{"paper_id":"f9aff90e-4984-47ca-8931-ba60d96a1044","body_text":"Chaichian et al. BMC Women’s Health           (2022) 22:33  \nhttps://doi.org/10.1186/s12905-022-01607-2\nRESEARCH\nHyaluronic acid gel application \nversus ovarian suspension for prevention \nof ovarian adhesions during laparoscopic \nsurgery on endometrioma: a double-blind \nrandomized clinical trial\nShahla Chaichian1, Seyed Reza Saadat Mostafavi2*, Abolfazl Mehdizadehkashi3*, Zahra Najmi4, \nKobra Tahermanesh3, Mahin Ahmadi Pishkuhi1, Fatemeh Jesmi1 and Bahram Moazzami1 \nAbstract \nBackground: This study aimed to compare the effect of ovarian suspension and hyaluronic acid gel to prevent re-\nadhesions after laparoscopic endometrioma surgery.\nMethods: This randomized clinical trial was conducted at Rasoul-e-Akram and Pars Hospitals, Tehran, Iran, 2016-\n18. Fifty patients with bilateral endometrioma and pelvic adhesions, the candidates of laparoscopic surgery, were \nincluded. In each patient, at the end of ovarian cystectomy and adhesiolysis, one of the ovaries was randomly sutured \nto the abdominal wall, and the HYAcorp Endogel covered the other; the adhesion rate was compared between the \ngroups by ultrasonography, three-month after surgery.\nResults: Mean age of patients was 32.6 years. Presurgical variables were similar between right and left ovaries and \nthe study groups (P > 0.05). Postsurgical ultrasonography showed that ovarian soft markers, including < 1/3 ovarian \nadhesions (minimal adhesions) in 80.5% of ovaries of the Endogel group and 35.5% of the ovarian suspension group \n(P < 0.001) with higher ovarian mobility in the Endogel group (65% vs. 22%) (P = 0.001). In addition, site-specific ten-\nderness and ovarian fading margin were lower in the Endogel group (P < 0.001).\nTrial registration Clinical trial registry number: IRCT2015081723666N1, 12.19.2015, Date of registration: 01/02/2016; \nhttps:// en. irct. ir/ trial/ 20174? revis ion= 20174. Date and number of IRB: 2015, I.R.IUMS.REC.1394.24703.\nConclusion: Hyaluronic acid gel can be more effective than ovarian suspension in preventing ovarian adhesions \nafter laparoscopic treatment of endometriosis.\nKeywords: Adhesions, Hyaluronic acid, Laparoscopy, Endometriosis, Ovarian suspension\n© The Author(s) 2022. 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/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nIntroduction\nAdhesions are considered an important etiology of pain, \ninfertility, bowel and ureteral obstructions in patients \nwith endometriosis [1] and are supposed to be formed by \ninflammation, reduced apoptosis, and increased angio -\ngenesis and neurogenesis in endometriotic tissues [2], \nsignificantly intensified at higher stages of endometriosis \nOpen Access\n*Correspondence:  reza_sm1357@yahoo.com; amehdizadehkashi@yahoo.\ncom\n2 Department of Radiology, Iran University of Medical Sciences, Tehran, \nIran\n3 Endometriosis Research Center, Iran University of Medical Sciences, \nTehran, Iran\nFull list of author information is available at the end of the article\n\nPage 2 of 8Chaichian et al. BMC Women’s Health           (2022) 22:33 \n[3]. As adhesions can make the surgical procedure more \ncomplicated and time-consuming and cause several \nproblems, such as the continuation of pain and infertil -\nity, it is necessary to reduce the risk of adhesion in each \nsurgical procedure [4].\nAlthough numerous surgical techniques, such as ovar -\nian suspension, traditionally used to separate the ovaries \nfrom the pelvis [5–7], or other preventive methods [8], \nby using normal saline, heparinized lactated ringer solu -\ntion, corticosteroids, and peritoneal lavage by Dextran \n32% [9], polytetrafluoroethylene (Gore-Tex) and oxidized \nregenerated cellulose (Interceed), chemically modified \nsodium hyaluronic acid/carboxymethylcellulose (Sepra -\nfilm) [10] have been approved as an efficient method for \nthe adhesion prevention, none of them could completely \nprevent adhesion recurrence after laparoscopic surgery \nfor endometriosis.