Endometriosis: Clinical Advances and Challenges

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

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 19757

Special Issue Editors

Department of Obstetrics and Gynecology, Cantonal Hospital Fribourg, 1708 Fribourg, Switzerland
Interests: endometriosis; fertility; assisted reproductive medicine
Special Issues, Collections and Topics in MDPI journals
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

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 burdens, mainly due to its elusiveness and its chronic development pathway. Despite current research efforts, diagnosis and treatment options still remain challenging. Thus, a bold research area exists to be explored in the expectation of improving the way we approach and treat this disease.

This Special Issue aims to provide a collection of manuscripts providing an overview of the current and evidence-based knowledge of endometriosis. These should cover all main issues of both endometriosis and adenomyosis, including the diagnosis, classification systems, as well as 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 or complementary and alternative therapies, are warmly encouraged. We welcome both original research articles and reviews.

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

Manuscript Submission Information

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Keywords

  • endometriosis
  • adenomyosis
  • diagnosis
  • classification
  • therapy
  • progesterone
  • complementary therapies

Published Papers (8 papers)

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Research

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12 pages, 753 KiB  
Article
Presence of Adenomyosis Impairs Clinical Outcomes in Women Undergoing Frozen Embryo Transfer: A Retrospective Cohort Study
by Noémie Sachs-Guedj, Buenaventura Coroleu, María Ángela Pascual, Ignacio Rodríguez and Nikolaos P. Polyzos
J. Clin. Med. 2023, 12(18), 6058; https://doi.org/10.3390/jcm12186058 - 19 Sep 2023
Cited by 1 | Viewed by 1639
Abstract
(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental [...] Read more.
(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p < 0.001). The presence of adenomyosis significantly decreased the clinical pregnancy rates (aOR 0.62, 95% CI: 0.39–0.98, p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27–0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98–4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)
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13 pages, 507 KiB  
Article
Endometriosis and the Temporomandibular Joint—Preliminary Observations
by Małgorzata Wójcik, Tomasz Goździewicz, Zuzana Hudáková and Idzi Siatkowski
J. Clin. Med. 2023, 12(8), 2862; https://doi.org/10.3390/jcm12082862 - 14 Apr 2023
Cited by 4 | Viewed by 2202
Abstract
(1) Background: The complete picture of the disease is not fully recognized and extends far beyond the pelvis. The disease’s impacts lead to systemic inflammation, in turn resulting in sensitization to pain. The aim of this study was to check whether statistical correlations [...] Read more.
(1) Background: The complete picture of the disease is not fully recognized and extends far beyond the pelvis. The disease’s impacts lead to systemic inflammation, in turn resulting in sensitization to pain. The aim of this study was to check whether statistical correlations exist in women with endometriosis with regard to their experience of pain: headache, pelvic pain, temporomandibular joint pain, along with teeth clenching and the treatment of the disease. We constructed contingency tables, followed by Pearson’s chi-square test and Cramer’s V coefficient values. (2) Methods: A survey was conducted among 128 women aged 33.43 ± 5.79 with a diagnosis of endometriosis (disease duration 6.40 ± 5.88 years). (3) Results: There was a correlation between the occurrence of pain on the right and left sides of the pelvis and pain on the right and left sides of the temporomandibular joint, p-value = 0.0397, V = 0.2350, and between the presence of pelvic pain and the treatment of endometriosis, p-value = 0.0104, V = 0.3709, and between the presence of pain outside the pelvis and the treatment of endometriosis, p-value = 0.0311, V = 0.4549. There was a highly significant correlation between teeth clenching and temporomandibular joint pain, p-value = 0.0005, V = 0.3695. (4) Conclusions: The study revealed a correlation between pelvic endometriosis symptoms and symptoms in the temporomandibular joint. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)
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16 pages, 1295 KiB  
