Preeclampsia affects 2–8% of pregnancies globally and remains a leading cause of maternal and perinatal morbidity, with limited preventive options beyond low-dose aspirin. Low-molecular-weight heparin (LMWH) has emerged as a promising therapeutic candidate due to its pleiotropic effects extending beyond anticoagulation, including anti-inflammatory, pro-angiogenic, and placental-protective properties. This comprehensive narrative review examines LMWH’s effects on preeclampsia-associated biomarkers and evaluates clinical evidence for its preventive efficacy. LMWH exerts multifaceted effects on disease pathophysiology, including restoration of angiogenic balance through sFlt-1 reduction and PlGF preservation, attenuation of inflammatory responses via decreased TNF-α and IL-6 production, normalization of coagulation parameters, and enhancement of trophoblast invasion and placental vascularization. Clinical trials reveal heterogeneous results, with meta-analyses suggesting significant benefit primarily in high-risk subgroups. Women with previous severe placenta-mediated complications demonstrate relative risk reductions of 40–60% for recurrent preeclampsia with LMWH prophylaxis, particularly when initiated before 16 weeks’ gestation. Combination therapy with low-dose aspirin appears to enhance protective effects. However, larger trials in unselected populations have failed to demonstrate significant benefit, highlighting the importance of appropriate patient selection. Current international guidelines reflect this evidence heterogeneity, with most recommending against routine LMWH use while acknowledging potential benefit in selected high-risk populations, particularly those with antiphospholipid syndrome or previous severe early-onset disease. Future research should focus on biomarker-guided patient selection, optimal dosing regimens, and integration with multimodal preventive strategies to maximize therapeutic benefit while minimizing unnecessary interventions.
Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load.Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, peri-operative adverse events, and quality of life.Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86–1.07]) and progression-free survival (HR = 0.98, 95% CI [0.89–1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71–1.09]) nor for patients with metastatic lesions >5 cm (HR = 0.86, 95% CI [0.69–1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10 cm (HR = 0.94, 95% CI [0.78–1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48–3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16–0.72].Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death.
27 April 2023 in European Journal of Obstetrics & Gynecology and Reproductive Biology
Background/Objectives: Cervical insufficiency affects 1–2% of pregnancies and represents a significant cause of second-trimester loss and spontaneous preterm birth. This review synthesizes current evidence across the clinical spectrum of cervical insufficiency, providing evidence-based management guidance and identifying areas requiring further investigation. Methods: We conducted a comprehensive review of the current literature, evidence-based clinical guidelines, and landmark randomized controlled trials examining diagnostic frameworks, therapeutic interventions, and clinical outcomes across different presentations of cervical insufficiency. Our analysis incorporated data from major obstetric databases, professional society recommendations, and recent comparative effectiveness research. Results: Cervical insufficiency diagnosis encompasses three primary categories: history-based, ultrasound-based, and physical examination-based. Vaginal progesterone achieves a 31% reduction in preterm birth before 33 weeks (RR 0.69, 95% CI 0.55–0.88; NNT= 14). Ultrasound-indicated cerclage achieves a 30% relative risk reduction for delivery <35 weeks. The landmark SuPPoRT trial (n = 386) demonstrated no statistically significant differences among cerclage, pessary, and progesterone (p = 0.4), though formal equivalence trials have not been conducted. Multiple gestations show no benefit from singleton-derived interventions (RR 0.99–1.04). Conclusions: Optimal cervical insufficiency management emphasizes individualized approaches based on comprehensive risk stratification and objective cervical assessment, with vaginal progesterone and cervical cerclage serving as cornerstone therapies supported by robust clinical evidence.