The long road to recovery: at six months since the first COVID-19 wave, elective orthopedic care has still not fully recovered in Belgium.

PURPOSE: The primary aim of our study was to investigate elective orthopaedic care during the first wave government-imposed COVID-19 lockdown and at four weeks and 21 weeks after resuming elective care. The secondary aim of our study was to evaluate the implementation of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) COVID-19 Guidelines and Recommendations for Resuming Elective Surgery in the clinical practice of Belgian knee surgeons. METHODS: We sent three anonymous online surveys to 102 Belgian Knee Society members (BKS) at times mentioned above. Addressed topics were: (1) participant demographics, (2) elective surgeries, (3) outpatient visits, (4) ESSKA Guidelines, (5) patient and surgeon safety. RESULTS: During the COVID-19 lockdown, there was a decrease of 97% in elective knee surgeries and 91% in outpatient visits. At four and 21 weeks after resuming elective care, volumes were respectively 67% and 89% for elective surgeries and 81% and 91% for outpatient visits. Regarding ESSKA guidelines, 91% of surgeons had no COVID-19 testing prior to resuming elective care. Ninety-two per cent reported preoperative (< 72 h) patient PCR testing, and 45% gave preference to young patients without comorbidities. Seventy-two per cent did not use additional personal protective equipment (PPE) if a patient PCR test was negative. Forty-nine per cent continued to give preference to general anaesthesia. CONCLUSION: Our study shows that elective surgeries and outpatient visits were almost completely interrupted during the COVID-19 lockdown and were still below normal at four and 21 weeks after resuming elective care. Regarding ESSKA COVID-19 guidelines, our study observes good compliance in preoperative patient COVID-19 testing, but lower compliance for preoperative health care personnel testing, patient selection, use of PPE, and locoregional anaesthesia. LEVEL OF EVIDENCE: V.

Worldwide policies on epilepsy and blood donation: a survey among blood services.

BACKGROUND AND OBJECTIVES: Epilepsy is a common neurological disorder characterized by the appearance of seizures. Often, epilepsy patients are temporarily or permanently excluded from blood donation. To gain a better understanding of the policies that are currently applied, we performed a survey among blood services. METHODS: A cross-sectional, Web-based questionnaire using the online Questback tool was developed and distributed to 46 representatives of blood services worldwide. The questionnaire was composed of nine questions. RESULTS: A total of 27 respondents, representing blood services in 26 countries on five continents, participated in the survey. Current policies range from permanent acceptance over temporary exclusion to permanent exclusion. Rationales for these different policies are diverse. The majority of blood services (59·3%) apply temporary exclusion as their policy, though no consensus exists on the length of time that epilepsy patients have to be medication-free or seizure-free. None of the respondents could provide data about adverse events in epilepsy patients during the blood donation process. CONCLUSIONS: The results of this survey indicate a large discrepancy in policies applied worldwide. A lack of scientific evidence could be one of the underlying reasons. Therefore, it is of paramount importance to further research the potential risks for donors and recipients regarding blood donation by people with epilepsy. This can then serve as a base for evidence-based policymaking and lead to safer and more effective blood transfusion programmes.

Persistent aggregates in apheresis platelet concentrates are commonly collected from donors with a history of aggregate donation.

Platelet apheresis sometimes causes persistent aggregates (PA). This study (n = 211) shows that changing the apheresis settings to reach fixed product volumes instead of yields does not influence PA incidence, even though PA products on average contain more platelets than controls. Furthermore, logistic regression was used to model if PA can be predicted on the basis of certain predonation parameters. PA donation history was the only parameter retained, proving a strong determinant of predictability [AUC = 0.735 (SE = 0.022)]. Consequently, donations from a donor with previous PA history are 7.8 times more likely to contain PA than from a donor without preceding history.

The contribution of von Willebrand factor-GPIbα interactions to persistent aggregate formation in apheresis platelet concentrates.

