Correction: Methods for Developing Evidence Reviews in Short Periods of Time: A Scoping Review.

[This corrects the article DOI: 10.1371/journal.pone.0165903.].

Methods for Developing Evidence Reviews in Short Periods of Time: A Scoping Review.

INTRODUCTION: Rapid reviews (RR), using abbreviated systematic review (SR) methods, are becoming more popular among decision-makers. This World Health Organization commissioned study sought to summarize RR methods, identify differences, and highlight potential biases between RR and SR. METHODS: Review of RR methods (Key Question 1 [KQ1]), meta-epidemiologic studies comparing reliability/ validity of RR and SR methods (KQ2), and their potential associated biases (KQ3). We searched Medline, EMBASE, Cochrane Library, grey literature, and checked reference lists, used personal contacts, and crowdsourcing (e.g. email listservs). Selection and data extraction was conducted by one reviewer (KQ1) or two reviewers independently (KQ2-3). RESULTS: Across all KQs, we identified 42,743 citations through the literature searches. KQ1: RR methods from 29 organizations were reviewed. There was no consensus on which aspects of the SR process to abbreviate. KQ2: Studies comparing the conclusions of RR and SR (n = 9) found them to be generally similar. Where major differences were identified, it was attributed to the inclusion of evidence from different sources (e.g. searching different databases or including different study designs). KQ3: Potential biases introduced into the review process were well-identified although not necessarily supported by empirical evidence, and focused mainly on selective outcome reporting and publication biases. CONCLUSION: RR approaches are context and organization specific. Existing comparative evidence has found similar conclusions derived from RR and SR, but there is a lack of evidence comparing the potential of bias in both evidence synthesis approaches. Further research and decision aids are needed to help decision makers and reviewers balance the benefits of providing timely evidence with the potential for biased findings.

Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.

BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotrophin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimens have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006 and 2011. OBJECTIVES: To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists compared with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycles. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched from inception to May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to 28 April 2015), Ovid MEDLINE (1966 to 28 April 2015), EMBASE (1980 to 28 April 2015), PsycINFO (1806 to 28 April 2015), CINAHL (to 28 April 2015) and trial registers to 28 April 2015, and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). We contacted the authors of eligible studies for missing or unpublished data. The evidence is current to 28 April 2015. SELECTION CRITERIA: Two review authors independently screened the relevant citations for randomised controlled trials (RCTs) comparing different GnRH agonist versus GnRH antagonist protocols in women undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary review outcomes were live birth and ovarian hyperstimulation syndrome (OHSS). Other adverse effects (miscarriage and cycle cancellation) were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). 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 73 RCTs, with 12,212 participants, comparing GnRH antagonist to long-course GnRH agonist protocols. The quality of the evidence was moderate: limitations were poor reporting of study methods.Live birthThere was no conclusive evidence of a difference in live birth rate between GnRH antagonist and long course GnRH agonist (OR 1.02, 95% CI 0.85 to 1.23; 12 RCTs, n = 2303, I(2)= 27%, moderate quality evidence). The evidence suggested that if the chance of live birth following GnRH agonist is assumed to be 29%, the chance following GnRH antagonist would be between 25% and 33%.OHSSGnRH antagonist was associated with lower incidence of any grade of OHSS than GnRH agonist (OR 0.61, 95% C 0.51 to 0.72; 36 RCTs, n = 7944, I(2) = 31%, moderate quality evidence). The evidence suggested that if the risk of OHSS following GnRH agonist is assumed to be 11%, the risk following GnRH antagonist would be between 6% and 9%.Other adverse effectsThere was no evidence of a difference in miscarriage rate per woman randomised between GnRH antagonist group and GnRH agonist group (OR 1.04, 95% CI 0.82 to 1.30; 33 RCTs, n = 7022, I(2) = 0%, moderate quality evidence).With respect to cycle cancellation, GnRH antagonist was associated with a lower incidence of cycle cancellation due to high risk of OHSS (OR 0.47, 95% CI 0.32 to 0.69; 19 RCTs, n = 4256, I(2) = 0%). However cycle cancellation due to poor ovarian response was higher in women who received GnRH antagonist than those who were treated with GnRH agonist (OR 1.32, 95% CI 1.06 to 1.65; 25 RCTs, n = 5230, I(2) = 68%; moderate quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence that the use of GnRH antagonist compared with long-course GnRH agonist protocols is associated with a substantial reduction in OHSS without reducing the likelihood of achieving live birth.

Culture media for human pre-implantation embryos in assisted reproductive technology cycles.

