Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue

Abstract

In recent years cryopreservation of ovarian tissue prior to potentially gonadotoxic treatment for malignant disease has proved to be an option for preservation of the reproductive function including fertility [1]. Following successful cancer treatment women have chosen to have transplantation of their frozen-thawed tissue if ovarian failure occurred as a consequence of cancer treatment. The autotransplanted tissue has in various centers resulted in the re-establishment of ovarian function leading to the return of fertility and the birth of healthy children [2, 3]. However, the ovarian reserve in the transplanted tissue typically is very low as currently only a limited number of follicles survive the entire procedure including freezing, thawing and transplantation [4]. This diminished reserve is reflected by persistent low levels of AMH [4], limiting the efficacy of controlled ovarian stimulation (COS) with exogenous FSH. In terms of fertility treatment, the women who have had frozen/thawed ovarian tissue transplanted often resemble poor responder patients and patients of advanced reproductive age. Attempts to augment the number of developing follicles by administration of oral DHEA for some months in the latter category of women have been reported [5–7], there being a growing literature describing a higher oocyte yield following COS and oocytes showing a better quality and thereby improving the reproductive outcome [5–7]. The particular mechanism by which DHEA may enhance follicle survival and growth has not yet been fully elucidated, but conversion of DHEA to androgens and an androgen priming effect on early stages of follicular development leading to an increased FSH receptor expression is one possible mechanism [8]. Although the vast majority of DHEA in the body is produced by the adrenals one obstacle in defining a more precise function of DHEA in improving follicle recruitment is the fact that the circulating DHEA is the sum of the local productions in the ovaries and those of adrenal glands [9]. In this study we observed the ovarian and endocrine events following DHEA administration in a woman, who had normal adrenal function but with very low ovarian reserve consequent to transplantation of frozen/thawed ovarian tissue, being postmenopausal at the time of transplantation. Only a fraction of frozen/thawed tissue from one ovary had been grafted with subsequent low ovarian reserve and evidenced by few follicles. This situation allowed a more direct evaluation of the endocrinological effect of DHEA administration on the synthesis of sex steroids.