Daily Endocrinology Research Analysis
Analyzed 98 papers and selected 3 impactful papers.
Summary
Analyzed 98 papers and selected 3 impactful articles.
Selected Articles
1. Preimplantation genetic testing for aneuploidy versus no genetic testing in couples undergoing intracytoplasmic sperm injection for severe male infertility: multicentre, open label, randomised controlled trial.
In 450 couples undergoing ICSI for severe male infertility, PGT-A did not increase live birth rates after the first transfer or cumulatively over 12 months, but it reduced pregnancy loss. Findings suggest limited benefit for routine PGT-A use in this indication despite a reduction in miscarriage.
Impact: A large multicenter RCT in BMJ directly addresses a contentious practice in reproductive endocrinology and is poised to influence ART protocols for severe male factor infertility.
Clinical Implications: For severe male factor ICSI cycles, routine PGT-A should not be expected to increase live birth and should be weighed against costs and potential embryo biopsy risks; it may be considered selectively when reducing miscarriage risk is prioritized.
Key Findings
- Live birth after first transfer: 48.4% (PGT-A) vs 46.2% (no PGT-A), OR 1.09 (95% CI 0.76–1.58), P=0.64
- Cumulative live birth within 12 months: 60.4% vs 60.9%, OR 0.98 (95% CI 0.67–1.43), P=0.92
- PGT-A significantly reduced pregnancy loss after the first transfer
Methodological Strengths
- Multicenter randomized controlled design with intention-to-treat analysis
- Clearly defined primary outcomes and prospective registration (ClinicalTrials.gov NCT02941965)
Limitations
- Open-label design without blinding
- Conducted in four centers within one country, which may limit generalizability
Future Directions: Stratified RCTs by maternal age and embryo stage/PGT-A platform, with cost-effectiveness and patient-reported outcomes, are needed to refine indications for PGT-A.
OBJECTIVE: To assess the efficacy of preimplantation genetic testing for aneuploidies (PGT-A) compared to intracytoplasmic sperm injection (ICSI) alone in couples undergoing ICSI treatment because of severe male infertility. DESIGN: Multicentre, open label, randomised controlled trial. SETTING: Four reproductive medicine centres across China. PARTICIPANTS: 450 couples with severe male factor infertility scheduled for ICSI were randomly assigned (1:1) to undergo PGT-A or not (225 couples in each group). INTERVENTIONS: ICSI with genetic testing of blastocysts before transfer in the PGT-A group, and ICSI without genetic testing for the no PGT-A group. MAIN OUTCOME MEASURES: Primary outcomes were live birth after the first embryo transfer and cumulative live birth (up to three transfer cycles) within 12 months after randomisation. Primary analysis was based on intention-to-treat principle. RESULTS: Between 15 July 2018 and 6 January 2023, 450 of 1347 screened couples gave informed consent and were randomised to the intervention, ICSI with PGT-A (n=225), or ICSI with no additional genetic testing (n=225). In total, 109 couples in the PGT-A group (48.4%) and 104 couples in the no PGT-A group (46.2%) had a live birth after the first embryo transfer (odds ratio 1.09 (95% confidence interval (CI) 0.76 to 1.58), P=0.64). The cumulative live birth rates per woman were 60.4% (136/225) and 60.9% (137/225) in the PGT-A and no PGT-A groups, respectively (0.98 (0.67 to 1.43), P=0.92). The PGT-A group had significantly lower rates of pregnancy loss after the first embryo transfer (13 (5.8%) PGT-A group CONCLUSION: PGT-A did not improve live birth rates in ICSI for severe male infertility compared to ICSI alone, but reduced rates of pregnancy loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT02941965.
2. Effects of insulin regimens for type 2 diabetes mellitus: a systematic review and network meta-analysis.
Across 58 RCTs (n=19,122), complex insulin regimens (basal-bolus, biphasic, prandial) yielded only modest HbA1c advantages over basal insulin but with greater weight gain and suggested higher severe hypoglycemia risk. Evidence supports individualized regimen choices balancing glycemic goals against adverse trade-offs.
Impact: This comprehensive network meta-analysis synthesizes head-to-head and indirect comparisons to guide insulin regimen selection in T2D, addressing a common clinical decision point.
Clinical Implications: Start with basal insulin when feasible; escalate to complex regimens only when necessary, while counseling on weight and hypoglycemia risks and aligning choices with patient preferences and resources.
Key Findings
- Included 58 RCTs with 19,122 adults; basal insulin served as the reference regimen
- Complex regimens showed only modest HbA1c improvements versus basal insulin
- Complex regimens were associated with more weight gain and suggested higher risk of severe hypoglycemia
- Overall certainty of evidence was moderate; PROSPERO-registered methodology and RoB-2 assessments were used
Methodological Strengths
- Registered systematic review with comprehensive database searches through September 2025
- Network meta-analysis enabling comparison across multiple insulin regimens; risk of bias assessed with Cochrane RoB-2
Limitations
- Heterogeneity across trials in populations, insulin titration algorithms, and outcome definitions
- Indirect comparisons inherent to network meta-analysis; many trials of relatively short duration (≥12 weeks)
Future Directions: Head-to-head pragmatic trials comparing modern basal analogs and simplified bolus strategies with patient-centered outcomes, and integration with GLP-1RA/SGLT2i backbones, are needed.
