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Fertility Medications
Fertility medications are often used to stimulate follicle
growth or to trigger ovulation. For example Clomiphene Citrate
(Clomid) and FSH.
"Clomiphene citrate [Clomid] was first synthesized
in 1956, introduced for clinical trial in 1960, and approved
for clinical use in the United States in 1967. Clomiphene
citrate is an orally active nonsteroidal agent distantly
related to diethylstilbestrol.
"…The similarity of clomiphene's structure to
an estrogenic substance is the clue to its mechanism of
action. Clomiphene exerts only a very weak biologic estrogenic
effect… When exposed to clomiphene, the hypothalamic-pituitary
axis is blind to the endogenous estrogen level in the circulation.
Because receptor capacity is reduced and the true estrogen
signal falsely lowered, negative feedback is diminished
and the neuroendocrine mechanism for GnRH secretion is activated.
When clomiphene is administered to normally cycling women,
FSH and luteinizing hormone (LH) pulse frequency (but not
amplitude) is increased, suggesting an increase in GnRH
pulse frequency. Anovulatory women, however, respond in
a different fashion. Clomiphene stimulates an increase in
gonadotropin pulse amplitude, presumably because GnRH pulses
are already operating at maximal frequency in anovulatory
women with polycystic ovaries. Nevertheless, the experimental
data indicate that the primary site of action is the hypothalamus.
"During clomiphene administration, circulating levels
of FSH and LH rise. The subsequent ovulation that occurs
after clomiphene therapy is a manifestation of the hormone
and morphologic changes produced by the growing follicles.
Clomiphene therapy does not directly stimulate ovulation,
but it retrieves and magnifies the sequence of events that
are the physiologic features of a normal cycle. The effectiveness
of the drug, however, may not be restricted to its ability
to cause an appropriate GnRH discharge."
(Excerpts from: Clinical Gynecologic Endocrinology and Infertility.
Speroff, Glass, and Kase. Lippincott Williams & Wilkins.
1999)
"Recombinant FSH (recFSH) has now become available
for clinical work. It is prepared from ovarian cell cultures
from the Chinese hamster and has a high purity and specific
activity (10,000 IU/mg). RecFSH contains a series of isohormones.
Receptor binding activity and activity in vitro are highest
for the most basic isohormones, whereas the most acidic
fractions are most active in vivo. This difference may be
due to their sialic acid content, which is correlated with
biological activity, and to the more rapid clearance of
basic forms from the circulation.
"When used for ovarian stimulation,
recFSH compares favorably with urinary gonadotropins. This
advantage is conferred by its high purity, high specific
activity, absence of biological contamination and lack of
contaminating LH activity. RecFSH is safe and well tolerated;
its elimination half-life resembles that of urinary FSH.
"RecFSH has been used for IVF. It led to multiple follicle
growth as well as the same mean number of oocytes, fertilization
and pregnancies as obtained with urinary FSH. It is safe
and effective. Its efficiency was assessed in a European
multicentric trial involving 1000 women undergoing IVF.
Pregnancy rates were 22% with recFSH and 18% with urinary
FSH (uFSH). More oocytes were recovered from patients treated
with recFSH, and the number of dominant follicles, preovulatory
levels of estradiol and number of embryos were all higher
with recFSH.
"RecFSH could offer advantages for ovarian stimulation.
Any clarification of the roles of its various isoforms could
improve its efficiency. The lack of any LH response could
help in averting the occurrence of high tonic LH levels.
Whether it will displace hMG in terms of efficiency and
cost remains to be seen."
(Excerpts from: Principles and Practice of Assisted Human
Reproduction. Edwards and Brody. W.B Saunders Company, 1995)
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