Hyaluronic acid gel application versus ovarian suspension for prevention of ovarian adhesions during laparoscopic surgery on endometrioma: a double-blind randomized clinical trial

Background: This study aimed to compare the effect of ovarian suspension and hyaluronic acid gel to prevent re- adhesions after laparoscopic endometrioma surgery.

This randomized clinical trial was conducted at Rasoul-e-Akram and Pars Hospitals, Tehran, Iran, 2016- 18. Fifty patients with bilateral endometrioma and pelvic adhesions, the candidates of laparoscopic surgery, were included. In each patient, at the end of ovarian cystectomy and adhesiolysis, one of the ovaries was randomly sutured to the abdominal wall, and the HYAcorp Endogel covered the other; the adhesion rate was compared between the groups by ultrasonography, three-month after surgery.

Mean age of patients was 32.6 years. Presurgical variables were similar between right and left ovaries and the study groups (P > 0.05). Postsurgical ultrasonography showed that ovarian soft markers, including < 1/3 ovarian adhesions (minimal adhesions) in 80.5% of ovaries of the Endogel group and 35.5% of the ovarian suspension group (P < 0.001) with higher ovarian mobility in the Endogel group (65% vs. 22%) (P = 0.001). In addition, site-specific ten- derness and ovarian fading margin were lower in the Endogel group (P < 0.001). Trial registration Clinical trial registry number: IRCT2015081723666N1, 12.19.2015, Date of registration: 01/02/2016; https:// en. irct. ir/ trial/ 20174? revis ion= 20174. Date and number of IRB: 2015, I.R.IUMS.REC.1394.24703.

Hyaluronic acid gel can be more effective than ovarian suspension in preventing ovarian adhesions after laparoscopic treatment of endometriosis.

Adhesions, Hyaluronic acid, Laparoscopy, Endometriosis, Ovarian suspension © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. 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.

Adhesions are considered an important etiology of pain, infertility, bowel and ureteral obstructions in patients with endometriosis [1] and are supposed to be formed by inflammation, reduced apoptosis, and increased angio - genesis and neurogenesis in endometriotic tissues [2], significantly intensified at higher stages of endometriosis Open Access *Correspondence: [email protected]; amehdizadehkashi@yahoo. com 2 Department of Radiology, Iran University of Medical Sciences, Tehran, Iran 3 Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article Page 2 of 8Chaichian et al. BMC Women’s Health (2022) 22:33 [3]. As adhesions can make the surgical procedure more complicated and time-consuming and cause several problems, such as the continuation of pain and infertil - ity, it is necessary to reduce the risk of adhesion in each surgical procedure [4]. Although numerous surgical techniques, such as ovar - ian suspension, traditionally used to separate the ovaries from the pelvis [5–7], or other preventive methods [8], by using normal saline, heparinized lactated ringer solu - tion, corticosteroids, and peritoneal lavage by Dextran 32% [9], polytetrafluoroethylene (Gore-Tex) and oxidized regenerated cellulose (Interceed), chemically modified sodium hyaluronic acid/carboxymethylcellulose (Sepra - film) [10] have been approved as an efficient method for the adhesion prevention, none of them could completely prevent adhesion recurrence after laparoscopic surgery for endometriosis. Hyaluronic acid gel, known as hyalobarrier gel (used under different brands), is suggested to be used alone or in combination with carboxymethylcellulose, membrane to prevent adhesions [11, 12]. Furthermore, in the present study, we aimed to compare the effect of hyalobarrier gel and ovarian suspension during laparoscopic cystectomy for treatment of bilateral endometrioma on postopera - tive pelvic adhesions. To reduce the confounding effect of different immunological and inflammatory responses of the endometriotic patients, we randomized the ova - ries instead of randomizing patients, as previously used in other bilateral organs [13]. We evaluated the postop - erative pelvic adhesions by ultrasound examination as an accurate diagnostic tool for assessing pelvic adhesions in endometriotic patients [14, 15].

