{"paper_id":"23d1183b-ab26-47da-b140-b2392418e145","body_text":"Vol.:(0123456789)\nThe Journal of Obstetrics and Gynecology of India (May–June 2025) 75(3):185–191 \nhttps://doi.org/10.1007/s13224-025-02176-8\nEDITORIAL\nRise and Rise of Endometriosis—An Enigma\nSujata Dalvi1 \nReceived: 22 May 2025 / Accepted: 6 June 2025 / Published online: 20 June 2025 \n© The Author(s) 2025\nAbstract\nEndometriosis is considered ‘silent disease’ but is debilitating that impacts quality of life. It is chronic, benign condition \nwhich is oestrogen dependent and has chronic inflammatory component. Endometriosis is associated with menstruation \nwith increased sensitivity to oestrogen receptors and with low progesterone levels. Locally produced prostaglandins from \nendometriotic lesions leads to pain. There is delay in diagnosis by several years, as symptoms are not specific. This can lead \nto decline in fertility and quality of life. Imaging techniques and bio markers are not very specific but definitive diagnosis \ncan be with Laparoscopy and histopathology. The first line of therapy will be medical, for relief of pain and fertility. Surgery \nis advised after failure of medical therapy, for severe degree of disease and deep infiltrating endometriosis (DIE). Assisted \nreproductive technology (ART) therapy is proposed for improved fertility outcome after surgery. Recurrence is known to \noccur after therapy.\nKeywords Endometriosis · Oestrogen · DIE–deep infiltrating endometriosis · Laparoscopy\nIntroduction\n‘Endometriosis’ word is derived from Greek word endon, \nmeaning ‘within’, metra means ‘uterus’ and osis means \n‘abnormal or diseased condition’. Endometriosis (En’do-\nme-tri-o’sis) is ‘ectopic occurrence of endometrial tissue, \nfrequently forming cysts containing blood’. It is complex \ngynaecological disease where functional endometrial glands/\nstroma which are part of innermost lining of uterine cav -\nity (endometrium) are present outside the uterine cavity. \nThe locations being ovaries, fallopian tubes, outer surface \nof uterus, uterosacral ligaments, pelvic peritoneum, cervix, \nvagina, GI tract, bladder, ureter, urethra, rectovaginal sep-\ntum, abdominal wall and rarely pericardium/pleura/central \nnervous system [1].\nIt is highly prevalent in women of reproductive age \ngroup [2]. It is more common in Caucasians as compared to \nAfrican/Asian and was more reported in developed countries \n[3]. It is oestrogen dependent and has chronic inflamma-\ntory component. Endometriosis is complex disease due to \nsymptoms; fertility related issues hence negatively impact \nthe quality of life.\nIncidence\nIt affects 6–10% of women of reproductive age group. The \nAmerican Society of Reproductive Medicine (ASRM) states \nthat 24–50% of women with fertility issues and 20% with \nchronic pelvic pain has endometriosis [4]. It is estimated that \n247 million women of reproductive age globally, of which \n42 million in India are affected by Endometriosis [5 ]. This \nmeans 10% of women of reproductive age group are affected \nwith endometriosis, which is 1/6 th of Global burden [5 , 6] \n(2024).\nClinical Phenotypes of Endometriosis \nin India\nEndometriosis is heterogeneous condition with distinct \nlesion phenotypes. They are superficial peritoneal endome-\ntriosis (SUP), cystic ovarian endometriosis or endometrioma \nSujata Dalvi, Editor in Chief, MD, DGO, FCPS, FICOG, Hon. \nClinical Associate, Nowrosjee Wadia Hospital, Consultant, Glen \nEagles, Saifee, Bhatia, St. Elizabeth Hospitals, Ex-Associate \nProfessor, Unit Head, KEM Hospital and Seth GS Medical College. \nMumbai.\n * Sujata Dalvi \n sujata.dalvi@hotmail.com\n1 Nowrosjee Wadia Maternity Hospital, Mumbai, India\n\n186 S. Dalvi\n(OMA) and deep infiltrating endometriosis (DIE) lesions \n> 5 mm beneath peritoneum. Single lesion is found in 46%, \ntwo lesions in 38% and three in 18% of women [5 ]. Ovar-\nian endometrioma is present in 17–44% with bilateral in \n50%. These cysts are well defined, with chocolate coloured \nfluid due to degenerated blood products. Superficial lesions \nare accidental findings and are seen in obese women. DIE \ninvolves rectovaginal septum, bladder, ureter and bowel and \nare seen in underweight women [3].