\nHyaluronic acid gel, known as hyalobarrier gel (used \nunder different brands), is suggested to be used alone or \nin combination with carboxymethylcellulose, membrane \nto prevent adhesions [11, 12]. Furthermore, in the present \nstudy, we aimed to compare the effect of hyalobarrier gel \nand ovarian suspension during laparoscopic cystectomy \nfor treatment of bilateral endometrioma on postopera -\ntive pelvic adhesions. To reduce the confounding effect \nof different immunological and inflammatory responses \nof the endometriotic patients, we randomized the ova -\nries instead of randomizing patients, as previously used \nin other bilateral organs [13]. We evaluated the postop -\nerative pelvic adhesions by ultrasound examination as an \naccurate diagnostic tool for assessing pelvic adhesions in \nendometriotic patients [14, 15].\nMethods\nStudy design\nIn the present randomized clinical trial (RCT), patients \nwith severe endometriosis (stages 3 or 4; according to \nrASRM staging system for endometriosis and bilateral \nendometrioma), who referred to Rasoul-e-Akram and \nPars Hospitals, Tehran, Iran, for laparoscopic surgery \nduring 2016 to 2018 were included into the study. To \neliminate or reduce the effect of genetic, epigenetic, and \nimmunologic factors, we decided to allocate the ovaries \nrather than the patients, so 100 ovaries were recruited as \nthe case/control groups of the study. For the allocation of \novaries, a simple randomization technique by application \nof quadruple blocks was used. We used concealed enve -\nlopes opened by a technician that informed the surgeon \nduring laparoscopy for the concealment.  For blinding \npatients, the sutures for ovarian suspension and wound \nrepair on the opposite abdominal wound were done by \n3-0 Vicryl and cut simultaneously on the 3rd day of the \nsurgery. The sonologist wasn’t aware of the surgical site.\nIn this study, the purpose of ovarian suspension was \nnot clearance of the surgical field. Instead, we aimed to \nmake the ovary far away from the pelvis during the first \nthree days of surgery to prevent scar tissue formation \naround it and prevent the anti-adhesive effect of endogel \napplied  around the opposite ovary.  We could not con -\nsider internal suspension because we have to release the \nsuspended ovary before ending the surgery.\nAccording to Dhanawat’s study [16], three days of \novarian suspension is an appropriate length of time for \npreventing adhesion. At the end of 72  h, the suspended \novary should be returned to the pelvic cavity by releas -\ning the suspension suture. This is especially important for \nendometriosis patients who may need ART, that oocyte \nretravel is crucial and necessitates the appropriate pelvic \npositioning of the ovary.\nThe Ethics Committee of the Iran University of Medical \nSciences approved the study protocol.\nEthics code: I.R.IUMS.REC.1394.24703) and registered \non the Iranian RCT website (IRCT2015081723666N1).\nSample size\nThe study sample size was calculated at 50 ovaries in each \ngroup, using the formula for binary dependent variables, \nconsidering an alpha error of 0.05, study power of 80%, \nand minimum clinically significant difference in the prev-\nalence of postoperative ovarian adhesion between two \nstudy groups at 50% reduction. According to Hoo et  al. \n[6], the prevalence of postoperative ovarian adhesions as \nthe primary outcome in the ovarian suspension group \nwas 38.5% and in the unsuspended group was 51.9%.