
Key EDMaRC researcher in the project:

Casper Hagen (PI)
MD, DMsc
The Danish Turner Cryopreservation Study – DANTE Cryo Study
Design: National combined prospective intervention study.
Duration: 2022 – 2050
Background
Turner’s Syndrome (TS) is a condition in which a girl lacks one of her X-chromosomes, either completely or partially with or without mosaicism. It occurs in app. 1:2,500 live births, making it the most common chromosomal abnormality in females.
Reduced fertility due to premature ovarian insufficiency (POI) is one of the predominant issues in patients with Turner’s Syndrome and remain the major concern for these patients and their parents throughout life. We hypothesize that selected patients will benefit from cryopreservation of an ovary during childhood. Following autotransplantation in adulthood, this could enable pregnancy.
Aim and Methods
This study is a nationwide study in cooperation with colleagues in Aarhus (AUH) and Odense (OUH), investigating multiple aspects of TS. We will primarily be investigating the ovarian function, while colleagues in Aarhus will examine genetic and epigenetic factors, and the natural history of POI. Colleagues in Odense will be researching bone formation and -mineralization.
Our primary objective is firstly to assess the occurrence of pregnancies, abortions, and live births in women with TS following cryopreservation of ovarian tissue in childhood, followed by autotransplantation in adulthood.
All girls with a diagnosis of Turner’s Syndrome aged 2-17 will be eligible for inclusion. Should the girl and her parents accept to participate in this study, the girl will undergo an examination of her fertility potential through a medical examination, and an ultrasound of her ovaries followed by a venous blood sample to examine the girl’s sex hormones (AMH, FSH, LH, E2, androstendion, and inhibin B).
Based on initial examination, the family will be informed on their daughters fertility potential and her chances of becoming pregnant as an adult. Should the girl prove to be a potential candidate for fertility treatment, the family will be offered a laparoscopic operation with complete removal of one ovary. The ovary will then be cryopreserved following biopsies for histological, functional, and genomic analyses.
In the case that the patient in adult life presents with a fertility wish, she will undergo a new medical examination, and be offered a laparoscopic operation to re-insert the once removed ovary and begin fertility treatment.
We will follow the patients closely during childhood and adolescence regarding e.g. circulating levels of reproductive hormones and ultrasound of internal genitalia. In adulthood, we will record information concerning e.g. maternal age at pregnancy, fertility treatment procedures, the number of pregnancies and pregnancy related complications, and live births.
The Reasearch Team
At Copenhagen University Hospital, Rigshospitalet: Casper Hagen (PI), Line Cleeman, Katharina M. Main, Margit Bistrup Fischer, Anette Tønnes Pedersen, Karin Sundberg, Lisa Neerup Jensen, Eva Fallentin, Magdalena Fossum, Inge Ifaoui, Stine Gry Kristensen, Linn Salto Mamsen, and Claus Yding Andersen. At Aarhus University Hospital: Claus H. Gravholt, Mette H. Viuff, Anne Skakkebæk, Margit Dueholm, Vinnie Greve, Niels Birkebæk. At Odense University Hospital: Dorte Hansen.
Funding
The study has recieved funding from the Novo Nordisk Foundation