BACKGROUND: Many media are commercially available for culturing pre-implantation human embryos in assisted reproductive technology (ART) cycles. It is unknown which culture medium leads to the best success rates after ART. OBJECTIVES: To evaluate the safety and effectiveness of different human pre-implantation embryo culture media in used for in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register, the Medical Research Council's Clinical Trials Register and the NHS Center for Reviews and Dissemination databases from January 1985 to March 2015. We also examined the reference lists of all known primary studies, review articles, citation lists of relevant publications and abstracts of major scientific meetings. SELECTION CRITERIA: We included all randomised controlled trials which randomised women, oocytes or embryos and compared any two commercially available culture media for human pre-implantation embryos in an IVF or ICSI programme. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies, assessed their risk of bias and extracted data. We sought additional information from the authors if necessary. We assessed the quality of the evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods. The primary review outcome was live birth or ongoing pregnancy. MAIN RESULTS: We included 32 studies in this review. Seventeen studies randomised women (total 3666), three randomised cycles (total 1018) and twelve randomised oocytes (over 15,230). It was not possible to pool any of the data because each study compared different culture media.Only seven studies reported live birth or ongoing pregnancy. Four of these studies found no evidence of a difference between the media compared, for either day three or day five embryo transfer. The data from the fifth study did not appear reliable.Six studies reported clinical pregnancy rate. One of these found a difference between the media compared, suggesting that for cleavage-stage embryo transfer, Quinn's Advantage was associated with higher clinical pregnancy rates than G5 (odds ratio (OR) 1.56; 95% confidence interval (CI) 1.12 to 2.16; 692 women). This study was available only as an abstract and the quality of the evidence was low.With regards to adverse effects, three studies reported multiple pregnancies and six studies reported miscarriage. None of them found any evidence of a difference between the culture media used. None of the studies reported on the health of offspring.Most studies (22/32) failed to report their source of funding and none described their methodology in adequate detail. The overall quality of the evidence was rated as very low for nearly all comparisons, the main limitations being imprecision and poor reporting of study methods. AUTHORS' CONCLUSIONS: An optimal embryo culture medium is important for embryonic development and subsequently the success of IVF or ICSI treatment. There has been much controversy about the most appropriate embryo culture medium. Numerous studies have been performed, but no two studies compared the same culture media and none of them found any evidence of a difference between the culture media used. We conclude that there is insufficient evidence to support or refute the use of any specific culture medium. Properly designed and executed randomised trials are necessary.

Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology.

BACKGROUND: Human chorionic gonadotropin (HCG) is routinely used for final oocyte maturation triggering in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles, but the use of HCG for this purpose may have drawbacks. Gonadotropin-releasing hormone (GnRH) agonists present an alternative to HCG in controlled ovarian hyperstimulation (COH) treatment regimens in which the cycle has been down-regulated with a GnRH antagonist. This is an update of a review first published in 2010. OBJECTIVES: To evaluate the effectiveness and safety of GnRH agonists in comparison with HCG for triggering final oocyte maturation in IVF and ICSI for women undergoing COH in a GnRH antagonist protocol. SEARCH METHODS: We searched databases including the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of Controlled Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and trial registers for published and unpublished articles (in any language) on randomised controlled trials (RCTs) of gonadotropin-releasing hormone agonists versus HCG for oocyte triggering in GnRH antagonist IVF/ICSI treatment cycles. The search is current to 8 September 2014. SELECTION CRITERIA: RCTs that compared the clinical outcomes of GnRH agonist triggers versus HCG for final oocyte maturation triggering in women undergoing GnRH antagonist IVF/ICSI treatment cycles were included. DATA COLLECTION AND ANALYSIS: Two or more review authors independently selected studies, extracted data and assessed study risk of bias. Treatment effects were summarised using a fixed-effect model, and subgroup analyses were conducted to explore potential sources of heterogeneity. Treatment effects were expressed as mean differences (MDs) for continuous outcomes and as odds ratios (ORs) for dichotomous outcomes, together with 95% confidence intervals (CIs). Primary outcomes were live birth and rate of ovarian hyperstimulation syndrome (OHSS) per women randomised. Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods were used to assess the quality of the evidence for each comparison. MAIN RESULTS: We included 17 RCTs (n = 1847), of which 13 studies assessed fresh autologous cycles and four studies assessed donor-recipient cycles. In fresh autologous cycles, GnRH agonists were associated with a lower live birth rate than was seen with HCG (OR 0.47, 95% CI 0.31 to 0.70; five RCTs, 532 women, I(2) = 56%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving live birth with the use of HCG, the chance of a live birth with the use of an GnRH agonist would be between 12% and 24%.In women undergoing fresh autologous cycles, GnRH agonists were associated with a lower incidence of mild, moderate or severe OHSS than was HCG (OR 0.15, 95% CI 0.05 to 0.47; eight RCTs, 989 women, I² = 42%, moderate-quality evidence). This suggests that for a woman with a 5% risk of mild, moderate or severe OHSS with the use of HCG, the risk of OHSS with the use of a GnRH agonist would be between nil and 2%.In women undergoing fresh autologous cycles, GnRH agonists were associated with a lower ongoing pregnancy rate than was seen with HCG (OR 0.70, 95% CI 0.54 to 0.91; 11 studies, 1198 women, I(2) = 59%, low-quality evidence) and a higher early miscarriage rate (OR 1.74, 95% CI 1.10 to 2.75; 11 RCTs, 1198 women, I² = 1%, moderate-quality evidence). However, the effect was dependent on the type of luteal phase support provided (with or without luteinising hormone (LH) activity); the higher rate of pregnancies in the HCG group applied only to the group that received luteal phase support without LH activity (OR 0.36, 95% CI 0.21 to 0.62; I(2) = 73%, five RCTs, 370 women). No evidence was found of a difference between groups in risk of multiple pregnancy (OR 3.00, 95% CI 0.30 to 30.47; two RCTs, 62 women, I(2) = 0%, low-quality evidence).In women with donor-recipient cycles, no evidence suggested a difference between groups in live birth rate (OR 0.92, 95% CI 0.53 to 1.61; one RCT, 212 women) or ongoing pregnancy rate (OR 0.88, 95% CI 0.58 to 1.32; three RCTs, 372 women, I² = 0%). We found evidence of a lower incidence of OHSS in the GnRH agonist group than in the HCG group (OR 0.05, 95% CI 0.01 to 0.28; three RCTs, 374 women, I² = 0%).The main limitation in the quality of the evidence was risk of bias associated with poor reporting of methods in the included studies. AUTHORS' CONCLUSIONS: Final oocyte maturation triggering with GnRH agonist instead of HCG in fresh autologous GnRH antagonist IVF/ICSI treatment cycles prevents OHSS to the detriment of the live birth rate. In donor-recipient cycles, use of GnRH agonists instead of HCG resulted in a lower incidence of OHSS, with no evidence of a difference in live birth rate.Evidence suggests that GnRH agonist as a final oocyte maturation trigger in fresh autologous cycles is associated with a lower live birth rate, a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) and a higher rate of early miscarriage (less than 12 weeks). GnRH agonist as an oocyte maturation trigger could be useful for women who choose to avoid fresh transfers (for whatever reason), women who donate oocytes to recipients or women who wish to freeze their eggs for later use in the context of fertility preservation.

