Υποβοηθούμενη αναπαραγωγή- κίνδυνος εμφάνισης συγγενών ανωμαλιών. Γενετική μελέτη

Η παρούσα διατριβή μελετά τα χαρακτηριστικά και τις συγγενείς ανωμαλίες της τεχνικής υποβοηθούμενης αναπαραγωγής σε δείγμα 230 ασθενών που προσήλθαν στο Ιατρείο Κλινική Γενετικής του ΕΚΠΑ κατά την τελευταία δεκαετία και που είχαν συλληφθεί με χρήση της τεχνικής υποβοηθούμενης αναπαραγωγής. Συλλέχθηκαν δεδομένα για την παθολογία και τις διαγνώσεις, το αίτιο υπογονιμότητας, την τεχνική υποβοηθούμενης αναπαραγωγής, τη φαρμακευτική αγωγή πριν από την υποβοηθούμενη αναπαραγωγή, το αποτέλεσμα της κύησης, τα αποτελέσματα του ελέγχου καρυότυπου καθώς και τα αποτελέσματα DNA κ.α. ανάλογος των γενετικών νοσημάτων και συνδρόμων. Πραγματοποιήθηκε εκτενής βιβλιογραφική ανασκόπηση, που περιλαμβάνει στοιχεία για την υποβοηθούμενη αναπαραγωγή και τις συγγενείς ανωμαλίες, συγκεκριμένα τα χαρακτηριστικά των συγγενών ανωμαλιών μετά από υποβοηθούμενη αναπαραγωγή, τους παράγοντες που επηρεάζουν την εμφάνιση συγγενών ανωμαλιών μετά από υποβοηθούμενη αναπαραγωγή και τη συσχέτιση της υποβοηθούμενης αναπαραγωγής με τα διάφορα είδη συγγενών ανωμαλιών. Τα αποτελέσματα έδειξαν ότι το 5,8% του δείγματος είχε διαγνωστεί με γενετικά σύνδρομα, ενώ οι υπόλοιπες σημαντικότερες διαγνώσεις περιλάμβαναν ψυχοκινητική καθυστέρηση (ΨΚΚ) (14,1%), ανωμαλίες προσώπου (9,5%), μορφολογικές ανωμαλίες κορμού και άκρων (9,5%), μορφολογικές ανωμαλίες κεφαλής/κρανίου (8,1%),αναπτυξιακές διαταραχές(ΔΑΦ,ΔΕΠΥ) (7,9%), καρδιοπάθειες (7,6%) και νευρολογικές παθήσεις (7,6%). Επιπλέον, ο έλεγχος καρυοτύπου έδειξε ότι στο 10,5% των ασθενών υπήρχαν παθολογικά ευρήματα (έλλειμμα), ενώ με βάση τις μοριακές αναλύσεις, το 21,9% των περιστατικών ανέδειξε την ύπαρξη παθολογικών ευρημάτων. Ακολούθως, συζητούνται τα συμπεράσματα της παρούσας μελέτης και πραγματοποιείται σύνδεση με την βιβλιογραφική ανασκόπηση, ενώ, τέλος, αναφέρονται οι περιορισμοί της μελέτης και παρέχονται προτάσεις για μελλοντική έρευνα.The present thesis examined the characteristics and congenital anomalies and disorders related to assisted reproduction in a sample of 230 children and adolescents who had been conceived using assisted reproductive technology and who were admitted to the Genetics Clinic of the National and Kapodistrian University of Athens during the last decade. Data were collected regarding pathology and diagnoses, cause of infertility, assisted reproduction technique, medication prior to assisted reproduction, pregnancy outcome, as well as karyotype test results and molecular analysis test results on genetic diseases and syndromes. An extensive literature review was conducted that included information and data on assisted reproduction and congenital abnormalities, focusing on the characteristics of congenital abnormalities following assisted reproduction and the factors affecting the occurrence of congenital abnormalities following assisted reproduction. Results showed that 5.8% of the sample had been diagnosed with genetic syndromes, while other major diagnoses included psychomotor retardation (14.1%), facial abnormalities (9.5%), body morphology abnormalities (9, 5%), head/skull morphological abnormalities (8.1%), developmental disorders (7.9%), heart disease (7.6%) and neurological disorders (7.6%). The karyotype test showed that there were abnormal findings (deficits) for 10.5% of the sample of children and adolescents, while based on molecular analyses, 21.9% of the cases revealed abnormal findings. The conclusions of the present study are then discussed and linked to the literature review. Finally, some of the limitations of the study are highlighted and suggestions for future research are provided

