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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 27-30

Platelet-rich plasma improves embryo implantation in women with repeated implantation failures: A quasi-experiment


1 Department of IVF, Parsian Hospital, Tehran, Iran
2 Department of Physiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
3 School of Medicine, Islamic Azad University, Tehran, Iran

Date of Submission03-Mar-2021
Date of Acceptance17-Sep-2021
Date of Web Publication17-Dec-2021

Correspondence Address:
Dr. Parvin Zareian
Department of Physiology, School of Medicine, AJA University of Medical Sciences, Etemadzadeh Street, Western Fatemi Street, Tehran.
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tofj.tofj_2_21

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  Abstract 

Background: Various methods have been used for the treatment and management of repeated implantation failures (RIFs). One approach that has recently been considered for the treatment of RIF is intrauterine infusion of platelet-rich plasma (PRP). Objective: In the present study, the effect of intrauterine injection of PRP on pregnancy outcome was investigated in women with RIFs. Study Design: This study was performed on 17 patients with RIF history. The number of embryos (5-day blastocyst) transferred in each patient was 1 or 2. An aliquot of 12 mL of venous blood was taken from the patient. After two centrifugal stages, 0.5–1 mL of PRP was obtained. PRP was injected into the womb cavity. Results: The implantation and clinical pregnancy were confirmed in 35.3% (n = 6) of the patients. One patient had a miscarriage in the second month of pregnancy. Live birth rate was 29.4% (n = 5). Conclusion: This study showed the effectiveness of intrauterine infusion of PRP in patients with RIFs.

Keywords: Embryo implantation, platelet-rich plasma, repeated implantation failure


How to cite this article:
Zareian ZJ, Zareian P, Movahed E. Platelet-rich plasma improves embryo implantation in women with repeated implantation failures: A quasi-experiment. Onco Fertil J 2021;4:27-30

How to cite this URL:
Zareian ZJ, Zareian P, Movahed E. Platelet-rich plasma improves embryo implantation in women with repeated implantation failures: A quasi-experiment. Onco Fertil J [serial online] 2021 [cited 2022 Jan 28];4:27-30. Available from: https://www.tofjonline.org/text.asp?2021/4/1/27/332638




  Introduction Top


Repeated implantation failure (RIF) is the failure of the embryo to implant onto the side of the uterus wall following several in-vitro fertilization (IVF) treatment cycles. RIF is only applicable to patients undergoing assisted reproductive technology (ART). According to the European Society of Human Reproduction and Embryology consortium, RIF is defined as the absence of gestational sac on ultrasound at 5 weeks or more after embryo transfer (ET) following 3 ETs with high-quality embryos or after transfer of 10 or more embryos in multiple transfers.[1],[2] Numerous factors have an important role in implantation failure. These include mechanical, inflammatory, and systemic factors.[3] Mechanical factors include congenital uterine anomalies and acquired intra-cavitary conditions. Inflammatory factors include endometriosis, adenomyosis, and endometritis. Hypothyroidism, vitamin D deficiency, obesity, smoking, inflammatory bowel disease, and autoimmunity are among the systemic factors that influence the success rate of implantation.[3] Various methods have been used for the treatment and management of RIFs such as hysteroscopy,[4] endometrial stimulation,[5] immunotherapy,[6],[7],[8] growth hormone, aspirin and heparin treatment,[9],[10] infusion of intralipid solution,[11] endometrial scratching,[12] pre-implantation genetic screening,[13] blastocyte transfer,[14] zygote intrafallopian transfer,[15] salpingectomy,[16] and autologous endometrial cell co-culture.[17] Despite many studies regarding these therapies, the effects of these treatments have not yet been fully elucidated. One approach that has recently been considered for the treatment of RIF is intrauterine infusion of platelet-rich plasma (PRP). PRP is made from fresh whole blood, which has higher platelet concentrations than basal blood plasma. PRP contains several growth factors that are essential in the healing process.[18] Despite many studies on the therapeutic effects of PRP in various medical fields, there are limited reports in the field of gynecology.[19],[20],[21] In this study, we investigated the effect of intrauterine infusion of PRP on the pregnancy outcome in women with RIF.