Post-embryo transfer interventions for assisted reproduction technology cycles.

BACKGROUND: In women undergoing in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), embryos transferred into the uterine cavity can be expelled due to many factors including uterine peristalsis and contractions, low site of deposition and negative pressure generated when removing the transfer catheter. Techniques to reduce the risk of embryo loss following embryo transfer (ET) have been described but are not standard in all centres conducting ET. OBJECTIVES: To evaluate the efficacy of interventions used to prevent post-transfer embryo expulsion in women undergoing IVF and ICSI. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials to June 2014 and PubMed, MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, World Health Organization ICTRP, and trial registers from inception to June 2014, with no language restrictions. Additionally, we handsearched reference lists of relevant articles, and ESHRE and ASRM conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions used to prevent post-transfer embryo expulsion in women undergoing IVF and ICSI. Two review authors independently screened titles and abstracts and reviewed the full-texts of all potentially eligible citations to determine whether they met our inclusion criteria. Disagreements were resolved by consensus. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of included trials using standardised, piloted data extraction forms. Data were extracted to allow intention-to-treat analyses. Disagreements were resolved by consensus. The overall quality of the evidence was rated using GRADE methods. MAIN RESULTS: We included four RCTs (n = 1392 women) which administered the following interventions: bed rest (two trials), fibrin sealant (one trial), and mechanical closure of the cervix (one trial). Our primary outcome, live birth rate, was not reported in any of the included trials; nor were the data available from the corresponding authors. For the ongoing pregnancy rate, two trials comparing more bed rest with less bed rest showed no evidence of a difference between groups (odds ratio (OR) 0.88; 95% confidence interval (CI) 0.60 to 1.31, 542 women, I(2) = 0%, low quality evidence). Secondary outcomes were sporadically reported with the exception of the clinical pregnancy rate, which was reported in all of the included trials. There was no evidence of a difference in clinical pregnancy rate between more bed rest and less bed rest (OR 0.88; 95% CI 0.60 to 1.31, 542 women, I(2) = 0%, low quality evidence) or between fibrin sealant and usual care (OR 0.98; 95% CI 0.54 to 1.78, 211 women, very low quality evidence). However, mechanical closure of the cervix was associated with a higher clinical pregnancy rate than usual care (OR 1.92; 95% CI 1.40 to 2.63, very low quality evidence). The quality of the evidence was rated as low or very low for all outcomes. The main limitations were failure to report live births, imprecision and risk of bias. Overall, the risk of bias of the included trials was high. The use of a proper method of randomisation and allocation concealment was fairly well reported, while only one trial clearly reported blinding. There was no evidence that any of the interventions had an effect on adverse event rates but data were too few to reach any conclusions. AUTHORS' CONCLUSIONS: There is insufficient evidence to support any specific length of time for women to remain recumbent, if at all, following embryo transfer, nor is there sufficient evidence to recommend the use of fibrin sealants added to the embryo transfer fluid. There is very limited evidence to support the use of mechanical pressure to close the cervical canal following embryo transfer. Further well-designed and powered studies are required to determine the true effectiveness and safety of these interventions.