A Genetic study in assisted reproduction and the risk of congenital anomalies

In vitro fertilization is one of the most common and effective procedure for thousands of couples worldwide who want to have a child and are unable to do so for various reasons. Diverse studies show that couples who conceive naturally after one year of trying had newborns with an increased risk of prematurity and low birth weight, compared with couples who conceived before completing one year of trying. Children from assisted reproduction (AR), have a 30% increased risk of prematurity and low birth weight, compared with children from infertile fathers. Regarding the conflicting results the present study aimed to record the frequency of genetic, congenital anomalies in children and adolescents who had examined in the last decade to the Clinical Genetics Clinic of the National and Kapodistrian University of Athens whose mothers had undergone assisted reproduction. The research process was conducted at the "Aghia Sofia" Children's Hospital based in Athens. However, the cases that were studied came from all over Greece. Initially, the researcher recorded the cases that came to the clinic of Clinical Genetics and whose conception occurred after technical assisted reproduction. After telephone communication and the consent of the parents, a live appointment was scheduled. In this meeting-interview all the provisions of the investigation and the protocol were asked and some elements of the medical history of the cases were confirmed. The total sample included 230 children and adolescents. The resulting data were recorded on a printed form/questionnaire. Then, they were registered electronically in the program SPSS 25.0 (Statistical Package for Social Sciences) with a specific unit code for each case/patient, followed by the processing and statistical analysis of the data as well as the recording of the results. The gender of the participants was male for 118 participants (51.3%) and 112 females (48.7%). Mean and standard deviation (SD) of maternal, paternal (at the time of delivery) age was equal to 36.38 (5.94) and 39.94 (6.58) respectively. The observed abdormalities were 35.53% psychomotor retardation, 23.68% facial abnormalities, 23.68% spinal cord abnormalities, 21.05% morphological abnormalities, 20.61% short stature, 19.74% developmental disorders, 19.30% heart disease, 16.67% neurological diseases, 14.47% genetic syndromes, 11.40% genital abnormalities, 8.33% limb abnormalities, 7.46% dermatological abnormalities, 6.14% eye abnormalities, 6.14% hypothyroidism, 5.70% endocrine disorders, 5.26%otolaryngology abnormalities, 2.63% disease of kidney, intestine, 2.19% vascular malformations. Regarding the karyotype chromosome analysis by G-banding technique, from the 230 children in: 24 (10.43%) a pathological result was found, in 158 children (68.70%) it was found normal (46, XX or 46, XY by case) without other findings, while in 48 children (20.87%) the test was not performed for various reasons. Regarding the results of molecular analysis (DNA) from the 230 children, in 50 (21.74%) a pathological finding was found, in 56 children (24.35%) no abnormalities were found and in 124 children (53.91%) no molecular analysis was performed for various reasons. In conclusion, the sample of this descriptive study is characterized as uniform in terms of the method of assisted reproduction since 96.24% had followed the classic IVF. Full-term pregnancy was associated with the appearance of malignancy and head morphological abnormalities (64.6%), normal pregnancy was associated with genetic syndromes (18.2%) and facial abnormalities (11.1%). It is recommended the screening oocyte and sperm donors in order to help protect the safety and health of donors, recipients, and future offspring. The present study confirms the association of the presence of congenital anomalies after in vitro fertilization (IVF). However, the absolute risk of developing severe dysplasias after an IVF procedure is limited