\nThe study’s inclusion criteria consisted of women \nof reproductive age with clinical and ultrasonography \ndiagnosis of bilateral endometrioma and pain score > 7, \nwho were candidate for laparoscopic surgery and have \nsigned the written informed consent form for the study. \nEvery patient who did not sign the consent form was \nnot included in the study. The exclusion criteria encom -\npassed patients diagnosed with unilateral endometrioma \nor another cyst type (rather than endometrioma) during \nsurgery. Patients who did not refer for a follow-up exami-\nnation and or rejected to continue were excluded from \nthe study.\nThe gynecologist diagnosed endometriosis based on \nclinical and imaging criteria. Diagnosis of bilateral endo -\nmetrioma and presence of adhesions were confirmed \nby the same sonographer. During gynecological exami -\nnation, patients’ pain severity was evaluated by visual \nanalog scale (VAS) and marked by patient herself on a \n10-point Likert scale; patients with a score ≥ 7, who were \nirresponsive to medical treatment, were invited to par -\nticipate to the study. Patients with unilateral endome -\ntrioma or deep endometriosis (D.E.) were not included \n\nPage 3 of 8\nChaichian et al. BMC Women’s Health           (2022) 22:33 \n \nin the study. Before enrolling patients into the study, the \nresearcher explained them the study objectives to the eli -\ngible patients and asked them to read and sign the writ -\nten informed consent. All patients were referred to our \ninfertility clinic for standard recommendations by fertil -\nity experts and possible fertility preservation.\nData collection\nPatients’ demographics, including age, marital status, and \nbody mass index (BMI), were recorded from the hospital’s \nmedical records. Hormonal medications were discontin -\nued three months before laparoscopy (washout period). \nThe ovaries were allocated into two groups of ovarian \nsuspension and hyaluronic gel application using quad -\nruple block randomization, prepared by a statistician, \nby simple randomization method using Excel software \nwithout duplicates. The CONSORT 2010 flow diagram \n(Fig. 1) shows the process of sampling and ovarian alloca-\ntion and utilization of intention to treat policy for analy -\nsis. In the operating room, the responsible technician \nFig. 1 CONSORT 2010 flow diagram of patients’ enrollment into the study\n\nPage 4 of 8Chaichian et al. BMC Women’s Health           (2022) 22:33 \nwas asked to open the result of the randomized block \nto declare the side of ovarian suspension and hyaluronic \ngel application for performing the allocation. Patient and \nsonographer were unaware of the group allocation, and \nthe analyst also analyzed the data with codes instead of \npatients’ names.\nSurgical techniques\nAll patients underwent laparoscopic surgery by the same \nsurgical team. After direct umbilical trocarization by \n11-mm trocar, carbon dioxide  (CO2) insufflation was per-\nformed. Then two 5.5-mm side trocars and one 11-mm \nsuprapubic trocar were inserted. Abdominal and pelvic \ncavity exploration was done by a zero-degree optic, and \nbilateral endometriomas were confirmed. The ovarian \nadhesions to the uterus, contralateral ovary,  bowel, and \nabdominal wall were released. Each ovary was opened by \nscissor, and the cyst wall was separated from the ovar -\nian tissue by gentle tractions and counter tractions, as \nmuch as possible, and by opening the endometrioma, \nits content was aspirated, and the ovaries were repaired \nusing 3-0 Vicryl by mattress suture, after careful hemo -\nstasis, preferably by sutures. Based on the  randomiza -\ntion method, one ovary was sutured by 3-0 Vicryl to the \nabdominal wall (Fig.  2); the suture thread was brought \nout at the site of the relevant  5.5-mm  trocar and then \nanother  5.5-mm  trocar site was sutured by 3-0Vic -\nryl too, so the patient couldn’t find out the ovarian sus -\npension side by looking at the  suture  material (Fig.  3). \nAnother ovary was covered by one sterile pre-filled HYA-\ncorp Endogel (BioScience GmbH, Germany) container, \ninjected all around the ovary via laparoscopic needle. On \nthe third day, the suspended ovary and other abdomi -\nnal sutures were released by cutting the sutures [16, 17]. \nAny patient who was diagnosed with unilateral endo -\nmetrioma or any other cyst (rather than endometrioma) \nduring surgery, patients who did not refer for a follow-up \nexamination, and or rejected to continue the study were \nexcluded from the study.