Adhesions
<1/3 enclosed
1/3–2/3 enclosed
>2/3 enclosed
Right ovary
Filmy
1
2
4
Right
Dense
4
8
16
Adnexa
Right tube
Filmy
1
2
4
Dense
4a
8a
16
Left ovary
Filmy
1
2
4
Left
Dense
4
8
16
Adnexa
Left tube
Filmy
1
2
4
Dense
4a
8a
16
Some authors have modified this system. In the Intergel Pivotal Study, a modified AFS score was calculated (mAFS score). In this score, the same method and score for an individual site was used but a total of 24 individual anatomical sites was included; the final score was an average of these sites (final score 0–16) [43]. Other authors have used a similar mAFS score [44].
There is some evidence of a direct correlation between AFS adhesion score and pregnancy rate. In one study the classification of minimal, mild, moderate and severe correlated with 70, 67, 17 and 10 % rate of pregnancy respectively. In this study there was also a direct correlation between adhesion groups and follicle recovery and embryo transfer at in-vitro fertilization [45]. However in a study looking at 55 pairs of surgeons evaluating surgical video recordings correlation in calculating the AFS score was less than a third (λ 0.7) [46].
Effects on Fertility
Adhesions are thought to be responsible to 15–20 % of all cases of secondary female infertility [47]. The effect on fertility observed could be due to a number of different possible mechanisms.
Mechanical Tubal Blockage, Distortion of Tubo-Ovarian Relationships, and Reduced Mobility of Reproductive Viscera
Adhesions can distort the normal anatomy of the fallopian tube with or without causing tubal blockage. There can be fimbrial disease that affects the normal function or adhesions that completely enclose the fimbria. Adhesions can also lead to significantly distorted relationship or mobility of the uterus, tubes and ovaries resulting in reduced ovum pickup [10].
Ovarian Compromise and Follicular Entrapment
There has been conflicting evidence regarding this as an explanation for adhesion related infertility. A study by Mahadevan et al. found fewer follicles present after stimulated cycles in patients with peri-ovarian adhesive disease [48]. Similarly, Molloy et al. noted that there was a poor oestradiol response and fewer follicles in patients with severe pelvic adhesions (“frozen pelvis”) in the studied IVF programme [49]. Bowman et al. correlated a higher AFS score with raised basal FSH concentration (a possible marker of ovarian compromise) although all FSH values were in the normal range [50]. Possible mechanisms were proposed for these findings – follicular entrapment limiting the enlargement of developing follicles, compromised ovarian blood supply due to contortion of adnexal structures or as a primary consequence of the initial insult that led to the adhesions [48, 51]. Contrary to the above evidence, a subsequent study published by Diamond et al. [51] looked at the effect of peri-ovarian adhesions on follicular development after ovarian stimulation for IVF-embryo transfer. The authors concluded that follicular development as assessed by E2 level the day after administration of HCG, and ultrasound was not impaired by adhesions [51].
Ectopic Pregnancy
This is an important cause of failure to achieve a live birth. Non-occlusive tubal disease and adnexal adhesions may distort the anatomy and alter motility and transit leading to ectopic pregnancy [52].
Effects on Assisted Conception Techniques
The significance of pelvic adhesion disease in respect to fertility is reduced for patients that are undergoing reproductive medicine techniques such as in-vitro fertilisation and embryo transfer. Transvaginal oocyte recovery has reduced the importance of ovarian access that would previously have required adhesiolysis in laparoscopic recovery [10]. As described above, there is no clear evidence that folliculogenesis is impaired by peri-ovarian adhesions and it is generally considered not necessary to perform adhesiolysis prior to an IVF cycle with ultrasound guided follicular aspiration.
Diagnosis, Investigation and Treatment of Adhesions
Laparoscopy is the gold standard for the diagnosis of intraperitoneal adhesions; it has the important benefit of allowing adhesiolysis when performed by a suitably experienced surgeon on properly consented patient. Less invasive investigative and screening techniques have been proposed as a means of reducing the number of negative laparoscopies or to allow appropriate patient counselling for further diagnostic or therapeutic investigations, none have yet found their way into routine clinical practice [53, 54].
