Endometriosis Concepts

Endometriosis Concepts is maintaned by Dr. Dan Martin, a retired gynecologist & REI specialist.

IntroductionConcepts and TheoriesEndometriosis Fertility IndexIs there a Stage 5?

Endometriosis Concepts and Theories (PDF) • Mobile Summary

Laparoscopic Appearance 1988 (PDF) • Color Atlas 1990 (PDF)

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Introduction

Studying endometriosis is like nailing Jell-O to a tree.

Clinical descriptions suggesting the presence of endometriosis were first written almost 4,000 years ago (Redwine 2012, Nezhat 2012). But a microscopic description did not occur until 1860 when Rokitansky [Appendix II] described the histologic characteristics of either ovarian endometriosis or endometriosis-associated ovarian cancer.

The difficulties in recognizing endometriosis were noted by Russell (1899) who discovered small, unseen, microscopic, intra-ovarian endometriosis and endometriosis hidden by ovarian adhesions. Sampson (1921 & 1927) subsequently found endometriosis within deep cul-de-sac adhesions.

Sampson published a series of articles from 1921 to 1940 in which he first used the term endometriosis in 1925. He discussed that endometriosis was different than endometrium "both in structure and in function," ectopic endometrium and endometriosis could coexist in one patient with a recognizable transition, and there was an associated inflamatory reaction similar to that seen in cancer and infection. Sampson concluded that retrograde flow does not explain all endometriosis and suggested additional theories such as celomic metaplasia or venous dissemination. He also discussed lymphatic dissemination, transplantation endometriosis, direct extension from perforating ovaries, tubal epithelium as the origin, metaplasia of peritoneal epithelium due to the stimulus of menstrual blood from perforating ovaries, metaplasia of the mesothelial lining of the processus vaginalis peritoneii or of the endothelial lining of dilated vessels, extraperitoneal endometriosis remnants from Wolffian bodies, developmentally misplaced endometrial (Müllerian) tissue, and why endometriosis was a better designation than Müllerianosis. He described lesions including chocolate cysts, blebs, adenomyomatous infiltration, adherent surfaces, red raspberries, purple raspberries, blueberries, deep infiltration, inflammatory reactions, peritoneal pockets, and cancer arising in endometriotic implants.

Many of the anatomic phenotypes that Sampson described, in addition to look-alike lesions, can be seen in:

Fallon (1950) added to our understanding with clarification of colorless, amenorrheic lesions while Karnaky (1969) published an age dependent appearance of endometriosis starting with an initial water blister appearance.

Goldstein (1980) found petechial-like endometriosis and blebs in adolescents with chronic pain. Jansen (1986) subsequently confirmed Sampson's, Karnaky's, and Goldstein's finding with six different descriptions and also noted an additional six look-a-like lesions that were not endometriosis. Redwine (1988) then added the more descriptive term “near-contact laparoscopy” to update Goldstein’s “close-up view.”

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Concepts and Theories

Of the more than 300 concepts and theories since 1855 BC covered in "Endometriosis Concepts and Theories," it generally takes eighteen to discuss what I saw or published and many more to introduce what I have read. But, those are only a small sampling of the more than 27,139 articles in PubMed (NIH), 388,000 articles listed in scholar.google.com and 291,000 array- and sequence-based data in the NIH GEO database.


Endometriosis Concepts and Theories is periodically updated.

A mobile summary is also available.

An endometriosis concept or theory may be useful in guiding research, explaining treatment, acting as a framework for education, and studying endometriosis. However, no concept or theory is completely adequate or determines if a treatment works. Treatment should be based on evidence of success and updated as knowledge changes.

Theories of develoment and progression are divided into the Cell of Origin, methods of Dissemination, stimuli for Induction or Activation, and the pathophysiological Transformation from an original Müllerian or non-Müllerian precursor cell to endometriosis. Those are opposed by the complimentary mechanisms of Inactivation and Clearance.