\nStudy outcomes\nThe study’s primary outcome was three-months pelvic \nadhesions surveillance, evaluated by transvaginal ultra -\nsound and comparison with presurgical indices. Revised \nASRM classification and ultrasonography soft mark -\ners (ovarian mobility, site-specific tenderness [SST], and \novarian fading margin) of endometriosis were used to \nexamine the incidence and severity of ovarian adhesions. \nThe secondary outcomes were adhesions to the bladder, \novary, bowel, anterior and posterior peritoneum, pelvic \nand ovarian adhesions, and maximum ovarian diameter \nwere determined by the sonographer and recorded in the \nstudy checklist before and three-months after surgery. \nAny patient who required conversion to laparotomy for \nany reason or became pregnant during the follow-up \nperiod was excluded from the study.\nStatistical analysis\nThe data were described using frequency (percentage) \nfor categorical variables, mean ± standard deviation \n(S.D.) for numeric variables with a normal distribution, \nand median (interquartile range) for numeric variables \nwithout normal distribution, based on the results of \nthe Kolmogorov Smirnov test. According to the results \nof this test, in case of rejection of the normal distribu -\ntion of the data, Wilcoxon test was used to compare the \nL.O.\nFig. 2 A panoramic view of pelvic cavity after suspension of the left \novary to abdominal wall, according to block randomization\nFig. 3 The abdomen’s view at the end of procedure. Note that the \nsuspension thread (3-0 Vicryl) exited from the right 5-mm trocar \nincision and the wound repaired by the same size suture. Then \nright 5-mm incision was repaired similarly by 3-0 Vicryl (We ordinary \nrepair these incisions by 4-0 Vicryl sutures) to blind the patient from \ntreatment modalities\n\nPage 5 of 8\nChaichian et al. BMC Women’s Health           (2022) 22:33 \n \nnumeric variables among the groups. Mc Nemar’s was \nused to compare the percentage of interested outcomes \namong the study groups. The statistical software IBM \nSPSS Statistics for Windows version 21.0 (IBM Corp. \n2012. Armonk, NY: IBM Corp) was used for the statis -\ntical analysis. P values of < 0.05 were considered statisti -\ncally significant.\nResults\nOne hundred ovaries of 50 patients were included in the \nstudy. Two patients became pregnant during the three-\nmonths follow-up period, and one patient required lapa -\nrotomy for bowel resection. So, six ovaries were excluded \nfrom the study. In one patient, the application of Endogel \nand suturing of the ovary were mistakenly performed on \nthe right and left ovary. Still, we decided not to exclude \nthese two ovaries and counted them as the intention to \ntreat group. So, finally, data of 47 patients and 94 ova -\nries were analyzed (Fig.  1). The mean age of patients \nwas 32.6 ± 4.12 years (minimum of 24 and maximum of \n42 years), mean BMI was 23.79 ± 3.07 kg/m2, and 59.6% \nof participants were married. In each patient, both ova -\nries (94 ovaries) were evaluated and treated by either \novarian suspension or Endogel.