{"paper_id":"4bde9598-670a-4e85-acf6-4075954477f8","body_text":"Submit Manuscript | http://medcraveonline.com\nIntroduction: endometriosis and infertility\nEndometriosis and especially cystic ovarian endometriosis \nare considered a major cause of female infertility. Cystic ovarian \nendometriosis is moreover generally associated with ovarian and \ntubal adhesions causing mechanical infertility. 1 Cystic ovarian \nendometriosis is also associated with superficial pelvic endometriosis \nand with deep endometriosis.1,2 It remains debated why endometriosis \nby itself decreases fertility. 3 The hypotheses vary from an effect on \novarian function and ovulation, 4–6 toxic factors for spermatozoa and \noocytes in peritoneal fluid, an altered tubal transport and implantation \nproblems because of immunologic changes, to endometrial changes in \nendometriosis7 and a different endometrial microbiome.8 \nThe pathophysiology of endometriosis has been updated \nrecently. The Sampson hypothesis of retrograde menstruation \nand implantation 9,10 cannot explain all clinical presentations of \nendometriosis and this theory is not compatible with observations as \na different clonality of all endometriosis lesions, 11 and endometriosis \nin the absence of a uterus. The Genetic-epigenetic (G-E) theory 7 is \ncompatible with all observations today. The basic hypothesis is that a \nspecific set of G-E alterations of a body cell, of endometrium, of a stem \ncell or of a bone marrow cell will induce cellular alterations which \nmake them look microscopically as endometrium, but with a different \nbehaviour as known for the different presentations of endometriosis. \nThese G-E changes are favourised by 7 a predisposition , which are \nthe G-E incidents inherited at birth, by radiation and environmental \nfactors as hormone disruptors, by the oxidative stress of retrograde \nmenstruation and by the endometrial, upper genital tract and peritoneal \nmicrobiome.8 Following the G-E incident the endometriosis lesions \nwill develop according to the type of the incidents into typical, cystic \nor deep lesions. This development and growth moreover will vary \nwith the woman-specific endocrine and microbiome environment \nof the peritoneal cavity and with the immunology. 12 Growth is \nvariable but, in most women, self-limiting after a period of growth \nof 4to 6 years before becoming symptomatic(PK et al submitted). \nAn important consequence of understanding the pathophysiology \nof endometriosis is that prevention of recurrences after surgery and \nprevention of growth become conceivable by reducing the oxidative \nstress after surgery and by preventing ascending infection eventually \nby changing the peritoneal microbiome by diet and exercise.8 \nThis recent understanding of the pathophysiology of endometriosis \nchanges our views on the endometriosis associated infertility and its \ntreatment. First endometriosis becomes an heterogeneous disease. 13 \nIndividual lesions even in the same woman, vary from no to high \naromatase activity, from normal progesterone responsiveness to \nprogesterone resistance and thus with a variable response to treatment.14 \nWe can postulate that endometriosis is not a direct cause of infertility, \nbut that women with a predisposition to develop endometriosis have \na decreased fertility, albeit because of the many associated changes \nin the endometrium, 7 because of a different endometrial microbiota 8 \nor because of a different immunity. 12 The infertility thus becomes \na consequence of the ‘endometriotic’ constitution rather than a \nconsequence of the endometriosis lesion. This is consistent with the \nobservation that the results of IVF treatment of women with a small \nendometrioma are similar with or without previous surgery 15 and it \nexplains that the surgical destruction of superficial and/or typical \nlesions does not clearly improve fertility.16 \nCystic ovarian endometriosis\nIn addition of being endometriosis, cystic ovarian endometriosis \nstrongly affects spontaneous fertility because of the associated \nadhesions1 and/or by affecting ovulatory function eventually \nObstet Gynecol Int J. 2020;11(2):122‒125. 122\n©2020 Schindler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nCystic ovarian endometriosis and infertility: \narguments for an early but less aggressive surgical \ntreatment\nVolume 11 Issue 2 - 2020\nLarissa Schindler,1 Sandra Schindler,2 Ussia \nAnastasia,3 Stephan Gordts,4 Arnaud \nWattiez,5,6 Philippe R Koninckx3,5\n1Dubai Fertility Centre of the Dubai Healthy Authority, UAE\n2Department of Human Reproduction, Medical school of the \nFederal University of Bahia, Brazil\n3Gruppo Italo Belga, Villa Del Rosario Rome Italy, Consultant \nUniversità Cattolica, Italy\n4Leuven Institute for Fertility & Embryology, Leuven, Belgium\n5Latifa Hospital, Dubai, UAE\n6Department of obstetrics and gynaecology, University of \nStrassbourg, France\nCorrespondence: Philippe R Koninckx, Department of \nObstetrics and Gynecology, KU Leuven, Belgium +32486271061, \nEmail \nReceived: March 19, 2020 | Published: April 17, 2020\nAbstract\nCystic ovarian endometriosis is a cause of pain and infertility. For infertility, surgical \ntreatment has been suggested for cysts larger than 3 or 4cm in diameter only. Surgical \ntreatment is moreover postponed as long as possible or until pain becomes too severe in \norder to avoid ovarian damage and a decreased ovarian reserve and to avoid recurrences and \nrepeat surgery and adhesion formation. \nOur recent understanding of the pathophysiology of endometriosis, of its initiation and its \ngrowth, probably permits a more effective prevention of recurrences. In addition, adhesion \nfree surgery has become a reality. We therefore suggest performing surgery for cystic \novarian endometriosis early in life when cysts are small followed by an active prevention of \nrecurrences. When cysts are small superficial destruction instead of excision seems logical. \nAlso, THL and under-water coagulation should be considered\nIn conclusion, without discussing the management of larger symptomatic cystic \nendometriosis, we suggest that early surgical treatment of small cyst is the way to go.