Role of PRP in Thin Endometrium (A Pilot Study )

1. DR. EKIKA SINGH
D I R E C TO R & C O N S U LTAN T
S H AR D A N AR AYAN H O S P I TAL . M AU
Role of PRP in Thin Endometrium
(A Pilot Study )

2. • Endometrium is one of the main factor in pregnancy.
• During assisted reproductive technology (ART) treatments, some cycles are
cancelled due to inadequate endometrial growth.
• Thin endometrium significantly increases the risk of embryo implantation
failure,as the pregnancy rate in women with ≤ 6mm of endometrial thickness
was only 19.43%.
2
Introduction

3.  Some FET cycles are cancelled due to thin endometrium despite routine treatment, and
there is no established protocol for this condition.
 Various strategies have been developed for the treatment of thin endometrium, including
extended use of exogenous estrogen , use of low-dose aspirin , vitamin E and vaginal
sildenafil citrate , electroacupuncture and application of granulocyte colony stimulation
factor (G-CSF) .
 However, a number of women with thin endometrium remain non-responsive even after
these remedies have been performed.
3

4.  Intrauterine infusion of platelet-rich plasma (PRP) is a new approach that has been
suggested for the treatment of thin endometrium. It has anti inflammatory and pro
regenerative functions.
 The factors secreted by activated platelets in PRP help regulate cell migration,
attachment, proliferation and differentiation, and promote extracellular matrix
accumulation and angiogenesis which leads to tissue regeneration.
 It is being found that cytokines and growth factors become bioactive in PRP. These
factors include vascular endothelial growth factor (VEGF), transforming growth factor
(TGF), platelet-derived growth factor (PDGF) and epidermal growth factor (EGF),
cytokines and chemokines.
4

5. Material and Method
 This pilot study was conducted at Sharda Narayan Hospital
,Mau from Dec 2017-May 2018. 18 patients with thin
endometrium where included after written, informed consent
and approval .
5

6. Inclusion Criteria
• Age :- 22-37yrs at time of study.
• Cycle cancellation due to thin
endometrium < 7mm in HRT cycle .
• More than two cycles of previous therapy
for increasing endometrium thickness
ie- Hysteroscopy evaluation and
management followed by high does
estradiol valerat and trans vaginal sidenafil
citrate
Exclusion Criteria
• History of Hematological
disorder, Auto immune diseases.
• Chromosomal abnormity in
couples.
• Uncontrolled endocrine or any
other medical disorder
6

7. Autologous PRP Preparation
PRP was prepared from autologous blood using a
two-step centrifuge process. On the 12th day of the
mensural cycle, 10 ml of peripheral venous blood was
drawn in the syringe that contained 2.5 ml of Acid Citrate
A Anticoagulant solution (ACD-A) (Arya Mabna
Tashkhis, Iran) and centrifuged immediately at 1200 rpm
for 12 min to separate the red blood cells. The plasma
was centrifuged again at 3300 rpm for 7 min to obtain the
PRP. Then, 0.5 ml of PRP was infused into the uterine
cavity with the IUI catheter .
7

8. Hormone replacement therapy (HRT) was started for endometrial preparation in all
patients:
Estradiol valerate 8 mg/d was started on the 2nd day of the mensural cycle
and was gradualy increased to 12 mg/d till Day -12 because of inadequate endometrial growth
(< 7 mm). PRP was performed on day 12th in all the patients due to thin endometrium and it was
repeated on day 15th .After 48 hrs Progesterone Inj 100 mg/ml/day was started and embryo
transfer (ET) was carried out on day 6. Estradiol valerate and progesterone supplementation
were continued for 2 weeks after ET and if the serum βHCG was positive, hormone
supplementations were continued until 12 weeks of gestation.
8
Endometrial Preparation

9. Data Analysis
 Statical analysis was performed using one way ANOVA test to
compare the differences between pre PRP and post PRP
endometrium thickness. A p value of <0.05 was considered
statistically significant. Pregnancy outcome was analysed using
fisher’s exact test.
9

10. Result
• The general characteristics , hysteroscopic findings and endometrium
thickness on final priming day is being summarized in table 1.
• The average age of patients was 30.78 ±0.85. the mean duration of infertility
was 9.39 ± 0.87.
• Hysteroscopic adhesiolysis was done in 8 patients and hysteroscopic
septoplasty in one patient.
• The mean endometrium thickness on final priming day was 5.91 ±0.11.
10