\nTable  1 indicates the preoperative characteristics \nof ovaries. As shown, there were no differences in the \ncharacteristics of the ovaries of the two arms of the study, \nincluding the maximum diameter of the ovary, ovarian \nmargin adhesion, endometrioma, and ovarian mobil -\nity (P > 0.05). Moreover, the preoperative characteristics \nof ovaries, including ovarian margin adhesion, mobility, \nand fading margin, were not different among the study \ngroups (P > 0.05; Table 1).\nAs indicated in Table  2, after laparoscopy, the Endogel \ngroup had a lower frequency of ovarian adhesion > 1/3 \nand site specific tenderness (SST) (both P < 0.001) and a \nhigher frequency of positive ovarian mobility (P = 0.001) \nand fading ovarian margin < 1/3 (P < 0.001), compared to \nthe ovarian suspension group.\nComparing the frequency of adhesions at different \nsites before and three-months after the surgery showed \nthat the frequency of adhesion to the bladder, right or \nleft ovary, large and small bowel, anterior and posterior \nperitoneum, right and left pelvic areas, as well as sliding \nsigns did not significantly change after the intervention \n(P > 0.05, Table 3).\nDiscussion\nThe ultrasonographic parameters (ovarian adhesion, \nmobility, fading margin, and SST) showed the superiority \nof the application of Endo gel on the ovaries compared \nto ovarian suspension within three months. These results \nTable 1 Comparing the characteristics of right and left ovaries before surgery in the studies patients\nRight ovary Left ovary p-value Ovarian suspension Endo gel p-value\nMaximum ovarian diameter, Number (percent)\n < 3 0 1 (2.1%) .189 – – –\n3–6 12 (24.5%) 14 (29.7%) – – –\n > 6 35 (74.5%) 32 (68.2%) – – –\nOvarian adhesion\n < 1/3 0 0 .304 0 0 .060\n1/3–2/3 4 (8.5%) 13 (27.7%) 5 (10.6%) 12 (25.5%)\n > 2/3 43 (91.5%) 34 (72.3%) 42 (89.4%) 35 (74.5%)\nSite specific tenderness\nNo 1 (2.1%) 2 (2.1%) 1.00 0 1 (2.1%) 1.00\nYes 46 (97.9%) 45 (95.7%) 47 (100%) 46 (97.9%)\nEndometrioma\nNo 1 (2.1%) 0 Not computable – – –\nYes 46 (97.9%) 47 (100%) – – –\nOvarian mobility\nYes 24 (51.1%) 13 (24.4%) .096 21 (44.7%) 14 (29.8%) .180\nNo 23 (48.9%) 34 (75.6%) 26 (55.3%) 31 (70.2%)\nOvarian fading margin\nNo – – – 11 (23.4%) 7 (14.9%) .661\n < 1/3 – – – 19 (40.4%) 18 (38.3%)\n1/3–2/3 – – – 10 (21.3%) 12 (25.5%)\n > 2/3 – – – 7 (14.9%) 10 (21.3%)\n\nPage 6 of 8Chaichian et al. BMC Women’s Health           (2022) 22:33 \nare in agreement with previous studies, suggesting Endo -\ngel as an effective adhesion-preventing factor [11, 12] \nin gynecologic laparoscopic and hysteroscopic surgery \n[18]. However, they have not addressed ovarian adhe -\nsions solely and have considered various gynecological \nprocedures. HYAcorp Endogel is shown to be superior \nto lactate ringer solution on preventing postoperative \nadhesions after laparoscopic ovarian drilling in patients \nwith polycystic ovarian syndrome (PCOS) [19], which \nconfirms the results of the present study. However, the \ntype of disease, surgical procedure, and the control group \nwere different. Confirming the current study results, a \nreview of adhesion preventive techniques showed that \nH.A. alone or cross-linked with various agents such as \nnanoparticles are efficient easy-to-use gel, suggested to \nbe used around the adnexal region or myomectomy site \nin gynecological diseases [20]. The mechanism of this \nefficacy is that this glycosaminoglycan, one of the compo-\nnents of the extracellular matrix, deposits around the sur-\ngical site and reduces the chance of adhesion formation \nwith favorable biocompatibility and safety profile [21, \n22]. On the contrary, comparing the effect of Hyalobar -\nrier® with the control group (no intervention) in women \nwith periadenexal adhesions at the time of laparoscopy \nshowed the influence of Hyalobarrier ® neither on adhe -\nsion and pregnancy rate two years after surgery, nor on \nfollicular development (three months after surgery) [23]. \nThis difference between the results of this study and ours \nTable 2 Comparing the