{"paper_id":"881c29e0-90e7-44ba-bf05-8a33548530d2","body_text":"Al Shukri et al. \nMiddle East Fertility Society Journal           (2023) 28:17  \nhttps://doi.org/10.1186/s43043-023-00141-x\nRESEARCH Open Access\n© The Author(s) 2023. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.\nMiddle East Fertility\nSociety Journal\nReproductive outcome and gynecologic \ncomorbidities in women with endometriosis \nin a non-IVF setting: a retrospective study\nMaryam Nasser Al Shukri1*  , Al Shimaa Abdullah Al Riyami2, Wadha Mohammed Al Ghafri3   and \nVaidyanathan Gowri3   \nAbstract \nBackground Endometriosis-related infertility is a disease associated with significant morbidity and distress \nto the couple and requires timely, multidisciplinary, and often high-cost care involving assisted reproductive technol-\nogies (ART). Many health care systems in the Middle East do not provide coverage for ART. This study aims to describe \nthe reproductive outcome in a form of a clinical pregnancy rate in women with endometriosis-related infertility \nin a health care system that does not provide coverage for ART.\nResults This is a retrospective observational cohort study on women who attended the gynecology clinic \nin a tertiary center in Oman with the diagnosis of endometriosis from January 2011 to December 2019. Women \nof reproductive age seeking pregnancy were included in the analysis. Out of total women with endometriosis, \n(144/262) 55.0% were included in the analysis with a mean age of 31.10 ± 5.73 years. The mean duration of follow-up \nwas 30.18 months and 43/144 (29.9%) of our patients had a follow-up > 60 months. Based on surgical staging, 11.8% \nhad mild disease, 70.1% had moderate to severe disease and 18.1% were not operated. After a thorough assess-\nment, (30.2%) were advised to seek in vitro fertilization (IVF) as a primary treatment for infertility but 23.08% declined \nthe advice. Of the 144, 24.3% achieved a clinical pregnancy. (16/144), 11% conceived spontaneously. 11/144) 7.6% \nconceived with ovulation induction ± intrauterine insemination (OI ± IUI) and the rest conceived with a self-sponsored \nIVF. The overall clinical pregnancy rate was not statistically different between those who had surgery and those did \nnot have surgery (P value 0.474). The pregnancy rate based on the management plan were; surgery + IVF (7/25, \n28.0%), surgery + OI/IUI (10/47, 21.3%), surgery alone (9/33, 27.3%). The pregnancy rate was not statistically different \nbetween the groups (P value 0.782).\nIn addition to endometriosis, a significant proportion (63/144, 43.8%) of these women have a coexisting gynecologic \nmorbidity including 2.1% non-endometrioma ovarian cyst, 13.9% myomas, 4.2% adenomyosis, 8.3% Mullerian anoma-\nlies, 2.1% polycystic ovary syndrome, 6.3% pelvic inflammatory disease or tubo-ovarian abscess and 1.4% biopsy-\nproven endometritis.\nConclusion The reproductive outcome of patients with endometriosis in this study population was generally poorer \nthan what is reported in the literature with an overall pregnancy rate of 24.3% and a spontaneous pregnancy rate \nof 11%. Several causes can be noted for such an outcome, including advanced disease stage, coexisting gynecologic \nmorbidities, and poor access to advance fertility management.\n*Correspondence:\nMaryam Nasser Al Shukri\nmnalshukri@gmail.com; mariamn@squ.edu.om\nFull list of author information is available at the end of the article\n\nPage 2 of 9Al Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \nKeywords Endometriosis, Infertility, Assisted reproductive technique, Clinical pregnancy rate, IVF, Adenomyosis, \nMyoma, Tubo-ovarian abscess\nBackground\nEndometriosis is a chronic disease characterized by \nthe presence of endometrial glands and stroma out -\nside the uterine cavity [1 , 2]. It is classified into three \nhistological phenotypes; superficial or peritoneal, \novarian endometrioma, and deep infiltrating endo -\nmetriosis [3 ]. Its reported prevalence vary between 5 \nand 15% depending on the studied population and the \nmethod of diagnosis [1 , 2, 4– 7]. The literature on the \nprevalence of endometriosis was summarized in a sys -\ntematic review describing the overall prevalence to be \n18% [8 ]. Women with endometriosis may be asymp -\ntomatic or may have symptoms of pain or infertility. \nThe pain syndromes are of the variable spectrum of \ndysmenorrhea, dyspareunia, dyschezia, dysuria, and \nor chronic pelvic pain [9 , 10]. The reported prevalence \nof endometriosis in women with chronic pelvic pain is \n23% and with infertility is 31% [8 ]. In Middle Eastern \nwomen, the prevalence of endometriosis with subfer -\ntility is 24% and in women undergoing laparoscopy for \nany indication is 12.9% [6 , 11].\nAs recognized globally, fertility is a very important \ndeterminant of health. WHO defines infertility as a \n“disease characterized by the failure to establish a clini -\ncal pregnancy after 12 months of regular, unprotected \nsexual intercourse” . It is a disease that generates dis -\nability [12, 13]. It is also a social stigma that often has \na negative impact on women socially, mentally, and \nphysically [13, 14]. In the Middle East countries, infer -\ntility is a significant social stigma and endometriosis-\nrelated infertility can be an excuse for a man to divorce \na woman or for polygamy [13].\nThe presence of infertility in women with endome -\ntriosis is estimated to be 35 to 50%. In our population, \n45.4% of women with endometriosis presented with \ninfertility [15].