 case-control study reported almost two times higher risk of deep endometriosis with low birth weight.
- Deep and cystic ovarian endometriosis are consistently found to be clonal in origin, and some 50% of endometriosis lesions can be attributed to hereditary factors; prevalence is increased by 6%–9% in first-degree relatives and by 15% for severe disease.
- The paper proposes that subtle/microscopic lesions are not a disease until genetic or epigenetic changes occur, after which typical, cystic, and deep endometriosis become three different diseases sharing only endometrium-like tissue.
Methods
- Narrative review and hypothesis paper; no systematic review, primary data collection, or formal meta-analysis is reported.
- It synthesizes historical literature, clinical observations, histologic and biochemical findings, genetics/epigenetics, and animal-model evidence to develop two separate hypotheses: Hypothesis I (neonatal uterine bleeding and stem/progenitor cells) and Hypothesis II (genetic/epigenetic changes and benign tumor-like growth).
- No quantitative analysis or statistical testing is described.
Limitations
- Stated: the pathophysiology of deep endometriosis remains debated; there is no animal model mimicking specific endometrial functions such as placentation or permitting induction of the different clinical manifestations of endometriosis, so data are limited to clinical, histologic, and biochemical observations.
- Stated: the neonatal origin of early-onset endometriosis remains hypothetical, though falsifiable by systematic registration of neonatal menstruation; the role of genetics and epigenetics still needs to be unraveled.
- Evident: as a narrative review, it lacks a systematic search strategy or quantitative synthesis, and its central hypotheses are speculative and not directly tested in the paper.
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Claims the paper makes
80 Not checked yet · 39 Own interpretation · 20 No basis given · accuracy not yet measured
None of the sources cited for this claim have been checked yet.
In the paper
“In most bowel lesions lymph nodes are invaded (17,18).”
§ Pathogenesis of deep endometriosis > Abstract
What the sources say
- Not checked yetcites [17] Mechsner, 2008, Estrogen and progestogen receptor positive endometriotic lesions and disseminated cells in pelvic sentinel lymph nodes of patients with deep infiltrating rectovaginal endometriosis: a pilot study, Hum Reprod source
- Not checked yetcites [18] Jerman, 2015, The role of the lymphatic system in endometriosis: a comprehensive review of the literature, Biol Reprod source
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In the paper
“The recent observation (38) of ''ontogenetic'' uterine P resistance refers to the observation that the endometrial stromal compartment is not intrinsically P responsive at birth.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [38] Brosens, 2017, The impact of uterine immaturity on obstetrical syndromes during adolescence, Am J Obstet Gynecol source
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In the paper
“In a study of 368 patients with histologically proven deep infiltrating endometriosis Borghese et al. (36) observed that with low birth weight (defined as birth weight <2,500 g) had a higher risk of endometriosis, especially deep infiltrating endometriosis, compared with the reference group.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [36] Borghese, 2015, Low birth weight is strongly associated with the risk of deep infiltrating endometriosis: results of a 743 case-control study, PLoS One source
plaincorrelationaln = 368- Asserted: passes — The authors put it forward as true.
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In the paper
“There are three major observations that support the hypothesis of neonatal menstruation and the risk of early including the rare premenarcheal endometriosis that presents the same phenotype with angiogenic peritoneal implants and the formation of OMA as adolescent endometriosis, is unexplained by Sampson's hypothesis (33,34).”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
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In the paper
“The high correlation between the presence of deep endometriosis and the presence of peritoneal and ovarian endometriosis raises the question whether they are three different entities with a common or different pathogenesis.”
§ Pathogenesis of deep endometriosis > Abstract
What the sources say
- Not checked yetcites [21] Somigliana, 2004, Association rate between deep peritoneal endometriosis and other forms of the disease: pathogenetic implications, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Deep endometriosis as the only form of disease in absence of other endometriotic lesions was present in only 6.5% (21).”
§ Pathogenesis of deep endometriosis > Abstract
What the sources say
- Not checked yetcites [21] Somigliana, 2004, Association rate between deep peritoneal endometriosis and other forms of the disease: pathogenetic implications, Hum Reprod source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In a classic autopsy study of the neonatal endometrium the Harvard pathologists Ober and Bernstein (23) described that in 5% of the neonates the endometrium is P responsive and responds with decidualization and menstrual changes.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [23] Ober, 1955, Observations on the endometrium and ovary in the newborn, Pediatrics source
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In the paper
“Fourth, and probably most important, is the occurrence of the uterine immaturity in the young adolescent.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
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In the paper
“In 95% of the neonates, however, the endometrium responds with weak proliferation or secretory changes despite the high maternal P levels during pregnancy.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [23] Ober, 1955, Observations on the endometrium and ovary in the newborn, Pediatrics source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In adult life, endometriosis can be related to uterine preconditioning by cyclic menstruations acting as a priming mechanism (39).”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
What the sources say
- Not checked yetcites [39] Brosens, 2009, A role for menstruation in preconditioning the uterus for successful pregnancy, Am J Obstet Gynecol source
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“It has been shown that preeclampsia and placental insufficiency increase significantly the risk of the neonatal menstruation (37).”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [37] Levy, 1964, [Genital crisis in the newborn. repercussion of certain maternal or pregnancy factors on the frequency of neonatal metrorrhagia], Arch Franc Ped
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In the paper
“These histologic findings are in agreement with the occurrence of neonatal menstruation during the first week after birth in approximately 5% of the neonates (24) (Fig. 1).”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [24] Brosens, 2013, Is neonatal uterine bleeding involved in the pathogenesis of endometriosis as a source of stem cells?, Fertil Steril source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“At birth the endometrial cell in the neonatal uterus expresses a variable response to maternal P.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Proteins that are known to be involved in fibrogenesis, such as THY-1 and PPAR-g, were also aberrantly expressed in these conditions.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [49] Liu X, Zhang Q, Guo SW. Histological and immunohistochemical characterization of the similarity and difference between ovarian endometriomas and deep infiltrating endometriosis. Reprod Sci 2017 July 18. http://dx.doi.org/10.1177/1933719117718275. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These non-OMAs are also lined, similarly to the OMA, by endometrial surface epithelium with or without stroma or by polypoid endometriotic tissue.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
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In the paper
“Fukunaga (44) confirmed the presence of SMM as a focal, microscopic change or an incomplete rim of SMM surrounding the endometriotic cyst in both the endometrial stroma and the endometriotic cyst.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [44] Fukunaga, 2000, Smooth muscle metaplasia in ovarian endometriosis, Histopathology source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“''Endometrial glands and stroma'' outside the uterus are not always pathology.”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [62] Koninckx, 2016, Microscopic endometriosis: impact on our understanding of the disease and its surgery, Fertil Steril source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Endometriosis can be viewed as a disorder of exaggerated menstrual preconditioning that confers protection against placentation-related disorders such as preeclampsia.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A recent study (59), looking at the anogenital distance, a biomarker of prenatal hormonal environment, suggests that endometriosis and especially deep infiltrating endometriosis might have a prenatal origin.”
