Annouschka Laenen

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with increased short- and long-term risks for both mother and child. Screening and treatment between 24 and 30 weeks’ gestation reduces adverse pregnancy outcomes, while emerging evidence suggests that earlier diagnosis and treatment (<20 weeks’) in high-risk populations may further improve neonatal outcomes. Currently, self-monitoring of blood glucose (SMBG) remains the standard of care for management but provides only intermittent glycemic data and limited insight into overall glucose patterns. Real-time continuous glucose monitoring (rt-CGM) has transformed management in pregnancies complicated by type 1 diabetes but has shown conflicting results in GDM; it is thus unclear whether similar benefits may extend to women with GDM, including women with early GDM. Methods: The Continuous Glucose Monitoring for Women With Gestational Diabetes (CORDELIA) study is an ongoing, large, open-label, multicenter randomized controlled trial conducted across 14 centers in Belgium and two centers in Australia. Women diagnosed with GDM are randomized in a 1:1 ratio to either rt-CGM (intervention group) or standard care with SMBG (control group). Both women with early GDM diagnosed before 20 weeks’ gestation and those diagnosed between 24.0 and 29.6 weeks’ gestation are included. Participants attend the following visits: baseline visit at GDM diagnosis, an additional visit at 20.0–23.9 weeks’ (if early GDM), 31.0–33.6 weeks’ and 36.0–38.6 weeks’, and a postpartum oral glucose tolerance test (OGTT) assessment (6.0–23.6 weeks after delivery). At each visit, clinical assessment, HbA1c, and (blinded) CGM are evaluated, alongside validated patient-reported outcome questionnaires. The primary objective is to compare the incidence of a composite of adverse pregnancy outcomes between the rt-CGM and SMBG groups. The primary outcome is a composite of adverse pregnancy outcomes including preterm delivery 24 h, neonatal respiratory distress, stillbirth or neonatal death, phototherapy, birth trauma, and shoulder dystocia. Secondary outcomes include maternal glycemia, insulin use, pregnancy and neonatal outcomes, glycemic variability, patient-reported outcomes, and prespecified secondary analyses according to timing of GDM diagnosis and maternal BMI. Trial Registration: ClinicalTrials.gov: NCT06310356. First posted: 15 March 2024.

Tamoxifen increases the risk of endometrial cancer (ECa) when treating breast cancer (BC)in postmenopausal women, but the impact in premenopausal women is not well established. A retrospective study in South-Korea suggested that premenopausal BC patients were 3.77 times more likely to develop ECa when treated with tamoxifen. We aimed to validate these results in a large-scale nationwide study in Belgium.We conducted a retrospective cohort study in women, aged 18–53, diagnosed with non-metastatic BC in Belgium between 2008 and 2020. Patients treated with tamoxifen were compared to those not treated with tamoxifen by baseline characteristics and diagnosis of ECa. The primary endpoint was time to ECa diagnosis. A Cox proportional hazards model assessed the primary endpoint, with treatment group as the main variable and patient/tumor characteristics as covariates.We included 23 289 patients (60%; median age 47 years) in the tamoxifen group and 15 568 patients (40%; median age 47 years) in the non-tamoxifen group. Tamoxifen users were more likely to have low-grade and lobular tumors, and less likely to receive (neo-)adjuvant or targeted (chemo)therapy. 96 ECa events occurred in the tamoxifen group (0.41%) and 27 in the non-tamoxifen group (0.17%). This translated to 0.51% and 0.22% of survivors, respectively which was a statistically significant difference (HR 2.05, CI: 1.34-3.15). After adjusting for potential confounders—diabetes, cardiovascular profile, tumor grade, pT, pN, chemotherapy, and targeted therapy—the risk remained significantly elevated in the tamoxifen group (adjusted HR 1.93, CI: 1.14-3.28; p = 0.0141).

