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

TY - JOUR

T1 - Cryopreservation of ovarian tissue may be considered in young girls with galactosemia

AU - Mamsen, Linn Salto

AU - Kelsey, Thomas W

AU - Ernst, Erik

AU - Macklon, Kirsten Tryde

AU - Lund, Allan Meldgaard

AU - Andersen, Claus Yding

PY - 2018/7/1

Y1 - 2018/7/1

N2 - PURPOSE: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.

AB - PURPOSE: 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.METHODS: 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).RESULTS: 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.CONCLUSIONS: 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.

KW - Adolescent

KW - Anti-Mullerian Hormone/metabolism

KW - Child

KW - Child, Preschool

KW - Cryopreservation/methods

KW - Female

KW - Fertility/physiology

KW - Fertility Preservation/methods

KW - Galactosemias/metabolism

KW - Growth Differentiation Factor 9/metabolism

KW - Humans

KW - Infant

KW - Ovarian Follicle/metabolism

KW - Ovary/metabolism

KW - Retrospective Studies

U2 - 10.1007/s10815-018-1209-2

DO - 10.1007/s10815-018-1209-2

M3 - Journal article

C2 - 29804175

SN - 1058-0468

VL - 35

SP - 1209

EP - 1217

JO - Journal of Assisted Reproduction and Genetics

JF - Journal of Assisted Reproduction and Genetics

IS - 7

ER -