post-intervention ovarian characteristics \nbetween study groups\n*P-values < .05 are considered significant, calculated based on the results of chi \nsquare test\nOvarian suspension \n(47 ovaries)\nEndo gel (47 ovaries) p-value*\nFrequency Percent \n(%)\nFrequency Percent \n(%)\nOvarian adhesion\n < 1/3 17 38.5 37 80.5  < .001\n1/3–2/3 23 53.8 7 14.6\n > 2/3 6 7.7 2 4.9\nSite specific tenderness\nNo 18 38.3 35 74.4  < .001\nYes 29 61.7 12 25.6\nOvarian mobility\nYes 9 22.0 26 65.0 .001\nNo 32 78 14 35\nOvarian fading margin\nNo 11 23.4 10 21.3  < .001\n < 1/3 13 27.6 31 66\n1/3–2/3 20 42.5 4 8.5\n > 2/3 3 6.5 2 4.2\nTable 3 Comparing the rate of adhesions before and after \nsurgery in the studied population\n*P-values < .05 are considered significant, calculated based on the results of chi \nsquare test\nBefore surgery Three months after \nsurgery\np-value*\nFrequency Percent Frequency Percent\nAdhesion to bladder\nNo 13 27.7 39 82.9 .462\nMild to mod-\nerate\n27 57.4 3 6.4\nSevere 7 14.9 5 10.6\nAdhesion to right ovary\nNo 0 0 17 38.6 .256\nMild to mod-\nerate\n3 6.4 21 47.7\nSevere 44 93.6 6 13.6\nAdhesion to left ovary\nNo 0 0 22 50 1.00\nMild to mod-\nerate\n2 2.1 19 43.2\nSevere 45 47.9 3 6.8\nAdhesion to colon\nNo 0 0 25 55.6 .520\nMild to mod-\nerate\n2 2.1 19 42.2\nSevere 45 47.9 1 2.2\nAdhesion to small intestine\nNo 31 66 47 100 –\nMild to mod-\nerate\n12 25.5 0 0\nSevere 4 8.5 0 0\nAdhesion to anterior peritoneum\nNo 9 19.1 47 100 –\nMild to mod-\nerate\n31 66 0 0\nSevere 7 14.9 0 0\nAdhesion to posterior peritoneum\nNo 0 0 2 4.4 –\nMild to mod-\nerate\n1 2.1 43 95.6\nSevere 46 97.9 0 0\nAdhesion to right pelvic area\nMild 5 10.6 15 32 1.00\nModerate 13 27.7 5 10.6\nSevere 29 61.7 0 0\nAdhesion to left pelvic area\nMild 5 10.6 15 32 1.00\nModerate 13 27.7 5 10.6\nSevere 29 61.7 0 0\nSliding sign\nNo 30 63.8 30 63.8 1.00\nDecreased 16 34 15 31.9\n\nPage 7 of 8\nChaichian et al. BMC Women’s Health           (2022) 22:33 \n \ncould be due to the different H.A. brand use, as well as \nthe fact that we have not compared the results of the two \nbrands but with another intervention (ovarian suspen -\nsion). As the severity of adhesion and infertility depends \non genetic and epigenetic characteristics and immu -\nnologic and inflammatory responses of the individuals \n[24], we allocated the ovaries to control the effect of this \nconfounding factor via using both allocation methods in \nevery patient [6].\nOvarian suspension or oophoropexy, performed by dif -\nferent techniques, maintains the ovaries suspended far \nfrom the pelvic organs [25]. The choice of time for releas-\ning the suspended ovaries from the abdominal wall was \nbased on the study by Landi et al., which considered ovar-\nian suspension release three days after surgery [17]. In a \nrecent survey, Dhanawat and colleagues also confirmed \nthe formation of fibrin deposits as early as 3 h after injury \nand suggested fibrinolysis formation three days after sur -\ngery [16]. In a previous study, unilateral or bilateral tran -\nsient ovarian suspension of 336 ovaries showed a reduced \nrisk of adhesion formation by distancing the ovaries from \nthe pelvic cavity during wound healing in patients who \nunderwent surgery for severe endometriosis [26]. All of \nthe ultrasonographic criteria, including ovarian adhe -\nsion and soft markers, were better in the Endogel group, \nwhich could be due to more manipulation and foreign \nbody (suture material) in the ovarian suspension group. \nThe higher rate of ovarian fading margin in the Endogel \ngroup may be due to the intrinsic effect of non-absorbed \nEndogel around the ovary. Despite the significant reduc -\ntion in severe ovarian adhesions on both sides, the com -\nparison of postoperative values with the preoperative \nvalues was not statistically significant. Furthermore, nei -\nther of the techniques used in this study could influence \nthe formation of adhesion in other sites, such as bladder, \nlarge and small bowel, anterior and posterior perito -\nneum, right or left pelvic areas.