Article
Pelvic Pain, Mental Health and Quality of Life in Adolescents with Endometriosis after Surgery and Dienogest Treatment
by Elena P. Khashchenko, Elena V. Uvarova, Vladimir D. Chuprynin, Margarita Yu. Pustynnikova, Timur Kh. Fatkhudinov, Andrey V. Elchaninov, Zhanna R. Gardanova, Tatyana Yu. Ivanets, Mikhail Yu. Vysokikh and Gennady T. Sukhikh
J. Clin. Med. 2023, 12(6), 2400; https://doi.org/10.3390/jcm12062400 - 20 Mar 2023
Viewed by 2089
Abstract
Background: Diagnostic and treatment delays have caused significant impacts on the physical and emotional well-being of adolescents with endometriosis, though such research is limited. This study aimed to assess the effects of one-year dienogest therapy on the clinical picture, pain patterns, psycho-emotional status, [...] Read more.
Background: Diagnostic and treatment delays have caused significant impacts on the physical and emotional well-being of adolescents with endometriosis, though such research is limited. This study aimed to assess the effects of one-year dienogest therapy on the clinical picture, pain patterns, psycho-emotional status, and quality-of-life indicators in adolescents with endometriosis after surgical treatment. Methods: The study enrolled 32 girls aged 13–17 with peritoneal endometriosis to analyze one-year dynamics of the Visual Analog Scale (VAS), McGill Pain Questionnaire, Beck Depression Scale (BDI), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI) and SF-36 quality-of-life survey scores along with clinical and laboratory indicators before surgery and after one-year dienogest therapy. Results. The therapy provided a significant alleviation of endometriosis-associated clinical symptoms, including dysmenorrhea, pelvic pain, gastrointestinal/dysuria symptoms, decreased everyday activity (<0.001), a decrease in anxiety/depression scores (BDI, HADS, STAI), and quality-of-life improvement (<0.001). These effects were accompanied by beneficial dynamics in hormone and inflammatory markers (prolactin, cortisol, testosterone, estradiol, CA-125, neutrophil/lymphocyte ratio; <0.005) within reference ranges. A low body mass index and high C-reactive protein levels were associated with higher VAS scores; a high estradiol level was a factor for anxiety/depression aggravation (<0.05). Conclusions: Dienogest, after surgical treatment, significantly improved quality of life and reduced pain symptoms while showing good tolerability and compliance, and reasoning with timely hormonal therapy in adolescents with endometriosis. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)
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8 pages, 252 KiB  
Article
Does Endometriosis Impact the Composition of Follicular Fluid in IL6 and AMH? A Case-Control Study
by Khadija Kacem-Berjeb, Marouen Braham, Cyrine Ben Massoud, Hela Hannachi, Manel Hamdoun, Sana Chtourou, Linda Debbabi, Maha Bouyahia, Anis Fadhlaoui, Fethi Zhioua, Anis Feki, Nozha Chakroun and Olfa Bahri
J. Clin. Med. 2023, 12(5), 1829; https://doi.org/10.3390/jcm12051829 - 24 Feb 2023
Viewed by 1120
Abstract
Objective: The aim of this study was to compare follicular liquid levels of IL6 and AMH in women with and without endometriosis and to evaluate their potential impact on ICSI outcomes. Materials and Methods: It is a prospective case-control study conducted on 25 [...] Read more.
Objective: The aim of this study was to compare follicular liquid levels of IL6 and AMH in women with and without endometriosis and to evaluate their potential impact on ICSI outcomes. Materials and Methods: It is a prospective case-control study conducted on 25 women with proven endometriosis and 50 patients diagnosed with other causes of infertility. All these patients were candidates for ICSI cycles. Their follicular fluid was collected at the time of oocyte retrieval and used to evaluate IL-6 and AMH titers by electro-chemiluminescent immunoassay (Cobas e411-Roche). Results: The IL-6 levels in follicular fluid were higher in the endometriosis group than in the control group (152.3 vs. 19.9 pg/mL; p = 0.02). The median level for AMH was 2.2 ± 1.88 ng/mL with no statistical difference between the two groups (2.2 vs. 2.7 ng/mL, p = 0.41). No significant correlation between the follicular IL6 and AMH levels was observed. Conclusions: The oocyte quality seems to be preserved in patients with endometriosis with the adequate response to ovarian stimulation. High levels of follicular IL6 are in accordance with the inflammatory phenomenon of the disease; however, this increase has no impact on ICSI outcomes. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)