Objective: To examine the associations between continuous glucose monitoring (CGM) metrics, including glucose management indicator (GMI) and overnight glucose levels, and pregnancy outcomes in women with type 1 diabetes. Research Design and Methods: Secondary exploratory analysis of the CRISTAL trial including 95 pregnant women with type 1 diabetes using CGM. Associations were assessed using logistic regression and Spearman correlations, presented as odds ratios (95% confidence intervals [CIs]) adjusted for baseline HbA1c. GMI validity was assessed using scatter and Bland–Altman plots. Results: Each 5% increase in overall pregnancy-specific time-in-range (TIRp) decreased the odds of gestational hypertension (odds ratio [OR] 0.63, 95% CI 0.41–0.97), birthweight >4.5 kg (OR 0.56, 95% CI 0.32–0.96), and neonatal hypoglycemia requiring hospital care (OR 0.09, 95% CI 0.01–0.57). Each 5% increase in overnight TIRp decreased the odds of gestational hypertension (OR 0.71, 95% CI 0.52–0.98) and neonatal hypoglycemia requiring hospital care (OR 0.15, 95% CI 0.03–0.79). Each 5% increase in overall time-above-range (TARp) increased the odds of birthweight >4.5 kg (OR 1.76, 95% CI 1.05–2.96), respiratory distress (OR 1.55, 95% CI 1.02–2.37), and neonatal hypoglycemia requiring hospital care (OR 5.10, 95% CI 1.14–22.78). Each 5% increase in TARp overnight increased the odds of hospital care for neonatal hypoglycemia (OR 2.55, 95% CI 1.15–5.66). Each 0.28 mmol/L increase in mean glucose and 0.5% increase in GMI were associated with increased respiratory distress (OR 1.54, 95% CI 1.07–2.23 and OR 6.15, 95% CI 1.33–28.40). Every 0.28 mmol/L increase in glycemic variability (SD) was associated with gestational hypertension (OR 1.69, 95% CI 1.02–2.80) and birthweight >4.5 kg (OR 2.31, 95% CI 1.20–4.43). Several combinations of CGM metrics (TIRp[-night], TARp[-night], SD, mean glucose) improved discriminative performance for pregnancy outcomes. GMI and HbA1c values were discordant. Conclusions: Specific combinations of CGM metrics, including overnight TIRp/TARp, may be informative for predicting pregnancy outcomes. GMI and HbA1c should not be considered interchangeable for glycemic control during pregnancy.

