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Pregnancy after treatment for breast cancer (BC) does not impact prognosis but young cancer survivors have low chances of becoming mothers. As cancer treatment can hinder fertility, artificial reproductive technologies (ART), using either fresh gametes after ovarian stimulation or gametes that were cryopreserved prior to gonadotoxic treatment may be required to become pregnant. For those bearing a deleterious BRCA germline mutation, which increases the risk of breast and ovarian cancer, these challenges can be amplified due to defects in DNA repair pathways. The objectives of this thesis were to evaluate 1/ the impact of ART on BC survivors, including those who are carriers of a BRCA mutation, 2/ the impact of ionizing radiation exposure from medical imaging, for BC stage and risk assessment, on oocyte quality during ovarian stimulation for fertility preservation (FP). We have conducted three clinical trials. The first, the ACCESS study, was a retrospective multicentric matched cohort (1:2) study addressing the impact of ART after BC. BC survivors who underwent ART between January 2006 and December 2016 (n=39) and matched BC survivors (n=73) were selected from eight Belgian fertility clinics and two oncological centers. After a median follow-up time of >4 years, similar oncological outcomes were observed, irrespective of ART cycle after treatment for BC.Second, the BRCA ART study was a retrospective, international, multicenter study (NCT02308085) that specifically addressed the impact of ART in BRCA-mutated survivors. BC survivors with BRCA1/2 mutations diagnosed between January 2000 and December 2012 were included and those who were pregnant after ART (n=22) were compared to those who achieved spontaneous pregnancies (n=146). Oncological outcomes were similar at >3 years of follow-up, although ART-exposed patients were older at diagnosis with more favorable disease features than non-ART exposed patients. Finally, the CARLOTA study evaluated ionizing radiation-relat, Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished

Diffusion-weighted magnetic resonance imaging (MRI) is a proven, quick, and noninvasive tech-nique which requires no ionizing radiation or contrast media administration and is able to de-tect, characterize and stage malignant tumors, and to monitor treatment response. Over the two last decades, many clinical applications of diffusion-weighted imaging (DWI) have emerged in the field of women’s oncology. This technique provides both qualitative and quanti-tative information offering a promising new tumor biomarker in clinical routine. This thesis work was therefore conducted to demonstrate the critical role of DWI in the man-agement of adnexal masses and breast cancers. The dissertation is divided into 5 chapters. Chapter 1 presents the general background. Chapter 2 is dedicated to the contribution of DWI in assessing adnexal masses. Chapter 3 is focused on the role of DWI in the evaluation of breast cancer response to neoadjuvant treatments with emphasis on the early response to neoadju-vant chemotherapy (NAC) and to neoadjuvant radiotherapy. Chapter 4 explores the performance of whole-body MRI (WB-MRI) including DWI in the initial staging of breast cancer patients at high risk of metastasis. Chapter 5 contains the discussion, future perspectives, and general con-clusion.Initially, we validated prospectively the ADNEX MR scoring system in the assessment of inde-terminate ovarian and adnexal masses with ultrasound (US) in 323 patients. We also evaluated a new, modified ADNEX MR scoring system that incorporates DWI including apparent diffusion coefficient (ADC) mapping. It showed an improvement of the classical ADNEX MR scoring sys-tem in diagnosing lesions with a score of 4 or 5 when adding DWI data analysis including ADC mapping, from 95.5% sensitivity and 86.6% specificity to 95.7% and 93.3%, respectively.Afterwards, we evaluated the added value of quantitative DWI in the diagnosis of indetermi-nate adnexal masses with US in a cohort of 163 patients with 201, Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished

Objective: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective. Methods: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications. Temporal trends and between-site/device consistency were explored. Proportions of run standard deviations exceeding pre-specified caps of 0.4%, 0.4% and 0.6% were computed. Results: Overall, 661 RCA runs between April 2019 and July 30, 2022 tested 39,756 samples. In the first 24, subsequent 9, and final 7 months, proportions of capped chromosome 21 runs dropped from 39% to 22% to 6.0%; for chromosome 18, rates were 76%, 36%, and 4.0%. Few chromosome 13 runs were capped using the original 0.60%, but capping at 0.50%, rates were 28%, 16%, and 7.6%. Final rates occurred after reformulated reagents and imaging software modifications were fully implemented across all devices. Revised detection and false positive rates are estimated at 98.4% and 0.3%, respectively. After repeat testing, failure rates may be as low as 0.3%. Conclusion: Current RCA-based screening performance estimates are equivalent to those reported for other methods, but with a lower test failure rate after repeat testing., SCOPUS: ar.j, info:eu-repo/semantics/published

The transfer of immunoglobulins from the mother to her fetus is the major defensive tool of the neonate against infectious diseases during the first few months of life. The mechanism of antibody transfer is selective, and only maternal immunoglobulins G (IgG) are able to pass across the placental barrier. This mechanism depends on many factors, such as maternal IgG concentration, IgG subtypes, maternal diseases that affect placental integrity, gestational age, and birthweight. The infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases maternal, obstetrical, and neonatal adverse outcomes. In contrast, infants with SARS-CoV-2 immunity are protected against the disease-related hospitalization. The aim of this chapter is to review the incidence of transplacental transfer of SARS-CoV-2 and the possible risk factors that could influence this transfer and that are specific to SARS-CoV-2 infection and vaccination., SCOPUS: ch.b, info:eu-repo/semantics/published