11. 11
No. Age Infertility Cause Duration{years} Hysteroscopy Finding Surgical History ET(mm) on Final Priming Day
1 26 tubal 6 flimsy adhesions not specific 6.2
2 32 male factor 10 no specific 6.3
3 34 unexplained 10 Adhesion 5.8
4 30 tubal factor 8 incomplete septum 6.7
5 28 tubalfactor+IUA 6.5 synechiae 5.6
6 29 male factor 9 no specific 5.5
7 35 unexplained 11 flimsy adhesions h/o dnc 4.8
8 25 tubal factor 4.5 no specific 5.8
9 27 IUA+tubal factor 6 IUA at fundus h/o repeated dnc 5.2
10 34 male factor 14 no specific 6.4
11 35 unexplained 10.5 no specific h/o dnc 5.9
12 29 unexplained 19 flimsy adhesions h/o dnc 5.7
13 26 male factor 5 no specific 6.4
14 36 tubal factor 7 no specific lscs 5.8
15 31 male factor 8.5 no specific 6.5
16 29 tubal factor 8 Adhesion 5.7
17 33 unexplained 12 no specific 6.1
18 35 tubal +male factor 14 flimsy adhesions h/o dnc 5.9

12. 12
No. Age Day 12 Endo.
Thickness(mm)
Endo. Thickness after 1st PRP
Infusion(mm)
Endo. Thickness after 2nd PRP
Infusion(mm)
1 26 6.2 6.6 7.2
2 32 6.3 6.8 7.4
3 34 5.8 6.4 6.9
4 30 6.7 6.9 7.6
5 28 5.6 5.9 6.4
6 29 5.5 6.5 7.6
7 35 4.8 5.2 6
8 25 5.8 5.9 6.3
9 27 5.2 5.7 6.2
10 34 6.4 6.8 7.5
11 35 5.9 6.6 7.4
12 29 5.7 6.2 6.5
13 26 6.4 6.8 7.7
14 36 5.8 6.1 6.6
15 31 6.5 7.5 7.5
16 29 5.7 5.9 6.5
17 33 6.1 6.6 7.8
18 35 5.9 6.6 7.4

13. • The average thickness after 2nd PRP
infusion was 6.99 ±0.15 (P value
<0.05) which is significant .
• The mean increase in endometrium
thickness was 0.97mm.
13
Result

14. • Two embryos in blastocyst stage (Gr -I) were transferred in all the patients
• The gestational sac was confirmed in 61 % (n= 11) with implantation rate (44%. )
• Two patients had missed abortion at < 10 weeks of gestational age (16.6%).
• One patient had blighted ovum.
• Seven patients delivered without obstetrical complication . The live birth rate
was 38.8 %.
• 3 out of 9 patients in whom hysteroscopic adhenolysis was done delivered healthy live
babies.
14
Result

15. 15
No Final Endo. Thickness No. & Gr. Of Blastocyst
Transferred
BhcG No. of G. Sac Obstetric Outcome
Week Result
1 7.2 2AAX2 1269 1 37WK+5 SLF
2 7.4 4AA,3AA 2419 2 34WK+3D TWIN
3 7.6 4AA,3AA 32OO 2 36WK+2 SLF , ONE MISSED
4 7.6 4AA,3BA 1412 1 36WK+3D SLF
5 7.5 3AB,4AA 800 2 35WK+2D ONE LIVE ISSUE
6 6.5 2AA,3AA 1650 1 38WK SLF
7 7.8 3AAX2 1500 1 37WK+3 SLF
8 6.4 3AA,4AB 400 1 8WK+2D MISSED
9 6.3 5AA,4AA 4123 2 14WK+3D ABORTED
10 7.5 3AAX2 2116 2 6WK +3D MISSED
11 6.3 2AA,4BA 789 1 BLIGHTED MISSED
12 6.9 3AAX2 96 None NONE NONE
13 6.0 3AB,3AA 0.5 NONE NONE NONE
14 6.2 2AA,3BA 123 NONE NONE NONE
15 7.4 4AAX2 33 NONE NONE NONE
16 7.7 3AAX2 0.1 NONE NONE NONE
17 6.6 4BA,2AA 67 NONE NONE NONE
18 7.4 4AAX2 I.8 NONE NONE NONE
LBR:- 38.8% ABR :- 22.2%
11 Pt. (61.1 %) IR :-44 %
6.99 ±0.15

