{"paper_id":"87faac7a-9691-4d95-b298-e8c2e5ed02d6","body_text":"Abstract\nPurpose: Researching reproductive outcome after laparoscopic radical resection of grade III and IV \nendometrial lesions. \nMethods and Materials: A retrospective analysis of 54 women was carried out. The patients underwent \nlaparoscopic radical resection in the Gynecology Department of a secondary health care center between \nJanuary 2009 and December 2013. Diagnostic investigation, with histological confirmation of moderate \nto severe endometriosis, preceded surgical intervention in a multidisciplinary setting. Thirty seven of the \n54 patients had an active desire for pregnancy. The outcome measure was the number of pregnancies in \nthe subgroup of 37 women with an active desire for pregnancy. \nResults: Within the subgroup of 37 patients, 28 women became pregnant within the study period. \nTwelve patients became pregnant spontaneously and 16 had medically assisted pregnancies. Within the \nmedically assisted group, 4 patients conceived after Intra-Uterine Insemination (IUI) and 12 after In-\nVitro Fertilization (IVF). The pregnancy rate was 76%, a result similar to findings of earlier studies.\nConclusion: The results of this retrospective analysis suggest that extensive laparoscopic surgery for \nmoderate to severe endometriosis has a beneficial effect on fertility in both spontaneous and medically \nassisted pregnancies.\nOutcome of Fertility after Radical Conservative Surgery in Grade III-IV \nEndometriosis Lesions: A Retrospective Analysis\nPublication History:\nReceived: January 21, 2016\nAccepted: May 17, 2016\nPublished: May 19, 2016\nKeywords:\nDeep infiltrating endometriosis, \nPregnancy rate, Infertility, \nLaparoscopy, Colorectal \nEndometriosis, Dysmenorrhea, IVF\nResearch Article Open Access\nBackground\nEndometriosis is a prevalent condition defined by endometrial \ntissue outside the uterine cavity. The condition is estrogen-dependent \nand occurs mainly during the fertile period of women [1] .Prevalence \nis hard to quantify as definitive diagnosis requires laparoscopic \ninvestigation. Prevalence is estimated to be between 5 and 7% in all \nwomen [2]; in infertile populations prevalence may be up to 30% [3].\nSome observational studies describing an elevated chance of \npregnancy using GnRH without surgical approach exist, although the \n2014 Cochrane review of these studies showed little evidence. Benefit \nof this approach remains controversial [12]. A recent, randomized \ntrial confirmed that the use of GnRH agonists does not improve \nfertility in grade III to IV endometrial lesions [13].\nThe surgical approach of grade III to IV endometriosis lesions \nis often discussed in the current literature. The aims of the surgical \napproach are to remove all visible endometrial lesions using classical \nexcision or ablation, restoring normal anatomy by opening adhesions. \nDiscussion remains over whether the surgical approach is beneficial \nin relation to fertility in cases with grade III to IV endometrial lesions. \nConsidering the invasive character of this approach, and the high risk \nof severe complications, such as transection of a ureter, pelvic abscesses \nor rectal damage, this discussion is extremely relevant [14, 15]. Many \nstudies researching the outcome on fertility after laparoscopic surgery \nfor grade III to IV lesions are published, with often contradictory \nresults. Adamson G, et al. [16] conducted an extensive meta-analysis \non this topic in 1996, concluding that the surgical approach for grade \nIII and IV lesions increases the chance of pregnancy by up to 44% \nin the laparoscopic approach, and up to 62% in laparotomy. Y et \ndiscussion persists over which surgical approach gives the maximal \nchance of pregnancy and minimal chance of complications. A recent \nprospective cohort study by Vercellini P . et al. [17] showed that, in \nthe case of rectovaginal endometriosis, the surgical approach did \nnot increase fertility in comparison to the control group with the \nconservative approach.