P-751 Immediate versus postponed frozen-thawed embryo transfer after IVF/ICSI: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Bergenheim ◽  
M Saupstad ◽  
N Pistoljevic ◽  
A Nyboe Andersen ◽  
J Lyng Forman ◽  
...  

Abstract Study question Can frozen embryo transfer (FET) be offered immediately after a stimulated IVF/ICSI cycle without compromising live birth rate (LBR)? Summary answer FET in the menstrual cycle immediately following the stimulated IVF/ICSI cycle was associated with a slightly higher LBR compared to standard postponed FET. What is known already It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle. This practice is thought to minimize any possible residual negative effect of ovarian stimulation, with excessive steroid levels and multiple corpora lutea, on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Even so, elective deferral of FET is an empirical strategy based on suggestions rather than solid scientific evidence and may unnecessarily delay time to pregnancy, causing frustration and decreased quality of life to couples. Study design, size, duration Systematic review and meta-analysis according to PRISMA guidelines. Original studies on subfertile women aged 18-46 with any indication for treatment with IVF/ICSI investigating the timing of FET after IVF/ICSI were included. Intervention was defined as FET in the menstrual cycle immediately following the stimulated IVF/ICSI cycle. Comparator was defined as FET in the second or subsequent menstrual cycle following IVF/ICSI. Risk of bias was assessed using Robins-I and quality of evidence using GRADE. Participants/materials, setting, methods PubMed (MEDLINE) and EMBASE databases were searched for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020. There were no limitations regarding year of publication or duration of follow-up but to English language. The primary outcome was LBR. Secondary outcomes were implantation rate, pregnancy rate, clinical pregnancy rate (CPR), time-to-pregnancy, miscarriage rate (MR), cycle cancellation rate and patient wellbeing. Main results and the role of chance Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n = 2,076) compared to postponed FET (n = 3,833), with a pooled aOR of 1.20 (95% CI 1.01-1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07-1.39) for CPR. Limitations, reasons for caution Limitations include the retrospective design and heterogeneity of studies included, limiting comparison and pooling of data. With little transparency regarding cancellation rates, the risk of selection bias is apparent. Further, confounding by embryo quality is a limitation. Small sample sizes are a limitation to subgroup meta-analyses. Wider implications of the findings The standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. Randomized controlled trials including data on cancellation rates are highly needed to provide high grade evidence regarding clinical practice and patient counseling. Trial registration number not applicable

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Bergenheim ◽  
M Saupstad ◽  
N Pistoljevic ◽  
A Nybo. Andersen ◽  
J Lyn. Forman ◽  
...  

Abstract Study question Can frozen embryo transfer (FET) be offered immediately after a stimulated IVF/ICSI cycle without compromising live birth rate (LBR)? Summary answer FET in the menstrual cycle immediately following the stimulated IVF/ICSI cycle was associated with a slightly higher LBR compared to standard postponed FET. What is known already It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle. This practice is thought to minimize any possible residual negative effect of ovarian stimulation, with excessive steroid levels and multiple corpora lutea, on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Even so, elective deferral of FET is an empirical strategy based on suggestions rather than solid scientific evidence and may unnecessarily delay time to pregnancy, causing frustration and decreased quality of life to couples. Study design, size, duration Systematic review and meta-analysis according to PRISMA guidelines. Original studies on subfertile women aged 18–46 with any indication for treatment with IVF/ICSI investigating the timing of FET after IVF/ICSI were included. Intervention was defined as FET in the menstrual cycle immediately following the stimulated IVF/ICSI cycle. Comparator was defined as FET in the second or subsequent menstrual cycle following IVF/ICSI. Risk of bias was assessed using Robins-I and quality of evidence using GRADE. Participants/materials, setting, methods PubMed (MEDLINE) and EMBASE databases were searched for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020. There were no limitations regarding year of publication or duration of follow-up but to English language. The primary outcome was LBR. Secondary outcomes were implantation rate, pregnancy rate, clinical pregnancy rate (CPR), time-to-pregnancy, miscarriage rate (MR), cycle cancellation rate and patient wellbeing. Main results and the role of chance Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n = 2,076) compared to postponed FET (n = 3,833), with a pooled aOR of 1.20 (95% CI 1.01–1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07–1.39) for CPR. Limitations, reasons for caution: Limitations include the retrospective design and heterogeneity of studies included, limiting comparison and pooling of data. With little transparency regarding cancellation rates, the risk of selection bias is apparent. Further, confounding by embryo quality is a limitation. Small sample sizes are a limitation to subgroup meta-analyses. Wider implications of the findings: The standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. Randomized controlled trials including data on cancellation rates are highly needed to provide high grade evidence regarding clinical practice and patient counseling. Trial registration number Not applicable


Author(s):  
Sara J Bergenheim ◽  
Marte Saupstad ◽  
Nina Pistoljevic ◽  
Anders Nyboe Andersen ◽  
Julie Lyng Forman ◽  
...  

