Barrier agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic adhesions can form secondary to inflammation, endometriosis, or surgical trauma. Strategies to reduce pelvic adhesion formation include placing barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene, and fibrin or collagen sheets between pelvic structures. OBJECTIVES: To evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth, and postoperative adhesions in women of reproductive age. SEARCH METHODS: We searched the following databases in August 2019: the Cochrane Gynaecology and Fertility (CGF) Specialised Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries. We searched reference lists of relevant papers, conference proceedings, and grey literature sources. We contacted pharmaceutical companies for information and handsearched relevant journals and conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) on the use of barrier agents compared with other barrier agents, placebo, or no treatment for prevention of adhesions in women undergoing gynaecological surgery. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for eligibility and risk of bias and extracted data. We calculated odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) using a fixed-effect model. We assessed the overall quality of the evidence using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods. MAIN RESULTS: We included 19 RCTs (1316 women). Seven RCTs randomised women; the remainder randomised pelvic organs. Laparoscopy (eight RCTs) and laparotomy (11 RCTs) were the primary surgical techniques. Indications for surgery included myomectomy (seven RCTs), ovarian surgery (five RCTs), pelvic adhesions (five RCTs), endometriosis (one RCT), and mixed gynaecological surgery (one RCT). The sole indication for surgery in three of the RCTs was infertility. Thirteen RCTs reported commercial funding; the rest did not state their source of funding. No studies reported our primary outcomes of pelvic pain and live birth rate. Oxidised regenerated cellulose versus no treatment at laparoscopy or laparotomy (13 RCTs) At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose at laparoscopy reduced the incidence of de novo adhesions (OR 0.50, 95% CI 0.30 to 0.83, 3 RCTs, 360 participants; I² = 75%; very low-quality evidence) or of re-formed adhesions (OR 0.17, 95% CI 0.07 to 0.41, 3 RCTs, 100 participants; I² = 36%; very low-quality evidence). At second-look laparoscopy, we are uncertain whether oxidised regenerated cellulose affected the incidence of de novo adhesions after laparotomy (OR 0.72, 95% CI 0.42 to 1.25, 1 RCT, 271 participants; very low-quality evidence). However, the incidence of re-formed adhesions may have been reduced in the intervention group (OR 0.38, 95% CI 0.27 to 0.55, 6 RCTs, 554 participants; I² = 41%; low-quality evidence). No studies reported results on pelvic pain, live birth rate, adhesion score, or clinical pregnancy rate. Expanded polytetrafluoroethylene versus oxidised regenerated cellulose at gynaecological surgery (two RCTs) We are uncertain whether expanded polytetrafluoroethylene reduced the incidence of de novo adhesions at second-look laparoscopy (OR 0.93, 95% CI 0.26 to 3.41, 38 participants; very low-quality evidence). We are also uncertain whether expanded polytetrafluoroethylene resulted in a lower adhesion score (out of 11) (MD -3.79, 95% CI -5.12 to -2.46, 62 participants; very low-quality evidence) or a lower risk of re-formed adhesions (OR 0.13, 95% CI 0.02 to 0.80, 23 participants; very low-quality evidence) when compared with oxidised regenerated cellulose. No studies reported results regarding pelvic pain, live birth rate, or clinical pregnancy rate. Collagen membrane with polyethylene glycol and glycerol versus no treatment at gynaecological surgery (one RCT) Evidence suggests that collagen membrane with polyethylene glycol and glycerol may reduce the incidence of adhesions at second-look laparoscopy (OR 0.04, 95% CI 0.00 to 0.77, 47 participants; low-quality evidence). We are uncertain whether collagen membrane with polyethylene glycol and glycerol improved clinical pregnancy rate (OR 5.69, 95% CI 1.38 to 23.48, 39 participants; very low-quality evidence). One study reported adhesion scores but reported them as median scores rather than mean scores (median score 0.8 in the treatment group vs median score 1.2 in the control group) and therefore could not be included in the meta-analysis. The reported P value was 0.230, and no evidence suggests a difference between treatment and control groups. No studies reported results regarding pelvic pain or live birth rate. In total, 15 of the 19 RCTs included in this review reported adverse events. No events directly attributed to adhesion agents were reported. AUTHORS' CONCLUSIONS: We found no evidence on the effects of barrier agents used during pelvic surgery on pelvic pain or live birth rate in women of reproductive age because no trial reported these outcomes. It is difficult to draw credible conclusions due to lack of evidence and the low quality of included studies. Given this caveat, low-quality evidence suggests that collagen membrane with polyethylene glycol plus glycerol may be more effective than no treatment in reducing the incidence of adhesion formation following pelvic surgery. Low-quality evidence also shows that oxidised regenerated cellulose may reduce the incidence of re-formation of adhesions when compared with no treatment at laparotomy. It is not possible to draw conclusions on the relative effectiveness of these interventions due to lack of evidence. No adverse events directly attributed to the adhesion agents were reported. The quality of the evidence ranged from very low to moderate. Common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out.

