Transcript ROLE OF GnRHA IN ENDOMETRIOSIS & FIBROIDS

DR.B.KALPANA MD(OG)
FNB(REPRODUCTIVE MEDICINE)
FICOG
GnRH
Synthesized from arcuate
nucleus of ventral hypo thalamus
Released into the portal system
of pituitary gland in pulsatile
fashion
GnRH



It is a deca peptide
It is a single chain peptide
having 10 Amino acids
Crucial positions are
1,2,3,6,10
GnRH



Position 2& 3 are responsible for
Gn release
Position 6 is involved in
enzymatic cleavage
Position 1,6,10 are responsible
for its structure
GnRH


CnRH released into portal
circulation
CnRH binds to specific
receptors of the anterior
pituitary
GnRH

CnRH pulse frequency varies
from 71 minutes (Late folliculae
phase) to 216 minutes (Late
lacteal phase)
GnRH


Native CnRH has short plasma
half life
It is rapidly inactivated by
enzymatic cleavage
Nona peptides







Leuprolide
Buserelin
Goserelin
Histrelin
Decapeptide
Nafarelin
Triptorelin
GnRH


90% biological activity is lost with
splitting of 10th glycine
It is restored with the attachment
of NH2 ethylamide to the pro line
at position-9
GnRH




Replacement of glycine at position 6
by D-amino acid decreases
enzymatic degradation
NH2 ethylamide substitutes 10th
Glycine
Product is protected against
enzymatic degradation
Product has highest receptor
binding capacity
Route of administration


All CnRH agonists are given
parenterally
Oral, rectal administration results
in low bio-availability
Intranasal Spray



Effective
Bio availability is 3-5%
Fast elimination kinetics needs
frequent dosing 2-6 times/day
Depot preparation


It is given I.M
Therapeutic level is maintained
for 28-35 days
GnRH

Results in initial flare followed
by down regulation through
reception down regulation
Side effects





Hot flushes
Reduced libido
Vaginal dryness
Reduced BMD
Reduced breast
size
Side effects



No increased birth defects
Small soft cleft palate – Ronel et
al
Attention deficit hyper activity
disorder –Lahatel et al
LAP SURGERY

Lap surgical removal of
endometriosis improves fertility in
stage I, II
Jacobson et al
2010 ,wes H. R. Feb 8-2013
LAP SURGERY


No RCT assessed whether surgery
improves fertility in stge III and IV
in deep endometriosis.
wes H. R. Feb 8-2013
LAP SURGERY




Lap surgery for deep endometriosis
including colorectal endometriosis
should be considered a 2nd line of
treatment after failed IVF
(unless IVF is not feasible or
the patient has severe pain
symptoms)
wes H. R. Feb 8-2013
LAP SURGERY


PR after repeat surgery lowest, half
that after first surgery and 2 cycles
of IVF might be more effective
wes H. R. Feb 8-2013
LAP SURGERY






Benefit of lap removal of endometriosis
prior to IVF is unclear with respect to IVF
out come
Benschop edition
2010
It may improve access to the ovaries,
reduce the chance of infection related to
OR
Consensus of current
Management of endometriosis
Society
H. R. Feb 8-2013
LAP SURGERY


Although some non randomized
studies have suggested that surgical
removal of endometrioma prior to
IVF may affect the success rate
PR obtained by Ricks et al 2002
(surgical removal done) were
similar to surrey 2002(surgical
removal not done)
LAP SURGERY





Surgery should be considered for
women with endometriosis related
infertility
who are symptomatic or
enlarging endometrioma, or
IVF is repeatedly unsuccessful.
wes H. R. Feb 8-2013
Medical adjuvant therapy

The advantage of pre op or post op
medical therapy are debatable
Medical adjuvant therapy


Medical adjuvant therapy with lap
surgery has not been shown to
improve fertility.
Furness et al 2009 wes H. R.
Feb 8-2013
Pre op medical therapy


It may facilitate operative
procedure
Cochrane review found that
hormonal suppression decreases the
size of endometriotic implants,
there by reducing the extent of
surgery
Laparoscopic management of
endometriosis- review of
best evidence

Pre op hormonal suppression may be
helpful in decreasing endometriosis
disease score
Patrick peter etal
Vol.16. issue 3 june 2009
Journal of minimally invasive gynecology
Post op medical therapy


Post op medical therapy may delay
pregnancy at a time when fertility
has been improved by surgery
wes H. R. Feb 8-2013
Post op medical therapy

There is a beneficial impact of
CnRHa on recurrence of ovarian
endometrioma after surgery
byung etal F. S Jan -2009
Post op medical therapy


It may be effective in decreasing
endometriosis recurrence
In Cochrane review, no benefit was
observed for the out come of pain
or PR
Laparoscopic management of
endometriosis- review of
best evidence

Post op hormonal suppression may
be helpful in reducing pain and
increasing time to recurrence of
symptoms
Patrick peter etal
Vol.16. issue 3 june 2009
Journal of minimally invasive gynecology
COH IUI


Medical treatment , prior to CoH
and IUI is not recommended, there
are insufficient data demonstrating
benefit.
Tanohatoe et al 2005wes H.
R. Feb 8-2013
IVF


CnRHa for 3-6 months prior to IVF
may improve IVF success
Sallam et al 2006,wes H. R.
Feb 8-2013
Interventional review on long term pituitary
down regulation in IVF for endometriosis

Administration of CnRH agoinst for
3-6 moths prior to IVF increases the
odd ratio of PR by four fold
Hassan N. sallam etal cochrane
library Jan 2009
After CnRHa


Improvement in LBR could be due to
improvement in the uterine receptivity
leading to better IR.
FR,CR not different in gp received and
gp not received CnRHa
Surrey etal 2002
GnRH

CnRH a can be used to induce
oocyte maturation after co
treatment with CnRH antag in high
risk patients
F. S. Vol.89-Jan 2008
Pre op CnRHa for leiomyoma



Reduction of size
Shortened duration of surgery
Reduced blood loss
Gotan et al
Nov 6, 1992 HR
Pre op CnRHa for leiomyoma



In myomectomy whether CnRHa
make the process of shelling out a
fibroid difficult has not been
answered by there trial
? Risk of recurrence because small
fibroids are not seen at the time of
surgery
Difference in PR after myomectomy
is very small
Cochrane review 2009
Pre op CnRHa for leiomyoma




Reduction in fibroid size
Reduction is blood loss
There is inadequate evidence to
support the use of CnRHa for all
women with fibroids under going
hysterectomy or myomectomy
Can be recommended for a large
fibroids,who may be benefited from
vaginal rather than abdominal
procedure
GnRHa in COH

GnRHa is usefull for down regulation,
inducing flare response during COH.
GnRH in L.S

GnRHa may be effective in providing Luteal phase
support in ART
Pirard et al
H.R Feb.2006
THANK YOU
GnRHa
IN
COH
GnRHa IN LS
MR guided focused ultra sound surgery
of uterine fibroids

CnRHa potentiate the thermal
effects of MRg FVS smart etal
European Journal of
radiology
Vol-59, Aug-2006