{"paper_id":"cf8bc30e-8463-4b8e-a582-1fa1c836b01d","body_text":"~ 882 ~ \nInternational Journal of Clinical Obstetrics and Gynaecology 2026; 10(3): 882-893 \n \nISSN (P): 2522-6614 \nISSN (E): 2522-6622 \nIndexing: Embase \nImpact Factor (RJIF): 6. 71 \n© Gynaecology Journal \nwww.gynaecologyjournal.com \n2026; 10(3): 882-893 \nReceived: 14-03-2026 \nAccepted: 16-04-2026 \n \nDr. Suresh Chandra Mondal \nAssociate Professor, Department of \nObstetrics and Gynecology , Malda \nMedical College & Hospital, Malda, \nWest Bengal, India \n \nDr. Soham Chowdhury \nAssistant professor, MS(G&O), \nMBBS(HONS), G&O, Malda \nMedical College & Hospital, Malda, \nWest Bengal, India \n \nDr. Pinaki Sarkar  \nMBBS (Cal) MS (G& O), \nResidential Medical Officer, \nBalurghat Nursing Home, \nBalurghat, West Bengal, India \n \nDr. Sangeeta Das \nMS Obstetrics & Gynaecology, \nResidential Medical Officer, \nBalurghat Nursing Home, \nBalurghat, West Bengal, India \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCorresponding Author: \nDr. Suresh Chandra Mondal \nAssociate Professor, Department of \nObstetrics and Gynecology , Malda \nMedical College & Hospital, Malda, \nWest Bengal, India \n \nPathogenesis and treatment of endometriosis: A \nsystemic literature review \n \nSuresh Chandra Mondal, Soham Chowdhury, Pinaki Sarkar and Sangeeta \nDas \n \nDOI: https://www.doi.org/10.33545/gynae.2026.v10.i3l.2359  \n \nAbstract \nEndometriosis is a chronic gynecological disorder characterized by the abnormal growth of endometrial -\nlike tissue outside the uterine cavity, leading to inflammation, pelvic pain, infertility, menstrual \nirregularities, and significant deterioration in the quality of life among affected women . Despite decades of \nclinical investigation, the exact pathogenesis of endometriosis remains incompletely understood due to its \nmultifactorial nature involving hormonal imbalance, immune dysfunction, genetic s usceptibility, \ninflammatory responses, environmental exposure, and altered cellular signaling mechanisms . This \nsystematic literature review critically examines the current understanding of the biological mechanisms \nresponsible for the initiation and progre ssion of endometriosis while simultaneously evaluating \ncontemporary therapeutic approaches used in its management . The review synthesizes evidence from \nrecent clinical studies, experimental investigations, epidemiological analyses, and molecular research t o \nidentify the major pathogenic pathways associated with the disease . Findings from the literature indicate \nthat retrograde menstruation alone cannot fully explain the development of endometriosis, and increasing \nevidence supports the combined role of estr ogen dependency, chronic inflammatory activation, oxidative \nstress, angiogenesis, immune escape mechanisms, and epigenetic alterations in disease progression . The \nreview further highlights the contribution of cytokines, growth factors, and abnormal immune cell activity \nin facilitating ectopic implantation and survival of endometrial tissues . In terms of treatment, the study \nevaluates both medical and surgical management strategies, including hormonal therapy, nonsteroidal anti -\ninflammatory drugs, gonadotrop in-releasing hormone agonists, laparoscopic interventions, fertility -\npreserving approaches, and emerging targeted molecular therapies . The analysis reveals that although \ncurrent treatments provide symptomatic relief and temporary disease suppression, recur rence rates remain \nconsiderably high, and long -term therapeutic outcomes continue to present clinical challenges . \nFurthermore, delays in diagnosis, variability in symptom presentation, and limitations in noninvasive \ndiagnostic techniques significantly affe ct early disease management and patient prognosis . The review \nconcludes that effective management of endometriosis requires an integrated multidisciplinary approach \ncombining early diagnosis, personalized treatment planning, continuous monitoring, and advanced research \ninto molecular-targeted therapies capable of improving long -term reproductive and clinical outcomes . The \nstudy emphasizes the urgent need for further translational research to better understand disease mechanisms \nand develop safer, more effec tive, and patient -centered therapeutic strategies for endometriosis \nmanagement.  \n \nKeywords: Endometriosis, Pathogenesis, Hormonal Therapy, Inflammation, Gynecological Disorders \n \nIntroduction  \nEndometriosis is characterized by the existence of endometrial glands and stroma outside the \nuterine cavity , primarily, but not only , inside the pelvic region . It is a chronic inflammatory \ndisease dependent on estrogen , affecting women during their period of reproduction , and is \nlinked to pelvic pain and infertility  [1]. The incidence of endometriosis is around 5% , especially \nbetween the ages of 25 and 35 . A 0 . 1% yearly incidence of endometriosis has been found \namong women aged 15 to 49 years . The condition appears prevalent among adolescent females \nexperiencing chronic pelvic pain  [2]. Around 10% of women of reproductive age suffer with \nendometriosis, with over one third experiencing infertility , approximately twice  the incidence \nrate among women without the condition  [3]. As many as 50% of infertil e women are diagnosed \nwith endometriosis [4]. It progresses during menstrual cycles and affects many organs , leading to \nlocalized gynecologic lesions and systemic inflammatory conditions  [5]. Lesions can be \ncategorically classified as peritoneal/superficial implants , ovarian endometriotic \ncysts/endometriomas, deep endometriosis, and extra-abdominal localizations. Endometriosis is  \n\n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 883 ~ \nlinked to painful manifestations , including chronic pelvic pain , \ndysmenorrhea, dyspareunia, infertility, reduced sexual function , \nand psychological distress  [6]. Moreover, asymptomatic \nendometriotic lesions can be identified in about fifty percent of \nwomen undergoing infertility treatment  [7]. Due to ongoing \ninflammation and immunological dysregulation , women with \nendometriosis have an elevated risk of cardiovascular disease , \nrheumatoid arthritis , asthma, melanoma, ovarian cancer , and \nbreast cancer [8]. The main aim of the present systematic review \nwas to critically review and evaluate the mechanism behind \nendometriosis and treatments to alleviate the pain and infertility \nin women with endometriosis.  \n \nMaterials and Methods \nPresent systemic literature review was conducted in accordance \nwith the Preferred Reporting Items for Systematic Review and \nMeta-analysis (PRISMA) statement . Studies were identified by \nsearching the google scholar, PubMed databases. In addition, the \nreferences of all selected articles were searched . Studies \npublished in English were considered . Keywords for literature \nsearch for treatment section  used was ((\"therapeutics\" [MeSH \nTerms]. OR \"therapeutics\"  [All Fields ]. OR \"treatments\"  [All \nFields]. OR \"therapy\"  [MeSH Subheading]. OR \"therapy\"  [All \nFields]. OR \"treatment\"  [All Fields ]. OR \"treatment s\"  [All \nFields].) AND (\"endometriosis\"  [MeSH Terms ]. OR \n\"endometriosis\" [All Fields]. OR \"endometrioses\" [All Fields].)) \nand for pathogenesis section was \n(\"etiology\" [MeSH Subheading]. OR \"etiology\" [All Fields]. OR \n\"pathogenesis\" [All Fields ].) AND (\"endometriosis\"  [MeSH \nTerms]. OR \"endometriosis\"  [All Fields ]. OR \"endometrioses\"  \n[All Fields].).  \n \nInclusion/exclusion criteria \nStudies for pathogenesis section were included if involving any \nmechanism for endometriosis related pain or infertility . For \ntreatment section only studies were involved in which  patients \nsuffering from endometriosis, reported outcome were pain relief, \nsymptom relief (dysmenorrhea, dyspareunia), pregnancy rate, \nlive birth rate , conception rate, fecundity rate . Studies which \nwere review paper , case reports , editorials, commentary, \nsystemic review, metanalysis, non-English articles and in which \npatients were suffering from other serious fetal disease like \ncancer, chronic heart disease, HIV were excluded.  \nSearch using the specific keywords generated 39048 records \nwithout duplicates. Potential studies were selected via their title \nand abstract . Of these , 7254 were excluded after reading the \ncontent of the abstracts and titles , and 3 8 met the inclusion \ncriteria and were selected for systemic review . The initial search \nwas performed  by two independent author ……… . , who \nassessed the eligibility criteria independently and in a masked \nmanner. There were no discrepancies between the authors.  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nRecords identified from \ndatabases: \n \nPubMed (n=37079) \nGoogle scholar (n= 5980) \n  \n \nRegisters (n = ) \nRecords removed before \nscreening: \nDuplicate and non-English \nrecords removed (n = 4011) \n \nRecords screened  \n(n = 39048) \n \nRecords excluded review paper, case \nreports, editorials, revies, systemic \nreviews, metanalysis, commentary. \n(n = 31755 ) \nReports assessed for eligibility \nbased on abstract and title \n(n = 7293) \nReports excluded not following \ninclusion criteria  \n \nStudies included in the review \n(n = 38) \n \nIdentification of studies via databases and registers \nIdentification \nScreening \n \nIncluded \n \n \nPathogenesis of endometriosis \nUnderstanding the pathogenesis of endometriosis is crucial . \nNone of the proposed theories have been able to \ncomprehensively explain the natural history of the disease and \nits associated diverse clinical presentations  [4]. Common \nmechanism lies is dysregulated hormonal signaling , enhanced \nproinflammatory microenvironment that has the potential to \ndrive the initiation , maintenance, and progression of the disease  \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 884 ~ \n[4]. Among the existing theories following stand out and could \nexplain the origin and progression of endometriosis.  \n \nRetrograde menstruation theory \nRetrograde menstruation based theory is the most commonly \naccepted a nd washypothesized by Sampson in 1927  [9]. \nFunctional endometrial tissue translocate into the pelvic cavity \nvia the fallopian tubes during menstruation, adheres to peritoneal \nmesothelial cells , proliferates, and ultimately invades pelvic \nstructures. As per Kruitwagen RFPM et al . , refluxed \nendometrial cells may migrate to the right hypochondrium via \nthe clockwise peritoneal fluid flow and are likely to implant \nmore readily on the right diaphragmatic leaf due to entrapment \nby the falciform ligament . The observed prevalence of ri ght-\nsided endometriotic implants in 90% of patients corroborates the \nmenstrual reflux theory  [10]. Early age at menarche , prolonged \nduration and heavy menstrual flow are all well -known \nepidemiological risk factors for developing endometriosis. The \nanatomical prevalence of endometriosis on the right side of both \nhemipelvis and diaphragm further substantiates this theory [11].  \n \nCoelomic metaplasia and mullerian remnants hypotheses \nEndometriotic lesions arise in situ from embryological remains \nor via metaplasia . According to the mullerian remnants theory , \n[12] endometriosis results from the abnormal migration and \ndifferentiation of embryonic cell remnants derived from the \nMullerian ducts during organogenesis . This concept elucidates \nthe occurrence of endometriosis in adolescents prior to or shortly \npost menarche, as well as in fetuses. As Signorile PG et al. have \nobserved the dislocation of primitive endometrial tissue outside \nthe uterine cavity during organogenesis . Such e mbryological \nresearch studies  [13] substantiate the existence of Mullerian \nremains in the cul -de-sac region , uterosacral ligaments , and \nmedial wide ligaments.  \n \nHematogenous and lymphovascular dissemination \nAccording to this hypothesis , endometrial cells ent er to ectopic \nregions after entering the uterine lymphatic or vasculature after \nmenstruation. Sampson JA . et al . observed the presence of \nendometrial tissue in the uterine vasculature  [14] and Mechsner S \net al . detected the emboli in sentinel lymph nodes  [15]. \nEndometriosis-derived cells can migrate and micrometastasize to \nvarious extra-pelvic organs, such as the brain , liver, spleen, and \nlung, in mouse models of surgically induced endometriosis [16].  \n \nStem cell theory: Abnormal stem cell trafficking contributes to \nthe etiology and pathophysiology of endometriosis  [17]. \nSubsequent research has validated the contribution of bone \nmarrow to the endometrium  [18, 19]. Taylor et al . observed \nthatendometrial cells originating from donors were found in \nendometrial biopsy specimens from all bone marrow recipients , \ncomprising 0. 2% to 48% of epithelial cells and 0. 3% to 52% of \nstromal cells . Thus, BMDSCs traverse the circulatory system \nand contribute to the composition of eutopic endometrium. After \ntheir migration to the endometrium , these BMDSCs may \nbecome confined to an endometrial cell lineage [17].  \n \nGenetic etiology:  No definitive inheritance pattern has been \nidentified; nonetheless , familial clusters of endometriosis have \nbeen observed in humans . A recent cross -sectional study by \nBianco et al. involving 213 infertile women with endometriosis  \nwho underwent IVF procedures revealed that single nucleotide \nvariants of FSHB and FSHR independently affected the \nhormonal profile (both FSH and LH levels) and consequently \ninfluenced the number of oocytes collected at any stage of the \ndisease [20].  \n \nTable 1: Different theories for pathogenesis of endometriosis \n \nS. \nNo.  \nTheory for pathogenesis of \nendometriosis Key concept \n1.  Retrograde menstruation theory \nFunctional endometrial tissue translocate into the pelvic cavity via the fallopian tubes during \nmenstruation, adheres to peritoneal mesothelial cells, proliferates, and ultimately invades pelvic \nstructures \n2.  Coelomic metaplasia and mullerian \nremnants hypotheses Endometriotic lesions arise in situ from embryological remains or via metaplasia.  \n3.  Hematogenous and lymphovascular \ndissemination \nEndometrial cells enter to ectopic regions after entering the uterine lymphatic or vasculature after \nmenstruation \n4.  Stem cell theory Abnormal stem cell trafficking contributes to the etiology and pathophysiology of endometriosis. \nBMDSCs traverse the circulatory system and contribute to the composition of eutopic endometrium.  \n5.  Genetic etiology Single nucleotide variants affects the hormonal profile and influence the no of oocyts.  \n \nMechanisms of endometriosis associated infertility: Although \nthere is a clinically established correlation between \nendometriosis and infertility , the mechanisms involved in \nendometriosis-related infertility remain ambiguous , and this \ndisorder is presently considered highly complex.  \n \nRole of pain: When superficial dyspareunia (pain in or around \nthe vaginal introitus) makes intercourse difficult to attain or deep \ndyspareunia makes intercourse difficult to sustain , resulting in \navoidance of sexual activity, pain may be a contributing factor to \ninfertility caused by endometriosis . The disease-related chronic, \nnon-menstrual pelvic pain may affect sexual life by decreasing \narousal, orgasm, frequency of sexual activity , and desire . \nIntimate relationships , emotional health , and overall quality of \nlife will all suffer greatly as a result [4]. One cross-sectional study \nincluding 300 women with histologically  diagnosed \nendometriosis by Kj W et al. demonstrated that the severity of \nsuperficial dyspareunia was correlated with increased chances of \ninfertility issues [21].  \n \nMechanical factors \nAnatomical abnormalities and mechanical factors may interfere \nwith oocyte release from the ovary , obstruct tubal ovum pickup \nor transport , and/or impede sperm transfer into the fallopian \ntube. In an in vivo study including 21 cynomolgus monkeys, The \nimpaired fertility appeared to be mediated primarily by failure of \nfollicular rupture and/or pelvic adhesions [22].  \n \nDeclined Ovarian reserve:  Increasing molecular , histological, \nand morphological data indicates that endometriomas adversely \naffect ovarian function. An endometrioma is a distinctive benign \ncyst lacking a true capsule , resulting in the interchange of cystic \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 885 ~ \ncontents with the neighboring healthy ovarian cortex . The \ndischarge of toxic cyst contents into the surrounding ovarian \nparenchyma may result in oxidative stress , fibrosis, depletion of \ncortical stroma , smooth muscle cell meta plasia, compromised \nvascularization, and, subsequently, diminished follicular \nmaturation and atresia in early follicles  [4]. \nA histopathological investigation showed increased fibrotic \ntissue around endometriomas compared to other benign cysts [23].  \n \nOocyte quality , embryo transport , sperm function and \nmotility, sperm-oocyte interaction \nThe inflammatory effects caused by endometriomas have been \ndemonstrated to influence both egg production and ovulation in \nthe affected ovary  [24]. The functional quality  of sperm is \ndiminished, maybe due to the inflammatory and toxic effects of \nperitoneal fluid and elevated levels of activated macrophages [25]. \nLeyendecker G et al. demonstrated that the transport of gametes \nis i nfluenced by the inflammatory milieu , \nanatomical abnormalities, and uterotubal dysperistalsis linked to \nendometriosis [26].  \n \nEffect on Implantation: Impaired implantation may result from \ndiminished endometrial receptivity or decidualization ability in \nthese patients. The functional dysregulation of steroid hormone \nsignaling in endometriosis, including the increase of E2 -induced \ncell proliferation , inflammation, and progesterone resistance , \nappears to significantly reduce endometrial receptivity in these \nindividuals [27]. Taylor et al. observed that reduced expression of \nimplantation-related genes HOXA10 and HOXA11 has been \nimplicated with compromised endometrial receptivity, leading to \ndecreased implantation rates [28].  \n \nMechanism of Chronic Pelvic Pain in Endometriosis \nMultiple processes may underlie pain in individuals with \nendometriosis; understanding these mechanisms may assist \nhealthcare professionals in elucidating the nature of the pain \nsymptoms and determining appropriate  therapies for \nendometriosis-related pain.  \n \nInflammation: Endometriotic lesions and the peritoneal fluid of \nindividuals with endometriosis exhibit increased levels of \ninflammatory cells , cytokines, and chemokines , culminating in \nan inflammatory environment . Macrophages, mast cells , and \nneutrophils, together with other inflammatory cells , are \nactivated, resulting in increased production of various \ninflammatory mediators, including interleukins (IL) such as IL -\n1β, IL-37, and IL -6; tumor necrosis factor (TNF) -α; nerve \ngrowth factor (NGF); and pain -associated molecules like \nprostaglandin, substance P , and glycodelin . Cytokines, \nchemokines, and inflammatory mediators linked with \ninflammation can affect inflammatory cells , increasing their \nrecruitment [29]. This detrimental cycle may accelerate the \nproliferation and invasion of endometriotic lesions, resulting in a \nchronic inflammatory microenvironment and thus , chronic \npelvic pain  [29]. Tamburro S et al . found that the severity of \ndysmenorrhea is also  correlated with elevated levels of TGF -β1 \n[30]. Mast cells participate in neuropathic pain by directly \nsensitizing or activating primary nociceptive neurons through \nmediators like histamine and leukotriene . The number of mast \ncells and activated mast cells is elevated in endometriosis , \nparticularly in cases of deep-infiltrating endometriosis [31].  \n \nNerve fibres in endometriotic  lesions: The abnormal \ninnervation of endometriotic lesions is considered  crucial in the \netiology of chronic pelvic pain in patients with endometriosis  \n[32]. Mechsner et al and Arnold J et al reported that the number \nof nerve fibers , including Aγ  sensory, C sensory , cholinergic, \nand adrenergic types , is found to be  elevated in peritoneal \nendometrial tissue relative to healthy peritoneum  [33, 34]. \nMcKinnon B et al . revealed that peritoneal fluid from \nindividuals with endometriosis enhanced the emergence of \nsensory neurites from the dorsal root ganglia  [34]. Women with \nendometriosis exhibiting elevated pain scores for dysmenorrhea \nand pelvic pain had substantially increased levels of neuronal \nmarkers (neurofilament and protein gene product) , and severe \ndysmenorrhea had a positive association with nerve fibers \nrelating to endometriosis  [34, 35]. Kajitani et al . observed that \nelevated NGFs in endometriosis patients correlated with a higher \ndensity of nerve supply , which was associated with intense pain  \n[36].  \n \nEndometriosis and Peripheral Sensitization:  Peripheral \nsensitization is a process that elucidates the continued pain in the \nabsence of lesions [37]. Anaf et al. have found perineural invasion \nin individuals with endometriosis [38].  \n \nEndometriosis and Central Sensitization: Central sensitization \nmay also arise from changes in cerebral activity or structure . \nChanges in brain activity in women with chronic pain have been \nexamined using functional magnetic resonance imaging and \npositron emission tomography . Women with dysmenorrhea \nexhibited higher  sensitivity to painful thermal stimuli in \ncomparison to women without dysmenorrhea  [38, 39]. As-Sanie S \net al . demonstrated that Women experiencing endometriosis -\nrelated pain had enhanced  resting connectivity between the \nanterior insula , the principal region for pain processing , and \nother brain areas, in contrast to healthy controls or endometriosis \npatients devoid of pain . Women suf fering from painful \nendometriosis had elevated levels of excitatory neurotransmitters \nin the anterior insula in comparison to the other two control \ngroups. Elevations in neurotransmitters correlated with a link \nbetween the anterior insula and the medial pr efrontal cortex, a \nregion involved in pain modulation  [40]. An central sensitization \nassessment tool  indicated that over 40% of patients with \nendometriosis had central sensitization [41].  \n \nCross Sensitization:  Cross-organ sensitization refers to the \nphenomenon when pain in one visceral organ stimula tes the \nsensitivity to pain in another organ  [42]. Women with \nendometriosis experience a co -occurrence of bladder pain \nsyndrome, characterized by bladder pain accompanied by urine \nsymptoms such as urgency  and frequency  [43]. The precise \nprocess of cross -sensitization remains unidentified . Visceral \nafferents from the uterus, bladder, and colon converge at a same \nplace in the spinal cord , therefore sensitizing neighboring cells \ndue to their spatial proximity [44, 45].  \nDichotomizing afferents , which are individual peripheral \nneuronal cell bodies capable of producing several axons to \nsimultaneously innervate various abdominal organs , are \nproposed as a mechanism for cross -sensitization [46, 47]. Phan et \nal. observed that women suffering from endometriosis -related \nchronic pelvic pain frequently exhibit myofascial dysfunction \nand sensitization expanding beyond the pelvic area , potentially \ntriggered or sustained by chronic pelvic floor spasms [48].  \n \nPsychosocial Factors: The severity of pain can be influenced by \npsychological factor s like depression , anxiety, pain \ncatastrophizing, pain expectation , and focus on pain  [49, 50]. \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 886 ~ \nAlthough the actual mechanism connecting psychological \nvariables to endometriosis -related chronic pain remains \nunidentified, Furthermore, van Aken MAW et al . found that \nwomen with endometriosis had markedly elevated pain \ncatastrophizing scores [51].  \n \nTable 2: Mechanism behind pathogenesis of endometriosis \n \nMechanisms of endometriosis associated infertility \nS. No.  Mechanism  Key concept \n 1.   Role of pain Pain in or around the vaginal introitus during intercourse, non-menstrual pelvic pain may \naffect sexual life thus may be a contributing factor to infertility.  \n2.  Mechanical factors \nAnatomical abnormalities and mechanical factors may interfere with oocyte release from \nthe ovary, obstruct tubal ovum pickup or transport, and/or impede sperm transfer into the \nfallopian tube.   \n3.  Declined Ovarian reserve \nThe discharge of endometriomas contents into the surrounding ovarian parenchyma may \nresult in oxidative stress, fibrosis, depletion of cortical stroma, smooth muscle cell \nmetaplasia, compromised vascularization, and, subsequently, diminished follicular \nmaturation and atresia in early follicles.  \n4.  Oocyte quality, embryo transport, sperm \nfunction and motility, sperm-oocyte interaction \nThe inflammatory effects caused by endometriomas have been demonstrated to influence \negg production and ovulation, quality of sperm.   \n5.  Effect on Implantation Due to diminished endometrial receptivity or decidualization Impaired implantation may \nresult in infertility issues.  \nMechanism of Chronic Pelvic Pain in Endometriosis \nS. No.  Mechanism  Key concept \n1.  Inflammation \nEndometriotic lesions and the peritoneal fluid of individuals with endometriosis exhibit \nincreased concentrations of inflammatory cells, cytokines, and chemokines, establishing \nchronic inflammatory milieu that promotes lesion progression and chronic pelvic pain.  \n 2.  Nerve fibres in endometriotic lesions The abnormal innervation of endometriotic lesions is considered crucial in the etiology of \nchronic pelvic pain in patients with endometriosis.  \n 3.  Endometriosis and Peripheral sensitization Perineural invasion elucidates the continued pain in endometriosis.  \n 4.  Endometriosis and Central Sensitization Central sensitization may also arise from changes in cerebral activity or structure. Changes \nin brain activity in women with chronic pain,  \n 5.  