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Diagnosis and Management of Endometriosis and Uterine Fibroids
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Diagnosis and Management of Endometriosis and Uterine Fibroids

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 (30 June 2021) | Viewed by 106659

Special Issue Editor

Prof. Dr. Simone Ferrero

E-Mail Website
Guest Editor
1. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy
2. Unit of Obstetrics and Gynaecology, IRCCS AOU San Martino – IST, Genova, Italy
Interests: gynecology; endometriosis; fibroids; laparoscopy; hormonal therapy; hysteroscopy; ultrasonography; gynecological surgery; minimally invasive surgery; infertility
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Endometriosis and uterine fibroids are the most frequent gynecological disorders of reproductive-aged women. Endometriosis typically caused pain symptoms (dysmenorrhea, deep dyspareunia, non-menstrual pelvic pain, and dyschezia) and infertility. Uterine fibroids cause heavy menstrual bleeding, and may affect fertility. These conditions significantly impair quality of life, working efficiency, and sexual life. Although research has improved our knowledge of the genetic and molecular pathways involved in the establishment and progression of these conditions, their pathogenesis remains to be fully understood. Ultrasonography plays a pivotal role in the diagnosis of endometriosis and uterine fibroids; other imaging techniques (such as magnetic resonance imaging, double contrast barium enema) can be used for the diagnosis of endometriosis. Hysteroscopy and sonohysterography may be used to assess the characteristics of uterine fibroids. Hormonal therapies have been widely used for the treatment of symptoms caused by endometriosis and uterine fibroids; however, these therapies are not curative, and symptoms usually recur after the discontinuation of therapies. Alternatively, these conditions can be treated by minimally invasive surgical techniques.

Prof. Simone Ferrero
Guest Editor

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Keywords

  • endometriosis
  • fibroids
  • laparoscopy
  • hormonal therapy
  • hysteroscopy
  • ultrasonography
  • gynecological surgery
  • diagnosis
  • infertility

Published Papers (17 papers)

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Research

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15 pages, 5709 KiB  
Article
Markers of Inflammation and Vascular Parameters in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids
by Iwona Szydłowska, Marta Grabowska, Jolanta Nawrocka-Rutkowska, Andrzej Kram, Małgorzata Piasecka and Andrzej Starczewski
J. Clin. Med. 2021, 10(16), 3721; https://doi.org/10.3390/jcm10163721 - 21 Aug 2021
Cited by 7 | Viewed by 2415
Abstract
The exact mechanism of selective progesterone receptor modulator action in leiomyoma still challenges researchers. The aim of the study was to assess the effects of ulipristal acetate (UPA) on immunoexpression of inflammatory markers and vascularization in fibroids. UPA-treated patients were divided into three [...] Read more.
The exact mechanism of selective progesterone receptor modulator action in leiomyoma still challenges researchers. The aim of the study was to assess the effects of ulipristal acetate (UPA) on immunoexpression of inflammatory markers and vascularization in fibroids. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction), (3) and no response to treatment (no decrease or increase in fibroid volume). The percentage of TGFβ, IL6, IL10, CD117, and CD68-positive cells were significantly lower in the group with a good response to treatment vs. the control group. Moreover, the percentage of IL10 and CD68-positive cells in the group with a good response to treatment were also significantly lower compared to the no response group. Additionally, a significant decrease in the percentage of IL10-positive cells was found in the good response group vs. the weak response group. There were no statistical differences in the percentage of TNFα-positive cells and vessel parameters between all compared groups. The results of the study indicate that a good response to UPA treatment may be associated with a decrease of inflammatory markers, but it does not influence myoma vascularization. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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13 pages, 3353 KiB  
Article
Markers of Cellular Proliferation, Apoptosis, Estrogen/Progesterone Receptor Expression and Fibrosis in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids
by Iwona Szydłowska, Marta Grabowska, Jolanta Nawrocka-Rutkowska, Małgorzata Piasecka and Andrzej Starczewski
J. Clin. Med. 2021, 10(4), 562; https://doi.org/10.3390/jcm10040562 - 03 Feb 2021
Cited by 9 | Viewed by 2057
Abstract
There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone [...] Read more.