\nWith rising incidence and awareness, endometriosis has \nbecome one of the major benign gynaecological disorders \nleading to infertility and chronic pelvic pain.\nPredisposing/Risk Factors\nEarly menarche, short menstrual cycle (< 26 days), menor -\nrhagia (bleeding > 7 days or 80 ml), nulliparity, low birth \nweight, obesity are related to high risk of endometriosis. \nMost factors are associated with elevated oestrogens or pro-\nlonged menstruation, strengthening oestrogen dependency \nand association with menstruation [7 ].\nProstaglandins are locally produced leading to pain. It \nincreases uterine contractility with vasoconstrictive effect \nleading to dysmenorrhoea.\nExposure to environmental agents like dioxins, polyhalo-\ngenated aromatic hydrocarbons, organochloride pesticides, \nphthalates, bisphenols causing growth factor activation, gene \nregulation, immune suppression and altered oestrogen sup-\npression pathways causes endometriosis.\nEndometrial cells get implanted in pelvis through retro-\ngrade menstruation, leading to inflammatory reaction. This \nincreases the blood flow, initiates defence mechanism, caus-\ning swelling, redness and release of cytokines from injured \ncells. This is followed by angiogenesis, adhesions, neuronal \ninfiltration and oxidative stress.\nGenetic predisposition with strong link with heredity like \nmonozygotic twins, first-Possibility of functional obstruction \ndegree relatives are seen. Epigenetic changes occur due to \ngenetic/environmental factors causing proliferation of endo-\nmetriotic tissue and decreased apoptosis.\nProtecting Factors\nParity, breast feeding, oral pills, tubal ligation and smoking \nleads to decrease in incidence. Tubal ligation hampers men-\nstrual flow reflux whereas anovulation decreases irritation \nand inflammatory process. Smoking otherwise is risk factor \nfor many health issues but not in endometriosis [3].\nTheories on Endometriosis\nSampson’s Theory: Retrograde menstruation, viable cells, \nimplantation of viable cells that continue to grow and form \nlesions.\nCoelomic Metaplasia Theory: Ovaries and Muller -\nian ducts are derived from coelomic epithelium, which \nundergoes metaplastic transformation to form tissue like \nendometrium.\nEmbryonic Rest Theory: Cells of Mullerian origin in \nperitoneal cavity can be induced to form endometrial tissue \nwith appropriate stimulation.\nLymphatic and Vascular metastasis: Explains why endo-\nmetriosis occurs in ovary and extra peritoneal sites.\nTIAR (Tissue Injury and Repair) Theory: Chronic peri-\nstalsis or hyper peristalsis causes micro-traumatization \nleading to injury/repair increasing production of local \noestrogens.\nQuinn’s ‘Denervation—Reinnervation’ Theory: Injuries \ncaused due to straining during defecation/vaginal delivery \ncauses denervation. Ectopic endometrial cells from retro-\ngrade menstruation adhere to this injured tissue, (peritoneal \ncavity/USL) followed by re innervation causing pelvic pain.\nStem Cell Theory: Overt vaginal bleeding occurs in 5% \nof neonates, due to endometrium of foetus transforming into \ndecidualized layer that sheds after birth. There is a possibil-\nity of functional obstruction of endo cervical canal, leading \nto regurgitation of endometrial cells into peritoneal cavity. \nThese cells later implant/survive long-term causing adoles-\ncent endometriosis [8].\nOther Causative Factors\nOxidative stress: Plays role locally and systematically. Anti-\noxidants play major role in preventing damage and improv-\ning rates of pregnancy in endometriotic patients.\nIron in pathogenesis of Endometriosis: Increased iron lev-\nels have been found in endometrial lesions/peritoneal fluid/\nperitoneal macrophages leading to growth of lesions. Iron \nchelator treatment could be beneficial to prevent iron load in \nperitoneal cavity and decrease in cellular proliferation [9 ].\nEndometriosis and Ovarian cancer (EAOC): Endome-\ntriosis associated ovarian carcinoma includes clear cell car-\ncinoma, serous–mucinous, endometroid carcinoma and is \noestrogen dependent. Combined screening with CA 125, HE \n4 and USG is recommended, as possible non-invasive test \nfor specific diagnosis [10].