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PLATELET RICH PLASMA (PRP)
In
Reproductive Medicine: Current
Status
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
ABOUBAKR ELNASHAR
INTRODUCTION
 PRP
 Preparation: simple& easily performed.
 Contain high concentrations of
1. Cytokines
2. Growth factors
ABOUBAKR ELNASHAR
1/12/2020
2
 Mechanisms of action
 High concentration of growth factors: tissue
regeneration& healing.
 The fibrin framework present over platelets
support the regenerative matrix: rapid
establishment of the proper morphological and molecular
configuration for wound healing
ABOUBAKR ELNASHAR
Preparation
Centrifuge at 1,200 rpm for 12 min
 Upper: platelets & WBC
 Intermediate thin: rich in WBC
 Bottom: RBC
Centrifuged at 3,300 rpm for 7 min
ABOUBAKR ELNASHAR
1/12/2020
3
 Platelet activation
 triggers the release of these growth factors by
 thrombin
 calcium chloride
 collagen.
 Each method influences both
 physical form of PRP
 amount of growth factors released
 kinetics of release.
ABOUBAKR ELNASHAR
OBJECTIVE:
To review uses of PRP in reproductive medicine.
METHODS
 A literature search for English articles, related to uses of
PRP in reproductive medicine, including articles published in
Pub Med.
 From 2000 to october 2019
 Keywords: PRP, ICSI, Endometrium, Ovary
ABOUBAKR ELNASHAR
1/12/2020
4
RESULTS
 21 studies
 Intraovarian: 5 studies
 Intrauterine: 16 studies
ABOUBAKR ELNASHAR
Indication No of
patients
Type of
study
1. Diminished ovarian reserve
 Sills et al, 2018, Gynecol Endocrinol. 4
Case series
2. Poor responders
 Sfakianoudis et al, 2019, Gynecol
Obstet Invest.
 Farimani et al, 2019, Mol Biol Rep J
3
19
Case series
Case series
3. Premature ovarian failure
 Pantos et al., 2019, Cell Transp
 Sfakianoudis et al, 2018. J. Clin. Med.
3
1
Case series
Case report
Total 30
INTRA OVARIAN PRP
ABOUBAKR ELNASHAR
1/12/2020
5
Intra ovarian infusion Procedure
 Timing:
 At the end of the periods
 Minimal sedation
 Injection:
 under direct TVS guidance
 using oocyte pick up needle (17-gauge)
 Slowly& steadily. To ensure
 Uniform distribution of infusion in all layers
 Needle is gently retracted while injecting
 3 punctures per ovary, intramedullary injection,
and diffusion in the subcortical layers.(Sfakianoudis et
al, 2018)
 Amount into each ovary
 2 mL
(Farimani et al, 2019)
 4 ml
(Pantos et al, 2019)
 5 mL
(Sills et al, 2018)
 After the procedure
 supine position for 10–15 min
 rest for one hour.
 Repeat procedure
/month for 2-3 months.ABOUBAKR ELNASHAR
1/12/2020
6
1. DIMINISHED OVARIAN RESERVE
One study
 Sills et al, 2018, Gynecol Endocrinol.
 4 women with diminished ovarian reserve
 PRP
 5 mL injected into each ovary under direct TVS guidance.
 Improved ovarian function in all cases
 Increase AMH
 Decrease FSH or both
 2 months after tt.
 IVF after 78 ± 22 (range = 59-110) days
 retrieval of 5.3 ± 1.3 MII oocytes.ABOUBAKR ELNASHAR
2. POOR RESPONDERS
2 studies
Sfakianoudis et al, 2019, Gynecol Obstet Invest.
 3 poor responders
 failed IVF attempts, poor oocyte yield, and poor embryo quality.
 PRP ovarian infusion
 Within a 3-month interval
 FSH decreased by 67.33%
 AMH increased by 75.18%.
 improved embryo quality.
 Natural conception at 24 ws, an uncomplicated
healthy pregnancy at 17 ws and a successful live birth.
ABOUBAKR ELNASHAR
1/12/2020
7
3. PREMATURE OVARIAN FAILURE
Ovarian rejuvenation
2 studies
Pantos et al., 2016, Annual Meeting of ESHRE
 8 perimenopausal/ POF
 PRP injected
 successful ovarian rejuvenation 1–3 months after PRP tt.
