Triumphs and trials with the UK abortion law: The power of collaboration in abortion reform.

The UK is usually viewed as having liberal abortion regulations, providing good access to abortion care within a publicly funded health service. However, the underlying laws are authoritarian, dating from an era when public executions drew large crowds and 67 years before women were able to vote. Abortion is only legal when two doctors certify it meets the permitted grounds, and the penalty for self-managed abortion is up to life imprisonment for both the woman and any accomplice. These laws had prevented the use of mifepristone and misoprostol at home. Changes to the regulations for misoprostol in 2018 and mifepristone in 2020 permitted home use, but the government announced they were rescinding the approval for mifepristone in 2022. This article discusses how, despite the opposition of government, significant progressive changes to the abortion laws were achieved. Early medical abortion at home is now protected in law, and safe access zones protect patients and staff from harassment and intimidation from protesters. Despite this progress, increasing numbers of women are facing criminal investigation and face long prison sentences if convicted. The need for decriminalization and for abortion care to be regulated like all other health care is the next pressing issue.

Acceptability of no-test medical abortion provided via telemedicine during Covid-19: analysis of patient-reported outcomes.

INTRODUCTION: The English government approved both stages of early medical abortion (EMA), using mifepristone and misoprostol under 10 weeks' gestation, for at-home use on 30 March 2020. MSI Reproductive Choices UK (MSUK), one of the largest providers of abortion services in England, launched a no-test telemedicine EMA pathway on 6 April 2020. The objectives of this study were to report key patient-reported outcome measures and to assess whether our sample was representative of the whole population receiving no-test telemedicine EMA. METHODS: A sample of all MSUK's telemedicine EMA patients between April and August 2020 were invited to opt in to a follow-up call to answer clinical and satisfaction questions. A total of 1243 (13.7% of all telemedicine EMAs) were successfully followed-up, on average within 5 days post-procedure. RESULTS: Patients reported high confidence in telemedicine EMA and high satisfaction with the convenience, privacy and ease of managing their abortion at home. The sample responding were broadly equivalent to the whole population receiving telemedicine. No patient reported that they were unable to consult privately. The majority (1035, 83%) of patients reported preferring the telemedicine pathway, with 824 (66%) indicating that they would choose telemedicine again if COVID-19 were no longer an issue. CONCLUSIONS: Telemedicine EMA is a valued, private, convenient and more accessible option that is highly acceptable for patients seeking an abortion, especially those for whom in-clinic visits are logistically or emotionally challenging. Evidence that this pathway would be a first choice again in future for most patients supports the case to make telemedicine EMA permanent.

Cervical priming before surgical abortion between 14 and 24 weeks: a systematic review and meta-analyses for the National Institute for Health and Care Excellence-new clinical guidelines for England.

OBJECTIVE: This study aimed to determine the optimal cervical priming regimen before surgical abortion between 14+0 and 24+0 weeks' gestation. DATA SOURCES: Embase, MEDLINE, and the Cochrane Library were searched for publications up to February 2020. Experts were consulted for any ongoing or missed trials. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials, published in English after 1985, that compared (1) mifepristone, misoprostol, and osmotic dilators against each other, alone or in combination; (2) different doses of mifepristone and misoprostol; (3) different intervals between priming and abortion; or (4) different routes of administration of misoprostol were included. METHODS: Risk of bias was assessed using the Cochrane Collaboration checklist for randomized controlled trials, and data were meta-analyzed in Review Manager 5.3. Dichotomous outcomes were analyzed as risk ratios using the Mantel-Haenszel method, and continuous outcomes were analyzed as mean differences using the inverse variance method. Fixed effects models were used when there was no significant heterogeneity (I2<50%), random effects models were used for moderate heterogeneity (I2≤50% and <80%), and evidence was not pooled when there was high heterogeneity (I2≥80%). Subgroup analyses were undertaken based on parity where available. The overall quality of the evidence was assessed using Grades of Recommendation Assessment, Development, and Evaluation. RESULTS: A total of 15 randomized controlled trials (N=2454) were included and showed decreased difficulty of procedure and/or increased cervical dilation and decreased patient acceptability with regimens that included dilators compared with those that did not include dilators; increased preoperative expulsion of the pregnancy with sublingual misoprostol and mifepristone compared with sublingual misoprostol alone; increased difficulty of procedure with dilators and misoprostol compared with dilators and mifepristone; decreased difficulty of procedure with dilators and mifepristone compared with dilators alone; and increased cervical dilation when dilators were placed the day before abortion compared with the same day. CONCLUSION: Considered alongside clinical expertise, the published data support the use of osmotic dilators, misoprostol, or mifepristone before abortion for pregnancies at 14+0 to 16+0 weeks' gestation; osmotic dilators or misoprostol for pregnancies at 16+1 to 19+0 weeks' gestation; and osmotic dilators alone or with mifepristone for pregnancies at 19+1 to 24+0 weeks' gestation. The effectiveness of pharmacologic agents alone beyond 16+0 weeks' gestation and the optimal timing of dilator placement remain important questions for future research.

