Selective oestrogen receptor modulators (SERMs) for endometriosis.

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. This chronic and recurring condition occurs in women of reproductive age. It is a common cause of pain or infertility and can cause non-specific symptoms such as lower back pain, dyspareunia (pain during or after intercourse), and dysmenorrhoea (menstrual pain). Endometriosis is an oestrogen-dependent disease. Medical treatment aims to relieve symptoms and shrink lesions by suppressing the normal menstrual cycle. In this review, we consider medication specifically aiming to modulate oestrogen receptors as an alternative method of treatment. OBJECTIVES: To evaluate the effectiveness and safety of selective oestrogen receptor modulators (SERMs) in the management of endometriosis. SEARCH METHODS: We searched for trials in the following databases (from their inception to 28 May 2020): Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies (CRS Online), MEDLINE, Embase, CINAHL, PsycINFO, and registers of ongoing trials. In addition, we searched all reference lists of included trials, and we contacted experts in the field, in an attempt to locate trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing selective oestrogen receptor modulators (SERMs) with placebo, no treatment, other medical treatment, or surgery for endometriosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two review authors independently selected trials for inclusion, assessed risk of bias, and extracted data using data extraction forms. We used risk ratios (RRs) with 95% confidence intervals (CIs) for reporting dichotomous data. Primary review outcomes were relief of pelvic pain and adverse events. Secondary outcomes included quality of life, recurrence rate, and economic and fertility outcomes. MAIN RESULTS: We included only one RCT, which included 93 women, comparing the SERM raloxifene with placebo in biopsy-proven endometriosis. All women first underwent complete surgical excision of all lesions. Evidence was of very low quality: the main limitation was imprecision - with very sparse data from only one small study, which included only women after surgical treatment. Relief of pelvic pain The included study did not specifically measure the primary outcome of pain relief. Study authors reported that time to return of pelvic pain (defined as two months of pain equal to or more severe than pain at study entry) was more rapid in the raloxifene group (P = 0.03). Adverse events The included study reported adverse events such as pelvic pain, ovarian cyst, headache, migraine, and depression. We are uncertain whether raloxifene improves the incidence of pelvic pain (RR 1.25, 95% CI 0.63 to 2.45), ovarian cysts (RR 1.57, 95% CI 0.55 to 4.43), headache (RR 1.09, 95% CI 0.49 to 2.43), migraine (RR 0.73, 95% CI 0.28 to 1.95), depression (RR 1.96, 95% CI 0.63 to 6.06), or other adverse events (RR 0.08, 95% CI 0.00 to 1.30) (all: 1 study, n = 93; very low-quality evidence). Quality of life The study described a statistically significant difference in mental health quality of life (QoL) by 12 months, in favour of placebo treatment (mean difference 11.1, 95% CI 0.01 to 21.19). Other QoL data did not differ between groups but were not reported in detail. Recurrence rate, fertility, and economic outcomes We are uncertain whether raloxifene improves the recurrence rate of endometriosis, proven by biopsy, when compared to placebo (RR 1.20, 95% CI 0.66 to 2.21; 1 study, n = 93; very low-quality evidence). This suggests that if 28% of women taking placebo have biopsy-proven recurrence of endometriosis, between 19% and 62% of those taking raloxifene will do so. These outcomes are prone to bias, as not all women had an actual second laparoscopy. Recurrence based on symptoms (non-menstrual pain, dysmenorrhoea, or dyspareunia) was described; in these cases, symptoms improved after use of raloxifene as well as after use of placebo. The included study did not report data on economic outcomes. No comparative data were available on pregnancy, as the study included only women who agreed to postpone pregnancy until after the study endpoint; the few pregnancies that did occur were uneventful but were regarded as an adverse event.  AUTHORS' CONCLUSIONS: Based on a single, small RCT and incomplete data, we are uncertain of the effects of SERMs on pain relief in surgically treated patients with endometriosis. The included study was stopped prematurely because of higher pain scores among women who took SERMs when compared to scores among those receiving placebo. Further research is needed to fully evaluate the role of SERMs in endometriosis.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. SEARCH METHODS: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. SELECTION CRITERIA: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. MAIN RESULTS: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. AUTHORS' CONCLUSIONS: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

Measuring patient-centredness in publicly funded fertility care: A New Zealand validation and international comparison of the Patient-Centred Questionnaire-Infertility.

