Andrew Watson

Laparoscopic entry techniques

BACKGROUNDnLaparoscopy is a common procedure in many surgical specialities. Complications arising from laparoscopy are often related to initial entry into the abdomen. Life-threatening complications include injury to viscera e.g. the bowel or bladder, or to vasculature e.g. major abdominal and anterior abdominal wall vessels. Minor complications can also occur, such as postoperative wound infection, subcutaneous emphysema, and extraperitoneal insufflation. There is no clear consensus as to the optimal method of laparoscopic entry into the peritoneal cavity.nnnOBJECTIVESnTo evaluate the benefits and risks of different laparoscopic entry techniques in gynaecological and non-gynaecological surgery.nnnSEARCH METHODSnThis updated review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group. In addition, MEDLINE, EMBASE, CENTRAL and PsycINFO were searched through to September 2014.nnnSELECTION CRITERIAnWe included randomised controlled trials (RCTs) in which one laparoscopic entry technique was compared with another.nnnDATA COLLECTION AND ANALYSISnTwo authors independently selected studies, assessed risk of bias, and extracted data. We expressed findings as Peto odds ratios (Peto ORs) with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of evidence for the main comparisons using GRADE methods.nnnMAIN RESULTSnThe review included 46 RCTs including three multi-arm trials (7389 participants) and evaluated 13 laparoscopic entry techniques. Overall there was no evidence of advantage using any single technique for preventing major vascular or visceral complications. The evidence was generally of very low quality; the main limitations were imprecision and poor reporting of study methods. Open-entry versus closed-entry There was no evidence of a difference between the groups for vascular (Peto OR 0.14, 95% CI 0.00 to 6.82, three RCTs, n = 795, I(2) = n/a; very low quality evidence) or visceral injury (Peto OR 0.61, 95% CI 0.06 to 6.08, three RCTs, n = 795, I(2) = 0%; very low quality evidence). There was a lower risk of failed entry in the open-entry group (Peto OR 0.16, 95% CI 0.04 to 0.63, n = 665, two RCTs, I(2) = 0%; very low quality evidence). This suggests that for every 1000 patients operated on, 31 patients in the closed-entry group will have failed entry compared to between 1 to 20 patients in the open-entry group. No events were reported in any of the studies for mortality, gas embolism or solid organ injury. Direct trocar versus Veress needle entry There was a lower risk of vascular injury in the direct trocar group (Peto OR 0.13, 95% CI 0.03 to 0.66, five RCTs, n = 1522, I(2) = 0%; low quality evidence) and failed entry (Peto OR 0.21, 95% CI 0.14 to 0.30, seven RCTs, n = 3104; I ²= 0%; moderate quality evidence). This suggests that for every 1000 patients operated on, 8 patients in the Veress needle group will experience vascular injury compared to between 0 to 5 patients in the direct trocar group; and that 64 patients in the Veress needle group will experience failed entry compared to between 10 to 20 patients in the direct trocar group. The vascular injury significance is sensitive to choice of statistical analysis and may be unreliable. There was no evidence of a difference between the groups for visceral (Peto OR 1.02, 95% CI 0.06 to 16.24, four RCTs, n = 1438, I(2) = 49%; very low quality evidence) or solid organ injury (Peto OR 0.16, 95% Cl 0.01 to 2.53, two RCTs, n = 998, I(2) = n/a; very low quality evidence). No events were recorded for mortality or gas embolism. Direct vision entry versus Veress needle entry There was no evidence of a difference between the groups in the rates of visceral injury (Peto OR 0.15, 95% CI 0.01 to 2.34, one RCT, n = 194; very low quality evidence). Other primary outcomes were not reported. Direct vision entry versus open-entry There was no evidence of a difference between the groups in the rates of visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.50, two RCTs, n = 392; low quality evidence), solid organ injury (Peto OR 6.16, 95% CI 0.12 to 316.67, one RCT, n = 60, I(2) = n/a; very low quality evidence), or failed entry (Peto OR 0.40, 95% CI 0.04 to 4.09, one RCT, n = 60; low quality evidence). Vascular injury was reported, however no events occurred. Our other primary outcomes were not reported. Radially expanding (STEP) trocars versus non-expanding trocars There was no evidence of a difference between the groups for vascular injury (Peto OR 0.24, 95% Cl 0.05 to 1.21, two RCTs, n = 331, I(2) = 0%; low quality evidence), visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.37, two RCTs, n = 331, I(2) = n/a; low quality evidence), or solid organ injury (Peto OR 1.05, 95% CI 0.07 to 16.91, one RCT, n = 244; very low quality evidence). Other primary outcomes were not reported. Comparisons of other laparoscopic entry techniquesThere was a higher risk of failed entry in the group in which the abdominal wall was lifted before Veress needle insertion than in the not-lifted group (Peto OR 4.44, 95% CI 2.16 to 9.13, one RCT, n = 150; very low quality evidence). There was no evidence of a difference between the groups in rates of visceral injury or extraperitoneal insufflation. The studies had small numbers and excluded many patients with previous abdominal surgery, and women with a raised body mass index. These patients may have unusually high complication rates.nnnAUTHORS CONCLUSIONSnOverall, there is insufficient evidence to recommend one laparoscopic entry technique over another.An open-entry technique is associated with a reduction in failed entry when compared to a closed-entry technique, with no evidence of a difference in the incidence of visceral or vascular injury.An advantage of direct trocar entry over Veress needle entry was noted for failed entry and vascular injury. The evidence was generally of very low quality with small numbers of participants in most studies; our findings should be interpreted with caution.