Study design In the present randomized clinical trial (RCT), patients with severe endometriosis (stages 3 or 4; according to rASRM staging system for endometriosis and bilateral endometrioma), who referred to Rasoul-e-Akram and Pars Hospitals, Tehran, Iran, for laparoscopic surgery during 2016 to 2018 were included into the study. To eliminate or reduce the effect of genetic, epigenetic, and immunologic factors, we decided to allocate the ovaries rather than the patients, so 100 ovaries were recruited as the case/control groups of the study. For the allocation of ovaries, a simple randomization technique by application of quadruple blocks was used. We used concealed enve - lopes opened by a technician that informed the surgeon during laparoscopy for the concealment.  For blinding patients, the sutures for ovarian suspension and wound repair on the opposite abdominal wound were done by 3-0 Vicryl and cut simultaneously on the 3rd day of the surgery. The sonologist wasn’t aware of the surgical site. In this study, the purpose of ovarian suspension was not clearance of the surgical field. Instead, we aimed to make the ovary far away from the pelvis during the first three days of surgery to prevent scar tissue formation around it and prevent the anti-adhesive effect of endogel applied  around the opposite ovary.  We could not con - sider internal suspension because we have to release the suspended ovary before ending the surgery. According to Dhanawat’s study [16], three days of ovarian suspension is an appropriate length of time for preventing adhesion. At the end of 72  h, the suspended ovary should be returned to the pelvic cavity by releas - ing the suspension suture. This is especially important for endometriosis patients who may need ART, that oocyte retravel is crucial and necessitates the appropriate pelvic positioning of the ovary. The Ethics Committee of the Iran University of Medical Sciences approved the study protocol. Ethics code: I.R.IUMS.REC.1394.24703) and registered on the Iranian RCT website (IRCT2015081723666N1). Sample size The study sample size was calculated at 50 ovaries in each group, using the formula for binary dependent variables, considering an alpha error of 0.05, study power of 80%, and minimum clinically significant difference in the prev- alence of postoperative ovarian adhesion between two study groups at 50% reduction. According to Hoo et  al. [6], the prevalence of postoperative ovarian adhesions as the primary outcome in the ovarian suspension group was 38.5% and in the unsuspended group was 51.9%. The study’s inclusion criteria consisted of women of reproductive age with clinical and ultrasonography diagnosis of bilateral endometrioma and pain score > 7, who were candidate for laparoscopic surgery and have signed the written informed consent form for the study. Every patient who did not sign the consent form was not included in the study. The exclusion criteria encom - passed patients diagnosed with unilateral endometrioma or another cyst type (rather than endometrioma) during surgery. Patients who did not refer for a follow-up exami- nation and or rejected to continue were excluded from the study. The gynecologist diagnosed endometriosis based on clinical and imaging criteria. Diagnosis of bilateral endo - metrioma and presence of adhesions were confirmed by the same sonographer. During gynecological exami - nation, patients’ pain severity was evaluated by visual analog scale (VAS) and marked by patient herself on a 10-point Likert scale; patients with a score ≥ 7, who were irresponsive to medical treatment, were invited to par - ticipate to the study. Patients with unilateral endome - trioma or deep endometriosis (D.E.) were not included Page 3 of 8 Chaichian et al. BMC Women’s Health (2022) 22:33 in the study. Before enrolling patients into the study, the researcher explained them the study objectives to the eli - gible patients and asked them to read and sign the writ - ten informed consent. All patients were referred to our infertility clinic for standard recommendations by fertil - ity experts and possible fertility preservation. Data collection Patients’ demographics, including age, marital status, and body mass index (BMI), were recorded from the hospital’s medical records. Hormonal medications were discontin - ued three months before laparoscopy (washout period). The ovaries were allocated into two groups of ovarian suspension and hyaluronic gel application using quad - ruple block randomization, prepared by a statistician, by simple randomization