During a natural cycle usually only one egg is produced - see follicular stimulation. The success of fertility treatments such as IUI (Intra Uterine Insemination) and IVF/ET (In vitro fertilisation with embryo transfer) is significantly increased if more than one egg is produced. In many women the influence of the LH (luteinizing hormone) component of the gonadotrophins produced by the pituitary is too great. Hormones are secreted into the blood stream to effect target cells elsewhere in the body. Current protocols for superovulation are designed to either reduce or eliminate the influence of the luteinizing hormone.
The control of ovulations is from the hypothalamus and via the pituitary gland in the brain. The gonadotrophin releasing hormone (GnRH) from the hypothalamus stimulates target cells in the pituitary gland to secrete gonadotrophin hormones which will control the growth of follicles in the ovary. A feed back mechanism of hormones circulating in the blood controls activities between 'distant' tissues/glands.
The secretory cells in the anterior pituitary have receptor sites (small black blobs on the schematic cell within the pituitary). These respond to the GnRH hormone so that secretion of FSH and LH begins.
The effect of the release of these hormones is to stimulate the development of a group of follicles in the ovary. See the graphic on the LEFT.
In many women with ovulatory dysfunction the LH secretion is too high
and this can compromise the quality of the eggs.
Protocols based on the administration of exogenous (from the outside)
analogue agonists of GnRH (e.g. Buserulin), by injection or nasal
administration, effectively compete for the receptor sites in the pituitary so
that there are fewer available sites for the endogenous (internal &
natural) GnRH from the hypothalamus. See graphic on the RIGHT.
The result is that the secretion of the FSH and
LH from the pituitary, after an initial burst, is significantly reduced. See
graphic BELOW RIGHT.
This allows a more effective response from gonadotrophins often administered in the form of pure urinary derived FSH, or recombinant FSH; this is now providing a more effective control of ovulation with better egg quality.
Exogenous gonadotrophins (FSH) can then be applied to stimulate the production of follicles within the ovary, whilst continuing the agonist regime.
SEE graphic on RIGHT
When the leading follicle reaches an appropriate size (e.g. 17mm diameter on ultrasound) the administration of hCG (human chorionic gonadotrophin) mimics the action of LH in completing the maturation of the follicle. Ovulation would take place 36.5 hours later unless egg collection/pickup/retrieval takes place before that time. Recombinant LH (soon to be available ?) will have a significant impact on follicular stimulation since it has a shorter half-life than hCG and so will, it is hoped, reduce the incidence of Ovarian hyperstimulation syndrome (OHSS).
The introduction of antagonists (as opposed to agonists) will block totally the natural production of gonadotrophins from the pituitary providing, it is hoped, even more effective hyperstimulation in the future.