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

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 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


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 10 (7) ◽  
pp. 1478
Author(s):  
Alexandra Voinescu ◽  
Jie Sui ◽  
Danaë Stanton Fraser

Neurological disorders are a leading cause of death and disability worldwide. Can virtual reality (VR) based intervention, a novel technology-driven change of paradigm in rehabilitation, reduce impairments, activity limitations, and participation restrictions? This question is directly addressed here for the first time using an umbrella review that assessed the effectiveness and quality of evidence of VR interventions in the physical and cognitive rehabilitation of patients with stroke, traumatic brain injury and cerebral palsy, identified factors that can enhance rehabilitation outcomes and addressed safety concerns. Forty-one meta-analyses were included. The data synthesis found mostly low- or very low-quality evidence that supports the effectiveness of VR interventions. Only a limited number of comparisons were rated as having moderate and high quality of evidence, but overall, results highlight potential benefits of VR for improving the ambulation function of children with cerebral palsy, mobility, balance, upper limb function, and body structure/function and activity of people with stroke, and upper limb function of people with acquired brain injury. Customization of VR systems is one important factor linked with improved outcomes. Most studies do not address safety concerns, as only nine reviews reported adverse effects. The results provide critical recommendations for the design and implementation of future VR programs, trials and systematic reviews, including the need for high quality randomized controlled trials to test principles and mechanisms, in primary studies and in meta-analyses, in order to formulate evidence-based guidelines for designing VR-based rehabilitation interventions.


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.


2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Mariano Mascarenhas ◽  
Theodoros Kalampokas ◽  
Sesh Kamal Sunkara ◽  
Mohan S Kamath

Abstract STUDY QUESTION Are systematic reviews published within a 3-year period on interventions in ART concordant in their conclusions? SUMMARY ANSWER The majority of the systematic reviews published within a 3-year period in the field of assisted reproduction on the same topic had discordant conclusions. WHAT IS KNOWN ALREADY Systematic reviews and meta-analyses have now replaced individual randomized controlled trials (RCTs) at the top of the evidence pyramid. There has been a proliferation of systematic reviews and meta-analyses, many of which suffer from methodological issues and provide varying conclusions. STUDY DESIGN, SIZE, DURATION We assessed nine interventions in women undergoing ART with at least three systematic reviews each, published from January 2015 to December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS The systematic reviews which included RCTs were considered eligible for inclusion. The primary outcome was extent of concordance between systematic reviews on the same topic. Secondary outcomes included assessment of quality of systematic reviews, differences in included studies in meta-analyses covering the same search period, selective reporting and reporting the quality of evidence. MAIN RESULTS AND THE ROLE OF CHANCE Concordant results and conclusions were found in only one topic, with reviews in the remaining eight topics displaying partial discordance. The AMSTAR grading for the majority of the non-Cochrane reviews was critically low whilst it was categorized as high for all of the Cochrane reviews. For three of the nine topics, none of the included systematic reviews assessed the quality of evidence. We were unable to assess selective reporting as most of the reviews did not have a pre-specified published protocol. LIMITATIONS, REASONS FOR CAUTION We were limited by the high proportion of reviews lacking a pre-specified protocol, which made it impossible to assess for selective reporting. Furthermore, many reviews did not specify primary and secondary outcomes which made it difficult to assess reporting bias. All the authors of this review were Cochrane review authors which may introduce some assessment bias. The categorization of the review’s conclusions as beneficial, harmful or neutral was subjective, depending on the tone and wording of the conclusion section of the review. WIDER IMPLICATIONS OF THE FINDINGS The majority of the systematic reviews published within a 3-year period on the same topic in the field of assisted reproduction revealed discordant conclusions and suffered from serious methodological issues, hindering the process of informed healthcare decision-making. STUDY FUNDING/COMPETING INTEREST(S) All the authors are Cochrane authors. M.S.K. is an editorial board member of Cochrane Gynaecology and Fertility group. No grant from funding agencies in the public, commercial or not-for-profit sectors was obtained.


2021 ◽  
Author(s):  
Alaa Abd-alrazaq ◽  
Dari Alhuwail ◽  
Eiman Al-Jafar ◽  
Arfan Ahmed ◽  
Shuja Mohd Reagu ◽  
...  