Review

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28 pages, 414 KiB  
Review
Surgical Management of Ovarian Endometrioma: Impact on Ovarian Reserve Parameters and Reproductive Outcomes
by Angelos Daniilidis, Georgios Grigoriadis, Dimitrios Rafail Kalaitzopoulos, Stefano Angioni, Üzeyir Kalkan, Adrien Crestani, Benjamin Merlot and Horace Roman
J. Clin. Med. 2023, 12(16), 5324; https://doi.org/10.3390/jcm12165324 - 16 Aug 2023
Cited by 4 | Viewed by 3848
Abstract
Ovarian endometriomas have a negative impact on a patient’s reproductive potential and are likely to cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-Müllerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include [...] Read more.
Ovarian endometriomas have a negative impact on a patient’s reproductive potential and are likely to cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-Müllerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include cystectomy, ablative methods, ethanol sclerotherapy and combined techniques. The optimal surgical approach remains a matter of debate. Our review aimed to summarize the literature on the impact of surgical management of endometrioma on AMH, AFC and fertility outcomes. Cystectomy may reduce recurrence rates and increase chances of spontaneous conception. However, a postoperative reduction in AMH is to be anticipated, despite there being evidence of recovery during follow-up. The reduction in ovarian reserve is likely multi-factorial. Cystectomy does not appear to significantly reduce, and may even increase, AFC. Ablative methods achieve an ovarian-tissue-sparing effect, and improved ovarian reserve, compared to cystectomy, has been demonstrated. A single study reported on AMH and AFC post sclerotherapy, and both were significantly reduced. AMH levels may be useful in predicting the chances of conception postoperatively. None of the aforementioned approaches has a clearly demonstrated superiority in terms of overall chances of conception. Surgical management of endometrioma may, overall, improve the probability of pregnancy. Evidence on its value before medically assisted reproduction (MAR) is conflicting; however, a combination of surgery followed by MAR may achieve the optimal fertility outcome. In view of the complexity of available evidence, individualization of care, combined with optimal surgical technique, is highly recommended. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)
13 pages, 647 KiB  
Review
Fertility Preservation in Women with Endometriosis
by Sabrina Rangi, Christine Hur, Elliott Richards and Tommaso Falcone
J. Clin. Med. 2023, 12(13), 4331; https://doi.org/10.3390/jcm12134331 - 28 Jun 2023
Cited by 2 | Viewed by 1856
Abstract
Several mechanisms have been implicated in the pathogenesis of endometriosis-related infertility. For patients considering surgery, the risk of iatrogenic injury is among the most important factors in the context of fertility preservation, along with age and individual reproductive goals. In the case of [...] Read more.
Several mechanisms have been implicated in the pathogenesis of endometriosis-related infertility. For patients considering surgery, the risk of iatrogenic injury is among the most important factors in the context of fertility preservation, along with age and individual reproductive goals. In the case of endometrioma excision, evidence overwhelmingly demonstrates the negative impact of surgery on ovarian reserve, with significant reductions in antimullerian hormone (up to 30% in unilateral versus up to 44% in bilateral endometriomas). The surgical endometriosis patient should be thoroughly counseled regarding fertility preservation and discussion should include tissue, embryo, and oocyte cryopreservation options. For the latter, data support cryopreservation of 10–15 oocytes in women ≤35 years and over 20 for those >35 years for a realistic chance to achieve one or more live births. When performing surgical interventions for endometriosis, reproductive surgeons should employ fertility-conserving surgical methods to reduce the likelihood of postoperative iatrogenic diminished ovarian reserve. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)
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14 pages, 331 KiB  
Review
Understanding Psychological Symptoms of Endometriosis from a Research Domain Criteria Perspective
by Katharina van Stein, Kathrin Schubert, Beate Ditzen and Cornelia Weise
J. Clin. Med. 2023, 12(12), 4056; https://doi.org/10.3390/jcm12124056 - 15 Jun 2023
Cited by 7 | Viewed by 4865
Abstract
Endometriosis is currently the second most common gynecological disease and is associated with severe pain, vegetative impairment, and infertility. In association, there are considerable psychological symptoms that limit the quality of life of those affected. In this narrative review, the Research Domain Criteria [...] Read more.
Endometriosis is currently the second most common gynecological disease and is associated with severe pain, vegetative impairment, and infertility. In association, there are considerable psychological symptoms that limit the quality of life of those affected. In this narrative review, the Research Domain Criteria (RDoC) framework was utilized to display the different transdiagnostic processes involved in disease progression and maintenance in regard to psychosocial functioning. Using the RDoC framework, it becomes clear that immune/endocrinological dysregulation is interlocked with (pelvic) pain chronification processes and psychological symptoms such as depressive mood, loss of control, higher vigilance toward the onset or worsening of symptoms, social isolation, and catastrophizing. This paper will discuss and identify promising treatment approaches, in addition to medical care, as well as further research implications. Endometriosis can come with substantial psychosomatic and social burden, requiring more research to understand the interdependence of different factors involved in its chronic development pathway. However, it is already clear that standard care should be extended with multifaceted treatments addressing pain, as well as the psychological and social burden, in order to halt the cycle of aggravation of symptoms and to improve quality of life for patients. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)