 All cases underwent natural IVF cycles: follicles
of 15.20±2.05 mm in diameter,
 ICSI& all resulting embryos were
cryopreserved.
ABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
Proposed mechanism of
action for alteration of adult
ovarian function by
application of activated PRP
(Sills & Wood, 2019)
1/12/2020
8
ABOUBAKR ELNASHAR
Proposed mechanism of action for
alteration of adult ovarian function by
application of activated PRP
(Sills & Wood, 2019)
PLT-derived growth factors
trigger or enable differentiation of
OSCs
 Reduced FSH and/or
 Increased AMH
 consistent with improved or ‘re-
potentiated’ ovarian function.
ABOUBAKR ELNASHAR
 The traditional dogma
 Oocyte stores
 Limited
 non-renewable
 No evidence for neo-oogenesis in adult monkey
Stem Cells.
(Yuan et al.,2013)
 Existence of adult ovarian Germline SCs
 an unlimited source of oocytes
(Hanna et al; 2014)
 potential roles in infertility TT&fertility preservation
(Dunlop et al,2013)
 Female mice lack adult germ-line stem cells
Transformation of somatic cells into stem cell-like
cells under specific in vitro conditions
(Lee et al,2013)
1/12/2020
9
 Comment
 Number of studies: Few
 Number of patients: Few
 Type of studies: all case series, or case report,
No RCT
 Journal of publication:
 Cl Med
 Gyn Endocr
 Cell transplantation
 Experimental
ABOUBAKR ELNASHAR
Indication No of
patients
Type of
study
1. Thin endometrium
 Chang et al.;2015, Int J Clin Exp Med.
 Colombo et al.,2017,J Biol Regul Homeost Agents
 Zadehmodarres et al., 2017, JBRA Assist Reprod
 Tandulwadkar et al, 2017,J Hum Reprod Sci
 Wang et al, 2018, J Cell Biochem
 Kim et al, 2019, Front Endocrinol
 Chang et al, 2019, Medicine
 Li et al, 2017, ESHRE annual meeting
 Eftekhar et al, 2018, Taiwan J Obstet Gynecol.
 Nazari et al, 2019, Int J Reprod Biomed
5
8
10
68
20
22
60
42
40
30
Case series
Case series
Case series
Case series
Case series
Case series
Case series
RCT
RCT 102
RCT
 Total 245
Intrauterine PRP
10 studies
ABOUBAKR ELNASHAR
1/12/2020
10
Intrauterine infusion procedure
Using IU catheter
Amount:
0.5-1 ml
(Aghajanova et al, 2018)
 0.7ml
(Dieamant 2019 )
 How many times:
2 or 3 times in the same cycle
ABOUBAKR ELNASHAR
 Timing:
 D10 of HRT cycle& repeat after 72 h: if EnT still <7 mm
(Chang et al.;2015, Li et al, 2017)
 D11-12 of HRT cycle& repeat after 48 h
(Nazari et al, 2019)
 D13 of HRT cycle& repeat after 48 h
(Eftechar et al, 2018)
 ET
 24 hr after final infusion
(Farimani et al, 2017)
 72 hr after the final infusion
(Kim et al, 2019) ABOUBAKR ELNASHAR
1/12/2020
11
 Li et al, 2017: ESHRE annual meeting 2017: RCT
PRP group
42 cycles
Control group
51 cycles
EnT(mm) 7.7±0.2 6.5±0.3
Cancellation rate (%) 19 41
IR (%) 28 12
CPR (%) 44 20
 PRP for thin endometrium improved
 Endometrium proliferation
 Implantation rate
 CPR
ABOUBAKR ELNASHAR
 Comment
 Number of studies: 10
 Number of patients: 245
 Type of studies: all are case series, only 3 RCC
(102 patients)
 Results: promising
 PRP may be effective in improving endometrial
growth& possibly pregnancy outcomes in women with
thin endometrium.
 More RCT are required to confirm efficacy
ABOUBAKR ELNASHAR
1/12/2020
12
Indication No of
patients
Type of
study
2. Repeated implantation failure
 Farimani et al, 2017, Int J Reprod Biomed
 Nazari et al., 2016, Int J Reprod Biomed
 Mehrafza et al, 2019, J Rep Inf
 Coksuer et al, 2019, Gynecol Endocrinol
1
20
60
34
Case report
Case series
Case series
Case series
Total 135
ABOUBAKR ELNASHAR
 Nazari et al., 2016, Int J Reprod Biomed (Yazd)
 20 with a history of RIF
 younger than 40 years
 BMI below 30 kg/m2.