method using Excel software without duplicates. The CONSORT 2010 flow diagram (Fig. 1) shows the process of sampling and ovarian alloca- tion and utilization of intention to treat policy for analy - sis. In the operating room, the responsible technician Fig. 1 CONSORT 2010 flow diagram of patients’ enrollment into the study Page 4 of 8Chaichian et al. BMC Women’s Health (2022) 22:33 was asked to open the result of the randomized block to declare the side of ovarian suspension and hyaluronic gel application for performing the allocation. Patient and sonographer were unaware of the group allocation, and the analyst also analyzed the data with codes instead of patients’ names. Surgical techniques All patients underwent laparoscopic surgery by the same surgical team. After direct umbilical trocarization by 11-mm trocar, carbon dioxide (CO2) insufflation was per- formed. Then two 5.5-mm side trocars and one 11-mm suprapubic trocar were inserted. Abdominal and pelvic cavity exploration was done by a zero-degree optic, and bilateral endometriomas were confirmed. The ovarian adhesions to the uterus, contralateral ovary,  bowel, and abdominal wall were released. Each ovary was opened by scissor, and the cyst wall was separated from the ovar - ian tissue by gentle tractions and counter tractions, as much as possible, and by opening the endometrioma, its content was aspirated, and the ovaries were repaired using 3-0 Vicryl by mattress suture, after careful hemo - stasis, preferably by sutures. Based on the  randomiza - tion method, one ovary was sutured by 3-0 Vicryl to the abdominal wall (Fig.  2); the suture thread was brought out at the site of the relevant  5.5-mm  trocar and then another  5.5-mm  trocar site was sutured by 3-0Vic - ryl too, so the patient couldn’t find out the ovarian sus - pension side by looking at the  suture  material (Fig.  3). Another ovary was covered by one sterile pre-filled HYA- corp Endogel (BioScience GmbH, Germany) container, injected all around the ovary via laparoscopic needle. On the third day, the suspended ovary and other abdomi - nal sutures were released by cutting the sutures [16, 17]. Any patient who was diagnosed with unilateral endo - metrioma or any other cyst (rather than endometrioma) during surgery, patients who did not refer for a follow-up examination, and or rejected to continue the study were excluded from the study. Study outcomes The study’s primary outcome was three-months pelvic adhesions surveillance, evaluated by transvaginal ultra - sound and comparison with presurgical indices. Revised ASRM classification and ultrasonography soft mark - ers (ovarian mobility, site-specific tenderness [SST], and ovarian fading margin) of endometriosis were used to examine the incidence and severity of ovarian adhesions. The secondary outcomes were adhesions to the bladder, ovary, bowel, anterior and posterior peritoneum, pelvic and ovarian adhesions, and maximum ovarian diameter were determined by the sonographer and recorded in the study checklist before and three-months after surgery. Any patient who required conversion to laparotomy for any reason or became pregnant during the follow-up period was excluded from the study. Statistical analysis The data were described using frequency (percentage) for categorical variables, mean ± standard deviation (S.D.) for numeric variables with a normal distribution, and median (interquartile range) for numeric variables without normal distribution, based on the results of the Kolmogorov Smirnov test. According to the results of this test, in case of rejection of the normal distribu - tion of the data, Wilcoxon test was used to compare the L.O. Fig. 2 A panoramic view of pelvic cavity after suspension of the left ovary to abdominal wall, according to block randomization Fig. 3 The abdomen’s view at the end of procedure. Note that the suspension thread (3-0 Vicryl) exited from the right 5-mm trocar incision and the wound repaired by the same size suture. Then right 5-mm incision was repaired similarly by 3-0 Vicryl (We ordinary repair these incisions by 4-0 Vicryl sutures) to blind the patient from treatment modalities Page 5 of 8 Chaichian et al. BMC Women’s Health (2022) 22:33 numeric variables among the groups. Mc Nemar’s was used to compare the percentage of interested outcomes among the study groups. The statistical software IBM SPSS Statistics for Windows version 21.0 (IBM Corp. 2012. Armonk, NY: IBM Corp) was used for the statis - tical analysis. P values of < 0.05 were considered statisti - cally significant.