\nThe chronicity of endometriosis and its recurrent \nnature requires a lifelong cost-effective approach for \npreserving reproductive capacity for women [16– 19]. \nManaging endometriosis-related infertility is a chal -\nlenge to the patients, the health care systems, and the \nscientific community. As evidence accumulated over \ntime, there has been a noticeable shift in the recom -\nmendations for the management of women with endo -\nmetriosis from surgery being the gold standard for \ndiagnosis and management to become selective and \nprioritized if medical management failed [19]. ART \nis becoming the best option for the management of \nendometriosis-related infertility in cases of severe dis -\nease, deep infiltrating endometriosis, and low endome -\ntriosis fertility index [19].\nThese guidelines and practice trends are difficult to \nimplement in an area like the Middle East which includes \ncountries with different social and cultural contexts and \nhealth care systems. In these countries, the prevalence \nof endometriosis and endometriosis-related infertility \nare underestimated [2]. In addition to the cultural beliefs \nand social stigma, in many of these countries; infertility \ntreatment is not prioritized as an important health issue, \nis not available in the public-funded health care services, \nand is not covered by health insurance; hence, access to \nART for endometriosis patients is too limited.\nThe purpose of this study is to present real-world data \non the reproductive outcome of women with endome -\ntriosis-related infertility in a Middle Eastern health care \nsystem that does not provide funding for ART in endo -\nmetriosis-related fertility.\nMethods\nThe sample\nThis is a retrospective observational cohort study on \nwomen who attended the gynecologic outpatient depart -\nment at Sultan Qaboos University Hospital (SQUH) with \nendometriosis as a diagnosis over 9  years period from \nJan 2011 to December 2019. This is a subgroup of our \noverall sample of endometriosis patients in the hospital \ndescribed in Al Shukri et al. [15, 19]. SQUH is a tertiary \nreferral center for primary and secondary health care \ninstitutions. The electronic medical record system of the \nhospital (TrackCare ®) mandates the treating gynecolo -\ngist to enter the diagnosis for the international classifica -\ntion of Disease Version 10 (ICD-10). Hence, these women \nwere identified by searching the system for the diagnosis \nof endometriosis as a keyword. The ethical approval for \nthe study was granted by the Medical Research and Eth -\nics Committee of the College of Medicine and Health \nSciences at Sultan Qaboos University, Oman. Women \nwith endometriosis and infertility were evaluated for \nendometriosis-related factors and assessed for surgical \nor medical management. The couple seeking fertility is \nfurther evaluated for ovarian reserve, uterine, tubal, and \nmale factors. Those who were considered candidates for \novulation induction with or without intrauterine insemi -\nnation were referred to the infertility team for assessment \nand further management. Those judged to be candidates \nfor higher-level fertility management options like IVF/\n\nPage 3 of 9\nAl Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \n \nICSI were advised to seek help in private health institu -\ntions that provide ART services and they were provided \nwith the required documentation and reports to facilitate \ntheir care. Usually, those couples will seek the fertility \ncenter of their choice and at their own cost inside or out -\nside the country. Women with poor ovarian reserve and \ncandidates for surgical management are advised to seek \nfertility help by having ovulation induction and embryo \nfreezing prior to the surgical management. Most of \nthose women return for care after ART with or without \npregnancy.\nData analysis\nThe data was collected and analyzed using Statistical \nPackage for Social Sciences IBM- SPSS software, ver -\nsion 23. The sample demographics were presented with \ndescriptive statistics. For continuous variables, mean and \nstandard deviation were used to present the data. Lev -\nene’s test is used for continuous variables to test the dif -\nference in the mean when there is a significant difference \nin the size of the groups and they do not have a normal \ndistribution.\nFor categorical variables, frequencies and percentages \nwere reported. The chi-square test was used to test signif-\nicance for categorical variables and a P value ≤ 0.05 was \nchosen for statistical significance.\nResults\nOut of the total number of women with endometriosis, \n(144/262) 55.0% were interested in pregnancy. For this \nanalysis, we are including those in the reproductive age \ngroup as defined by the World Health Organization (15–\n45 years of age) with primary or secondary infertility and \nactively seeking infertility treatment. Figure 1 outlines the \nstudy population. For those who met these inclusion cri -\nteria, the youngest was 17 years of age and the eldest was \n45  years with a mean age of 31.10 ± 5.73  years. Twenty-\nsix entered our care, not in a relationship but interested \nin preserving fertility, and 11 of them got married and \nbecame actively seeking fertility treatment during follow-\nup so they were included in the primary infertility group \nto become 98 women. Of the 144 women, 68% had pri -\nmary infertility, and 21.5% had secondary infertility. Of \nthe 55.6% who attempted treatment, 22.5% got pregnant \nand about 44% of women though interested in pregnancy, \nthey did not pursue treatment with us.