Transvaginal ultrasound has been studied in the diagnosis of pelvic adhesions. Guerriero et al. calculated sensitivity and specificity of three ultrasound markers to indicate the presence of adhesions – blurring of the margins of the ovary, fixation of the ovary to the uterus and augmentation of the usual distance of the ovary from the probe. The last two findings were only considered if they persisted after abdominal palpation. Adhesions were confirmed by laparoscopy within 2 days of the scan. If there was at least one positive marker present then sensitivity of the investigation was 93 %, specificity 53 %. If all three markers were positive then sensitivity was 30 % and specificity 94 % [55]. Hysterosalpingography is able to detect proximal tubal occlusion but has been shown to have a low accuracy and is of no use for the detection of peritubal adhesions (sensitivity 65 %, specificity 83 %) [56].
Adhesiolysis
Adhesiolysis is a commonly performed procedure [57] and the efficacy of this operation in patients with infertility was demonstrated by Tulandi et al. [58]. The authors showed a cumulative pregnancy rate at 12 and 24 month follow up after open salpingoovariolysis of 32 and 45 %, compared to 11 and 16 % in a non-treated group with no significant difference in the degree of adhesions prior to treatment [58].
Lysis of adhesions can be open or laparoscopic. Division through the laparoscopic route can be performed by electocoagulation, laser or sharp dissection (with blunt dissection sufficient in some filmy adhesions) [10]. Gomel and Semm described the technique of adhesiolysis [59, 60]. Identified adhesions are put under traction with grasping forceps or a probe and then divided in layers using scissors with electrocoagulation or laser used for vascular adhesions [10].
Adhesiolysis can be considered “high-risk” surgery and is associated with a considerable risk of inadvertent enterotomy, occurring during laparoscopic entry or during adhesiolysis itself [61]. Bowel perforations are recognised during the operation in only 35 % of patients, the majority being recognised a mean of 4 days after the injury [62]. Consideration of open versus Veress needle for laparoscopic entry and use of primary trocar placement in the left upper quadrant have been advocated as ways to reduce these risks in high-risk laparoscopy [1].
The twin problems of reformation of the divided adhesions in addition to de-novo adhesions at new intraperitoneal sites limits the benefit of surgical adhesiolysis. The rate of reformation of the lysed adhesions has been reported as 55–100 % [10]. In a multicentre trial using an early second-look laparoscopy after the initial procedure, de novo adhesions were noted at sites that were adhesion free at the initial surgery in 51 % [63]. De novo adhesion formation has been found to be influenced various surgical covariates including surgery duration, blood loss, number and size of incision, suturing and number of knots [64].
Second Look Laparoscopy
The use of a “second-look” laparoscopy has been suggested to identify and treat re-formed and de-novo adhesions. The rationale behind it is to prevent the transformation of fibrinous attachments into permanent adhesions, advocated by some surgeons to be performed a week from the adhesiolysis. Others have advocated a delayed approach after 3–12 months to allow selection of patients in which pregnancy has not occurred [61]. However, there has not been evidence that the use of SLL enhances fertility. Results from meta-analysis of two trials comparing pregnancy rates between patients undergoing fertility surgery and patients having a second-look laparoscopy have shown no significant difference in pregnancy rate or live births [65–67]. The use of SLL in a clinical role is not recommended [10, 68].
Prevention of Post-operative Adhesions
The clinical complications and burden of adhesion disease has been established, furthermore the difficulty with treatment due to the high risk of lysed adhesions reforming and secondary surgery causing de novo adhesions. It is generally accepted therefore that the best solution to the overall problem would be prevention. Prevention falls into two broad categories. The first category can be thought of as choices of surgical techniques available in an attempt to minimise the surgical insult leading to adhesion formation. The second category is the use of anti-adhesion agents at initial surgery, through pharmacological action or physical separation of viscera with solid, liquid and gel barriers.
Surgical Techniques That Influence Formation
Good Surgical Principles
The principles of microsurgery in fertility surgery were described by Levinson and Swolin [36]. These points of good surgical practice theoretically reduce peritoneal and visceral injury, inflammation and presence of the fibrinous clot that leads to adhesion formation.