STUDY QUESTION: Does a natural cycle result in higher clinical pregnancy rates (CPR) with foetal heartbeat compared to an artificial cycle for frozen-thawed embryo transfer (FET) preparation in ovulatory women? SUMMARY ANSWER: The CPR with foetal heartbeat did not differ between natural and artificial cycles in ovulatory women undergoing FET. WHAT IS KNOWN ALREADY: Several protocols for endometrial preparation have been developed for the increasing number of FET cycles in reproductive medicine. In natural cycle FET (NC-FET), spontaneous ovulation is used to time the embryo thawing and transfer, while in artificial cycle FET (AC-FET), endometrial preparation involves sequential oestrogen and progesterone administration. Current evidence on pregnancy rates does not favour one regimen over the other in women with regular ovulatory cycles. STUDY DESIGN, SIZE, DURATION: We conducted a multicentre, open-label, randomised trial comparing NC-FET with AC-FET across five Belgian fertility centres. Between October 2018 and October 2024, 561 women were randomised (1:1) using a computer-generated allocation after written informed consent. The primary outcome was CPR with foetal heartbeat per cycle analysed on an intention-to-treat basis. Secondary outcomes included endometrial thickness, number of clinic visits for FET cycle monitoring and the rates of (biochemical) pregnancy, ongoing pregnancy, live birth, miscarriage, ectopic pregnancy, multiple pregnancy and cycle cancellation. Obstetric outcomes were recorded for all ongoing pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18–45 with regular ovulatory cycles and normal uterine cavities undergoing FET after vitrification and warming of one or two day-3 embryos or blastocysts were included. In NC-FET, spontaneous ovulation was detected by serial ultrasounds and serum LH and oestradiol measurements. In AC-FET, oestradiol valerate (6 mg/day) was administered from cycle day 2 (increased to 8 mg/day after 1 week if endometrial thickness was <7 mm) and micronized progesterone (600 mg/day) was initiated once endometrial thickness reached ≥7 mm. MAIN RESULTS AND THE ROLE OF CHANCE: Clinical pregnancy rates with foetal heartbeat were similar between NC-FET and AC-FET in both intention-to-treat (33.1% [94/284] vs 28.9% [80/277]; RR 1.15, 95% CI 0.89, 1.47) and as-treated analyses (34.3% [97/283] vs 31.8% [77/242]; RR 1.08, 95% CI 0.85, 1.38). Cycle cancellations were less frequent in NC-FET (3.9% vs 9.4%; RR 0.41, 95% CI 0.21, 0.82), but NC-FET required more monitoring visits (mean 3.0 vs 2.4; P = 0.0002). Caesarean section was more common after AC-FET (42.7% vs 20.2%; P = 0.003). Other reproductive, obstetric, and perinatal outcomes did not differ significantly between groups. LIMITATIONS, REASONS FOR CAUTION: The sample size was powered to detect a difference in CPR with foetal heartbeat, not for comparing live birth rates or obstetric outcomes. The study was performed in ovulatory women undergoing FET, and therefore, results may not be applicable to other populations. WIDER IMPLICATIONS OF THE FINDINGS: This RCT demonstrates no significant difference in CPR with foetal heartbeat in NC-FET and AC-FET in ovulatory women. Given recent data suggesting higher obstetric risks with AC-FET, NC-FET may be preferred in women with normal ovulatory cycles. STUDY FUNDING/COMPETING INTEREST(S): The study was an investigator-initiated study supported by internal KU Leuven funding (Project number C14/18/106 and C14/24/152) and funding from the Research Foundation Flanders (G.084515N and G.0B1819N to J.V.). K.P. has received grants from Ferring. C.B. has received speaker fees from Gedeon Richter, paid to her institution; travel support from Gedeon Richter, Ferring Pharmaceuticals, and Intuitive; and holds a leadership role as Senior Deputy of the ESHRE SIG Endometriosis and Endometrial Disorders. C.T. has received grants from Merck SA, paid to her institution; consulting fees and speaker fees from Gedeon Richter; travel support from Ferring and Gedeon Richter; and holds leadership roles as Deputy Editor of JNIG and as a board member. A.V. has received speaker fees from Gedeon Richter, paid to his institution, and holds a leadership role as Senior Deputy of the ESHRE SIG Endometriosis and Endometrial Disorders. The other authors declare that there is no conflict of interest to disclose with respect to the content of this article. TRIAL REGISTRATION NUMBER: This trial has been registered at ClinicalTrials.gov (NCT03642665). TRIAL REGISTRATION DATE: 17 July 2018. DATE OF FIRST PATIENT’S ENROLMENT: 27 October 2018.

Objective: The aim of this study was to determine whether single-day embryo selection (day 3 or day 5) achieves comparable sensitivity, specificity, and accuracy to 2-day selection (day 2 + day 3 or day 3 + day 5). Design: This was a retrospective cohort study conducted over a 15-year period (2008–2023). Setting: The review was conducted in a single assisted reproductive technology (ART) center. Participants: A total of 9,095 patients undergoing ART were included: 7,365 were managed under a day 3 policy (77,543 embryo assessments) and 1,730 patients under a day 5 policy (14,538 embryo assessments). Methods: All patients underwent routine ART procedures with morphological embryo scoring according to established criteria. Cleavage-stage selection based on a 2-day assessment (day 2 + day 3) was compared with a hypothetical selection of a single-day assessment (day 3). Blastocyst-stage selection based on a 2-day assessment (day 3 + day 5) was compared with a hypothetical selection of a single-day assessment (day 5). Sensitivity, specificity, and overall accuracy were calculated retrospectively for single-day versus 2-day evaluation. Results: Day 3 single-day assessment demonstrated sensitivity of 98.9%, specificity of 93.6%, and accuracy of 96.7%, comparable to day 2 + day 3 scoring. Day 5 single-day assessment yielded sensitivity of 99.5%, specificity of 89.7%, and accuracy of 93.4%, similar to day 3 + day 5 evaluation. Limitations: Limitations of this study include the retrospective design and the inherently subjective nature of embryo selection, in which prior assessments can bias subsequent evaluations. In addition, 2-day scoring reflected routine clinical practice, whereas single-day scoring represented a hypothetical approach based solely on embryo scores. This hypothetical single-day selection did not take the clinical context into account, as it was performed by a single embryologist based only on morphological scores, whereas actual clinical selection typically incorporates broader clinical considerations. Prospective randomized trials are therefore needed. Conclusion: Single-day embryo selection on day 3 or day 5 provides diagnostic accuracy (≥90%) comparable to 2-day protocols. Our data show that single-day assessments can be considered to cope with increased workload.