\nFor these women, the mean age at first presenta -\ntion to the clinic was 32.12 ± 7.25  years and a range of \n15–45 years. There were 98 women in the primary infer -\ntility group with a mean age of 29.9 ± 5.28  years and a \nrange of 17–45. In the secondary infertility group, there \nwere 31 women, the mean age 33.32 ± 5.6, and the age \nrange of 22–43. The mean duration of follow-up for these \nwomen was 30.18 months with a range of 0–92 months. \nTwo women had a single visit to the clinic with no fol -\nlow-up as they came for a second opinion. The follow-\nup duration was 6  months or less in 19.4%) of women \nand 29.9% of women had a follow-up duration of more \nthan 5 years (> 60 months). Table 1 is showing the preg -\nnancy rate in relation to the type of management patients \nreceived. The overall clinical pregnancy rate in these \nwomen was 34/144 (24.3%). Spontaneous conception \noccurred in 16 women, 11 got pregnant with OI ± IUI, \nand seven conceived with IVF in a private health institu -\ntion in the country or abroad.\nAfter a thorough assessment, 39/129 (30.2%) were \nadvised to seek IVF as a treatment for infertility. How -\never, 11/39 (28%) declined that advice and opted to have \nOI + IUI which was carried out for a maximum of five \nattempts. None of these women achieved a pregnancy. \nThe remaining 28 women did seek IVF services and 7/28 \n(25%) of them achieved a pregnancy.\nPatients with primary infertility were more likely to \nundergo fertility treatment 64/96, (65.3%) compared to a \npatient with secondary infertility 15/30, (48.4%) with a p \nvalue of 0.009.\nFigure  2 shows the proportion of women who has \nsurgery per stage of disease. When it came to surgical \nintervention for those interested in pregnancy, 80.6% \n(116/144) had a fertility-preserving surgical intervention \nfor endometriosis in the past. This surgical intervention \nwas either at our center or before the presentation to our \ncenter. Twenty-eight women (19.4) did not have a surgi -\ncal intervention for endometriosis. We have been selec -\ntive in surgical intervention in our center and those who \ndid not have surgery were they had their initial diagnosis \nof endometriosis at our center and continued to follow \nwith us.\nTable 2 shows the pregnancy rate per revised American \nSociety Of Reproductive Medicine (rASRM) stage. The \nwas no statistical difference between the different stages \nin pregnancy rate with a p value of 0.154. There was no \ndifference in the mean age for those who were operated \n31.01  years (± 5.18), and not 31.14 operated (± 7.72) for \nendometriosis. Also, the difference in the pregnancy \nrate between those who had surgery (26/116, 22.4%) and \nthose who did not have surgery (8/28, 28.6%) was not sig-\nnificant with a p value of 0.474.\nThe pregnancy rate in the group of surgery and IVF \nwas 7/25 (28.0%) in the group who had surgery and OI/\nIUI was 10/47 (21.3%) and in those who had surgery \nalone was 9/33 (27.3%). There is no significant difference \nbetween the groups with a p value of 0.782.\nA significant proportion (63/144) 43.8% of those inter -\nested in pregnancy had another gynecologic morbidity as \ndetailed in Table 3.\n\nPage 4 of 9Al Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \nDiscussion\nIn women with pelvic endometriosis aged 15–45  years, \nthe pregnancy rate was 24.3% overall, spontaneous \nconception rate was 11.0%, 32.2% pregnancy was with \nOI ± IUI, and 25.0% pregnancy with ART. Our patients’ \npregnancy rate is low compared to other endometriosis \npopulations reported in the literature, overall, and in the \nsubgroups of the type of management they received. The \nspontaneous pregnancy rate following surgery alone was \nreported to be 37.4% by Coccia and 40% by Vidal et  al. \n[20, 21]. It is 27.3% of our study population. It is also \nreported that the rate of spontaneous pregnancy was sig -\nnificantly higher in the first 6 months following the surgi-\ncal intervention compared to the later intervals [16, 22]. \nOur lower rate is can be explained by several reasons. \nThe majority of our patients were having severe disease, \nwith 71.6% rASRM stage III/IV. Many of the patient pop-\nulation in the study had surgical intervention outside our \ncenter and from our knowledge of the local and regional \nmedical environment, we believe that the surgical inter -\nvention the patients had was of variable quality. They \nunderwent surgery either in Oman or abroad and with \nFig. 1 Study sample\nTable 1 Reproductive outcome in relation to type of fertility \ntreatment\na Ovulation induction ± intra-uterine insemination\nb In vitro fertilization\nAttempted fertility treatment Total\nNo treatment aOI ± IUI bIVF\nPregnancy after attending  \nour clinic\n48 40 21 109\n16 11 7 34\nTotal 64 51 28 144\n\nPage 5 of 9\nAl Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \n \nvariable levels of surgical expertise in moderate to severe \nendometriosis. Also, some women were advised ART, \nadvice that they have declined.\nLaparoscopic surgical intervention for endometriosis \nhas been recommended as the gold standard for the man-\nagement of endometriosis [17]. The proposed benefits \nare removal of visible disease lesions decreases disease \nburden and so the related inflammatory mediator [23].