Other

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8 pages, 1201 KiB  
Brief Report
Epidemiological and Immune Profile Analysis of Italian Subjects with Endometriosis and Multiple Sclerosis
by Brunella Zizolfi, Virginia Foreste, Simona Bonavita, Valentina Rubino, Giuseppina Ruggiero, Vincenzo Brescia Morra, Roberta Lanzillo, Antonio Carotenuto, Francesca Boscia, Maurizio Taglialatela and Maurizio Guida
J. Clin. Med. 2023, 12(5), 2043; https://doi.org/10.3390/jcm12052043 - 04 Mar 2023
Cited by 2 | Viewed by 1159
Abstract
Objective: To report for the first time an Italian epidemiological analysis of the prevalence of multiple sclerosis (MS) in patients with endometriosis (EMS), through the study of the endometriosis population of our referral center; to analyze the clinical profile and perform a laboratory [...] Read more.
Objective: To report for the first time an Italian epidemiological analysis of the prevalence of multiple sclerosis (MS) in patients with endometriosis (EMS), through the study of the endometriosis population of our referral center; to analyze the clinical profile and perform a laboratory analysis to examine the immune profile and the possible correlation to other autoimmune diseases of the enrolled patients. Methods: We evaluated 1652 women registered with EMS in the University of Naples Federico II and retrospectively searched patients with a co-diagnosis of MS. Clinical features of both conditions were recorded. Serum autoantibody and immune profiles were analyzed. Results: 9 out of 1652 patients presented a co-diagnosis of EMS and MS (9/1652 = 0.005%). Clinically, EMS and MS presented in mild forms. Hashimoto’s thyroiditis was found in two patients (2/9). Even if not statistically significant, a trend of variation in CD4- CD8 T lymphocytes and of B cells were found. Conclusion: Our findings suggest an increased risk of MS in women with EMS. However, large-scale prospective studies are needed. Full article
(This article belongs to the Special Issue Endometriosis: Clinical Advances and Challenges)
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