  Patients and methods Top


This study was performed on 17 patients with RIF history (three or more failed IVF cycles) referred to the IVF department of Parsian Hospital, Tehran, Iran (February 2017 to April 2018). The age of patients was 26–49 years. The mean duration of infertility was 4–8 years. The number of embryos transferred in each patient was 1or 2. All patients had normal uterine cavity established by hysteroscopy and hysterosalpingography. Estradiol (Novonordifk Company, Denmark) was started at a dose of 4 mg orally and increased every 4 days as needed. The maximum dose of estradiol given was 10 mg. When the endometrial thickness was over 8.5 mm, progesterone (Iran Hormone Company; Iran) at a dose of 100 mg was started to protect the luteal phase. The blastocyte (5 days) was transferred on the 6th day of the onset of progesterone administration under ultrasound guidance. On the day before embryo transfer, 12 mL of venous blood from the patient was combined with 5 mL of anticoagulant (ACD-A). After two centrifugal stages, 0.5–1 mL of PRP was obtained. PRP was injected into the womb cavity by using an ET catheter. Luteal phase support was given; 14 days later, the beta test was done for the patients; if it was positive, hormone supplementation was continued until 12 weeks of gestation.

The study was approved by the Ethics Committee of AJA University of Medical Sciences, Tehran, Iran, and all patients gave informed consent before participation in the study.


  Results Top


A total of 17 patients with RIF history were recruited.

Patients characteristics are shown in [Table 1].
Table 1: Patients’ characteristics

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The implantation and clinical pregnancy were confirmed in 35.3% (n = 6) of the patients. One patient had a miscarriage in the second month of pregnancy. Live birth rate was 29.4% (n = 5).


  Discussion Top


Despite recent development in advanced reproductive (AR) technology, implantation failure is a significant challenge for struggling couples and physician. Currently, the implantation rate per embryo among RIFs is only about 15%[2],[22] for cleavage stage and 25.4 till 21.2% for blastocyte transfer.[14],[23] There are several factors involved in successful implantation, the most important of which is receptive endometrium. In the endometrial receptivity process, a number of genetic factors and molecules of certain substances, known as growth factors, and cytokinins regulate mitosis of endometrial cellular components in vitro.[24] Cytokines are important for the early stages of embryo implantation.[25] PRP is plasma with many more platelets than what is typically found in blood. When platelets are activated, they release growth factors, cytokines, and chemokines from platelet granules. These substances stimulate cell migration, cell proliferation, and angiogenesis, thus inducing tissue regeneration.[26]

Previous studies proved that PRP could be used for the management of various medical disorders.[27],[28] But with our current knowledge, there are few studies on the effect of PRP on pregnancy outcome in women with RIFs. Farimani et al.[19] reported efficacy of intrauterine PRP administration in successful implantation in a 45-year-old woman with RIF. In a similar case report, a 35-year-old woman with chronic endometritis underwent intrauterine PRP treatment. ET resulted in a twin pregnancy and birth.[20] Results of a pilot study performed on 22 patients (age 20–45 years) with a refractory thin endometrium showed that intrauterine injection of PRP resulted in increased uterine thickness. In that study, implantation rates and clinical pregnancy rates were 12.7% and 30%, respectively.[21] The present study examined the effect of intrauterine PRP infusion on implantation and pregnancy outcome in RIF patients. Implantation and clinical pregnancy occurred in 6 of the 17 patients studied and 5 out of 6 pregnant patients had normal pregnancies.

It seems that the effectiveness of PRP in increasing the chances of pregnancy depends on the method of PRP preparation. Weibrich et al.[29] reported when PRP is used with a platelet concentration of approximately 1,000,000/μL (503,000–1,729,000/μL) it exerts optimal biological effect. Higher concentrations might have a paradoxically inhibitory effect.


  Conclusion Top


This study showed the effectiveness of intrauterine infusion of PRP in women with RIFs. Further studies are needed to confirm the efficacy of PRP in the treatment of RIF.

Acknowledgments

We sincerely thank the staff of the Department of IVF, Parsian Hospital, especially Ms. Tabai, Ms Ghaffari, and Ms Jafari for their great help and support to do this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: Definition and management. Reprod Biomed Online 2014;28:14-38.  Back to cited text no. 1
    
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Friedler S, Margalioth EJ, Kafka I, Yaffe H. Treatable uterine cause for in-vitro fertilisation failures. Lancet 1993;341:1213.  Back to cited text no. 5
    
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7.
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8.
Stephenson MD, Fluker MR. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: A randomized, placebo-controlled Canadian trial. Fertil Steril 2000;74:1108-13.  Back to cited text no. 8
    
9.
Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies or antiphospholipid antibodies. Br Med J 1997;314:253.  Back to cited text no. 9
    
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Altmäe S, Mendoza-Tesarik R, Mendoza C, Mendoza N, Cucinelli F, Tesarik J. Effect of growth hormone on uterine receptivity in women with repeated implantation failure in an oocyte donation program: A randomized controlled trial. J Endocr Soc 2018;2:96-105.  Back to cited text no. 10
    