BACKGROUND AND OBJECTIVES: Apheresis platelet concentrates sometimes contain persistent aggregates (PA). Because apheresis involves extracorporeal circulation, we hypothesized that interactions between GPIbα and von Willebrand factor (VWF) underlie their origin. MATERIALS AND METHODS: Platelets in donations with PA were compared to aggregate-free (AF) controls. Flow cytometry was used to determine platelet bound VWF. Degranulation was measured using P-selectin expression in flow cytometry and cytokine release using immunosorbent assays. Platelet adhesion to VWF was assessed in hydrodynamic flow and real-time video microscopy. RESULTS: Platelets in PA concentrates had significantly more (P = 0·009, n ≥ 8) bound VWF compared to AF platelets, but differences in VWF concentration, VWF collagen binding, activated VWF or GPIbα expression were not found. Degranulation was higher (P = 0·030, n = 7) in PA than AF concentrates on day 1 of storage, but adhesion to immobilized VWF under hydrodynamic flow conditions was normal at that moment. On day 6, however, significantly less VWF adhesion (P = 0·009, n ≥ 6) was found for PA platelets compared to AF, indicating accelerated storage lesion in PA products. In a model that mimicks PA formation by chemically induced binding of VWF to platelets, we found that degranulation, phosphatidylserine expression and metabolism did not differ with paired controls at any time during subsequent storage. CONCLUSION: Accelerated storage lesion is found in concentrates with PA, but this cannot be explained solely by increased platelet bound VWF following apheresis. Therefore, additional stressors are probably responsible for the increases observed in platelet degranulation and storage lesion in products with PA.

Persistent aggregates in apheresis platelet concentrates.

BACKGROUND: Aggregates often appear during apheresis. Sometimes, these persist throughout storage, causing product wastage. This study assessed product quality of apheresis concentrates containing persistent aggregates (PA) and aimed to identify the factors that contribute to their formation. METHODS: Donation (n = 180) and platelet indices (n ≥ 10) from apheresis concentrates with PA were compared with aggregate-free products. RESULTS: The proportion of donors with at least one previous PA donation was twofold higher in the PA group (P < 0·0001) indicating a donor dependence. Significantly higher donor whole blood platelet counts (286 ± 50 vs. 266 ± 49 × 10(3) /µl, P < 0·0001) and higher apheresis yields (6·0 ± 1·6 vs. 5·4 ± 1·5 × 10(11) , P < 0·0001) were noted in the PA group. Haematocrit was also slightly higher, but age, gender and body mass were similar. The pH of PA products on day six postdonation was significantly lower (P < 0·001), in line with higher lactic acid concentrations. Flow cytometry showed no differences in GPIbα levels or phosphatidylserine exposure. However, there was slightly more integrin activation as well as increased degranulation measured by P-selectin expression. Cytokine concentrations were also significantly higher in PA concentrates. Aggregation was normal in response to SFLLRN peptide and collagen stimulation, but agglutination at low-dose ristocetin was significantly higher (P = 0.01) in PA products. Finally, PA were disintegrated by plasmin-mediated thrombolysis but not by integrin αIIb ß3 inhibition. CONCLUSION: Products with PA have acceptable quality parameters, but additional functional studies are warranted. Furthermore, PA are more likely to recur in certain donors who have higher platelet counts.

Riboflavin and amotosalen photochemical treatments of platelet concentrates reduce thrombus formation kinetics in vitro.

BACKGROUND: Photochemical treatment (PCT) of platelet concentrates using photosensitizers and ultraviolet light illumination reduces the proliferation potential of pathogens by damaging biomolecules. MATERIALS AND METHODS: The impact of riboflavin (RF-PRT)- and amotosalen (AS-PCT)-based pathogen inactivation on platelets was studied using microfluidic flow chambers on immobilized collagen using standard platelet concentrates prepared from buffy coats in additive solution. Flow cytometry, metabolic parameters and light transmission aggregometry with thrombin-related peptide, collagen and ristocetin were determined concurrently. RESULTS: Both PCTs significantly decreased the platelet surface coverage kinetics in flow chambers over the course of the 7-day study. Platelet aggregation was affected following RF-PRT in response to all agonists, while AS-PCT mainly impacted low-dose ristocetin agglutination. RF-PRT induces premature platelet activation because integrin αII b ß3 was spontaneously activated, and α-degranulation, phosphatidylserine/-ethanolamine exposure and anaerobic metabolism significantly increased following treatment, which was not the case for AS-PCT. On the other hand, AS-PCT significantly diminished thrombus growth onto von Willebrand factor under shear flow. This defect was caused by fewer integrin αII b ß3 interactions, not by defective GPIbα-VWF binding as shown by adhesion experiments in the presence of tirofiban. Moreover, integrin αII b ß3 activation was also affected following the activation of platelets via GPVI-FcγRIIa or PAR1. Finally, amotosalen illumination as such is sufficient to induce platelet damage, with no additional measurable effect of the chemical adsorption step. Gamma irradiation caused no significant difference compared to controls on any time-point or for any parameter. CONCLUSION: Both PCTs significantly reduce thrombus formation rate but by different biochemical mechanisms.

