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Advances in Diagnosis and Treatment of Endometriosis
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Advances in Diagnosis and Treatment of Endometriosis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: 15 September 2026 | Viewed by 3546

Special Issue Editors

Prof. Dr. Arrigo Fruscalzo

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Cantonal Hospital Fribourg, 1708 Fribourg, Switzerland
Interests: endometriosis; elasticity imaging technology; pregnancy complications
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Anis Feki

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Hôpital Fribourgeois, Fribourg, Switzerland
Interests: embryonic stem cells; induced pluripotent stem cells; developmental biology; disease modeling; neurodegenerative diseases; neurodevelopmental diseases; 2D and 3D cellular models; organoids; co-culture cellular systems; drug screening; personalized medicine; cellular replacement therapy and regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endometriosis is one of the most common gynecological pathologies. Despite its benign nature, it is linked to extensive clinical, social, and health financial burden, mainly due to its elusiveness and chronic pathway of development. Even so current research efforts, diagnosis and treatment options remain challenging. Thus, a prominent research area exists to be explored with the expectation of improving the way we approach and treat this disease.

In the past Special Issue (https://www.mdpi.com/journal/jcm/special_issues/O71E5E0N2A), we provided a collection of nine manuscripts covering various relevant topics related to endometriosis, ranging from psychological and mental health issues to the main topic of infertility concerns in endometriosis as a chronic disease, finally also addressing research on an immunologic fingerprint common to endometriosis-related comorbidities.

This new Special Issue aims to provide an overview of the current knowledge of endometriosis. This should cover all main issues of both endometriosis and adenomyosis, including diagnosis, classification systems, and conservative and surgical therapies for pain and infertility concerns. Manuscripts approaching less common topics, such as endometriosis during adolescence and menopause, extra-pelvic endometriosis, primary and secondary prevention strategies, new non-invasive diagnostic approaches, and new therapies are warmly encouraged. We welcome both original research articles and reviews.

Prof. Dr. Arrigo Fruscalzo
Prof. Dr. Anis Feki
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • endometriosis
  • adenomyosis
  • diagnosis
  • classification
  • therapy
  • progesterone

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Related Special Issue

Published Papers (4 papers)

