Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 7, pp 1209–1217 | Cite as

Cryopreservation of ovarian tissue may be considered in young girls with galactosemia

  • Linn Salto Mamsen
  • Thomas W. Kelsey
  • Erik Ernst
  • Kirsten Tryde Macklon
  • Allan Meldgaard Lund
  • Claus Yding Andersen
Fertility Preservation



The aim was to describe the first experience with fertility preservation by cryopreservation of ovarian tissue (OTC) in pre-pubertal girls with galactosemia and further to characterize ovarian follicular morphology and expression of proteins important for ovarian function.


Retrospectively, follicle density was estimated in ovarian cortical tissues from 6 pre-pubertal girls below the age of 12 years diagnosed with galactosemia and from 31 girls below the age of 18 years who had one ovary removed for fertility preservation for other reasons prior to gonadotoxic treatment. Additionally, expression of 4 glycoproteins important for follicle development were analyzed with immunohistochemistry in two galactosemic ovaries (aged 0.9 and 1.7 years) and compared to normal age-matched controls. The proteins included were: anti-Müllerian hormone (AMH) pro-mature and C-terminal, growth differentiation factor-9 (GDF-9), bone morphogenetic protein 15 (BMP-15), and pregnancy-associated plasma protein A (PAPP-A).


Girls with galactosemia below the age of 5 years presented with morphological normal follicles and follicle densities within the 95% confidence interval (CI) of controls. No follicles were detected in the ovary from an 11.7-year-old girl with galactosemia. Expression of AMH, GDF-9, BMP-15, and PAPP-A appeared similar in follicles from girls with galactosemia and controls.


These findings suggest that young girls with galactosemia maintain follicles in early childhood and fertility cryopreservation may be considered an option in this patient group. The pathophysiology of galactosemia leading to an accelerated follicle loss is unknown and it is currently unknown to what extent transplanted ovarian tissue can sustain fertility in adult life.


Galactosemia Premature ovarian failure Fertility preservation Ovarian function AMH PAPP-A GDF-9 BMP-15 



We thank Marianne Sguazzino for the excellent technical assistance.

Authors’ role

L.S.M. and C.Y.A. designed and drafted the study. L.S.M. was responsible for the IHC staining and estimating the follicle densities in ovaries from patients with galactosemia. T.W.K. designed the mathematics for follicle density estimation and developed the density prediction model. E.E. and K.T.M. did the initial fertility preservation counseling with the parents and was responsible for the collection of the tissue. A.M.L. is the physician in charge of the girls with galactosemia and obtained their genetic information. The final manuscript was approved by all authors.

Funding information

The Novo Nordisk Foundation and the EU interregional project ReproUnion funded this study. They had no role in the study design, collection and analysis of data, and data interpretation or in writing the report.

Compliance with ethical standards

The study was approved by the Scientific Ethical Committee for the Capital Region (KF (01) 170/99).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Linn Salto Mamsen
    • 1
  • Thomas W. Kelsey
    • 2
  • Erik Ernst
    • 3
    • 4
  • Kirsten Tryde Macklon
    • 5
  • Allan Meldgaard Lund
    • 6
  • Claus Yding Andersen
    • 1
  1. 1.Laboratory of Reproductive Biology, Section 5712, The Juliane Marie Centre for Women, Children, and ReproductionCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  2. 2.School of Computer ScienceUniversity of St AndrewsSt AndrewsUK
  3. 3.Fertility ClinicRegional Hospital HorsensHorsensDenmark
  4. 4.Department of Obstetrics and GynaecologyUniversity Hospital of Aarhus, Skejby SygehusAarhusDenmark
  5. 5.Fertility ClinicCopenhagen University Hospital, RigshospitaletCopenhagenDenmark
  6. 6.Centre for Inherited Metabolic Diseases, Departments of Paediatrics and Clinical GeneticsCopenhagen University Hospital, RigshospitaletCopenhagenDenmark

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