BACKGROUND: The Patient-Centred Questionnaire-Infertility (PCQ-Infertility) has proven to be a reliable instrument to assess the extent of patient-centredness of fertility care in European countries. AIMS: To validate the PCQ-Infertility in New Zealand (NZ) and to compare results with international experience. MATERIALS AND METHODS: A cross-sectional 46-item questionnaire study among 409 women undergoing publicly funded fertility care (intrauterine insemination or in vitro fertilisation / intracytoplasmic sperm injection) in three fertility clinics in the Northern Auckland region was performed between October 2015 and September 2016. Inclusion of eligible participants was both retro- and prospective. The questionnaire was distributed by email link and women were asked to complete it with their partner. Internal consistency and construct validity were determined and correction for case mix was performed. Mean dimension scores, adjusted for 'current pregnancy', 'educational level' and 'treatment type', were calculated for each dimension of the PCQ-Infertility. NZ results were compared with PCQ-Infertility results from five countries. RESULTS: Of 409 invited women, 255 questionnaires were submitted (response rate 62%), of which 216 (53%) were analysable. The dimension 'Care organization' had poor internal consistency, but overall the questionnaire had high internal consistency (Cronbach's α = 0.93). Construct validity was also good. International comparison showed NZ to have the second highest overall score. In New Zealand, the lowest scoring domain was 'Continuity and transition'. CONCLUSIONS: The NZ version of the PCQ-infertility proved a valid instrument for the assessment of patient-centredness of publicly funded fertility care. Future research should focus on international inequities in patient-centred fertility care and use of the tool for quality improvement. Local use of the PCQ-Infertility is encouraged.

Clinical trial registration in fertility trials - a case for improvement?

STUDY QUESTION: What is the prevalence and source of prospectively and retrospectively registered and unregistered trials in fertility treatments? SUMMARY ANSWER: Trial registration is low and does not appear to be changing over the 5 years studied. WHAT IS KNOWN ALREADY: Trial registration is associated with lower risk of bias than in unregistered trials. STUDY DESIGN, SIZE, DURATION: The Cochrane Gynaecology and Fertility Group's specialised register was searched on 5 November 2015 for randomised controlled trials (RCTs) published from January 2010 to December 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible trials included randomised women or men for fertility treatments, were published in full text, and written in English. Two reviewers independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. MAIN RESULTS AND ROLE OF CHANCE: Of 693 eligible RCTS, only 44% were registered trials. Of 309 registered trials, 21.7% were prospectively registered, 15.8% were registered within 6 months of first patient enrolment and 62.5% were retrospectively registered trials. Prospective trial registration by country varied from 0% to 100%. The highest frequency of prospective trial registration amongst the top 10 publishing countries was 31% in the Netherlands. LIMITATIONS, REASONS FOR CAUTION: Only English language trials were included in this review. WIDER IMPLICATIONS OF THE FINDINGS: Prospective trial registration is still low. Journals, funders and ethics committees could have a greater role to increase trial registration. STUDY FUNDING/COMPETING INTERESTS: University of Auckland. No competing interests.

Antibiotic prophylaxis for elective hysterectomy.

