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Endocrine Practice : Official Journal... Feb 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight and Cardiometabolic Parameters in Individuals With Obesity and Without Diabetes: A Systematic Review and Meta-Analysis.
OBJECTIVE
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese individuals without diabetes. Our goal was to examine existing research for conclusive evidence on various types of GLP-1 RAs for weight loss and cardiometabolic benefits in obesity without diabetes.
METHODS
We conducted an electronic search on PubMed, Scopus, and Cochrane Central using keywords, such as "GLP-1 RA," "obesity," and "weight loss." We considered all available global GLP-1 RAs for inclusion. Our analysis focused on weight loss, blood pressure (BP) changes (systolic and diastolic BPs), and lipid profile effects (high-density lipoprotein, low-density lipoprotein, total cholesterol, and triacylglycerol). We used a random-effects meta-analysis with the standardized mean difference (SMD), mean difference (MD), odds ratio, and relative risk to present the results.
RESULTS
Our search yielded a total of 7535 articles. We included 15 trials in our study. GLP-1 RAs led to significant weight loss (MD, -8.77 kg; P <.01) in obese individuals. GLP-1 RAs also improved the systolic BP (MD, -4.13 mm Hg; P <.01), diastolic BP (MD, -1.39 mm Hg; P <.01), and lipid profiles, including improved levels of triacylglycerol (SMD, -0.99 mg/dL; P <.01), total cholesterol (SMD, -0.73 mg/dL; P <.01), very low-density lipoprotein (SMD, -1.11 mg/dL; P <.01), and low-density lipoprotein (SMD, -0.27 mg/dL; P <.01), and significantly increased high-density lipoprotein levels (SMD, 0.11 mg/dL; P <.01). However, GLP-1 RAs were associated with an increased risk of gastrointestinal adverse events.
CONCLUSION
GLP-1 RAs were found to be beneficial for not only weight loss but also reduction in risk factors for cardiovascular disease such as BP and lipid profile. Consistent beneficial results were observed across the various subtypes of GLP-1 RAs.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor Agonists; Glucagon-Like Peptide 1; Obesity; Cardiovascular Diseases; Weight Loss; Lipids; Triglycerides; Lipoproteins, HDL; Lipoproteins, LDL; Cholesterol; Glucagon-Like Peptide-1 Receptor
PubMed: 38029929
DOI: 10.1016/j.eprac.2023.11.007 -
BMJ Open Mar 2023To compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis.
OBJECTIVE
To compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in overweight or obese adults with or without diabetes mellitus.
METHODS
PubMed, ISI Web of Science, Embase and Cochrane Central Register of Controlled Trials database were comprehensively searched to identify randomised controlled trials (RCTs) of effects of GLP-1RAs and SGLT-2is in overweight or obese participants from inception to 16 January 2022. The efficacy outcomes were the changes of body weight, glucose level and blood pressure. The safety outcomes were serious adverse events and discontinuation due to adverse events. The mean differences, ORs, 95% credible intervals (95% CI), the surface under the cumulative ranking were evaluated for each outcome by network meta-analysis.
RESULTS
Sixty-one RCTs were included in our analysis. Both GLP-1RAs and SGLT-2is conferred greater extents in body weight reduction, achieving at least 5% wt loss, HbA1c and fasting plasma glucose decrease compared with placebo. GLP-1RAs was superior to SGLT-2is in HbA1c reduction (MD: -0.39%, 95% CI -0.70 to -0.08). GLP-1RAs had high risk of adverse events, while SGLT-2is were relatively safe. Based on intraclass comparison, semaglutide 2.4 mg was among the most effective interventions in losing body weight (MD: -11.51 kg, 95% CI -12.83 to -10.21), decreasing HbA1c (MD: -1.49%, 95% CI -2.07 to -0.92) and fasting plasma glucose (MD: -2.15 mmol/L, 95% CI -2.83 to -1.59), reducing systolic blood pressure (MD: -4.89 mm Hg, 95% CI -6.04 to -3.71) and diastolic blood pressure (MD: -1.59 mm Hg, 95% CI -2.37 to -0.86) with moderate certainty evidences, while it was associated with high risk of adverse events.
