{"paper_id":"27718131-853d-405b-8986-430f5c229a63","body_text":"66\nPage 66-75\nReceived: 03 October 2022 Accepted: 26 January 2023\nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nEpaarachchi, E. A. K.1  & De Silva, B. S. S.2\n1kumudumalie93@gmail.com, 2bssil@ou.ac.lk\n1School of Nursing, Faculty of Humanities and Sciences, SLIIT, Malabe, Sri Lanka.\n2The Open University of Sri Lanka, Nawala, Nugegoda 11222, Sri Lanka.\nAbstract\nEndometriosis is a progressive stirring disease marked by the appearance of endometrial glands \nand stroma exterior of the uterus. It affects 8%–10% of reproductive-age women and is linked to \ndeveloping primary or secondary infertility in 30% of these women. The main objective of this \nsystematic review was to critically analyse the current related literature to explore the maternal \nand neonatal adverse outcomes of pregnancies diagnosed with endometriosis. Pregnant women \nwith endometriosis are more likely to develop negative pregnancy outcomes and complicated \nneonatal outcomes, and therefore they may benefit from extra screening and early detection. \nTherefore, eight studies are critically analysed in terms of study design, sample size, sample \ntype, exclusive criteria, comprehensive criteria, data analysis, and key findings based on data \navailability to identify common adverse outcomes of pregnancies with endometriosis. After \ncritically analysing the eight studies, authors explored that pregnant women diagnosed with \nendometriosis are at elevated risk to develop Placenta previa, hypertensive disorders, postpartum \nhemorrhage, emergency caesareans and preeclampsia as common maternal outcomes and \npremature birth, Low birth weight and stillbirth as common neonatal outcomes. In conclusion, \nwomen with endometriosis are at elevated risk of developing adverse maternal and neonatal \noutcomes in their pregnancies. \nKeywords:  Adverse effects, Endometriosis, Maternal outcomes, Neonatal outcomes.\nIntroduction\nEndometriosis is a progressive stirring disease \nmarked by the appearance of endometrial \nglands and stroma-like lesions outside the \nuterus (Leyland et al., 2010). Furthermore, \nit is associated with chronic pelvic pain, \nwhich often affects 8%–10% of reproductive-\nage women, and it is linked to primary or \nsecondary infertility in 30% of these women \n(Velasco, 2004). However, endometriosis can \ncontinue as a minor or non-existent condition \nin some cases, or it can disappear on its own \nin others (Ozkan et al., 2008). But, there have \nbeen many studies in literature, especially \nwithin the past 10 years, showing increasing \nDOI: https://doi.org/10.4038/sjhs.v3i1.52\nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\n\n67\nevidence of the association between \nendometriosis and increased risk of pregnancy \ncomplications such as placenta Previa, \nhypertensive disorders of pregnancy (HDP), \nsmall for gestational age (SGA), placental \nabruption, postpartum hemorrhage (PPH) \nand neonatal complications, such as preterm \nbirth and low birth weight(Chen et al., 2018; \nBerlac et al., 2017). In America, the effects \nof endometriosis on perinatal outcomes have \nremained provocative, while and neonatal \noutcomes such as preterm delivery, low birth \nweight have been commonly observed (Zullo \net al., 2017). However, in Canada, women \nwith endometriosis who had developed \npre-eclampsia, gestational hypertension, \ngestational Diabetic Mellitus (GDM), placenta \nPrevia, and partum hemorrhage, emergency \ncesareans as maternal complications. \nFurthermore, neonates had preterm births, low \nbirth weight and even neonatal deaths (Lalani \net al., 2018). \nNot only in European countries, but also \nAsian countries such as Japan, placenta \nprevia and post-partum haemorrhage in the \nendometriosis group were significantly higher \nwith endometriosis women, incidences of \npreterm birth, GDM, and placental abruption \nbetween were noted (Miura et al., 2019).  \nHowever, in Sri Lanka no exact studies were \ndone related to the research topic,  but articles \nhave mentioned major social, public health, \nand economic ramifications that can be caused \nto reduce quality of life due to endometriosis \nbecause of extreme pain, exhaustion, sadness, \nanxiety, and infertility.  