There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone receptor (PR) immunoexpression, proliferation, apoptosis and tissue fibrosis, and to compare the above parameters in untreated (surgical attention only) and UPA-treated leiomyomas. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction) and (3) no response to treatment (no decrease or increase in fibroid volume). The study observed a significant decrease in the percentage of collagen volume fraction and ER and PR immunoexpression in the good response group, in the percentage of proliferating cell nuclear antigen (PCNA)- and Ki67-positive cells in the groups with good and weak reactions vs. control group; significantly higher apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells) in the good reaction group vs. control group. The results of the study indicate that a good response to UPA, manifested by a volume reduction of myoma, may be associated with a decrease in fibrosis, ER/PR and PCNA and Ki67 immunoexpression and an increase in cell apoptosis within the myoma. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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9 pages, 239 KiB  
Article
Early Pregnancy Outcomes in Fresh Versus Deferred Embryo Transfer Cycles for Endometriosis-Associated Infertility: A Retrospective Cohort Study
by Justin Tan, Maria Cerrillo, Maria Cruz, Gustavo Nardini Cecchino and Juan Antonio Garcia-Velasco
J. Clin. Med. 2021, 10(2), 344; https://doi.org/10.3390/jcm10020344 - 18 Jan 2021
Cited by 8 | Viewed by 2160
Abstract
Given the estrogen-dependence associated with endometriosis, hyper-stimulation associated with assisted reproduction treatment may exacerbate the disease process and adversely affect endometrial receptivity and subsequent implantation. In this way, a freeze-all deferred embryo transfer (ET) approach may benefit patients with endometriosis, although controversy exists [...] Read more.
Given the estrogen-dependence associated with endometriosis, hyper-stimulation associated with assisted reproduction treatment may exacerbate the disease process and adversely affect endometrial receptivity and subsequent implantation. In this way, a freeze-all deferred embryo transfer (ET) approach may benefit patients with endometriosis, although controversy exists regarding the mechanism of endometriosis-associated infertility and benefits of deferred ET on endometrial receptivity. Hence, the purpose of this study was to compare in vitro fertilization (IVF) outcomes in women with endometriosis, diagnosed by histology, undergoing fresh versus deferred-ET after elective cryopreservation. Of the 728 women included, no significant differences were observed in baseline patient characteristics and response to gonadotrophin stimulation between fresh and deferred ET groups. Furthermore, no significant differences in implantation rate (49.7 vs. 49.9%, p = 0.73), clinical pregnancy rate (40.9 vs. 39.9%, p = 0.49), and miscarriage rate (9.4 vs. 9.9%, p = 0.63) were observed between fresh and deferred ET groups, respectively. Hence, contrary to previous studies, our results suggest that a deferred ET “freeze-all” IVF strategy does not improve early pregnancy outcomes among women with endometriosis. However, prospective studies are required to validate these findings and further insight into the etiology and pathogenesis of endometriosis-associated infertility are necessary to optimize IVF protocols in this population. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
10 pages, 1604 KiB  
Article
Affected Ovary Relative Volume: A Novel Sonographic Predictor of Ovarian Reserve in Patients with Unilateral Endometrioma—A Pilot Study
by Stefano Cosma, Andrea Roberto Carosso, Martina Moretto, Fulvio Borella, Domenico Ferraioli, Marialuisa Bovetti, Fiammetta Gervasoni, Claudia Filippini, Alberto Revelli, Simone Ferrero and Chiara Benedetto
J. Clin. Med. 2020, 9(12), 4076; https://doi.org/10.3390/jcm9124076 - 17 Dec 2020
Cited by 2 | Viewed by 1840
Abstract
Background: The assessment of ovarian reserve in the case of endometrioma is of pivotal importance for planning a tailored management. However, both the antral follicle count (AFC) and the antimüllerian hormone (AMH) dosage are subject to a fair degree of variability in ovarian [...] Read more.