The techniques and principles that have been advised in this regard are as follows [36, 68, 69]:
minimally invasive surgery
tissue sparing techniques
gentle tissue handling
sparing use of electrocautery to elicit a meticulous haemostasis
removal of clot with irrigation
excision of necrotic tissue
minimising operating time
reducing peritoneal dehydration with moist swabs and lavage
use of a low insufflation pressure after trocar insertion at laparoscopy
using humidified gases at laparoscopy to avoid desiccation
limiting foreign bodies – sutures, meshes, surgical glove powder
use of fine, inert, absorbable sutures
adherence to surgical asepsis and use of antibiotics as appropriate
Laparoscopy Versus Laparotomy
The route of operative treatment may be an important factor in the process of formation of adhesions but evidence for laparoscopic route versus laparotomy is conflicting. Cohort studies have observed a lower incidence of adhesions when laparoscopic surgery is performed compared to open surgery [32, 70]. However, when the SCAR group examined data from 1996 for gynaecological surgery in Scotland, there were comparable risks of adhesion related readmissions in 15,197 patients that underwent laparoscopic surgery and 8,849 patients that had laparotomies. The exception was laparoscopic sterilization which had a low risk of adhesion-related readmission (0.2 %).
Laparoscopy may be beneficial because the magnitude of surgical insult may be less with reduced tissue handling and contamination. It is also thought to have a favourable effect on haemostasis, causing a tamponade effect with a milder effect on the peritoneal plasminogen system [71]. However, there has been evidence in animal studies that the pneumoperitoneum created in laparoscopic surgery may desiccate the peritoneum, cause mesothelial hypoxia by affecting peritoneal perfusion and thus creating reactive oxygen species that promote the development of adhesions [72]. Adhesion risk has been shown to increase with time and insufflation pressure [73, 74]. Considering clinical outcomes and the incidence of adhesions, a systematic review and meta-analysis concluded that there was little evidence for the surgical principle that using less invasive techniques reduced the extent and severity of adhesions [65].
Peritoneal Closure
The closure of the parietal peritoneum at laparotomy remains controversial. The healing process of remesothelisation at peritoneal healing is different from the reepithelialisation of skin. Rather than proliferation of the epithelial cells from the periphery inwards, the peritoneum becomes mesothelialised simultaneously regardless of the size of injury [16]. Malvasi et al. performed light microscopy and scanning electron microscopy on specimens taken from patients at repeat caesarean, having had closure of the peritoneum in their first caesarean and concluded that closure appeared to enhance the inflammatory reaction [75].
A recent systematic review found three trails eligible for meta-analysis and found that adhesions were less after non-closure of the peritoneum [65]. Two of these trials were in patients operated upon with ovarian cancer [76, 77], the other after caesarean section [75]. A Cochrane systematic review of non-closure versus closure of the peritoneum at caesarean section also supported non-closure. However, in contrast to these results, Lyell et al. published a prospective cohort study of women undergoing first repeat caesarean delivery and found parietal peritoneal closure to be associated with significantly fewer dense and filmy adhesions; the authors concluded that the practice of non-closure should be questioned [78].
Methods of Haemostasis
Electrocautery and laser can both used to achieve haemostasis after division of vascular adhesions. In a prospective randomized study comparing the carbon-dioxide laser and microdiathermy needle there was no difference in pregnancy rate at 2 year follow-up [79]. In a study comparing use of electrocautery and the Nd:YAG laser on polycystic ovaries, second look laparoscopy 3–4 weeks after surgery demonstrated a similar number of adhesions (85 % electrocautery and 80 % laser) with no significant difference in pregnancy rate at 6 months [66].
Foreign Bodies: Gloves, Sutures, and Mesh
Attempts should be made when possible to minimise any foreign bodies being introduced into the intraperitoneal environment, in order to prevent needless trauma and reduce inflammatory reaction. One such foreign body is surgical glove powder, which can be deposited in the abdominal cavity and result in the formation of adhesions. Lycopodium was used as a glove powder until the 1930s when it between realised that the chemical caused granulomas and adhesion formation; talcum powder used in the 1940s was shown to have similar complications; a modified cornstarch powder was introduced in 1947. There have been similar concerns about adhesion formation with this powder and many authorities have banned the use of powdered gloves in clinical environments [80].
Suturing promotes adhesion formation and it is known that choice of suture material can influence formation in animal models [81, 82]. Fine, non-reactive and absorbable sutures are advised to be used when possible [83]. Mesh products are another type of foreign body commonly used in a range of intra-peritoneal surgery. Bioprosthetic mesh in vitro appears to elicit fewer lower-grade adhesions than synthetic mesh [84].
Ovariopexy
Transient abdominal ovariopexy is a technique used in pelvic surgery for endometriosis. The aim is to separate the suspended ovary from the pelvic sidewall during initial peritoneal healing in an attempt to prevent adhesion formation and hopefully improve fertility outcome. A retrospective study was performed to assess adhesion formation after ovariopexy. It showed significantly decreased adnexal adhesions scores at second look laparoscopy performed at a mean of 12 months later with the authors concluding it a safe, simple and effective procedure [85]. Adverse effects of ovariopexy on adhesions have been reported [86] but a retrospective study looking specifically at safety of this operation showed encouraging short and long-term results. These were assessed by immediate complications (occurring in 0.7 %) and long term vaginal access to the ovaries, ovarian function and vascularisation [87].