Pain relief in hysterosalpingography.

BACKGROUND: Hysterosalpingography (HSG) is a method of testing for tubal patency. However, women struggle to tolerate the procedure, as it is associated with some discomfort. Various pharmacological strategies are available that may reduce pain during the procedure, though there is no consensus as to the best method. OBJECTIVES: To compare the effectiveness of different types of pharmacological interventions for pain relief in women undergoing HSG for investigation of subfertility. SEARCH METHODS: This review has drawn on the search strategy developed for the Cochrane Menstrual Disorders and Subfertility Group (MDSG). We searched the following databases to 15 April 2015: MDSG Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO. SELECTION CRITERIA: All identified randomised controlled trials investigating pharmacological interventions for pain relief during HSG were investigated for selection. DATA COLLECTION AND ANALYSIS: Four review authors independently extracted data. We combined data to calculate mean differences (MDs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. We assessed the overall quality of the evidence for the main comparisons using GRADE methods. MAIN RESULTS: The search identified 23 trials (1272 women) that were eligible for inclusion into the study. Oral opioid analgesia versus placebo/no treatmentThere was no evidence of effect for oral opioid analgesia in reducing pain during the procedure (MD -0.91, 95% CI -1.88 to 0.06, 1 study, n = 128, low quality evidence) or more than 30 minutes after the procedure (MD -0.99, 95% CI -1.75 to -0.23, 1 study, n = 128, moderate quality evidence)No studies reported on the effect of oral opioid analgesia, when taken prior to the procedure, in reducing pain within 30 minutes after the procedureThere was insufficient evidence to reach conclusions regarding adverse effects. Intravenous opioid analgesia versus placebo/no treatmentThere was evidence that intravenous opioids may improve pain relief during the procedure compared to no treatment (MD -3.53, 95% CI -4.29 to -2.77, 1 study, n = 62, moderate quality evidence)No studies reported on the effect of intravenous opioid analgesia, when taken prior to the procedure, in reducing pain within 30 minutes and more than 30 minutes after the procedureIn terms of adverse effects, one trial reported 1/32 participants had apnoea with intravenous remifentanil. Recovery time was nearly 4 minutes longer in the remifentanil group compared to the control. Oral non-opioid analgesia versus placebo/no treatmentThere was no evidence of effect for oral non-opioid analgesia in reducing pain during the procedure (MD -0.13, 95% CI -0.48 to 0.23, 3 studies, n = 133, I² = 61%, low quality evidence), less than 30 minutes after the procedure (MD -0.30, 95% CI -1.03 to 0.43, 2 studies, n = 45, I² = 97%, very low quality evidence), or more than 30 minutes after the procedure (MD -0.36, 95% CI -1.06 to 0.34, 3 studies, n = 133, I² = 58%, low quality evidence).There was insufficient evidence to reach conclusions regarding adverse effects. Topical anaesthesia versus placebo/no treatmentThere was evidence that topical anaesthetics may reduce pain during the procedure (MD -0.63, 95% CI -1.06 to -0.19, 9 studies, n = 613, I² = 66%, low quality evidence).There was no evidence of effect for topical anaesthesia, when applied prior to the procedure, in reducing pain less than 30 minutes after the procedure (MD 0.42, 95% CI -0.03 to 0.86, 5 studies, n = 373, I² = 59%, very low quality evidence).There was evidence of effect for topical anaesthesia, when applied prior to the procedure, in reducing pain more than 30 minutes after the procedure (MD -1.38, 95% CI -3.44 to -0.68, 2 studies, n = 166, I² = 92%, very low quality evidence).There was insufficient evidence to reach conclusions regarding adverse effects. Locally injected anaesthesia versus placebo/no treatmentThere was evidence