Background: The assessment of ovarian reserve in the case of endometrioma is of pivotal importance for planning a tailored management. However, both the antral follicle count (AFC) and the antimüllerian hormone (AMH) dosage are subject to a fair degree of variability in ovarian endometriosis. This study aimed to identify a sonographic parameter of ovarian reserve that could implement current available markers in patients with unilateral endometrioma. Methods: Patients with unilateral endometrioma admitted to our Endometriosis Center between March 2018 and April 2019 were enrolled. Transvaginal ultrasonography for the evaluation of eight sonographic indicators and AMH level determination were performed. The relationship between AMH level and each indicator was assessed. Results: Thirty-four women were included. There was a positive significant correlation between AMH level and the healthy ovary AFC (HO-AFC) (r = 0.36 p = 0.034). A stronger, negative correlation between AMH level and the ratio between the volume of the affected and the healthy ovary (affected ovary relative volume, AORV) (r = −0.47; p = 0.005) was evidenced. AORV had a satisfactory accuracy (AUC 0.73; CI 0.61–0.90; p = 0.0008), and the cut-off value of 5.96 had the best balance of sensitivity/specificity in distinguishing between patients with a good ovarian reserve (AMH ≥ 2 ng/mL) and those at risk of ovarian reserve depletion after excisional surgery. Conclusion: AORV may be a useful tool to assess ovarian reserve in patients with unilateral endometrioma without previous surgery and to guide physicians in clinical management. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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22 pages, 2137 KiB  
Article
CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis
by Monika Abramiuk, Ewelina Grywalska, Izabela Korona-Głowniak, Paulina Niedźwiedzka-Rystwej, Grzegorz Polak, Jan Kotarski and Jacek Roliński
J. Clin. Med. 2020, 9(9), 3035; https://doi.org/10.3390/jcm9093035 - 21 Sep 2020
Cited by 6 | Viewed by 2799
Abstract
The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we [...] Read more.
The causes of endometriosis (EMS) remain unknown; however, a number of immunological abnormalities contribute to the pathogenesis of the disease. The cluster of differentiation-200 (CD200) and its receptor (CD200R) maintain peripheral self-tolerance by negatively regulating immune responses. In this comparative cross-sectional study, we investigated the expression of CD200 and CD200R on T and B lymphocytes and the serum level of soluble CD200 (sCD200) using flow cytometry and ELISA, respectively. Peripheral blood samples were collected from 54 female patients and 20 healthy, age-matched controls. Results were tested for correlation with disease severity and selected clinical parameters. We demonstrated that the differences in sCD200 levels (p = 0.001), the frequencies of CD200-positive T and B lymphocytes (p < 0.001 and p = 0.004, respectively), and the frequencies of CD200R-positive T and B lymphocytes (p < 0.001 for all comparisons) in the study group correlated positively with disease severity. Receiver operating characteristic (ROC) analysis indicated that aberrant expression of CD200/CD200R might serve as a marker to distinguish between EMS cases. Finally, negative co-stimulatory factors may contribute to the induction and persistence of inflammation associated with EMS. It seems that it is essential to determine whether alteration in the CD200/CD200R pathway can be therapeutically targeted in EMS. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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10 pages, 595 KiB  
Article
Laparoscopic Outcomes after Normal Clinical and Ultrasound Findings in Young Women with Chronic Pelvic Pain: A Cross-Sectional Study
by Nicola Tempest, Ekaterina Efstathiou, Zena Petros and Dharani K. Hapangama
J. Clin. Med. 2020, 9(8), 2593; https://doi.org/10.3390/jcm9082593 - 10 Aug 2020
Cited by 9 | Viewed by 3010
Abstract
Chronic pelvic pain (CPP) is one of the most common chronic pain problems experienced by women, with prevalence rates comparable to asthma and back pain. However, it is poorly understood and causative pathology is only seldom found. We aimed to establish prevalence of [...] Read more.
Chronic pelvic pain (CPP) is one of the most common chronic pain problems experienced by women, with prevalence rates comparable to asthma and back pain. However, it is poorly understood and causative pathology is only seldom found. We aimed to establish prevalence of abnormal findings at diagnostic laparoscopy in young women with CPP after normal findings at clinical examination and pelvic ultrasound scan. Information was retrospectively collected on all laparoscopies undertaken on women aged 16–30 years with normal preoperative findings over a 24-month period. One-hundred-and-fifty women (mean age 25 years and BMI 24.5) were included with laparoscopic examination revealing normal anatomy in 110 (73.3%) and pathology in 40 (27.2%). Endometriosis was detected in 30 (20%); 25 (16.7%) stage 1, 2 (1.3%) stage 2, 2 (1.3%) stage 3 and 1 (0.7%) stage 4. Most laparoscopies carried out on young women with CPP and normal clinical examination and pelvic ultrasound scan showed no significant clinical stigmata of pelvic disease. Women should be fully informed of the multifactorial nature of CPP and there should be a comprehensive management pathway for these women, as proceeding with invasive laparoscopy does not provide additional benefit when investigating CPP in the context of risk, cost and effect on long-term wellbeing. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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15 pages, 1972 KiB  
Article
Long-Term Evolution of Quality of Life and Symptoms Following Surgical Treatment for Endometriosis: Different Trajectories for Which Patients?
by Aurélie Comptour, Céline Lambert, Pauline Chauvet, Claire Figuier, Anne-Sophie Gremeau, Michel Canis, Bruno Pereira and Nicolas Bourdel
J. Clin. Med. 2020, 9(8), 2461; https://doi.org/10.3390/jcm9082461 - 31 Jul 2020
Cited by 6 | Viewed by 2727
Abstract
Many studies have shown a global efficacy of laparoscopic surgery for patients with endometriosis in reducing painful symptoms and improving quality of life (QoL) in the short and long-term. The aim of this study was to analyze the different trajectories of long-term evolution [...] Read more.