16. 16
0
1
2
3
4
5
6
7
8
ABORTED MISSED NONE SLF TWIN
ENDOMETRIAL THICKNESS (MM)
PRETRETMENT POST-TREAMENT
5.8 5.93 5.69
6.1 6.3
6.3
6.6
6.88
7.36 7.4
0
1
2
3
4
5
6
7
8
ABORTED MISSED NONE SLF TWIN
Endometrial thickness (mm)
PRETREATMENT POST TREATMENT

17. • The purpose of the present study was to determine intrauterine administration
of PRP would improve the pregnancy outcomes of patients with refractory
thin endometrium.
• Total of 18 women were enrolled and LBR of 38.8% was achieved for these
patients with poor prognosis.
17
Discussion:-

18. PRP has high concentration of growth factors and cytokines which can stimulate the
mitogenesis and proliferation of endometrial cells or endometrial stem cells, and then activate
endocrine-paracrine pathways for improving the endometrial response to promote embryo
implantation and pregnancy.
18
Discussion:-

19. It is suggested that the levels of 12 proteins increased in activated PRP in
comparison with whole blood plasma or platelet-poor plasma. Six growth factors
(i.e., PDGF-AA, PDGF-AB, PDGF-BB, TGF-b1, TGF-b2, and EGF), three anti-
inflammatory cytokines (i.e., IL-4, IL-13, and IFN-a), and three pro-inflammatory
cytokines (i.e., IL-8, IL-17,and TNF-a) . These cytokines and growth factors may
increase endometrial receptivity.
19
Discussion:-

20. Since date only few study on in vivo autologus PRP on
human endometrium has been published.
20
Discussion:-

21. 21

22. Maryam Eftekhar etal : A randomized clinical trial Taiwanese Journal of Obstetrics & Gynecology 57 (2018)
Can autologous platelet rich plasma expand endometrial thickness
and improve pregnancy rate during frozen-thawed embryo transfer cycle ?
83 women with poor endometrial response to standard hormone replacement therapy (HRT)
(endometrium thickness < 7 mm) in the 13th day of the cycle in a frozen-thawed embryo transfer (FET) were entered in two
groups. In the PRP group (n= 40), in addition to HRT, 0.5e1 cc of PRP was infused into the uterine cavity on the 13th day of
HRT cycle. The control group (n= 43) was only received HRT
Results:
Endometrial thickness increased significantly to 8.67 ± 0.64 in PRP group than in controls (p =0.001). This increase
was higher in women who conceived in PRP group (p value: 0.031). The implantationrate and per-cycle clinical pregnancy
rate were significantly higher in PRP group (p =0.002and 0.044, respectively (p =0.002).
22
Discussion:-

23. Yajie Chang etal : a prospective cohort study : Medicine (2019) 98:3(e14062)
Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo
transfer cycles for women with thin endometrium
64 patients with thin endometrium (<7mm) were recruited. PRP intrauterine infusion was given
in PRP group during hormone replacement therapy (HRT)cycle in FET cycles.
Results:
After PRP infusion, the endometrium thickness in PRP group was 7.65±0.22mm, which was significantly thicker than that
in control group (6.52±0.31mm) (P<.05). Furthermore, PRP group had lower cycle cancellation rate when compared to control
group (19.05% vs. 41.18%, P<.01). The implantation rate and clinical pregnancy rate in PRP group were significantly higher than
those in control group (27.94% vs 11.67%, P<.05; 44.12% vs 20%, P<.05, respectively). PRP blood contained 4 folds higher
platelets and significantly greater amounts of growth factors including platelet-derived growth factor (PDGF)-AB, PDGF-BB, and
transforming growth factor (TGF)-b than peripheral blood (P<.01).
23
Discussion:-

24. 24
Our study showed that the use of autologous PRP improved the implantation,
pregnancy, and live birth rates (LBR) of the patients with refractory thin endometrium.
The Implantation and live birth rates reached upto 44% and 38.8% respectively.
However there are limitations in this study. First, the study population was small to
show a statistically significant result on pregnancy outcome
Second, this study was not an RCT; thus, the effectiveness of the PRP treatment
was shown only by comparison with the most recent previous cycle of each patient.
Discussion:-

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