\nKeywords: endometriosis, cystic ovarian, spermatozoa, ovulation, fertility, peritoneal \nfluid\nObstetrics & Gynecology International Journal \nCase Report\n Open Access\n\n\nCystic ovarian endometriosis and infertility: arguments for an early but less aggressive surgical treatment\n123\nCopyright:\n©2020 Schindler et al. \nCitation: Schindler L, Schindler S, Anastasia U, et al. Cystic ovarian endometriosis and infertility: arguments for an early but less aggressive surgical treatment. \nObstet Gynecol Int J. 2020;11(2):122‒125. DOI: 10.15406/ogij.2020.11.00498\npreventing ovulation.6 Following surgical destruction or removal of the \nendometriotic cyst, some 60% of women will conceive spontaneously \nwithin 1 year.17 Since IVF results in women with and without a small \ncystic ovarian endometrioma do not differ, 18 this suggests that the \nendometrioma does not affect quality of oocytes and implantation but \nrather causes mechanical infertility or ovulation impairment.\nSurgery for cystic ovarian endometriosis is associated with a \nvariable reduction in ovarian reserve. It remains debated to what \nextend the cystic ovarian endometriosis decrease oocyte reserve \nby toxicity or compression and to what extend surgery itself is \ntraumatic;19–22 this is the unsolved question of the singer versus the \nsong.23 Whatever the mechanism of the reduction in oocyte reserve \nsize of the cystic ovarian endometriosis matters. 24 Size matters for \nthe decrease in ovarian reserve before surgery, for the difficulty of \nbeing complete when superficial destruction of the cyst wall and for \nthe damage to the ovary after surgical excision. \nThe surgical treatment of cystic ovarian endometriosis remains \ndebated. Superficial destruction by vaporisation or coagulation is less \ntraumatic for the ovary whereas cyst wall excision is associated with a \nlower recurrence rate.25,26 However, considering that the endometriosis \ncovering the cyst wall is only superficial with a depth of invasion of \nonly 1 to 2mm. 27–29 the cyst wall seems mainly a fibrotic reaction to \nthe endometriosis and cyst wall removal seems overtreatment. The \nhigher recurrence rate following superficial destruction thus probably \nis the consequence of an incomplete destruction in some areas. \nManagement of cystic ovarian endometriosis \nin infertility\nThe best approach to cystic ovarian endometriosis and infertility \nremains unclear. Surgery does not improve the results of IVF \ntreatment,24 but a sequential use of surgery, and IVF in those that \ndo not conceive spontaneously probably results in slightly higher \ncumulative pregnancy rates.30 \nIVF in women with a cystic ovarian endometriosis results in \nspilling of chocolate fluid in the peritoneal cavity. Fortunately, this \nchocolate fluid does not induce endometriosis as demonstrated in \nnude mice.31 However, spilling of this chocolate fluid is expected to \nincrease the oxidative stress while being adhesiogenic. \nConsidering the risk of ovarian damage during surgery and the \nexcellent results of IVF, actual guidelines32 therefore have concluded on \nclinical but arbitrary grounds that small cystic ovarian endometriosis, \ndefined as less than 3-4cm, should not undergo surgery, especially if \nIVF is indicated.\nAdhesion free surgery \nPostoperative adhesions remain a major cause of infertility. \nAlthough adhesion formation has been considered an inevitable side \n-effect of surgery, recent understanding begins to permit adhesion \nfree surgery.33 During surgery, care should be taken not to damage the \nmesothelial cells by cooling the peritoneal cavity to 30˚C, by adding \nsome 10% of N 2O to the CO 2 pneumoperitoneum,34 by keeping the \ninsufflation pressure to minimum permitting surgery, by preventing \ndesiccation and by gentle tissue handling together with surgery of a \nshort duration. At the end of surgery, the remaining fibrin and blood \nshould be kept to a minimum, dexamethasone should be administered \ntogether with a barrier. \nAlso underwater surgery during THL is associated with a minimal \namount of postoperative adhesions as demonstrated for ovarian \ndrilling.35 \nNew approaches to cystic ovarian \nendometriosis \nThese new concepts of the pathophysiology of endometriosis and \nof its growth permitting postoperative prevention of recurrences, \ntogether with the new concepts permitting adhesion free surgery, \nshould be considered to change our attitude towards cystic ovarian \nendometriosis.