CONCLUSIONS
Semaglutide 2.4 mg showed the greatest effects on losing body weight, controlling glycaemic level and reducing blood pressure while it was associated with high risk of adverse events.PROSPERO registration numberCRD42021258103.
Topics: Adult; Humans; Blood Glucose; Body Weight; Diabetes Mellitus; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Network Meta-Analysis; Obesity; Overweight; Sodium-Glucose Transporter 2 Inhibitors; Weight Loss
PubMed: 36882248
DOI: 10.1136/bmjopen-2022-061807 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2022Xylazine is an alpha-2-adrenergic agonist used for its sedative and analgesic properties in veterinary medicine. While not approved by the Food and Drug Administration...
PURPOSE
Xylazine is an alpha-2-adrenergic agonist used for its sedative and analgesic properties in veterinary medicine. While not approved by the Food and Drug Administration for use in humans, anecdotal evidence suggests that exposures in humans is on the rise. We sought to systematically review and synthesize the evidence on xylazine exposure in humans focusing on the clinical presentation, management, and outcomes.
METHODS
We conducted a systematic review of the literature including PubMed, Embase, and Scopus from their inception to September 9, 2021. We searched abstracts from selected emergency medicine and toxicology conferences from 2011 through 2021. We included clinical reports of xylazine exposure in humans. We excluded animal studies, studies, laboratory studies, or articles in a language other than English. From each included article, we extracted subjective and objective data that focused on clinical presentation, management, and outcomes of patients exposed to xylazine.
RESULTS
We evaluated a total of 1409 records, rendering a final set of 17 articles and 2 abstracts meeting inclusion criteria. We identified a total of 98 patients amongst reports ranging from 1979 to 2020 and across nine countries. The most common types of xylazine exposures reported were unintentional exposure and intentional misuse/abuse. Common symptoms on presentation included hypotension, bradycardia, drowsiness, lethargy, while apnea with intubation and death were less frequently reported.
CONCLUSION
Human exposure to xylazine appears to be a rising concern within the prehospital and emergency medicine setting. Although a standardized treatment algorithm cannot be recommended at this time, further research is needed to improve the care of patients exposed to xylazine.
Topics: Adrenergic Agonists; Bradycardia; Humans; Hypnotics and Sedatives; Hypotension; United States; Xylazine
PubMed: 35442125
DOI: 10.1080/15563650.2022.2063135 -
Diabetes & Metabolic Syndrome Mar 2022The importance of glucagon-like peptide-1 (GLP-1) agonists is increasing because of its blood sugar controlling and weight loss properties. The data regarding safety of... (Review)
Review
BACKGROUND AND AIM
The importance of glucagon-like peptide-1 (GLP-1) agonists is increasing because of its blood sugar controlling and weight loss properties. The data regarding safety of GLP-1 agonists are limited. This study aims to review case reports and case series on adverse drug reactions (ADRs) of GLP-1 agonist.
METHODOLOGY
A comprehensive search was performed in PubMed/Medline, Scopus and Embase to identify literatures. Bibliographic search and open search in Google, Google Scholar, SpringerLink and ResearchGate was performed to identify additional studies. Case reports and case series published the ADRs by the use of GLP-1 agonists in type 2 diabetes patients were included in the study. Reviews, experimental studies, observational studies, grey literature and non English studies were excluded.
RESULTS
The study identified 120 cases of GLP-1 agonists associated ADRs (liraglutide - 46, exenatide - 46, dulaglutide - 20, semaglutide - 4, albiglutide - 2, lixisenatide - 2). The major ADRs reported was gastrointestinal disorders (n = 40) followed by renal (n = 23), dermatologic (n = 14), hepatic (n = 10), immunologic (n = 13), endocrine/metabolic (n = 7), hematologic (n = 3), angioedema (n = 3), neurologic (n = 2), cardiovascular (n = 2) and 1 from each of psychiatric, reproductive, generalized edema problems.