One hundred ovaries of 50 patients were included in the study. Two patients became pregnant during the three- months follow-up period, and one patient required lapa - rotomy for bowel resection. So, six ovaries were excluded from the study. In one patient, the application of Endogel and suturing of the ovary were mistakenly performed on the right and left ovary. Still, we decided not to exclude these two ovaries and counted them as the intention to treat group. So, finally, data of 47 patients and 94 ova - ries were analyzed (Fig.  1). The mean age of patients was 32.6 ± 4.12 years (minimum of 24 and maximum of 42 years), mean BMI was 23.79 ± 3.07 kg/m2, and 59.6% of participants were married. In each patient, both ova - ries (94 ovaries) were evaluated and treated by either ovarian suspension or Endogel. Table  1 indicates the preoperative characteristics of ovaries. As shown, there were no differences in the characteristics of the ovaries of the two arms of the study, including the maximum diameter of the ovary, ovarian margin adhesion, endometrioma, and ovarian mobil - ity (P > 0.05). Moreover, the preoperative characteristics of ovaries, including ovarian margin adhesion, mobility, and fading margin, were not different among the study groups (P > 0.05; Table 1). As indicated in Table  2, after laparoscopy, the Endogel group had a lower frequency of ovarian adhesion > 1/3 and site specific tenderness (SST) (both P < 0.001) and a higher frequency of positive ovarian mobility (P = 0.001) and fading ovarian margin < 1/3 (P < 0.001), compared to the ovarian suspension group. Comparing the frequency of adhesions at different sites before and three-months after the surgery showed that the frequency of adhesion to the bladder, right or left ovary, large and small bowel, anterior and posterior peritoneum, right and left pelvic areas, as well as sliding signs did not significantly change after the intervention (P > 0.05, Table 3).

The ultrasonographic parameters (ovarian adhesion, mobility, fading margin, and SST) showed the superiority of the application of Endo gel on the ovaries compared to ovarian suspension within three months. These results Table 1 Comparing the characteristics of right and left ovaries before surgery in the studies patients Right ovary Left ovary p-value Ovarian suspension Endo gel p-value Maximum ovarian diameter, Number (percent) 6 35 (74.5%) 32 (68.2%) – – – Ovarian adhesion 2/3 43 (91.5%) 34 (72.3%) 42 (89.4%) 35 (74.5%) Site specific tenderness No 1 (2.1%) 2 (2.1%) 1.00 0 1 (2.1%) 1.00 Yes 46 (97.9%) 45 (95.7%) 47 (100%) 46 (97.9%) Endometrioma No 1 (2.1%) 0 Not computable – – – Yes 46 (97.9%) 47 (100%) – – – Ovarian mobility Yes 24 (51.1%) 13 (24.4%) .096 21 (44.7%) 14 (29.8%) .180 No 23 (48.9%) 34 (75.6%) 26 (55.3%) 31 (70.2%) Ovarian fading margin No – – – 11 (23.4%) 7 (14.9%) .661 2/3 – – – 7 (14.9%) 10 (21.3%) Page 6 of 8Chaichian et al. BMC Women’s Health (2022) 22:33 are in agreement with previous studies, suggesting Endo - gel as an effective adhesion-preventing factor [11, 12] in gynecologic laparoscopic and hysteroscopic surgery [18]. However, they have not addressed ovarian adhe - sions solely and have considered various gynecological procedures. HYAcorp Endogel is shown to be superior to lactate ringer solution on preventing postoperative adhesions after laparoscopic ovarian drilling in patients with polycystic ovarian syndrome (PCOS) [19], which confirms the results of the present study. However, the type of disease, surgical procedure, and the control group were different. Confirming the current study results, a review of adhesion preventive techniques showed that H.A. alone or cross-linked with various agents such as nanoparticles are efficient easy-to-use gel, suggested to be used around the adnexal region or myomectomy site in gynecological diseases [20]. The mechanism of this efficacy is that this glycosaminoglycan, one of the compo- nents of the extracellular matrix, deposits around the sur- gical site and reduces the chance of adhesion formation with favorable biocompatibility and safety profile [21, 22]. On the contrary, comparing the effect of Hyalobar - rier® with the control group (no intervention) in women with periadenexal adhesions at the time of laparoscopy showed the influence of Hyalobarrier ® neither on adhe - sion and pregnancy rate two years after surgery, nor on follicular development (three months after surgery) [23]. This difference