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Research

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12 pages, 366 KB  
Article
Non-Invasive Diagnosis of Endometriosis by Questionnaires in Patients Using Contraception
by Felix Zeppernick, Samira Balimuttajjo, Christian Schorr, Florian Sibelius, Manuela Schuler, Sebastian Harth, Sarah Seeger, Anna Löffelmann, Muhammad A. Riaz, Ivo Meinhold-Heerlein and Lutz Konrad
J. Clin. Med. 2026, 15(1), 30; https://doi.org/10.3390/jcm15010030 - 20 Dec 2025
Viewed by 810
Abstract
Background/Objectives: The assessment of endometriosis (EMS)-associated pain is important, but only very few studies address the potential use of questionnaires for non-invasive prediction of the disease. Methods: In a prospective observational study from 2016 to 2024 with patients (n = 228) using hormonal [...] Read more.
Background/Objectives: The assessment of endometriosis (EMS)-associated pain is important, but only very few studies address the potential use of questionnaires for non-invasive prediction of the disease. Methods: In a prospective observational study from 2016 to 2024 with patients (n = 228) using hormonal contraception, all women with suspected EMS answered two questionnaires and were examined physically and with transvaginal ultrasound (TVUS). If deep infiltrating EMS (DIE) was suspected, magnetic resonance imaging (MRI) was performed. EMS diagnosis was confirmed by histological examination. Statistical analysis was mainly performed using 2 × 2 contingency tables. The decision tree was created manually. Results: The mean numerical rating scales (NRSs) of EMS-positive compared to EMS-negative patients were ~4-fold higher (4.45 and 1.15, respectively). Patients with EMS have, significantly, ~3 times more significant parameters compared to patients without EMS (18.5 and 5.9, respectively). In combination with dysuria and lightning-like pain, this resulted in very good prediction. A decision tree yielded a sensitivity of 0.924, a specificity of 0.917, a positive predictive value (PPV) of 0.924, a negative predictive value (NPV) of 0.917, and a positive likelihood ratio of 11.2, indicating a very good diagnostic test. There is no typical endometriosis pain, but various pain patterns are predictive of EMS. Conclusions: Thus, a reliable non-invasive EMS diagnosis by questionnaires is possible and could reduce the delay in the detection of EMS. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Endometriosis)
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28 pages, 14273 KB  
Article
Adenomyosis-Modern Techniques for Ultrasound and Histo-Pathological Diagnosis of the Endo-Myometrial Junction Zone Changes
by Elena Iuliana Anamaria Berbecaru, George-Lucian Zorilă, Anca-Maria Istrate-Ofiţeru, Gabriela-Camelia Roșu, Elvira Brătilă, Daniel Pirici, Cristina Jana Busuioc, Laurențiu Mogoantă, Răzvan Grigoraș Căpitănescu, Dominic-Gabriel Iliescu and Marian Valentin Zorilă
J. Clin. Med. 2025, 14(24), 8744; https://doi.org/10.3390/jcm14248744 - 10 Dec 2025
Viewed by 1272
Abstract
Background/Objectives: Adenomyosis (A) is a benign but invasive uterine condition frequently associated with structural changes in the uterine wall that may contribute to infertility. Methods: This is a retrospective study involving 140 patients: 100 diagnosed with primary infertility (PI) or secondary [...] Read more.
Background/Objectives: Adenomyosis (A) is a benign but invasive uterine condition frequently associated with structural changes in the uterine wall that may contribute to infertility. Methods: This is a retrospective study involving 140 patients: 100 diagnosed with primary infertility (PI) or secondary infertility (SI) and 40 in the control group. All patients were assessed using transvaginal two-dimensional, three-dimensional, and hysterosalpingo-contrast sonography (HyCoSy), performed in the early proliferative phase. Evaluated parameters included uterine dimensions, endometrial thickness, and characteristics of the junctional zone (JZ). Criteria such as JZmax > 5 mm or JZmax − JZmin > 5 mm, alongside other findings, supported the diagnosis of adenomyosis. Results: Patients with PI showed larger uterine longitudinal diameters, while SI patients had thicker JZ measurements. PI patients were significantly younger. Histopathological examination confirmed the presence of endometrial glands and periglandular stroma disrupting myometrial architecture, forming chronic lesions potentially linked to infertility. Conclusions: HyCoSy revealed variable depths of myometrial invasion by A, with some cases extending near the serosa. The chronic lesions found in histopathological examination were potentially linked to infertility. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Endometriosis)
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Review