CONCLUSION
Gastrointestinal problems, particularly pancreatitis was the more frequently reported adverse drug reaction associated with GLP-1 agonist. The most adverse drug reactions were observed with liraglutide and exenatide.
Topics: Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Liraglutide
PubMed: 35217468
DOI: 10.1016/j.dsx.2022.102427 -
Lancet (London, England) Dec 2014Combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin has been proposed as a treatment strategy for type 2 diabetes that could provide... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin has been proposed as a treatment strategy for type 2 diabetes that could provide robust glucose-lowering capability with low risk of hypoglycaemia or weight gain. We thus did a systematic review and meta-analysis of randomised controlled trials to assess the effect of this combination treatment on glycaemic control, hypoglycaemia, and weight gain in patients with type 2 diabetes.
METHODS
We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA.gov, and ClinicalTrials.gov for randomised controlled trials (published between Jan 1, 1950, and July 29, 2014; no language restrictions) comparing GLP-1 agonist and basal insulin combination treatment to other anti-diabetic treatments. Our main endpoints were glycaemic control, hypoglycaemia, and change in weight. We assessed pooled data by use of a random-effects model.
FINDINGS
Of 2905 identified studies, 15 were eligible and were included in our analysis (N=4348 participants). Compared with other anti-diabetic treatments, GLP-1 agonist and basal insulin combination treatment yielded an improved mean reduction in glycated haemoglobin (HbA1c) of -0·44% (95% CI -0·60 to -0·29), an improved likelihood of achieving the target HbA1c of 7·0% or lower (relative risk [RR] 1·92; 95% CI 1·43 to 2·56), no increased relative risk of hypoglycaemia (0·99; 0·76 to 1·29), and a mean reduction in weight of -3·22 kg (-4·90 to -1·54). Furthermore, compared with basal-bolus insulin regimens, the combination treatment yielded a mean reduction in HbA1c of -0·1% (-0·17 to -0·02), with lower relative risk of hypoglycaemia (0·67, 0·56 to 0·80), and reduction in mean weight (-5·66 kg; -9·8 to -1·51).
INTERPRETATION
GLP-1 agonist and basal insulin combination treatment can enable achievement of the ideal trifecta in diabetic treatment: robust glycaemic control with no increased hypoglycaemia or weight gain. This combination is thus a potential therapeutic strategy that could improve the management of patients with type 2 diabetes.
FUNDING
None.
Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Receptors, Glucagon; Weight Loss
PubMed: 25220191
DOI: 10.1016/S0140-6736(14)61335-0 -
The Lancet. Gastroenterology &... Apr 2022There are no licensed treatments for non-alcoholic fatty liver disease (NAFLD), but three different classes of antihyperglycaemic drugs-peroxisome proliferator-activated... (Review)
Review
Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review.
There are no licensed treatments for non-alcoholic fatty liver disease (NAFLD), but three different classes of antihyperglycaemic drugs-peroxisome proliferator-activated receptor (PPAR) agonists, glucagon-like peptide-1 receptor (GLP-1R) agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors-show promise in the treatment of the disease. We did a systematic review of randomised controlled trials examining the efficacy of PPAR agonists, GLP-1R agonists, or SGLT2 inhibitors for specifically treating NAFLD in adults with or without type 2 diabetes. A total of 25 active-controlled or placebo-controlled trials met our inclusion criteria: eight for PPAR agonists, ten for GLP-1R agonists, and seven for SGLT2 inhibitors. 2597 individuals (1376 [53%] men vs 1221 [47%] women; mean age 52 years (SD 6); mean BMI 32 kg/m (SD 3); 1610 [62%] with type 2 diabetes) were included. Pioglitazone, lanifibranor, and GLP1-R agonists (mostly liraglutide and semaglutide) improved individual histological features of NASH (ie, steatosis, ballooning, lobular inflammation) or achieved resolution of NASH without worsening of fibrosis. SGLT2 inhibitors (mostly empagliflozin and dapagliflozin) reduced liver fat content, as assessed by magnetic resonance-based techniques.