 16 (80%) CPR
 PRP was effective in improving pregnancy
outcomes in RIF.
ABOUBAKR ELNASHAR
1/12/2020
13
Indication No of
patients
Type of
study
3. Chronic endometritis
 Sfakianoudis et al, 2019, In Vivo 1 Case report
4. Asherman syndrome.
 Aghajanova et al, 2018, Fert Ster. 7 RCT
ABOUBAKR ELNASHAR
 In RIF due to persistent CHRONIC ENDOMETRITIS
(CE): (Sfakianoudis et al, 2019, In Vivo)
 IU PRP& subsequent ET:
 No signs of CE
 Twin pregnancy.
 PRP may be employed as a first-line treatment of
CE, especially for patients who fail to respond to
antibiotic.
ABOUBAKR ELNASHAR
1/12/2020
14
PRP in ASHERMAN SYNDROME (AS)
 combined with standard surgical& medical tt
 significant increase in EnT
 a feasible& promising experimental tool in
management of AS.
ABOUBAKR ELNASHAR
CONCLUSION
 PRP
 An innovative therapeutic modality
 Affordable, simple, easily performed.
 Intraovarian PRP
 Diminished ovarian reserve
 Poor ovarian response experimental
 Premature ovarian failure
ABOUBAKR ELNASHAR
1/12/2020
15
 Intrauterine PRP
 Thin endometrium:
promising & more RCT are required
 RIF
 CE experimental
 AS
ABOUBAKR ELNASHAR
 There is a need for
1. Research on cellular& molecular level to improve
our knowledge on PRP mode of action
2. Standardization of PRP
1. Preparation methods
2. Application methods
3. Well-designed, large RCT to confirm its efficacy
&safety
 Without strong, unbiased evidence, any
intervention is a suspect until proven otherwise.ABOUBAKR ELNASHAR
1/12/2020
16
You can get this lecture and 446 lecture from:
1.My scientific page on Face book: Aboubakr
Elnashar Lectures.
https://www.facebook.com/groups/2277448840913
51/
2.Slide share web site
3. elnashar53@hotmail.com
4.My clinic: Althwara st, Mansura, Egypt
ABOUBAKR ELNASHAR

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platelet rich plasma in reproductive medicine

  • 1. 1/12/2020 1 PLATELET RICH PLASMA (PRP) In Reproductive Medicine: Current Status Prof. Aboubakr Elnashar Benha university Hospital, Egypt ABOUBAKR ELNASHAR INTRODUCTION  PRP  Preparation: simple& easily performed.  Contain high concentrations of 1. Cytokines 2. Growth factors ABOUBAKR ELNASHAR
  • 2. 1/12/2020 2  Mechanisms of action  High concentration of growth factors: tissue regeneration& healing.  The fibrin framework present over platelets support the regenerative matrix: rapid establishment of the proper morphological and molecular configuration for wound healing ABOUBAKR ELNASHAR Preparation Centrifuge at 1,200 rpm for 12 min  Upper: platelets & WBC  Intermediate thin: rich in WBC  Bottom: RBC Centrifuged at 3,300 rpm for 7 min ABOUBAKR ELNASHAR
  • 3. 1/12/2020 3  Platelet activation  triggers the release of these growth factors by  thrombin  calcium chloride  collagen.  Each method influences both  physical form of PRP  amount of growth factors released  kinetics of release. ABOUBAKR ELNASHAR OBJECTIVE: To review uses of PRP in reproductive medicine. METHODS  A literature search for English articles, related to uses of PRP in reproductive medicine, including articles published in Pub Med.  From 2000 to october 2019  Keywords: PRP, ICSI, Endometrium, Ovary ABOUBAKR ELNASHAR
  • 4. 1/12/2020 4 RESULTS  21 studies  Intraovarian: 5 studies  Intrauterine: 16 studies ABOUBAKR ELNASHAR Indication No of patients Type of study 1. Diminished ovarian reserve  Sills et al, 2018, Gynecol Endocrinol. 4 Case series 2. Poor responders  Sfakianoudis et al, 2019, Gynecol Obstet Invest.  Farimani et al, 2019, Mol Biol Rep J 3 19 Case series Case series 3. Premature ovarian failure  Pantos et al., 2019, Cell Transp  Sfakianoudis et al, 2018. J. Clin. Med. 3 1 Case series Case report Total 30 INTRA OVARIAN PRP ABOUBAKR ELNASHAR