\n\n187\nRise and Rise of Endometriosis—An Enigma\nSigns/Symptoms\nSymptoms vary widely and include pelvic pain (40–50%), \ndysmenorrhoea (58–80%), dyspareunia (40–50%), dysu -\nria (1–2%), dyschezia (1–2%), GI discomfort (1–2%) and \ndecreased libido [2 , 11]. The pain is chronic, cyclical and \nprogressive. In addition, cyclical leg pain may be present \n[12]. Patients with DIE have allodynia, condition where with \nnon-application of painful stimulus, there is intolerable pain-\nful reaction. This is because of neuronal damage, release of \nmediators like serotonin, prostaglandins, nerve growth fac-\ntors and increase in local vascular permeability. The degree \nof clinical manifestation is not directly proportional to the \nextent of disease or size of endometrial lesion.\nInfertility, which is common finding, [13] may be due to \ninflammatory response impacting various aspect of concep-\ntion in early stage and later due to adhesions formation and \ndistorted anatomy [14].\nThe symptoms associated with endometriosis are also \npresent in other gynaecological disorders, leaving it mis-\ndiagnosed or overlooked [15]. This contributes an average \ndelay of 7–8 years from onset of symptoms to confirmation \nof diagnosis [7].\nEndometriosis negatively impacts social, sexual and pro-\nfessional quality of life and is associated with depression, \nanxiety and stress.\nD/D needs to be kept in mind like adenomyosis, myoma, \ncervical stenosis, pelvic congestion—pain, pelvic inflamma-\ntory disease, irritable bowel syndrome (IBS) and interstitial \ncystitis. Neurologic and psychosomatic disorder should be \nruled out in case of persistent pelvic pain.\nDiagnosis\nDiagnosis of endometriosis gets delayed being a chronic \npathology with not very specific symptoms. It can take sev-\neral years for the diagnosis, as pelvic pain is natural biologi-\ncal side effect related to menstrual cycles and non-availabil-\nity of pathognomonic/bio marker test to detect the disease.\nNon‑invasive Tests\nUSG—transvaginal ultrasound (TVS) is used for making \ndiagnosis, as it can map the disease significantly and allows \ndynamic assessment. Implants outside peritoneum, adhe-\nsions, infiltrations are difficult to be diagnosed.\nESHRE (European Society of Human Reproduction & \nEmbryology) provided consensus protocol on International \ndeep endometriosis analysis (IDEA). It requires evaluation \nof: Uterus, Ovaries and Adnexa (Component 1), DIE Deep \ninfiltrating endometriosis (Component 2), Sliding sign \n(Component 3), presence of USG soft markers (Component \n4) (Table  1).\nTransrectal sonography (TRUS) is recommended by \nESHRE to diagnose endometriomas in unmarried and rec -\ntal endometriosis. It has good sensitivity and specificity but \nrequires training.\nDoppler blood flow is limited in ovarian endometrioma. \nThose with dense vascularity do not prove to be Endome-\ntrioma [16].\nMagnetic Resonance Imaging (MRI): has limited role but \noffers larger field of view with effect of adhesions on sur -\nrounding structures. It is recommended to diagnose DIE, but \nsmall superficial implants < 5 mm cannot be picked up. MRI \nis advised when malignancy is suspected, doubtful diagnosis \nor when TVS not possible (Table 2).\nBiomarkers: CA 125 is elevated in ovarian endometrioma \nbut is also increased in other ovarian pathology. Extra cellu-\nlar matrix (ECM) protein levels in peritoneal fluid, menstrual \nblood, eutopic endometrium related to endometriosis are under \nstudy [18]. MicroRNA may have potential in diagnostic/thera-\npeutic decisions [14].\nFertility: Tests for evaluation for ovarian reserve—FSH \n(early follicular phase), AMH (Anti Mullerian Hormone), \nAFC (Antral Follicle Count) and Ovarian volume should be \ndone.\nLaparoscopy and histology give definite diagnosis; it is no \nlonger Gold Standard [19]. Laparoscopy being an invasive \nprocedure, current guidelines recommend laparoscopy, only \nif imaging results are negative or empirical treatment has not \nbeen successful/inappropriate. The lesions appear red, white, \nclear vesicular—peritoneal defects, black powder burnt—gun \nshot appearance. Direct visualization with histological biopsy \nis considered. If lesions are not visible—biopsy can be taken \nfrom suspicious area for HP diagnosis.