Context and Objective: To evaluate treatment adherence and satisfaction of a blended mobile health (mHealth) lifestyle intervention among women with prediabetes following gestational diabetes mellitus (GDM). Methods: Secondary analysis of the mobile-based lifestyle intervention in women with glucose intolerance after a recent history of gestational diabetes trial evaluating a mHealth lifestyle intervention in women with postpartum prediabetes after GDM. Treatment satisfaction was assessed with the self-designed treatment satisfaction questionnaire. High treatment adherence was defined as app use ≥1 in 5 days and ≥80% attendance at monthly telephonic coaching sessions. Results: Eighty-two participants with complete data at baseline and 1 year postrandomization were included. The most frequently used app components were the step tracker (61.5%), dietary tips (59.5%), and recipes (34.9%). Telephone coaching was valued by 75.6% of participants, and 84.1% found the app easy to use. High treatment adherence was achieved by 54.9%, and high treatment satisfaction by 41.5% of the participants. Participants with both high treatment adherence and high treatment satisfaction showed the most favorable metabolic outcomes, including lower BMI (23.7 vs 27.7 kg/m², P = .031), smaller waist circumference (80.5 vs 89.7 cm, P = .010), and greater postpartum weight reduction (−3.8 kg vs + 0.95 kg, P = .047). Conclusion: The blended mHealth intervention was feasible and generally well accepted. Women with both high treatment adherence and high treatment satisfaction showed the most favorable metabolic outcomes.

To investigate the diagnostic performance and interreader agreement of intraprostatic prostate cancer (PCa) detection, local extension and staging using [1

Purpose To investigate the relationship between [¹⁸F]PSMA-1007 PET parameters and biochemical recurrence-free survival (BCR-FS) in high-risk primary prostate cancer patients receiving neoadjuvant hormonal treatment. Methods This prospective randomized, double-blind, placebo-controlled phase II trial included 89 high-risk primary prostate cancer patients who received a pelvic [¹⁸F]PSMA-1007 PET/MRI prior to and following neoadjuvant hormonal treatment. Patients were randomly assigned to neoadjuvant hormonal treatment with degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 3 months followed by radical prostatectomy and extended pelvic lymph node dissection. The following [¹⁸F]PSMA-1007 PET parameters were determined on the pre- and posttreatment [¹⁸F]PSMA-1007 PET: (i) semi-quantitative [¹⁸F]PSMA-1007 PET parameters such as SUV_max, SUV_mean, PSMA-expressing volume and total lesion activity, and their absolute and relative differences; (ii) number of pelvic lymph node, distant and extraprostatic (i.e. pelvic lymph node and distant) metastases determined on [¹⁸F]PSMA-1007 PET; (iii) [¹⁸F]PSMA-1007 PET-based response criteria (aPERCIST and RECIP 1.0); (iv) molecular imaging TNM-stage as determined by PROMISE V2. Results 35% of included patients developed BCR within a median follow-up time of 38 months. Multivariate regression analyses revealed that PSMA-expressing volume posttreatment, the number of distant metastases pretreatment and miN1 + miN2 vs. miN0 pretreatment were significant predictors of BCR-FS with hazard ratios of 1.184 (95% CI 1.070–1.309, p = 0.0010), 5.820 (95% CI 2.498–13.561, p < 0.0001) and 4.024 (95% CI 1.740–9.307, p = 0.0011), respectively. Conclusion Our results indicate that [¹⁸F]PSMA-1007 PET might be used to aid in patient stratification for determining which patients would benefit from additional (neo)adjuvant treatment.