In relation to many \nof these cases, endocrine and ovulatory \nabnormalities in women with endometriosis \ninclude luteinized unruptured follicle \nsyndrome, compromised folliculogenesis, \nluteal phase defect, and premature or \nmultiple luteinizing hormone (LH) spikes, \nall of which have a significant effect on \ntheir pregnancies and outcomes (American \nSociety for Reproductive Medicine, 1996). \nInvasion and tissue penetration, development \nof endometriomas or “chocolate cysts”, \nextreme pelvic adhesions, or pelvic blockage \nthat may damage other organs, as well \nas pelvic carcinomas, can trigger severe \nsymptomatology (Oxholm et al. 2007). \nFurthermore, currently, there is no satisfactory \ntreatment for all endometriosis patients. \nEndometriosis treatments are problematic \nbecause they can reduce pain, increase \npregnancy symptoms and outcomes, and \nalso improve infertility, but they do not \ncure the disorder. However, it can be \nconcluded that having endometriosis may \nlead to developing serious complications in \npregnancies.  Consequently, to overcome the \npossible negative outcomes, clinicians should \nbe aware of the potential endometriosis-\nrelated complications, particularly during \npregnancy and labor (Farland et al., 2019). \nThe prevalence of endometriosis has been \nstudied in a variety of ways, with diverse \nestimates reflecting the variations in diagnosis \nparameters and population size (Berlac et al., \n2017). Therefore, increased interest towards \nendometriosis around the world resulted in \nfinding long-term health and endometriosis-\nrelated comorbid conditions in both women and \nnewborns (Farland et al., 2019). Consequently, \nmany research works have been conducted to \nidentify the maternal and neonatal outcomes \nrelated to endometriosis and are reviewed \nwith different and occasionally contrastive \noutcomes. Through this systematic review, \nthe researcher intended to synthesize and \nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75\n\n68\ndiscuss the common possible adverse \noutcomes of pregnant women diagnosed with \nendometriosis, and adverse neonatal outcomes \nassociated with endometriosis.\nMethods and Materials\nSelection of articles\nIn the current study, a systematic review method \nis followed as the study design. Literature from \nthe following online databases like CINAHL, \nMEDLINE and PUBMED is used as search \nlibraries to collect relevant literature for the \ntopic of maternal and neonatal outcomes of \npregnancies diagnosed with endometriosis. \nRetrospective cohort studies and primarily \nwritten articles which are less than 5 years \nago were considered and their eligibility \ncriteria for the study are based mainly on the \nPICO approach, date of publication, and the \nstudy design. Articles on the neonatal and \nmaternal outcomes of pregnant mothers with \ndiagnosed endometriosis were considered \nfor the study, and no restrictions were made \nbased on the country, patient’s age, and \nrace.  Using the keywords ‘Endometriosis’, \n‘Maternal outcomes’, ‘Neonatal outcomes’, \nand ‘Adverse effects’, a total number of 1569 \nrelated articles were found and of which 825 \narticles from CINAHL, 505 articles from \nMEDLINE and 239 articles from PUBMED. \nOut of which articles in duplicates, not in \nEnglish language or English translations and \nsubsequently further modified and restricted \nfor the search keywords were excluded, \nreducing the number of total articles. The \narticle’s title and abstract were appraised, and \nthe search period was confined to a time span \nfrom 2016 to 2020. After the above process, \nfurther 646 articles were excluded from the \nfiltered literature, and the number of related \narticles were reduced to 63. After conducting \na further eligible review of the selected 63 \narticles, the number of related literatures was \nfurther reduced to 23 articles. Eventually, the \nselected 23 articles from the search databases \nwere subjected to filtering according to their \nmethodological quality and research findings. \nAfter the exclusion of all irrelevant articles, \n8 research articles were finalised using CASP \nmethod for critical appraisal of the systematic \nreview using the PRISM flow chart (Fig. 1). \nFigure 1.\nPRISMA flow chart of the article selection.