of effect that locally injected anaesthetic can reduce pain during the procedure (MD -1.31, 95% CI -1.55 to -1.07, 2 studies, n = 125, I² = 0%, very low quality evidence).There was no evidence of effect for locally injected anaesthesia, when applied prior to the procedure, in reducing pain less than 30 minutes after the procedure (MD -1.31, 95% CI -2.14 to -0.49, 2 studies, n = 125, I² = 46%, low quality evidence).No studies were included into the analysis of the effect of locally injected anaesthesia, when injected prior to the procedure, in reducing pain more than 30 minutes after the procedure.There was insufficient evidence to reach conclusions regarding adverse effects. Any analgesic versus any other analgesicThere was no evidence of a difference between the groups when oral non-opioid analgesia was compared to opioid analgesia for pain relief during the procedure (MD 1.10, 95% CI -0.26 to 2.46, 1 study, n = 91, low quality evidence); less than 30 minutes following the procedure (MD -0.30, 95% CI -1.00 to 0.40, 1 study, n = 91, low quality evidence); and more than 30 minutes following the procedure (MD -0.60, 95% CI -1.56 to 0.36, 1 study, n = 91, low quality evidence). Topical anaesthetics were found to be more effective than paracervical block for pain relief during HSG (MD -2.73, 95% CI -3.86 to -1.60, 1 study, n = 20, moderate quality evidence). This benefit did not extend to within 30 minutes following HSG (MD -1.03, 95% CI -2.52 to 0.46, 1 study, n = 20, low quality evidence); or 30 minutes or more after HSG (MD 0.31, 95% CI -0.87 to 1.49, 1 study, n = 20, low quality evidence).There was insufficient evidence to reach conclusions regarding adverse effects. AUTHORS' CONCLUSIONS: Topical anaesthetic applied before the procedure may be associated with effective pain relief during HSG, though the quality of this evidence is low. Intravenous opioids may also be effective in pain relief, though this must be weighed against their side effects and their effects on the recovery time. There is insufficient evidence to draw conclusions on the efficacy of other analgesics for HSG, or to reach any other conclusions regarding adverse effects.

Barrier agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic adhesions can form as a result of inflammation, endometriosis or surgical trauma. During pelvic surgery, strategies to reduce pelvic adhesion formation include placing barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene or fibrin sheets between the pelvic structures. OBJECTIVES: To evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth and postoperative adhesions in women of reproductive age. SEARCH METHODS: We searched the following databases in February 2015: the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL) and trial registries. We handsearched relevant journals, conference proceedings and grey literature sources and we contacted pharmaceutical companies for information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of the use of barrier agents compared with other barrier agents, placebo or no treatment for the prevention of adhesions in women undergoing gynaecological surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and risk of bias and extracted the data. We calculated odds ratios (ORs) or mean differences (MD) with 95% confidence intervals (CIs) using a fixed effect model. The overall quality of the evidence was assessed using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods. MAIN RESULTS: Eighteen RCTs (1262 women) were included. Six RCTs randomised women; the remainder randomised pelvic organs. Laparoscopy (eight RCTs) and laparotomy (10 RCTs) were the primary surgical techniques. Indications for surgery included myomectomy (six RCTs), ovarian surgery (five RCTs), pelvic adhesions (five RCTs), endometriosis (one RCT) and mixed (one RCT). The sole indication for surgery in three of the RCTs was infertility. Twelve RCTs reported commercial