BACKGROUND: Elective hysterectomy is commonly performed for benign gynaecological conditions. Hysterectomy can be performed abdominally, laparoscopically, or vaginally, with or without laparoscopic assistance. Antibiotic prophylaxis consists of administration of antibiotics to reduce the rate of postoperative infection, which otherwise affects 40%-50% of women after vaginal hysterectomy, and more than 20% after abdominal hysterectomy. No Cochrane review has systematically assessed evidence on this topic. OBJECTIVES: To determine the effectiveness and safety of antibiotic prophylaxis in women undergoing elective hysterectomy. SEARCH METHODS: We searched electronic databases to November 2016 (including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Studies (CRSO), MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as clinical trials registers, conference abstracts, and reference lists of relevant articles. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing use of antibiotics versus placebo or other antibiotics as prophylaxis in women undergoing elective hysterectomy. DATA COLLECTION AND ANALYSIS: We used Cochrane standard methodological procedures. MAIN RESULTS: We included in this review 37 RCTs, which performed 20 comparisons of various antibiotics versus placebo and versus one another (6079 women). The quality of the evidence ranged from very low to moderate. The main limitations of study findings were risk of bias due to poor reporting of methods, imprecision due to small samples and low event rates, and inadequate reporting of adverse effects. Any antibiotic versus placebo Vaginal hysterectomyModerate-quality evidence shows that women who received antibiotic prophylaxis had fewer total postoperative infections (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.19 to 0.40; five RCTs, N = 610; I2 = 85%), less urinary tract infection (UTI) (RR 0.58, 95% CI 0.43 to 0.77; eight RCTs, N = 1790; I2 = 44%), fewer pelvic infections (RR 0.28, 95% CI 0.20 to 0.39; 11 RCTs, N = 2010; I2 = 57%), and fewer postoperative fevers (RR 0.43, 95% CI 0.34 to 0.54; nine RCTs, N = 1879; I2 = 48%) than women who did not receive such prophylaxis. This suggests that antibiotic prophylaxis reduces the average risk of postoperative infection from about 34% to 7% to 14%. Whether this treatment has led to differences in rates of other serious infection remains unclear (RR 0.20, 95% CI 0.01 to 4.10; one RCT, N = 146; very low-quality evidence).Data were insufficient for comparison of adverse effects. Abdominal hysterectomyWomen who received antibiotic prophylaxis of any class had fewer total postoperative infections (RR 0.16, 95% CI 0.06 to 0.38; one RCT, N = 345; low-quality evidence), abdominal wound infections (RR 0.64, 95% CI 0.45 to 0.92; 11 RCTs, N = 2434; I2 = 0%; moderate-quality evidence), UTIs (RR 0.39, 95% CI 0.29 to 0.51; 11 RCTs, N = 2547; I2 = 26%; moderate-quality evidence), pelvic infections (RR 0.50, 95% CI 0.35 to 0.71; 11 RCTs, N = 1883; I2 = 11%; moderate-quality evidence), and postoperative fevers (RR 0.60, 95% CI 0.51 to 0.70; 11 RCTs, N = 2581; I2 = 51%; moderate-quality evidence) than women who did not receive prophylaxis, suggesting that antibiotic prophylaxis reduces the average risk of postoperative infection from about 16% to 1% to 6%. Whether this treatment has led to differences in rates of other serious infection remains unclear (RR 0.44, 95% CI 0.12 to 1.69; two RCTs, N = 476; I2 = 29%; very low-quality evidence).It is unclear whether rates of adverse effects differed between groups (RR 1.80, 95% CI 0.62 to 5.18; two RCTs, N = 430; I2 = 0%; very low-quality evidence). Head-to-head comparisons between antibiotics Vaginal hysterectomyWe identified four comparisons: cephalosporin versus penicillin (two RCTs, N = 470), cephalosporin versus tetracycline (one RCT, N = 51), antiprotozoal versus lincosamide (one RCT, N = 80), and cephalosporin versus antiprotozoal (one RCT, N = 78). Data show no evidence of differences between groups for any of the primary outcomes, except that fewer cases of total postoperative infection and postoperative fever were reported in women who received cephalosporin than in those who received antiprotozoal.Only one comparison (cephalosporin vs penicillin; two RCTs, N = 451) yielded data on adverse effects and showed no differences between groups. Abdominal hysterectomyWe identified only one comparison: cephalosporin versus penicillin (N = 220). Data show no evidence of differences between groups for any of the primary outcomes. Adverse effects were not reported. Combined antibiotics versus single antibiotics Vaginal hysterectomyWe identified three comparisons: cephalosporin plus antiprotozoal versus cephalosporin (one RCT, N = 78), cephalosporin plus antiprotozoal versus antiprotozoal (one RCT, N = 78), and penicillin plus antiprotozoal versus penicillin (one RCT, N = 230). Data were unavailable for most outcomes, including adverse effects. We found no evidence of differences between groups, except that fewer women receiving cephalosporin with antiprotozoal received a diagnosis of total postoperative infection, UTI, or postoperative fever compared with women receiving antiprotozoal. Abdominal hysterectomyWe identified one comparison (penicillin plus antiprotozoal vs penicillin only; one RCT, N = 230). Whether differences between groups occurred was unclear. Adverse effects were not reported. Comparison of cephalosporins in different regimensSingle small trials addressed dose comparisons and provided no data for most outcomes, including adverse effects. Whether differences between groups occurred was unclear. No trials compared route of administration.The quality of evidence for all head-to-head and dose comparisons was very low owing to very serious imprecision and serious risk of bias related to poor reporting of methods. AUTHORS' CONCLUSIONS: Antibiotic prophylaxis appears to be effective in preventing postoperative infection in women undergoing elective vaginal or abdominal hysterectomy, regardless of the dose regimen. However, evidence is insufficient to show whether use of prophylactic antibiotics influences rates of adverse effects. Similarly, evidence is insufficient to show which (if any) individual antibiotic, dose regimen, or route of administration is safest and most effective. The most recent studies included in this review were 14 years old at the time of our search. Thus findings from included studies may not reflect current practice in perioperative and postoperative care and may not show locoregional antimicrobial resistance patterns.