Abstract BACKGROUND In Europe, the number of frozen embryo transfer (FET) cycles is steadily increasing, now accounting for more than 190 000 cycles per year. It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or after a freeze-all cycle. The purpose of this practice is to minimise the possible residual negative effect of ovarian stimulation on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Although elective deferral of FET may unnecessarily delay time to pregnancy, immediate FET may be inefficient in a clinical setting, following an increased risk of irregular ovulatory cycles and the presence of functional cysts, increasing the risk of cycle cancellation. OBJECTIVE AND RATIONALE This review explores the impact of timing of FET in the first cycle (immediate FET) versus the second or subsequent cycle (postponed FET) following a failed fresh transfer or a freeze-all cycle on live birth rate (LBR). Secondary endpoints were implantation, pregnancy and clinical pregnancy rates (CPR) as well as miscarriage rate (MR). SEARCH METHODS We searched PubMed (MEDLINE) and EMBASE databases for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020, in English language. There were no limitations regarding year of publication or duration of follow-up. Inclusion criteria were subfertile women aged 18-46 years with any indication for treatment with IVF/ICSI. Studies on oocyte donation were excluded. All original studies were included, except for case reports, study protocols and abstracts only. Covidence, a Cochrane-tool, was used for sorting and screening of literature. Risk of bias was assessed using the Robins-I tool and the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. OUTCOMES Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n =2,076) compared to postponed FET (n =3,833), with a pooled aOR of 1.20 (95% CI 1.01–1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07–1.39) for CPR. WIDER IMPLICATIONS The results of this review indicate a slightly higher LBR and CPR in immediate versus postponed FET. Thus, the standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. However, as only retrospective cohort studies were assessed, the presence of selection bias is apparent, and the quality of evidence thus seems low. Randomised controlled trials including data on cancellation rates and reasons for cancellation are highly needed to provide high-grade evidence regarding clinical practice and patient counselling.


2021 ◽  
Vol 10 (12) ◽  
pp. 2609
Author(s):  
Adrian V. Hernandez ◽  
John Ingemi ◽  
Michael Sherman ◽  
Vinay Pasupuleti ◽  
Joshuan J. Barboza ◽  
...  

There are no proven prophylactic interventions for COVID-19. We systematically reviewed the efficacy of prophylactic hydroxychloroquine for COVID-19. Studies evaluating hydroxychloroquine for prophylaxis of COVID-19 were searched in several engines until 8 December 2020. Primary outcomes included RT-PCR positivity, COVID-19 infections (positive RT-PCR or compatible COVID-19 symptoms), and all-cause mortality. Random effects meta-analyses were performed for all outcomes. Five randomized controlled trials (RCTs) (n = 5579) and one cohort (n = 106) were included. Placebo was the comparator in four RCTs, and usual care in one RCT. Compared to the controls, five RCTs showed that hydroxychloroquine prophylaxis did not reduce RT-PCR positivity (RR 1.01, 95% CI 0.88–1.16), COVID-19 infection (RR 0.98, 95% CI 0.78–1.22), or all-cause mortality (RR 0.73, 95% CI 0.27–1.99). There were no differences of effects by pre- or post-exposure prophylaxis. Prophylaxis with hydroxychloroquine increased the risk of diarrhea, abdominal pain, or vomiting (RR 4.56, 95% CI 1.58–13.19). There were no effects of hydroxychloroquine on other secondary outcomes. Quality of evidence was low to very low for all outcomes. Hydroxychloroquine was not efficacious as a prophylaxis for COVID-19 infections, defined either as RT-PCR positivity or as a composite of RT-PCR positivity or compatible symptoms. Hydroxychloroquine did not reduce all-cause mortality, clinical worsening, or adverse events.


Author(s):  
Beatrice Heim ◽  
Florian Krismer ◽  
Klaus Seppi

AbstractDifferential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology. Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP-parkinsonism. Several studies have used midbrain to pons ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing PSP patients from those with Parkinson's disease. The current meta-analysis aimed to compare the performance of these measures in discriminating PSP from multiple system atrophy (MSA). A systematic MEDLINE review identified 59 out of 2984 studies allowing a calculation of sensitivity and specificity using the MRPI or M/P. Meta-analyses of results were carried out using random effects modelling. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eight studies were suitable for analysis. The meta‐analysis showed a pooled sensitivity and specificity for the MRPI of PSP versus MSA of 79.2% (95% CI 72.7–84.4%) and 91.2% (95% CI 79.5–96.5%), and 84.1% (95% CI 77.2–89.2%) and 89.2% (95% CI 81.8–93.8%), respectively, for the M/P. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection and index test, as all patients were seen in a specialized outpatient department without avoiding case control design and no predefined threshold was given regarding MRPI or M/P cut-offs. Planimetric brainstem measurements, in special the MRPI and M/P, yield high diagnostic accuracy for the discrimination of PSP from MSA. However, there is an urgent need for well-designed, prospective validation studies to ameliorate the concerns regarding the risk of bias.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Åsa Kettis ◽  
Hanna Fagerlind ◽  
Jan-Erik Frödin ◽  
Bengt Glimelius ◽  
Lena Ring

