10. Pre-gonadotrophic folliculogenesis
KIT Ligand expression
It remains to be determined if activation can be
influenced by gonadotrophins but it certainly seems to
proceed normally in their absence
13. Gonadotrophin dependence
1) enhance granulosa cell sensitivity and
responsiveness to FSH
2) suppress LH-responsive thecal androgen
synthesis
FSH
1) promote androgen synthesis
2) Androgens in turn synergize with FSH
to augment inhibin synthesis
The principle requirement for LH
is to sustain androgen synthesis, without which there is no estrogen synthesis
Follicular antrum formation and antral expansion are absolutely dependent on FSH.
16. Follicular activation
Meiotic resumption
in late follicular phase
Zhang M et al. Mol. Hum. Reprod. 2009;15:399-409
LH stimulated paracrine signals are thereby able to
impact oocytes even in follicles whose granulosa
cells do not express LH-R
18. Gonadotrophic manipulation of paracrine signalling
Paracrine signalling explains how gonadotrophins are potentially able
to benefit oocyte function
and by extension how inappropriate use of
exogenous gonadotrophins might be deleterious
21. Too much or too little LH activity
can have negative outcomes
LH window
22. Gynecol Endocrinol. 2012 Sep;28(9):674-7. doi: 10.3109/09513590.2011.652716. Epub 2012 Feb
8.
Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro
fertilization in downregulated patients.
Lisi F, et al.
follicular priming with LH
J Clin Endocrinol Metab. 1999 Aug;84(8):2951-6.
Androgen and follicle-stimulating hormone interactions in primate ovarian follicle
development.
Weil S, et al.
Li M et al. Mol. Hum. Reprod. 2009;15:149-154
23. Granulosa cells express androgen receptor (AR) through which theca-derived
testosterone amplifies FSH-stimulated PKA signalling
LH-driven thecal androgen production may be a component of the natural mechanism
through which antral follicles initially acquire sensitivity to FSH.
28. biphasic stimulation regimes using FSH followed by LH activity to target the gold standard
oocyte and its nearest neighbours (in developmental terms) could have potential clinical
merit
31. P. Platteau MD, MRCOG
Centre for Reproductive Medicine
Brussels Free University
Belgium
Antagonist study
A.Nazzaro, MD
A.Salerno MSc, PhD
AORN “G. Rummo
Italy
33. Ideal antagonist protocol
• Estroprogestin till Wednesday (last pill)
• GnRh-antagonist started on Monday for 3 days
• Blood test (E2 + P4 + LH)
• rFSH oh Thursday
• GnRh-antagonist added-back
on the 6th day of COH
• Blood test (E2 + P4 + LH) + US Tuesday and
Thursday
• OPU between Monday and wednesday
if P4 >1 ng/ml one more
antagonist ampule (rFSH
started one day later)
44. CONCLUSION
• The apparent beneficial effect of r-LH on implantation and
pregnancy outcomes in our study could be explained by
two different mechanisms:
1. Firstly, the embryo quality could be superior in the group
supplemented with r-LH.
2. Secondly, there may be an effect of LH supplementation
on the endometrium, which could promote implantation.
r-LH supplementation in GnRH-a cycles seems to improve implantation and pregnancy
rates via an improvement in oocyte quality and/or uterine receptivity
45. Translational implications
• The current emphasis on oocyte quality over quantity in ART procedures calls for a more
intelligent approach to ovarian stimulation based on sound physiological principles
• Follicular responses in standard FSH/hMG alone regimes are inevitably asynchronous,
yielding many oocytes that do not fertilize or are unable undergo normal embryonic
development.
• We have highlighted paracrine pathways emanating in thecal cells and granulosa cells
that potentially impact oocytes and which can be manipulated by sequential and/or
combined use of FSH and LH
• We have to designe tactics to increase follicular responsiveness to FSH/LH, synchronize
oocyte competence and maximize oocyte quality
There can be no one-size-fits-all approach to ovarian stimulation
Factors such as age, genotype and general health will always affect individual responses
However, treatment tailored to personal needs based on paracrine principles will
always be more likely to achieve the desired outcome.