Many studies have shown a global efficacy of laparoscopic surgery for patients with endometriosis in reducing painful symptoms and improving quality of life (QoL) in the short and long-term. The aim of this study was to analyze the different trajectories of long-term evolution in QoL and symptoms following surgical treatment for endometriosis, and to identify corresponding patient profiles. This prospective and multicenter cohort study concerned 962 patients who underwent laparoscopic treatment for endometriosis. QoL was evaluated using the Short Form (SF)-36 questionnaire and intensity of pain was reported using a visual analog scale prior to surgery and at 6, 12, 18, 24 and 36 months after surgery. Distinctive trajectories of pain and QoL evolution were identified using group-based trajectory modeling, an approach which gathers individuals into meaningful subgroups with statistically similar trajectories. Pelvic symptom trajectories (models of the evolution of dysmenorrhea, dyspareunia and chronic pelvic pain intensity over years) correspond to (1) patients with no pain or pain no longer after surgery, (2) patients with the biggest improvement in pain and (3) patients with continued severe pain after surgery. Our study reveals clear trajectories for the progression of symptoms and QoL after surgery that correspond to clusters of patients. This information may serve to complete information obtained from epidemiological methods currently used in selecting patients eligible for surgery. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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11 pages, 644 KiB  
Article
Recurrence Patterns after Surgery in Patients with Different Endometriosis Subtypes: A Long-Term Hospital-Based Cohort Study
by Konstantinos Nirgianakis, Lijuan Ma, Brett McKinnon and Michael D. Mueller
J. Clin. Med. 2020, 9(2), 496; https://doi.org/10.3390/jcm9020496 - 11 Feb 2020
Cited by 56 | Viewed by 7795
Abstract
Recurrence of endometriosis after surgery constitutes a serious challenge. Whether there is an evolution of lesion subtypes with each recurrence and whether certain lesions subtypes tend to recur faster than others is not adequately addressed. Medical records of all patients who underwent surgery [...] Read more.
Recurrence of endometriosis after surgery constitutes a serious challenge. Whether there is an evolution of lesion subtypes with each recurrence and whether certain lesions subtypes tend to recur faster than others is not adequately addressed. Medical records of all patients who underwent surgery for endometriosis between 1997 and 2018 in the Department of Gynecology and Obstetrics, University of Bern, were reviewed. Inclusion criteria was surgically confirmed endometriosis recurrence, defined as a subsequent surgery for endometriosis after a previous complete surgical excision of endometriosis lesions. Three subtypes of endometriosis were defined: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). Time to recurrence and variation in endometriosis subtype between the first and recurrent surgeries were the primary outcome measures. Out of the 322 patients with recurrent surgery that were identified, for 234 of them, the endometriosis subtype at first surgery was confirmed and classified (SUP = 56, OMA = 124, DIE = 54). No statistically significant difference was found for time to recurrence between lesion subtypes. SUP compared to the other groups had a higher possibility of presenting with SUP at recurrence (Odds Ratio (OR): 3.65, 95% confidence interval (CI): 1.74–7.51) and OMA compared to the other groups had a higher possibility of presenting with OMA at recurrence (OR: 3.72, 95% CI: 2.04–6.74). Nevertheless, a large number of SUP patients subsequently presented with OMA (10/56: 17.9%) or DIE (27/56: 48.2%) lesions at recurrence. Similarly, a large number of OMA patients subsequently presented with DIE (49/124: 39.5%) lesions at recurrence. In conclusion, although SUP and OMA patients compared to the others are more likely to present with the same subtype at recurrence, increasing lesion subtype severity occurs in a substantial proportion of patients. Time to recurrence is independent from the lesion subtype at first surgery. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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12 pages, 773 KiB  
Article
Long-Term Administration of Dienogest for the Treatment of Pain and Intestinal Symptoms in Patients with Rectosigmoid Endometriosis
by Fabio Barra, Carolina Scala, Umberto Leone Roberti Maggiore and Simone Ferrero
J. Clin. Med. 2020, 9(1), 154; https://doi.org/10.3390/jcm9010154 - 06 Jan 2020
Cited by 42 | Viewed by 6583
Abstract
Background: Rectosigmoid endometriosis is a severe form of deep endometriosis, which may be responsible for pain symptoms and a wide range of intestinal complains such as diarrhea, constipation, and abdominal cramping. The primary objective of this study was to evaluate the efficacy of [...] Read more.