Cervical priming before surgical abortion up to 13+6 weeks' gestation: a systematic review and metaanalyses for the National Institute for Health and Care Excellence-new clinical guidelines for England.

OBJECTIVE: This study aimed to determine the optimal cervical priming regimen before surgical abortion up to and including 13+6 weeks' gestation. DATA SOURCES: Embase, MEDLINE, and the Cochrane Library were searched for publications up to February 2020. Experts were consulted for any ongoing or missed trials. STUDY ELIGIBILITY CRITERIA: This study included randomized controlled trials published in English after 2000 that compared the following: (1) mifepristone and misoprostol against each other, placebo, or no priming; (2) different doses of mifepristone or misoprostol; (3) different intervals between priming and abortion; or (4) different routes of misoprostol administration. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias was assessed using the Cochrane Collaboration checklist for randomized controlled trials, and data were metaanalyzed in Review Manager 5.3. Dichotomous outcomes were analyzed as risk ratios using the Mantel-Haenszel method, and continuous outcomes were analyzed as mean differences using the inverse variance method. Fixed effects models were used when there was no substantial heterogeneity (I2<50%), random effects models were used for moderate heterogeneity (I2≤50% and <80%), and evidence was not pooled when there was high heterogeneity (I2≥80%). Subgroup analyses were undertaken based on parity where available. The overall quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A total of 18 randomized controlled trials (n=8538) were included and showed the following: decreased incomplete abortion rate (risk ratio=0.44; 95% confidence interval, 0.21-0.9) and force required to dilate the cervix (mean difference= -7.08 N; 95% confidence interval, -11.67 to -2.49) and increased preoperative bleeding (risk ratio=5.90; 95% confidence interval, 5.08-6.86) with misoprostol compared with no priming; decreased preoperative bleeding when sublingual misoprostol was given 1 hour before abortion compared with 3 hours before (risk ratio=0.14; 95% confidence interval, 0.03-0.56); and increased force required to dilate the cervix (mean difference=14.3 N; 95% confidence interval, 2.13-26.47) when mifepristone was given 24 hours before abortion compared with 48 hours before. The quality of the evidence base was limited by low event rates and risk of bias in included studies. CONCLUSION: Cervical priming with misoprostol decreases the force needed to dilate the cervix for first trimester surgical abortion and reduces the risk of incomplete abortion. Considered alongside clinical expertise, this evidence supports the use of routine cervical priming before first trimester surgical abortion with 400 µg misoprostol or, if misoprostol cannot be used, 200 mg oral mifepristone.

Access to and sustainability of abortion services: a systematic review and meta-analysis for the National Institute of Health and Care Excellence-new clinical guidelines for England.