§ Pathogenesis of deep endometriosis > A POSSIBLE EMBRYONIC ORIGIN?
What the sources say
- Not checked yetcites [59] Mendiola, 2016, Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment, Hum Reprod source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Recurrent ectopic bleeding, however, occurs as a common feature in all three entities.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
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In the paper
“This association is independent of the macroscopic type of the lesions or their anatomical locations and may be related to recurrent cyclic microbleeding in the implants (42).”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
What the sources say
- Not checked yetcites [42] Fauconnier, 2005, Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications, Hum Reprod Update source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In a case-controlled study (36) of 743 patients with low birth weight the risk of developing deep endometriosis is almost two times more, reflecting the possibility of the influence of placental insufficiency on the embryonic development and also favoring the occurrence of neonatal uterine bleeding.”
§ Pathogenesis of deep endometriosis > A POSSIBLE EMBRYONIC ORIGIN?
What the sources say
- Not checked yetcites [36] Borghese, 2015, Low birth weight is strongly associated with the risk of deep infiltrating endometriosis: results of a 743 case-control study, PLoS One source
plaincorrelationaln = 743- Asserted: passes — The authors put it forward as true.
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In the paper
“Autopsy of 36 human fetuses of different gestational age (57) showed the presence of misplaced endometrium at five ectopic sites in 11%.”
§ Pathogenesis of deep endometriosis > A POSSIBLE EMBRYONIC ORIGIN?
What the sources say
- Not checked yetcites [57] Signorile, 2009, Ectopic endometrium in human foetuses is a common event and sustains the theory of mullerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer, J Exp Clin Cancer Res source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Menstrual preconditioning implies that P withdrawal bleedings or menstruations evolved in the human because of the need to initiate decidualization in the absence of pregnancy and protect uterine tissues from the profound hyperinflammation and oxidative stress that are associated with deep placentation (39).”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
What the sources say
- Not checked yetcites [39] Brosens, 2009, A role for menstruation in preconditioning the uterus for successful pregnancy, Am J Obstet Gynecol source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Based on randomized trials (41) against placebo, endometriosis appears to be responsible for chronic pelvic pain symptoms in more than half of confirmed cases.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
What the sources say
- Not checked yetcites [41] Brown, 2014, Endometriosis: an overview of Cochrane Reviews, Cochrane Database Syst Rev source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whatever the location, the ReTIAR in the formation of both OMA and deep infiltrating endometriosis appears to be the mechanism of progressive endometriosis.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Neither implantation, metaplasia, lymphatic, nor hematologic spread can explain all clinical manifestations including extrapelvic localizations (61).”
§ Pathogenesis of deep endometriosis > HYPOTHESIS II: DEEP ENDOMETRIOSIS IS A SPECIFIC TYPE OF ABNORMAL ENDOMETRIUM-LIKE CELL, A BENIGN TUMOR
What the sources say
- Not checked yetcites [61] Davis, 2017, Extrapelvic endometriosis, Semin Reprod Med
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“They showed that these conditions may share the same pathogenesis/pathophysiology.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [49] Liu X, Zhang Q, Guo SW. Histological and immunohistochemical characterization of the similarity and difference between ovarian endometriomas and deep infiltrating endometriosis. Reprod Sci 2017 July 18. http://dx.doi.org/10.1177/1933719117718275. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“A causal association between severe dysmenorrhea and endometriosis is very probable.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
What the sources say
- Not checked yetcites [42] Fauconnier, 2005, Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications, Hum Reprod Update source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Zhang et al. (48) investigated with in vitro experimentations the roles of activated platelets in driving epithelial-to-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in endometriosis and concluded that endometriotic lesions and their microenvironment contain all the necessary molecular machinery to promote SMM and fibrogenesis.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [48] Zhang, 2016, Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, Mol Cell Endocrinol source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“He investigated a series of ovaries with endometrioma in situ and documented the presence of progressive smooth muscle metaplasia (SMM) of the invaginated cortical wall to the extent that in advanced cases the invaginated pseudocyst was mimicking a uterine structure.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [43] Hughesdon, 1957, The structure of endometrial cysts of the ovary, J Obstet Gynaecol Br Emp source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The metaplastic phenomenon in the pathogenesis of deep infiltrating endometriosis, whether located in peritoneum, ovary, rectovaginal septum, or uterosacral ligament was at least partially confirmed by immunohistochemical studies (45).”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [45] Anaf, 2000, Smooth muscles are frequent components of endometriotic lesions, Hum Reprod source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the emergence of cyclic menstruation may serve to protect uterine tissues from the profound hyperinflammation and oxidative stress associated with deep placentation, a process known as preconditioning.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“This misplaced endometrium was located at sites correlating with the common location and the incidence of endometriosis in women.”
§ Pathogenesis of deep endometriosis > A POSSIBLE EMBRYONIC ORIGIN?