Barrier agents for adhesion prevention after gynaecological surgery

BACKGROUNDnPelvic 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.nnnOBJECTIVESnTo evaluate the effects of barrier agents used during pelvic surgery on rates of pain, live birth and postoperative adhesions in women of reproductive age.nnnSEARCH METHODSnWe 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.nnnSELECTION CRITERIAnRandomised 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.nnnDATA COLLECTION AND ANALYSISnTwo 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.nnnMAIN RESULTSnEighteen 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.nnnAUTHORS CONCLUSIONSnWe 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.

Fluid and pharmacological agents for adhesion prevention after gynaecological surgery

BACKGROUNDnAdhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by various conditions including pelvic inflammatory disease and endometriosis. Adhesions are associated with considerable co-morbidity, including pelvic pain, subfertility and small bowel obstruction. Patients may require further surgery-a fact that has financial implications.nnnOBJECTIVESnTo evaluate the role of fluid and pharmacological agents used as adjuvants in preventing formation of adhesions after gynaecological surgery.nnnSEARCH METHODSnThe following databases were searched up to April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO. Studies involving hydroflotation, gel and such pharmacological agents as steroids, noxytioline, heparin, promethazine, N,O-carboxymethyl chitosan and gonadotrophin-releasing hormone agonists were evaluated.nnnSELECTION CRITERIAnRandomised controlled trials investigating the use of fluid and pharmacological agents to prevent adhesions after gynaecological surgery. Gels were defined as fluid agents.nnnDATA COLLECTION AND ANALYSISnThree review authors independently assessed trials for eligibility, extracted data and evaluated risk of bias. Results were expressed as odds ratios (ORs), mean differences (MDs) or standard mean differences (SMDs) as appropriate, with 95% confidence intervals (CIs).nnnMAIN RESULTSnTwenty-nine trials were included (3227 participants), and nine were excluded. One study examined pelvic pain and found no evidence of a difference between use of hydroflotation agents and no treatment. We found no evidence that any of the antiadhesion agents significantly affected the live birth rate. When gels were compared with no treatment or with hydroflotation agents at second-look laparoscopy (SLL), fewer participants who received a gel showed a worsening adhesion score when compared with those who received no treatment (OR 0.16, 95% CI 0.04 to 0.57, P value 0.005, two studies, 58 women, I(2) = 0%, moderate-quality evidence) and with those given hydroflotation agents (OR 0.28, 95% CI 0.12 to 0.66, P value 0.003, two studies, 342 women, I(2) = 0%, high-quality evidence). Participants who received steroids were less likely to have a worsening adhesion score (OR 0.27, 95% CI 0.12 to 0.58, P value 0.0008, two studies, 182 women, I(2) = 0%, low-quality evidence). Participants were less likely to have adhesions at SLL if they received a hydroflotation agent or gel than if they received no treatment (OR 0.34, 95% CI 0.22 to 0.55, P value < 0.00001, four studies, 566 participants, I(2) = 0%, high-quality evidence; OR 0.25, 95% CI 0.11 to 0.56, P value 0.0006, four studies, 134 women, I(2) = 0%, high-quality evidence, respectively). When gels were compared with hydroflotation agents, participants who received a gel were less likely to have adhesions at SLL than those who received a hydroflotation agent (OR 0.36, 95% CI 0.19 to 0.67, P value 0.001, two studies, 342 women, I(2) = 0%, high-quality evidence). No studies evaluated quality of life. In all studies apart from one, investigators stated that they were going to assess serious adverse outcomes associated with treatment agents, and no adverse effects were reported.Results suggest that for a woman with a 77% risk of developing adhesions without treatment, the risk of developing adhesions after use of a gel would be between 26% and 65%. For a woman with an 83% risk of worsening of adhesions after no treatment at initial surgery, the chance when a gel is used would be between 16% and 73%. Similarly, for hydroflotation fluids for a woman with an 84% chance of developing adhesions with no treatment, the risk of developing adhesions when hydroflotation fluid is used would be between 53% and 73%.Several of the included studies could not be included in a meta-analysis: The findings of these studies broadly agreed with the findings of the meta-analyses.The quality of the evidence, which was assessed using the GRADE approach, ranged from low to high. The main reasons for downgrading of evidence included imprecision (small sample sizes and wide confidence intervals) and poor reporting of study methods.nnnAUTHORS CONCLUSIONSnGels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but no evidence indicates that they improve fertility outcomes or pelvic pain, and further research is required in this area. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society (mAFS) score. Statistical findings should be reported in full.