\nInstead of postponing surgery, in order to prevent recurrences \nwith eventual repeat surgery and ovarian damage and adhesions, \nwe might consider early surgical destruction of small cystic ovarian \nendometriosis. Considering that the endometriosis in cystic ovarian \nendometriosis is only superficial, a superficial destruction by \nelectrosurgery, CO2 laser or alcohol should be sufficient. \nTherefore instead of letting the cystic ovarian endometriosis grow, \nwhile permitting women to develop more lesions, and postponing \nsurgery until pain becomes too severe or until fertility becomes \nan issue, we suggest early treatment of cystic endometriosis with \nminimal superficial destruction of the endometriosis together with the \ndestruction of eventual other initiating lesions (Figure 1). Key is this \nnew concept is prevention of recurrences by reducing the oxidative \nstress of retrograde menstruation and adhesion free surgery. With \nthese concepts, the use of THL in women with infertility should be \nreconsidered. \nFigure 1  Treatment of cystic ovarian endometriosis. When small cysts \nare detected by ultrasound, or during laparoscopy of THL, early superficial \ntreatment without adhesion formation, followed by active prevention of \nendometriosis will result in minimal ovarian damage and maximally preserved \nfertility.\nTransvaginal hydro-laparoscopy (THL) 36–38 offers a minimal \ninvasive procedure for early diagnosis and treatment of small \n\n\nCystic ovarian endometriosis and infertility: arguments for an early but less aggressive surgical treatment\n124\nCopyright:\n©2020 Schindler et al. \nCitation: Schindler L, Schindler S, Anastasia U, et al. Cystic ovarian endometriosis and infertility: arguments for an early but less aggressive surgical treatment. \nObstet Gynecol Int J. 2020;11(2):122‒125. DOI: 10.15406/ogij.2020.11.00498\nendometrioma up to a diameter of 20mm (Figure 2). Not seldom these \nsmall endometriotic cyst are missed at routine vaginal ultrasound \nexamination in approximately 50% of the cases. It is always surprising \nafter opening of such small cysts to see the pronounced presence of \ninflammation and neo-angiogenesis, a signature for the aggressivity \nof the disease in these early stages. Dealing with a growing concern \nof impaired ovarian reserve after surgery, treatment in these early \nstages and in absence of markers for progressivity, using an ablative \ntechnique with a bipolar 5Fr probe causes a minimal trauma and a \nlower risk for recurrences.39,40 \nFigure 2 A. Insight view of small endometriotic cyst at THL showing neo-\nangiogenesis, inflammation and endometrial like tissue. B. View after bipolar \ncoagulation using a 5Fr. coagulation probe causing minimal tissue damage.\nDiscussion\nConsidering new possibilities of prevention of recurrences and \nof growth together with adhesion free surgery, we suggest early and \nsuperficial treatment when cysts are still small. The treatment and the \ntechnique of surgery of the larger cystic ovarian endometrioma are \nbeyond the scope of this article. In order to keep the message clear, we \nalso will not discuss the management of adolescent endometriosis with \npain and/or small cystic ovarian endometriosis and the management \nof infertility or the role of THL in the work-up.\nThat the endometriotic constitution increases the risk of \nendometriosis and the risk of infertility instead of infertility being \na consequence of endometriosis can be viewed as a classic example \nof correlation analysis. During the eighties a strong correlation was \nobserved between dog bites and the selling of roses; this seemed \nstrange until we realised that having a dog and buying roses increased \nwith the standard of living. However strong a correlation might be, \nit remains difficult to establish causality between the 2 factors and \nin addition, both can be the consequence of a common factor. For \nendometriosis and infertility, it becomes logical that surgery of \nendometriosis does not increase fertility unless during other factors \nas adhesions and dyspareunia were resolved. It also becomes logical \nthat women with and without endometriosis have a different fertility \nwhether spontaneous of during IVF treatment. With a common causal \nfactors, also all other associated factors will be mutually correlated as \nrecently observed for BCL6.41 \nIt is logical that the size of a cystic ovarian endometriosis is \nimportant for the oocyte reserve albeit by compression of by toxic \nfactors, and that excision of larger cysts will cause more ovarian \ndamage since the remaining capsule will be less vascularised and \nthinner, that superficial destruction risks to be less complete and \nthat surgery will take longer. Similar to the volume of a cyst which \nincreases with the third power of the diameter, common sense expects \nthat the relationship between size and these risks will be exponential. \nUnfortunately, the available data today are limited to educated guesses \nmaking classes of less than 3 or 4cm. A simple mathematical analysis \nindeed would permit to ascertain until which size the relationship with \ninfertility is flat and from which size onwards exponential.\nAcknowledgments\nWe thank Dr. Muna Tahlak, Dr. Bedaya Amro, Dr. Shaima \nAlsuwaidi, Dr. Hanan Gharbi and Dr. Razan Adil, Dr Basma Al-\nMaamari and Dr Zeinab Hakim, Latifa Hospital, Dubai, United Arab \nEmirates, for discussions and input.\nFunding \nNone.\nConflicts of interest \nThe author and co-authors have no conflicts of interest relevant to \nthis article.\nReferences\n1. Koninckx PR, Meuleman C, Demeyere S, et al. 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