Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
Rationale: Infertility due is a major concern for girls with Turner syndrome (TS) and their
 parents. Physicians are often asked about possible options to preserve their fertility.
 However, despite some experimental case reports, clear evidence for fertility preservation in
 these girls is lacking and many questions remain. Without evidence on the effectiveness of
 fertility preservation it cannot routinely be offered to girls with TS.

 Objective: To investigate the occurrence of live birth in women with TS after ovarian tissue
 cryopreservation in childhood followed by auto transplantation in adulthood.

 Study design: A national multicentre exploratory intervention study

 Study population: Girls diagnosed with Turner Syndrome, aged 2-18 years.

 Intervention: Ovarian tissue cryopreservation in childhood followed by auto transplantation
 in adulthood. In order to obtain the ovarian tissue for cryopreservation, all girls must
 undergo a laparoscopy under general anaesthesia which will be performed in
 academic/university clinics with paediatric surgery. During the laparoscopic intervention, a
 unilateral oophorectomy will be performed, thereby leaving the other ovary intact for hormone
 production, ovulation, spontaneous pregnancies and as an auto transplantation site for
 cryopreserved-thawed ovarian cortical tissue later on. Furthermore, a small sample of the
 ovarian cortex will be used to assess the oocyte quality and genetics (e.g. the presence of
 germ line mosaicism). Oocytes will be karyotyped by using Fluorescence in situ hybridization
 (FISH). Karyotypic and hormonal data will be collected once at the yearly clinical visit at
 the paediatric-endocrinologist. Therefore, a buccal swab and one extra blood sample will be
 taken and evaluated during the routine laboratory evaluation.

 In the future, auto transplantation of frozen-thawed ovarian cortex strips will be performed.
Nature and extent of the burden and risks associated with participation, benefit and group
 relatedness:

 The primary objective remains to preserve the fertility of the respective (minor) patient,
 facing a very high risk of premature ovarian insufficiency (POI) of 95-98%. Disadvantages of
 participating in this study are the potential risk of complications related to the
 laparoscopic unilateral oophorectomy and/or the unknown effect on future fertility of these
 girls. Moreover, the procedure might raise false hope in patients (and/or parents) about the
 chance of getting pregnant after auto transplantation of cryopreserved-thawed ovarian tissue
 in the future. However, we attempt to overcome this by extensive and objective information
 provision by both written materials and face to face counselling.
Inclusion criteria

 In order to be eligible to participate in this study, a subject must meet all of the
 following criteria:

 -  Girls and young females with classic Turner (i.e. 45X monosomy) or Turner variants
 (e.g. 45X / 46XX mosaicism, ring X mosaicism, isochromosome X),

 -  Aged 2 through 18 years,

 -  who completed the diagnostic work up phase of TS including routine cardiac screening*,

 -  whose agreement to participate in this study has been signed by the parents (girls
 2-11 years old),

 -  whose agreement to participate in this study has been signed by the patient and her
 parents (girls 12-17 years old),

 -  whose agreement to participate in this study has been signed by the patient
 (adolescents of 18 years old).

 Exclusion Criteria:

 A potential subject who meets any of the following criteria will be excluded from
 participation in this study:

 -  Contra-indications for laparoscopic unilateral oophorectomy under general anaesthesia
 (e.g. severe cardiovascular comorbidity and/or BMI >40 kg/m2)*,

 -  Contra-indications for cryopreservation (i.e. active HIV, hepatitis-B or hepatitis-C
 infection)

 -  Based on the international Cincinnati Turner Guideline consensus Meeting, July
 2016 and consultation of Dutch cardiologists, paediatric-cardiologists and
 anaesthesists between 2016-2017 there are no absolute cardiovascular
 contra-indications for surgical intervention and/or pregnancy. Advice against
 surgical intervention and/or pregnancy should be based on the patient-specific
 cardiovascular risk profile. The 2% mortality risk due to acute aortic dissection
 is based on one survey and literature review study that reported the outcomes of
 101 pregnancies in patients with TS after oocyte donation. Only 50% of the
 patients were screened by a cardiologist before entering the oocyte donation
 programme. Therefore, all girls who want to participate in this study should have
 completed the diagnostic work up phase of TS including routine cardiac screening
 and will be screened by a paediatric anaesthesist. Exclusion will be based on the
 patient specific risk profile. See: References.