\nIt restores the pelvic anatomy which results in improved \nendometriosis-related pain symptoms, and may improve \nsexual function and frequency of sexual relations [21]. \nRestoration of pelvic anatomy plays a role in tubal factor \nFig. 2 Reproductive outcome based on surgical staging\nTable 2 Endometriosis stage and reproductive outcome\nStage of \nendometriosis\nPregnancy \nafter SQUH \ntreatment\nNo. of patients % of total sample\nNo Yes No\nStage 1 3 2 5 3.5%\nStage II 6 6 12 8.3%\nStage III 29 7 36 25.0%\nStage IV 53 12 65 45.1%\nNo surgery 10 7 26 18.1%\nTotal 110 34 144 100%\nTable 3 Coexisting gynecologic conditions\na PID/TOA pelvic inflammatory disease/tubo-ovarian abscess\nb RPL recurrent pregnancy loss\nc PCOS polycystic ovary syndrome\nd FSH follicle-stimulating hormone\nCo-existing gynecologic condition Pregnancy after treatment at SQUH Total no % of 144 women\nNo Yes\nNone 60 21 81 56.3%\nOther ovarian cyst 1 2 3 2.1%\nFibroids 18 2 20 13.9%\nAdenomyosis 5 1 6 4.2%\naPID/TOA 9 1 9 6.3%\nbRPL 2 1 3 2.1%\nMullerian anomalies 8 4 12 8.3%\ncPCOS 1 2 3 2.1%\nBiopsy proven endometritis 2 0 2 1.4%\ndFSH > 20 4 0 4 2.8%\nEndometrial hyperplasia 1 0 1 0.9%\n\nPage 6 of 9Al Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \nrelated to endometriosis [17, 24]. In 2020, a Cochrane \nreview of randomized controlled trials for the treatment \nof endometriosis-related pain and infertility showed \nmoderate quality evidence that laparoscopic interven -\ntion increases the chance of spontaneous pregnancy \n[21]. For patients planned for ART, surgical intervention \nprevented the risk of cyst rupture, allows transvaginal \nassessment of ovarian follicles, and decreases the diffi -\nculty of ovum pick-up. It is also reported that pathologi -\ncal examination of the removed endometriomas shows \nmalignancy at a rate of 0.7% [25].\nFor those who had surgical intervention followed by \nOI ± IUI, the pregnancy rate was 21.3% in our group of \npatients. A study from the Cleveland clinic reported a \npregnancy rate of 10% for severe disease (rASRM III/\nIV) with OI + IUI [23]. The role of OI + IUI in the man -\nagement of endometriosis-related infertility did not have \na significant focus in the literature compared to other \ntreatment modalities. Also, studies had contradicting \nresults. Some studies showed that OI + IUI increased \nthe live birth rate significantly [26, 27]. For women with \nmoderate to severe endometriosis following a surgi -\ncal intervention and having at least one patent tube, \nthe reported pregnancy rate is 40% [28]. However, the \naforementioned study from the Cleveland clinic, com -\npared the fertility outcome for 2 subsets of patients, the \nmild disease (rASRM I/II) and the more severe disease \n(rASRM III/IV). The spontaneous pregnancy rate in \nstage I/II was 45% and 42% with OI + IUI, and in stage \nIII/IV was 20% for spontaneous pregnancy rate and 10% \nfor OI + IUI [23]. In both subsets of disease severity, \nOI + IUI did not improve the pregnancy rates compared \nto the chance of spontaneous pregnancy. The most widely \nquoted guidelines for the management of endometriosis-\nrelated infertility; European Society of Human Repro -\nduction and Embryology (ESHRE) in their most recent \nupdate (ESHRE 2022) is endorsing the use of OI + IUI \nfor mild disease compared to expectant management as \nit improves the chances of a pregnancy [19]. However, \nthey do acknowledge that its role in severe disease with \npatent tubes is controversial, and they leave that to the \ndiscretion of the treating team and the couple for it to be \nconsidered [19].\nIn our study, the combined approach laparoscopy-IVF \nresulted in a pregnancy rate of 28.0%. It is reported that the \nintegrated laparoscopy-IVF treatment approach achieved \na pregnancy rate of 56.1% [20, 21]. Currently, IVF is con-\nsidered the most effective treatment for endometriosis-\nrelated infertility [18, 24]. There are two major issues with \nthis treatment approach. The first is the availability and \naffordability of IVF in a country. Unlike in many Euro -\npean countries; in many health care systems including \nour system, at the time of writing this article, ART is not \nprovided in any government health care institution, nor is \nsponsored by the government for any indication except for \npre-implantation genetic diagnosis (IVF-PDG) for proven \ngenetic disease. It is also not covered by any health insur -\nance company. This places a significant financial burden on \nthe couple and many cannot afford it [29–31]. This results \nin delays in seeking timely and appropriate treatment \nresulting in decreasing chances of pregnancy even if they \npursue IVF later. This also might explain the couple resort-\ning to desperate measures of attempting OI + IUI when it \nis not the best choice. The other issue with IVF is that our \ncommunity like any other; has its own set of traditional \nbeliefs around childlessness and treatment of infertility[14, \n32]. Like in many cultures, there is difficulty accepting the \ndiagnosis of infertility, there is a lack of awareness resulting \nin the assumption that IVF babies are unnatural, seeking \nIVF is a social stigma and there is difficulty accepting it as a \nfirst-line treatment without spending a long time trying for \nspontaneous pregnancy or trying other less invasive meas-\nures like IUI [13, 14]. There is also the IVF-associated emo-\ntional strain, cultural myths, social stigma, and moral, and \nethical dilemmas associated with it that might make the \ncouple avoid it or drop out from treatment [14, 33, 34]. Sec-\nondary infertility usually is in older women, who have diffi-\nculty accepting the fact that they need help to get pregnant \nbecause they have conceived spontaneously previously.