Pedicle digital pad transfer and negative pressure wound therapy for reconstruction of the weight-bearing surface after complete digital loss in a dog.

A young Labrador Retriever was presented for treatment of severe distal hindlimb necrosis caused by bandage ischemia. During digit amputation at the metatarsophalangeal joints, the third and fourth digital pads were salvaged and transferred to the metatarsal stump to create a weight-bearing surface. Negative pressure wound therapy (NPWT) was utilized for flap immobilization and to promote granulation tissue in the remaining wound defect. Sturdy adherence of the digital pads was achieved after only four days. The skin defect healed completely by second intention and the stump was epithelialized with a thin pad after three months. At the nine month follow-up examination, the stump had a thick hyperkeratinized pad. The dog walked and ran without any apparent signs of discomfort and compensated for the loss of limb length by extending the stifle and tarsocrural joints. Despite a challenging wound in a difficult anatomical location, digital pad flap transfer and NPWT proved successful in restoring long-term ambulation in an active large breed dog.

Vessel sealing versus suture ligation for canine ovarian pedicle haemostasis: a randomised clinical trial.

Vessel sealing (VS) is well established in laparoscopic ovariectomy (OVE) in dogs. The objectives of this study were to evaluate the efficacy of ovarian pedicle haemostasis by VS using a commercially available VS tool in open OVE and compare it with suture ligation (SL). A prospective, randomised clinical trial including 20 female dogs was designed. Open OVE was performed via a standard mid-line celiotomy by a single surgeon using a standardised protocol. At random, the right ovarian pedicle was sealed (VS) or ligated (SL) whereas the left pedicle was treated by the alternative technique. Surgical times for procedural stages and intra-operative complications were recorded and statistically evaluated. Total surgical time was 29.28±11.13 minutes (range 12.50-62.13 minutes) and time from identification to removal of the ovary was significantly less when sealing (VS 2.22±0.58 minutes) than when ligating (SL 4.10±1.13 minutes P=0.0001). Intra-operative complications were rare for both techniques (failure of the electrode of the VS device (n=3); ovarian pedicle haemorrhage due to ligature slippage (n=1)). The results of the current study indicate that ovarian pedicle haemostasis achieved by VS is significantly faster than by placement of ligatures without appearing to compromise safety.

Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion.

BACKGROUND AND OBJECTIVE: Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF-PRT). METHODS: Activity and antigen of plasma components were determined following RF-PRT in the presence or absence of dissolved molecular oxygen. RESULTS: Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23 ± 8% and 29 ± 9% (n = 24), respectively, which corroborates with a mean decrease of 25% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF-PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3·1 ± 0·8 vs. 1·6 ± 0·5 nmol/mg protein) following RF-PRT, but not in the absence of dissolved molecular oxygen (1·8 ± 0·4 nmol/mg). CONCLUSIONS: RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.

Evaluation of 6 years of confidential unit exclusion at the Belgian Red Cross Flanders Blood Service.