Topics: Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Peroxisome Proliferator-Activated Receptors; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35030323
DOI: 10.1016/S2468-1253(21)00261-2 -
Hormone and Metabolic Research =... Jul 2022Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in... (Meta-Analysis)
Meta-Analysis
Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in overweight/obese patients without diabetes. The random-effect model was used to pool data extracted from included literatures. The weighted mean difference (WMD), odds ratio and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD 42020173199). The sources of intertrial heterogeneity, bias and the robustness of results were evaluated by subgroup analysis, sensitivity analysis and regression analysis, respectively. A total of 24 RCTs were recruited in the present analysis which included 5867 patients. The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo [WMD=-5.39, 95% CI (-6.82, -3.96)] and metformin [WMD=-5.46, 95% CI (-5.87, -5.05)]. The subgroup analysis showed that semaglutide displayed the most obvious antiobesity effect in terms of weight loss, the reduction of body mass index (BMI) and waist circumference (WC). However, GLP-1RAs treatments had more gastrointestinal adverse events (such as nausea and vomiting) than placebo and Met. The subgroup analysis also represented that semaglutide displayed the lowest risk of gastrointestinal adverse events among three kinds of GLP-1RAs. Our meta-analysis demonstrated that GLP-1RA had a superior antiobesity effect than placebo/Met in overweight/obese patients without diabetes in terms of body weight, BMI, and WC, especially for semaglutide, which had more obvious antiobesity effect and lower GI adverse events than liraglutide and exenatide.
Topics: Anti-Obesity Agents; Exenatide; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Liraglutide; Obesity; Weight Loss
PubMed: 35512849
DOI: 10.1055/a-1844-1176 -
Diabetes Research and Clinical Practice Apr 2023To investigate the efficacy and safety of oral semaglutide 7 and 14 mg, the only orally delivered glucagon-like peptide-1 (GLP-1) receptor agonist tablet approved for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To investigate the efficacy and safety of oral semaglutide 7 and 14 mg, the only orally delivered glucagon-like peptide-1 (GLP-1) receptor agonist tablet approved for type 2 diabetes mellitus (T2DM) patients.
METHODS
Search several databases for randomized controlled trials (RCTs) of oral semaglutide in patients with T2DM from inception through May 31, 2021. The primary outcomes included change from baseline in hemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes.
RESULTS
This meta-analysis included 11 RCTs with a total of 9821 patients. Compared with placebo, semaglutide 7 and 14 mg reduced HbA1c by 1.06% (95% CI, 0.81-1.30) and 1.10% (95% CI, 0.88-1.31), respectively. While in comparison with other antidiabetic agents, semaglutide 7 and 14 mg reduced HbA1c by 0.26% (95% CI, 0.15-0.38) and 0.38% (95%CI, 0.31-0.45). Both doses of semaglutide could significantly reduce body weight. Semaglutide 14 mg did increase the incidence of medication discontinuation and gastrointestinal events (nausea, vomiting and diarrhea).
CONCLUSION
Once-daily semaglutide 7 and 14 mg can significantly lowered HbA1c and body weight in patients with T2DM, and this effect increases with dose. Significantly, more gastrointestinal events occurred with semaglutide 14 mg.
Topics: Humans; Glycated Hemoglobin; Treatment Outcome; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Body Weight; Glucagon-Like Peptide-1 Receptor
PubMed: 36871874
DOI: 10.1016/j.diabres.2023.110605 -
The Cochrane Database of Systematic... Jul 2015Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques(ART), progesterone and/or hCG levels are low, so the luteal phase is supported with progesterone, hCG or gonadotropin-releasing hormone (GnRH) agonists to improve implantation and pregnancy rates.