  • 5. 1/12/2020 5 Intra ovarian infusion Procedure  Timing:  At the end of the periods  Minimal sedation  Injection:  under direct TVS guidance  using oocyte pick up needle (17-gauge)  Slowly& steadily. To ensure  Uniform distribution of infusion in all layers  Needle is gently retracted while injecting  3 punctures per ovary, intramedullary injection, and diffusion in the subcortical layers.(Sfakianoudis et al, 2018)  Amount into each ovary  2 mL (Farimani et al, 2019)  4 ml (Pantos et al, 2019)  5 mL (Sills et al, 2018)  After the procedure  supine position for 10–15 min  rest for one hour.  Repeat procedure /month for 2-3 months.ABOUBAKR ELNASHAR
  • 6. 1/12/2020 6 1. DIMINISHED OVARIAN RESERVE One study  Sills et al, 2018, Gynecol Endocrinol.  4 women with diminished ovarian reserve  PRP  5 mL injected into each ovary under direct TVS guidance.  Improved ovarian function in all cases  Increase AMH  Decrease FSH or both  2 months after tt.  IVF after 78 ± 22 (range = 59-110) days  retrieval of 5.3 ± 1.3 MII oocytes.ABOUBAKR ELNASHAR 2. POOR RESPONDERS 2 studies Sfakianoudis et al, 2019, Gynecol Obstet Invest.  3 poor responders  failed IVF attempts, poor oocyte yield, and poor embryo quality.  PRP ovarian infusion  Within a 3-month interval  FSH decreased by 67.33%  AMH increased by 75.18%.  improved embryo quality.  Natural conception at 24 ws, an uncomplicated healthy pregnancy at 17 ws and a successful live birth. ABOUBAKR ELNASHAR
  • 7. 1/12/2020 7 3. PREMATURE OVARIAN FAILURE Ovarian rejuvenation 2 studies Pantos et al., 2016, Annual Meeting of ESHRE  8 perimenopausal/ POF  PRP injected  successful ovarian rejuvenation 1–3 months after PRP tt.  All cases underwent natural IVF cycles: follicles of 15.20±2.05 mm in diameter,  ICSI& all resulting embryos were cryopreserved. ABOUBAKR ELNASHAR ABOUBAKR ELNASHAR Proposed mechanism of action for alteration of adult ovarian function by application of activated PRP (Sills & Wood, 2019)
  • 8. 1/12/2020 8 ABOUBAKR ELNASHAR Proposed mechanism of action for alteration of adult ovarian function by application of activated PRP (Sills & Wood, 2019) PLT-derived growth factors trigger or enable differentiation of OSCs  Reduced FSH and/or  Increased AMH  consistent with improved or ‘re- potentiated’ ovarian function. ABOUBAKR ELNASHAR  The traditional dogma  Oocyte stores  Limited  non-renewable  No evidence for neo-oogenesis in adult monkey Stem Cells. (Yuan et al.,2013)  Existence of adult ovarian Germline SCs  an unlimited source of oocytes (Hanna et al; 2014)  potential roles in infertility TT&fertility preservation (Dunlop et al,2013)  Female mice lack adult germ-line stem cells Transformation of somatic cells into stem cell-like cells under specific in vitro conditions (Lee et al,2013)
  • 9. 1/12/2020 9  Comment  Number of studies: Few  Number of patients: Few  Type of studies: all case series, or case report, No RCT  Journal of publication:  Cl Med  Gyn Endocr  Cell transplantation  Experimental ABOUBAKR ELNASHAR Indication No of patients Type of study 1. Thin endometrium  Chang et al.;2015, Int J Clin Exp Med.  Colombo et al.,2017,J Biol Regul Homeost Agents  Zadehmodarres et al., 2017, JBRA Assist Reprod  Tandulwadkar et al, 2017,J Hum Reprod Sci  Wang et al, 2018, J Cell Biochem  Kim et al, 2019, Front Endocrinol  Chang et al, 2019, Medicine  Li et al, 2017, ESHRE annual meeting  Eftekhar et al, 2018, Taiwan J Obstet Gynecol.  Nazari et al, 2019, Int J Reprod Biomed 5 8 10 68 20 22 60 42 40 30 Case series Case series Case series Case series Case series Case series Case series RCT RCT 102 RCT  Total 245 Intrauterine PRP 10 studies ABOUBAKR ELNASHAR