11.
Ndukwe G. Recurrent embryo implantation failure after in vitro fertilisation: Improved outcome following intralipid infusion in women with elevated T Helper 1 response. Hum Fertil (Camb.) 2011;14:21-2.  Back to cited text no. 11
    
12.
Gibreel A, Badawy A, El-Refai W, El-Adawi N. Endometrial scratching to improve pregnancy rate in couples with unexplained subfertility: A randomized controlled trial. J Obstet Gynaecol Res 2013;39:680-4.  Back to cited text no. 12
    
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Rubio C, Bellver J, Rodrigo L, Bosch E, Mercader A, Vidal C, et al. Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: Two randomized trials. Fertil Steril 2013;99:1400-7.  Back to cited text no. 13
    
14.
Guerif F, Bidault R, Gasnier O, Couet ML, Gervereau O, Lansac J et al. Efficacy of blastocyst transfer after implantation failure. Reprod Biomed Online 2004;9:630-6.  Back to cited text no. 14
    
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Farhi J, Weissman A, Nahum H, Levran D. Zygote intrafallopian transfer in patients with tubal factor infertility after repeated failure of implantation with in vitro fertilization-embryo transfer. Fertil Steril 2000;74:390-3.  Back to cited text no. 15
    
16.
Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Salpingectomy for hydrosalpinx prior to in vitro fertilization. Fertil Steril 2008;90(5 Suppl.):S66-8.  Back to cited text no. 16
    
17.
Eyheremendy V, Raffo FG, Papayannis M, Barnes J, Granados C, Blaquier J. Beneficial effect of autologous endometrial cell coculture in patients with repeated implantation failure. Fertil Steril 2010;93:769-73.  Back to cited text no. 17
    
18.
Scherer SS, Tobalem M, Vigato E, Heit Y, Modarressi A, Hinz B, et al. Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-myofibroblast differentiation in vivo and in vitro. Plas Reconstr Surg 2012;129:46e-54e.  Back to cited text no. 18
    
19.
Farimani M, Poorolajal J, Rabiee S, Bahmanzadeh M. Successful pregnancy and live birth after intrauterine administration of autologous platelet-rich plasma in a woman with recurrent implantation failure: A case report. Int J Reprod Biomed (Yazd) 2017;15:803-6.  Back to cited text no. 19
    
20.
Sfakianoudis K, Simopoulou M, Nitsos N, Lazaros L, Rapani A, Pantou A, et al. Successful implantation and live birth following autologous platelet-rich plasma treatment for patient with recurrent implantation failure and chronic endometritis. In Vivo 2019;33:515-21.  Back to cited text no. 20
    
21.
Kim H, Shin JE, Koo HS, Kwon H, Choi DH, Kim JH. Effect of autologous platelet-rich plasma treatment on refractory thin endometrium during the frozen embryo transfer cycle: A pilot study. Front Endocrinol (Lausanne) 2019;10:61.  Back to cited text no. 21
    
22.
Orvieto R, Brengauz M, Feldman B. A novel approach to normal responder patient with repeated implantation failures—A case report. Gynecol Endocrinol2015;31:435-7.  Back to cited text no. 22
    
23.
Levitas E, Lunenfeld E, Har-Vardi I, Albotiano S, Sonin Y, Hackmon-Ram R et al. Blastocyst-stage embryo transfer in patients who failed to conceive in three or more day 2–3 embryo transfer cycles: A prospective, randomized study. Fertil Steril 2004;81:567-71.  Back to cited text no. 23
    
24.
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25.
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26.
Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, Corrêa do Amaral RJ, Granjeiro JM, et al. Platelet-rich plasma preparation for regenerative medicine: Optimization and quantification of cytokines and growth factors. Stem Cell Res Ther 2013;4:67.  Back to cited text no. 26
    
27.
Yu W, Wang J, Yin J. Platelet-rich plasma: A promising product for treatment of peripheral nerve regeneration after nerve injury. Int J Neurosci 2011;121:176-80.  Back to cited text no. 27
    
28.
Glynn LG, Mustafa A, Casey M, Krawczyk J, Blom J, Galvin R, et al. Platelet-rich plasma (PRP) therapy for knee arthritis: A feasibility study in primary care. Pilot Feasibility Stud 2018; 4:93.  Back to cited text no. 28
    
29.
Weibrich G, Hansen T, Kleis W, Buch R, Hitzler WE. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 2004;34:665-71.  Back to cited text no. 29
    



 
 
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