\n*Corresponding Author: Dr. Baekelandt Jan, Department of Gynaecology \nand Obstetrics, AZ Imelda Hospital, Bonheiden, Belgium; E-mail:  \njan.baekelandt@imelda.be \nCitation: Baekelandt J, Vandenbroucke A, Aelvoet C, Pelckmans S, Bosteels J \n(2016) Outcome of Fertility after Radical Conservative Surgery in Grade III – IV \nEndometriosis Lesions: A Retrospective Analysis. Int J Gynecol Clin Pract 3: 119. \ndoi:  http://dx.doi.org/10.15344/2394-4986/2016/119\nCopyright: © 2016 Baekelandt et al. This is an open-access article distributed \nunder the terms of the Creative Commons Attribution License, which permits \nunrestricted use, distribution, and reproduction in any medium, provided the \noriginal author and source are credited.\nInternational Journal of\nGynecology & Clinical Practices\nJan Baekelandt¹*, Annemarie Vandenbroucke¹, Chris Aelvoet ², Sophie Pelckmans¹and Jan Bosteels¹\n1Department of Gynaecology and Obstetrics, AZ Imelda Hospital, Bonheiden, Belgium\n2Department of Surgery, AZ Imelda Hospital, Bonheiden, Belgium\nInt J Gynecol Clin Pract                                                                                                                                                                                          IJGCP , an open access journal                                                                                                                                          \nISSN: 2394-4986                                                                                                                                                                                                       Volume 3. 2016. 119                                            \n                     Baekelandt et al., Int J Gynecol Clin Pract 2016, 3: 119\n                     http://dx.doi.org/10.15344/2394-4986/2016/119\nThe question remains whether the surgical approach to grade III \nand IV lesions improves the chance of pregnancy in patients with \nendometriosis. This question is central to our study, where the surgical \napproach for endometriosis is performed in a multidisciplinary \nsetting. \nMaterial and Methods\nAll patients who were operated on between January 2009 and \nDecember 2013 were included in this retrospective follow-up. They \nwere treated with a radical conservative endometriosis removal. \nAll patients were diagnosed preoperatively with grade III to IV \nendometriosis by clinical evaluation, transvaginal ultrasound, MRI \nand diagnostic laparoscopic surgery. This included rectovaginal \nplaques, deep infiltrativenodules, endometriomata, and grade IV \nsacro-uterine adhesions. Preoperatively all patients were treated with \nGnRH-analogues for 3 months. The purpose of this treatment was to \nreduce the volume of the lesions as much as possible prior to surgery.\nPostoperative histological survey confirmed the diagnosis of \nendometriosis in all patients. Histological criteria were the presence \nof glandular endometrial tissue or endometrial stroma in the biopsies. \nSymptoms were clinically monitored pre- and postoperatively per \nconsultation in the Department of Gynecology at this center. \nOne patient was lost to follow-up and her data were not included in \nthis survey. During post-operative contact, patients were questioned \n\nInt J Gynecol Clin Pract                                                                                                                                                                                          IJGCP , an open access journal                                                                                                                                          \nISSN: 2394-4986                                                                                                                                                                                                       Volume 3. 2016. 