What the sources say
- Not checked yetcites [57] Signorile, 2009, Ectopic endometrium in human foetuses is a common event and sustains the theory of mullerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer, J Exp Clin Cancer Res source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that the immunologic defect might be preexisting to the development of endometriosis.”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“As discussed recently (62), microscopic endometriosis in the peritoneum, in the bowel at a distance from a deep endometriotic nodule, and in lymph nodes is not associated with pain or infertility, and there is no evidence so far for their subsequent development.”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [62] Koninckx, 2016, Microscopic endometriosis: impact on our understanding of the disease and its surgery, Fertil Steril source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“However, progression from subtle to more severe lesions, or from typical to cystic or deep, or from cystic to deep has never been observed and remains speculation.”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [63] Canis, 2016, Endometriosis may not be a chronic disease: an alternative theory offering more optimistic prospects for our patients, Fertil Steril source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In addition the extremely sensitive mesothelial cells react to retrograde menstruation by mesothelial cell retraction thus facilitating implantation of endometrial cells (111, 112).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Endometriosis is-erroneously (63)-considered a progressive disease.”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [63] Canis, 2016, Endometriosis may not be a chronic disease: an alternative theory offering more optimistic prospects for our patients, Fertil Steril source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The growth of endometriosis cells varies with the hormonal and immunologic environment.”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Most rectovaginal deep endometriosis lesions, which were followed clinically without surgery, did not progress (clinical observations as acknowledged) (64).”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [64] Koninckx, 2016, Epidemiology of subtle, typical, cystic, and deep endometriosis: a systematic review, Gynaecol Surg source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Retrograde menstruation and bleeding in endometriosis lesions generate an iron overload and oxidative stress in the peritoneal cavity (109) and/or in the endometriosis tissue (110).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
What the sources say
- Not checked yetcites [109] Donnez, 2016, Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis, Fertil Steril source
- Not checked yetcites [110] Harlev, 2015, Targeting oxidative stress to treat endometriosis, Expert Opin Ther Targets
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Clinically, typical cystic and deep endometriosis lesions, thus seem to be three different end points as suggested previously (22,67).”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [22] Nisolle, 1997, Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities, Fertil Steril source
- Not checked yetcites [67] Donnez, 1998, Pelvic endometriosis—the same or different entities in disguise? Reply, Fertil Steril
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many cystic lesions can remain unchanged during longer periods of time as evidenced by ultrasound.”
§ Pathogenesis of deep endometriosis > Clinical Observations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deep endometriosis is also an heterogeneous disease.”
§ Pathogenesis of deep endometriosis > Clinical Observations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Estrogen and P concentrations in PF (Supplemental Fig. 1) are much higher than in plasma, especially after ovulation (13).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
What the sources say
- Not checked yetcites [13] Koninckx, 1980, Biochemical characterization of peritoneal fluid in women during the menstrual cycle, J Clin Endocrinol Metab source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“As discussed recently (62), microscopic endometriosis in the peritoneum, in the bowel at a distance from a deep endometriotic nodule, and in lymph nodes is not associated with pain or infertility, and there is no evidence so far for their subsequent development.”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [62] Koninckx, 2016, Microscopic endometriosis: impact on our understanding of the disease and its surgery, Fertil Steril source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“A strong argument is that deep (174, 175) and cystic (176-178) ovarian endometriosis are consistently found to be clonal in origin.”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [174] Mayr, 2003, Does endometriosis really have premalignant potential? A clonal analysis of laser-microdissected tissue, FASEB J source
- Not checked yetcites [175] Wu, 2003, Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay, Fertil Steril source
- Not checked yetcites [176] Tamura, 1998, Analysis of clonality in human endometriotic cysts based on evaluation of X chromosome inactivation in archival formalin-fixed, paraffin-embedded tissue, Lab Invest
- Not checked yetcites [177] Yano, 1999, Molecular analysis of clonality in ovarian endometrial cysts, Gynecol Obstet Invest source
- Not checked yetcites [178] Jimbo, 1997, Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts, Am J Pathol
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whatever the original cell might be, endocrine, immunologic, or biochemical observations cannot explain why some initial lesions will progress and develop into severe endometriosis lesions.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The baboon model with induction of deep endometriosislike lesions by transplantation of endometrium and myometrium (223) is difficult to interpret.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
What the sources say
- Not checked yetcites [223] Donnez, 2013, Induction of endometriotic nodules in an experimental baboon model mimicking human deep nodular lesions, Fertil Steril source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Spontaneous deep endometriosis has not been reported in primates.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests an initial chromosomal or epigenetic change.”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It was calculated that after ovulation these steroids are secreted predominantly into the PF from where they are resorbed into plasma.”
§ Pathogenesis of deep endometriosis > SUPPLEMENTAL FIGURE 1
What the sources say
- Not checked yetcites [13] Koninckx, 1980, Biochemical characterization of peritoneal fluid in women during the menstrual cycle, J Clin Endocrinol Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First typical, cystic, and deep endometriosis are three distinct pathologies that only look similar by pathology.”
§ Pathogenesis of deep endometriosis > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Key in the endometriotic disease theory is that typical, cystic, and deep endometriosis lesions thus should be composed of slightly abnormal cells, similar to many other benign tumors.”
§ Pathogenesis of deep endometriosis > The Endometriotic Disease Theory or Genetic/ Epigenetic Changes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The many observations in women with endometriosis can be interpreted as the expression of predisposition and/or as the consequence of endometriosis instead of being the cause.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deep endometriosis thus becomes one specific type of endometriotic disease.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Typical, cystic, and deep endometriosis become three different diseases, which only have endometrium-like tissue in common.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Microscopic and subtle endometriosis lesions are not associated with pain or infertility.
- Rests on an assumption: Most endometriosis lesions do not progress to more severe pathology.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The key factor is the local (peritoneal) environment that induces the different types of endometriosis.”
§ Pathogenesis of deep endometriosis > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Each of them are (epi)genetically different endometriotic diseases with eventually clinical symptoms.”
§ Pathogenesis of deep endometriosis > FIGURE 3
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subtle endometriosis by implantation or metaplasia is not a disease until (epi)genetic changes occur.”
§ Pathogenesis of deep endometriosis > FIGURE 3
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- Rests on an assumption: Microscopic and subtle endometriosis lesions are not associated with pain or infertility.
- Rests on an assumption: Most endometriosis lesions do not progress to more severe pathology.
None of the sources cited for this claim have been checked yet.
In the paper
“More than 200 differences between the endometrium of women with and without endometriosis were described (for recent reviews, see Refs.[169][170][171][172][173]).”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [169] Carvalho, 2011, Role of eutopic endometrium in pelvic endometriosis, J Minim Invasive Gynecol source
- Not checked yetcites [170] Lessey, 2013, Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects, Semin Reprod Med source
- Not checked yetcites [171] Herndon, 2016, Global transcriptome abnormalities of the eutopic endometrium from women with adenomyosis, Reprod Sci source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition the endometriosis developing after total body radiation in primates can have a delay of 5 years, again suggesting a genomic effect.”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [191] Wood, 1983, Proton irradiation and endometriosis, Aviat Space Environ Med
- Not checked yetcites [192] Fanton, 1991, Radiation-induced endometriosis in Macaca mulatta, Radiat Res source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Key is genetic or epigenetic changes, which will lead to typical, cystic, deep, or other lesions as M€ ullerianosis and extra pelvic localizations.”