Tubal flushing for subfertility

BACKGROUNDnEstablishing the patency of the fallopian tubes is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and taking radiographs. However, it has been noted that many women conceive in the first three to six months after the tubal flushing, which has raised the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates.nnnOBJECTIVESnTo evaluate the effect of flushing fallopian tubes with oil- or water-soluble contrast media on live birth and pregnancy rates in women with subfertility.nnnSEARCH METHODSnWe searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, MEDLINE, EMBASE, Biological Abstracts, trial registers and reference lists of identified articles. The most recent search was conducted in June 2014.nnnSELECTION CRITERIAnRandomised controlled trials (RCTs) comparing tubal flushing with oil-soluble or water-soluble contrast media, or with no treatment, in women with subfertility.nnnDATA COLLECTION AND ANALYSISnTwo authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods.nnnMAIN RESULTSnThirteen trials involving 2914 women were included, of whom 2494 were included in the analysis. Oil-soluble contrast media (OSCM) versus no interventionThe OSCM group had a higher rate of live birth (odds ratio (OR) 3.09, 95% CI 1.39 to 6.91, 1 RCT, 158 women, low quality evidence) and ongoing pregnancy (OR 3.59, 95% CI 2.06 to 6.26, 3 RCTs, 382 women, I(2) = 0%, low quality evidence) than women who had no intervention. Our findings suggest that among subfertile women with a 17% chance of an ongoing pregnancy if they have no intervention, the rate will increase to between 29% and 55% if they have tubal flushing with OSCM. Water-soluble contrast media (WSCM) versus no interventionThere was no evidence of a difference between the groups in rates of live birth (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, very low quality evidence) or ongoing pregnancy (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, very low quality evidence). OSCM versus WSCMTwo RCTs reported live birth: one found a higher live birth rate in the oil-soluble group and the other found no evidence of a difference between the groups. These studies were not pooled due to very high heterogeneity (I(2) = 93%). There was no evidence of a difference between the groups in rates of ongoing pregnancy, however there was high heterogeneity (OR 1.44, 95% CI 0.84 to 2.47, 5 RCTs, 1454 women, I(2) = 76%, random-effects model, very low quality evidence). OSCM plus WSCM versus WSCM aloneThere was no evidence of a difference between the groups in rates of live birth (OR 1.06, 95% CI 0.64 to 1.77, 1 RCT, 393 women, very low quality evidence) or ongoing pregnancy (OR 1.23, 95% CI 0.87 to 1.72, 4 RCTs, 633 women, I(2) = 0%, low quality evidence).There was no evidence of a difference between any of the interventions in rates of adverse events, but such events were poorly reported in most studies.nnnAUTHORS CONCLUSIONSnThe evidence suggests that tubal flushing with oil-soluble contrast media may increase the chance of pregnancy and live birth compared to no intervention. Findings for other comparisons were inconclusive due to inconsistency and lack of statistical power. There was insufficient evidence on adverse events to reach firm conclusions. Further robust randomised controlled trials are needed.