\n \nFurthermore, full-text articles in English or \ntranslations were considered in the inclusive \ncriteria. The researcher excluded the studies \nthat are not reliably extracted, duplicates, or \nconsist of overlapping data. Furthermore, \narticles not in the English language and \narticles with no full-text availability are also \nexcluded. \nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75\n\n69\nResults and Discussion\nRelated literature within 5 years (2016-2021) \nwas taken for research, and a few related \nliteratures over 5 years were taken due to \nthe availability of relevant information. \nNevertheless, as with a comprehensive review \nof observational studies, it is constrained by \nthe nature and variability of the studies used. \nMost of the papers found during the search \nprocess are closely related to the research topic, \nmaking it easy for researchers to find the right \nsolution to their current problem. However, \ncontrol composition was not standardized in \nmost trials, and some studies used a wider range \nof controls compared to the affected groups. \nAs a result, there is a risk of reliability and \nprejudice issues when considering the results. \nDespite these restrictions, some studies have \ntaken into account or limited the amount of \ntime, equality, and pregnancy. These variables \ncontributed to the heterogeneity of the study, \nas expected in a systematic empirical sample.\nEach study is critically analysed in terms \nof study design, sample size, sample type, \nexclusive criteria, comprehensive criteria, \ndata analysis, and key findings based on data \navailability (Table 1). \nTable 1.\nFactors influencing on maternal and neonatal outcomes of the eight studies.\nAuthor Study Design and Focus Time frame and \nsample size\nFactors influencing on\nMaternal \noutcomes\nNeonatal \noutcomes\nShmueli \net al.\n (2017)\nRetrospective Cohort \nStudy.\nTo explore the obstetrical \nand neonatal outcomes of \npregnancies complicated \nby endometriosis\n2007 to 2014\nEndometriosis \ngroup\n(135)\nControl group\n(61400)\nPostpartum \nhaemorrhage, \nemergency \ncaesareans, \nplacenta Previa.\nno neonatal \ncomplications \nwere noted\nUccella \net al. \n(2014)\nRetrospective Cohort \nStudy.\nTo identify maternal and \nneonatal outcomes of \nendometriosis specified \nwith the location of the \ndisease\n2011 to 2014.\nEndometriosis \ngroup\n(118)\nControl group\n(1680)\nPlacenta \nPrevia. \nHypertensive \ndisorders.\npreterm deliveries\nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75\n\n70\nPan \net al.\n(2017)\nNationwide population-\nbased longitudinal study.\nTo explore the risk of \ngestational hypertension \nand preeclampsia in \nwomen with preceding \nendometriosis.\n1998 to 2012\nEndometriosis \ngroup\n(2578)\nControl group\n(10312)\npreeclampsia\nHypertensive \ndisorders.\npreterm deliveries\nLow birth weight\nLi et al. \n(2017)\nRetrospective Cohort \nStudy.\nTo explore the obstetrical \nand neonatal outcomes of \npregnancies complicated \nby endometriosis\n2011 to 2013\nEndometriosis \ngroup\n(98)\nControl group\n(300)\nGestational \ndiabetes \nmellitus\nplacenta Previa\npostpartum \nhaemorrhage\npreterm deliveries\nFarland \net al. \n(2019)\nProspective cohort study.\nto explore the maternal \nand neonatal outcomes \nof pregnancies associated \nwith endometriosis\n1989\nEndometriosis \ngroup (8875)\nControl group\n(196,722)\nGestational \ndiabetes \nmellitus \nHypertensive \ndisorders\nStill birth\nConti \net al.\n (2014)\nMulti-centric, \nobservational, and cohort \nstudy.\nTo evaluate pregnancy, \ndelivery, and neonatal \noutcomes in singleton \nprimiparous versus \nmultiparous women with \nor without endometriosis\nEndometriosis \ngroup\n(316)\nControl group\n(1923)\nGestational \ndiabetes \nmellitus\nPreterm Delivery\nLow birth weight\nMiura \net al. \n(2019)\nCase-control study.