§ Pathogenesis of deep endometriosis > FIGURE 3
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- It may state two separate claims as one. 55
- Probably not a substantial claim. 31
- The quote only partly states this claim. 1
None of the sources cited for this claim have been checked yet.
In the paper
“Mesothelial-to-mesenchymal transition in the peritoneal cavity is well known (124, 125) with a specific role of platelets (48).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: What is the Original Cell?
What the sources say
- Not checked yetcites [124] Sandoval, 2016, Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions, J Pathol source
- Could not verifycites [125] Cheng, 2017, Characteristics of Human endometrium-derived mesenchymal stem cells and their tropism to endometriosis, Stem Cells Int sourceExperimental — accuracy not yet measured
The Introduction discusses endometrial mesenchymal stem cells and their migration to endometriotic lesions, not mesothelial-to-mesenchymal transition in the peritoneal cavity. Searches for that transition and for platelets found no passage in our copy addressing either point. (LLM, conf=0.74)
- Not checked yetcites [48] Zhang, 2016, Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, Mol Cell Endocrinol source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“With this latter definition most deep endometriosis le-sions are unique (occasionally 2 and rarely 3) and big (mostly >1 cm in diameter).”
§ Pathogenesis of deep endometriosis > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Endometriosis in the adolescent is characterized by angiogenic and hemorrhagic peritoneal and ovarian lesions.”
§ Pathogenesis of deep endometriosis > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“These adenomyosis externa lesions occasionally invade nerves (14) and have some neurotropic effect (15,16).”
§ Pathogenesis of deep endometriosis > Abstract
What the sources say
- Not checked yetcites [14] Anaf, 2002, Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis, Hum Reprod source
- Not checked yetcites [15] Siquara De Sousa, 2015, Neural involvement in endometriosis: Review of anatomic distribution and mechanisms, Clin Anat source
- Not checked yetcites [16] Anaf, 2004, Preferential infiltration of large bowel endometriosis along the nerves of the colon, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent review study (35) on endometriosis in symptomatic adolescents has shown that early onset disease is frequently severe and often involves extensive adhesions and even OMAs.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [35] Brosens, 2013, Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, functional transition of the endometrium to a fully P responsive tissue may be present at birth in newborns showing neonatal uterine bleeding but, in most girls, full endometrial P response will be achieved during adolescence.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
What the sources say
- Not checked yetcites [38] Brosens, 2017, The impact of uterine immaturity on obstetrical syndromes during adolescence, Am J Obstet Gynecol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The lesions include superficial angiogenic peritoneal implants and adhesions, and OMA can occasionally occur.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Yet, it is striking that cyclic endometrial decidualization followed by menstrual shedding is confined to few species where placentation is characterized by deep trophoblast invasion and remodeling of the spiral arteries from their origin in the inner myometrium.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In postmenopause, endometriosis can develop or be reactivated in the presence or absence of exogenous estrogens (Es) and can spread to various organs and structures causing obstructive lesions (Supplemental Table 1).”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
What the sources say
- Not checked yetcites Supplemental Table 1
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The development of deep endometriosis at a later age suggests that deep infiltrating endometriosis is a delayed stage of endometriosis.”
§ Pathogenesis of deep endometriosis > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The typical lesions are peritoneal, ovarian, and deep or adenomyotic endometriosis.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Deep endometriosis was described in the early nineties as adenomyosis externa (11) with endometrial glands and stroma in fibromuscular tissue.”
§ Pathogenesis of deep endometriosis > Abstract
What the sources say
- Not checked yetcites [11] Cornillie, 1990, Deeply infiltrating pelvic endometriosis: histology and clinical significance, Fertil Steril source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At present we realize that this definition was a mistake and should be abandoned.”
§ Pathogenesis of deep endometriosis > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion the pathophysiology of deep endometriosis remains debated and the mechanisms of disease progression, as well as the role of genetics and epigenetics in the process, still needs to be unraveled.”
§ Pathogenesis of deep endometriosis > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subtle lesions are not a disease until epi(genetic) changes occur.”
§ Pathogenesis of deep endometriosis > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These deep endometriosis lesions seem to develop as a benign tumor, preferentially in the pouch of Douglas, with extension toward the uterine artery or the ureters, with a preferential invasion into the muscle of the bowel wall or the diaphragm, but not into the fat.”
§ Pathogenesis of deep endometriosis > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Because the glandular activity was more in phase (%75%) with the menstrual cycle at depths >5 mm deep endometriosis was defined as lesions >5 mm in the peritoneum (12).”
§ Pathogenesis of deep endometriosis > Abstract
What the sources say
- Not checked yetcites [12] Koninckx, 1992, Deep endometriosis: a consequence of infiltration or retraction or possibly adenomyosis externa?, Fertil Steril source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 5-mm definition permits the inclusion of slightly deeper typical lesions.”
§ Pathogenesis of deep endometriosis > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A classification should reflect that deep endometriosis is a specific disease.”
§ Pathogenesis of deep endometriosis > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
In the paper
“Anaf et al. (45) concluded that the definition of distinct endometriotic entities based on the difference in the tissue composition of the lesions (endometriotic nodules vs. adenomyotic nodules) is inconsistent with the very frequent presence of smooth muscle cells in endometriosis irrespective of its localization.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [45] Anaf, 2000, Smooth muscles are frequent components of endometriotic lesions, Hum Reprod source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the absence of an animal model mimicking specific endometrial functions such as placentation, and permitting the induction of the different clinical manifestations of endometriosis, the pathophysiology remains debated with hypotheses, theories, and speculation.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS II: DEEP ENDOMETRIOSIS IS A SPECIFIC TYPE OF ABNORMAL ENDOMETRIUM-LIKE CELL, A BENIGN TUMOR
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“The first phenotype characterized by poor sex steroid hormone response is along the M€ ullerian tract including the uterus, rectovaginal septum, and, to some extent, the uterine ligaments, and the second phenotype outside the M€ ullerian tract particularly the ovaries.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [53] Brosens, 2000, Redefining endometriosis: is deep endometriosis a progressive disease?, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Van Kaam et al. (47) characterized the fibromuscular tissue and showed that the tissue shared characteristics with pathological wound healing, although the process could not be explained by transforming growth factor-b (TGF-b) alone.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [47] Van Kaam, 2008, Fibromuscular differentiation in deeply infiltrating endometriosis is a reaction of resident fibroblasts to the presence of ectopic endometrium, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Hyperplasia of the surrounding smooth muscle and fibrous tissue results in nodule formation and, important, deep infiltrating endometriosis is focally associated with microendometriomas of 500-2,000 mm in diameter particularly in the submucosal layer of the vagina, rectum.or bladder.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Uterine immaturity in adolescence is manifested by a higher risk of preeclampsia.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“The two dominant phenotypes of ectopic endometrium largely depend on the localization and have a different sex steroid hormone response (53).”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [53] Brosens, 2000, Redefining endometriosis: is deep endometriosis a progressive disease?, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The many similarities between OMA and deep infiltrating endometriosis (DIE) indicate that the two conditions share the same pathophysiology and very likely the same pathogenesis.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Its natural history is unclear.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS II: DEEP ENDOMETRIOSIS IS A SPECIFIC TYPE OF ABNORMAL ENDOMETRIUM-LIKE CELL, A BENIGN TUMOR
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The differences may result from the different lesional microenvironments and, in addition, from the difference in the aging between both as the OMA is the typical severe lesion in adolescent whereas deep endometriosis is typical in the older adult.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Misplaced endometrial glands and embryonic-like duct remnants were also described in six of seven fetuses, supporting the theory that some subtypes of endometriosis are related to an abnormal embryogenesis (58).”