BACKGROUND AND OBJECTIVES: The effectiveness of the confidential unit exclusion (CUE) as a safety measure to the blood supply is debated. We therefore investigated the usefulness of CUE in our donor population. METHODS: Data of CUE use, donor deferrals due to different degrees of sexual or blood exposure and data of confirmed positive transfusion-transmissible infection (TTI) markers were analyzed for the study period January 1, 2004 to December 31, 2009. RESULTS: The CUE user tended to be of young age, male and first time donor whereas the CUE non-responder was more likely to be older, first time donor without a clear sex predilection. CUE had low sensitivity (0·33%) and low positive predictive value (0·02%) in detecting TTI marker positive donations. Of 46 incident cases, one donor designated his pre-conversion donation as CUE positive. 29·6% of the donors deferred due to reported sex or intravenous drug related risk factors on the donor history questionnaire had ticked 'I do practice risk behavior' on the CUE form. Deferrals for all sexual or blood-blood contact related risk factors were 19·2 times higher among CUE positive donors than among CUE negative donors (95% CI, 18·5-19·9). CONCLUSION: Although CUE use is associated with higher rates of TTI risk, CUE has low efficiency to detect window period donations. Moreover, misuse results in a significant loss of units. Our data indicate a low risk perception among donors, hence efforts should focus on improving donor knowledge of and on donor's responsibility to disclose TTI risk.

Worldwide policies on haemochromatosis and blood donation: a survey among blood services.

BACKGROUND AND OBJECTIVES: Haemochromatosis (HC) is a disorder of iron metabolism, requiring frequent phlebotomy to normalize high serum iron levels. There is currently no consensus relating to the eligibility of these patients to donate blood for transfusion. To gain a better understanding of the policies worldwide, a survey amongst blood services was performed. MATERIALS AND METHODS: A web-based questionnaire was developed and distributed among 44 blood services in 41 countries to identify the different policies relating to patients with HC and blood donation. RESULTS: Respondents from 35 blood services (80%) of 33 countries completed the questionnaire. In 24 blood services among them (69%), individuals with genetic susceptibility for HC and/or patients with HC are accepted as blood donors. In approximately one-third of these blood centres (33%), genetic carriers/patients are allowed to donate blood more frequently than regular donors. Prescription from/approval by the patient's treating physician and/or a donor physician is required in the majority of the blood services (87%). Similar policies were identified in a few countries; however, in general, the policies regarding blood donation from patients with HC remain widely variable. CONCLUSION: The results of our survey demonstrate large differences in the blood donation policies regarding carriers/patients with HC illustrating the need for uniform evidence-based and cost-effective policies which could benefit both HC patients and the blood supply around the world.

Rigour of development does not AGREE with recommendations in practice guidelines on the use of ice for acute ankle sprains.

OBJECTIVE This study evaluated whether the Appraisal of Guidelines Research and Evaluation (AGREE) rigour of development score of practice guidelines on ice for acute ankle sprains is related to the convergence between recommendations. DESIGN The authors systematically reviewed guidelines on ice for acute ankle sprains. Four appraisers independently used the AGREE instrument to evaluate the rigour of development of selected guidelines. For each guideline, one reviewer listed the cited evidence on ice and calculated a cited evidence score. The authors plotted the recommended durations and numbers of ice applications over the standardised rigour of development score to explore the relationships. DATA SOURCES Three reviewers searched for guidelines in Medline, Embase, Sportdiscus, PEDro, G-I-N Guideline Library, Trip Database, SumSearch, National Guideline Clearinghouse and the Health Technology Assessment database, and conducted a web-based search for guideline development organisations. ELIGIBILITY CRITERIA Eligible guidelines had a development methodology that included a process to search or use results from scientific studies and the participation of an expert group to formulate recommendations. RESULTS The authors identified 21 guidelines, containing clinically significant variations in recommended durations and numbers of ice applications. The median standardised rigour of development score was 57% (IQR 18 to 77). Variations occurred evenly among guidelines with low moderate or high rigour scores. The median evidence citation score in the guidelines was 7% (IQR 0 to 61). CONCLUSIONS There is no relationship between the rigour of development score and the recommendations in guidelines on ice for acute ankle sprains. The guidelines suffered from methodological problems which were not captured by the AGREE instrument.

Use of a new endovenous laser device: results of the 1,500 nm laser.