funding; the rest did not state their source of funding.No studies reported either of our primary outcomes of pelvic pain and live birth. Oxidised regenerated cellulose (Interceed) versus no treatment at laparoscopy or laparotomy (13 RCTs)At second-look laparoscopy oxidised regenerated cellulose at laparoscopy was associated with reduced incidence of de novo adhesions (OR 0.50, 95% CI 0.30 to 0.83, three RCTs, 360 participants, I(2) = 75%, very low-quality evidence) and of re-formed adhesions (OR 0.17, 95% CI 0.07 to 0.41, three RCTs, 100 participants, I(2) = 36%, low quality evidence).At second-look laparoscopy no evidence was found of any difference between the groups in the incidence of de novo adhesions after laparotomy (OR 0.72, 95% CI 0.42 to 1.25, one RCT, 271 participants, I(2) = 41%, low-quality evidence). However, the incidence of re-formed adhesions was lower in the intervention group (OR 0.38, 95% CI 0.27 to 0.55, six RCTs, 554 participants, moderate-quality evidence). Expanded polytetrafluoroethylene (Gore-Tex) versus no treatment at gynaecological surgery (one RCT) The evidence suggested that at second-look laparoscopy expanded polytetrafluoroethylene was associated with a reduction in new adhesion formation (OR 0.17, 95% CI 0.03 to 0.94, one RCT, 42 participants, low-quality evidence). Expanded polytetrafluoroethylene (Gore-Tex) versus oxidised regenerated cellulose (Interceed) at gynaecological surgery (two RCTs)One RCT found no difference between the groups at second-look laparoscopy in the incidence of de novo adhesions (OR 0.93, 95% CI 0.26 to 3.41, 38 participants, very low-quality evidence). A second RCT suggested that the expanded polytetrafluoroethylene group had a lower adhesion score (out of 11) (MD -3.79, 95% CI -5.12 to -2.46, 62 participants, very low-quality evidence) and a lower risk of re-formed adhesions (OR 0.13, 95% CI 0.02 to 0.80, 23 participants, very low-quality evidence). This last finding was sensitive to choice of effect estimate and no longer suggested a difference between the groups when a risk ratio was calculated (RR 0.36, 95% CI 0.13 to 1.01). Sodium hyaluronate and carboxymethylcellulose (Seprafilm) versus no treatment at gynaecological surgery (one RCT)Sodium hyaluronate and carboxymethylcellulose was associated with a lower adhesion score (out of 4) at second-look laparoscopy (MD 0.49, 95% CI 0.53 to 0.45, one RCT, 127 participants, moderate-quality evidence). Fibrin sheet versus no treatment at laparoscopic myomectomy (one RCT)There was no evidence of a difference between the groups in the incidence of de novo adhesions at second-look laparoscopy (OR 1.20, 95% CI 0.42 to 3.41, one RCT, 62 participants) or in adhesion score (out of 4) (MD 0.14, 95% CI -0.67 to 0.39, one RCT, 48 participants, low-quality evidence).Fourteen of the 18 RCTs reported adverse events. No events directly attributed to adhesion agents were reported. AUTHORS' CONCLUSIONS: We found no evidence on the effects of barrier agents used during pelvic surgery on either pain or fertility outcomes in women of reproductive age.Low quality evidence suggests that oxidised regenerated cellulose (Interceed), expanded polytetrafluoroethylene (Gore-Tex) and sodium hyaluronate with carboxymethylcellulose (Seprafilm) may all be more effective than no treatment in reducing the incidence of adhesion formation following pelvic surgery. There is no conclusive evidence on the relative effectiveness of these interventions. There is no evidence to suggest that fibrin sheet is more effective than no treatment. No adverse events directly attributed to the adhesion agents were reported. The quality of the evidence ranged from very low to moderate. The most common limitations were imprecision and poor reporting of study methods. Most studies were commercially funded, and publication bias could not be ruled out.

Adhesion prevention agents for gynaecological surgery: an overview of Cochrane reviews.