\nThe limitations of the present study included the non -\nrandomized inclusion of patients into the study, which \ndecreases the generalizability of the results. Furthermore, \nwe have considered the patients three-months follow-up \nresults. In contrast, longer follow-ups can better indicate \nthe efficacy of treatments and evaluate their effectiveness \non long-term clinical outcomes, such as pregnancy rate. \nBesides, we recorded the ultrasonographic results for \nadhesion and did not include patients’ clinical symptoms \nor folliculogram, while not all patients with adhesions are \nsymptomatic.\nConclusions\nThe present study results on patients with bilateral ovar -\nian adhesions associated with severe endometriosis \nshowed that HYAcorp Endogel could effectively reduce \nthe risk of adhesion compared to ovarian suspension \nthree months after surgery. Future studies can indicate \nthe long-term outcome of using Endo gel, compared to \nother techniques, on the rate of adhesion, pregnancy, \netc., and demonstrate the most effective and safe strategy \nfor adhesion prevention.\nAcknowledgements\nThe authors thank the staff of the Rasoul-e-Akram and Pars Hospitals for their \ncooperation in performing this project.\nAuthors’ contributions\nS.C. designed and supervised all processes of the study and also edited the \nfinal manuscript text. A.M. supervised and managed the surgical team. S.M. \nhelped with the sonographic examinations. F.J. contributed to writing the \nmanuscript. M.P . analyzed data and prepared the tables and figures. Z.N., K.T., \nand B.M. helped with data gathering and surgical operations. All authors read \nand approved the final manuscript.\nFunding\nIran University of Medical Sciences and Pars Advanced and Minimally Invasive \nMedical Manners Research Center has supported this study.\nAvailability of data and materials\nThe datasets used and or analyzed during the current study are available from \nthe corresponding author on reasonable request.\nDeclarations\nEthics approval and consent to participate\nAll methods were carried out following relevant guidelines, and the Ethics \nCommittee approved the study protocol of Iran University of Medical Sciences \nEthics code: I.R.IUMS.REC.1394.24703). In addition, all patients signed the writ-\nten informed consent.\nConsent for publication\nNA.\nCompeting interests\nThe authors have no Competing interest.\nAuthor details\n1 Pars Advanced and Minimally Invasive Medical Manners Research Center, \nPars Hospital, Iran University of Medical Sciences, Tehran, Iran. 2 Department \nof Radiology, Iran University of Medical Sciences, Tehran, Iran. 3 Endometriosis \nResearch Center, Iran University of Medical Sciences, Tehran, Iran. 4 Zanjan \nUniversity of Medical Sciences, Zanjan, Iran. \nReceived: 29 May 2021   Accepted: 27 January 2022\nReferences\n 1. Abd El-Kader AI, Gonied AS, Mohamed ML, Mohamed SL. Impact of \nendometriosis-related adhesions on quality of life among infertile \nwomen. Int J Fertil Steril. 2019;13(1):72.\n 2. Mortazavi H, Nikfar B, Esmaeili S-A, Rafieenia F, Saburi E, Chaichian S, \net al. Potential cytotoxic and anti-metastatic effects of berberine on \ngynaecological cancers with drug-associated resistance. 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BMC Women’s Health           (2022) 22:33 \n•\n \nfast, convenient online submission\n •\n  \nthorough peer review by experienced researchers in your field\n• \n \nrapid publication on acceptance\n• \n \nsupport for research data, including large and complex data types\n•\n  \ngold Open Access which fosters wider collaboration and increased citations \n \nmaximum visibility for your research: over 100M website views per year •\n  At BMC, research is always in progress.