Gonadotrophins for idiopathic male factor subfertility.

BACKGROUND: Male factors leading to subfertility account for at least half of all cases of subfertility worldwide. Although some causes of male subfertility are treatable, treatment of idiopathic male factor subfertility remains empirical. Researchers have used gonadotrophins to improve sperm parameters in idiopathic male factor subfertility with the ultimate goal of increasing birth and pregnancy rates, but results have been conflicting. OBJECTIVES: To determine the effect of systemic follicle-stimulating hormone (FSH) on live birth and pregnancy rates when administered to men with idiopathic male factor subfertility . SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (14 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12 of 12, 2012), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE (1946 to 14 January 2013), Ovid EMBASE (1980 to week 2 of 2013), Ovid PsycINFO (1806 to week 2 of 2013), trial registers for ongoing and registered trials at ClinicalTrials.gov (19 January 2013), the World Health Organisation International Trials Registry Platform (19 January 2013), The Cochrane Library Database of Abstracts of Reviews of Effects (19 January 2013) and OpenGrey for grey literature from Europe (19 January 2013). Searches were not limited by language. Bibliographies of included and excluded trials and abstracts of major meetings were searched for additional trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which gonadotrophins were compared with placebo or no treatment for participants with idiopathic male factor subfertility. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, assessed risk of bias and extracted data on live birth, pregnancy and adverse effects. We included data on pregnancies that occurred during or after gonadotrophin therapy. Study authors and pharmaceutical companies were asked to provide missing and unpublished data and/or additional information. MAIN RESULTS: Six RCTs with 456 participants and variable treatment and follow-up periods were included. From the limited data, the live birth rate per couple randomly assigned (27% vs 0%; Peto odds ratio (OR) 9.31, 95% confidence interval (CI) 1.17 to 73.75, one study, 30 participants, very low-quality evidence) and the spontaneous pregnancy rate per couple randomly assigned (16% vs 7%; Peto OR 4.94, 95% CI 2.13 to 11.44, five studies, 412 participants, I(2) = 0%, moderate-quality evidence) were significantly higher in men receiving gonadotrophin treatment than in men receiving placebo or no treatment. No significant difference between groups was noted when intracytoplasmic sperm injection (ICSI) or intrauterine insemination (IUI) was performed. None of the included studies reported miscarriage rates, and adverse events data were sparse. AUTHORS' CONCLUSIONS: Encouraging preliminary data suggest a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility, but because the numbers of trials and participants are small, evidence is insufficient to allow final conclusions. Large multi-centre trials with adequate numbers of participants are needed.

Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

BACKGROUND: Various options exist for treating endometriosis, including surgical, medical, such as ovarian suppression, or a combination of these strategies. Surgical treatment of endometriosis aims to remove visible areas of endometriosis. The aim of medical therapy is to inhibit growth of endometriotic implants by induction of a hypo-estrogenic state. Treatment with a hormone-releasing intrauterine device, using levonorgestrel (LNG-IUD), has also been suggested. OBJECTIVES: To determine whether postoperative LNG-IUD insertion in women with endometriosis improves pain and reduces recurrence of symptoms compared with no postoperative treatment, postoperative insertion of a placebo, or postoperative therapy. SEARCH METHODS: The following databases were searched from inception to June 2012: Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, CINAHL, and the World Health Organization (WHO) International Clinical Trials Registry Platform. EMBASE was searched from 2010 to June 2012. The citation lists of relevant publications, review articles, abstracts of scientific meetings, and included studies were also searched. SELECTION CRITERIA: Trials were included if they compared women undergoing surgical treatment for endometriosis with uterine preservation and then randomised within three months to LNG-IUD insertion versus no postoperative treatment, placebo (inert IUD), or other treatment. Diagnostic laparoscopy alone was not considered suitable treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted data to allow for an intention-to-treat analysis. For dichotomous data, the risk ratio (RR) and 95% confidence interval (CI) were calculated using the Mantel-Haenszel random-effects method. For continuous data, the mean difference (MD) and 95% CI were calculated using the inverse variance random-effects method. MAIN RESULTS: Three randomised controlled trials were included. In two trials, there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUD group compared with expectant management (RR 0.22, 95% CI 0.08 to 0.60, 95 women, I(2) = 0%, moderate strength of evidence). The proportion of women who were satisfied with their treatment was also higher in the LNG-IUD group but did not reach statistical significance (RR 1.21, 95% CI 0.80 to 1.82, 95 women, I(2) = 0%). The number of women reporting a change in menstruation was significantly higher in the LNG-IUD group (RR 37.80, 95% CI 5.40 to 264.60, 95 women, I(2) = 0%) but the number of women not completing the allocated treatment did not differ between groups (RR 0.66, 95% CI 0.08 to 5.25, I(2) = 43%).In one trial, women receiving LNG-IUD noted lower pain scores compared with women receiving gonadotrophin-releasing hormone agonists (MD -0.16, 95% CI -2.02 to 1.70, 40 women) but this did not reach statistical significance. AUTHORS' CONCLUSIONS: There is limited but consistent evidence showing that postoperative LNG-IUD use reduces the recurrence of painful periods in women with endometriosis. Further well-designed RCTs are needed to confirm these findings.