Management of ovarian stimulation for IVF: narrative review of evidence provided for World Health Organization guidance.

In this paper, a review of evidence provided to the World Health Organization (WHO) guideline development, who prepare global guidance on the management of ovarian stimulation for women undergoing IVF, is presented. The purpose of ovarian stimulation is to facilitate retrieval of multiple oocytes during a single IVF cycle. Availability of multiple oocytes compensates for inefficiencies in subsequent stages of the cycle, which include oocyte maturation, IVF, embryo culture, embryo transfer, and implantation. Multiple embryos can be transferred in most women, and spare embryos can be frozen to allow for future chances of pregnancy without the need for repeated ovarian stimulation and oocyte retrieval. Our evidence synthesis team addressed 10 clinical questions on management of ovarian stimulation for IVF, prepared a narrative review of the evidence and drafted recommendations to be considered through WHO guideline development processes. Our main outcome measures were live birth, clinical pregnancy, and ovarian hyperstimulation syndrome.

Clinical trial registration was not an indicator for low risk of bias.

OBJECTIVES: To determine the prevalence of registered trials and to evaluate the risk of bias between registered and unregistered clinical trials. STUDY DESIGN AND SETTING: The Cochrane Gynecology and Fertility Group's specialized register was searched on November 5, 2015, for randomized controlled trials published from 2010 to 2014. Studies were selected if they had randomized women or men for fertility treatments, were published in full text and written in English. Two reviewers then independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. RESULTS: Of 693 eligible randomized controlled trials, only 44% were found to be registered. Unregistered clinical trials had smaller sample sizes than registered trials (P < 0.001). A random subsample of 125 registered and 125 unregistered trials was assessed for risk of bias using five of the Cochrane Risk of Bias "domains." Registered and unregistered trials differed in their risk of bias for random sequence generation (P = 0.001), allocation concealment (P = 0.003), and selective reporting (P < 0.001) but not blinding or incomplete outcome data (P > 0.05) domains. Only 54 (43.2%) of the 125 registered trials were registered prospectively. This study has the following limitations. Only English language trials were included in this review. We were unable to obtain protocols for the unregistered trials and therefore were unable to assess the risk of bias in the selective reporting domain. CONCLUSIONS: All available trials should be included in systematic reviews and assessed for risk of bias as there are both registered trials with high risk of bias and unregistered trials with low risk of bias and by excluding unregistered trials more than half of the available evidence will be lost.

Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33% in its mild form and 3% to 8% in its moderate or severe form. These numbers might even be higher for high-risk women such as those with polycystic ovaries or a high oocyte yield from ovum pickup. OBJECTIVES: The objective of this overview is to identify and summarise all evidence from Cochrane systematic reviews on interventions for prevention or treatment of moderate, severe and overall OHSS in couples with subfertility who are undergoing ART cycles. METHODS: Published Cochrane systematic reviews reporting on moderate, severe or overall OHSS as an outcome in ART cycles were eligible for inclusion in this overview. We also identified Cochrane submitted protocols and title registrations for future inclusion in the overview. The evidence is current to 12 December 2016. We identified reviews, protocols and titles by searching the Cochrane Gynaecology and Fertility Group Database of Systematic Reviews and Archie (the Cochrane information management system) in July 2016 on the effectiveness of interventions for outcomes of moderate, severe and overall OHSS. We undertook in duplicate selection of systematic reviews, data extraction and quality assessment. We used the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the quality of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables. MAIN RESULTS: We included a total of 27 reviews in this overview. The reviews were generally of high quality according to AMSTAR ratings, and included studies provided evidence that ranged from very low to high in quality. Ten reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Metformin treatment before and during an ART cycle for women with PCOS (moderate-quality evidence).• Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence).• GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence).• Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence).• Intravenous fluids (plasma expanders) around the time of hCG administration or oocyte pickup in ART cycles (very low-quality evidence).• Progesterone for luteal phase support in ART cycles (low-quality evidence).• Coasting (withholding gonadotrophins) - a promising intervention that needs to be researched further for reduction of OHSS.On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of embryo cryopreservation. AUTHORS' CONCLUSIONS: Currently, 27 reviews in the Cochrane Library were conducted to report on or to try to report on OHSS in ART cycles. We identified four review protocols but no new registered titles that can potentially be included in this overview in the future. This overview provides the most up-to-date evidence on prevention of OHSS in ART cycles from all currently published Cochrane reviews on ART. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise other outcomes such as pregnancy or live birth rate. Review results, however, are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. The dopamine agonist cabergoline was introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. As cabergoline seemed to be effective in preventing OHSS, other types of dopamine agonists, such as quinagolide and bromocriptine, have since been studied in ART to prevent OHSS. OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in high-risk women undergoing ART treatment. SEARCH METHODS: We searched several databases from inception to August 2016 (Cochrane Gynaecology and Fertility Specialised Register of trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Clinicaltrials.gov and the World Health Organization International Trials Registry Platform (ICTRP)) for randomised controlled trials (RCTs) assessing the effect of dopamine agonist in preventing OHSS. We handsearched the reference lists of relevant studies. SELECTION CRITERIA: We considered RCTs which compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in high-risk women for inclusion. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles, abstracts and full texts of publications, selected studies, extracted data and assessed risk of bias. We resolved any disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. In addition, we graded the overall quality of the evidence using GRADE criteria. MAIN RESULTS: The search identified 14 new RCTs since the last published version of this review, resulting in 16 included RCTs involving 2091 high-risk women for this updated review. They evaluated three types of dopamine agonists: cabergoline, quinagolide and bromocriptine.When compared with placebo or no intervention, dopamine agonists seemed effective in the prevention of moderate or severe OHSS (OR 0.27, 95% CI 0.19 to 0.39; 1022 participants; 8 studies; I2 = 0%; moderate quality evidence). This suggests that if 29% of women undergoing ART experience moderate or severe OHSS, the use of dopamine agonists will lower this to 7% to 14% of women. There was no evidence of a difference in live birth rate, clinical pregnancy rate, multiple pregnancy rate or miscarriage rate (very low to moderate quality evidence). However, taking dopamine agonists (especially quinagolide) may increase the incidence of adverse events such as gastrointestinal adverse effects (OR 4.54, 95% CI 1.49 to 13.84; 264 participants; 2 studies; I2 = 49%, very low quality evidence).When we compared dopamine agonist plus co-intervention with co-intervention, there was no evidence of a difference in the outcomes of moderate or severe OHSS, live birth rate, clinical pregnancy rate, miscarriage rate or adverse events. The co-interventions were hydroxyethyl starch (two RCTs) and albumin (one RCT).Cabergoline was associated with a lower risk of moderate or severe OHSS compared with human albumin (OR 0.21, 95% CI 0.12 to 0.38; 296 participants; 3 studies; I2 = 72%). However, there was no evidence of a difference between cabergoline and hydroxyethyl starch, coasting (withholding any more ovarian stimulation for a few days) or prednisolone. There was an increased clinical pregnancy rate in the cabergoline group when cabergoline was compared with coasting (OR 2.65, 95% CI 1.13 to 6.21; 120 participants; 2 studies; I2 = 0%). In other respects, there was no evidence of a difference in clinical pregnancy rate, multiple pregnancy rate or miscarriage rate between cabergoline and other active interventions.The quality of the evidence between dopamine agonist and placebo or no intervention ranged from very low to moderate, mainly due to poor reporting of study methods (mostly a lack of details on randomisation or blinding) and serious imprecision for some comparisons. AUTHORS' CONCLUSIONS: Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence). If a fresh embryo transfer is performed, the use of dopamine agonists does not affect the pregnancy outcome (live birth rate, clinical pregnancy rate and miscarriage rate) (very low to moderate quality evidence). However, dopamine agonists might increase the risk of adverse events, such as gastrointestinal symptoms. Further research should focus on dose-finding, comparisons with other effective treatments and consideration of combination treatments. Therefore, large, well-designed and well-executed RCTs that involve more clinical endpoints (e.g., live birth rate) are necessary to further evaluate the role of dopamine agonists in OHSS prevention.