Cell of Origin

  • Müllerian, Endometrium
  • Müllerian, Embryonic Remnants
  • Müllerian, Tubal Metaplasia / Differentiation
  • Müllerian, Uterocervical Extension
  • Non-Müllerian, Stem Cell Differentiation

Dissemination (Metastasis) or In Situ

  • Retrograde Menstruation
  • Hematogenous Dissemination
  • Lymphatic Dissemination
  • Traumatic / Surgical Dissemination
  • Abnormal Fetal Müllerian Locations
  • Non-Müllerian Tissue
  • In Situ - Normal Fetal Müllerian Locations and Coelomic Metaplasia

Induction or Activation

  • Estrogen
  • Inflammation
  • Infection
  • Trauma
Transformation and Growth

The transformation from a cell of origin to deep infiltrating endometriosis or an ovarian endometrioma holds significant promise for research and development of therapeutic options. Transformation involves the local environment, inflammation, cellular histological modifications, biochemical changes, immunologic changes, apoptosis, autophagy, fibrosis, muscular metaplasia, cancer-associated driver mutations, angiogenesis, genetic predisposition, genetic changes, genetic dysregulation, epigenetic changes, and more.

Inactivation and Clearance

Growth is opposed by immunology, inactivation, apoptosis, epigenetic reversibility, and scavenging mechanisms including autophagy/clearance.

Theories and concepts are covered in:

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Endometriosis Fertility Index

David Adamson's Endometriosis Fertility Index (EFI) is a clinical tool used to predict pregnancy rates after endometriosis surgery. It is the only system that is predictive of fertility, but is not a staging system. The EFI has 6 levels and is based 50% on history, 30% on surgical findings at the completion of surgery, and 20% on the American Fertility Society (rAFS) total and endometriosis sub-total scores.

Click for EFI Calculator

The revised American Fertility Society (rAFS) and American Society of Reproductive Medicine (rASRM) staging systems are the staging systems most commonly used at surgery but are not predictive of fertility. The 1984 rAFS staging system was renamed the rASRM staging system in 1996 after that organization changed their name. The two are otherwise the same. Thgey can be used to describe the appearance at surgery and is somewhat predictive of surgical difficulty. The rAFS/rASRM has 150 points. A score 40 or higher is stage 4. The system separates stage 4 into scores for 4A (40 to 70 points) and 4B (71 to 150 points). Scores of 71 and higher are generally seen with severe adhesions. Adhesions are a type of scar tissue that can block the pathway that eggs use to get from the ovary to the tube.


Adamson GD & Pasta DJ. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril 2010;94(5):1609–15

American Fertility Society. Revised American Fertility Society classification of endometriosis 1985. Fertil Steril 43(3):351-352, 1985

American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 67(5): 817-21, 1997

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Is there a stage 5 endometriosis?

Michel Canis (1992) suggested using a revised American Fertility Society (rAFS, 1985) score of >70 as a new stage 5 for endometriosis.

This is also the 4B sub-score of the Endometriosis Fertility Index (EFI) (Adamson 2010). The EFI is a clinical tool used to predict pregnancy rates after endometriosis surgery. It is the only system that is predictive of fertility, but is not a staging system. The EFI has 6 levels and uses the 1985 rAFS staging system’s total and endometriosis sub-total score separately.

The rAFS (or rASRM) is the staging system most commonly used in surgical research. It is useful in comparing the gross appearance at the beginning of surgery and is somewhat predictive of surgical difficulty. But, it is not predictive of fertility, pain, the depth of infiltration, or the volume of infiltrating endometriosis.

The rAFS has 150 points. A score of 40 or higher is rASRM stage 4. The EFI separates stage 4 into scores for 4A (40 to 70 points) and 4B (71 to 150 points). Scores of 71 and higher are generally seen only with severe adhesions. Adhesions, a type of scar tissue, can block the pathway that the eggs use to get to the tube.

Adamson GD & Pasta DJ. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril 2010;94(5):1609–15

American Fertility Society. Revised American Fertility Society classification of endometriosis 1985. Fertil Steril 43(3):351-352, 1985

American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 67(5): 817-21, 1997

Canis M, Pouly JL, Wattiez A, et al. Incidence of bilateral adnexal disease in severe endometriosis (revised American Fertility Society [AFS], stage IV): should a stage V be included in the AFS classification? Fertil Steril 1992;57:691–692.

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Updated July 12, 2020