Dynamics of angiogenic factors from pre-conception until 10 weeks of gestation

Introduction: The study objective was to characterize maternal circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) from the pre-implantation period through the first 10 weeks of pregnancy. Methods: This study evaluated sFlt-1 and PlGF in prospectively collected blood samples from participants enrolled in a randomized controlled trial at Copenhagen University Hospital—Herlev, Denmark. Women aged 18–40 years undergoing frozen embryo transfer (FET) were included, with eligibility restricted to a BMI ≤35kg/m2. Key exclusion criteria comprised smoking, preexisting cardiovascular disease, and use of donor oocytes. FET was performed in either modified natural, programmed, or gonadotrophin-stimulated cycles according to ovulatory status and assigned by randomization in the parent trial. The main longitudinal analyses of sFlt-1 and PlGF included women with ongoing pregnancies (n = 116). Samples were obtained at baseline (2nd or 3rd menstrual day), during endometrial preparation, at embryo transfer and at GA 4 + 2, 6 + 0, 8 + 0 and 9 + 6. Results: In women with ongoing FET pregnancies (n = 116), sFlt-1 concentrations increased significantly from early first trimester, with a rise observed between GA 4 + 2 and 6 + 0 (P ≤ 0.001), whereas PlGF concentrations remained low and stable until after GA 8 + 0 (P ≤ 0.001). No differences in biomarker trajectories were observed between FET protocols. Discussion: These findings could indicate that key angiogenic regulatory processes may be initiated shortly after implantation, preceding the phase of PlGF-driven placental angiogenesis. Measurement of sFlt-1 could provide clinically relevant information on placental development earlier than PlGF, supporting its potential role in very early risk stratification.