Cross Sensitization  Sensitization expanding beyond the pelvic area in women suffering from endometriosis-\nrelated chronic pelvic pain,  \n6.  Psychosocial Factors The severity of pain can be influenced by psychological factors like depression, anxiety, \npain catastrophizing, pain expectation, and focus on pain.  \n \nDiagnosis \nDiagnosing endometriosis necessitates a comprehensive set of \ntools encompassing clinical evaluation , biological indicators , \nand techniques for imaging , including non-invasive procedures \nlike ultrasonography and invasive methods for visual inspection . \nAssessing symptomatology and conducting a physical \nexamination are the initial steps in diagnosing endometriosis  [52, \n53]. A physical examination suggests a diagnosis of \nendometriosis when multiple criteria are fulfilled , including \npalpable nodularity and atypical pelvic anatomy , particularly in \nthe vagina, rectovaginal space, pouch of Douglas , rectosigmoid \nregion, and posterior wall of the urinary bladder  [52-54]. \nAdditional signs, including tenderness, reduced mobility, and a \nretroverted uterus , as observed during palpation , may also \nsuggest the presence of endometriosis  [55]. Various potential \nbiomarkers including inflammatory cytokines  [56]. , growth \nfactors [57]. , angiogenesis markers [58]. , stem cell markers  [58]. as \nwell as tissue matrix metalloproteinases and adhesion molecules \nhave been investigated for laboratory testing  [59]. butnone have \ndemonstrated sufficient reliability as diagnostic tools.  \nUltrasonography is a cost -effective, readily accessible, and non-\ninvasive imaging technique for evaluating endometriosis , \nemploying transabdominal, transvaginal, or transrectal methods. \nIt is commonly employed as an initial screening test for \nendometriosis and as a preoperative tool for assessing the extent \nof surgical procedures  [60]. At present , transvaginal \nultrasonography is preferred technique for detecting ovarian \nendometriomas, with good sensitivity (93%) and specificity \n(97%) when performed by an experienced practiti oner [61]. \nMagnetic resonance imaging (MRI) is increasingly employed for \nassessing patients with e ndometriosis, serving as a \nsupplementary technique to transvaginal ultrasonography , \nespecially when the physician suspects the existence of deep \ninfiltrative lesions  [62]. Surgical exploration is an invasive \nvisualization method employed specifically to get qualitative \nevaluation data regarding the actual extent of endometriotic \nlesions. Despite the array of imaging techniques , laparoscopic \nexamination coupled with histological examination remains the \nabsolute standard for the confirming diagnosis of endometriosis  \n[63].  \n \nTreatment of endometriosis: The selection of treatment will be \nbased upon the severity of symptoms, the degree and location of \nthe disease , the desire for p regnancy, and the patient's age . It \nmay involve pharmacological treatment, surgical intervention, or \na combination of both approaches . Pharmacological treatment \nfor endometriosis seeks to alleviate symptoms or avert \nrecurrence of postsurgical disease [64].  \n \nManagement of endometriosis associated pain \nConsidering the substantial number of inappropriately treated \npatients, multi modal treatment is the need of the hour and  it is \nimperative for gynecologists in private practice to familiarize \nthemselves with multimodal therapy principles , as they serve as \nthe primary point of contact for their patients [65].  \n  \nPharmacologic management of endometriosis associated \npain: Main objective of pharmacological treatment for \nendometriosis is to alleviate symptoms or avert recurrence of \npostsurgical disease. Certain pharmaceuticals induce conditions \nlike hyperprogestogenic treatment, which includes combination \noral contraceptives and progestins . These medications are the \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 887 ~ \nprimary option; they function by suppressing ovulation, inducing \ndecidualization, and leading to a reduction in lesion size . \nHypoestrogenic therapy , utilizing Gonadotropin -Releasing \nHormone (GnRH) agonists , constitutes the secondary \ntherapeutic option for this condition . It is an efficacious \nmedication for women who are unresponsive to combination \noral contraceptives or progestins . They are  not provided orally \ndue to degradation during digestion; thus , their administration is \nadvised via parenteral, subcutaneous, intramuscular, nasal spray, \nor intravaginal routes [64].  \nMuzii et al. found that the use of dienogest in medical treatment \nmarkedly decreases the diameter of endometriom as and \nalleviates associated pain , while maintaining ovarian reserve , \nevidenced by a notable enhancement in antral follicle count \n(AFC) and no significant alteration in anti -Müllerian hormone \n(AMH) levels  [66]. When the effects of dienogest and \nNorethindrone acetate in symptomatic women with ovarian \nendometriomas were compared  by et al . then a reduction in \novarian endometrioma size was observed during treatment in \nboth groups , with no significant differences between groups \ndienogest and Norethindrone acetate . Even Progestin treatment \nutilizing dienogest and Norethindrone acetate demonstrates \nefficacy alleviating associated symptoms , with dienogest \nexhibiting superior symptom ( dysmenorrhea, dyspareunia, \nchronic pelvic pain)  relief and enhanced tolerability among \nwomen [67]. Another multi centric case control study by Angioni \nS et al . also demonstrated a significant decrease in the pain \nwhile treating the ovarian endometriomas patients with \ndienogest [68]. As per Bergqvist et al. two months of triptorelin \ntreatment has been found to be efficacious in reducing the pain \nsymptoms in laparoscopically verified endometriosis patients . \nThe reduction of endometriotic l esions was 50% with triptorelin \ntherapy, a much greater degree than that observed with placebo  \n[69].  \nBy blocking the release of GnRH and the peak of luteinizing \nhormone (LH), hyperandrogenic therapy (danazol or gestrinone) \ncreates a pseudomenopause by raising levels of androgen \nhormones (free testosterone) and lowering levels of estrogen \n(inhibits ovarian production) , which results in endometriotic \nimplant atrophy  [64]. This group of drugs is unsuitable for \nextended use mostly owing to androgenic effects , including \nseborrhea, hypertrichosis, weight gain, adverse effects on serum \nlipoprotein cholesterol distribution , decreased HDL levels , and \nincreased LDL levels [64].  \n \nNon-drug management of endometriosis associated pain: \nConsidering side effects associated with pharmacological \ntreatments, such as menopausal disorders , other non -drug \ntherapies may serve as complement or alternatives for medical \ntreatment of endometriosis patients . Acupuncture's ability to \nreduce pain has bee n linked to a few  physiological and \npsychological mechanisms [70]. Sousa et al observed a decrease \nin visual analogue scale (VAS) scores for chronic pelvic pain \nand dyspareunia  in the endometriosis patients who received \nacupuncture therapy than placebo. Two months post-therapy, the \nfindings were sustained only in the experimental group . In the \nview of  quality of life , they observed an improvement in all \nevaluated measures , however statistical significance was \nachieved just in the experimental group [71].  \nPhysical activity and exercises also have been utilized over three \ndecades ago for the treatment of symptoms related with \nendometriosis [72]. A primary mechanism via which physical \nactivity confers beneficial health effects is its ability to diminish \nchronic low -grade inflammation  [73]. The amount of IL -6 \nreleased is dependent upon the mass of muscle recruited , the \nintensity and duration of the exercise and is related (inversely) to \nthe glycogen status of the muscles  [73]. Goncalves et al . \ndemonstrated that in women with endometriosis, yoga practice is \nfound to improve their quality of life and a decrease in their \nlevels of chronic pelvic pain  [74]. Nutritional intervention also \nfound to be effective in pain management in endometriosis \npatients. Marziali M et al . found that painful symptoms of \nendometriosis were decreased after 12 months of gluten free diet \nwhen provided during severe painful endometriosis [75].  \n \nTreatment of endometriosis associated infertility : In women \nwith endometriosis, infertility mostly results from chronic pelvic \ninflammation. Adhesions resulting from this inflammatory \nprocess may impair pelvic anatomy , and local detrimental \nenvironment to conception  can be established by inflammatory \nmolecules [76].  \nCurrent treatment of endometriosis -associated infertility focuses \non improving fecundity by rem oving or reducing ectopic \nendometrial implants and restoring normal pelvic anatomy [77].  \n \nPharmacological treatment endometrio sis associated \ninfertility: Pharmacological treatments for endometriosis \nencompass hormonal agents such as combination  oral \ncontraceptives, progestins, danazol, and gonadotropin -releasing \nhormone agonists or antagonists (GnRH analogs) . Hormonal \nmedical therapy does not improve  infertility in women with \nendometriosis. No advantages have been demonstrated in the \nmanagement of infertility related with endometriosis. Shaw et al \nreported that goserelin depot and danazol treatment for \nendometriosis have shown no statistically significant difference \nbetween the groups in terms of percentage of pregnancies nor \nmean time to concept ion. Shaw 1992 Medical treatment should \ngenerally be avoided in individuals with endometriosis and \nsubfertility seeking a live birth . The one exception to this \nregulation is to individuals undergoing in -vitro fertilization \n(IVF) [77]. Research indicates that extended administration of \nGnRH agonists prior to IVF or ICSI may enhance pregnancy \noutcomes in women with severe endometriosis . Guo et al  \nreported that upon treatment with GnRH agonists combined with \ntransvaginal ultrasound-guided cyst aspiration serum E2 levels , \nthe quantity of ovarian follicles measuring 14 mm or more , the \nnumber of retrieved oocytes , the rate of high -quality embr yos, \nthe implantation rate , and the clinical pregnancy rate were \nsignificantly elevated in the experimental group compared to the \ncontrol group (all P < 0 . 05) [78, 79]. Like GnRHa, the use of oral \ncontraceptives has demonstrated enhanced results when \nadministered for 6 -8 weeks prior to ART . A randomize d \ncontrolled study conducted by de Ziegler et al. demonstrated that \ncontinuous use of oral contraceptive (OC) for 6 to 8 weeks \nbefore to assisted reproduction therapy (ART) have shown \nsimilar ART results to those of age -matched individuals without \nendometriosis [80].  \n \nSurgery: The surgical therapy options for endometriosis -\nassociated infertility include laparotomy , laparoscopy, and \nrobotic surgery . Laparoscopic intervention  is predominantly \nemployed owing to its benefits , such as reduced costs , \nhospitalization and faster  recovery [81]. Marcoux et al . findings \nindicated that resection or ablation of minimal and mild \nendometriosis markedly improved fecundity in infertile women \ncompared to diagnostic laparoscopy alone (cumulative \nprobability, 30. 7% and 17 . 7%, respectively; P=0 . 006). The \nfecundity rates were 4 . 7 and 2 . 4 per 100 person months , \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 888 ~ \nrespectively, and the absolute increase in the 36 -week chance of \na pregnancy extending beyond 20 weeks due to surgery was 13 \npercent. No substantial difference was seen between excisional \nand ablative procedures  [82]. Laparoscopic cystectomy of \nendometriomas emerged as a better choice than fenestration and \ncoagulation because the former  has been associated reduced \nrecurrence of signs and symptoms , a decreased incidence of \nreoperation, and an elevated cumulative pregnancy rate \ncompared to the latter  [83, 84]. When comparison between \ncystectomy (group 1) and fenestration and coagulation (group 2) \nfor the management of endometriomas was made by Alborzi et \nal. then it was found after two years , the recurrence of \nsymptoms, including pelvic pain and dysmenorrhea, was 15. 8% \nin group 1 and 56 . 7% in group 2 . The reoperation rates were 5 . \n8% in group 1 and 22 . 9% in group 2 , with these differences \nbeing statistically significant . The cumulative pregnancy rate \nduring the 1 -year follow -up was mu ch greater in group 1 (59 . \n4%) compared to group 2 (23 . 3%) [83]. Similar results were also \nreported by Beretta et al in their study [84].  \n \nSuperovulation and Intraut erine Insemination:  Numerous \nrandomized controlled trials have demonstrated that ovulation \ninduction and superovulation, both with and without intrauterine \ninsemination (IUI) , enhance conception rates in people with \nnormal anatomy and with minimal-mild endometriosis [85, 86]. As \nper Tummon et al study, superovulation and IUI was associated \nwith superior live birth rate (14%) than no treatment (2%) in \nwomen with minimal or mild endometriosis  [85]. A similar trial  \nby Deaton et al indicated an advantage of clomiphene citrate and \nIUI over controls (fecundity 0. 