Search

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence of moderate to severe OHSS ranges from 0.6% to 5% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intravascular compartment to the third space, resulting in profound intravascular depletion and haemoconcentration. OBJECTIVES: To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles. SEARCH METHODS: For the update of this review, we searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE (PubMed), CINHAL, PsycINFO, Embase, Google, and clinicaltrials.gov to 6 July 2016. SELECTION CRITERIA: We included only randomized controlled trials (RCTs) in which coasting was used to prevent OHSS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data. They resolved disagreements by discussion. They contacted study authors to request additional information or missing data. The intervention comparisons were coasting versus no coasting, coasting versus early unilateral follicular aspiration (EUFA), coasting versus gonadotrophin releasing hormone antagonist (antagonist), coasting versus follicle stimulating hormone administration at the time of hCG trigger (FSH co‐trigger), and coasting versus cabergoline. We performed statistical analysis in accordance with Cochrane guidelines. Our primary outcomes were moderate or severe OHSS and live birth. MAIN RESULTS: We included eight RCTs (702 women at high risk of developing OHSS). The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data. Coasting versus no coasting Rates of OHSS were lower in the coasting group (OR 0.11, 95% CI 0.05 to 0.24; I² = 0%, two RCTs; 207 women; low‐quality evidence), suggesting that if 45% of women developed moderate or severe OHSS without coasting, between 4% and 17% of women would develop it with coasting. There were too few data to determine whether there was a difference between the groups in rates of live birth (OR 0.48, 95% CI 0.14 to 1.62; one RCT; 68 women; very low‐quality evidence), clinical pregnancy (OR 0.82, 95% CI 0.46 to 1.44; I² = 0%; two RCTs; 207 women; low‐quality evidence), multiple pregnancy (OR 0.31, 95% CI 0.12 to 0.81; one RCT; 139 women; low‐quality evidence), or miscarriage (OR 0.85, 95% CI 0.25 to 2.86; I² = 0%; two RCTs; 207 women; very low‐quality evidence). Coasting versus EUFA There were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 0.98, 95% CI 0.34 to 2.85; I² = 0%; 2 RCTs; 83 women; very low‐quality evidence), or clinical pregnancy (OR 0.67, 95% CI 0.25 to 1.79; I² = 0%; 2 RCTs; 83 women; very low‐quality evidence); no studies reported live birth, multiple pregnancy, or miscarriage. Coasting versus antagonist One RCT (190 women) reported this comparison, and no events of OHSS occurred in either arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.74, 95% CI 0.42 to 1.31; one RCT; 190 women; low‐quality evidence), or multiple pregnancy rates (OR 1.00, 95% CI 0.43 to 2.32; one RCT; 98 women; very low‐quality evidence); the study did not report live birth or miscarriage. Coasting versus FSH co‐trigger Rates of OHSS were higher in the coasting group (OR 43.74, 95% CI 2.54 to 754.58; one RCT; 102 women; very low‐quality evidence), with 15 events in the coasting arm and none in the FSH co‐trigger arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.92, 95% CI 0.43 to 2.10; one RCT; 102 women; low‐quality evidence). This study did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage, but stated that there was no significant difference between the groups. Coasting versus cabergoline There were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 1.98, 95% CI 0.09 to 5.68; P = 0.20; I² = 72%; two RCTs; 120 women; very low‐quality evidence), with 11 events in the coasting arm and six in the cabergoline arm. The evidence suggested that coasting was associated with lower rates of clinical pregnancy (OR 0.38, 95% CI 0.16 to 0.88; P = 0.02; I² =0%; two RCTs; 120 women; very low‐quality evidence), but there were only 33 events altogether. These studies did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage. AUTHORS' CONCLUSIONS: There was low‐quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low‐quality evidence from a single small study to suggest that using FSH co‐trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes.

Stevens- Johnson syndrome (SJS) is a severe and life-threatening condition. Although allopurinol, an antihyperuricemia drug, is the drug most commonly associated with SJS, more than 100 different causative drugs have been reported. Among hematologic drugs recently introduced into the market, drugs such as rituximab, imatinib, and bortezomib are reported. Here, we describe a patient with SJS while receiving lenalidomide in combination with prednisolone for treatment-naive multiple myeloma. Although SJS has been reported rarely as an adverse reaction to Lenalidomide, this drug should be considered in the etiology of SJS, and the increased number of prescriptions of Lenalidomide for the therapy of multiple myeloma has to stress the awareness of its potentially serious side-effects.

Despite advances in understanding the molecular pathogenesis of multiple myeloma and promising new therapies, almost all patients eventually relapse with resistant disease. There is therefore a strong rationale for combining novel therapies that target intrinsic molecular pathways mediating multiple myeloma cell resistance. One such protein family is the heat shock proteins (HSP), especially the HSP90 family. Heat shock protein inhibitors have been identified as promising cancer treatments as, while they only inhibit a single biologic function, the chaperone–protein association, their effect is widespread as it results in the destruction of numerous client proteins. This article reviews the preclinical and clinical data, which support the testing of HSP90 inhibitors as cancer drugs and update the reader on the current status of the ongoing clinical trials of HSP90 inhibitors in multiple myeloma.

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, I2 = 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, I2 = 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.

Tubal sterilisation is the most popular contraceptive method in the world. Approximately 138 million women of reproductive age have had tubal sterilisation and there is evidence that increasingly younger women are being sterilized. With such large numbers of women choosing this option of birth control it is clear that even if a small percentage of women later regret the decision large numbers of women will seek counselling regarding reversal from their physicians. The objectives were to compare the efficacy of surgical tubal reanastomosis and in vitro fertilisation in terms of live birth rates. The morbidity and cost-effectiveness of both techniques were also to be compared. The following databases were searched: Cochrane Menstrual Disorders and Subfertility Review Group Specialised Register MEDLINE (1966 to 2005) EMBASE (1980 to 2005) and other electronic databases. We hand-searched the reference lists of trials reviews and relevant textbooks; searched abstracts from relevant conferences and personally communicated with experts in the field. Randomised and quasi-randomised trials comparing surgical reversal of tubal sterilisation with in vitro fertilisation (IVF). The method of allocation will be assessed and results subgrouped according to whether the trials were randomised or quasi-randomised. No trials were found that met the selection criteria. No data exist on which to report. There is a need for well-designed controlled clinical trials to compare the efficacy and safety of surgical reversal of tubal sterilisation and IVF in restoring fertility in women seeking pregnancy following tubal sterilisation. (authors)

Reason for Withdrawal This review has been withdrawn from Issue 4, 2005 for updating. To view the published versions of this article, please click the 'Other versions' tab.