Are all human-derived follicle-stimulating hormone products the same? A systematic review and meta-analysis using direct and adjusted indirect analyses, to determine whether Fostimon® is more efficient than Metrodin-HP®.

BACKGROUND: Randomized trials (RCTs) and systematic reviews have challenged the claim for superiority of recombinant follicle-stimulating hormone (recFSH) compared with human-derived FSH (hFSH). Even so, much of the evidence comes from unavailable products. If the efficacy of the currently available Fostimon(®) is superior, the off-market Metrodin-HP(®), then data from the latter should not be used, gauge of the former. METHODS: Electronic/hand searches were performed to identify RCTs comparing Fostimon(®) vs. Metrodin-HP(®) or either product with recFSH. Primary outcomes were live-birth rate (LBR), ongoing pregnancy rate (OPR), and OPR/LBR. Secondary outcomes were clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), ovarian hyperstimulation syndrome (OHSS), abortion rates, and cycle demographics. Data were extracted, allowed for an intention-to-treat analysis, and meta-analyzed using combined direct/adjusted indirect methods. RESULTS: Twenty-two RCTs met the inclusion criteria: Fostimon(®) vs. Metrodin-HP(®) (n = 2); Fostimon(®) vs. recFSH (n = 8); and Metrodin-HP(®) vs. recFSH (n = 12). LBR (odds ratio = 1.72; 95% confidence interval = 1.05-2.80), OPR/LBR, and CPR were all significantly higher favoring Fostimon(®). OPR, MPR, OHSS, and miscarriage rates were not significantly different. Pooled results for cycle demographics were not reported due to high heterogeneity. Conclusions. Fostimon(®) is superior to Metrodin-HP(®) regarding clinical outcomes. Therefore, care should be taken not to assume that all hFSH products have the same efficacy.

Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.

BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-estrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotropin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimes have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006. OBJECTIVES: To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycle SEARCH STRATEGY: We performed electronic searches of major databases, for example Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE (from 1987 to April 2010); and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). A date limited search of Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL from April 2010 to April 2011 was run. Eighteen studies have been entered into the Classification pending references section of this update. These studies will be appraised for inclusion or exclusion in the next update of this review, due April 2012. SELECTION CRITERIA: Two review authors independently screened the relevant citations for randomised controlled trials (RCTs) comparing different agonist versus antagonist protocols in women undergoing IVF or ICSI. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial risk of bias and extracted data. If relevant data were missing or unclear, the authors were contacted for clarification. MAIN RESULTS: Forty-five RCTs (n = 7511) comparing the antagonist to the long agonist protocols fulfilled the inclusion criteria. There was no evidence of a statistically significant difference in rates of live-births (9 RCTs; odds ratio (OR) 0.86, 95% CI 0.69 to 1.08) or ongoing pregnancy (28 RCTs; OR 0.87, 95% CI 0.77 to 1.00). There was a statistically significant lower incidence of OHSS in the GnRH antagonist group (29 RCTs; OR 0.43, 95% CI 0.33 to 0.57). AUTHORS' CONCLUSIONS: The use of antagonist compared with long GnRH agonist protocols was associated with a large reduction in OHSS and there was no evidence of a difference in live-birth rates.

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles.