\nAs described in Table  2, 43.8% of our study population \nof women with endometriosis seeking fertility had a co-\nexisting gynecologic condition that has also an impact \non the reproductive outcome. These conditions are also \ncommon among women in general. Endometriosis, \nadenomyosis, uterine myomas, PCOS, premature ovar -\nian insufficiency, endometritis, Mullerian anomalies and \nendometrial hyperplasia are all associated with compro -\nmised fertility potential. Endometriosis, adenomyosis, \nuterine myomas, PCOS, and endometrial hyperplasia \nare characterized as estrogen-dependent conditions that \naffect the reproductive tract of women in the reproduc -\ntive age group [35]. Endometriosis, adenomyosis, and \nuterine myomas may present in the same woman [36]. \nThey were also likely to share environmental, genetic, \ndietary, and inflammatory factors that play a role in their \ndevelopment [36]. Although there is no hypo- or hyper- \nsecretion of estrogen in these disorders, hypersensitivity \nof estrogen receptors with genetic predisposition is pro -\nposed to play a significant role and they respond similarly \nupon treatment with GnRH agonist [36–38].\nThe risk of endometriosis was significantly increased \nin women with uterine leiomyoma to about 3-folds \n[39]. The literature describes that myomas are present \nin 12 to 20% of women with endometriosis. Twenty \npercent of women undergoing surgery for uterine myo -\nmas are found to have a concomitant endometriosis \n\nPage 7 of 9\nAl Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \n \n[40]. Women with endometriosis being evaluated by \nultrasound found that 3.1% had uterine myomas, 21.2% \nhad adenomyosis and 14.6% had the 3 conditions of \nendometriosis, adenomyosis, and uterine myomas [41]. \nThe coexistence of endometriosis and uterine myoma \nhas significant surgical and reproductive implications.\nAdenomyosis is considered to be a closer relative of \nendometriosis in that they both share the pathology of \nthe existence of endometrial glands and stroma outside \nthe endometrial cavity [42]. They do frequently co-exist \nespecially deep infiltrating endometriosis and adenomy -\nosis of the outer myometrium in more than 50%women \n[43– 47]. We do strongly believe that adenomyosis is \nunderdiagnosed in our group of endometriosis patients \nwhich reflects the clinical ignorance of the disease and \nthe lack of agreed criteria for diagnosis [48].\nIn our group of endometriosis patients, 8.1% of them \nhad associated Mullerian anomalies. The strong associa -\ntion between endometriosis and Mullerian anomalies is \nwell established in gynecologic history as it is the bases \nfor retrograde menstruation theory for the development \nof endometriosis [36, 49].\nThere is an element of inflamed endometrium seen in \nendometriosis, adenomyosis and chronic endometritis. \nThis inflammation affects endometrial receptivity result -\ning in infertility or recurrent pregnancy loss [50, 51]. \nLiterature also shows an association between endome -\ntriosis and chronic endometritis where in about 52.9% of \nwomen with endometriosis, there is histological evidence \nof chronic endometritis [52]. The cause of endometritis \nin endometriosis is not fully understood and it might be \nindependent pathology [52]. However, some speculated \nthat some humoral and cellular factors produced by the \nendometriosis can be transmitted to the endometrial cav-\nity through the fallopian tubes resulting in an inflamed \nenvironment [50, 52].\nThere was 6.8% of our endometriosis patients had con -\ncomitant PID/TOA. Lin K et al. in a study from Taiwan \ndemonstrated that tubo-ovarian infection is a signifi -\ncant comorbidity in patients with endometriosis with an \nadjusted hazards ratio of 2.86 compared to patients with -\nout endometriosis [53]. Studies also suggested that tubo-\novarian abscesses occur not only more often, but also \nmore severe in patients with endometriosis compared to \nthose without endometriosis [51]. Plausible mechanisms \nare that endometriosis is associated with changes in the \nimmunological environment resulting in impaired abil -\nity to clear infection, the blood content of the endome -\ntrioma is an ideal culture medium for bacterial growth, \nand endometriosis is associated with an increased risk of \nbacterial contamination increasing the risk of PID [53].\nEndometriosis and PCOS co-existed in 2.1% of our \nstudy population. The association between these 2 \ncommon disorders has been described for a long time \n[54]. Endometriosis is present in 11.8–16.5% of women \nwith PCOS [54, 55]. Women with PCOS have 2.86 times \nthe risk of endometriosis compared to women without \nPCOS. Mostly, these cases are diagnosed by laparoscopy \nand both are recognized causes of infertility [56].\nThe strengths of this study are that it provides real-\nworld pooled reproductive outcome data of patients \nwith endometriosis in a setting with limited access to \nIVF. The management and outcomes in this study are \nnot optimized for research but reflect a clinical set-up. \nIt also provides important information over a significant \nfollow-up period. This information is much needed for \nthe physicians involved in the care of women with endo -\nmetriosis and health policy makers taking into consid -\neration the presence of other gynecologic morbidities \nwith endometriosis. However, the fact that it is a retro -\nspective study is a significant limitation. Although the \ntotal sample size is adequate, the number of patients \nfor subgroup analysis of treatment methods or gyneco -\nlogic comorbidities is small and not sufficient to draw \nconfirmatory conclusions. The results are also biased \ntowards gloomier results than what is reported in the \nliterature reflecting the fact that these are more severe \ncases, failed management of symptoms in another insti -\ntution, and many had multiple surgical interventions.