\nASRM—The American Society of Reproductive Medicine \n(1996) has classified endometriosis from stage I to IV with \nscoring system. It is done by surgical observation like appear-\nance, location, type and depth of lesion [14], where symptoms \nof patient are not considered.\nStage I (minimal)—superficial lesions—flimsy adhesions/\nStage II (mild)—additional deep lesions in cul de sac/Stage \nIII (moderate)—additional presence of endometriomas/adhe-\nsions Stage IV (severe)—additional large lesions, extensive \nadhesions, implants beyond uterus.\nOn histology for diagnosis, at least 2 of the 3 criteria should \nbe present—presence of endometrial stroma, epithelium with \nglands, chronic haemorrhage with haemosiderin deposits.\nEndometriosis Fertility Index (EFI): Scoring system was \ndeveloped in 2010 [20]. Age, duration of infertility, previ-\nous fertility, severity of endometriosis, least function score \n(impact on adnexal structures), American Fertility Society \n\n188 S. Dalvi\n(AFS) Endometriosis—total score. High score indicates bet-\nter chance of conception. EFI does not consider age, male \nfactor, lifestyle factors like smoking, alcohol, BMI and emo-\ntional impact.\nRise of Endometriosis??\nPrevalence of diagnosis of Endometriosis seems to be \nincreasing. Incidence being variable, does not necessar -\nily mean that endometriosis is increasing. Endometrio -\nsis is being diagnosed more frequently in different stages \nbecause of increased awareness, more women seeking \nmedical help for pelvic pain and heavy menstrual bleed-\ning (HMB), infertility, access to better diagnostic tools and \nchanges in reporting system. [ 21] The age-adjusted preva -\nlence rate of endometriosis has increased from 2.12 per \n1,000 in 2002 to 3.56 per 1,000 in 2013. This is because \nof genetic link (mother, sister, daughter) and early age \nof menarche (10—11 years). The prevalence of endome-\ntriosis temporarily decreased in 2007, but it continued to \nincrease over the next 5 years. This could be because of \nchanges in lifestyle and environmental factors [22].\nTable 1  TVS: ESHRE (European Society of Human Reproduction & Embryology) provided consensus protocol on International Deep Endome-\ntriosis Analysis (IDEA)\nCompartment 1 Uterus—Adenomyosis\nOvaries—Ovarian endometriomas—diagnosed as complex cyst with homogeneous low levels ground glass echoes, unilocular \nbut can be multilocular. Bilateral cysts may be present\nSensitivity of 80–90% and specificity of 60–98%\nFertility patient, AFC—antral follicle count/ovarian margins should be assessed. Superficial endometriosis/adhesions may \ncause blurring of margins\nASRM, ESHRE suggests surgery, if size > 4 cm\nAdnexa—Exclusion of hydrosalpinx, hematosalpinx and peritoneal inclusion cyst\nCompartment 2 DIE—Deep Infiltrating Endometriosis:\nMapping of Disease: Divide pelvis into anterior/posterior by plane passing through endometrium and vagina\nAnterior pelvic area includes bladder, ureter, anterior serosa covering uterus—vagina done by placing probe in anterior vaginal \nfornix. Bladder is scanned in the end or in beginning. Moderately distended bladder gives accurate diagnosis of bladder \ndome. Ureteric involvement can be missed hence proper vigilance\nPosterior component is scanned by placing probe in posterior fornix. Structures that are seen are utero sacral space, USL, \nbowel (Recto- sigmoid), posterior serosa covering uterus, cervix and vaginal wall. USL ligaments change from hyperechoic \nto hypoechoic, with nodularity and thickening\nDIE nodule appears hypoechoic, linear—round, smooth—irregular border with minimal/nil vascularity. Nodule measured in \nthree dimensions\nCompartment 3 Sliding sign:\nAssesses POD obliteration due to adhesions, fixity of rectum or recto-sigmoid with cervix with or without USL fusion. Done \nin sagittal plane pressing cervix and assessing movement of anterior rectum with cervix and by pressing abdominal wall \nagainst fundus, movement of bowel against posterior uterine fundus is assessed\nPositive—preservation of relative movement\nNegative—adhesions and obliterated spaces\nCompartment 4 Site Specific Tenderness: Soft markers\nSeeing specific probe tenderness and decreased ovarian—uterine mobility suggests