Laboratory of Reproductive Biology, Section 5712, The Juliane Marie Centre for Women, Children, and Reproduction, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark.
School of Computer Science, University of St Andrews, KY16 9SX, St Andrews, UK.
J Assist Reprod Genet. 2018 Jul;35(7):1209-1217. doi: 10.1007/s10815-018-1209-2. Epub 2018 May 26.
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.
描述首例通过冷冻卵巢组织（OTC）对患有半乳糖血症的青春期前女孩进行生育力保存的经验，并进一步描述卵巢滤泡形态和对卵巢功能重要的蛋白质的表达。
回顾性地，在 6 名年龄在 12 岁以下被诊断为半乳糖血症的青春期前女孩和 31 名年龄在 18 岁以下因性腺毒性治疗前为生育力保存而切除一侧卵巢的女孩的卵巢皮质组织中估计卵泡密度。此外，在两个半乳糖血症卵巢（年龄分别为 0.9 岁和 1.7 岁）中用免疫组织化学分析了对卵泡发育很重要的 4 种糖蛋白的表达，并与正常年龄匹配的对照组进行比较。这些蛋白质包括：抗苗勒管激素（AMH）前成熟和 C 端、生长分化因子 9（GDF-9）、骨形态发生蛋白 15（BMP-15）和妊娠相关血浆蛋白 A（PAPP-A）。
年龄在 5 岁以下的半乳糖血症女孩表现出形态正常的卵泡和卵泡密度在对照组的 95%置信区间（CI）内。一名 11.7 岁的半乳糖血症女孩的卵巢中未检测到卵泡。半乳糖血症女孩和对照组的卵泡中 AMH、GDF-9、BMP-15 和 PAPP-A 的表达似乎相似。
这些发现表明，年幼的半乳糖血症女孩在幼儿期保留卵泡，并且可能考虑在该患者群体中进行生育力冷冻保存。导致卵泡迅速丢失的半乳糖血症的病理生理学尚不清楚，目前尚不清楚移植的卵巢组织在成年后能在多大程度上维持生育能力。