AIMS/HYPOTHESIS: Insulin therapy is essential for managing hyperglycaemia in type 2 diabetes mellitus when oral or non-insulin injectable agents are no longer effective. However, the comparative effectiveness and safety of different insulin regimens remain uncertain. We aimed to compare the effects of basal, basal-bolus, biphasic and prandial insulin regimens on glycaemic management, weight, severe hypoglycaemia, insulin dose and quality of life in adults with type 2 diabetes. METHODS: We conducted a systematic review and network meta-analysis of RCTs. PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched through to September 2025. The inclusion criteria for studies were RCTs enrolling adults with type 2 diabetes that compared at least two of the specified insulin regimens over ≥12 weeks. Pairs of reviewers independently screened studies, extracted data and assessed risk of bias using the Cochrane RoB-2 tool. Network meta-analyses were performed using a frequentist random-effects model, with basal insulin as the reference. RESULTS: Fifty-eight RCTs involving 19,122 participants were included. Compared with basal insulin, HbA CONCLUSIONS/INTERPRETATION: Complex insulin regimens provide modest glycaemic benefits over basal insulin but are associated with greater weight gain and a suggested higher risk of hypoglycaemia. These results are based on evidence of moderate confidence. These trade-offs support the need for individualised regimen selection, informed by clinical context, patient preferences and treatment goals. TRIAL REGISTRATION: PROSPERO registration no. CRD42020181473. FUNDING: This research was supported by the Committee for the Development of Higher Education Personnel (CAPES) and the Hospital de Clínicas de Porto Alegre - FIPE HCPA.
3. Increased prospective cardiovascular disease risk in 127,517 Nordic women with polycystic ovary syndrome. A national cohort study.
In a tri-national Nordic registry including 127,517 women with PCOS and 587,810 controls, PCOS was associated with a 32% higher adjusted risk of CVD over 8–10 years, persisting even in women with BMI <25 and without T2D. Results support proactive cardiometabolic risk assessment in PCOS regardless of adiposity.
Impact: This very large, multi-country, prospective cohort with consistent findings across nations strengthens causally-informative evidence for CVD risk in PCOS, including among lean women.
Clinical Implications: PCOS care should incorporate routine cardiovascular risk assessment and prevention (BP, lipids, lifestyle, and appropriate pharmacotherapy) even in normal-weight patients.
Key Findings
- Adjusted HR for CVD with PCOS across all countries combined: 1.32 (95% CI 1.25–1.39)
- In women with BMI <25 kg/m2 and no T2D, adjusted HR for CVD was 1.40 (95% CI 1.26–1.55)
- Country-specific unadjusted HRs: Denmark 1.30, Finland 1.45, Sweden 1.52; associations persisted after adjustment
Methodological Strengths
- National registry-based cohorts across three countries with very large sample size and long follow-up
- Consistent results with adjustment for obesity and education; combined meta-analysis across cohorts
Limitations
- Outcome definitions based on administrative ICD-10 codes may introduce misclassification
- Residual confounding (e.g., lifestyle, medication use) cannot be fully excluded in observational data
Future Directions: Intervention trials in PCOS targeting cardiometabolic risk and mechanistic studies dissecting PCOS phenotypes (including lean PCOS) are needed to inform tailored prevention.
BACKGROUND: Cardiovascular disease (CVD) risk factors are prevalent in women with PCOS, but prospective data regarding CVD in population-based cohorts are limited. AIM: To investigate prospective risk of CVD in Nordic women with PCOS. DESIGN: National register-based study in women with PCOS and age-matched controls originating from Denmark (PCOS Denmark, N = 27,298, controls, N = 135,019), Finland (PCOS Finland, N = 20,765, controls, N = 59,122), and Sweden (PCOS Sweden, N = 79,454, controls, N = 393,669). The main study outcome was CVD. CVD was defined according to ICD-10 diagnostic codes for major adverse cardiac events, pulmonary embolism and/or deep venous thrombosis. Cox regression analyses estimated HR with 95% CI and adjusted analyses included BMI and education. RESULTS: The median age at cohort entry was 28 years (Denmark) and 29 years (Finland and Sweden) and the median follow-up time was 8.0 to 10.0 years. The unadjusted hazard ratio (HR, 95% CI) for CVD in women with PCOS was 1.30 (1.20; 1.41) in Denmark, 1.45 (1.31; 1.60) in Finland, and 1.52 (1.44; 1.60) in Sweden. Models remained significant after adjusting for obesity and level of education. In a combined meta-analysis including all countries (PCOS, N = 127,517, controls, N = 587,810, the adjusted HR for CVD in women with PCOS was 1.32 (1.25; 1.39). In women with BMI < 25 kg/m2 and no type 2 diabetes, the adjusted HR for CVD risk was 1.40 (1.26; 1.55). CONCLUSION: The risk of CVD was increased in women with PCOS across the three Nordic countries, also among women with BMI < 25 kg/m2.