presence of superficial endometriosis/adhe-\nsions. With severe adhesions, ovaries become fixed to each other in cul de sac ‘kissing ovaries’ sign. Usually associated with \nbowel and fallopian tube endometriosis\nTable 2  MRI Accuracy [17]\nLesions Sensitivity (%) Speci-\nficity \n(%)\nEndometrioma 95 91\nUSL 85 80\nBowel 83 88\nPOD Obliteration 89 94\n\n189\nRise and Rise of Endometriosis—An Enigma\nManagement\nMedical management includes hormonal therapy that can \nhalt the progress of the disease and non-hormonal therapy \nto alleviate symptoms and increase fertility. An empirical \nmedical therapy can be given even without confirmation, \nprovided symptoms are like that of endometriosis. Therapy \nis to alleviate symptoms and not for cure, as endometriosis \nis a chronic disease. Relief of symptoms does not prove \ndisease to be an endometriosis, and it may not improve \nfertility rate (Table  3).\nDietary inclusion of anti-inflammatory, high fibre, anti -\noxidants along with medical therapy helps in improvement \nof patients’ symptoms. Yoga/meditation/regular exercise \nis beneficial in improving stress/anxiety.\nSurgical Therapy\nSurgery is considered in cases of no response or contra \nindications to medical therapy. Aim of surgical therapy \nis fertility enhancing and pain relief. Recommenda-\ntion during surgery is to excise all endometriotic lesions \n(implants—lesions—nodules) and adhesions causing \ndecrease in inflammatory environment.\nManagement of ovarian endometrioma is challenging \nas removal of the capsule of the cyst can decrease ovarian \nreserve and follicular loss. Drainage or ablation can lead to \nrecurrence and not much of pain relief. Final decision can \nbe taken after proper counselling and weighing benefits.\nIn DIE, after thorough counselling/informed choice, \nmultidisciplinary surgical approach should be followed \nto avoid injury to affected organs. Innovative surgical \ndevices like advanced bipolar, laser technology, robotic \nassisted surgery have been used to increase precision and \neffectiveness.\nRecurrence rate after surgery is 6–67% [3 ].\nFertility treatment: Surgery to remove deceased tissue \nwith care to be taken to preserve ovarian function without \nmuch damage. Post surgery, hormonal suppression therapy \n(downregulation) helps in reducing recurrence and achieving \npregnancy. ART therapy after surgical treatment is effective \nin improving fertility outcome. TVS guided endometrioma \naspiration performed prior to ICSI/IVF cycle, preserves fol-\nlicles by leaving behind pseudo capsule. The procedure is \nless invasive, but recurrence rate is high [24].\nHysterectomy was thought to be cure for those, who had \nfinished with childbearing but not in current scenario. Dur -\ning hysterectomy, endometriosis should be excised/removed.\nComplications\nChronic pelvic pain, infertility and sub fertility are conse-\nquences. It leads to decrease in quality of life and affects \nsocial—emotional—sexual wellbeing. High degree of stress \nlevel, improper sleep and digestive dysfunction like con-\nstipation are seen. Though it is chronic benign condition, \nhigher incidence of ovarian cancer has been noted [3 ].\nIn surgical therapy, there is risk of postoperative adhe -\nsions, that can lead to fertility issues and difficult repeat \nsurgery. Removal of only cyst from ovary is safe option in \novarian endometriomas. In DIE, increased incidence of intra \noperative injury to affected organ (ureter, bowel, bladder) is \nTable 3  Medical management\nNSAIDs First line therapy (Pain Relief)\nCOCs Cyclical/continuous—causes anovulation pelvic pain returns after stopping therapy\nProgesterone Only (Oral—LNG IUD—Implants) causes anovulation and hypoestrogenic milieu. Weight and acne are potential side effects\nDanazol Locally via vaginal (rings)/IU route (IUS)—effective in relieving pain/menorrhagia, avoiding systemic side effects (use \nrestricted till strong evidence) [23]\nDienogest (2 mg) Inhibits gonadotropin secretion/exerts anti proliferative and anti-inflammatory action on endometrial lesions. Can be \ngiven up to 5 years with good safety—tolerability\nProgesterone receptor \nmodulators like \nMifepristone\nHave potential to manage pain caused by