BACKGROUND: A new endovenous laser wavelength (1,500 nm diode laser) in the treatment of great saphenous vein (GSV) reflux was evaluated. We studied the occlusion rate at 6 months and noted possible side effects. METHODS: In 129 patients, 158 GSVs were treated using the 1,500 nm diode laser. An average linear endovenous energy density of 53.4 J/cm and an average endovenous fluence of 32.21 J/cm(2) were administrated to the vein. RESULTS: The occlusion rate at 6 months postoperative was 93.3%. Some of the nonoccluded veins closed spontaneously. A postoperative foam treatment was necessary in 3.4% of the treated veins. We found a marked shrinkage of the treated veins. There were limited side effects: moderate or severe ecchymosis in 19%, moderate pain in 1%, moderate periphlebitis in 8.2%, with no paresthesias. CONCLUSION: Endovenous laser treatment of the GSV using a 1,500 nm diode laser is effective and safe. The marked shrinkage of the treated veins can guarantee good long-term results.

Barrier agents for adhesion prevention after gynaecological surgery.

BACKGROUND: Pelvic adhesion can form as a result of inflammation, endometriosis or surgical trauma. During pelvic surgery, strategies to reduce pelvic adhesion formation may include placing synthetic barrier agents such as oxidised regenerated cellulose, polytetrafluoroethylene or Fibrin sheets between the pelvic structures. OBJECTIVES: To assess the effect of physical barriers used during pelvic surgery in women of reproductive age on pregnancy rates, pelvic pain, or postoperative adhesion reformation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched September 2007) which is based on regular searches of MEDLINE, EMBASE, CINAHL, PsycINFO and CENTRAL, plus handsearching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. In addition, companies were contacted for unpublished trials. SELECTION CRITERIA: Any randomised controlled trials (RCTs) comparing the use of physical barriers versus no treatment or other physical barriers in the prevention of adhesions in women undergoing gynaecological surgery. DATA COLLECTION AND ANALYSIS: Review authors assessed trial eligibility and quality. MAIN RESULTS: Sixteen RCTs were included. Five trials randomised patients while the remainder randomised pelvic organs. Laparoscopy (six trials) and laparotomy (10 trials) were the primary surgical techniques. Indications for surgery included myomectomy (five trials), ovarian surgery (five trials), pelvic adhesions (four trials), endometriosis (one trial), and mixed (one trial). Eleven 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. A single trial assessed Fibrin sheet versus no treatment. No studies reported pregnancy or reduction in pain as outcomes. The use of Interceed was associated with reduced incidence of pelvic adhesion formation, both new formation and reformation following laparoscopic surgery or laparotomy. However, this result should be interpreted with caution. Gore-Tex was more effective than no barrier or Interceed in preventing adhesion formation. There was only limited evidence that Seprafilm was effective in preventing adhesion formation following myomectomy and no evidence to support Fibrin sheet. AUTHORS' CONCLUSIONS: The absorbable adhesion barrier Interceed reduces the incidence of adhesion formation following 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 and Fibrin sheet in preventing adhesion formation.

Cycle regimens for frozen-thawed embryo transfer.

BACKGROUND: Pregnancy rates following frozen-thawed embryo transfer (FET) treatment have always been found to be lower than following embryo transfer using fresh embryos. Nevertheless, FET increases the (cumulative) pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period compared to repeated 'fresh' cycles. FET is performed using different cycle regimens: spontaneous ovulatory cycles, cycles in which ovulation is induced by drugs and cycles in which the endometrium is artificially prepared by oestrogen (O) and progesterone (P) hormones, with or without a gonadotrophin releasing hormone agonist (GnRHa). OBJECTIVES: To determine whether there is a difference in outcome between natural cycle FET, artificial cycle FET and ovulation induction cycle FET. SEARCH STRATEGY: Our search included CENTRAL,DARE, MEDLINE (1950 to 2007), EMBASE (1980 to 2007) and CINAHL (1982 to 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET in assisted reproductive technology (ART). DATA COLLECTION AND ANALYSIS: The two authors independently extracted data. Dichotomous outcomes results (e.g. clinical pregnancy rate) were expressed as an odds ratio (OR) with 95% confidence intervals (CI) for each study. Continuous outcome results (endometrial thickness) were expressed as weighted mean difference (WMD). Where suitable, results were combined for meta-analysis with RevMan software using the Peto-modified Mantel-Haenszel method. MAIN RESULTS: Seven randomised controlled studies assessing six comparisons and including 1120 women in total were included in this review.1) O + P FET versus natural cycle FET: this comparison demonstrated no significant differences in outcomes but confidence intervals remain wide, and therefore moderate differences in either direction remain possible (OR 1.06, 95% CI 0.40 to 2.80, P 0.91).2) GnRHa + O + P FET versus O + P FET: this comparison showed that the live birth rate per woman was significantly higher in the former group (OR 0.38, 95% CI 0.17 to 0.84, P 0.02). The clinical pregnancy rate was also higher but not significantly so (OR 0.76, 95% CI 0.52 to 1.10, P 0.14).3) O + P FET versus follicle stimulating hormone (FSH) FET, 4) O + P FET versus clomiphene FET and 5) GnRHa + O + P FET versus clomiphene FET: there were no differences in the outcomes in the comparison of these cycle regimens.6) Clomiphene + human menopausal gonadotrophin (HMG) FET versus HMG FET: in a comparison of two ovulation induction regimes the pregnancy rate was found to be significantly higher in the HMG group (OR 0.46, 95% CI 0.23 to 0.92). There were also fewer cycle cancellations and a lower multiple pregnancy rate when HMG was used without clomiphene but these did not reach statistical significance. AUTHORS' CONCLUSIONS: At the present time there is insufficient evidence to support the use of one intervention in preference to another.