between the results of this study and ours Table 2 Comparing the post-intervention ovarian characteristics between study groups *P-values < .05 are considered significant, calculated based on the results of chi square test Ovarian suspension (47 ovaries) Endo gel (47 ovaries) p-value* Frequency Percent (%) Frequency Percent (%) Ovarian adhesion < 1/3 17 38.5 37 80.5 2/3 6 7.7 2 4.9 Site specific tenderness No 18 38.3 35 74.4 < .001 Yes 29 61.7 12 25.6 Ovarian mobility Yes 9 22.0 26 65.0 .001 No 32 78 14 35 Ovarian fading margin No 11 23.4 10 21.3 < .001 2/3 3 6.5 2 4.2 Table 3 Comparing the rate of adhesions before and after surgery in the studied population *P-values < .05 are considered significant, calculated based on the results of chi square test Before surgery Three months after surgery p-value* Frequency Percent Frequency Percent Adhesion to bladder No 13 27.7 39 82.9 .462 Mild to mod- erate 27 57.4 3 6.4 Severe 7 14.9 5 10.6 Adhesion to right ovary No 0 0 17 38.6 .256 Mild to mod- erate 3 6.4 21 47.7 Severe 44 93.6 6 13.6 Adhesion to left ovary No 0 0 22 50 1.00 Mild to mod- erate 2 2.1 19 43.2 Severe 45 47.9 3 6.8 Adhesion to colon No 0 0 25 55.6 .520 Mild to mod- erate 2 2.1 19 42.2 Severe 45 47.9 1 2.2 Adhesion to small intestine No 31 66 47 100 – Mild to mod- erate 12 25.5 0 0 Severe 4 8.5 0 0 Adhesion to anterior peritoneum No 9 19.1 47 100 – Mild to mod- erate 31 66 0 0 Severe 7 14.9 0 0 Adhesion to posterior peritoneum No 0 0 2 4.4 – Mild to mod- erate 1 2.1 43 95.6 Severe 46 97.9 0 0 Adhesion to right pelvic area Mild 5 10.6 15 32 1.00 Moderate 13 27.7 5 10.6 Severe 29 61.7 0 0 Adhesion to left pelvic area Mild 5 10.6 15 32 1.00 Moderate 13 27.7 5 10.6 Severe 29 61.7 0 0 Sliding sign No 30 63.8 30 63.8 1.00 Decreased 16 34 15 31.9 Page 7 of 8 Chaichian et al. BMC Women’s Health (2022) 22:33 could be due to the different H.A. brand use, as well as the fact that we have not compared the results of the two brands but with another intervention (ovarian suspen - sion). As the severity of adhesion and infertility depends on genetic and epigenetic characteristics and immu - nologic and inflammatory responses of the individuals [24], we allocated the ovaries to control the effect of this confounding factor via using both allocation methods in every patient [6]. Ovarian suspension or oophoropexy, performed by dif - ferent techniques, maintains the ovaries suspended far from the pelvic organs [25]. The choice of time for releas- ing the suspended ovaries from the abdominal wall was based on the study by Landi et al., which considered ovar- ian suspension release three days after surgery [17]. In a recent survey, Dhanawat and colleagues also confirmed the formation of fibrin deposits as early as 3 h after injury and suggested fibrinolysis formation three days after sur - gery [16]. In a previous study, unilateral or bilateral tran - sient ovarian suspension of 336 ovaries showed a reduced risk of adhesion formation by distancing the ovaries from the pelvic cavity during wound healing in patients who underwent surgery for severe endometriosis [26]. All of the ultrasonographic criteria, including ovarian adhe - sion and soft markers, were better in the Endogel group, which could be due to more manipulation and foreign body (suture material) in the ovarian suspension group. The higher rate of ovarian fading margin in the Endogel group may be due to the intrinsic effect of non-absorbed Endogel around the ovary. Despite the significant reduc - tion in severe ovarian adhesions on both sides, the com - parison of postoperative values with the preoperative values was not statistically significant. Furthermore, nei - ther of the techniques used in this study could influence the formation of adhesion in other sites, such as bladder, large and small bowel, anterior and posterior perito - neum, right or left pelvic areas. The limitations of the present study included the non - randomized inclusion of patients into the study, which decreases the generalizability of the results. Furthermore, we have considered the patients three-months follow-up results. In contrast, longer follow-ups can better indicate the efficacy of treatments and evaluate their effectiveness on long-term clinical outcomes, such as pregnancy rate. Besides, we recorded the ultrasonographic results for adhesion and did not include patients’ clinical symptoms or folliculogram, while not all patients with adhesions are symptomatic.