Background: Rectosigmoid endometriosis is a severe form of deep endometriosis, which may be responsible for pain symptoms and a wide range of intestinal complains such as diarrhea, constipation, and abdominal cramping. The primary objective of this study was to evaluate the efficacy of long-term therapy with dienogest (DNG), a fourth-generation progestin, for ameliorating quality of life, pain, and intestinal symptoms of patients affected by rectosigmoid endometriosis. Methods: A retrospective analysis of a prospectively collected database was done on patients with endometriotic nodules infiltrating at least the muscular layer of the rectosigmoid wall with an estimated colorectal stenosis <60%. The diagnosis of rectosigmoid endometriosis was based on transvaginal ultrasonography. Patients accepting to participate in the study received continuous oral treatment with DNG at the dose of 2 mg/day. Results: At the end of the first year of treatment, a significant decrease in dysmenorrhea (P < 0.001), chronic pelvic pain (P < 0.001), dyspareunia (P < 0.001), dyschezia (P < 0.001), and in intestinal symptoms (P < 0.001) was observed. A progressive increase of the Endometriosis Health Profile-30 (EHP-30) and Gastrointestinal Quality of Life Index (GIQLI) scores was observed in the first two years of therapy (P < 0.001 and P < 0.001, respectively). Improvements of patients’ symptoms and quality of life were maintained until the end of the study. The regimen was well tolerated, and the frequency and amount of irregular bleeding decreased as treatment progressed. Conclusion: The current study confirms the efficacy of long-term therapy with DNG for treating symptoms caused by rectosigmoid endometriosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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Review

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19 pages, 957 KiB  
Review
What We Know about the Long-Term Risks of Hysterectomy for Benign Indication—A Systematic Review
by Obianuju Sandra Madueke-Laveaux, Amro Elsharoud and Ayman Al-Hendy
J. Clin. Med. 2021, 10(22), 5335; https://doi.org/10.3390/jcm10225335 - 16 Nov 2021
Cited by 12 | Viewed by 5688
Abstract
Hysterectomy is the most common treatment option in women with uterine fibroids, providing definitive relief from the associated burdensome symptoms. As with all surgical interventions, hysterectomy is associated with risk of complications, short-term morbidities, and mortality, all of which have been described previously. [...] Read more.
Hysterectomy is the most common treatment option in women with uterine fibroids, providing definitive relief from the associated burdensome symptoms. As with all surgical interventions, hysterectomy is associated with risk of complications, short-term morbidities, and mortality, all of which have been described previously. However, information on the potential long-term risks of hysterectomy is only recently becoming available. A systematic literature review was performed to identify studies published between 2005 and December 2020 evaluating the long-term impact of hysterectomy on patient outcomes. A total of 29 relevant studies were identified. A review of the articles showed that hysterectomy may increase the risk of cardiovascular events, certain cancers, the need for further surgery, early ovarian failure and menopause, depression, and other outcomes. It is important to acknowledge that the available studies examine possible associations and hypotheses rather than causality, and there is a need to establish higher quality studies to truly evaluate the long-term consequences of hysterectomy. However, it is of value to consider these findings when discussing the benefits and risks of all treatment options with patients with uterine fibroids to allow for preference-based choices to be made in a shared decision-making process. This is key to ensuring that patients receive the treatment that best meets their individual needs. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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20 pages, 725 KiB  
Review
Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?
by Lutz Konrad, Raimund Dietze, Muhammad A. Riaz, Georgios Scheiner-Bobis, Judith Behnke, Fabian Horné, Alena Hoerscher, Christoph Reising and Ivo Meinhold-Heerlein
J. Clin. Med. 2020, 9(6), 1915; https://doi.org/10.3390/jcm9061915 - 18 Jun 2020
Cited by 50 | Viewed by 4231
Abstract
Epithelial–mesenchymal transition (EMT) is an important process of cell remodeling characterized by the gradual loss of the epithelial phenotype and progressive gain of a mesenchymal phenotype. EMT is not an all-or-nothing process, but instead a transition of epithelial to mesenchymal cells with intermediate [...] Read more.
