Inhibin B does seem concerning to fertility, as low levels of inhibin B is
related to impaired ovulation, low pregnancy rates and increased risk of
miscarriage 9. Groome, et al. (1994)
indicate that inhibin B a granulosa cell product has a main role in follicular
growth with the possibility that serum inhibin B level correlates with follicular
function and oocyte number 10.
Another study by Klein, et al.
(1996) indicated that decline inhibin B secretion was a reflection of a reduced ovarian follicular pool in older women. Magoffin and Jakimiuk, (1997) found that the amount of both Inhibin proteins
secreted into follicular fluid seems to increase with follicle development,
although their concentrations may faintly decrease in the largest follicles due
to strength in a greater fluid volume 11.
Inhibin B is an important indicator of ovarian reserve (the ovary’s
capacity to respond to gonadotropin stimulation), predicts magnitude of
retrievals, and is used to determine Ovarian Hyper-stimulation Syndrome
determines gonadotropin dosage for Assisted Reproductive Technologies (ART) 12. Chang,
et al. (2002) found that inhibin B in follicular fluid may serve as an
effective marker for follicular development 13.
Histidine-rich glycoprotein interacts with other
angiogenic factors, such as vascular endothelial growth factor VEGF and
fibroblast growth factor FGF but no studies to date have shown how HRG affects
angiogenesis in the follicle 14. Apparently, the exact role of HRG in
reproduction remains to be investigated as its exact bimolecular function is
In this study, although there was no significant difference in the
concentration of AMH, but there was increase in the level of AMH in infertile
women group comparing with control group. The latest studies have shown that
AMH consider a good predictor of ovarian reserve and the success rates of in
vitro fertilization IVF though; both AMH and FSH are still used as ovarian reserve test 16.
Takahashi, et al. (2008) showed that there was no significant
correlation between AMH levels and oocyte number 17.
Gonadotropin therapy plays an essential
role in ovarian stimulation for infertility management. In the last century, efforts have been made
over to improve gonadotropin preparations. Undoubtedly, current gonadotropins
have best quality and safety as well as clinical activity than previously
ones. A major performance has been
introducing recombinant technology in the manufacturing processes for
follicle-stimulating hormone, luteinizing hormone, and human chorionic
gonadotropin 18. Gonadotropins play a significant role in the secretion of
several substances by granulosa cells (eg: hyaluronic acid) in turn affecting
oocyte development and maturation 19 as well as treatment of infertility 20.
Gonadotrophin therapy is based on the physiological concept that initiation and
maintenance of follicle growth may be achieved by a transient raise in FSH
above a threshold dose for sufficient duration to generate a limited number of
developing follicle 21.
The studied of HRG genotype affects the number of fertilized oocytes.
Women given lower gonadotropins dosages get the most fertilized oocytes. The
number percentage did not differ based on HRG genotype. This indicates that the
HRG does not appear to influence oocyte maturity 22.
The level of AMH gradually depleted after gonadotropin treatment during controlled ovarian
stimulation. This decline could be an effective directly or indirectly
on the negative influence of FSH on AMH ovarian secretion.
FSH medication elevates estradiol, which could be the source of AMH drooping as estradiol negatively influences the regulation of
AMH in the ovary, so it is recommended to use initial low doses of
gonadotropins and protocols with a GnRH antagonist. It is also necessary to
direct women to fertility therapy facilities as soon as possible to select the right
treatment 23. Recently, it has been suggested that AMH may exhibit a
physiological role in down regulating the aromatizing capacity of granulosa
cells until the time of follicular selection 24.
has become a significant drug in our armamentarium for treating infertility, yet surprisingly
little effort has been devoted toward optimizing its effectiveness 25. Letrozol
as an aromatase inhibitor, when using it in the initial follicular phase has a
negative feedback effect on the hypothalamus and pituitary glands lead to GnRH,
LH and FSH secretion with resultant ovarian follicular growth stimulation. letrozole
and its drug group has safety, reliable and cheap with therapeutic effect. It
is likely that letrozole does not produce harmful effects similar to that found
with clomiphene citrate on the endometrium, even
though it can cause pregnancy 26. Durlinger, et al. (2002) demonstrated
that AMH and inhibin B are produced by granulosa cells and appear to have both
autocrine and paracrine effects within the follicle. In larger, pre-antral
follicles, the oocyte increases in size as the follicle develops more layers of
granulosa cells. The later stages of
follicle maturation from antrum formation to ovulation are gonadotrophin:
dependent and are highly regulated by the cyclical changes in LH and FSH.
During these gonadotrophin dependent stages, the primary oocyte does not grow
significantly but undergoes both cytoplasmic and nuclear maturation 27.
Inhibin B is
considered a better marker for predicting infertility than AMH.
HRG and AMH are responsive to
leterozol and gonadotrophin treatment, as there is an increase in the
level of HRG and decrease in the level of AMH in infertile women group after
antral follicle developed into mature oocyte after medication with
gonadotrophin plus letrozole.