§ Pathogenesis of deep endometriosis > A POSSIBLE EMBRYONIC ORIGIN?
What the sources say
- Not checked yetcites [58] Bouquet de, 2014, Endometriosis: a new cellular and molecular genetic approach for understanding the pathogenesis and evolutivity, Front Surg
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The conclusion by Tosti et al. (50) that the specific pathogenic features, such as apoptosis, neuroangiogenesis, oxidative stress, and inflammation, may explain the more severe symptomatology of deep endometriosis should include that OMA is a most severe reproductive disease with an early onset in reproductive life and with great delay in diagnosis.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [50] Tosti, 2015, Pathogenetic mechanisms of deep infiltrating endometriosis, Reprod Sci source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The differentiation has also therapeutic implications, but the current long delay of diagnosis implicates increasing SMM and fibrosis and loss of sex steroid hormone response in all locations.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The fact that OMA causes ovarian fibrosis is a medical problem that should arouse widespread concern in clinicians worldwide.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Cornillie et al. (11) showed that infiltration by endometrial glands and stroma occurs into adjacent fibromuscular tissue along the loose connective tissue and that penetration is arrested at the border of the underlying fat tissue.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
What the sources say
- Not checked yetcites [11] Cornillie, 1990, Deeply infiltrating pelvic endometriosis: histology and clinical significance, Fertil Steril source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Whether normal or abnormal, these cells develop in an environment different from the uterus with its specific relationship to the junctional zone.”
§ Pathogenesis of deep endometriosis > HYPOTHESIS II: DEEP ENDOMETRIOSIS IS A SPECIFIC TYPE OF ABNORMAL ENDOMETRIUM-LIKE CELL, A BENIGN TUMOR
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Fortunately, with the advancement in imaging techniques, the OMA is increasingly diagnosed at an earlier stage when the endometrioma may be less fibrotic and more responsive to medical treatment, making an evaluation of medical options critically important.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Deep infiltrating endometriosis is found not only in the rectovaginal septum, but also in all fibromuscular pelvic structures such as the uterosacral and utero-ovarian ligaments and the muscular wall of pelvic organs.”
§ Pathogenesis of deep endometriosis > A Disease Characterized by Recurrent Bleeding
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The critical factor in the progression of endometriosis is aging, but unfortunately the long delay in diagnosis of pelvic endometriosis prevents management at the early stage.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Their results suggested that endometriotic lesions are wounds that undergo repeated injury and healing, highlighting the importance of platelets in the development of endometriosis.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
What the sources say
- Not checked yetcites [48] Zhang, 2016, Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, Mol Cell Endocrinol source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, due to the commonality shared with endometriosis (i.e., cyclic bleeding), adenomyotic lesions behave just like endometriotic lesions, which are essentially wounds that undergo ReTIAR.”
§ Pathogenesis of deep endometriosis > ReTIAR as Pathogenetic Mechanism of Progressive endometriosis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The endometrium is the candidate because shredded menstrual endometrium is viable, was demonstrated in 1927 (113) and has implantation potential as demonstrated by subcutaneous injection (114) as early as 1958.”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: What is the Original Cell?
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Some lesions-estimated at <1%-are fast progressive and they do have a different aspect during surgery.”
§ Pathogenesis of deep endometriosis > Clinical Observations
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Instead of becoming at rest during a pregnancy, some deep lesions do progress and can cause bowel (65,66), uterus, or bladder perforations.”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [65] Setubal, 2014, Bowel complications of deep endometriosis during pregnancy or in vitro fertilization, Fertil Steril source
- Not checked yetcites [66] Vigano, 2015, Beyond infertility: obstetrical and postpartum complications associated with endometriosis and adenomyosis, Fertil Steril source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Most lesions are painful, especially during menstruation, but a minority (around 5%) does not cause pain.”
§ Pathogenesis of deep endometriosis > Clinical Observations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Clinical observation by surgeons suggests that the prevalence and severity of deep endometriosis is increasing during the past 20 years (64).”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [64] Koninckx, 2016, Epidemiology of subtle, typical, cystic, and deep endometriosis: a systematic review, Gynaecol Surg source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, glycodelins in concentrations as secreted by endometriosis cells in PF (107) decrease the natural killer activity (108), which can be viewed as an autoprotective mechanism of the endometriotic cell.”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
What the sources say
- Not checked yetcites [107] Koninckx, 1992, CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis, Fertil Steril source
- Not checked yetcites [108] Okamoto, 1991, Suppression by human placental protein 14 of natural killer cell activity, Am J Reprod Immunol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, at the moment of clinical diagnosis most lesions are no longer progressive, although they had obviously progressed before.”