OBJECTIVES
To determine the relative effectiveness and safety of methods of luteal phase support provided to subfertile women undergoing assisted reproduction.
SEARCH METHODS
We searched databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and trial registers. We conducted searches in November 2014, and further searches on 4 August 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of luteal phase support using progesterone, hCG or GnRH agonist supplementation in ART cycles.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials, extracted data and assessed risk of bias. We calculated odds ratios (ORs) and 95%confidence intervals (CIs) for each comparison and combined data when appropriate using a fixed-effect model. Our primary out come was live birth or ongoing pregnancy. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
Ninety-four women RCTs (26,198 women) were included. Most studies had unclear or high risk of bias in most domains. The main limitations in the evidence were poor reporting of study methods and imprecision due to small sample sizes.1. hCG vs placebo/no treatment (five RCTs, 746 women)There was no evidence of differences between groups in live birth or ongoing pregnancy (OR 1.67, 95% CI 0.90 to 3.12, three RCTs,527 women, I2 = 24%, very low-quality evidence, but I2 of 61% was found for the subgroup of ongoing pregnancy) with a random effects model. hCG increased the risk of ovarian hyperstimulation syndrome (OHSS) (1 RCT, OR 4.28, 95% CI 1.91 to 9.6, low quality evidence).2. Progesterone vs placebo/no treatment (eight RCTs, 875 women)Evidence suggests a higher rate of live birth or ongoing pregnancy in the progesterone group (OR 1.77, 95% CI 1.09 to 2.86, five RCTs, 642 women, I2 = 35%, very low-quality evidence). OHSS was not reported.3. Progesterone vs hCG regimens (16 RCTs, 2162 women)hCG regimens included comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. No evidence showed differences between groups in live birth or ongoing pregnancy (OR 0.95, 95% CI 0.65 to 1.38, five RCTs, 833 women, I2 = 0%, low quality evidence) or in the risk of OHSS (four RCTs, 615 women, progesterone vs hCG OR 0.54, 95% CI 0.22 to 1.34; four RCTs,678 women; progesterone vs progesterone plus hCG, OR 0.34, 95% CI 0.09 to 1.26, low-quality evidence).4. Progesterone vs progesterone with oestrogen (16 RCTs, 2577 women)No evidence was found of differences between groups in live birth or ongoing pregnancy (OR 1.12, 95% CI 0.91 to 1.38, nine RCTs,1651 women, I2 = 0%, low-quality evidence) or OHSS (OR 0.56, 95% CI 0.2 to 1.63, two RCTs, 461 women, I2 = 0%, low-quality evidence).5. Progesterone vs progesterone + GnRH agonist (seven RCTs, 1708 women)Live birth or ongoing pregnancy rates were lower in the progesterone-only group and increased in women who received progester one and one or more GnRH agonist doses (OR 0.62, 95% CI 0.48 to 0.81, nine RCTs, 2861 women, I2 = 55%, random effects, low quality evidence). Statistical heterogeneity for this comparison was high because of unexplained variation in the effect size, but the direction of effect was consistent across studies. OHSS was reported in one study only (OR 1.00, 95% CI 0.33 to 3.01, 1 RCT, 300 women, very low quality evidence).6. Progesterone regimens (45 RCTs, 13,814 women)The included studies reported nine different comparisons between progesterone regimens. Findings for live birth or ongoing pregnancy were as follows: intramuscular (IM) versus oral: OR 0.71, 95% CI 0.14 to 3.66 (one RCT, 40 women, very low-quality evidence);IM versus vaginal/rectal: OR 1.24, 95% CI 1.03 to 1.5 (seven RCTs, 2309 women, I2 = 71%, very low-quality evidence); vaginal/rectal versus oral: OR 1.19, 95% CI 0.83 to 1.69 (four RCTs, 857 women, I2 = 32%, low-quality evidence); low-dose versus high-dose vaginal: OR 