GnRH is widely used in the embryo fertilization program (FIV) as one of the ovarian stimulation regimens. At the implantation window, GnRH agonists are known to have an effect on the endometrium directly or indirectly. GnRH estimated has a negative effect on the development of endometrial cells after ovarian stimulation. This study is to analyze the impact of GnRH agonist on ovarian stimulation procedures on receptor expression and endometrial cell apoptosis. The study sample was a stored biological material (BBT) from serum and the endometrial tissue of Macaca nemestrina. The total sample is 8 and divided into 2 groups, the stimulated and control groups. Each sample will be examined 2 types which are the enzyme-linked immunosorbent assay (ELISA) for serum and immunohistochemistry (IHC) for endometrial tissue. IHC was performed with anti-GnRH and caspase 3 antibody. Concentration is measured using an ELISA reader and then converts Optical Density (OD) to a concentration using SoftMax Pro Software. Calculations of stained and unmarked cells were performed using the Image-J Analyzer programs and scored by HSCORE. There is no significant difference between GnRH serum in stimulation or control group (p=0.773). There was no correlation between GnRH in serum with GnRH receptor in endometrial tissue (p=0.060) and activation of caspase (p=0.193). There was no difference between stimulation group and control group in the amount of GnRH in serum, presence of active GnRHR, and Caspase 3 activation. Keywords: GnRH receptors, Macaca nemestria, GnRH Agonist, Controlled ovarian stimulation

1.
Bliss
SP
,
Navratil
AM
,
Xie
J
,
Roberson
MS
.
GnRH signaling, the gonadotrope and endocrine control of fertility
.
Front Neuroendocrinol.
2010
Jul;
31
(
3
):
322
40
.
2.
Finch
AR
,
Caunt
CJ
,
Armstrong
SP
,
McArdle
CA
.
Agonist-induced internalization and downregulation of gonadotropin-releasing hormone receptors
.
Am J Physiol - Cell Physiol.
2009
Sep;
297
(
3
):
C591
600
.
3.
Kumar
P
,
Sharma
A.
Gonadotropin-releasing hormone analogs: Understanding advantages and limitations
.
J Hum Reprod Sci.
2014
;
7
(
3
):
170
4
.
4.
Stimpfel
M
,
Vrtacnik-Bokal
E
,
Pozlep
B
,
Virant-Klun
I.
Comparison of GnRH Agonist, GnRH Antagonist, and GnRH Antagonist Mild Protocol of Controlled Ovarian Hyperstimulation in Good Prognosis Patients
.
Int J Endocrinol [Internet].
2015
[cited
2018 Aug 18
];
2015
. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381687/
5.
Ovarian Stimulation Protocol in IVF: An Up-to-Date Review of the Literature. -
PubMed - NCBI [Internet].
[cited
2019
Jul 13]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26775651
6.
Perkumpulan Obstetri dan Ginekologi Indonesia
.
Konsensus Infertilitas.
2013
. :
90
.
7.
Depalo
R
,
Jayakrishan
K
,
Garruti
G
,
Totaro
I
,
Panzarino
M
,
Giorgino
F
, et al. 
GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET
).
Reprod Biol Endocrinol.
2012
;
10
(
1
):
26
.
8.
Maggi
R
,
Cariboni
AM
,
Marelli
MM
,
Moretti
RM
,
Andrè
V
,
Marzagalli
M
, et al. 
GnRH and GnRH receptors in the pathophysiology of the human female reproductive system
.
Hum Reprod Update.
2016
;
22
(
3
):
358
81
.
9.
Gonadotropin-releasing Hormone (GnRH) and the GnRH Receptor (GnRHR) | GLOWM [Internet]
. [cited
2018
Aug 18]. Available from: http://www.glowm.com/section_view/heading/Gonadotropin-releasing Hormone (GnRH) and the GnRH Receptor (GnRHR)/item/284
10.
Wu
H-M
,
Wang
H-S
,
Huang
H-Y
,
Soong
Y-K
,
MacCalman
CD
,
Leung
PCK
.
GnRH signaling in intrauterine tissues
.
Reproduction.
2009
May 1;
137
(
5
):
769
77
.
11.
Ullah
K
,
Rahman
TU
,
Pan
H-T
,
Guo
M-X
,
Dong
X-Y
,
Liu
J
, et al. 
Serum estradiol levels in controlled ovarian stimulation directly affect the endometrium
.
J Mol Endocrinol.
2017
May 24;
59
(
2
):
105
19
.
12.
Elevated progesterone during ovarian stimulation for IVF - Reproductive BioMedicine Online [Internet]
. [cited
2018
Aug 18]. Available from: https://www.rbmojournal.com/article/S1472-6483(12)00029-6/fulltext
13.
Fleming
R
,
Jenkins
J.
The source and implications of progesterone rise during the follicular phase of assisted reproduction cycles
.
Reprod Biomed Online.
2010
Oct;
21
(
4
):
446
9
.
14.
Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis
. -
PubMed - NCBI [Internet].