Prophylactic Anti-adhesion Agents
Many agents have been investigated to try and provide a means of preventing adhesions and they generally fall in to two groups. The first are pharmacological agents that modulate the immunological and fibrinolytic process involved in the formation of adhesions. The second group of agents are barrier agents that have their effect by physically separating apposing raw peritoneal surfaces. The ideal barrier agent should be non-reactive, non-inflammatory, non-immunogenic, persist through the healing process over at least 3 days, stay in place without sutures, remain active in the presence of blood and be completely biodegradable [8, 68]. In addition, the ideal agent must be cost-effective; an agent that satisfies all these criteria has not yet been identified [88].
A large number of barrier agents have been designed and trialled, many published studies looking at individual agents small and a number of systematic reviews and meta-analysis have been performed and published. The types of barriers for purposes of meta-analysis in two Cochrane reviews have been divided into hydroflotation agents, gel barriers and solid barriers [8, 9]. Meta-analyses for this diverse range of interventions in the heterogeneous and complex clinical problem of adhesion disease are faced with significant challenges in providing evidence for their use. The lack of important clinical outcomes recorded such as pregnancy rate, live birth rate and quality of life data means that the main body of evidence that has been gathered is for secondary outcomes that rely on a subjective assessment of amount of adhesion disease present. Wide variation in the scoring systems used and format the recorded data is presented in has limited inclusion of trials. Additionally, most trials lack differentiation between de novo adhesion and reformed adhesions. Many of the trials are commercially funded.
The evidence for the use of adhesion prevention agents in Obstetrics and Gynaecology has been the subject of a scientific impact paper produced by the Royal College of Obstetricians and Gynaecologists [88]. The subsections below consider the main evidence for the groups of agents.
Pharmacological Agents
Steroids were assessed in a Cochrane review by Metwally et al. [8]. Five studies involving women undergoing elective open microsurgery for infertility were identified, with a range of methods of administration (systemic, intraperitoneal and post-operative hydrotubation). Meta-analysis failed to demonstrate a reduction in adhesion formation or an improvement in pregnancy rate.
Individual randomised controlled trails have looked at intraperitoneal pelvic irrigation with a heparin solution [89], systemic administration the anti-histamine promethazine [90] and intraperitoneal instillation of noxytioline (an antibacterial agent) [91]. None of these have found to be affective in adhesion prevention [88]. Non-steroidal anti-inflammatory drugs have not undergone randomised controlled trials for adhesion prevention in humans and this lack of data limits recommendation of their use.
Barriers
Hydroflotation Agents
Hydroflotation agents are administered as a peritoneal instillate. Crystalloid solutions, Icodextrin and Dextran have been used for this purpose. A meta-analysis performed by Wiseman et al. on 350 studies using crystalloids did not show evidence of a reduction in adhesion formation [92]. The failure of crystalloid solutions as an anti-adhesion agent is attributed to the rapid absorption from the peritoneal cavity, therefore not being present to separate structures before the healing process is complete [88].
Dextran was considered in Cochrane meta-analysis, with four randomised controlled trails examining the use of instillation of 32 % Dextran 70 against control groups of either Ringer’s solution or normal saline. No difference was found in the mean adhesion score or pregnancy rate. Dextran facilitates the development of a large transudate in the peritoneal cavity but it is likely that this is reabsorbed before healing is complete. Significant adverse effects of dextran have been reported including anaphylaxis, pleural effusion and peritonitis [8, 88].
Four percent Icodextrin ADEPT® (Baxter, Norfolk, UK) is a cornstarch derived, water soluble glucose polymer, functioning as a colloid osmotic agent and allowing retention of a fluid reservoir within the peritoneal cavity for 3–4 days [93]. There have been three randomised controlled trials with conflicting results. The first of these compared Icodextrin to Ringer’s solution in 62 randomised patients and recorded a mAFS score at second look laparoscopy without finding a benefit [94]. Brown et al. conducted a multicentre trial which studied 449 patients randomised to icodextrin or Ringer’s solution. They found a significant reduction in number of adhesion sites and number of patients with de-novo adhesions [95]. Trew et al. published a double blind, multicentre trial with 498 participants randomised to Icodextrin or Ringer’s solution. The authors concluded that although the trial confirmed the safety of Icodextrin, there was no evidence of a clinical effect as measured by the mean AFS score reduction or incidence of de novo adhesions [64]. As all three of these studies used different outcome measures of adhesions at SLL as detailed above, meta-analysis has not been possible.