0.97, 95% CI 0.84 to 1.11 (five RCTs, 3720 women, I2 = 0%, moderate-quality evidence); short versus long protocol:OR 1.04, 95% CI 0.79 to 1.36 (five RCTs, 1205 women, I2 = 0%, low-quality evidence); micronised versus synthetic: OR 0.9, 95%CI 0.53 to 1.55 (two RCTs, 470 women, I2 = 0%, low-quality evidence); vaginal ring versus gel: OR 1.09, 95% CI 0.88 to 1.36 (oneRCT, 1271 women, low-quality evidence); subcutaneous versus vaginal gel: OR 0.92, 95% CI 0.74 to 1.14 (two RCTs, 1465 women,I2 = 0%, low-quality evidence); and vaginal versus rectal: OR 1.28, 95% CI 0.64 to 2.54 (one RCT, 147 women, very low-quality evidence). OHSS rates were reported for only two of these comparisons: IM versus oral, and low versus high-dose vaginal. No evidence showed a difference between groups.7. Progesterone and oestrogen regimens (two RCTs, 1195 women)The included studies compared two different oestrogen protocols. No evidence was found to suggest differences in live birth or ongoing pregnancy rates between a short and a long protocol (OR 1.08, 95% CI 0.81 to 1.43, one RCT, 910 women, low-quality evidence) or between a low dose and a high dose of oestrogen (OR 0.65, 95% CI 0.37 to 1.13, one RCT, 285 women, very low-quality evidence).Neither study reported OHSS.
AUTHORS' CONCLUSIONS
Both progesterone and hCG during the luteal phase are associated with higher rates of live birth or ongoing pregnancy than placebo.The addition of GnRHa to progesterone is associated with an improvement in pregnancy outcomes. OHSS rates are increased with hCG compared to placebo (only study only). The addition of oestrogen does not seem to improve outcomes. The route of progester one administration is not associated with an improvement in outcomes.
Topics: Chorionic Gonadotropin; Drug Therapy, Combination; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Live Birth; Luteal Phase; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Maintenance; Progesterone; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted
PubMed: 26148507
DOI: 10.1002/14651858.CD009154.pub3 -
The Cochrane Database of Systematic... Jul 2017Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among subfertile couples undergoing assisted reproductive technology (ART), pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles have historically been found to be lower than following embryo transfer undertaken two to five days following oocyte retrieval. Nevertheless, FET increases the cumulative pregnancy rate, reduces cost, is relatively simple to undertake and can be accomplished in a shorter time period than repeated in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles with fresh embryo transfer. FET is performed using different cycle regimens: spontaneous ovulatory (natural) cycles; cycles in which the endometrium is artificially prepared by oestrogen and progesterone hormones, commonly known as hormone therapy (HT) FET cycles; and cycles in which ovulation is induced by drugs (ovulation induction FET cycles). HT can be used with or without a gonadotrophin releasing hormone agonist (GnRHa). This is an update of a Cochrane review; the first version was published in 2008.
OBJECTIVES
To compare the effectiveness and safety of natural cycle FET, HT cycle FET and ovulation induction cycle FET, and compare subtypes of these regimens.
SEARCH METHODS
On 13 December 2016 we searched databases including Cochrane Gynaecology and Fertility's Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. Other search sources were trials registers and reference lists of included studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing the various cycle regimens and different methods used to prepare the endometrium during FET.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Our primary outcomes were live birth rates and miscarriage.