\nIn conclusion, the reproductive outcome of patients \nwith endometriosis in this study is generally poorer than \nwhat is reported in the literature with an overall preg -\nnancy rate of 24.3% and a spontaneous pregnancy rate of \n11.2%. Several causes can be noted for such an outcome, \nmost of these patients have severe disease, and do not \nhave a timely access to advanced fertility treatment. Also, \na significant number of these women with endometrio -\nsis (43.8%) have co-existing gynecologic morbidity that is \nlikely to play a role in impairing fertility.\nAuthors’ contributions\nMA: data collection, data analysis, manuscript writing. SA: data collection. WA: \noriginated the idea, manuscript editing. VG: brainstorming the manuscript ideas \nand editing the manuscript. All authors read and approved the final manuscript.\nFunding\nThis is a non-funded project.\nAvailability of data and materials\nThe datasets used and/or analyzed during the current study are available from \nthe corresponding author upon reasonable request.\nDeclarations\nEthics approval and consent to participate\nThis study is approved by the research and ethics committee of the college of \nmedicine and biomedical sciences at Sultan Qaboos University. MREC # 1696.\nConsent for publication\nConsent from individual participants was not required.\n\nPage 8 of 9Al Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \nCompeting interests\nAll authors declare that they have no competing interests.\nAuthor details\n1 Department of Obstetrics and Gynecology and Reproductive Sciences, \nGynecologic Endoscopic Surgery, Sultan Qaboos University Hospital, P .O \nBox 35, Postal Code: 123 Muscat, Sultanate of Oman. 2 College of Medicine \nand Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman. \n3 Department of Obstetrics and Gynecology, Sultan Qaboos University Hospi-\ntal, Muscat, Sultanate of Oman. \nReceived: 18 September 2022   Accepted: 13 June 2023\nReferences\n 1. Missmer SA (2004) Incidence of laparoscopically confirmed endometrio-\nsis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol \n160:784–796. https:// doi. org/ 10. 1093/ aje/ kwh275\n 2. Mousa, M., Al-Jefout, M., Alsafar, H., Becker, C.M., Zondervan, K.T. and Rah-\nmioglu, N. (2021) Impact of endometriosis in women of Arab ancestry \non: health-related quality of life, work productivity, and diagnostic delay. \nFrontiers in global women’s health, Frontiers Media SA, 2, 708410. https:// \ndoi. org/ 10. 3389/ fgwh. 2021. 708410\n 3. Chapron, C., Pietin-Vialle, C., Borghese, B., Davy, E., Foulot, H.E. and Chopin, \nN. Endometriosis associated ovarian endometrioma is a marker for \ngreater severity of deeply infiltrating endometriosis. https:// doi. org/ 10. \n1016/j. fertn stert. 2008. 06. 003\n 4. Houston DE (1984) Evidence for the risk of pelvic endometriosisi by age, \nrace and socioecomomic status. Epidemiol Reviews Oxford Academic \n6:167–191. https:// doi. org/ 10. 1093/ OXFOR DJOUR NALS. EPIREV. A0362 70\n 5. De Oliveira R, Adami F, Mafra FA, Bianco B, Vilarino FL, Barbosa CP (2016) \nCauses of endometriosis and prevalent infertility in patients undergoing \nlaparoscopy without achieving pregnancy. Minerva Ginecol 68:250–258\n 6. Mousa M, Al-Jefout M, Alsafar H, Kirtley S, Lindgren CM, Missmer SA, \nBecker CM, Zondervan KT, Rahmioglu N (2021) Prevalence of common \ngynecological conditions in the Middle East: systematic review and meta-\nanalysis. Front Reprod Health Frontiers 3:7. https:// doi. org/ 10. 3389/ frph. \n2021. 661360\n 7. Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of \nendometriosis. Fertil Steril 98:511–519. https:// doi. org/ 10. 1016/j. fertn \nstert. 2012. 06. 029\n 8. Moradi, Y., Shams-Beyranvand, M., Khateri, S., Gharahjeh, S., Tehrani, S., \nVarse, F., Tiyuri, A. and Najmi, Z. (2021) A systematic review on the preva-\nlence of endometriosis in women. Indian Journal of Medical Research, \nWolters Kluwer -- Medknow Publications, 154, 446. https:// doi. org/ 10. \n4103/ ijmr. IJMR_ 817_ 18\n 9. Nnoaham KE, Hummelshoj L, Webster P , de Cicco Nardone F, de Cicco \nNardone C, Jenkinson C, Kennedy SH, Zondervan KT, Carmona F, Kennedy \nS (2011) Impact of endometriosis on quality of life and work productiv-\nity: a multicenter study across ten countries Europe PMC Funders Group. \nFertil Steril 96:366–373. https:// doi. org/ 10. 1016/j. fertn stert. 2011. 05. 090\n 10. Sulaiman M, Al-Farsi Y, Al-Khaduri M, Saleh J, Waly M (2018) Polycystic \novarian syndrome is linked to increased oxidative stress in Omani \nwomen. Int J Womens Health Dove Medical Press Ltd 10:763–771. \nhttps:// doi. org/ 10. 2147/ IJWH. S1664 61\n 11. Darwish, A., Hassanin, M.S. and Sekkin, A. (2006) Epidemiology and risk \nfactors associated with laparoscopically diagnosed typical and atypical \nendometriosis among Egyptian women. Middle East Fertility Society \nJournal, 11, 196–201. http:// www. bioli ne. org. br/ pdf? mf060 33\n 12. Zegers-Hochschild, F., Adamson, G.D., Dyer, S., Racowsky, C., de Mouzon, \nJ., Sokol, R., Rienzi, L., Sunde, A., Schmidt, L., Cooke, I.D., Simpson, J.L. and \nvan der Poel, S. (2017) The international glossary on infertility and fertility \ncare, 2017. Fertility and Sterility, Elsevier Inc., 108, 393–406. https:// doi. \norg/ 10. 1016/J. FERTN STERT. 2017. 06. 005\n 13. Borght, M. Vander and Wyns, C. (2018) Fertility and infertility: definition \nand epidemiology. https:// doi. org/ 10. 1016/j. clinb iochem. 2018. 03. 012\n 14. Okafor, N.I., Joe-Ikechebelu, N.N. and Ikechebelu, J.I. (2017) Perceptions \nof infertility and in vitro fertilization treatment among married couples \nin Anambra State, Nigeria. African Journal of Reproductive Health, 21, \n55–66. https:// doi. org/ 10. 