119                                            \nCitation: Baekelandt J, Vandenbroucke A, Aelvoet C, Pelckmans S, Bosteels J (2016) Outcome of Fertility after Radical Conservative Surgery in Grade III – IV \nEndometriosis Lesions: A Retrospective Analysis. Int J Gynecol Clin Pract 3: 119. doi:  http://dx.doi.org/10.15344/2394-4986/2016/119\n       Page 2 of 4\nhydrosalpinx (3%). IVF was commenced immediately after surgery. \nIn 11 patients, surgery was extended to the rectal wall (30%). Lesions \nwere removed either by shaving the rectal wall, or by rectal resection. \nFive patients underwent radical rectum resection (14%) and shaving \nwas performed in six patients (16%). The decision to use either of \nthese techniques was based upon invasion depth of the lesions in the \nrectal wall. In 7 patients surgical re-intervention was necessary due to \npersisting pelvic pain(19%).These results are shown in Table 3.\nResults\nIn the subpopulation of 37 patients, 18 spontaneous pregnancies \noccurred in 12 women. Two women became pregnant three times, two \nwomen twice and seven women once. The median period to conception \nin this subpopulation was 6 months (1-32). Four pregnancies were \nconceived using Intra-Uterine Insemination after ovarian induction \nin 4 women. The time to conception was 6.5 months (3-15). Thirteen \nwomen in total tried IUI. Thirteen pregnancies were conceived after \nIVF in 12 women. In these pregnancies 2 women combined IVF with \nIntra-Cytoplasmic Sperm Injection (ICSI). \nA total number of 17 women attempted fertility treatment using \nIVF . As 12 of them fell pregnant, the total success rate of postoperative \nIVF treatment was 71%. \nabout child wish, smoking behavior, spontaneous pregnancy, \nmedically assisted pregnancies, sperm examination and other \nimportant non-medical parameters such as separation of partners. \nOur primary endpoint postoperatively was number of pregnancies, \nincluding both spontaneous and medically assisted pregnancies.\nOperative Procedure\nThe patient was placed in the lithotomy position under general \nanaesthesia. A double-J stent was placed in each ureter and a Foley \ncatheter was inserted into the bladder. All procedures were performed \nby BJ (first author) in a multidisciplinary setting where rectal resections \nwere performed by AC (third author). A pneumoperitoneum was \ncreated by placing a Verress needle and insufflating 3 liters of CO₂. Two \n10 mm trocars were placed: one in the umbilicus and one in the right \niliac fossa. Five mm trocars were placed suprapubically and in the left \niliac fossa. All endometriotic lesions were excised using monopolar \nand bipolar instruments. All bladder endometriosis was excised using \nmonopolar instruments; the bladder was sutured laparoscopically. For \nendometriomas a cystectomy was performed. Rectovaginal nodules \nwere excised after rectal shaving using a monopolar hook electrode. \nWhen a rectal resection was indicated, a reanastomosis was performed \nusing transanal stapling.\nPatients\nThe number of women operated between January 2009 and \nDecember 2013 was 54.\nPreoperative pain was scored in 4 grades of dysmenorrhea. \nThe median score was 2 [0-4]. Postoperative pain was not scored \nsystematically, and pre- versus postoperative pain could therefore not \nbe compared.\nWithin the 54 patient group, there were 14 patients (26%) for \nwhom the indication for surgery was pain-reduction and not \ninfertility. This subgroup was excluded. The remaining40 patients \n(74%) were operated due to subfertility and active child wish. Patients \nwith conflicting fertility factors, such as active smoking behavior \nand obesity (BMI >30) [18], were also excluded. Two patients were \nexcluded as their relationship ended shortly after surgery. One patient \nwas lost to follow-up, and her data were excluded from this study. \nAfter these exclusions a subpopulation of 37 patients remained (69%) \nand an overview of their results is presented in Table 1.\nThe median duration of preoperative sub fertility was 19,4 months \n(0-72). The WHO definition of 2009 defines infertility as an absence \nof pregnancy for at least 12 months [19], thus this population was \nclassified as infertile. The median age at surgery was 31,5 years [23-\n38], median BMI 23,4 (17,7-31,1), median preoperative parity was 0 \n[0-1],and gravidity was 0 [0-3] Table 2.\nThe anatomic characteristics of the population are more \nheterogeneous. Within the subgroup of 37 patients, there were 26 deep \nnodules (70%), 10 vesical nodules (27%), 7 accompanying extensive \nperitoneal lesions (19%),and 12 accompanying endometriomata \n(32%).