BACKGROUND: Intraperitoneal adhesions are associated with considerable co-morbidity and have large financial and public health repercussions. They have secondary effects that include chronic pelvic pain, dyspareunia, subfertility and bowel obstruction. In women with adhesions, subsequent surgery is more difficult, often takes longer, and is associated with a higher complication rate (Broek 2013). The significant burden of adhesions has led to the development of several anti-adhesion agents, although there is disagreement as to their relative effectiveness. OBJECTIVES: To summarise evidence derived from Cochrane systematic reviews on the clinical safety and effectiveness of solid agents, gel agents, liquid agents and pharmacological agents, used as adjuvants to prevent formation of adhesions after gynaecological pelvic surgery. METHODS: The Cochrane Database of Systematic Reviews was searched using the keyword 'adhesion' up to August 2014. The Cochrane information management system was also searched for any titles or protocols of reviews in progress. Two review authors independently extracted information from the reviews, with disagreements being resolved by a third review author. The quality of the included reviews was described in a narrative manner, and the AMSTAR tool was used to formally assess each review included in this overview. The quality of evidence provided in the original reviews was described using GRADE methods. MAIN RESULTS: We included two reviews, one with 18 studies comparing solid agents (oxidised regenerated cellulose expanded polytetrafluoroethylene, sodium hyaluronate and carboxymethylcellulose, and fibrin sheets) with control or with each other. The other review included 29 studies which compared liquid agents (4% icodextrin, 32% dextran, crystalloids), gel agents (carboxymethylcellulose and polyethylene oxide, polyethylene glycol gels, hyaluronic acid based gel, 0.5% ferric hyaluronate gel, sodium hyaluronate spray) and pharmacological agents (gonadotrophin-releasing hormone agonist, reteplase plasminogen activator, N,O-carboxymethyl chitosan, steroid agents, intraperitoneal noxytioline, intraperitoneal heparin, systemic promethazine) with control or each other. Both reviews met all of the criteria of the AMSTAR assessment.The reviews included as outcomes both the primary outcomes of this overview (pelvic pain, pregnancy, live birth rate and quality of life (QoL)) and our secondary outcomes (adverse effects, presence or absence of adhesions at second-look laparoscopy (SLL) and adhesion score). However, neither of the reviews identified any primary studies of solid, gel or pharmacological agents that reported any of our primary outcomes. The only studies in either review that reported any of our primary outcomes were studies comparing liquid agents versus control (saline or Hartmann's solution), which reported pelvic pain (two studies), live birth (two studies) and pregnancy (three studies).An external source of funding was stated for 25 of the 47 studies across both reviews; in 24 of these studies the funding was commercial. Solid agents (18 studies)None of our primary outcomes were reported. Adverse events were reported as an outcome by only 9 of the 18 studies. These reported no adverse events. Liquid agents (nine studies)There was no evidence of a difference between liquid agents and control (saline or Hartmann's solution) with respect to pelvic pain (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.37 to 1.14, 1 study, n = 286, moderate quality evidence), pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14, 3 studies, n = 310, moderate quality evidence) or live birth rate (OR 0.67, 95% CI 0.29 to 1.58, 2 studies, n = 208, moderate quality evidence). No studies of liquid agents reported QoL. Adverse events were not reported as an outcome by any of the nine studies. Gel agents (seven studies)None of our primary outcomes were reported. Adverse events were not reported as an outcome by any of the seven studies. Pharmacological agents (seven studies)None of our primary outcomes were reported. Adverse events were reported as an outcome by only one of the seven primary studies. This study reported no evidence of difference in ectopic pregnancy rates between intraperitoneal noxytioline and no treatment (OR 4.91, 95% CI 0.45 to 53.27, 1 study, n = 33, low quality evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to allow us to draw any conclusions about the effectiveness and safety of anti-adhesion agents in gynaecological surgery, due to the lack of data on pelvic pain, fertility outcomes, quality of life or safety. A substantial proportion of research in this field has been funded by private companies that manufacture these agents, and further high powered, independent trials will be needed before definitive conclusions can be made.

Lymphocytic hypophysitis in males.

Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland that typically affects women in the peripartum period. We describe two male patients (ages 43 years and 36 years), who presented with headaches, visual disturbance and hypopituitarism. MRI revealed a heterogeneous pituitary lesion that extended into the suprasellar region and with a thickened pituitary stalk. In both patients a histopathological diagnosis of LH was made after endoscopic transsphenoidal surgery. LH in males, although rare, should be considered as a differential diagnosis in those with hypopituitarism and a heterogeneous pituitary fossa mass, extending into pituitary stalk.