§ Pathogenesis of deep endometriosis > Clinical Observations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The natural killer activity is decreased in PF and in plasma of women with endometriosis (103-105) and after excision of deep endometriosis their activity remains low, whereas elevated CA-125 concentrations return to normal (106).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
What the sources say
- Not checked yetcites [103] Oosterlynck, 1991, Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium, Fertil Steril source
- Not checked yetcites [104] Oosterlynck, 1992, The natural killer activity of peritoneal fluid lymphocytes is decreased in women with endometriosis, Fertil Steril source
- Not checked yetcites [105] Tanaka, 1992, Decreased natural killer cell activity in women with endometriosis, Gynecol Obstet Invest source
- Not checked yetcites [106] Oosterlynck, 1994, CO2-laser excision of endometriosis does not improve the decreased natural killer activity, Acta Obstet Gynecol Scand source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This is a common observation for typical lesions and consistent with their burnt out aspect by pathology.”
§ Pathogenesis of deep endometriosis > Clinical Observations
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“However, when traumatized by clinical examination or by puncture for oocyte pick-up, deep endometriosis lesions seem to be activated and might start growing again (63).”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [63] Canis, 2016, Endometriosis may not be a chronic disease: an alternative theory offering more optimistic prospects for our patients, Fertil Steril source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The epidemiology of endometriosis is unclear because of a variable inclusion of subtle lesions and because of diagnostic uncertainties of hospital-based discharge records (64).”
§ Pathogenesis of deep endometriosis > Clinical Observations
What the sources say
- Not checked yetcites [64] Koninckx, 2016, Epidemiology of subtle, typical, cystic, and deep endometriosis: a systematic review, Gynaecol Surg source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Pelvic endometriosis is associated with a low-grade inflammation of the peritoneal cavity with higher concentrations of activated macrophages and thus with higher concentrations of the many different cytokines (68-72) and angiogenic factors (73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: Players and Mechanisms
What the sources say
- Not checked yetcites [68] Koninckx, 1998, Endometriotic disease: the role of peritoneal fluid, Hum Reprod Update source
- Not checked yetcites [69] Barcz, 2000, Role of cytokines in pathogenesis of endometriosis, Med Sci Monit
- Not checked yetcites [70] Harada, 2001, Role of cytokines in endometriosis, Fertil Steril source
- Not checked yetcites [71] Wu, 2003, The role of cytokines in endometriosis, Am J Reprod Immunol source
- Not checked yetcites [72] Kyama, 2009, Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis, Front Biosci (Elite Ed) source
- Not checked yetcites [73] Oosterlynck, 1993, Angiogenic activity of peritoneal fluid from women with endometriosis, Fertil Steril source
- Not checked yetcites [74] Morgan, 1996, Angiogenesis in normal, hyperplastic, and neoplastic endometrium, J Pathol source
- Not checked yetcites [75] Taylor, 1997, Angiogenesis and macrophage activation in endometriosis
- Not checked yetcites [76] Healy, 1998, Angiogenesis: a new theory for endometriosis, Hum Reprod Update source
- Not checked yetcites [77] Matsuzaki, 1998, Angiogenesis in endometriosis, Gynecol Obstet Invest source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“More recently pluripotent stem cells were found in the endometrium and in the peritoneal cavity.”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: What is the Original Cell?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“For development on the chicken allantoic membrane, tissue integrity is important (115).”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: What is the Original Cell?
What the sources say
- Not checked yetcites [115] Nap, 2003, Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane, Hum Reprod source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The genetic/epigenetic hypothesis is attractive as it is consistent with heredity and clonality and as it explains why not all women with retrograde menstruation and implantation develop endometriosis.”
§ Pathogenesis of deep endometriosis > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Well established are familial clustering in humans (156) and primates (157).”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hypothesis that genetic or epigenetic changes are a prerequisite for development into typical cystic or deep endometriosis is a unifying theory and compatible with all clinical manifestations of endometriosis.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
- Rests on an assumption: Microscopic and subtle endometriosis lesions are not associated with pain or infertility.
- Rests on an assumption: Most endometriosis lesions do not progress to more severe pathology.
In the paper
“The statement of Novak and De Lima (226) was based on the association of adenomyosis and endometriosis, and observation confirmed more recently by the association of deep endometriosis and adenomyosis.”
§ Pathogenesis of deep endometriosis > DISCUSSION
What the sources say
- Not checked yetcites [226] Novak, 1948, A correlative study of adenomyosis and pelvic endometriosis, with special reference to the hormonal reaction of ectopic endometrium, Am J Obstet Gynecol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Deep endometriosis and adenomyosis are morphologically very similar.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The importance of the original cell is weakened by pluripotent stem cells, some of them originating from bone marrow in adult life and by mesothelial-to-mesenchymal transition.”
§ Pathogenesis of deep endometriosis > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“That E receptors (ERs) and PRs are present not only in glands and stroma but also in the smooth muscle component of deep endometriosis (229), and the expression of a-smooth muscle actin and collagen I in and around endometriotic lesions support the notion of the metaplastic process (230).”
§ Pathogenesis of deep endometriosis > DISCUSSION
What the sources say
- Not checked yetcites [229] Noel, 2010, Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis, Fertil Steril source
- Not checked yetcites [230] Ibrahim, 2017, Myofibroblasts are evidence of chronic tissue microtrauma at the endometrial-myometrial junctional zone in uteri with adenomyosis, Reprod Sci source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deep endometriosis then becomes a benign tumor.”
§ Pathogenesis of deep endometriosis > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Some of these mesenchymal/ mesothelial cells of the peritoneal cavity (48), of the mesothelial repair after surgery (126) and in endometrium and endometriosis (127-131) are directly derived from bone marrow.”
§ Pathogenesis of deep endometriosis > Development of (Deep) Endometriosis: What is the Original Cell?