\nAdverse effects of \nendometriosis on \npregnancy\n2010 to 2017\nEndometriosis\nGroup\n(316)\nControl group\n(1923)\nRisk of \nplacenta Previa \nPostpartum \nhaemorrhage\nGestational \nDiabetic \nmellitus\nPreterm Delivery\nBerlac \net al. \n(2017)\nNational cohort study\nto assess the obstetrical \ncomplications and \nneonatal outcomes in \nwomen with endometriosis\n2007 to 2014\nEndometriosis \ngroup\n(135) Control \ngroup\n(61,400)\nplacenta Previa\npostpartum \nhaemorrhage\nno neonatal \ncomplications \nwere noted\nTable 1. (Continued)\nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75\n\n71\nThe results of the eight selected studies lead \nto the that endometriosis during pregnancy \ncan cause negative pregnancy outcomes for \nboth women and neonates. According to the \nresults, postpartum haemorrhage, emergency \ncaesareans, placenta Previa, Hypertensive \ndisorders, preeclampsia, and GDM are \nidentified as common maternal outcomes of \npregnancies diagnosed with endometriosis. \nPreterm deliveries, low birth weight, and \nstillbirth are identified as common neonatal \noutcomes. Therefore, the two main themes \nemerged after analysing the findings are as \nfollows: (i) Theme 1- Pregnant mothers are at \nhigh risk and (ii) Theme 2- Keep awareness of \nneonates.\nPregnant mothers are at high-risk.\nEndometriosis has been linked to several \nadverse pregnancy outcomes in previous \nstudies (Brosens et al., 2012; Chen et al., \n2018).  However, Maggiore et al. (2017) \npublished two interesting and detailed studies \nwhich displays that  the risk of endometriosis-\nrelated complications during pregnancy is \nlow. However, this study identified that among \nthe study participants with endometriosis, \na high incidence of placenta previa was \ndetected as one of the most frequent \nendometriosis pregnancy outcomes (Uccella \net al., 2014; Farland et al., 2019). These \nresults are in line with the previous research \nthat has stressed the connection between \nendometriosis and placenta previa (Maggiore \net al., 2017). In addition, researchers have \nfound an increase in placenta previa. This \nis a condition that affects only women with \ndeep infiltrative endometriosis. Pregnant \nwomen with endometriosis generally need \nto be reassured about the course of their \npregnancy (Maggiore et al., 2017). Moreover, \ncurrent studies show that the women with \nendometriosis have a higher incidence of \nemergency caesarean sections and lower \nvaginal delivery rates for both selective and \nnon-selective purposes. Previously, a similar \npattern of emergency caesarean section was \nobserved in several studies, demonstrating the \nsame fact (Exacoustos et al., 2016). Similarly, \ncurrent studies have observed that obstetric \ncomplications such as placenta accreta \nand postpartum bleeding are significantly \nassociated with endometriosis.\nOn the other side, obstetrical problems, \nsuch as placenta accreta and postpartum \nhaemorrhage, were found to be substantially \ncorrelated with endometriosis in the current \nstudy. Marcellin et al. (2015) established that \nthe decidua of women with endometriosis \ncan produce endometriosis-like lesions as it \nencounters the fetal membranes in an in-vitro \nanalysis. Furthermore, this finding may help \nin explaining the increased risk of placenta \naccreta and postpartum haemorrhage.  In \naddition, the study found that women with \na history of endometriosis were at increased \nrisk of developing gestational diabetes \n(GDM) or hypertensive pregnancy disorders. \nThe finding was also published in a recent \nmeta-analysis of 12 studies, which found that \nwomen with endometriosis had a 26% higher \nrisk of GDM and hypertensive disease than \nwomen without endometriosis (Maggiore et \nal., 2017). Furthermore, the endometriosis \ndisease stage has been linked to heterogeneity \nin the relationship between endometriosis and \nhypertensive disorders of pregnancy (Harada \net al., 2016). However, the current study \nshows that the entire population is at increased \nrisk of hypertensive pregnancy disorders, and \nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75\n\n72\nthe relationship is stronger in the second and \nsubsequent pregnancies (Farland et al., 2019). \nIn the current study, it was revealed that \nwomen with prior diagnosed endometriosis, \non the other hand, had a higher rate of \nPreeclampsia in subsequent pregnancies than \nwomen without endometriosis. According \nto Maggiore et al. (2017), a recent meta-\nanalysis of 13 studies also suggests that \nwomen with endometriosis are at increased \nrisk of preeclampsia (95%). Women who \nhave previously had endometriosis are more \nlikely to develop preeclampsia in subsequent \npregnancies and should have enhanced \nmaternal and fetal monitoring.