Abstract Background Effective patient-physician communication can improve patient understanding, agreement on treatment and adherence. This may, in turn, impact on clinical outcomes and patient quality of life (QoL). One way to improve communication is by using patient-reported outcome measures (PROMs). Heretofore, studies of the impact of using PROMs in clinical practice have mostly evaluated the use of standardized PROMs. However, there is reason to believe that individualized instruments may be more appropriate for this purpose. The aim of this study is to compare the effectiveness of the standardized QoL-instrument, the European Organization for Research and Treatment of Cancer Quality of Life C-30 (EORTC-QOL-C30) and the individualized QoL instrument, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), in clinical practice. Methods In a prospective, open-label, controlled intervention study at two hospital out-patient clinics, 390 patients with gastrointestinal cancer were randomly assigned either to complete the EORTC-QOL-C30 or the SEIQoL-DW immediately before the consultation, with their responses being shared with their physician. This was repeated in 3–5 consultations over a period of 4–6 months. The primary outcome measure was patients’ health-related QoL, as measured by FACIT-G. Patients’ satisfaction with the consultation and survival were secondary outcomes. Results There was no significant difference between the groups with regard to study outcomes. Neither intervention instrument resulted in any significant changes in health-related QoL, or in any of the secondary outcomes, over time. This may reflect either a genuine lack of effect or sub-optimization of the intervention. Since there was no comparison to standard care an effect in terms of lack of deterioration over time cannot be excluded. Conclusions Future studies should focus on the implementation process, including the training of physicians to use the instruments and their motivation for doing so. The effects of situational use of standardized or individualized instruments should also be explored. The effectiveness of the different approaches may depend on contextual factors including physician and patient preferences.


2021 ◽  
pp. 146531252110272
Author(s):  
Despina Koletsi ◽  
Anna Iliadi ◽  
Theodore Eliades

Objective: To evaluate all available evidence on the prediction of rotational tooth movements with aligners. Data sources: Seven databases of published and unpublished literature were searched up to 4 August 2020 for eligible studies. Data selection: Studies were deemed eligible if they included evaluation of rotational tooth movement with any type of aligner, through the comparison of software-based and actually achieved data after patient treatment. Data extraction and data synthesis: Data extraction was done independently and in duplicate and risk of bias assessment was performed with the use of the QUADAS-2 tool. Random effects meta-analyses with effect sizes and their 95% confidence intervals (CIs) were performed and the quality of the evidence was assessed through GRADE. Results: Seven articles were included in the qualitative synthesis, of which three contributed to meta-analyses. Overall results revealed a non-accurate prediction of the outcome for the software-based data, irrespective of the use of attachments or interproximal enamel reduction (IPR). Maxillary canines demonstrated the lowest percentage accuracy for rotational tooth movement (three studies: effect size = 47.9%; 95% CI = 27.2–69.5; P < 0.001), although high levels of heterogeneity were identified (I2: 86.9%; P < 0.001). Contrary, mandibular incisors presented the highest percentage accuracy for predicted rotational movement (two studies: effect size = 70.7%; 95% CI = 58.9–82.5; P < 0.001; I2: 0.0%; P = 0.48). Risk of bias was unclear to low overall, while quality of the evidence ranged from low to moderate. Conclusion: Allowing for all identified caveats, prediction of rotational tooth movements with aligner treatment does not appear accurate, especially for canines. Careful selection of patients and malocclusions for aligner treatment decisions remain challenging.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ka Ying Bonnie Ng ◽  
George Cherian ◽  
Alexandra J. Kermack ◽  
Sarah Bailey ◽  
Nick Macklon ◽  
...  

AbstractIt is known that lifestyle factors affect sporadic miscarriage, but the extent of this on RPL (recurrent pregnancy loss) is less well known. A systematic review and meta-analysis was performed to assess the associations between lifestyle factors and RPL. Studies that analysed RPL in the context of BMI, smoking, alcohol and caffeine intake were included. The primary and secondary outcomes were odds of having RPL in the general population and odds of further miscarriage, respectively. Underweight and women with BMI > 25 are at higher odds of RPL in the general population (OR 1.2, 95% CI 1.12–1.28 and OR 1.21, 95% CI 1.06–1.38, respectively). In women with RPL, having BMI > 30 and BMI > 25 has increased odds of further miscarriages (OR 1.77, 95% CI 1.25–2.50 and OR 1.35, 95% CI 1.07–1.72, respectively). The quality of the evidence for our findings was low or very low. Being underweight and BMI > 25 contributes significantly to increased risk of RPL (general population). BMI > 25 or BMI > 30 increases the risk of further miscarriages (RPL population). Larger studies addressing the effects of alcohol, cigarette smoking and caffeine on the risk of RPL with optimisation of BMI in this cohort of women are now needed.