095 vs. 0. 033) [87]. It is crucial to \nnote that ovarian stimulation may worsen endometriosis; thus , it \nshould be conducted in a regulated way and restricted to 3 -4 \ncycles [77].  \n \nIn vitro  Fertilization: Nowadays, IVF is the most effective \ntreatment for infertile women suffering from endometriosis [88]. \nDespite its widespread application , the impact of endometriosis \non conception rates following ART and the efficacy of ART \ntherapies in women with endometriosis remain contentious \nconcerns. As per Geber et al study patients with endometrioma \nundergoing IVF exhibited improved pregnancy outcome . The \nexistence and severity of endometriosis do not affect IVF \noutcomes, and no evidence was found indicating a higher \nfrequency of miscarriage [89].  \n \nTable 3: Treatment of endometriosis \n \nS. \nNo.  \nStudy  \ndesign Study population Treatment/ \nDosage \nOutcomes and \n results Author, year \n1.  Prospective study 32 patients with unilateral \nendometrioma  \nMedical treatment with dienogest significantly reduces \nendometrioma diameter (40%) reduction and \nimprovement in Mean visual analog scale \nscoreassociated with pain ((0. 9 ± 1. 0, p < . 0001).  \nMuzii et al. \n2019 \n2.  Retrospective study \n135 symptomatic women \nwith ultrasonographic \ndiagnosis of ovarian \nendometrioma.  \nDinogest 2 mg/day \nand Norethindrone \nacetate 2. 5 mg/day \nThe mean diameter of endometriomas was reduced by \nboth Dinogest (D)-2. 51 mm at 6 months and -6. 54 \nmm at 12 months and Norethindrone acetate(N)-2. 94 \nmm at 6 months and -5. 80 mm at 12 months. A \nmarked decrease in pain was significantly higher in \ngroup D than in group N just after 6 months (chronic \npelvic pain P = 0. 002, dysmenorrhea P = 0. 001, \ndyspareunia P < 0. 001).  \nSimona Del \nForno et al. \n2019 \n3.  Prospectivemulticentric \ncase control study \n81 patients with ovarian \nendometriosis \n2 mg of dienogest \nand cyclic oral \nestro-progestins \n(ethinyl estradiol \n30 mcg [EE]. plus \ndienogest 2 mg) \nDinogestcause a 75% volume reductionthe size of the \nendometrioma cysts. significant improvement in the \nmean visual analog scale score(19 ± 15, p < . 001, \nDinogest).  \nAngioni Set al. \n2019 \n4.  Prospective, \nrandomized study \n49 women with symptoms \nof laparoscopically \nverified endometriosis. 24 \npatients had active \ntreatment and 25 received \nplacebo.  \n3. 75 mg of \ntriptorelin \n.  \nThe total pain score was significantly reduced in the \ntriptorelin group. The mean difference of pain score \nbetween the baseline and 6 months of triptorelin \ntreatment was 2. 85 (95%, CI 2. 23. 5). The average \narea of endometriotic lesions was reduced 45%.  \nBergqvist A et \nal. 1998 \n5.  Prospective \nrandomized trial \n42 women who were on \nthe waiting list to undergo \na video laparoscopy \nExperimental \ntreatment of \nacupuncture, and \nthe other received \nplacebo therapy, \nfor which the \nneedles were \ninserted 3 cm apart \nfrom the points of \nenergy.  \nAcupuncture reduced Chronic Pelvic Pain by 66% after \ntherapy and Dyspareunia was reduced by 65%. \nAcupuncture confers beneficial and long-lasting \neffects, even 2 months after therapy.  \nSousa et al. \n2016 \n6.  Randomized controlled \ntrial \n40 women were who \npracticed yoga (n = 28), or \nwho did not practice yoga \n(n = 12) \n90min scheduled \nyoga sessions \ntwice a week for 8 \nweeks.  \nThe degree of daily pain was significantly lower \namong the women who practiced yoga compared with \nthe non-yoga group (p = 0. 0007). Mean(SD) baseline \npain score were 60. 80 (15. 59), 58. 71 (15. 41) for \nyoga group andnon yoga group. Post therapymean pain \nscore 32. 39 (21. 95) 55. 05 (21. 49) foryoga group and \nnon-yoga group \nGoncalves et al. \n2016 \n7.  Retrospective study  Two hundred seven gluten-free diet in  After 12 months of gluten diet, 75%reported Marziali M et \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 889 ~ \npatients with severe \npainful endometriosis-\nrelated symptoms \na follow-up of 12 \nmonths  \nstatistically significant change in painful \nsymptoms(P<0. 005).  \nal. 2012 \n8. .  Randomized \ncomparative trial.  \n307 patients with \nlaparoscopically \ndiagnosed endometriosis \n3. 6-mg depot of \ngoserelin monthly \nsubcutaneously or \noral danazol200 \nmg three times a \nday administered \nfor 24 weeks.  \nNo statistically significant difference between the \ngroups in terms of percentage of pregnancies nor mean \ntime to conception. Ofthe 47 pregnant patients who had \nreceived goserelin, 34 (72. 3%) had live births; ofthe \n18 danazol-treated patients, 14 (77. 8%) had live births.  \nShaw et al 1992 \n9.  Retrospective \ncomparative study \n134 patients with ovarian \nendometriosis \nDiphereline, 3. 75 \nmg/ampoule and \ncontrol \nIn infertile patients with ovarian endometriosis GnRH-\na combined with transvaginal ultrasound-guided cyst \naspirationcan obtain better clinical pregnancy rate47. \n76% than control group 39. 21% (p= 0. 031)It also \nreduced abortion rate to 6. 25% than 22. 50%in control \ngroup(p= 0. 049.) \nGuo et al. 2012 \n10.  Pilot clinical study \n795 Women with \nendometriosis or without \nendometriosis \n0. 03 mg of ethinyl \nestradiol (EE) \n0. 125 mg of \nlevonorgestrel \n \n6 to 8 weeks of continuous use of oral contraception \n(OC) before assisted reproduction treatment (ART) \nmaintains ART outcomes comparable with the \noutcomes of age-matched controls without \nendometriosis. Clinical pregnancy rate in control \n(without endometriosis) was 35% and after treating \nwith OC in endometrioma patients it was 41. 4%.  \nZiegler, et al. \n2010 \n11.  \nRandomized, \ncontrolled prospective \nstudy \n341 infertile women 20 to \n39 years of age with \nminimal or mild \nendometriosis.  \nlaparoscopic \nsurgery \nLaparoscopic resection or ablation of minimal and mild \nendometriosis enhancespregnancy rate by 20%. Rates \nof fecundity were 2. 3 per 100 person-months, P=0. \n006 \nMarcoux \n S, et al. 1997 \n12.  A prospective, \nrandomized study \n100 patients with \nendometriomas who had \neither infertility or pelvic \npain.  \nlaparoscopic \novarian cystectomy \nversus fenestration \nand coagulation \nLaparoscopic cystectomy of endometriomas is a better \nchoice than fenestration and coagulation because the \nformer technique leads a higher cumulative pregnancy \nrate (59. 