BACKGROUND Memory, one of the main cognitive functions, is known to decline by age. Serious games have been used for improving memory among the elderly. The effectiveness of serious games in improving memory has been investigated by several systematic reviews; however, they are limited by design and methodological weaknesses. OBJECTIVE This study aims to assess the effectiveness of serious games in improving memory among the elderly with cognitive impairment. METHODS A systematic review of randomized controlled trials (RCTs) was carried out. The search sources included searching 8 databases, screening reference lists of the included studies and relevant reviews, and checking studies that cited the included studies. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. Extracted data were synthesized using a narrative approach and a statistical approach (i.e., meta-analysis), as appropriate. RESULTS Out of 466 citations retrieved, 18 studies met the eligibility criteria of this review. Of those, 15 RCTs were eventually included in 10 meta-analyses. We found that serious games are more effective than no or passive interventions in improving non-verbal memory (P=0.002) and working memory (P=0.02), but not verbal memory (P=0.13). The review also showed that serious games are more effective than conventional exercises in improving verbal memory (P=0.004), but not for non-verbal memory (P=0.12) and working memory (P=0.49). Serious games were as effective as conventional cognitive activities in improving verbal memory (P=0.07), non-verbal memory (P=0.94), and working memory (P=0.08) among the elderly with cognitive impairment. Lastly, the effect of adaptive serious games on working memory was comparable to non-adaptive serious games (P=0.08). CONCLUSIONS Serious games have the potential to improve verbal, non-verbal, and working memory among elderly people with cognitive impairment. However, our findings should be interpreted cautiously given that most meta-analyses were based on a few studies (≤3) and judged to have a low quality of evidence. Therefore, serious games should be offered as supplemental to existing proven and safe interventions, rather than a complete substitute until further, more robust evidence is available. Future studies should investigate the short and long-term effects of serious games on memory and other cognitive abilities among people from different age groups with or without cognitive impairment.


Author(s):  
Adrian Hernandez ◽  
John Ingemi III ◽  
Michael Sherman ◽  
Vinay Pasupuleti ◽  
Joshuan Barboza ◽  
...  

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n=1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR 0.80, 95%CI 0.47-1.36, I2=2%, 5 RCTs, low QoE), all-cause mortality (RR 0.77, 95%CI 0.16-3.68, I2=0%, 5 RCTs, very low QoE), symptom resolution (RR 0.94, 95%CI 0.77-1.16, I2=71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR 1.02, 95%CI 0.82-1.27, I2=65%, 2 RCTs, low QoE). There was a higher non-significant increase of adverse events with hydroxychloroquine vs. controls (RR 2.17, 95%CI 0.86-5.45, I2=92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.


Author(s):  
Igor Grabovac ◽  
Moritz Oberndorfer ◽  
Jismy Fischer ◽  
Winfried Wiesinger ◽  
Sandra Haider ◽  
...  

Abstract Introduction 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 assess the current evidence regarding 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 counseling) published between 1 January 2014 and 27 June 2020. Data from eligible studies were extracted and used for random-effects meta-analyses (PROSPERO registration number: CRD42019141414). Results The search yielded 13 950 publications with 12 studies being identified as eligible for systematic review (N = 8362) and 9 studies for random-effects meta-analyses (range: 30–6006 participants). The proportion of smokers achieving abstinence was 1.71 (95 CI: 1.02–2.84) times higher in nicotine EC users compared with non-nicotine EC users. The proportion of abstinent smokers was 1.69 (95 CI: 1.25–2.27) times higher in EC users compared with participants receiving NRT. EC users showed a 2.04 (95 CI: 0.90–4.64) times higher proportion of abstinent smokers in comparison with participants solely receiving counseling. Conclusions Our results suggest that nicotine ECs may be more effective in smoking cessation when compared with placebo ECs or NRT. When compared with counseling alone, nicotine ECs are more effective short term, but its effectiveness appears to diminish with later follow-ups. Given the small number of studies, heterogeneous design, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations. Implications The results of this study do not allow for a conclusive argument. However, pooling current evidence points toward a potential for ECs as a smoking cessation tool. Though, given the overall quality of evidence, future studies should aim for more clarity in terms of interventions and larger study populations.


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