Cryopreservation of ovarian tissue for fertility preservation in a large cohort of young girls: focus on pubertal development.
Is there an association between the need for medical puberty induction and the diagnosis or treatment received in girls who have undergone cryopreservation of ovarian tissue for fertility preservation?



There was a clear association between the intensity of treatment received and requirement for medical puberty induction but no association with the diagnosis.



Although it cannot be predicted which girls will become infertile or develop premature ovarian insufficiency (POI) following intensive chemotherapy or irradiation, patients who are at high risk of POI should be offered ovarian tissue cryopreservation (OTC). This includes girls who are planned to receive either high doses of alkylating agents, conditioning regimen before stem cell transplantation (SCT), total body irradiation (TBI) or high radiation doses to the craniospinal, abdominal or pelvic area.



This is a retrospective cohort study. In total, 176 Danish girls under 18 years of age have had OTC performed over a period of 15 years. An overview of the girls' diagnoses and mean age at OTC as well as the number of deceased is presented. Of the 176 girls, 38 had died and 46 girls were still younger than 12 years so their pubertal development cannot be evaluated yet. For the 60 girls who had OTC performed after 12 years of age, the incidence of POI was evaluated and in the group of 32 girls who were younger than 12 years at OTC, the association between the diagnosis and received treatment and the requirement for medical puberty induction was examined.



The need for medical puberty induction was assessed in 32 girls who were prepubertal at the time of OTC.



Indications for OTC were allogeneic SCT for leukaemia, myelodysplastic syndrome or benign haematological disorders, autologous SCT for lymphoma or sarcoma, and irradiation to the pelvis or to the spinal axis. The mean age at OTC of the 176 girls were 11.3 years. The two most prevalent diagnoses of the 176 girls were malignant tumours and malignant haematological diseases. Among the 32 prepubertal girls, 12 received high dose chemotherapy and either TBI prior to SCT or irradiation to the pelvis, abdomen or the spinal axis, 13 received high dose alkylating agents but no irradiation prior to SCT, six received alkylating agents as part of conventional chemotherapy and one patient had a genetic metabolic disorder and did not receive gonadotoxic treatment. Among these 32 girls, 23 did not undergo puberty spontaneously and thus received medical puberty induction. Among the nine girls, who went through spontaneous puberty, four had received high dose alkylating agents and five had received conventional chemotherapy.



All information was retrieved retrospectively from patient records, and thus some information was not available.



OTC should be recommended to all young girls, who present a high risk of developing ovarian insufficiency and/or infertility following high dose chemotherapy and/or irradiation.



The Childhood Cancer Foundation (2012-2016) and the EU interregional project ReproHigh are thanked for having funded this study. They had no role in the study design, collection and analysis of the data or writing of the report. The authors have no conflict of interest to disclose.
Laboratory of Reproductive Biology, Juliane Marie Centre, Section 5712, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark annetteklueverjensen@gmail.com.
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AK
Jensen
Department of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
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C
Rechnitzer
Fertility Clinic, Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
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KT
Macklon
Department of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
M R S
MR
Ifversen
Department of Paediatrics, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark.
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Birkebæk
Department of Paediatrics, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark.
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N
Clausen
Department of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.|Department of Growth and Reproduction, Juliane Marie Centre, Copenhagen University Hospital, Copenhagen, Denmark.
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K
Sørensen
Fertility Clinic, Odense University Hospital, 5000 Odense, Denmark.
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J
Fedder
Fertility Clinic, Aarhus University Hospital, Skejby, Denmark.
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Ernst
Laboratory of Reproductive Biology, Juliane Marie Centre, Section 5712, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
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Andersen
D000293:Adolescent; D002648:Child; D015925:Cryopreservation / Q000379:methods*; D003718:Denmark; D005260:Female; D059247:Fertility Preservation / Q000379:methods*; D006801:Humans; D010053:Ovary / Q000473:pathology*; D016649:Primary Ovarian Insufficiency / Q000473:pathology*; D011627:Puberty / Q000502:physiology*; D012189:Retrospective Studies
ovarian cryopreservation / fertility preservation / prepubertal patients / cancer / chemotherapy / irradiation / pubertal induction