What the sources say
- Not checked yetcites [48] Zhang, 2016, Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, Mol Cell Endocrinol source
- Not checked yetcites [126] Lucas, 2007, Stem cells for mesothelial repair: an understudied modality, Int J Artif Organs source
- Not checked yetcites [127] Fernandez Shaw, 1995, Bone marrow-derived cell populations in uterine and ectopic endometrium, Hum Reprod source
- Not checked yetcites [128] Du, 2007, Contribution of bone marrow-derived stem cells to endometrium and endometriosis, Stem Cells source
- Not checked yetcites [129] Zhang, 2012, A study in vitro on differentiation of bone marrow mesenchymal stem cells into endometrial epithelial cells in mice, Eur J Obstet Gynecol Reprod Biol source
- Not checked yetcites [130] Sakr, 2014, Endometriosis impairs bone marrow-derived stem cell recruitment to the uterus whereas bazedoxifene treatment leads to endometriosis regression and improved uterine stem cell engraftment, Endocrinology source
- Not checked yetcites [131] Moridi, 2016, Bone marrow stem cell chemotactic activity is induced by elevated CXCl12 in endometriosis, Reprod Sci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In twin sisters a prevalence of endometriosis (158-161) and age of onset (162) are similar.”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [158] Hadfield, 1997, Endometriosis in monozygotic twins, Fertil Steril source
- Not checked yetcites [159] Moen, 1993, The familial risk of endometriosis, Acta Obstet Gynecol Scand source
- Not checked yetcites [160] Moen, 1994, Endometriosis in monozygotic twins, Acta Obstet Gynecol Scand source
- Not checked yetcites [161] Treloar, 1999, Genetic influences on endometriosis in an Australian twin sample, Fertil Steril source
- Not checked yetcites [162] Kennedy, 1996, Age of onset of pain symptoms in non-twin sisters concordant for endometriosis, Hum Reprod source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Prevalence is increased by 6%-9% in first degree relatives (163, 164) and by 15% for severe disease (165, 166).”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [163] Simpson, 1980, Heritable aspects of endometriosis. I. Genetic studies, Am J Obstet Gynecol source
- Not checked yetcites [164] Coxhead, 1993, Familial inheritance of endometriosis in a British population. A case control study, J Obstet Gynecol source
- Not checked yetcites [165] Kennedy, 1998, The genetics of endometriosis, J Reprod Med
- Not checked yetcites [166] Kennedy, 1998, Magnetic resonance imaging to assess familial risk in relatives of women with endometriosis, Lancet source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Arcellana et al. (31) observed in one neonate with the McKusick-Kaufman syndrome not only the presence of tubal regurgitation of menstrual debris, as also observed by Sampson (6, 7), but in addition, for the first time, the serosal implantation of endometrial fragments.”
§ Pathogenesis of deep endometriosis > 885.e1
What the sources say
- Not checked yetcites [31] Arcellana, 1996, McKusick-Kaufman syndrome with legal complications of hydrometrocolpos and congenital endometriosis, J Perinatol
- Not checked yetcites [6] Sampson, 1925, Heterotopic or misplaced endometrial tissue, Am J Obstet Gynecol source
- Not checked yetcites [7] Sampson, 1927, Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity, Am J Obstet Gynecol source
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The interpretation that deep endometriosis is a specific disease is reflected in the distribution of deep lesions in all classes of The Revised American Fertility Society (AFS) classification with little association with cystic ovarian endometriosis (Fig. 4).”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
What the sources say
- Not checked yetcites [234] Koninckx, 1991, Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain, Fertil Steril source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The many associated effects are no longer considered the cause but either the consequence of (epi)genetic changes to endometriotic disease or they are factors signaling predisposition.”
§ Pathogenesis of deep endometriosis > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Abundant retrograde menstruation, for example, will increase peritoneal mesothelial cell retraction and oxidative stress, thus facilitating implantation and subtle lesions and also (epi)genetic changes.”
§ Pathogenesis of deep endometriosis > DISCUSSION
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, it is hardly conceivable that blocks of myometrium and junctional zone/myometrium are the cause of deep endometriosis in humans.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: Spontaneous deep endometriosis has not been reported in primates.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition it implies that subtle and microscopic lesions are a physiologic condition and that only after genetic/epigenetic changes into typical, cystic, or deep endometriosis does this occur.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- Rests on an assumption: Microscopic and subtle endometriosis lesions are not associated with pain or infertility.
- Rests on an assumption: Most endometriosis lesions do not progress to more severe pathology.
In the paper
“These experiments, however, emphasize the importance of tissue integrity-as for the chicken allantoic membrane experiments (115)-and of the special relationship of endometrium and junctional zone for growth and development.”
§ Pathogenesis of deep endometriosis > Gordts. Deep endometriosis: Pathogenesis. Fertil Steril 2017.
What the sources say
- Not checked yetcites [115] Nap, 2003, Tissue integrity is essential for ectopic implantation of human endometrium in the chicken chorioallantoic membrane, Hum Reprod source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is important to note that although Sampson observed tubal reflux of menstrual shedding (7) at the time of menstruation, but never reported the early stage of endometrial attachment to the mesothelium and invasion as documented by Witz et al. (32) in experimental conditions.”
§ Pathogenesis of deep endometriosis > 885.e1
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Endometriosis is an hereditary disease and some 50% of endometriosis lesions can be attributed to hereditary factors (153-155).”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [153] Sapkota, 2015, Genetic burden associated with varying degrees of disease severity in endometriosis, Mol Hum Reprod source
- Not checked yetcites [154] Saha, 2015, The heritability of endometriosis, Fertil Steril source
- Not checked yetcites [155] Baranov, 2015, Systems genetics view of endometriosis: a common complex disorder, Eur J Obstet Gynecol Reprod Biol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Both can have genomic or epigenetic effects (193).”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [193] Sofo, 2015, Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease, Arch Gynecol Obstet source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Genome-wide scanning resulted in 10 significant loci and a significant association of six of these (167, 168).”
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
What the sources say
- Not checked yetcites [167] Zondervan, 2016, Beyond endometriosis genome-wide association study: from genomics to phenomics to the patient, Semin Reprod Med source
- Not checked yetcites [168] Rahmioglu, 2015, Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci, Hum Mol Genet source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It cannot be excluded that the induction of deep endometriosis-like lesions by implantation of endometrium and myometrium signals that (epi)genetic modifications did occur (e.g., by the local environment as bleeding with oxidative stress).”
§ Pathogenesis of deep endometriosis > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
Microscopic and subtle endometriosis lesions are not associated with pain or infertility.
“Because microscopic and subtle endometriosis lesions are not associated with pain or infertility and most lesions do not progress to more severe pathology, ''endometriosis'' was suggested for subtle lesions to stress that this was not a clinical pathology.”
The paper relies on this without support.
Most endometriosis lesions do not progress to more severe pathology.
“Because microscopic and subtle endometriosis lesions are not associated with pain or infertility and most lesions do not progress to more severe pathology, ''endometriosis'' was suggested for subtle lesions to stress that this was not a clinical pathology.”
The paper relies on this without support.
Spontaneous deep endometriosis has not been reported in primates.
“First, spontaneous deep endometriosis has not been reported in primates.”
The paper relies on this without support.
Deep endometriosis and adenomyosis are morphologically very similar.
“Deep endometriosis, defined as adenomyosis externa, and adenomyosis are morphologically very similar.”
The paper relies on this without support.