Gel Agents
Gel agents comprise hyaluronic acid derivative products and polyethylene glycol based precursors. Hyaluronic acid is a polysaccharide of high molecular weight and a component of many body tissues. It is absorbed from the peritoneal cavity within 7 days. Several gel products based on this macromolecule have been developed.
A Cochrane meta-analysis [8] included four randomised controlled trials; HYALOBARRIER® (Anika Therapeutics, Massachusetts, USA) (auto-cross linked hyaluronic gel) used at laparoscopic myomectomy in infertile patients [96], GYNECARE INTERGEL® a 0.5 % ferric hyaluronate gel (Ethicon, New Jersey, USA) (0.5 % ferric hyaluronate gel) [43, 97] and SEPRACOAT® (Genzyme Corporation, Massachusetts, USA) (dilute hyaluronic acid solution) [98] used in laparotomy for benign gynaecological surgery. There was a significant reduction in the proportion of adhesions in women treated with hyaluronic acid derivatives when compared to no treatment or placebo [8] (Fig. 16.1). Two of these studies also recorded a separate outcome of deterioration in adhesion score, showing a significant reduction with the gel agents compared to no treatment [8] (Fig. 16.2). HYALOBARRIER® gel was also the subject of a meta-analysis of five trials demonstrating a significant reduction in intrauterine adhesions after hysteroscopic surgery and a non-significant reduction in intraperitoneal adhesions after laparoscopic surgery [99]. Pellicano et al. also studied HYALOBARRIER® and demonstrated a significant improvement in pregnancy rate 12 months after laparoscopic myomectomy [96]. INTERGEL® was voluntarily withdrawn from the market in 2003 after reports of late-onset post-operative pain and repeat surgery following the onset of pain. In some patients a residual material was present at the subsequent surgery.
Fig. 16.1
Comparison of Hyaluronic acid versus no hyaluronic acid, for outcome of proportion of adhesions at second look laparoscopy (From Metwally et al. [8] , with permission)
Fig. 16.2
Comparison of Hyaluronic acid versus no hyaluronic acid, for outcome of deterioration of adhesion score (From Metwally et al. [8], with permission)
A Cochrane review of anti-adhesion agents in non-gynaecological abdominal surgery [100] performed meta-analysis of six randomised controlled trials using SEPRAFILM® (Genzyme Corporation, Massachusetss, USA), a Hyaluronic acid/ Carboxymethyl cellulose membrane. This demonstrated a significant reduction in the incidence, extent and severity of peritoneal adhesions but not in the incidence of bowel obstruction or the need for operative intervention in adhesive intestinal obstruction [100] .
SPRAYGEL™ (Confluent Surgical, Massachusetts, USA) is a Polyethylene Glycol based liquid precursor that is applied as a spray, forming a gel barrier within seconds on the target tissue. Ten Broek et al. [101] performed a meta-analysis of three RCT using this agent in laparoscopic treatment of benign gynaecological disease and showed a significant reduction in the incidence of adhesion formation (Fig. 16.3).
Fig. 16.3
Comparison of PEG Barrier versus control, for outcome total incidence of adhesions, results of meta-analysis (From Ten Broek et al. [101], with permission)
Solid Agents
Oxidised regenerated cellulose is available as GYNECARE INTERCEED® (Ethicon, New Jersey, USA), and can be cut as necessary, requires no suturing and is absorbable. It forms a protective coat within eight hours of application and is absorbed within 2 weeks [9]. It has to be used after haemostasis is complete. In meta-analysis of 12 RCTs, INTERCEED® was associated with reduced incidence of adhesions compared to no treatment for reformed adhesions after laparotomy and laparoscopic surgery (Fig. 16.4), and de novo adhesions after laparoscopic surgery [9] (Fig. 16.5). Studies making up the analysis were small, and it was noted by the authors that there was a chance of bias when measuring de novo adhesions as the initial adhesion score would be lower.
Fig. 16.4
Comparison of Interceed versus no treatment at Laparoscopy, for outcome incidence of adhesions (From Ahmad et al. [9], with permission)
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