Epithelial–mesenchymal transition (EMT) is an important process of cell remodeling characterized by the gradual loss of the epithelial phenotype and progressive gain of a mesenchymal phenotype. EMT is not an all-or-nothing process, but instead a transition of epithelial to mesenchymal cells with intermediate cell states. Recently, EMT was described in endometriosis, and many EMT-specific pathways like Twist, Snail, Slug, Zinc finger E-box-binding homeobox 1/2 (ZEB1/2), E/N-cadherin, keratins, and claudins are involved. However, as pointed out in this review, a comparison of the eutopic endometrium of women with and without endometriosis yielded only subtle changes of these EMT markers. Furthermore, only very few alterations in cell–cell contacts could be found but without changes in the epithelial phenotype. This suggests only a partial EMT which is not a prerequisite for the detachment of endometrial cells and, thus, not critical for the first step(s) in the pathogenesis of endometriosis. In contrast, the majority of changes in the EMT-related marker expression were found in the ectopic endometrium, especially in the three endometriotic entities, ovarian, peritoneal, and deep infiltrating endometriosis (DIE), compared with the eutopic endometrium. In this review, we examine the most important EMT pathways described in endometriosis and propose that partial EMT might result from the interaction of endometrial implants with their surrounding microenvironment. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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21 pages, 27574 KiB  
Review
Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications
by Christopher J. Hill, Marwa Fakhreldin, Alison Maclean, Lucy Dobson, Lewis Nancarrow, Alice Bradfield, Fiona Choi, Diandra Daley, Nicola Tempest and Dharani K. Hapangama
J. Clin. Med. 2020, 9(6), 1905; https://doi.org/10.3390/jcm9061905 - 18 Jun 2020
Cited by 25 | Viewed by 15708
Abstract
Endometriosis is a common, oestrogen driven chronic condition, where endometrium-like epithelial and stromal cells exist in ectopic sites. At present, no curative treatments are available and the existing evidence for disease progression is conflicting. The pathogenesis is still unknown and evidently complex, as [...] Read more.
Endometriosis is a common, oestrogen driven chronic condition, where endometrium-like epithelial and stromal cells exist in ectopic sites. At present, no curative treatments are available and the existing evidence for disease progression is conflicting. The pathogenesis is still unknown and evidently complex, as mechanisms of initiation may depend on the anatomical distribution of endometriotic lesions. However, amongst the numerous theories and plethora of mechanisms, contributions of the fallopian tubes (FT) to endometriosis are rarely discussed. The FT are implicated in all endometriosis associated symptomatology and clinical consequences; they may contribute to the origin of endometriotic tissue, determine the sites for ectopic lesion establishment and act as conduits for the spread of proinflammatory media. Here, we examine the available evidence for the contribution of the human FT to the origin, pathogenesis and symptoms/clinical consequences of endometriosis. We also examine the broader topic linking endometriosis and the FT epithelium to the genesis of ovarian epithelial cancers. Further studies elucidating the distinct functional and phenotypical characteristics of FT mucosa may allow the development of novel treatment strategies for endometriosis that are potentially curative. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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31 pages, 1899 KiB  
Review
The Evolving Role of Natural Compounds in the Medical Treatment of Uterine Fibroids
by Michał Ciebiera, Mohamed Ali, Lillian Prince, Tia Jackson-Bey, Ihor Atabiekov, Stanisław Zgliczyński and Ayman Al-Hendy
J. Clin. Med. 2020, 9(5), 1479; https://doi.org/10.3390/jcm9051479 - 14 May 2020
Cited by 25 | Viewed by 14228
Abstract
Uterine fibroids (UFs) remain a significant health issue for many women, with a disproportionate impact on women of color, likely due to both genetic and environmental factors. The prevalence of UFs is estimated to be approximately 70% depending on population. UF-derived clinical symptoms [...] Read more.