BACKGROUND: For the last few decades urinary human chorionic gonadotrophin (hCG) has been used to induce final oocyte maturation triggering in in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) cycles. Recombinant technology has allowed the production of two drugs that can be used for the same purpose, to mimic the endogenous luteinizing hormone (LH) surge. This allows commercial production to be adjusted according to market requirements; the removal of all urinary contaminants; and the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice the effectiveness of the recombinant drugs should be known compared to the currently used urinary human chorionic gonadotrophin (uhCG). OBJECTIVES: To assess the efficacy and safety of subcutaneous recombinant hCG (rhCG) and high dose recombinant LH (rLH) compared with intramuscular uhCG for inducing final oocyte maturation triggering in IVF and ICSI cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010), MEDLINE (1966 to January 2010) and EMBASE (1980 to January 2010). SELECTION CRITERIA: Two review authors independently scanned titles and abstracts and selected those that appeared relevant for collection of the full paper. Only truly randomised controlled trials comparing rhCG and rLH with urinary hCG for final oocyte maturation triggering in IVF and ICSI cycles for treatment of infertility in normo-gonadotropic women were included. DATA COLLECTION AND ANALYSIS: Assessment for inclusion or exclusion, quality assessment and data extraction were performed independently by two authors. Discrepancies were discussed in the presence of a third author and consensus reached. Quality assessment included method of randomisation, allocation concealment, blinding of participants and assessors, reporting of a power calculation and intention-to-treat analysis. MAIN RESULTS: Fourteen RCTs (n = 2306) were identified; 11 compared rhCG with uhCG and three compared rhLH with uhCG. There was no evidence of a statistically significant difference between rhCG and uhCG regarding the ongoing pregnancy or live birth rate (6 RCTs: OR 1.04, 95% CI 0.79 to 1.37; P = 0.83, I(2) = 0%). There was no significant difference in the incidence of ovarian hyperstimulation syndrome (OHSS) between rhCG and uhCG (3 RCTs: OR 1.5, 95% CI 0.37 to 4.1; P = 0.37, I(2) = 0%). There was no evidence of statistically significant difference between rhLH and uhCG regarding the ongoing pregnancy or live birth rate (OR 0.94, 95% CI 0.50 to 1.76) and incidence of OHSS (OR 0.82, 95% CI 0.39 to 1.69). These results leave open the possibility of strong differences in favour of either treatment for both ongoing pregnancy and OHSS. AUTHORS' CONCLUSIONS: We conclude that there is no evidence of difference between rhCG or rhLH and uhCG in achieving final follicular maturation in IVF, with equivalent pregnancy rates and OHSS incidence. According to these findings uHCG is still the best choice for final oocyte maturation triggering in IVF and ICSI treatment cycles.

Intra-venous fluids for the prevention of severe 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 intravenous fluids such as albumin, hydroxyethyl starch, Haemaccel® and dextran as a possible way for preventing the severe form of OHSS. OBJECTIVES: To review the effectiveness and safety of administration of intravenous fluids such as albumin, hydroxyethyl starch, Haemaccel® and dextran in the prevention of severe ovarian hyperstimulation syndrome (OHSS) in IVF or ICSI treatment cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, to third quarter 2010), MEDLINE (1950 to November 2010), EMBASE (1980 to November 2010) and The National Research Register (to November 2010). The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. The authors were contacted to provide or clarify data that were unclear from the trial reports. SELECTION CRITERIA: Randomised controlled trials (RCTs) which compared the effects of intravenous fluids with placebo or no treatment for the prevention of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles. DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the abstracts, identified relevant papers, assessed inclusion of trials and trial quality and extracted relevant data. Validity was assessed in terms of method of randomisation, allocation concealment and outcomes. Where possible, data were pooled for analysis. A separate analysis of studies was performed for human albumin and hydroxyethyl starch versus placebo or no treatment. Other potential intravenous fluids have been identified, such as Haemaccel and dextran, however no randomised controlled studies on their applicability could be found. MAIN RESULTS: Nine RCTs involving 1660 (human albumin vs placebo) and 487 (HES vs placebo) randomised women, have been included in this review. There was a borderline statistically significant decrease in the incidence of severe OHSS with administration of human albumin (8 RCTs, OR 0.67, 95% CI 0.45 to 0.99).There was a statistically significant decrease in severe OHSS incidence with administration of hydroxyethyl starch (3 RCTs, OR 0.12, 95% CI 0.04 to 0.40). There was no evidence of statistical difference in the pregnancy rate between both groups of treatment. AUTHORS' CONCLUSIONS: There is limited evidence of benefit from intra-venous albumin administration at the time of oocyte retrieval in the prevention or reduction of the incidence of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles. Hydroxyethyl starch markedly decreases the incidence of severe OHSS.

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles.