\nKeep awareness of neonates\nEndometriosis causes complicated \noutcomes in neonates, similar to maternal \ncomplications. Women with a history of \nendometriosis were found to have a higher \nrisk of stillbirth or intrauterine death, preterm \nbirth, and low birth weight; all of which are \ncommon neonatal outcomes. According to \na recent study, women with endometriosis \nare at increased risk of preterm birth before \n34 weeks of gestation (Farland et al., 2016). \nGlavind et al. (2017) reported in a recent \nstudy in the Aarhus Birth cohort that women \nwith endometriosis are at increased risk of \npreterm delivery. Endometriosis causes local \nand systemic inflammation in women (Mu et \nal., 2018).  As Goldenberg et al. (2008) states, \ninflammation is one mechanism thought \nto be increasing the risk of preterm birth in \nthe endometriosis groups, compared to the \ncontrols. Leyland et al. (2010) contend that \nendometriosis can cause growth restriction \ndue to insufficient uterine contractility and \nimproper placentation. Current studies \nconfirm that pregnancy in women with \nendometriosis is highly associated with low \nbirth weight compared to women without \nendometriosis. Moreover, the current study \nshows an increased risk of neonatal death \nassociated with spontaneous abortion and \nectopic pregnancy compared with women \nwith no history of endometriosis. A recent \nmeta-analysis discovered that women with \nendometriosis have a 75% per cent higher risk \nof spontaneous abortion and a 21% and 29% \nper cent higher risk of stillbirth, respectively \n(Lalani et al., 2018). Progesterone resistance \nin endometriosis patients is thought to cause \nthe deregulation of genes involved in embryo \nimplantation, which could result in pregnancy \nloss (Vannuccini et al., 2016).\nConclusions\nEndometriosis increases a woman’s risk \nof significant negative prenatal, fetal, and \nneonatal outcomes. The women who have \npreviously been diagnosed with endometriosis \nare at a high risk of having placenta previa, \npostpartum haemorrhage, and hypertension \ndisorders as maternal outcomes. On the other \nhand stillbirth, preterm birth, and Low birth \nweight were identified as common neonatal \noutcomes of pregnancies diagnosed with \nendometriosis. These results inform women \npreviously diagnosed with endometriosis of \npotential obstetric complications associated \nwith endometriosis and provide prejudices \nor recommendations during the prenatal \nperiod. In addition, close monitoring by \nhealth professionals should be continued and \nprepared to overcome ongoing complications. \nThe neonatal intensive care unit should be \nnotified and prepared before delivery to avoid \nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75\n\n73\nunnecessary delays in managing neonatal \ncomplications. Finally, even though the \npurpose of this review was to integrate the \navailable knowledge on this significant topic, \nit is still unknown how endometriosis worsens \npregnancy outcomes.\nReferences\nAmerican Society for Reproductive Medicine \n(ASRM) (1996). Revised American \nSociety for Reproductive Medicine \nclassification of endometriosis. \nFertility and Sterility, 67, 817-821.\nBerlac, J. F., Hartwell, D., Skovlund, C. \nW., Langhoff-Roos, J. & Lidegaard, \nO. (2017). Endometriosis increases \nthe risk of obstetrical and neonatal \ncomplications. 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C., & Petraglia, F. (2016). Infertility \nand reproductive disorders: impact \nof hormonal and inflammatory \nmechanisms on pregnancy \noutcome. Human reproduction \nupdate, 22(1), 104-111.\nVelasco, J. A., Mahutte, N. G., Corona, \nJ., Zúñiga, V ., Gilés, J., Arici, A., \n& Pellicer, A. (2004). Removal \nof endometriomas before in vitro \nfertilization does not improve fertility \noutcomes: a matched, case-control \nstudy. Fertility and Sterility , 81(5), \n1194-1197.\nZullo, F., Spagnolo, E., Saccone, G., Acunzo, \nM., Xodo, S, Ceccaroni, M., & \nBerghella, V . (2017). Endometriosis \nand obstetrics complications: a \nsystematic review and meta-analysis/ \nFertility and Sterility, 108(4), 667-\n672.\nIdentification of Common Adverse Outcomes of Pregnancies Diagnosed with \nEndometriosis:  Review of Past Studies\nPage 66-75","source_license":"CC0","license_restricted":false}