Uterine fibroids (UFs) remain a significant health issue for many women, with a disproportionate impact on women of color, likely due to both genetic and environmental factors. The prevalence of UFs is estimated to be approximately 70% depending on population. UF-derived clinical symptoms include pelvic pain, excessive uterine bleeding, gastrointestinal and voiding problems, as well as impaired fertility. Nowadays numerous methods of UF treatment are available—from conservative treatment to invasive surgeries. Selecting an appropriate treatment option should be individualized and adjusted to the patient's expectations as much as possible. So far, the mainstay of treatment is surgery, but their negative impact of future fertility is clear. On the other hand, emerging new pharmaceutical options have significant adverse effects like liver function impairment, hot flashes, bone density loss, endometrial changes, and inability to attempt conception during treatment. Several natural compounds are found to help treat UFs and relieve their symptoms. In this review we summarize all the current available data about natural compounds that may be beneficial for patients with UFs, especially those who want to preserve their future fertility or have treatment while actively pursuing conception. Vitamin D, epigallocatechin gallate, berberine, curcumin, and others are being used as alternative UF treatments. Moreover, we propose the concept of using combined therapies of natural compounds on their own or combined with hormonal agents to manage UFs. There is a strong need for more human clinical trials involving these compounds before promoting widespread usage. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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25 pages, 1915 KiB  
Review
Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis
by Anna Zubrzycka, Marek Zubrzycki, Ewelina Perdas and Maria Zubrzycka
J. Clin. Med. 2020, 9(5), 1309; https://doi.org/10.3390/jcm9051309 - 02 May 2020
Cited by 44 | Viewed by 13028
Abstract
Endometriosis is a chronic gynecological disease, affecting up to 10% of reproductive-age women. The exact cause of the disease is unknown; however, it is a heritable condition affected by multiple genetic, epigenetic, and environmental factors. Previous studies reported variations in the epigenetic patterns [...] Read more.
Endometriosis is a chronic gynecological disease, affecting up to 10% of reproductive-age women. The exact cause of the disease is unknown; however, it is a heritable condition affected by multiple genetic, epigenetic, and environmental factors. Previous studies reported variations in the epigenetic patterns of numerous genes known to be involved in the aberrant modulation of cell cycle steroidogenesis, abnormal hormonal, immune and inflammatory status in endometriosis, apoptosis, adhesion, angiogenesis, proliferation, immune and inflammatory processes, response to hypoxia, steroidogenic pathway and hormone signaling are involved in the pathogenesis of endometriosis. Accumulating evidence suggest that various epigenetic aberrations may contribute to the pathogenesis of endometriosis. Among them, DNA methyltransferases, histone deacetylators, and non-coding microRNAs demonstrate differential expression within endometriotic lesions and in the endometrium of patients with endometriosis. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may contribute to the discovery of a useful prognostic biomarker, which could aid in the future earlier detection, timely diagnosis, and initiation of a new approach to the treatment of endometriosis, as well as inform us about the effectiveness of treatment and the stage of the disease. As the etiology of endometriosis is highly complex and still far from being fully elucidated, the presented review focuses on different approaches to identify the genetic and epigenetic links of endometriosis and its pathogenesis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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12 pages, 725 KiB  
Review
The Surgical Benefit of Hysterolaparoscopy in Endometriosis-Related Infertility: A Single Centre Retrospective Study with a Minimum 2-Year Follow-Up
by Atombosoba Adokiye Ekine, István Fülöp, István Tekse, Árpád Rúcz, Sara Jeges, Ágnes Koppán and Miklós Koppán
J. Clin. Med. 2020, 9(2), 507; https://doi.org/10.3390/jcm9020507 - 13 Feb 2020
Cited by 6 | Viewed by 3635
Abstract
Aim: This study examined the fertility performance of women after combined hysterolaparoscopic surgical management of endometriosis. Design: This study is a hospital-based retrospective review. Materials and Methods: Data collected from the records of all patients presented with endometriosis-related infertility using a checklist designed [...] Read more.