2021 ◽  
Vol 10 (11) ◽  
pp. 2415
Author(s):  
Yasaman Vali ◽  
Jenny Lee ◽  
Jérôme Boursier ◽  
René Spijker ◽  
Joanne Verheij ◽  
...  

(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M Oberndorfer ◽  
I Grabovac ◽  
S Haider ◽  
T E Dorner

Abstract Background Reports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to synthesise the current evidence regarding the effectiveness of ECs for smoking cessation. Methods PubMed, PsycInfo and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy (NRT) and or counselling) published between 01/01/2014 and 01/05/2019. Data from eligible studies were extracted and used for random-effects meta-analyses. Results Our literature review yielded 13190 publications with 10 studies being identified as eligible for systematic review, covering 8362 participants, and 8 for meta-analyses (n = 30 - 6006). Using the last follow-up of eligible studies, the proportion of smokers achieving abstinence was 1.67 [95CI:0.99 - 2.81] times higher in nicotine EC users compared to non-nicotine EC users. The proportion of abstinent smokers was 1.69 [95CI:1.25 - 2.27] times higher in EC users compared to participants receiving NRT. EC users showed a 2.70 [95CI:1.15 - 6.30] times higher proportion of abstinent smokers in comparison to participants solely receiving counselling. Conclusions Our analysis showed modest effects of nicotine-ECs compared to non-nicotine ECs. When compared to NRT or counselling, results suggest that nicotine EC may be more effective for smoking cessation. As ECs also help maintaining routinized behaviour and social aspects of smoking, we hypothesise that this may explain their advantage as a tool for smoking cessation. However, given the small number of included studies, different populations, heterogeneous designs, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. More comparable data is needed to strengthen confidence in the quality of evidence. Key messages The number of previous studies assessing the effectiveness of ECs for smoking cessation is limited. Further, comparability of these studies is restricted, weakening the quality of evidence. Although current evidence on the effectiveness of ECs for smoking cessation is inconclusive, our meta-analyses suggest that ECs could be a promising alternative tool in attempts to achieve abstinence.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ran Liu ◽  
Kun Zhang ◽  
Qiu-yu Tong ◽  
Guang-wei Cui ◽  
Wen Ma ◽  
...  

Abstract Background Acupuncture for post-stroke depression (PSD) has been evolving, but uncertainty remains. To assess the existing evidence from randomized clinical trials (RCTs) of acupuncture for PSD, we sought to draw conclusions by synthesizing RCTs. Methods An exhaustive literature search was conducted in seven electronic databases from their inception dates to April 19, 2020, to identify systematic reviews (SRs) and meta-analyses (MAs) on this topic. The primary RCTs included in the SRs/MAs were identified. We also conducted a supplementary search for RCTs published from January 1, 2015, to May 12, 2020. Two reviewers extracted data separately and pooled data using RevMan 5.3 software. The quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system. Results A total of 17 RCTs involving 1402 patients were included. Meta-analysis showed that participants who received a combination of acupuncture and conventional treatments exhibited significantly lower scores on the HAM-D17, HAM-D24 and HAM-D (MD, − 5.08 [95% CI, − 6.48 to − 3.67], I2 = 0%), (MD, − 9.72 [95% CI, − 14.54 to − 4.91], I2 = 65%) and (MD, − 2.72 [95% CI, − 3.61 to − 1.82], respectively) than those who received conventional treatment. However, there was no significant difference in acupuncture versus antidepressants in terms of the 17-item, 24-item and HAM-D scales (MD, − 0.43 [95% CI, − 1.61 to 0.75], I2 = 51%), (MD, − 3.09 [95% CI, − 10.81 to 4.63], I2 = 90%) and (MD, − 1.55 [95% CI, − 4.36 to 1.26], I2 = 95%, respectively). For adverse events, acupuncture was associated with fewer adverse events than antidepressants (RR, 0.16 [95% CI, 0.07 to 0.39], I2 = 35%), but there was no significant difference in the occurrence of adverse events between the combination of acupuncture and conventional treatments versus conventional treatments (RR, 0.63 [95% CI, 0.21 to 1.83], I2 = 38%). The quality of evidence was low to very low due to the substantial heterogeneity among the included studies. Conclusions The current review indicates that acupuncture has greater effect on PSD and better safety profile than antidepressants, but high-quality evidence evaluating acupuncture for PSD is still needed.


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