Growth hormone for in vitro fertilization

BACKGROUNDnIn an effort to improve outcomes of in-vitro fertilisation cycles the use of growth hormone has been considered. Improving the outcomes of in-vitro fertilisation is especially important for subfertile women who are considered poor responders.nnnOBJECTIVESnTo assess the effectiveness of adjuvant growth hormone in in-vitro fertilisation protocols.nnnSEARCH STRATEGYnWe searched the Cochrane Menstrual Disorders and Subfertility Groups trials register (June 2009), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2009), MEDLINE (1966 to June 2009), EMBASE (1988 to June 2009) and Biological Abstracts (1969 to June 2009).nnnSELECTION CRITERIAnAll randomised controlled trials were included if they addressed the research question and provided outcome data for intervention and control participants.nnnDATA COLLECTION AND ANALYSISnAssessment of trial risk of bias and extraction of relevant data was performed independently by two reviewers.nnnMAIN RESULTSnTen studies (440 subfertile couples) were included. Results of the meta-analysis demonstrated no difference in outcome measures and adverse events in the routine use of adjuvant growth hormone in in-vitro fertilisation protocols. However, meta-analysis demonstrated a statistically significant difference in both live birth rates and pregnancy rates favouring the use of adjuvant growth hormone in in-vitro fertilisation protocols in women who are considered poor responders without increasing adverse events, OR 5.39, 95% CI 1.89 to 15.35 and OR 3.28, 95% CI 1.74 to 6.20 respectively.nnnAUTHORS CONCLUSIONSnAlthough the use of growth hormone in poor responders has been found to show a significant improvement in live birth rates, we were unable to identify which sub-group of poor responders would benefit the most from adjuvant growth hormone. The result needs to be interpreted with caution, the included trials were few in number and small sample size. Therefore, before recommending growth hormone adjuvant in in-vitro fertilisation further research is necessary to fully define its role.

Gonadotrophin‐releasing hormone analogues for endometriosis: bone mineral density

BACKGROUNDnGonadotrophin-releasing hormone analogues (GnRHas) are generally well tolerated, and are effective in relieving the symptoms of endometriosis (Prentice 2003). Unfortunately the low oestrogen state that they induce is associated with adverse effects including an acceleration in bone mineral density (BMD) loss.nnnOBJECTIVESnTo determine the effect of treatment with gonadotrophin-releasing hormone analogues (GnRHas) on the bone mineral density of women with endometriosis, compared to placebo, no treatment, or other treatments for endometriosis, including GnRHas with add-back therapy.nnnSEARCH STRATEGYnWe searched the Cochrane Menstrual Disorders and Subfertility Groups specialised register of controlled trials (23rd October 2002) and the Cochrane Central Register of Controlled Trials (Cochrane Library, issue 4, 2002). We also carried out electronic searches of MEDLINE (1966 - March Week 2 2003) and EMBASE (1980 - March Week 2 2003). We also searched the reference lists of articles and contacted researchers in the field.nnnSELECTION CRITERIAnProspective, randomised controlled studies of the use of GnRHas for the treatment of women with endometriosis were considered, where bone density measurements were an end point. The control arm of the studies was either placebo, no treatment, another medical therapy for endometriosis, or GnRHas with add-back therapy.nnnDATA COLLECTION AND ANALYSISnTwo reviewers (JF and MS) independently assessed trial quality and extracted data. Study authors were contacted for additional information.nnnMAIN RESULTSnThirty studies involving 2,391 women were included, however only 15, involving 910 women, could be included in the meta-analysis. The meta-analysis showed that danazol and progesterone + oestrogen add-back are protective of BMD at the lumbar spine both during treatment and for up to six and twelve months after treatment, respectively. Between the groups receiving GnRHa and the groups receiving danazol/gestrinone, there was a significant difference in percentage change of BMD after six months of treatment, the GnRH analogue producing a reduction in BMD from baseline and danazol producing an increase in BMD (SMD -3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective; after six months of treatment absolute value BMD measurements of the lumbar spine did not differ significantly from the group receiving GnRH analogues (SMD 0.15, 95 % CI -0.21 to 0.52). In the comparison of GnRHa versus GnRHa + HRT add-back, that is oestrogen + progesterone or oestrogen only, there was a significantly bigger BMD loss in the GnRHa only group (SMD -0.49, 95 % CI -0.77 to -0.21). These numbers reflect the absolute value measurements at the lumbar spine after six months of treatment. Due to the small number of studies in the comparison we are unable to conclude whether calcium-regulating agents are protective. No difference was found between low and high dose add-back regimes but again only one study was identified for this comparison. Only one study comparing GnRH analogues with placebo was identified, but the study gave no data. No studies comparing GnRH with the oral contraceptive pill (OCP) or progestagens were identified.nnnREVIEWERS CONCLUSIONSnBoth danazol and progesterone + oestrogen add-back have been shown to be protective of BMD, while on treatment and up to six and 12 months later, respectively. However, by 24 months of follow-up there was no difference in BMD in those women who had HRT add-back. Studies of danazol versus GnRHa did not report long-term follow-up. The significant side effects associated with danazol limit its use.