Volume expanders for the prevention of ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially fatal complication of ovarian stimulation which affects 1% to 14% of all in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. A number of clinical studies with conflicting results have reported on the use of plasma expanders such as albumin, hydroxyethyl starch (HES), mannitol, polygeline and dextran as a possible intervention for the prevention of OHSS. Women with very high estradiol levels, high numbers of follicles or oocytes retrieved, and women with polycystic ovary syndrome (PCOS), are at particularly high risk of developing OHSS. Plasma expanders are not commonly used nowadays in ovarian hyperstimulation. This is mainly because clinical evidence on their effectiveness remains sparse, because of the low incidence of moderate and severe ovarian hyperstimulation syndrome (OHSS) and the simultaneous introduction of mild stimulation approaches, gonadotropin-releasing hormone (GnRH) antagonist protocols and the freeze-all strategy for the prevention of OHSS. OBJECTIVES: To review the effectiveness and safety of administration of volume expanders for the prevention of moderate and severe ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing IVF or ICSI treatment cycles. SEARCH METHODS: We searched databases including the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and trial registers to September 2015; no date restrictions were used as new comparators were included in this search. The references of relevant publications were also searched. We attempted to contact authors to provide or clarify data that were unclear from trial or abstract reports. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing volume expanders versus placebo or no treatment for the prevention of OHSS in high-risk women undergoing ovarian hyperstimulation as part of any assisted reproductive technique. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed risk of bias and extracted relevant data. The primary review outcome was moderate or severe OHSS. Other outcomes were live birth, pregnancy and adverse events. We combined data to calculate pooled Peto odds ratios (ORs) and 95% confidence intervals (CIs) for each intervention. Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for each comparison, using GRADE methods. MAIN RESULTS: We included nine RCTs (1867 women) comparing human albumin (seven RCTs) or HES (two RCTs) or mannitol (one RCT) versus placebo or no treatment for prevention of OHSS. The evidence was very low to moderate quality for all comparisons. The main limitations were imprecision, poor reporting of study methods, and failure to blind outcome assessment.There was evidence of a beneficial effect of intravenous albumin on OHSS, though heterogeneity was substantial (Peto OR 0.67 95% CI 0.47 to 0.95, seven studies, 1452 high risk women; I² = 69%, very low quality evidence) . This suggests that if the rate of moderate or severe OHSS with no treatment is 12%, it will be about 9% (6% to12%) with the use of intravenous albumin. However, there was evidence of a detrimental effect on pregnancy rates (Peto OR 0.72 95% CI 0.55 to 0.94, I² = 42%, seven studies 1069 high risk women, moderate quality evidence). This suggests that if the chance of pregnancy is 40% without treatment, it will be about 32% (27% to 38%) with the use of albumin.There was evidence of a beneficial effect of HES on OHSS (Peto OR 0.27 95% CI 0.12 to 0.59, I² = 0%, two studies, 272 women, very low quality evidence). This suggests that if the rate of moderate or severe OHSS with no treatment is 16%, it will be about 5% (2% to 10%) with the use of HES. There was no evidence of an effect on pregnancy rates (Peto OR 1.20 95% CI 0.49 to 2.93, one study, 168 women, very low quality evidence).There was evidence of a beneficial effect of mannitol on OHSS (Peto OR 0.38, 95% CI 0.22 to 0.64, one study, 226 women with PCOS, low quality evidence). This means that if the risk of moderate or severe OHSS with no treatment is 52%, it will be about 29% (19% to 41%) with mannitol. There was no evidence of an effect on pregnancy rates (Peto OR 0.85 95% CI 0.47 to 1.55; one study, 226 women, low quality evidence).Live birth rates were not reported in any of the studies. Adverse events appeared to be uncommon, but were too poorly reported to reach any firm conclusions. AUTHORS' CONCLUSIONS: Evidence suggests that the plasma expanders assessed in this review (human albumin, HES and mannitol) reduce rates of moderate and severe OHSS in women at high risk. Adverse events appear to be uncommon, but were too poorly reported to reach any firm conclusions, and there were no data on live birth. However, there was evidence that human albumin reduces pregnancy rates. While there was no evidence that HES, or mannitol had any influence on pregnancy rates, the evidence of effectiveness was based on very few trials which need to be confirmed in additional, larger randomised controlled trials (RCTs) before they should be considered for routine use in clinical practice.