\nLearn more biomedcentral.com/submissions\nReady to submit y our researc hReady to submit y our researc h  ?  Choose BMC and benefit fr om: ?  Choose BMC and benefit fr om: \n 5. Hoo W-L, Saridogan E, Cutner A, Pandis G, Jurkovic D. Effectiveness of \novarian suspension in preventing post-operative ovarian adhesions in \nwomen with pelvic endometriosis: a randomised controlled trial. BMC \nWomens Health. 2011;11(1):1–5.\n 6. Hoo WL, Stavroulis A, Pateman K, Saridogan E, Cutner A, Pandis G, \net al. 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Hyaluronate carboxymethylcel-\nlulose-based bioresorbable membrane (Seprafilm) reduces adhesion \nunder the incision to make unplanned re-laparotomy safer. Surg Today. \n2012;42(9):863–7.\n 12. Mais V, Cirronis MG, Peiretti M, Ferrucci G, Cossu E, Melis GB. Efficacy of \nauto-crosslinked hyaluronan gel for adhesion prevention in laparoscopy \nand hysteroscopy: a systematic review and meta-analysis of randomized \ncontrolled trials. Eur J Obste Gynecol Reprod Biol. 2012;160(1):1–5.\n 13. Mehdizadehkashi A, Kabir A, Chaichian S, Moghimi M. Criticizing the \neffect of ovarian suspension on adhesions in laparoscopic surgery for \nendometriosis. Hum Reprod. 2014;29(7):1596–7.\n 14. Holland TK, Cutner A, Saridogan E, Mavrelos D, Pateman K, Jurkovic D. \nUltrasound mapping of pelvic endometriosis: Does the location and \nnumber of lesions affect the diagnostic accuracy? A multicentre diagnos-\ntic accuracy study. BMC Womens Health. 2013;13(1):1–9.\n 15. Reid S, Leonardi M, Lu C, Condous G. The association between \nultrasound-based ‘soft markers’ and endometriosis type/location: a \nprospective observational study. Eur J Obstet Gynecol Reprod Biol. \n2019;234:171–8.\n 16. Dhanawat J, Pape J, Freytag D, Maass N, Alkatout I. Ovariopexy—before \nand after endometriosis surgery. Biomedicines. 2020;8(12):533.\n 17. Landi S, Ceccaroni M, Perutelli A, Allodi C, Barbieri F, Fiaccavento A, et al. \nLaparoscopic nerve-sparing complete excision of deep endometriosis: Is \nit feasible? Hum Reprod. 2006;21(3):774–81.\n 18. Mettler L, Sammur W, Schollmeyer T, Alkatout I. Cross-linked sodium \nhyaluronate, an anti-adhesion barrier gel in gynaecological endoscopic \nsurgery. Minim Invas Ther Allied Technol. 2013;22(5):260–5.\n 19. Elkhouly M, Behery MA, Farag EA, Wafa YA, Hassan NA, Elsehemy M, \net al. Prevention of adhesions after laparoscopic ovarian drilling using \nautocrossed linked sodium hyaluronate (Gel barrier). Int Inv J Med Med \nSci. 2016;3(8):147–52.\n 20. Metwally M, Cheong Y, Li TC. A review of techniques for adhesion \nprevention after gynaecological surgery. Curr Opin Obstet Gynecol. \n2008;20(4):345–52.\n 21. Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical \napplications. Adv Mater. 2011;23(12):H41–56.\n 22. Collins MN, Birkinshaw C. Hyaluronic acid based scaffolds for tissue \nengineering—a review. Carbohyd Polym. 2013;92(2):1262–79.\n 23. Cheong Y, Bailey S, Forbes J. Randomized controlled trial of Hyalobarrier® \nversus no Hyalobarrier® on the ovulatory status of women with periovar-\nian adhesions: a pilot study. Adv Ther. 2017;34(1):199–206.\n 24. Mehedintu C, Plotogea M, Ionescu S, Antonovici M. Endometriosis still a \nchallenge. J Med Life. 2014;7(3):349.\n 25. Ouahba J, Madelenat P , Poncelet C. Transient abdominal ovariopexy \nfor adhesion prevention in patients who underwent surgery for severe \npelvic endometriosis. Fertil Steril. 2004;82(5):1407–11.\n 26. Carbonnel M, Ducarme G, Dessapt A-L, Yazbeck C, Hugues J-N, Madelenat \nP , et al. Efficacy of transient abdominal ovariopexy in patients with severe \nendometriosis. Eur J Obstet Gynecol Reprod Biol. 2011;155(2):183–7.\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}