Aboubakr Elnashar

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PLATELET RICH PLASMA (PRP)
In
Reproductive Medicine: Current
Status
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
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INTRODUCTION
 PRP
 Preparation: simple& easily performed.
 Contain high concentrations of
1. Cytokines
2. Growth factors
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 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
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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
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 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.
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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
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RESULTS
 21 studies
 Intraovarian: 5 studies
 Intrauterine: 16 studies
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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
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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

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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.
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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.
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Proposed mechanism of
action for alteration of adult
ovarian function by
application of activated PRP
(Sills & Wood, 2019)

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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.
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 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)

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 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
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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
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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
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 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

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 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
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 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
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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
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 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.
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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
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 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.
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PRP in ASHERMAN SYNDROME (AS)
 combined with standard surgical& medical tt
 significant increase in EnT
 a feasible& promising experimental tool in
management of AS.
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CONCLUSION
 PRP
 An innovative therapeutic modality
 Affordable, simple, easily performed.
 Intraovarian PRP
 Diminished ovarian reserve
 Poor ovarian response experimental
 Premature ovarian failure
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 Intrauterine PRP
 Thin endometrium:
promising & more RCT are required
 RIF
 CE experimental
 AS
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 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

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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
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