BACKGROUND: Induced abortion is a common procedure. However, there is marked variation in accessibility of services across England. Accessing abortion services may be difficult, particularly for women who live in remote areas, are in the second trimester of pregnancy, have complex pre-existing conditions or have difficult social circumstances. OBJECTIVE AND RATIONALE: This article presents a two-part review undertaken for a new National Institute of Health and Care Excellence guideline on abortion care, and aiming to determine: the factors that help or hinder accessibility and sustainability of abortion services in England (qualitative review), and strategies that improve these factors, and/or other factors identified by stakeholders (quantitative review). Economic modelling was undertaken to estimate cost savings associated with reducing waiting times. SEARCH METHODS: Ovid Embase Classic and Embase, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), PsycINFO, Cochrane Library via Wiley Online, Cinahl Plus and Web of Science Core Collection were searched for articles published up to November 2018. Studies were included if they were published in English after 2001, conducted in Organization for Economic Co-operation and Development (OECD) countries and were: qualitative studies reporting views of patients and/or staff on factors that help or hinder the accessibility and sustainability of a safe abortion service, or randomized or non-randomized studies that compared strategies to improve factors identified by the qualitative review and/or stakeholders. Studies were excluded if they were conducted in OECD countries where abortion is prohibited altogether or only performed to save the woman's life. One author assessed risk of bias of included studies using the following checklists: Critical Appraisal Skills Programme checklist for qualitative studies, Cochrane Collaboration quality checklist for randomized controlled trials, Newcastle-Ottawa scale for cohort studies, and Effective Practice and Organization of Care risk of bias tool for before-and-after studies.Qualitative evidence was combined using thematic analysis and overall quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Confidence in the Evidence from Reviews of Qualitative Research (CERQual). Quantitative evidence was analysed in Review Manager 5.3 and overall quality of evidence was assessed using GRADE. OUTCOMES: Eight themes (service level barriers; financial barriers; logistical barriers; personal barriers; legal and policy barriers; privacy and confidentiality concerns; training and education; community prescribing and telemedicine introduce greater flexibility) and 18 subthemes were identified from 23 papers (n = 1016) included in the qualitative review. The quality of evidence ranged from very low to high, with evidence for one theme and seven subthemes rated as high quality. Nine studies (n = 7061) were included in the quantitative review which showed that satisfaction was better (low to high quality evidence) and women were seen sooner (very low quality evidence) when care was led by nurses or midwives compared with physician-led services, women were seen sooner when they could self-refer (very low quality evidence), and clinicians were more likely to provide abortions if training used an opt-out model (very low quality evidence). Economic modelling showed that even small reductions in waiting times could result in large cost savings for services. WIDER IMPLICATIONS: Self-referral, funding for travel and accommodation, reducing waiting times, remote assessment, community services, maximizing the role of nurses and midwives and including practical experience of performing abortion in core curriculums, unless the trainee opts out, should improve access to and sustainability of abortion services.

Simultaneous compared to interval administration of mifepristone and misoprostol for medical abortion up to 10+0 weeks' gestation: a systematic review with meta-analyses.

BACKGROUND: Medical abortion with mifepristone and misoprostol usually involves an interval of 36-48 hours between administering these drugs; however, it is possible that the clinical efficacy at early gestations may be maintained when the drugs are taken simultaneously. The objective of this systematic review was to determine the safety and effectiveness of simultaneous compared with interval administration of mifepristone and misoprostol for abortion up to 10+0 weeks' gestation. METHODS: We searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily, and Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations; and Cochrane Library on 11 December 2019. We included randomised controlled trials (RCTs), published in English from 1985, comparing simultaneous to interval administration of mifepristone and misoprostol for early abortion. Risk of bias was assessed using the Cochrane Collaboration checklist for RCTs. Meta-analysis of risk ratios (RRs) using the Mantel-Haenszel method were performed. The quality of the evidence was assessed using GRADE. RESULTS: Meta-analyses of three RCTs (n=1280) showed no differences in 'ongoing pregnancy' (RR 1.78, 95% CI 0.38 to 8.36), 'haemorrhage requiring transfusion or ≥500 mL blood loss' (RR 0.11, 95% CI 0.01 to 2.03) and 'incomplete abortion with the need for surgical intervention' (RR 1.30, 95% CI 0.76 to 2.25) between the interventions. Individual study results showed no difference in patient satisfaction, or 'need for repeat misoprostol', although 'time to onset of bleeding or cramping' was longer after simultaneous than interval administration. The quality of evidence was very low to moderate. CONCLUSION: The published data support the use of simultaneous mifepristone and misoprostol for medical abortion up to 9+0 weeks in women who prefer this method of administration.

Long-acting reversible contraception immediately after medical abortion: systematic review with meta-analyses.