BACKGROUND: Several systematic reviews compared recombinant gonadotrophin with urinary gonadotrophins (HMG, purified FSH, highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. Each of these reviews used different inclusion and exclusion criteria for trials. Our aim in producing this review is to bring together all randomised studies in this field under common inclusion criteria with consistent and valid statistical methods. OBJECTIVES: To compare the effectiveness of recombinant gonadotrophin (rFSH) with the three main types of urinary gonadotrophins (i.e. HMG, FSH-P and FSH-HP) for ovarian stimulation in women undergoing IVF or ICSI treatment cycles. SEARCH STRATEGY: An extended search was done according to Cochrane guidelines including the Menstrual Disorders & Subfertility Group's Specialised Register of controlled trials, The Cochrane Central Register of Controlled Trials, MEDLINE (1966 to May 2010), EMBASE (1980 to May 2010), CINAHL (1982 to May 2010), National Research Register, and Current Controlled Trials. SELECTION CRITERIA: All randomised controlled trials reporting data comparing clinical outcomes for women undergoing IVF/ICSI cycles and using recombinant FSH in comparison with HMG or highly purified HMG, purified urinary FSH (FSH-P), and highly purified urinary FSH (FSH-HP) for ovarian hyperstimulation in IVF or ICSI cycles were included. DATA COLLECTION AND ANALYSIS: Primary outcome measure was live birth rate and OHSS per randomised woman.Binary outcomes were analysed using odds ratios and also reported in absolute terms. Grouped analyses were carried out for all outcomes to explore whether relative effects differed due to key features of the trials. MAIN RESULTS: We included 42 trials with a total of 9606 couples. Comparing rFSH to any of the other gonadotrophins irrespective of the down-regulation protocol used, did not result in any evidence of a statistically significant difference in live birth rate (28 trials, 7339 couples, odds ratio 0.97, 95% CI 0.87 to 1.08). This suggests that for a group with a 25% live birth rate using urinary gonadotrophins the rate would be between 22.5% and 26.5% using rFSH. There was also no evidence of a difference in the OHSS rate (32 trials, 7740 couples, OR 1.18, 95% CI 0.86 to 1.61). This means that for a group with 2% risk of OHSS using urinary gonadotrophins, the risk would be between 1.7% and 3.2% using rFSH. AUTHORS' CONCLUSIONS: Clinical choice of gonadotrophin should depend on availability, convenience and costs. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety.

Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is still the standard medication for this purpose. The effectiveness of triggering with a GnRH agonist compared to HCG measured as pregnancy and ovarian hyperstimulation(OHSS) rates are unknown. OBJECTIVES: To compare the effectiveness of a GnRH agonist with HCG for triggering final oocyte maturation in IVF and ICSI patients undergoing controlled ovarian hyperstimulation in a GnRH antagonist protocol followed by embryo transfer.  SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE , EMBASE, the National Research Register, the Medical Research Council's Clinical Trials Register, and the NHS Centre for Reviews and Dissemination database. We also examined the reference lists of all known primary studies and review articles, citation lists of relevant publications and abstracts of major scientific meetings. SELECTION CRITERIA: All randomised controlled studies (RCTs) reporting data comparing clinical outcomes for women undergoing IVF and ICSI cycles and using a GnRH agonist in comparison with HCG for final oocyte maturation triggering. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We identified 11 RCTs (n = 1055). Eight studies assessed fresh autologous cycles and three studies assessed donor-recipient cycles. In fresh-autologous cycles, GnRH agonist was less effective than HCG in terms of the live birth rate per randomised woman (OR 0.44, 95% CI 0.29 to 0.68; 4 RCTs) and ongoing pregnancy rate per randomised woman (OR 0.45, 95% CI 0.31 to 0.65; 8 RCTs). For a group with a 30% live birth or ongoing pregnancy rate using HCG, the rate would be between 12% and 22% using an GnRH agonist. Moderate to severe ovarian hyperstimulation syndrome (OHSS) incidence per randomised woman was significantly lower in the GnRH agonist group compared to the HCG group (OR 0.10, 95% CI 0.01 to 0.82; 5 RCTs). For a group with a 3% OHSS rate using HCG the rate would be between 0% and 2.6% using GnRH agonist. In donor recipient cycles, there was no evidence of a statistical difference in the live birth rate per randomised woman (OR 0.92, 95% CI 0.53 to 1.61; 1 RCT). AUTHORS' CONCLUSIONS: We do not recommend that GnRH agonists be routinely used as a final oocyte maturation trigger in fresh autologous cycles because of lowered live birth rates and ongoing pregnancy rates. An exception could be made for women with high risk of OHSS, after appropriate counselling.

Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis.