Aim: This study examined the fertility performance of women after combined hysterolaparoscopic surgical management of endometriosis. Design: This study is a hospital-based retrospective review. Materials and Methods: Data collected from the records of all patients presented with endometriosis-related infertility using a checklist designed for the purpose. Result: A total of 81.3% (370/455) of women who have had the desire to have children became pregnant during the study period after the surgery. Of those who became pregnant, all three-hundred-forty-seven patients were followed to the end of their pregnancies. A successful live birth occurred in 94.2% (327/347) of individuals, and pregnancy loss occurred in 5.8% (20/347). The mean patient age was 34.1 ± 4.1 years, and the average duration of infertility was 3.4 ± 3.3 years. Pregnancy occurred spontaneously in 39.5% (146/370) of patients, after artificial insemination (AIH) in 3.8% (14/370) of women, and after in vitro fertilization-embryo transfer (IVF-ET) in 56.8% (210/370) of cases. Patients aged ≤ 35 years had a higher chance of conception post-surgery—84% versus 77%, respectively (p = 0.039). Based on the modes of pregnancy, the timely introduction of an assisted reproductive technique (ART) demonstrated a significant effect on fertility performance postsurgery. Comparatively, this effect was 91.3% vs. 74.1% among the ≤35- and >35-year-old age groups, respectively. There was no significant difference in reproductive performance based on stages of endometriosis, nor in the other parameters evaluated. Conclusion: Our data are consistent with previous clinical studies regarding the management options of endometriosis-related infertility. Overall, the combined hysterolaparoscopy treatment is a very effective and reliable procedure, and is even more effective when combined with ART. It enhances women’s wellbeing and quality of life, and significantly improves reproductive performance. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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15 pages, 1307 KiB  
Review
The Pathogenesis of Adenomyosis vis-à-vis Endometriosis
by Sun-Wei Guo
J. Clin. Med. 2020, 9(2), 485; https://doi.org/10.3390/jcm9020485 - 10 Feb 2020
Cited by 85 | Viewed by 11210
Abstract
Adenomyosis is used to be called endometriosis interna, and deep endometriosis is now called adenomyosis externa. Thus, there is a question as to whether adenomyosis is simply endometriosis of the uterus, either from the perspective of pathogenesis or pathophysiology. In this manuscript, a [...] Read more.
Adenomyosis is used to be called endometriosis interna, and deep endometriosis is now called adenomyosis externa. Thus, there is a question as to whether adenomyosis is simply endometriosis of the uterus, either from the perspective of pathogenesis or pathophysiology. In this manuscript, a comprehensive review was performed with a literature search using PubMed for all publications in English, related to adenomyosis and endometriosis, from inception to June 20, 2019. In addition, two prevailing theories, i.e., invagination—based on tissue injury and repair (TIAR) hypothesis—and metaplasia, on adenomyosis pathogenesis, are briefly overviewed and then critically scrutinized. Both theories have apparent limitations, i.e., difficulty in falsification, explaining existing data, and making useful predictions. Based on the current understanding of wound healing, a new hypothesis, called endometrial-myometrial interface disruption (EMID), is proposed to account for adenomyosis resulting from iatrogenic trauma to EMI. The EMID hypothesis not only highlights the more salient feature, i.e., hypoxia, at the wounding site, but also incorporates epithelial mesenchymal transition, recruitment of bone-marrow-derived stem cells, and enhanced survival and dissemination of endometrial cells dispersed and displaced due to iatrogenic procedures. More importantly, the EMID hypothesis predicts that the risk of adenomyosis can be reduced if certain perioperative interventions are performed. Consequently, from a pathogenic standpoint, adenomyosis is not simply endometriosis of the uterus, and, as such, may call for interventional procedures that are somewhat different from those for endometriosis to achieve the best results. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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39 pages, 6024 KiB  
Systematic Review
Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis
by Kjerstine Breintoft, Regitze Pinnerup, Tine Brink Henriksen, Dorte Rytter, Niels Uldbjerg, Axel Forman and Linn Håkonsen Arendt
J. Clin. Med. 2021, 10(4), 667; https://doi.org/10.3390/jcm10040667 - 09 Feb 2021
Cited by 27 | Viewed by 4754
Abstract
Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum [...] Read more.
Background: This systematic review and meta-analysis summarizes the evidence for the association between endometriosis and adverse pregnancy outcome, including gestational hypertension, pre-eclampsia, low birth weight, and small for gestational age, preterm birth, placenta previa, placental abruption, cesarean section, stillbirth, postpartum hemorrhage, spontaneous hemoperitoneum in pregnancy, and spontaneous bowel perforation in pregnancy. Methods: We performed the literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), by searches in PubMed and EMBASE, until 1 November 2020 (PROSPERO ID CRD42020213999). We included peer-reviewed observational cohort studies and case-control studies and scored them according to the Newcastle–Ottawa Scale, to assess the risk of bias and confounding. Results: 39 studies were included. Women with endometriosis had an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth, compared to women without endometriosis. These results remained unchanged in sub-analyses, including studies on spontaneous pregnancies only. Spontaneous hemoperitoneum in pregnancy and bowel perforation seemed to be associated with endometriosis; however, the studies were few and did not meet the inclusion criteria. Conclusions: The literature shows that endometriosis is associated with an increased risk of gestational hypertension, pre-eclampsia, preterm birth, placenta previa, placental abruption, cesarean section, and stillbirth. Full article
(This article belongs to the Special Issue Diagnosis and Management of Endometriosis and Uterine Fibroids)
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