\nTwo patients had an adnexectomy for extensive endometrial cysts \n(5%), two patients had an unilateral Fallopian tube resection (5%), \nand one patient had a bilateral Fallopian tube resection for bilateral\nInitial population n = 54 (100%)\nAntalgic indication n= 14(26%)\nPostoperative breakup n = 2 (3%)\nLost to follow-up n = 1 (2%)\nBMI > 35 n = 0    (0%)\nActive smoking n = 0 (0%)\nIncluded patients n = 37 (69%)\nTable1: Exclusion criteria.\nCharacteristics Median [range]\nAge 31,5 [23-38]\nPre-operative gravidity 0 [0-3]\nPre-operative parity 0 [0-1]\nDysmenorrhea 2 [0-4]\nBMI 23,4 [17-7;31-1]\nSubfertile period (months) 19,4 [0-72]\nTable 2: Patientdemography.\nCharacteristics n = 37 (100%)\nDeep Nodule n= 26 (70%)\nVesicalnodule n = 10 (27%)\nPeritoneallesions n =  7 (19%)\nEndometriomata n = 12(32%)\nAdnexectomy n = 2(5%)\nUnilat. Fallopian resection n = 2(5%)\nBilat.Fallopian resection n= 1(3%)\nRectal resection n= 5 (14%)\nShaving of the rectum n= 6(16%)\nTable 3: Type of surgery.\n\nInt J Gynecol Clin Pract                                                                                                                                                                                          IJGCP , an open access journal                                                                                                                                          \nISSN: 2394-4986                                                                                                                                                                                                       Volume 3. 2016. 119                                            \nCitation: Baekelandt J, Vandenbroucke A, Aelvoet C, Pelckmans S, Bosteels J (2016) Outcome of Fertility after Radical Conservative Surgery in Grade III – IV \nEndometriosis Lesions: A Retrospective Analysis. Int J Gynecol Clin Pract 3: 119. doi:  http://dx.doi.org/10.15344/2394-4986/2016/119\n       Page 3 of 4\ndrawing conclusions difficult. Another downside of this analysis is that \ndue to lack of data, only a pregnancy ratecould be determined, and \nnot acumulative pregnancy rate, which would make analysis of the \nresults more accurate. Further prospective, randomized studies with \nan adequate control arm are required in the future, not only focusing \non pregnancies but also on complications, relapses and quality of life \nin order to make a complete interpretation of the effects of surgical \nintervention. Further research should be conducted to understand \nthe physiological mechanisms of endometriosis and the concomitant \neffects on fertility. Results of such research will eventually lead to an \napproach other than surgical intervention or medical treatment with \nGnRH agonists [23].\nFurther challenges of surgical intervention for endometriosis are \nwhen to proceed with medically assisted pregnancy in the post-\noperative setting, and how long one should wait for spontaneous \nconception, to prevent starting premature and expensive IVF \ntreatment. Alternatively, how long can one wait before starting IVF \ntreatment so that time is not lost in worse prognostic categories. \nAdamson et al. published an interesting scoring system in 2010: \nthe Endometriosis Fertility Index (EFI). This staged scoring system \nattempts to quantify post-operative success rate of spontaneous \nconception (0-10) using several factors, including extensiveness \nof endometrial lesions, post-operative Fallopian functionality and \nhistorical factors [24]. This tool was verified in 2013 as a moderate \nqualitative indicator [25]. This scoring system can aid in deciding \nwhen to attempt medically assisted pregnancy in the post-operative \nsetting.\nCompeting Interests\n \nThe authors declare that they have no competing interests.\n \nReferences\n1. Jacobson TZ, Duffy JM, Barlow DH, Farquhar C, Koninckx PR et al. \n(2008) Laparoscopic surgery for subfertility associated with endometriosis. \nCochrane Database Syst Rev.\n2. Ozkan S, Murk W, Arici A (2008) Endometriosis and infertility: epidemiology \nand evidence-based treatments.  Ann N Y Acad Sci 1127: 92-100.