Abstract
Ovarian tissue cryopreservation (OTC) and transplantation of frozen/thawed ovarian tissue (OTT) are used for fertility preservation in girls and women. Here, we evaluated the hormonal characteristics of women with or without postmenopausal levels of FSH at the time of OTT to study differences and conditions that best support the initiation of ovarian function. A total of 74 women undergoing OTT (n = 51 with menopausal levels of FSH; n = 23 with premenopausal levels) were followed by measurements of FSH, LH, AMH, and oestradiol. Concentrations of FSH and LH returned to premenopausal levels after 20 weeks on average, with a concomitant increase in oestradiol. Despite resumption of ovarian activity, AMH concentrations were in most instances below the detection limit in the menopausal group, suggesting a low ovarian reserve. Despite a higher age in the premenopausal group, they more often experienced an AMH increase than the menopausal group, suggesting that conditions in the premenopausal ovary better sustain follicle survival, perhaps due to the higher concentrations of oestradiol. Collectively, this study highlights the need for improving follicle survival after OTT. Age and the amount of tissue transplanted are important factors that influence the ability to regain ovarian activity and levels of FSH may need to be downregulated and oestradiol increased prior to OTT.
Highlights
Successful ovarian tissue cryopreservation (OTC) and fertility preservation are critically dependent on three main conditions, namely, the small size of primordial follicles with a diameter of approximately 45–65 μm [1], which make them tolerable to freezing; a large number of follicles; and a favourable anatomy of the human ovary, with the majority of all primordial follicles located in the outermost one to two millimetres of the cortex [2,3]
The ages at Ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT) were significantly younger in the menopausal group than in the premenopausal group
4 of 11 4 of 10 the ages at OTC and OTT were significantly younger in the menopausal group than in the premenopausal group
Summary
Successful ovarian tissue cryopreservation (OTC) and fertility preservation are critically dependent on three main conditions, namely, the small size of primordial (i.e., nongrowing) follicles with a diameter of approximately 45–65 μm [1], which make them tolerable to freezing; a large number of follicles; and a favourable anatomy of the human ovary, with the majority of all primordial follicles located in the outermost one to two millimetres of the cortex [2,3]. The location of the nongrowing follicles in a thin outer cortex layer makes it possible to prepare pieces of tissue that can be equilibrated relatively fast with cryoprotectants that permit the cryopreservation procedure. The conditions that facilitate freezing of ovarian tissue do not necessarily coincide with conditions that best sustain the survival of follicles in connection with ovarian tissue transplantation (OTT) [4,5]. The survival of nongrowing follicles at OTT is limited [6,7,8,9], and revascularisation of tissue in connection with OTT is an important step to improve and optimise the function of grafted tissue [10,11,12]
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