Effects of GnRH agonists on the expression of developmental follicular anti-mullerian hormone in varying follicular stages in cyclic mice in vivo

Abstract

Gonadotrophin-releasing hormone (GnRH) agonists (GnRHa) have been widely used to induce a state of downregulation for in vitro fertilization, and its direct effects on the pituitary are well known. However, the effects of GnRHa on the expression of anti-mullerian hormone (AMH) by follicles in varying stages in vivo remain to be fully elucidated. In the present study 84 cyclic mice were randomly divided equally into four GnRHa groups and three cyclic mice were used as a control group. The expression levels of AMH in follicles of varying stages between days 0 and 7 following GnRHa administration were quantified using immunohistochemistry. The expression of AMH in follicles at various stages revealed dynamic changes during the process of downregulation. AMH in primary follicles initially increased and then decreased gradually. In small and large preantral follicles and in granulosa cells (GCs) surrounding the oocyte of small antral follicles, the expression of AMH began to increase on day 1, was attenuated on day 2, and then increased to a peak. The expression levels of AMH in the GCs surrounding the basement membrane, in contrast to the GCs surrounding the oocyte, were significantly lower and did not increase on day 1. In all stages of follicles, the expression of AMH declined gradually between the peak level and last day of downregulation. On day 7, the varying follicular stages all expressed lower levels of AMH than on day 0. This decrease was more prominent in the higher dose groups, compared with the lower dose groups. In conclusion, GnRHa was observed to induce time-dependent changes in the expression of AMH at varying follicular stages, which occurred in a dose-dependent manner.

Differential response of AMH to GnRH agonist among individuals: the effect on ovarian stimulation outcomes

“…Increased oocyte yield, however, is more likely to be associated with the size of selectable follicle cohort. In cyclic mice, immunochemistry assay revealed that AMH expression of individual follicle initially increased and then decreased gradually during GnRH agonist treatment up to 7 days [11], but the late preantral follicle count increased significantly following 8-day downregulation with pharmacological dose (25 μg/day) of GnRH agonist injection [12]. These data may partially support the positive effect of GnRH agonist on the size of selectable follicle rather than per-follicle expression.…”

“…The dual effect of GnRH agonist on AMH observed in rodent may also explain the observation of Su et al that the change in AMH transferred from decrease to increase after GnRH agonist treatment [5]. The initial decrease may be due to suppression of per-follicle expression [11] and the following increase may reflect the changes in size of selectable follicle [12]. These data may imply that the timing of AMH measurement is associated with the direction of observed change in AMH levels following GnRH agonist treatment.…”

The use of anti‐Müllerian hormone for controlled ovarian stimulation in assisted reproductive technology, fertility assessment and ‐counseling

“…The true ovarian reserve is given by the number of primordial follicles left in the ovaries, and as the number of antral follicles that produce AMH correlates well with the number of primordial follicles, the hormone level can be used as a surrogate marker for the true ovarian reserve . However, the biomarker cannot be used as a surrogate marker for the ovarian reserve in certain situations; in women with hypothalamic amenorrhea either normal or elevated AMH levels have been described and in contrast, AMH is decreased in current users of oral contraceptives , and during long‐term treatment with GnRH agonists . Being aware of the different hormonal values in these groups is essential to avoid false conclusions from the AMH levels.…”

Comparison of the predictive capability of antral follicle count vs. the anti-Müllerian hormone for ovarian response in infertile women

“…The absence of changes in serum AMH levels may be related to the continued development of small follicles, which have the potential to grow independently of cyclic changes. Therefore, AMH can be a valuable and intuitive indicator (7)(8)(9)(10)(11).…”