Typical lesions are too small to be investigated for clonality.
“Typical lesions are too small to be investigated for clonality.”
The paper relies on this without support.
The many studies that tried to identify a specific hereditary predisposition, especially those investigating detoxication mechanisms, failed.
“The many studies that tried to identify a specific hereditary predisposition, especially those investigating detoxication mechanisms, however, failed.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“DE is quite different from OE or PE2 and its histology resembles that of uterine adenomyosis6.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
“There are three major observations that support the hypothesis of neonatal menstruation”
§ Pathogenesis of deep endometriosis > HYPOTHESIS I: PATHOGENESIS OF EARLY ONSET ENDOMETRIOSIS BY NEONATAL UTERINE BLEEDING WITH THE CYCLIC MENSTRUATION AS DRIVING MECHANISM FOR ADENOMYOTIC FORMATION
“Fourth, and probably most important, is the occurrence of the uterine immaturity in the young adolescent.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pathogenesis of deep endometriosis > Arguments Pointing to Genetic or Epigenetic Changes
“In twin sisters a prevalence of endometriosis (158-161) and age of onset (162) are similar.”
§ Pathogenesis of deep endometriosis > References
“162. Kennedy S, Hadfield R, Mardon H, Barlow D. Age of onset of pain symp- toms in non-twin sisters concordant for endometriosis. Hum Reprod 1996;11:403-5.”
Citations
Cites
Sampson, J. A. (1927) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30003-x · Cited by 2,334
Nisolle, M., & Donnez, J. (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)00191-x · Cited by 1,279
(1984) · PubMed · Cited by 997
Koninckx, P. R., Meuleman, C., Demeyere, S., Lesaffre, E., & Cornillie, F. J. (1991) · Fertility and Sterility · doi:10.1016/s0015-0282(16)54244-7 · Cited by 849
Deeply infiltrating pelvic endometriosis: histology and clinical significance
Cornillie, F. J., Oosterlynck, D., Lauweryns, J. M., & Koninckx, P. R. (1990) · Fertility and Sterility · doi:10.1016/s0015-0282(16)53570-5 · Cited by 594
Self-citationRole of cytokines in endometriosis
Harada, T., Iwabe, T., & Terakawa, N. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(01)01816-7 · Cited by 567
Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications
Fauconnier, A., & Chapron, C. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi029 · Cited by 522
Heritable aspects of endometriosis
Simpson, J. L., Elias, S., Malinak, L. R., & Buttram, V. C. (1980) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(80)90917-5 · Cited by 468
Contribution of Bone Marrow-Derived Stem Cells to Endometrium and Endometriosis
Du, H., & Taylor, H. S. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0828 · Cited by 449
Oosterlynck, D. J., Cornillie, F. J., Waer, M., Vandeputte, M., & Koninckx, P. R. (1991) · Fertility and Sterility · doi:10.1016/s0015-0282(16)54414-8 · Cited by 441
Research works printed but not linked: 5
- Cullen, 1896, Adeno-myoma of the round ligament, Johns Hopkins Hosp Bull, 7, 112
- Cullen, 1896, Adenoma-myoma uteri diffusum benignum, Johns Hopkins Hosp Bull, 6, 133
- Cullen, 1919, The distribution of adenomyomata containing uterine mucosa, Am J Obstet Gynecol, 80, 130
- Meyer, 1923, Zur frage der Urnieren-genese van Adenomyomen, Zentralbl Gynakol, 15, 577
- Batt, 2007, Mullerianosis, Histol Histopathol, 22, 1161
Cited by
Sorted by citations
Pathogenesis of endometriosis: The genetic/epigenetic theory
Koninckx, P. R., Ussia, A., Adamyan, L., Wattiez, A., Gomel, V., & Martin, D. C. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.10.013 · Cited by 427
“These bleeding episodes are also repeated tissue injuries, which are believed to play a role in the maturation of endometriosis (263, 264).”
BackgroundSelf-citationDella Corte, L., Di Filippo, C., Gabrielli, O., Reppuccia, S., La Rosa, V. L., Ragusa, R., Fichera, M., Commodari, E., Bifulco, G., & Giampaolino, P. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17134683 · Cited by 387
“However, the 5‐mm definition permits the inclusion only of the deeper lesions, so it is preferable to define deep endometriosis, as adenomyosis externa or adenomyosis‐like nodules; these lesions can involve the uterosacral ligaments, vagina, intestinal wall, rectovaginal pouch, ureter, and bladder [16,17].”
BackgroundPathogenesis of uterine adenomyosis, invagination or metaplasia?
García-Solares, J., Donnez, J., Donnez, O., & Dolmans, M.-M. (2018) · Fertility and Sterility · doi:10.1016/j.fertnstert.2017.12.030 · Cited by 339
Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment
Rolla, E. D. (2019) · F1000Research · doi:10.12688/f1000research.14817.1 · Cited by 327
The Main Theories on the Pathogenesis of Endometriosis
Lamceva, J., Uljanovs, R., & Strumfa, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054254 · Cited by 324
“In this theory, it is supposed that some changes in cell differentiation or relocation of the Müllerian ducts during embryogenesis of the fetus can maintain the spreading of embryonic cells—primordial endometrial cells [34].”
Background
Metadata
- Authors
- Gordts, S., Koninckx, P., & Brosens, I.
- Affiliations
- Leuven Institute for Fertility and Embryology (BE)
- Universitair Ziekenhuis Leuven (BE)
- Corresponding author
- Gordts, Stephan
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 108
- Issue
- 6
- Pages
- 872-885.e1
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2765750028
- Semantic Scholar
- 288d3cf48ca710962bc3f7df4980f4c6af53fab7
- Cited by
- 241
- References
- 253
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 25 · 2023: 24 · 2022: 45 · 2021: 33 · 2020: 32 · 2019: 30 · 2018: 18 · 2017: 3
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Health Sciences › Medicine › Obstetrics and Gynecology › Ectopic Pregnancy Diagnosis and Management
- Keywords
- deep infiltrating endometriosis, pathogenesis, endometriosis classification, adolescent endometriosis, endometrioma, epigenetic modifications, genetic susceptibility, clonality, dioxins, radiation, disease progression
- MeSH terms
- Endometriosis, Endometrium, Female, Humans, Phenotype, Prognosis, Risk Factors, Severity of Illness Index, Disease Progression, Genetic Predisposition to Disease, Epigenesis, Genetic
About these checks
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