OBJECTIVE: To determine whether gonadotropin-releasing hormone (GnRH) analog cotreatment with chemotherapy provides better reproductive outcomes for women at risk of premature ovarian failure (POF) as a side-effect of gonadotoxic chemotherapy. DESIGN: Systematic review and meta-analysis. SETTING: University-affiliated research centers. PATIENT(S): None. INTERVENTION(S): Electronic and manual searches (e.g., MEDLINE, EMBASE, CENTRAL) up to January 2010 were performed to identify randomized controlled trials (RCTs) comparing GnRH cotreatment with chemotherapy alone in premenopausal women. MAIN OUTCOME MEASURE(S): Incidence of POF after treatment, incidence of women with resumption of ovulation, POF after an initial normal cycle, normal cycles but abnormal markers of ovarian reserve, spontaneous occurrence of pregnancy after treatment, and time to reestablishment of menstruation; data also extracted to allow for an intention-to-treat analysis. RESULT(S): Twenty-eight RCTs were identified, but only six met the inclusion criteria. Data were only available for the incidence of women with new onset of POF, resumption of ovulation, and occurrence of pregnancy. The incidence of POF or resumption of ovulation both demonstrated a statistically significant difference in favor of the GnRH cotreatment. The occurrence of spontaneous pregnancy showed no statistically significant difference between GnRH cotreatment and the control groups. CONCLUSION(S): Evidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, with higher rates of spontaneous resumption of menses and ovulation but not improvement in pregnancy rates. Data relating to study quality and possible bias for the majority of the outcomes in this review were not available, denoting possible selective reporting of trial data.

Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is still the standard medication for this purpose. The effectiveness of triggering with a GnRH agonist compared to HCG measured as pregnancy and ovarian hyperstimulation(OHSS) rates are unknown. OBJECTIVES: To compare the effectiveness of a GnRH agonist with HCG for triggering final oocyte maturation in IVF and ICSI patients undergoing controlled ovarian hyperstimulation in a GnRH antagonist protocol followed by embryo transfer.  SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE , EMBASE, the National Research Register, the Medical Research Council's Clinical Trials Register, and the NHS Centre for Reviews and Dissemination database. We also examined the reference lists of all known primary studies and review articles, citation lists of relevant publications and abstracts of major scientific meetings. SELECTION CRITERIA: All randomised controlled studies (RCTs) reporting data comparing clinical outcomes for women undergoing IVF and ICSI cycles and using a GnRH agonist in comparison with HCG for final oocyte maturation triggering. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We identified 11 RCTs (n = 1055). Eight studies assessed fresh autologous cycles and three studies assessed donor-recipient cycles. In fresh-autologous cycles, GnRH agonist was less effective than HCG in terms of the live birth rate per randomised woman (OR 0.44, 95% CI 0.29 to 0.68; 4 RCTs) and ongoing pregnancy rate per randomised woman (OR 0.45, 95% CI 0.31 to 0.65; 8 RCTs). For a group with a 30% live birth or ongoing pregnancy rate using HCG, the rate would be between 12% and 22% using an GnRH agonist. Moderate to severe ovarian hyperstimulation syndrome (OHSS) incidence per randomised woman was significantly lower in the GnRH agonist group compared to the HCG group (OR 0.10, 95% CI 0.01 to 0.82; 5 RCTs). For a group with a 3% OHSS rate using HCG the rate would be between 0% and 2.6% using GnRH agonist. In donor recipient cycles, there was no evidence of a statistical difference in the live birth rate per randomised woman (OR 0.92, 95% CI 0.53 to 1.61; 1 RCT). AUTHORS' CONCLUSIONS: We do not recommend that GnRH agonists be routinely used as a final oocyte maturation trigger in fresh autologous cycles because of lowered live birth rates and ongoing pregnancy rates. An exception could be made for women with high risk of OHSS, after appropriate counselling.

Effect of urinary versus recombinant FSH on clinical outcomes after frozen-thawed embryo transfers: a systematic review.

Recent randomized trials, systematic reviews and cost-effectiveness analyses have demonstrated the relative efficacy,and in some cases superiority, of urinary gonadotrophins (uFSH, human menopausal gonadotrophin) compared with recombinant FSH (rFSH). However, the effectiveness of frozen-embryo transfers (FET) following ovarian stimulation with uFSH versus rFSH in the fresh cycle has not been well investigated. The objective of this study was to determine whether there are differences in clinical outcomes in women undergoing FET according to the type of gonadotrophin used during ovarian stimulation. Following a meticulous search, all published comparative studies of FET using ovarian stimulation were reviewed. Data on clinical outcomes were extracted and systematically presented. Using the agonist long protocol for down-regulation, five trials provided extractable data for live-birth and ongoing pregnancy rates following FET, as well as the cumulative live-birth, ongoing pregnancy and clinical pregnancy rates following fresh-embryo transfer and FET from the same cycle. There was no evidence of significant effect difference between the uses of uFSH versus rFSH regarding any of the outcomes. In conclusion there is insufficient evidence to determine whether the use of a certain type of gonadotrophin during ovarian stimulation affects the clinical outcomes in subsequent FET.