29063/ ajrh2 017/ v21i4.6\n 15. Al Shukri, M., Al Riyami, A.S., Al Ghafri, W. and Gowri, V. (2022) Based on \nclinical profile: are there predictors of earlier diagnosis of endometriosis? \nA retrospective study in Oman. Oman Medical Journal. https:// doi. org/ 10. \n5001/ omj. 2023. 35\n 16. Vatsa R, Sethi A (2021) Impact of endometriosis on female fertility and the \nmanagement options for endometriosis-related infertility in reproductive \nage women: a scoping review with recent evidences. Fertil Soc J 26:36. \nhttps:// doi. org/ 10. 1186/ s43043- 021- 00082-3\n 17. Coccia ME, Nardone L, Rizzello F (2022) Endometriosis and infertility: a \nlong-life approach to preserve reproductive integrity. Int J Environ Res \nPublic Health 19:6162. https:// doi. org/ 10. 3390/ IJERP H1910 6162. (MDPI \nAG)\n 18. ESHRE Endometriosis Guideline Development Group. (2022) Endometrio-\nsis: Guideline of European Society of Human Reproduction and Embryol-\nogy. https:// www. eshre. eu/ guide lines\n 19. Becker, C.M., Bokor, A., Heikinheimo, O., Horne, A., Jansen, F., Kiesel, L., \nKing, K., Kvaskoff, M., Nap, A., Petersen, K., Saridogan, E., Tomassetti, C., van \nHanegem, N., Vulliemoz, N., Vermeulen, N. and Group, E.E.G. (2022) Endo-\nmetriosis: European Society of Human Reproduction and Emberyology. \nHuman Reproduction Open, hoac009. https:// doi. org/ 10. 1093/ hropen/ \nhoac0 09\n 20. Vidal, F., Guerby, P ., Simon, C., Lesourd, F., Cartron, G., Parinaud, J., Tanguy \nle Gac, Y. and Dupuis, N. (2021) Spontaneous pregnancy rate following \nsurgery for deep infiltrating endometriosis in infertile women: the impact \nof the learning curve. Journal of Gynecology Obstetrics and Human \nReproduction, Elsevier Masson, 50, 101942. https:// doi. org/ 10. 1016/J. \nJOGOH. 2020. 101942\n 21. Bafort, C., Beebeejaun, Y., Tomassetti, C., Bosteels, J. and Duffy, J.M.N. \n(2020) Laparoscopic Surgery for Endometriosis. The Cochrane database \nof systematic reviews, Cochrane Database Syst Rev, 10. https:// doi. org/ 10. \n1002/ 14651 858. CD011 031. PUB3\n 22. Bulletti C, Coccia ME, Battistoni S, Borini A (2010) Endometriosis and \nInfertility. J Assist Reprod Genet 27:441–447. https:// doi. org/ 10. 1007/ \ns10815- 010- 9436-1\n 23. Gandhi AR, Carvalho LF, Nutter B, Falcone T (2014) Determining the \nfertility benefit of controlled ovarian hyperstimulation with intrauterine \ninsemination after operative laparoscopy in patients with endometriosis. \nJ Minim Invasive Gynecol 21:101–108. https:// doi. org/ 10. 1016/J. JMIG. \n2013. 07. 009. (Elsevier)\n 24. Mon Khine, Y., Fuminori Taniguchi, • and Harada, • Tasuku. Clinical Man-\nagement of Endometriosis-Associated Infertility. https:// doi. org/ 10. 1007/ \ns12522- 016- 0237-9\n 25. Kobayashi H, Sumimoto K, Moniwa N, Imai M, Takakura K, Kuromaki T, \nMorioka E, Arisawa K, Terao T (2007) Risk of developing Ovarian cancer \namong women with ovarian endometrioma: a cohort study in Shizuoka, \nJapan. Int J Gynecol Cancer 17:37–43. https:// doi. org/ 10. 1111/j. 1525- \n1438. 2006. 00754.x. (England)\n 26. Tummon, I.S., Asher, L.J., Martin, J.S.B. and Tulandi, T. (1997) Randomized \ncontrolled trial of superovulation and insemination for infertility associ-\nated with minimal or mild endometriosis. Fertility and Sterility, Elsevier \nInc., 68, 8–12. https:// doi. org/ 10. 1016/ S0015- 0282(97) 81467-7\n 27. Nulsen JC, Walsh S, Dumez S, Metzger DA (1993) A randomized and \nlongitudinal study of human menopausal gonadotropin with intrauterine \ninsemination in the treatment of infertility. Obstet Gynecol 82:780–786 \n(United States)\n 28. Van Der Houwen LEE, Schreurs AMF, Schats R, Heymans MW, Lambalk CB, \nHompes PGA, Mijatovic V (2014) Efficacy and safety of intrauterine insemi-\nnation in patients with moderate-to-severe endometriosis. Reprod Biomed \nOnline 28:590–598. https:// doi. org/ 10. 1016/J. RBMO. 2014. 01. 005. (Elsevier)\n 29. Holoch KJ, Lessey BA (2010) Endometriosis and infertility. Clin Obstet \nGynecol 53:429–438. https:// doi. org/ 10. 1097/ GRF. 0b013 e3181 db7d71. \n(United States)\n 30. Roeder C, Lukyanov V, de Agustin Calvo E, Schwarze J (2022) POSC104 \ndetermining cost data for fertility treatment in a Spanish setting. Value \nHealth 25:S107. https:// doi. org/ 10. 1016/J. JVAL. 2021. 11. 509. (Elsevier BV)\n 31. Shahin, A. and Shahin, A.Y. (2007) The problem of IVF cost in developing \ncountries: has natural cycle IVF a place? 15, 51–56. https:// doi. org/ 10. \n1016/ S1472- 6483(10) 60691-8\n\nPage 9 of 9\nAl Shukri et al. Middle East Fertility Society Journal           (2023) 28:17 \n \n 32. Sharma, R.S., Saxena, R. and Singh, R. (2018) Infertility & assisted reproduc-\ntion: a historical & modern scientific perspective. The Indian Journal of \nMedical Research, Wolters Kluwer -- Medknow Publications, 148, S10. \nhttps:// doi. org/ 10. 4103/ IJMR. IJMR_ 636_ 18\n 33. Patel, A., Sharma, P .S.V.N. and Kumar, P . (2018) Role of mental health \npractitioner in infertility clinics: a review on past, present and future direc-\ntions. https:// doi. org/ 10. 4103/ jhrs. JHRS_ 41_ 18\n 34. Burns LH (2007) Psychiatric aspects of infertility and infertility treatments. \nPsychiatr Clin North Am 30:689–716. https:// doi. org/ 10. 1016/j. psc. 2007. \n08. 001\n 35. Verit FF, Yucel O (2013) Endometriosis, leiomyoma and adenomyosis: the \nrisk of gynecologic malignancy. Asian Pac J Cancer Prev 14:5589–5597. \nhttps:// doi. org/ 10. 7314/ APJCP . 2013. 14. 10. 5589\n 36. Petraglia F, Musacchio C, Luisi S, De Leo V (2008) Hormone-dependent \ngynaecological disorders: a pathophysiological perspective for appropri-\nate treatment. Best Pract Res Clin Obstet Gynaecol 22:235–249. https:// \ndoi. org/ 10. 