\n3. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, \net al. (2004) Incidence of laparoscopically confirmed endometriosis by \ndemographic, anthropometric, and lifestyle factors.  Am J Epidemiol 160: \n784-796.\n4. Davis CJ, McMillan L (2003) Pain in endometriosis: effectiveness of medical \nand surgical management.  Curr Opin Obstet Gynecol 15: 507-512.\n5. Bulun SE (2009) Endometriosis.  N Engl J Med 360: 268-279.\n6. [No authors listed] (1985) Revised American Fertility Society classification \nof endometriosis: 1985.  Fertil Steril 43: 351-352.\n7. Yap C, Furness S, Farquhar C (2004) Pre and post operative medical \ntherapy for endometriosis surgery.  Cochrane Database Syst Rev : \nCD003678.\n8. D'Hooghe TM, Debrock S, Hill JA, Meuleman C (2003) Endometriosis and \nsubfertility: is the relationship resolved?  Semin Reprod Med 21: 243-254.\n9. Bulun SE (2009) Endometriosis.  N Engl J Med 360: 268-279.\n10. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, et al. (2008) \nPathogenic mechanisms in endometriosis-associated infertility.  Fertil Steril \n90: 247-257.\n11. Witz CA, Burns WN (2002) Endometriosis and infertility: is there a cause \nand effect relationship?  Gynecol Obstet Invest 53 Suppl 1: 2-11.\n12. Brown J, Farquhar C (2014) Endometriosis: an overview of Cochrane \nReviews.  Cochrane Database Syst Rev 3: CD009590.\nCombining all these results, 28 of 37 women became pregnant, \nbringing the postoperative pregnancy rate to 76%. These results are \npresented in Table 4.\nDiscussion\nA pregnancy rate of 76% confirms earlier results presented by \nAdamson G et al. (44% pregnancy rate after laparoscopy and 62% \nafter laparotomy). Daraï et al. found a pregnancy rate of 45,5% after \nlaparoscopic resection or shaving of the rectal wall. In this study, a \nhigher percentage of spontaneous pregnancies were reported (75%) \n[20] . A recent large prospective cohort study showed a pregnancy \nrate of 51%. This study researched the benefit of rectum resection in \npatients with grade III to IV lesions [21].\nOur results show a pregnancy rate of 76%, which is higher than the \naverage percentages found in recent literature. A possible explanation \nfor this difference is the relatively small population size in this study. \nAs our study only included 37 patients, a form of selection bias may \nexplain the higher results compared to those found in the literature.\nMedian time to conception was 6 months with a range of 1-32. This \nnumber is similar to the result of Daraï et al., [21]who found a median \ntime to conception of 8 months with a range of 3-13.\nA striking conclusion in our study is the high success rate of post-\noperative IVF treatment. Bianchi P , et al. illustrated that radical \nresection of Deep infiltrative Endometriosis significantly improved \nIVF treatment success rates. In their prospective cohort analysis \na pregnancy rate of 24% without and 41% with surgery was found \n[22]. In our study, the post-operative success rate of IVF treatment \nwas remarkably higher, namely 71%. A possible explanation for this \nfinding is again the smaller number of patients included (37 patients \nin our study versus 179 patients in the study by Bianchi et al.) [22], as \nwell as different characteristics of the selected populations. The study \nperformed by Bianchi et al. mostly described women with DIE, while \nin this analysis we focused on grade III to IV lesions with rectovaginal \ninvolvement. \nConsidering the evaluation of post-operative pain, no standardized \npain scoring system was used. Seven of 37 (n=7, 19%) patients needed \nsurgical re-intervention due to persisting pelvic pain. \nAnalysis of results found in this study confirms that radical \nsurgery improves fertility in grade III to IV endometrial lesions. \nCareful interpretation of these results however is recommended. The \nretrospective character of this study, variable time of follow-up, lack of \na well-defined control population, and limited population size, make \nTotal population n = 37 Pregnancies\nSpontaneous pregnancy n = 12                         18\nNon-spontaneous pregnancy n = 16                         17\nIUI conception n = 4                            4\nIUI no conception n = 9                            0\nIVF conception n = 10                         11\nIVF + ICSI conception n = 2                            2\nIVF no conception n = 5                            0\nPregnancy Rate 76%\nTable 4: Pregnancy rate after surgery.