The present study results on patients with bilateral ovar - ian adhesions associated with severe endometriosis showed that HYAcorp Endogel could effectively reduce the risk of adhesion compared to ovarian suspension three months after surgery. Future studies can indicate the long-term outcome of using Endo gel, compared to other techniques, on the rate of adhesion, pregnancy, etc., and demonstrate the most effective and safe strategy for adhesion prevention.

The authors thank the staff of the Rasoul-e-Akram and Pars Hospitals for their cooperation in performing this project. Authors’ contributions S.C. designed and supervised all processes of the study and also edited the final manuscript text. A.M. supervised and managed the surgical team. S.M. helped with the sonographic examinations. F.J. contributed to writing the manuscript. M.P . analyzed data and prepared the tables and figures. Z.N., K.T., and B.M. helped with data gathering and surgical operations. All authors read and approved the final manuscript. Funding Iran University of Medical Sciences and Pars Advanced and Minimally Invasive Medical Manners Research Center has supported this study. Availability of data and materials The datasets used and or analyzed during the current study are available from the corresponding author on reasonable request. Declarations Ethics approval and consent to participate All methods were carried out following relevant guidelines, and the Ethics Committee approved the study protocol of Iran University of Medical Sciences Ethics code: I.R.IUMS.REC.1394.24703). In addition, all patients signed the writ- ten informed consent. Consent for publication NA. Competing interests The authors have no Competing interest. Author details 1 Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran. 2 Department of Radiology, Iran University of Medical Sciences, Tehran, Iran. 3 Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran. 4 Zanjan University of Medical Sciences, Zanjan, Iran. Received: 29 May 2021 Accepted: 27 January 2022

1. Abd El-Kader AI, Gonied AS, Mohamed ML, Mohamed SL. Impact of endometriosis-related adhesions on quality of life among infertile women. Int J Fertil Steril. 2019;13(1):72. 2. Mortazavi H, Nikfar B, Esmaeili S-A, Rafieenia F, Saburi E, Chaichian S, et al. Potential cytotoxic and anti-metastatic effects of berberine on gynaecological cancers with drug-associated resistance. Eur J Med Chem. 2020;187:111–951. 3. Leonardi M, Espada M, Choi S, Chou D, Chang T, Smith C, et al. Transvagi- nal ultrasound can accurately predict the American society of reproduc- tive medicine stage of endometriosis assigned at laparoscopy. J Min Invas Gynecol. 2020;27(7):1581–7.e1. 4. Rimbach S, Ulrich U, Schweppe K. Surgical therapy of endometriosis: chal- lenges and controversies. Geburtshilfe Frauenheilkd. 2013;73(09):918–23. Page 8 of 8Chaichian et al. BMC Women’s Health (2022) 22:33 • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year • At BMC, research is always in progress. Learn more biomedcentral.com/submissions Ready to submit y our researc hReady to submit y our researc h ? Choose BMC and benefit fr om: ? Choose BMC and benefit fr om: 5. Hoo W-L, Saridogan E, Cutner A, Pandis G, Jurkovic D. Effectiveness of ovarian suspension in preventing post-operative ovarian adhesions in women with pelvic endometriosis: a randomised controlled trial. BMC Womens Health. 2011;11(1):1–5. 6. Hoo WL, Stavroulis A, Pateman K, Saridogan E, Cutner A, Pandis G, et al. Does ovarian suspension following laparoscopic surgery for endometriosis reduce postoperative adhesions? An RCT. Hum Reprod. 2014;29(4):670–6. 7. Abuzeid OM, Hebert J, Ashraf M, Mitwally M, Diamond MP , Abuzeid MI. Safety and efficacy of two techniques of temporary ovarian suspension to the anterior abdominal wall after operative laparoscopy. Facts Views Vis ObGyn. 