1016/J. BPOBG YN. 2007. 07. 005\n 37. Vannuccini S, Clifton VL, Fraser IS, Taylor HS, Critchley H, Giudice LC, Petra-\nglia F (2016) Infertility and reproductive disorders: impact of hormonal \nand inflammatory mechanisms on pregnancy outcome. Hum Reprod \nUpdate 22:104–115. https:// doi. org/ 10. 1093/ HUMUPD/ DMV044\n 38. Khan, K.N., Kitajima, M., Hiraki, K., Fujishita, A., Nakashima, M., Ishimaru, T. \nand Masuzaki, H. Cell proliferation effect of GnRH agonist on pathological \nlesions of women with endometriosis, adenomyosis and uterine myoma. \nhttps:// doi. org/ 10. 1093/ humrep/ deq240\n 39. Lin, K.Y.H., Yang, C.Y., Lam, A., Chang, C.Y.Y. and Lin, W.C. (2021) Uterine \nleiomyoma is associated with the risk of developing endometriosis: a \nnationwide cohort study involving 156,195 women. PLoS ONE, Public \nLibrary of Science, 16. https:// doi. org/ 10. 1371/ JOURN AL. PONE. 02567 72\n 40. Maclaran K, Agarwal N, Odejinmi F (2014) Co-existence of uterine myo-\nmas and endometriosis in women undergoing laparoscopic myomec-\ntomy: risk factors and surgical implications. J Minim Invasive Gynecol \n21:1086–1090. https:// doi. org/ 10. 1016/J. JMIG. 2014. 05. 013. (Elsevier)\n 41. Capezzuoli T, Vannuccini S, Fantappiè G, Orlandi G, Rizzello F, Coccia ME, \nPetraglia F (2020) Ultrasound findings in infertile women with endome-\ntriosis: evidence of concomitant uterine disorders. Gynecol Endocrinol \n36:808–812. https:// doi. org/ 10. 1080/ 09513 590. 2020. 17360 27. (Taylor and \nFrancis Ltd)\n 42. Just PA, Moret S, Borghese B, Chapron C (2021) Endométriose et Adéno-\nmyose. Ann Pathol 41:521–534. https:// doi. org/ 10. 1016/J. ANNPAT. 2021. \n03. 012. (Elsevier Masson)\n 43. Maruyama S, Imanaka S, Nagayasu M, Kimura M, Kobayashi H (2020) \nRelationship between adenomyosis and endometriosis; different pheno-\ntypes of a single disease? Eur J Obstet Gynecol Reprod Biol 253:191–197. \nhttps:// doi. org/ 10. 1016/J. EJOGRB. 2020. 08. 019. (Elsevier)\n 44. Bourdon M, Santulli P , Oliveira J, Marcellin L, Maignien C, Melka L, Bor-\ndonne C, Millisher AE, Plu-Bureau G, Cormier J, Chapron C (2020) Focal \nadenomyosis is associated with primary infertility. Fertil Steril 114:1271–\n1277. https:// doi. org/ 10. 1016/J. FERTN STERT. 2020. 06. 018\n 45. Pinzauti S, Lazzeri L, Tosti C, Centini G, Orlandini C, Luisi S, Zupi E, Exa-\ncoustos C, Petraglia F (2015) Transvaginal sonographic features of diffuse \nadenomyosis in 18–30-year-old nulligravid women without endometrio-\nsis: association with symptoms. Ultrasound Obstet Gynecol 46:730–736. \nhttps:// doi. org/ 10. 1002/ UOG. 14834. (John Wiley and Sons Ltd)\n 46. Leyendecker G, Bilgicyildirim A, Inacker M, Stalf T, Huppert P , Mall G, \nBöttcher B, Wildt L (2015) Adenomyosis and endometriosis. Re-visiting \ntheir association and further insights into the mechanisms of auto-trau-\nmatisation. An MRI Study. Arch Gynecol Obstet 291:917–932. https:// doi. \norg/ 10. 1007/ S00404- 014- 3437-8/ FIGUR ES/ 12. (Springer Verlag)\n 47. Loring M, Chen TY, Isaacson KB (2021) A systematic review of adenomyo-\nsis: it is time to reassess what we thought we knew about the disease. J \nMinim Invasive Gynecol 28:644–655. https:// doi. org/ 10. 1016/J. JMIG. 2020. \n10. 012\n 48. Chapron C, Tosti C, Marcellin L, Bourdon M, Lafay-Pillet MC, Millischer AE, \nStreuli I, Borghese B, Petraglia F, Santulli P (2017) Relationship between \nthe magnetic resonance imaging appearance of adenomyosis and \nendometriosis phenotypes. Hum Reprod 32:1393–1401. https:// doi. org/ \n10. 1093/ HUMREP/ DEX088. (Oxford University Press)\n 49. Olive DL, Henderson DY (1987) Endometriosis and Mullerian anomalies. \nObstet Gynecol 69:412–415 (United States)\n 50. Pirtea P , Cicinelli E, De Nola R, de Ziegler D, Ayoubi JM (2021) Endometrial \ncauses of recurrent pregnancy losses: endometriosis, adenomyosis, and \nchronic endometritis. Fertil Steril 115:546–560. https:// doi. org/ 10. 1016/J. \nFERTN STERT. 2020. 12. 010. (Elsevier)\n 51. de Ziegler D, Pirtea P , Ayoubi JM (2019) Inflammation and uterine fibrosis: \nthe possible role of chronic endometritis. Fertil Steril 111:890–891. \nhttps:// doi. org/ 10. 1016/J. FERTN STERT. 2019. 02. 005\n 52. Takebayashi, A., Kimura, F., Kishi, Y., Ishida, M., Takahashi, A., Yamanaka, \nA., Takahashi, K., Suginami, H. and Murakami, T. (2014) The association \nbetween endometriosis and chronic endometritis. PloS one, PLoS One, 9. \nhttps:// doi. org/ 10. 1371/ JOURN AL. PONE. 00883 54\n 53. Gao, Y., Qu, P ., Zhou, Y. and Ding, W. (2020) Risk factors for the develop-\nment of tubo-ovarian abscesses in women with ovarian endometriosis: \na retrospective matched case-control study.https:// doi. org/ 10. 1186/ \ns12905- 021- 01188-6\n 54. Singh KB, Patel YC, Wortsman J (1989) Coexistence of polycystic ovary \nsyndrome and pelvic endometriosis. Obstet Gynecol 74:650–652. https:// \ndoi. org/ 10. 1111/j. 1447\n 55. Kichukova, D. (1996) Polycystic ovaries in association with pelvic \nendometriosis in infertile women diagnosed by laparoscopy. Folia Med \n(Plovdiv), 38, 71–3. https:// pubmed. ncbi. nlm. nih. gov/ 91455 94/\n 56. Schwartz CL, Christiansen S, Vinggaard AM, Axelstad M, Hass U, Svingen \nT (2019) Anogenital distance as a toxicological or clinical marker for fetal \nandrogen action and risk for reproductive disorders. Arch Toxikol 93:253–\n272. https:// doi. org/ 10. 1007/ S00204- 018- 2350-5. (Springer Verlag)\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in pub-\nlished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}