BACKGROUND: Long-acting reversible contraceptives (LARCs) are safe, effective and convenient post-abortal methods. However, there is concern that some LARCs may reduce the effectiveness of abortifacient drugs or result in other adverse outcomes. OBJECTIVE AND RATIONALE: We undertook two systematic reviews to examine the early administration of LARCs in women undergoing medical abortion with mifepristone and misoprostol. (i) For women who are having a medical abortion and who plan to use a progestogen-only contraceptive implant or injectable, does administration of the contraception at the same time as mifepristone influence the efficacy of the abortion? (Implant/injectable review). (ii) For women who have had a medical abortion, how soon after expulsion of the products of conception is it safe to insert an intrauterine contraceptive device/system? (LNG-IUS/Cu-IUD review). SEARCH METHODS: On 19 November 2018, we searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily and Epub Ahead-of-Print, In-Process and Other Non-Indexed Citations; the Cochrane Library; Cinahl Plus; and Web of Science Core Collection. Eligible studies were randomised controlled trials (RCTs), in English from 1985 (Implant/injectable review) or 2007 (LNG-IUS/Cu-IUD review) onwards, conducted in women undergoing medical abortion with mifepristone and misoprostol and studying either (i) simultaneous administration of mifepristone and a progestogen-only contraceptive implant or injectable compared to administration >24 h after mifepristone, or (ii) immediate insertion of intrauterine contraception after expulsion of the products of conception compared to early insertion (≤7 days) or to delayed insertion (>7 days) or early compared to delayed insertion. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist for RCTs. All the outcomes were analysed as risk ratios and meta-analysed in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed-effect model. The overall quality of the evidence was assessed using GRADE. OUTCOMES: Two RCTs (n = 1027) showed lower 'subsequent unintended pregnancy' rates and higher 'patient satisfaction' rates, and no other differences, after simultaneous administration of mifepristone and the implant compared to delayed administration. One RCT (n = 461) showed higher 'patient satisfaction' rates after simultaneous administration than after delayed administration of mifepristone and the injectable, but no other differences between these interventions. Three RCTs (n = 536) found no differences other than higher copper IUC uptake after early compared to delayed insertion at ≤9 weeks of gestation and higher rates of IUC expulsion, continuation and uptake after immediate compared to delayed insertion at 9+1-12+0 weeks of gestation and higher IUC continuation rates after immediate compared to delayed insertion at 12+1-20+0 weeks of gestation. The quality of this evidence ranged from very low to high and was mainly compromised by low event rates, high attrition and no blinding. WIDER IMPLICATIONS: The contraceptive implant or injectable should be offered on the day of taking mifepristone. Intrauterine methods of contraception should be offered as soon as possible after expulsion of the pregnancy.

Anti-D prophylaxis for rhesus D (RhD)-negative women having an abortion of a pregnancy up to 13+6 weeks' gestation: a systematic review and new NICE consensus guidelines.

BACKGROUND: In order to develop the 2019 National Institute for Health and Care Excellence (NICE) national guideline on abortion care for the National Health Service1 we undertook a systematic review comparing anti-D prophylaxis to no prophylaxis in rhesus D (RhD)-negative women undergoing medical or surgical abortion of pregnancy at ≤13+6 weeks' gestation METHODS: We searched Embase, Medline and the Cochrane Library on 19 October 2018. We also consulted experts and checked reference lists for any missed trials. Eligible studies were randomised controlled trials and non-randomised comparative studies, published in English from 1985 onwards, comparing anti-D prophylaxis to no anti-D prophylaxis in RhD-negative women undergoing medical or surgical abortion at ≤13+6 weeks' gestation, and reporting subsequent anti-D isoimmunisation/sensitisation or subsequent affected pregnancy. These outcomes were to be analysed as risk ratios in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed or random effect model. The overall quality of the evidence was planned to be assessed using GRADE. RESULTS: The search identified 426 potentially relevant studies of which none met the inclusion criteria. Recommendations for practice were therefore based on the clinical expertise of the guideline committee. CONCLUSIONS: (1) Offer anti-D prophylaxis to women who are Rhesus D negative who are having an abortion after 10+0 weeks' gestation. (2) Do not offer anti-D prophylaxis to women who are having a medical abortion up to and including 10+0 weeks' gestation. (3) Consider anti-D prophylaxis for women who are rhesus D negative and are having a surgical abortion up to and including 10+0 weeks' gestation.