endometriosis\nGnRh agonists Causes anovulation, hypoestrogenism and endometrial atrophy. Side effects are bone loss, hot flashes, vaginal atrophy, \nheadache\nGnRh antagonists: Oral preparation—Elagolix 200 mg twice daily (6 months)/150 mg once a day (2 years) depending upon severity of \nsymptoms. It is effective in improving dysmenorrhoea and non-menstrual pelvic pain. Side effects like hot flashes, \nnausea, night sweats and insomnia may be seen\nAromatase Inhibitors Blocks formation of oestrogens\nImmunomodulators/\nanti-angiogenic \nagents\nUnder study—being chronic inflammatory condition\n\n190 S. Dalvi\nseen. Proper precaution with intraoperative multidisciplinary \nsurgical approach should be adopted.\nProposed Newer Therapy\nBeing chronic long-term disease, repeated therapy is needed \nto treat symptoms and prevent recurrence. Non hormonal, \nanti-inflammatory agents like TNF alpha inhibitors, apop-\ntotic agents like metformin, anti-angiogenic agents like \ndopamine agonists, antioxidants are under study [25].\nFocus on Adolescent Endometriosis\nAdolescent age group endometriosis is difficult to deter -\nmine due to invasive method of definitive diagnosis. About \n60% of adult women with endometriosis experience symp-\ntoms before age of 20 years. It takes more than 12 years to \nmake diagnosis from onset of disease in adolescents [2 ]. \nThe most common cause of secondary dysmenorrhoea in \nadolescence is endometriosis and is more likely to have \nnon-cyclical pain.\nRisk factors are genetic, obstructed mullerian anomalies, \nearly menarche and low body mass index.\nHigh degree of suspicion in adolescents with severe dys-\nmenorrhoea interfering with daily activities, chronic pelvic \npain not responding to therapy, GI symptoms and dyspareu-\nnia in sexually active should be kept.\nClinical examination may be difficult. Rectal examination \nmay reveal tenderness over USL and rectovaginal nodularity.\nTVS may not be feasible, transabdominal (TAS) or tran-\nsrectal (TRS) scans or MRI may be considered to confirm \ndiagnosis in advanced lesions. Early lesions may be difficult \nto be picked up.\nLaparoscopy can be considered only in those adolescents \nwith suspected endometriosis where imaging is negative and \nmedical therapy has not been successful. Atypical lesions \nlike clear, white or red are more common. During laparos-\ncopy it is recommended to take biopsy to confirm diagnosis \non histology, but negative histology cannot rule out disease.\nStaging of endometriosis by Revised American Soci-\nety for Reproductive Medicine (rASRM) has been devised \nwhere scoring system has been added—Stage 1 (score 1–5), \nstage 2 (score 6–15), stage 3 (score 15–40), stage 4 (score \n> 40).\nManagement: NSAIDs for pain relief, COCs for anovula-\ntion with safety profile/effectiveness, progestins (Dienogest) \nare used. GnRh agonists can be used, if COCs or Progestins \ntherapy has failed, with add back therapy only after counsel-\nling patient and the relatives. Surgical therapy if considered, \nfertility preservation should be kept in mind.\nConclusion\nEndometriosis is complex debilitating disease, in women \nof reproductive age groups. The risk factors are well estab-\nlished being hyper oestrogenic with chronic inflammatory \npathology. Symptoms being non-specific, it takes several \nyears to reach diagnosis. Non-invasive method of diagnosis \nhas its own limitations and bio markers are inconclusive. \nLaparoscopy and histopathology are for definitive diagnosis. \nEndometriosis has been recognized, treated for many years, \nbut no treatment has been able to cure the disease. The aeti-\nology of disease being unclear, focus is mainly on relieving \npain and improving fertility. Medical and surgical therapy \nhas been effective; however, recurrence rate is high. WHO \naims to have effective policy for Endometriosis globally, in \nlow—middle income countries [26]. 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World Health Organization (WHO) – Endometriosis: https:// www. \nwho. int/ news- room/\nPublisher's Note Springer Nature remains neutral with regard to \njurisdictional claims in published maps and institutional affiliations.","source_license":"CC0","license_restricted":false}