Intra-uterine insemination for male subfertility.

BACKGROUND: Intra-uterine insemination (IUI) is one of the most frequently used fertility treatments for couples with male subfertility. Its use, especially when combined with ovarian hyperstimulation (OH) has been subject of discussion. Although the treatment itself is less invasive and expensive than others, its efficacy has not been proven. Furthermore, the adverse effects of OH such as ovarian hyperstimulation syndrome (OHSS ) and multiple pregnancy are a concern. OBJECTIVES: The aim of this review was to determine whether for couples with male subfertility, IUI improves the live birth rates or ongoing pregnancy rates compared with timed intercourse (TI), with or without OH. SEARCH STRATEGY: We searched the Cochrane Menstrual and Disorders Subfertility Group Trials Special Register, the Cochrane Central Register of Controlled Trials (the Cochrane Library, 2006, issue 3), MEDLINE (1966 to May 2006), EMBASE (1980 to May 2006), SCIsearch and the reference lists of articles. We hand searched abstracts of the American Society for Reproductive Medicine, the European Society for Human Reproduction and Embryology. Authors of identified articles were contacted for unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCT's) with at least one of the following comparisons were included: 1) IUI versus TI or expectant management both in natural cycles 2) IUI versus TI both in cycles with OH 3) IUI in natural cycles versus TI + OH 4) IUI + OH versus TI in natural cycles 5) IUI in natural cycles versus IUI + OH. Couples with abnormal sperm parameters only were included. DATA COLLECTION AND ANALYSIS: Two co-reviewers independently performed quality assessment and data extraction. Where possible data were pooled, and a meta-analysis was performed. Sensitivity and subgroup analyses were carried out where possible and appropriate. MAIN RESULTS: Three trials of parallel design, and five trials of cross-over design with pre-cross-over data were included in the meta-analysis. Three compared IUI with TI both in stimulated cycles. The remaining four of these studies compared IUI versus IUI + OH . Three studies reported on our main outcome of interest live birth rate per couple. For the comparison IUI versus TI both in natural cycles no evidence of difference between the probabilities of pregnancy rates per woman after IUI compared with TI was found (Peto OR 5.3, 95% CI 0.42 to 67). No statistically significant of difference between pregnancy rates (PR) per couple for IUI + OH versus IUI could be found (Peto OR 1.47, 95% CI 0.92 to 2.37). For the comparison IUI versus TI both in stimulated cycles there was no evidence of statistically significant difference in pregnancy rates per couple either (Peto OR 1.67, 95% CI 0.83 to 3.37). There were insufficient data available for adverse outcomes such as OHSS, multiple pregnancy, miscarriage rate and ectopic pregnancy to perform a statistical analysis. For the other two comparisons no RCT's were found which reported pregnancy rates per couple. A further 10 studies which included one of the comparisons of interests were found. Since these studies reported pregnancy rates per cycle only these data could not be included in the meta-analysis. AUTHORS' CONCLUSIONS: There was insufficient evidence of effectiveness to recommend or advise against IUI with or without OH above TI, or vice versa. Large, high quality randomised controlled trials, comparing IUI with or without OH with pregnancy rate per couple as the main outcome of interest are lacking. There is a need for such trials since firm conclusions cannot be drawn yet.

Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned due to the risk of postsurgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However, women with PCOS who are treated with gonadotrophins often have an over-production of follicles which may result in ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming requiring intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH STRATEGY: We used the search strategy of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: Sixteen trials were identified and nine were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost. MAIN RESULTS: There was no evidence of a difference in live birth or clinical pregnancy rate between LOD and gonadotrophins and the pooled odds ratios (OR) (all studies) were 1.04 (95% CI 0.59 to 1.85) and 1.08 (95% CI 0.69 to 1.71) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% versus 16%; OR 0.13, 95% CI 0.03 to 0.52). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 95% 0.36 to 1.86). AUTHORS' CONCLUSIONS: There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene-resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long-term effects of LOD on ovarian function.

WITHDRAWN: Bromocriptine for unexplained subfertility in women.

BACKGROUND: Bromocriptine improves hyperprolactinemic amenorrhea and so could also be helpful in the treatment of unexplained subfertility in women. OBJECTIVES: To assess the effects of bromocriptine in women with unexplained subfertility. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched. SELECTION CRITERIA: Randomised trials comparing bromocriptine with placebo or no treatment in women with unexplained subfertility. DATA COLLECTION AND ANALYSIS: Two reviewers applied the eligibility criteria and assessed trial quality independently. MAIN RESULTS: Three trials involving of 127 women were included. All trials were double-blind comparisons with placebo, and one was of crossover design. Conception rates with bromocriptine treatment did not improve compared with placebo (odds ratio was 1.12, 95% confidence interval 0.48 to 2.57). AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate bromocriptine use in women with unexplained subfertility. However trials for women with unexplained subfertility who also have expressible galactorrhea may be worthwhile.

WITHDRAWN: Oil-soluble versus water-soluble media for assessing tubal patency with hysterosalpingography or laparoscopy in subfertile women.

BACKGROUND: There has been debate in the literature for more than 40 years as to whether flushing of the Fallopian tubes enhances fertility and whether this presumed therapeutic effect is greater with oil-soluble media than with water-soluble media. A meta-analysis of the therapeutic role of oil-soluble contrast media at hysterosalpingography was published in March 1994 (Watson 1994). This Cochrane Review is an expansion and update of that overview. OBJECTIVES: To evaluate the effect of flushing the Fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy rates in infertility patients. SEARCH STRATEGY: 1. For randomised controlled trials (RCTs): we searched the Cochrane Subfertility Review Group specialised register of controlled trials. 2. For non-randomised controlled studies: Medline and manual search of eight relevant journals. SELECTION CRITERIA: Six RCTs and six non-randomised controlled studies. In two studies tubal flushing was compared with no treatment-controls. Eleven studies, comprising a total of 2635 subjects, compared oil- with water-soluble media. DATA COLLECTION AND ANALYSIS: Independently by first 2 authors for: 1. Methodological trial characteristics 2. Characteristics of participants 3. OUTCOMES: the main studied outcome was pregnancy rate per patient MAIN RESULTS: In comparison with no treatment, a significant benefit on pregnancy rates was seen by flushing the tubes with oil-soluble media (OR 1.80, 95% CI 1.29-2.50) but not with water-soluble media (OR 0.87, 95% CI 0.50-1.52). In the direct comparison of oil- and water-soluble media the former lead to significantly higher pregnancy rates (OR 1.92, 95% CI 1.60-2.29). The treatment effect appeared similar in RCTs and non-RCTs. Subgroup analysis suggested the therapeutic benefit was greatest for patients suffering from unexplained infertility and least for those with tubal factor infertility. REVIEWER'S CONCLUSIONS: Flushing of the tubes with oil-soluble media increases subsequent pregnancy rates in infertility patients. The hypothesis that tubal "plugs" are a cause of proximal tubal occlusion and that oil-soluble media may flush them out, is supported by new techniques such as falloposcopy. Clinicians should consider flushing the tubes with OSCM before contemplating more invasive therapies.