Initiation of abortion before there is definitive ultrasound evidence of intrauterine pregnancy: A systematic review with meta-analyses.

INTRODUCTION: Women are increasingly presenting for abortion at very early gestation. However, providers may be reluctant to conduct abortion at this stage as they may be concerned that they cannot exclude an ectopic pregnancy or that they may terminate a non-viable pregnancy, or may be concerned that both medical and surgical methods may be less effective at this stage of gestation. This provider concern may result in delays in the abortion as additional investigations may be required until an intrauterine pregnancy can be confirmed. Additional unnecessary visits may be distressing for women and waste health service resources. The objective of this systematic review was to determine whether it is safe and effective to initiate abortion before there is ultrasound evidence of an intrauterine pregnancy. MATERIAL AND METHODS: We searched Embase Classic, Embase; Ovid MEDLINE® Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, Ovid MEDLINE®; and Cochrane Library on 25 October 2019. Eligible studies were randomized and non-randomized comparative studies, published in English from 1985, comparing initiation of abortion before there is definitive evidence of an intrauterine pregnancy with initiation afterwards. We assessed risk-of-bias using the Newcastle-Ottowa scale. All outcomes were analyzed as risk ratios (RR) and meta-analyzed using the Mantel-Haenszel method. The quality of the evidence was assessed using GRADE. RESULTS: Two non-randomized studies (n = 3785) showed no differences in "missed ectopic pregnancy" (RR = 0.26, 95% CI 0.03-2.12), "ongoing pregnancy" (RR = 1.06, 95% CI 0.34-3.34), or "complete abortion without surgical intervention" (RR = 1, 95% CI 0.98-1.02) between initiation of medical abortion before or after ultrasound evidence of an intrauterine pregnancy. A third non-randomized study (n = 1530) showed no differences between initiation of surgical abortion before or after ultrasound evidence of an intrauterine pregnancy in "missed ectopic pregnancy" (no events), "ongoing pregnancy" (RR = 0.56, 95% CI 0.03-11.59) or "complete abortion without repeat surgical intervention" (RR = 1, 95% CI 0.99-1.01). The quality of evidence was very low. CONCLUSIONS: Initiation of abortion before there is definitive ultrasound evidence of an intrauterine pregnancy in women without signs or symptoms of an ectopic pregnancy should be considered.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

An analysis of characteristics of subjects examined for incretin effects on pancreatic pathology.

A recent autopsy analysis asserted that incretin drugs have the potential of increasing the risk for pancreatic cancer and for pancreatic neuroendocrine tumors. We examined the Network for Pancreatic Organ Donors with Diabetes (nPOD) database from which that analysis was derived. Our findings raise important questions about the comparability of the two groups of diabetes patients used for the analysis. Our review of the data available on the nPOD Web site and our reading of the earlier article lead us to the conclusion that the data, and the implications of the data, as expressed by the authors of the autopsy analysis are vastly overstated and are a misrepresentation of the information available.

Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation (anovulation), high levels of male hormones (hyperandrogenaemia) and high levels of insulin (hyperinsulinaemia secondary to increased insulin resistance). Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating the features of PCOS, including anovulation. OBJECTIVES: To assess the effectiveness of insulin-sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 3rd Quarter 2011), CINAHL (October 2011), MEDLINE (January 1966 to October 2011), and EMBASE (January 1985 to October 2011). SELECTION CRITERIA: Randomised controlled trials of insulin sensitising drugs compared with either placebo, no treatment, or an ovulation induction agent for women with PCOS, menstrual disturbance and subfertility. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and trial quality, and extracted data.   MAIN RESULTS: Forty-four trials (3992 women) were included for analysis, 38 of them using metformin and involving 3495 women.There was no evidence that metformin improved live birth rates, whether it was used alone (pooled OR 1.80, 95% CI 0.52 to 6.16, 3 trials, 115 women) or in combination with clomiphene (pooled OR 1.16, 95% CI 0.85 to 1.56, 7 trials, 907 women). However, clinical pregnancy rates were improved for metformin versus placebo (pooled OR 2.31, 95% CI 1.52 to 3.51, 8 trials, 707 women) and for metformin and clomiphene versus clomiphene alone (pooled OR 1.51, 95% CI 1.17 to 1.96, 11 trials, 1208 women). In the studies that compared metformin and clomiphene alone, there was evidence of an improved live birth rate (pooled OR 0.3, 95% CI 0.17 to 0.52, 2 trials, 500 women) and clinical pregnancy rate (pooled OR 0.34, 95% 0.21 to 0.55, 2 trials, 500 women) in the group of obese women who took clomiphene.Metformin was also associated with a significantly higher incidence of gastrointestinal disturbances than placebo (pooled OR 4.27, 95% CI 2.4 to 7.59, 5 trials, 318 women) but no serious adverse effects were reported. AUTHORS' CONCLUSIONS: In agreement with the previous review, metformin was associated with improved clinical pregnancy but there was no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the role of metformin in improving reproductive outcomes in women with PCOS appears to be limited.