[cited
2019
Jul 13]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/14505742
15.
Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through t… - PubMed - NCBI [Internet]
. [cited
2019
Jul 13]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15248835
16.
Expression of GnRH receptor gene in human ectopic endometrial cells and inhibition of their proliferation by leuprolide acetate. - PubMed - NCBI [Internet]
. [cited
2019
Jul 13]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10687850
17.
Menstrual-like breakdown and apoptosis in human endometrial explants. - PubMed - NCBI [Internet]
. [cited
2019
Jul 13]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15734750
18.
Yu
B
,
Ruman
J
,
Christman
G.
The role of peripheral gonadotropin-releasing hormone receptors in female reproduction
.
Fertil Steril.
2011
Feb 1;
95
(
2
):
465
73
.
19.
Apoptosis and endometrial receptivity: Relationship with in vitro fertilization treatment outcome [Internet]
. [cited
2019
Jul 14]. Available from: https://www.wjgnet.com/2218-6220/full/v5/i1/87.htm
20.
Bell
JD
,
Bergin
IL
,
Schmidt
K
,
Zochowski
MK
,
Aronoff
DM
,
Patton
DL
.
Nonhuman Primate Models Used to Study Pelvic Inflammatory Disease Caused by Chlamydia trachomatis [Internet]
.
Infectious Diseases in Obstetrics and Gynecology.
2011
[cited
2019
Jul 31]. Available from: https://www.hindawi.com/journals/idog/2011/675360/
21.
Reed
BG
,
Carr
BR
. The Normal Menstrual Cycle and the Control of Ovulation. In:
Feingold
KR
,
Anawalt
B
,
Boyce
A
,
Chrousos
G
,
Dungan
K
,
Grossman
A
, et al., editors.
Endotext [Internet]
.
South Dartmouth (MA)
:
MDText.com, Inc
.;
2000
[cited
2019
Jul 30]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK279054/
22.
Cakmak
H
,
Rosen
MP
. Chapter 8 - Current Clinical Approaches to Protecting the Ovary: GnRH Analogues. In:
Anderson
RA
,
Spears
N
, editors.
Cancer Treatment and the Ovary [Internet]
.
Boston
:
Academic Press
;
2015
[cited
2019
Jul 16]. p.
109
32
. Available from: http://www.sciencedirect.com/science/article/pii/B9780128015919000084
23.
Fritz
MA
,
Speroff
L.
Clinical Gynecologic Endocrinology and Infertility.
:
1451
.
24.
Magon
N.
Gonadotropin releasing hormone agonists: Expanding vistas
.
Indian J Endocrinol Metab.
2011
;
15
(
4
):
261
7
.
25.
Finch
A
,
Sedgley
K
,
Armstrong
S
,
Caunt
C
,
McArdle
C.
Trafficking and signalling of gonadotrophin-releasing hormone receptors: an automated imaging approach
.
Br J Pharmacol.
2010
Feb;
159
(
4
):
751
60
.
26.
Hayden
C.
GnRH analogues: applications in assisted reproductive techniques
.
Eur J Endocrinol.
2008
Dec 1;
159
(suppl
1
):
S17
25
.
27.
Beigi Boroujeni
M
,
Salehnia
M
,
Khalatbary
R
,
Pourbeiranv
S
,
Boroujeni
NB
,
Ebrahimi
S.
Effect of Ovarian Stimulation on the Endometrial Apoptosis at Implantation Period
.
Iran Biomed J.
2010
Oct;
14
(
4
):
171
7
.
28.
Meresman
GF
,
Olivares
C
,
Vighi
S
,
Alfie
M
,
Irigoyen
M
,
Etchepareborda
JJ
.
Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients
.
Reprod Biol Endocrinol RBE.
2010
Oct 22;
8
:
126
.
29.
Park
S-R
,
Cho
A
,
Park
ST
,
Park
CH
,
Lim
S
,
Jin
M
, et al. 
Double-edged sword of gonadotropin-releasing hormone (GnRH): A novel role of GnRH in the multiple beneficial functions of endometrial stem cells
.
Cell Death Dis.
2018
Aug 1;
9
(
8
):
828
.
30.
Cedrin-Durnerin
I.
Consequences on gonadotrophin secretion of an early discontinuation of gonadotrophin-releasing hormone agonist administration in short-term protocol for in-vitro fertilization
.
Hum Reprod.
2000
May 1;
15
(
5
):
1009
14
.
31.
Andreu-Vieyra
CV
,
Buret
AG
,
Habibi
HR
.
Gonadotropin-releasing hormone induction of apoptosis in the testes of goldfish (Carassius auratus
).
Endocrinology.
2005
Mar;
146
(
3
):
1588
96
.
32.
Limonta
P
,
Montagnani
Marelli M
,
Mai
S
,
Motta
M
,
Martini
L
,
Moretti
RM
.
GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies
.
Endocr Rev.
2012
Oct;
33
(
5
):
784
811
.
This content is only available via PDF.