MAIN RESULTS
We included 18 RCTs comparing different cycle regimens for FET in 3815 women. The quality of the evidence was low or very low. The main limitations were failure to report important clinical outcomes, poor reporting of study methods and imprecision due to low event rates. We found no data specific to non-ovulatory women. 1. Natural cycle FET comparisons Natural cycle FET versus HT FETNo study reported live birth rates, miscarriage or ongoing pregnancy.There was no evidence of a difference in multiple pregnancy rates between women in natural cycles and those in HT FET cycle (odds ratio (OR) 2.48, 95% confidence interval (CI) 0.09 to 68.14, 1 RCT, n = 21, very low-quality evidence). Natural cycle FET versus HT plus GnRHa suppressionThere was no evidence of a difference in rates of live birth (OR 0.77, 95% CI 0.39 to 1.53, 1 RCT, n = 159, low-quality evidence) or multiple pregnancy (OR 0.58, 95% CI 0.13 to 2.50, 1 RCT, n = 159, low-quality evidence) between women who had natural cycle FET and those who had HT FET cycles with GnRHa suppression. No study reported miscarriage or ongoing pregnancy. Natural cycle FET versus modified natural cycle FET (human chorionic gonadotrophin (HCG) trigger)There was no evidence of a difference in rates of live birth (OR 0.55, 95% CI 0.16 to 1.93, 1 RCT, n = 60, very low-quality evidence) or miscarriage (OR 0.20, 95% CI 0.01 to 4.13, 1 RCT, n = 168, very low-quality evidence) between women in natural cycles and women in natural cycles with HCG trigger. However, very low-quality evidence suggested that women in natural cycles (without HCG trigger) may have higher ongoing pregnancy rates (OR 2.44, 95% CI 1.03 to 5.76, 1 RCT, n = 168). There were no data on multiple pregnancy. 2. Modified natural cycle FET comparisons Modified natural cycle FET (HCG trigger) versus HT FETThere was no evidence of a difference in rates of live birth (OR 1.34, 95% CI 0.88 to 2.05, 1 RCT, n = 959, low-quality evidence) or ongoing pregnancy (OR 1.21, 95% CI 0.80 to 1.83, 1 RCT, n = 959, low-quality evidence) between women in modified natural cycles and those who received HT. There were no data on miscarriage or multiple pregnancy. Modified natural cycle FET (HCG trigger) versus HT plus GnRHa suppressionThere was no evidence of a difference between the two groups in rates of live birth (OR 1.11, 95% CI 0.66 to 1.87, 1 RCT, n = 236, low-quality evidence) or miscarriage (OR 0.74, 95% CI 0.25 to 2.19, 1 RCT, n = 236, low-quality evidence) rates. There were no data on ongoing pregnancy or multiple pregnancy. 3. HT FET comparisons HT FET versus HT plus GnRHa suppressionHT alone was associated with a lower live birth rate than HT with GnRHa suppression (OR 0.10, 95% CI 0.04 to 0.30, 1 RCT, n = 75, low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 0.64, 95% CI 0.37 to 1.12, 6 RCTs, n = 991, I = 0%, low-quality evidence) or ongoing pregnancy (OR 1.72, 95% CI 0.61 to 4.85, 1 RCT, n = 106, very low-quality evidence).There were no data on multiple pregnancy. 4. Comparison of subtypes of ovulation induction FET Human menopausal gonadotrophin(HMG) versus clomiphene plus HMG HMG alone was associated with a higher live birth rate than clomiphene combined with HMG (OR 2.49, 95% CI 1.07 to 5.80, 1 RCT, n = 209, very low-quality evidence). There was no evidence of a difference between the groups in either miscarriage (OR 1.33, 95% CI 0.35 to 5.09,1 RCT, n = 209, very low-quality evidence) or multiple pregnancy (OR 1.41, 95% CI 0.31 to 6.48, 1 RCT, n = 209, very low-quality evidence).There were no data on ongoing pregnancy.
AUTHORS' CONCLUSIONS
This review did not find sufficient evidence to support the use of one cycle regimen in preference to another in preparation for FET in subfertile women with regular ovulatory cycles. The most common modalities for FET are natural cycle with or without HCG trigger or endometrial preparation with HT, with or without GnRHa suppression. We identified only four direct comparisons of these two modalities and there was insufficient evidence to support the use of either one in preference to the other.
Topics: Clomiphene; Cryopreservation; Embryo Transfer; Endometrium; Estrogens; Female; Fertility Agents, Female; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Randomized Controlled Trials as Topic
PubMed: 28675921
DOI: 10.1002/14651858.CD003414.pub3