Two-quadrant high-volume sub-Tenon's anaesthesia for vitrectomy: a randomised controlled trial.

BACKGROUND: Total volume using a standard single inferonasal injection for sub-Tenon's anaesthesia is limited by an increase in intraocular pressure (IOP) and commonly requires the operating surgeon to top-up the block intraoperatively. This study compares the efficacy and safety of a two-quadrant technique that allows the use of a higher volume of local anaesthetic. METHODS: 54 patients undergoing vitrectomy were randomised into two groups. The control group (n=27) received a standard 5 ml single inferonasal sub-Tenon injection of a 50:50 mixture of 2% lidocaine and 0.5% bupivacaine with 150 IU hyaluronidase. The study group (n=27) received a 5 ml inferonasal and 5 ml superotemporal injection of the same mixture (10 ml total). The primary outcome measure was the number of intraoperative top-ups required. Secondary outcome measures were intraoperative and postoperative pain scores, IOP, block onset time, ocular akinesia, eyelid akinesia and chemosis. RESULTS: 24 patients required a top-up in the control group. No patients required a top-up in the study group (p<0.001). IOP measurements were similar in both groups. Block onset was shorter, eyelid akinesia was improved and pain scores were also reduced in the study group intraoperatively and at 0-2 h, 4-6 h, 10-14 h and 20-24 h postoperatively. CONCLUSIONS: Two-quadrant sub-Tenon's anaesthesia using 10 ml of a 50:50 mixture of 2% lidocaine and 0.5% bupivacaine with 150 IU hyaluronidase seems to be more effective than a single-quadrant technique at reducing intraoperative and postoperative pain during vitrectomy.

Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome. OBJECTIVES: To assess the effectiveness of insulin sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS and menstrual disturbance. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library, third Quarter 2008), CINAHL (searched September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008). All searches were rerun 13 August 2009 17 RCTs were located and await classification. SELECTION CRITERIA: Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent. DATA COLLECTION AND ANALYSIS: Thirty one trials (2537 women) were included for analysis, 27 of them using metformin and involving 2150 women. MAIN RESULTS: There is no evidence that metformin improves live birth rates whether it is used alone (Pooled OR = 1.00, 95% CI 0.16 to 6.39) or in combination with clomiphene (Pooled OR = 1.48, 95% CI 1.12 to 1.95). However, clinical pregnancy rates are improved for metformin versus placebo (Pooled OR = OR 3.86, 95% C.I. 2.18 to 6.84) and for metformin and clomiphene versus clomiphene alone (Pooled OR =1.48, 95% C.I. 1.12 to 1.95) ). In the studies that compared metformin and clomiphene alone, there was no evidence of an improved live birth rate (OR= 0.67, 95% CI 0.44 to 1.02) but the pooled OR resulted in improved clinical pregnancy rate in in the clomiphene group (OR = 0.63 , 95% 0.43 to 0.92), although there was significant heterogeneity.There is also evidence that ovulation rates are improved with metformin in women with PCOS for metformin versus placebo (Pooled OR 2.12, 95% CI 1.50 to 3.0) and for metformin and clomiphene versus clomiphene alone (Pooled OR = 3.46, 95% CI 1.97 to 6.07).Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported. AUTHORS' CONCLUSIONS: In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the use of metformin in improving reproductive outcomes in women with PCOS appears to be limited.