Barrier agents for preventing adhesions after surgery for subfertility

BACKGROUNDnPelvic adhesions can be the result of inflamation, endometriosis or surgical trauma. Prevention of postoperative adhesions (either new or reoccurance) has been postulated by using barriers to prevent two surfaces being in contact. When pelvic surgery is being undertaken strategies to reduce pelvic adhesions occurring may be undertaken and these include barrier agents which are placed between the pelvic structures. Two synthetic barriers with differential characteristics are commercially available: oxidised regenerated cellulose (Interceed) and polytetrafluoroethylene (PTFC) (GoreTex).nnnOBJECTIVESnThe objective of this review was to assess the effect of mechanical barriers (materials interposed between pelvic structures to prevent adherence of serosal surfaces) used during pelvic surgery in women of reproductive age on pregnancy rates, pelvic pain, or postoperative adhesion reformation.nnnSEARCH STRATEGYnThe Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled clinical trials was undertaken. In addition, companies were contacted for unpublished trials.nnnSELECTION CRITERIAnRandomised controlled trials or controlled clinical trials of barriers versus no treatment or other barriers in women undergoing fertility preserving pelvic surgery.nnnDATA COLLECTION AND ANALYSISnReviewers assessed eligibility and trial quality.nnnMAIN RESULTSn15 randomised controlled trials were included. Five trials randomised patients while the remainder randomised pelvic organs. Laparoscopy was the primary surgical technique in six trials while the remaining trials were laparotomy. Indications for surgery included myomectomy (five trials), ovarian surgery (four trials), pelvic adhesions (six trials), endometriosis (two trials) and mixed (one trial). Thirteen trials assessed Interceed versus no treatment, two assessed Interceed versus Gore-Tex, one trial assessed Gore-Tex versus no treatment, and one trial assessed Seprafilm versus no treatment. No study reported pregnancy or reduction in pain as an outcome. The use of Interceed in women was associated with reduced incidence of pelvic adhesion formation, both new formation and re-formation following laparoscopic surgery and after laparotomy. Gore-Tex was more effective than no barrier or Interceed in preventing adhesion formation. There was limited evidence that Seprafilm was effective in preventing adhesion formation in women following myomectomy.nnnREVIEWERS CONCLUSIONSnThe absorbable adhesion barrier Interceed reduces the incidence of adhesion formation, both new formation and re-formation, at laparoscopy and laparotomy, but there are insufficient data to support its use to improve pregnancy rates. Gore-Tex may be superior to Interceed in preventing adhesion formation but its usefulness is limited by the need for suturing and later removal. There was no evidence of effectiveness of Seprafilm in preventing adhesion formation.

Pain relief in hysterosalpingography

BACKGROUNDnHysterosalpingography (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.nnnOBJECTIVESnTo compare the effectiveness of different types of pharmacological interventions for pain relief in women undergoing HSG for investigation of subfertility.nnnSEARCH METHODSnThis 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.nnnSELECTION CRITERIAnAll identified randomised controlled trials investigating pharmacological interventions for pain relief during HSG were investigated for selection.nnnDATA COLLECTION AND ANALYSISnFour 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.nnnMAIN RESULTSnThe 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.nnnAUTHORS CONCLUSIONSnTopical 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.