4%) than the latter(23. 3%).  \n \nAlborzi et al. \n2004 \n13.  \nProspective, \nrandomized clinical \ntrial.  \nSixty-four patients with \nadvanced stages of \nendometriosis.  \nCystectomy versus \ndrainage and \ncoagulation \nThe median interval between the operation and the \nrecurrence of moderate to severe pelvic pain was \nlonger in cystectomy than in diagnostic laparoscopy \n(19 months versus 9. 5 months). The 24-month \ncumulative pregnancy rate was higher in cystectomy \ngroup than in diagnostic laparoscopy(66. 7% versus \n23. 5%).  \nBeretta et al. \n1998 \n14.  Prospective \nRandomized trial.  \n103 couples in whom \nminimal or mild \nendometriosis \nOvarian \nstimulation and \nIUI using ≥75 IU \nFSH \nTreatment with superovulation and lUI was associated \nwith superior outcome both by crude live-birth rates \n(11% in treatment group vs 2%inno-treatmentgroup.  \nTummon et al. \n1997 \n15.  Randomized, \nprospective trial  \n298 couple with \n1unexplained fertility or \nsurgically corrected \nendometriosis.  \nCC 50 mg oral and \nIUI \nClomiphene citrate (CC) and intrauterine insemination \n(lUI) results in increased fecundity (0. 095 vs 0. \n033)when compared with periovulatory intercourse in \ncouples with either unexplained infertility or surgically \ncorrected endometriosis.  \nDeaton, M. \n1990 \n16.  Prospective study \n140 patients with \nendometriosis undergoing \nIVF treatment \nIVF \nOur findings demonstrate that the presence and \nseverity of endometriosis do not influence IVF \noutcomes. The pregnancy rates per transfer were \ncomparable among the groups: 39% for male factor \ninfertility, 48% for unexplained infertility, 45% for \ntubal factor infertility, and 40% for endometriosis \npatients.  \nGeber at al 1995 \n \nEmerging therapies:  The predominant medical therapies for \nendometriosis are suppressive rather than curative , with \nsymptoms reappearing  upon withdrawal of medication; hence , \nthere is a need for  innovative advancements in this field . \nElagolix, an oral anti -gonadotrophic drug , is a unique and \npromising therapy approach for endometriosis , appearing to \nprevent disease progression and greatly alleviate pain  [6]. \nResveratrol is a natural molecule with anti -angiogenic, anti-\ncarcinogenic, pro-apoptotic, anti-oxidative, and anti -\ninflammatory properties , potentially offering new therapeutic \navenues for endome triosis therapy  [90]. Research indicates that \nantioxidants, including melatonin , vitamins E and C , may be \nbeneficial to existing endometriosis treatments  [91]. Furthermore, \nstem cell-based therapy have also demonstrated it’s potential for \nthe management of endometriosis . Stem cell treatment for \nendometriosis entails the administration of stem cells to areas \nimpacted by the condition , aiming to substitute a dysfunctional \nor nonviable endometrial cell population with its normal or \nrestorative counterparts [92]. Stem cell treatment is a compelling \ntherapeutic option for endometriosis due to its \nimmunomodulatory and tropic effects on inflammatory lesion \nsites. Stem cell treatment is a potential alternative for the \nregeneration of damaged endometrial tissue . This therapy has \ngenerated discussion over the role of stem cells in the disease's \netiology [93]. Mesenchymal ste m cell therapy have shown \npromising results and utilized in the treatment of infertility for \n\nInternational Journal of Clinical Obstetrics and Gynaecology https://www.gynaecologyjournal.com \n~ 890 ~ \nwomen with premature ovarian failure and Asherman’s \nsyndrome [94]. Preclinical studies indicate that angiogenesis in \nendometriotic lesions can be suppressed by inhibiting the \nrecruitment of endothelial pr ogenitor cells (EPCs) to these \nlesions. Adipose derived cells caused s significant reduction in \nsize and proliferative activity of endometriotic lesions and \nimproved pregnancy outcomes [95].  \n \nConclusion \nEndometriosis is a chronic condition that significantly affects \nwomen's lives and necessitates a lifelong care strategy . The \nexplanations behind endometriosis -related infertility remain \nincompletely elucidated , and this disease is multifaceted in \nnature. Pain and inflammation associated with endometriosis , \naltered pelvic architecture and adhesions , impaired ovarian \nfunction, and decreased endometrial receptivity significantly \ncontribute to infertility in women with endometriosis.  \nIdentifying innovative , non-invasive diagnostic tools for \nendometriosis that also predict an increased risk of infertility is a \nprimary research and clinical priority; delayed diagnosis \nfacilitates disease progression , which is detrimental to fertility . \nTreatment options for endometriosis -related pain should be \nselected based on efficacy , potential adverse effects , \nacceptability, adherence, cost, and patient preferences . The \npredominant medicinal treatments for endometrio sis are \nsuppressive rather than curative , with symptoms recurring upon \nwithdrawal of medication; hence , there is an obligation for \ninnovative advancements in this field. Surgery and ART remain \nthe mainstay of effective therapy of infertility associated with \nendometriosis. There is need of a multidisciplinary , tailored, \ncollaborative, and comprehensive strategy based on the patient's \nparticular characteristics, endometriosis subtype, and degree of \nimpairment.  \n \nConflict of Interest \nNot available.  \n \nFinancial Support  \nNot available.  \n \nReferences \n1. Giudice LC. Clinical practice. Endometr iosis. N Engl J \nMed. 2010 Jun 24;362(25):2389-98.  \n2. 2.  Vercellini P , Viganò P , Somigliana E , Fedele L. \nEndometriosis: pathogenesis and treatment. Nat Rev \nEndocrinol. 2014 May;10(5):261-75.  \n3. 3.  Macer ML, Taylor HS. Endometriosis and Infertility: A \nreview of the pathogenesis and treatment of endometriosis -\nassociated infertility. Obstet Gynecol Clin North Am. 2012 \nDec;39(4):535-49.  \n4. 4.  Bonavina G , Taylor HS. 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International Journal of \nClinical Obstetrics and Gynaecology. 2026;10(3):882-893.  \n \n \nCreative Commons (CC) License \nThis is an open access journal, and articles are distributed under the terms \nof the Creative Commons Attribution -Non-Commercial-Share Alike 4 . 0 \nInternational (CC BY -NC-SA 4. 0) License, which allows others to  remix, \ntweak, and build upon the work non -commercially, as long as appropriate \ncredit is given and the new creations are licensed under the identical terms.","source_license":"CC0","license_restricted":false}