[Symphysiotomy to relieve shoulder dystocia]. / Symfysiotomie voor het opheffen van schouderdystocie.

Symphysiotomy to manage shoulder dystocia is seldom used in the western world. For this reason, in well-resourced countries knowledge of its recuperation rate and the management of physical discomfort in the post-partum period is scarce. We describe two cases of symphysiotomy for shoulder dystocia. Both babies did very well in the postpartum period. The short-term 6-week and 6-month follow-up of both mothers is described. Short-term maternal complications were minor and based on prolonged immobilization. In accordance with the international literature, the short-term and long-term follow-up after symphysiotomy for shoulder dystocia was good and there were no major maternal or neonatal complications. We therefore wish to advocate symphysiotomy as a good and safe option to deliver a baby in cases of severe shoulder dystocia, when all other manoeuvres fail.

A multi-faceted strategy to improve the use of national fertility guidelines; a cluster-randomized controlled trial.

BACKGROUND Proper use of clinical practice guidelines can decrease variation in care between settings. However, actual use of fertility guidelines is suboptimal and in need of improvement. Hence, a cluster-randomized controlled trial was designed to study the effects of two strategies to implement national Dutch guidelines on comprehensive fertility care. METHODS Sixteen fertility clinics participated in the trial. A minimal, professional-oriented implementation strategy of audit and feedback was tested versus a maximal multi-faceted strategy that was both professional and patient oriented. The extent of adherence to guideline recommendations, reflected in quality indicator scores, was the primary outcome measure. To gain an insight into unwanted side effects, patient anxiety and depression scores were gathered as secondary outcomes. Data collection encompassed medical record search, patient and professional questionnaires. RESULTS A total of 1499 couples were included at baseline and 1396 at the after-measurement. No overall significant improvement in indicator scores was found for either strategy [odds ratios ranging from 0.23 (95% confidence interval (CI): 0.06-0.95) to 6.66 (95% CI: 0.33-132.8]. Secondary outcomes did not differ significantly for both groups, although selected anxiety scores appeared lower in the maximal intervention group. Process evaluation of the trial revealed positive patient experiences with the intervention material [e.g. an increased understanding of their doctor's treatment policy (61%), an increased ability to ask questions about the treatment (61%)]. Professionals' appreciation of intervention elements varied, and execution of the multi-faceted strategy appeared incomplete. DISCUSSION Absence of an intervention effect may be due to the nature of the strategies, incomplete execution or flaws in study design. Process evaluation data raise the question of whether professionals should be the only stakeholder responsible for guideline implementation. This study therefore contributes to an increased understanding of fertility guideline implementation in general, and the role of patients in particular.

Determinants of patients' experiences and satisfaction with fertility care.

OBJECTIVE: To assess determinants of patients' experiences and satisfaction with fertility care. DESIGN: Cross-sectional questionnaire study. SETTING: Sixteen fertility clinics in The Netherlands. PATIENT(S): A total of 1,499 infertile women in The Netherlands who visited a participating clinic in April-June 2005 for diagnostics or treatment. MAIN OUTCOME MEASURES: Patients experiences and satisfaction with several aspects of fertility care, and the patient and clinic characteristics that are determinants of those two concepts. RESULT(S): In general, patients' satisfaction with care was high (94%). Waiting times, information provision and emotional support were experienced the least positive aspects of care. Determinants of all care aspects were found to be significant at four different domains: three at patient level, i.e., demographic characteristics, type of received treatment and both general and mental health status, and one at clinic level, i.e., organization of care. CONCLUSION(S): This study provides an increased understanding of the determinants of patients' experiences and satisfaction with fertility care. This enables professionals to tailor their care to specific subgroups of patients and adjust their organization of fertility care where needed. Moreover, the study underlines the need to investigate whether case-mix correction is necessary whenever interpreting patient-surveys on care experiences, because both the patient's and the clinic's characteristics can influence the way that health care delivery is experienced. Demographic background of this regional patient sample was rather homogeneous, which should be taken into account when interpreting results.