Liquid and fluid agents for preventing adhesions after surgery for subfertility

BACKGROUNDnPelvic surgery is associated with high rates of both de novo adhesion formation and adhesion reformation. Although the role of pelvic and/or tubal surgery in the management of infertility is more limited since the development of in-vitro fertilisation such surgery remains indicated for a number of selected patients. Other forms of pelvic surgery will remain prevalent in women of reproductive age (e.g. endometriosis surgery, ovarian cystectomy, myomectomy). Since subsequent fertility is reduced with increasing severity of periadnexal adhesions, pelvic adhesions will remain a clinical problem in infertility patients. Adjuvant therapy has been promoted for many years to prevent adhesion formation. Numerous substances have been used experimentally in animal models, many have been advocated for use during human surgery, and some are widely used in clinical practice. Steroids and antihistamines are given in the belief that they will promote fibrinolysis during healing without preventing healing.nnnOBJECTIVESnTo investigate whether pharmacological and liquid agents used as adjuvants during pelvic surgery in infertility patients lead to a reduction in the incidence or severity of postoperative adhesion (re-)formation, and/or an improvement in subsequent pregnancy rates.nnnSEARCH STRATEGYnThe specialised database of the Menstrual Disorders and Subfertility Group was searched.nnnSELECTION CRITERIAnRandomised controlled trials investigating the use of pharmacological and liquid agents to prevent adhesion formation after pelvic surgery for infertility.nnnDATA COLLECTION AND ANALYSISnData were extracted independently by the first 2 authors. Differences of opinion were registered and resolved by consensus with the senior author (RJL). Two by two tables were generated for each trial for the dichotomous outcome of pregnancy and the effects on pregnancy rate of each study is expressed as an odds ratio with 95% confidence intervals.nnnMAIN RESULTSnNone of the pharmacological or liquid agents investigated in a randomised controlled fashion was shown to improve postoperative pregnancy rates. There was some evidence that steroids reduced the incidence and severity of postoperative adhesion formation. Dextran appeared to neither reduce the incidence or severity of adhesions.nnnREVIEWERS CONCLUSIONSnThe routine use of pharmacological agents to prevent post-operative adhesions after infertility surgery cannot be recommended on the basis of the available evidence derived from RCTs. In connection with adhesion prevention, the evidence with regard to steroids is far from perfect but tentatively suggests that they may be beneficial. Further randomised studies should be conducted to investigate this further.

Pain relief in office gynaecology: a systematic review and meta-analysis

Hysteroscopy, hysterosalpingography (HSG), sonohysterography and endometrial ablation are increasingly performed in an outpatient setting. The primary reason for failure to complete these procedures is pain. The objective of this review was to compare the effectiveness and safety of different types of pharmacological intervention for pain relief in office gynaecological procedures. A systematic search of medical databases including PubMed, EMBASE, Cochrane Central register of controlled trials, PsychInfo and CINHAL was conducted in 2009. Randomised controlled trials (RCTs) investigating the use of local anaesthetics, opioid analgesics, non-opioid analgesics and intravenous sedation for pain relief during and after hysteroscopy, HSG, sonohysterography and endometrial ablation were reviewed. Secondary outcomes included adverse effects and failure to complete procedures. Where RCTs were not identified, the best available evidence was sought. Each study was assessed against inclusion criterion. Results for each study were expressed as a standardised mean difference (SMD) with 95% confidence intervals and combined for meta-analysis with Revman 5 software. Meta-analysis revealed beneficial effect of the use of local anaesthetics during and within 30 min after hysteroscopy; SMD -0.45 (95% CI -0.73, -0.17) and SMD -0.51 (95% CI -0.81, -0.21) respectively. No beneficial effect was noted during HSG. One RCT found evidence of benefit for pain relief during hysterosalpingo-contrastsonography; SMD -1.04 [95% CI -1.44, -0.63]. There was no significant difference in failure to complete hysteroscopy due to cervical stenosis between the intervention and control groups (OR 1.31 (95% CI 0.66, 2.59)), but the incidence of failure to complete the procedure due to pain was significantly less in the intervention group (OR 0.29 (0.12, 0.69)). There is evidence of benefit for the use of local anaesthetics for outpatient hysteroscopy and hysterosalpingo-contrastsonography. Local anaesthetics may be considered when performing hysteroscopy in postmenopausal women to reduce the failure rate.