  • 10. 1/12/2020 10 Intrauterine infusion procedure Using IU catheter Amount: 0.5-1 ml (Aghajanova et al, 2018)  0.7ml (Dieamant 2019 )  How many times: 2 or 3 times in the same cycle ABOUBAKR ELNASHAR  Timing:  D10 of HRT cycle& repeat after 72 h: if EnT still <7 mm (Chang et al.;2015, Li et al, 2017)  D11-12 of HRT cycle& repeat after 48 h (Nazari et al, 2019)  D13 of HRT cycle& repeat after 48 h (Eftechar et al, 2018)  ET  24 hr after final infusion (Farimani et al, 2017)  72 hr after the final infusion (Kim et al, 2019) ABOUBAKR ELNASHAR
  • 11. 1/12/2020 11  Li et al, 2017: ESHRE annual meeting 2017: RCT PRP group 42 cycles Control group 51 cycles EnT(mm) 7.7±0.2 6.5±0.3 Cancellation rate (%) 19 41 IR (%) 28 12 CPR (%) 44 20  PRP for thin endometrium improved  Endometrium proliferation  Implantation rate  CPR ABOUBAKR ELNASHAR  Comment  Number of studies: 10  Number of patients: 245  Type of studies: all are case series, only 3 RCC (102 patients)  Results: promising  PRP may be effective in improving endometrial growth& possibly pregnancy outcomes in women with thin endometrium.  More RCT are required to confirm efficacy ABOUBAKR ELNASHAR
  • 12. 1/12/2020 12 Indication No of patients Type of study 2. Repeated implantation failure  Farimani et al, 2017, Int J Reprod Biomed  Nazari et al., 2016, Int J Reprod Biomed  Mehrafza et al, 2019, J Rep Inf  Coksuer et al, 2019, Gynecol Endocrinol 1 20 60 34 Case report Case series Case series Case series Total 135 ABOUBAKR ELNASHAR  Nazari et al., 2016, Int J Reprod Biomed (Yazd)  20 with a history of RIF  younger than 40 years  BMI below 30 kg/m2.  16 (80%) CPR  PRP was effective in improving pregnancy outcomes in RIF. ABOUBAKR ELNASHAR
  • 13. 1/12/2020 13 Indication No of patients Type of study 3. Chronic endometritis  Sfakianoudis et al, 2019, In Vivo 1 Case report 4. Asherman syndrome.  Aghajanova et al, 2018, Fert Ster. 7 RCT ABOUBAKR ELNASHAR  In RIF due to persistent CHRONIC ENDOMETRITIS (CE): (Sfakianoudis et al, 2019, In Vivo)  IU PRP& subsequent ET:  No signs of CE  Twin pregnancy.  PRP may be employed as a first-line treatment of CE, especially for patients who fail to respond to antibiotic. ABOUBAKR ELNASHAR
  • 14. 1/12/2020 14 PRP in ASHERMAN SYNDROME (AS)  combined with standard surgical& medical tt  significant increase in EnT  a feasible& promising experimental tool in management of AS. ABOUBAKR ELNASHAR CONCLUSION  PRP  An innovative therapeutic modality  Affordable, simple, easily performed.  Intraovarian PRP  Diminished ovarian reserve  Poor ovarian response experimental  Premature ovarian failure ABOUBAKR ELNASHAR
  • 15. 1/12/2020 15  Intrauterine PRP  Thin endometrium: promising & more RCT are required  RIF  CE experimental  AS ABOUBAKR ELNASHAR  There is a need for 1. Research on cellular& molecular level to improve our knowledge on PRP mode of action 2. Standardization of PRP 1. Preparation methods 2. Application methods 3. Well-designed, large RCT to confirm its efficacy &safety  Without strong, unbiased evidence, any intervention is a suspect until proven otherwise.ABOUBAKR ELNASHAR
  • 16. 1/12/2020 16 You can get this lecture and 446 lecture from: 1.My scientific page on Face book: Aboubakr Elnashar Lectures. https://www.facebook.com/groups/2277448840913 51/ 2.Slide share web site 3. elnashar53@hotmail.com 4.My clinic: Althwara st, Mansura, Egypt ABOUBAKR ELNASHAR