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15 pages, 746 KB  
Review
The Paradox of Endometriosis in Mayer-Rokitansky-Kuster-Hauser Syndrome: Applying Three Criteria to Discriminate Between Retrograde Menstruation/Implantation and Coelomic Metaplasia/Embryonic Cell Rests Theories
by Lutz Konrad, Muhammad Assad Riaz, Felix Zeppernick, Magdalena Zeppernick, Ivo Meinhold-Heerlein, Noemi Salmeri, Paola Viganò, Edgardo Somigliana and Paolo Vercellini
J. Clin. Med. 2026, 15(4), 1599; https://doi.org/10.3390/jcm15041599 - 19 Feb 2026
Viewed by 421
Abstract
Background/Objectives: The scientific community is still divided between supporters of the implantation theory and researchers who advocate the theory of coelomic metaplasia/embryonic cell remnants to explain the initiation of endometriosis. A frequently cited argument in favor of the coelomic metaplasia/embryonic cell remnants theory [...] Read more.
Background/Objectives: The scientific community is still divided between supporters of the implantation theory and researchers who advocate the theory of coelomic metaplasia/embryonic cell remnants to explain the initiation of endometriosis. A frequently cited argument in favor of the coelomic metaplasia/embryonic cell remnants theory is the occurrence of endometriosis in the Mayer-Rokitansky-Kuster-Hauser syndrome, since retrograde menstruation is not possible without endometrium. However, nearly all women with uterovaginal agenesis have uterine remnants that harbour islets of endometrium. Methods: To verify the validity of the coelomic metaplasia/embryonic cell rests theory, we analysed all reports of endometriosis in patients with Mayer-Rokitansky-Kuster-Hauser syndrome without endometrium, published between 1980 and 2025. Three criteria had to be met in order to clearly demonstrate the absence of endometrium and the presence of endometriosis: (i) preoperative imaging, (ii) surgical visualization, and (iii) histological examination. Results: None of the nine reports fully met all three criteria, and the presence of endometrium could never be ruled out. In addition, we used ten characteristics to assess the ‘goodness’ of a theory: testability, logical coherence, conceptual clarity and comprehensibility, external consistency, empirical validity, predictive power, parsimony, broad applicability, practical utility, and heuristic value. Conclusions: Overall, the implantation theory appears to fully satisfy all criteria to explain the onset of endometriosis in Mayer-Rokitansky-Kuster-Hauser syndrome. In contrast, the coelomic metaplasia/embryonic cell rests theory satisfies eight criteria only partly and does not satisfy two of them. Therefore, the null hypothesis that endometriosis can be present in the absence of endometrium in patients with utero-vaginal agenesis can be reasonably rejected. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Endometriosis)
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18 pages, 665 KB  
Review
Comprehensive Approaches to Endometriosis Management and Targeted Strategies for Bowel Endometriosis
by Arrigo Fruscalzo, Alexandre Vallée, Carolin Marti, François Pugin, Jean-Marc Ayoubi, Michael D. Mueller and Anis Feki
J. Clin. Med. 2026, 15(3), 1040; https://doi.org/10.3390/jcm15031040 - 28 Jan 2026
Viewed by 673
Abstract
Background: Deep infiltrating endometriosis (DIE) and, in particular, bowel endometriosis stand out for their complexity. While surgery for bowel endometriosis has proven to be effective, there is a lack of standardization concerning the technique used and the reported outcomes. Objectives: The [...] Read more.
Background: Deep infiltrating endometriosis (DIE) and, in particular, bowel endometriosis stand out for their complexity. While surgery for bowel endometriosis has proven to be effective, there is a lack of standardization concerning the technique used and the reported outcomes. Objectives: The objective is to perform a review aiming to summarize the state of the art of bowel endometriosis and to point out the gaps to be addressed by future research. We also propose a novel classification of surgical procedures to fill these gaps and improve management. Methods: A literature search was performed on PubMed from inception to October 2025. Results: The following three major procedures for the excision of bowel endometriosis have been proposed: the nodule shaving, the discoid excision, and the segmental intestinal resection. One further technique, NOSE (natural orifice specimen extraction), can be applied for the removal of the specimen in cases of discoid or segmental resection. To reduce surgical morbidity, current data support the choice of most conservative surgical options, namely nodule dissection and discoid resection, as well as the use of nerve-sparing techniques in case of segmental resection. Nonetheless, there is little evidence concerning the indication and the most appropriate technique to be used, including their relative risks and benefits in terms of pain control, urinary and gastrointestinal function, risk of future relapse, and fertility outcomes. Conclusions: Significant barriers in comparing surgical outcomes due to unclear definitions, lack of standardization, and incomplete reporting are some of the most relevant issues frequently encountered. To fill these gaps, we propose a new classification system for bowel surgery that describes the dimension and the number of the lesions, as well as the type of surgical technique used, supplemented by the information if vaginal opening was necessary for complete lesion resection. This proposition aims to open a discussion on this topic and boost focused research to evaluate the utility of a new classification in clinical practice. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Endometriosis)
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