\n\nInt J Gynecol Clin Pract                                                                                                                                                                                          IJGCP , an open access journal                                                                                                                                          \nISSN: 2394-4986                                                                                                                                                                                                       Volume 3. 2016. 119                                            \nCitation: Baekelandt J, Vandenbroucke A, Aelvoet C, Pelckmans S, Bosteels J (2016) Outcome of Fertility after Radical Conservative Surgery in Grade III – IV \nEndometriosis Lesions: A Retrospective Analysis. Int J Gynecol Clin Pract 3: 119. doi:  http://dx.doi.org/10.15344/2394-4986/2016/119\n13. Loverro G, Carriero C, Rossi AC, Putignano G, Nicolardi V, et al. (2008) \nA randomized study comparing triptorelin or expectant management \nfollowing conservative laparoscopic surgery for symptomatic stage III and \nIV endometriosis. Eur J Obstet Gynecol Reprod Biol 136:194-198.\n14. Ford J, English J, Miles WA, Giannopoulos T (2004) Pain, quality of life and \ncomplications following the radical resection of rectovaginal endometriosis.  \nBJOG 111: 353-356.\n15. Mohr C, Nezhat FR, Nezhat CH, Seidman DS, Nezhat CR (2005) Fertility \nconsiderations in laparoscopic treatment of infiltrative bowel endometriosis. \nSee comment in PubMed Commons below JSLS 9: 16-24.\n16. Adamson GD1, Pasta DJ (1994) Surgical treatment of endometriosis-\nassociated infertility: meta-analysis compared with survival analysis. See \ncomment in PubMed Commons below Am J Obstet Gynecol 171: 1488-\n1504.\n17. Vercellini P, Pietropaolo G, De Giorgi O, Daguati R, Pasin R, et al. \n(2006) Reproductive performance in infertile women with rectovaginal \nendometriosis: is surgery worthwhile?  Am J Obstet Gynecol 195: 1303-\n1310.\n18. Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, et al. \n(2011) Effect of body mass index on IVF treatment outcome: an updated \nsystematic review and meta-analysis.  Reprod Biomed Online 23: 421-439.\n19. Zegers-Hochschild F, Adamson G, Muzon J, Ishihara O, Mansour R, et \nal. (2009) International Committee for Monitoring Assisted Reproductive \nTechnology (ICMART) and the World Health Organization (WHO) revised \nglossary of ART terminology. Fertil Steril 92: 1520-1524.\n20. Daraï E, Marpeau O, Thomassin I, Dubernard G, Barranger E, et al. \n(2005) Fertility after laparoscopic colorectal resection for endometriosis: \npreliminary results.  Fertil Steril 84: 945-950.\n21. Meuleman C, Tomassetti C, Wolthuis A, Van Cleynenbreugel B, Laenen \nA, et al. (2014) Clinical outcome after radical excision of moderate-severe \nendometriosis with or without bowel resection and reanastomosis: a \nprospective cohort study.  Ann Surg 259: 522-531.\n22. Bianchi PH, Pereira RM, Zanatta A, Alegretti JR, Motta EL, et al. (2009) \nExtensive Excision of Infiltrative Endometriosis before In Vitro Fertilization \nSignificantly Improves Pregnancy Rates. J Minim Invasive Gynecol 16: \n174-180.\n23. D'Hooghe TM, Debrock S, Meuleman C, Hill JA, Mwenda JM (2003) Future \ndirections in endometriosis research.  Obstet Gynecol Clin North Am 30: \n221-244.\n24. Adamson GD, Pasta DJ (2010) Endometriosis fertility index: the new, \nvalidated endometriosis staging system.  Fertil Steril 94: 1609-1615.\n25. Tomassetti C, Geysenbergh B, Meuleman C, Timmerman D, Fieuws S, \net al. (2013) External validation of the endometriosis fertility index (EFI) \nstaging system for predicting non-ART pregnancy after endometriosis \nsurgery.  Hum Reprod 28: 1280-1288.\n     Page 4 of 4","source_license":"CC0","license_restricted":false}