2018;10(2):71. 8. Molinas C, Binda M, Manavella G, Koninckx P . Adhesion formation after laparoscopic surgery: What do we know about the role of the peritoneal environment? Facts Views Vis ObGyn. 2010;2(3):149. 9. Pados G, Makedos A, Tarlatzis B. Adhesion prevention strategies in laparo- scopic surgery. Endoscopy: IntechOpen; 2013. 10. Robertson D, Lefebvre G, Leyland N, Wolfman W, Allaire C, Awadalla A, et al. Adhesion prevention in gynaecological surgery: no. 243, June 2010. Int J Gynecol Obstet. 2010;111(2):193–7. 11. Hashimoto D, Hirota M, Yagi Y, Baba H. Hyaluronate carboxymethylcel- lulose-based bioresorbable membrane (Seprafilm) reduces adhesion under the incision to make unplanned re-laparotomy safer. Surg Today. 2012;42(9):863–7. 12. Mais V, Cirronis MG, Peiretti M, Ferrucci G, Cossu E, Melis GB. Efficacy of auto-crosslinked hyaluronan gel for adhesion prevention in laparoscopy and hysteroscopy: a systematic review and meta-analysis of randomized controlled trials. Eur J Obste Gynecol Reprod Biol. 2012;160(1):1–5. 13. Mehdizadehkashi A, Kabir A, Chaichian S, Moghimi M. Criticizing the effect of ovarian suspension on adhesions in laparoscopic surgery for endometriosis. Hum Reprod. 2014;29(7):1596–7. 14. Holland TK, Cutner A, Saridogan E, Mavrelos D, Pateman K, Jurkovic D. Ultrasound mapping of pelvic endometriosis: Does the location and number of lesions affect the diagnostic accuracy? A multicentre diagnos- tic accuracy study. BMC Womens Health. 2013;13(1):1–9. 15. Reid S, Leonardi M, Lu C, Condous G. The association between ultrasound-based ‘soft markers’ and endometriosis type/location: a prospective observational study. Eur J Obstet Gynecol Reprod Biol. 2019;234:171–8. 16. Dhanawat J, Pape J, Freytag D, Maass N, Alkatout I. Ovariopexy—before and after endometriosis surgery. Biomedicines. 2020;8(12):533. 17. Landi S, Ceccaroni M, Perutelli A, Allodi C, Barbieri F, Fiaccavento A, et al. Laparoscopic nerve-sparing complete excision of deep endometriosis: Is it feasible? Hum Reprod. 2006;21(3):774–81. 18. Mettler L, Sammur W, Schollmeyer T, Alkatout I. Cross-linked sodium hyaluronate, an anti-adhesion barrier gel in gynaecological endoscopic surgery. Minim Invas Ther Allied Technol. 2013;22(5):260–5. 19. Elkhouly M, Behery MA, Farag EA, Wafa YA, Hassan NA, Elsehemy M, et al. Prevention of adhesions after laparoscopic ovarian drilling using autocrossed linked sodium hyaluronate (Gel barrier). Int Inv J Med Med Sci. 2016;3(8):147–52. 20. Metwally M, Cheong Y, Li TC. A review of techniques for adhesion prevention after gynaecological surgery. Curr Opin Obstet Gynecol. 2008;20(4):345–52. 21. Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater. 2011;23(12):H41–56. 22. Collins MN, Birkinshaw C. Hyaluronic acid based scaffolds for tissue engineering—a review. Carbohyd Polym. 2013;92(2):1262–79. 23. Cheong Y, Bailey S, Forbes J. Randomized controlled trial of Hyalobarrier® versus no Hyalobarrier® on the ovulatory status of women with periovar- ian adhesions: a pilot study. Adv Ther. 2017;34(1):199–206. 24. Mehedintu C, Plotogea M, Ionescu S, Antonovici M. Endometriosis still a challenge. J Med Life. 2014;7(3):349. 25. Ouahba J, Madelenat P , Poncelet C. Transient abdominal ovariopexy for adhesion prevention in patients who underwent surgery for severe pelvic endometriosis. Fertil Steril. 2004;82(5):1407–11. 26. Carbonnel M, Ducarme G, Dessapt A-L, Yazbeck C, Hugues J-N, Madelenat P , et al. Efficacy of transient abdominal ovariopexy in patients with severe endometriosis. Eur J Obstet Gynecol Reprod Biol. 2011;155(2):183–7. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub- lished maps and institutional affiliations.