|Year : 2021 | Volume
| Issue : 1 | Page : 27-30
Platelet-rich plasma improves embryo implantation in women with repeated implantation failures: A quasi-experiment
Zahra Jahromi Zareian1, Parvin Zareian2, Emad Movahed3
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 Submission||03-Mar-2021|
|Date of Acceptance||17-Sep-2021|
|Date of Web Publication||17-Dec-2021|
Dr. Parvin Zareian
Department of Physiology, School of Medicine, AJA University of Medical Sciences, Etemadzadeh Street, Western Fatemi Street, Tehran.
Source of Support: None, Conflict of Interest: None
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 Sep 28];4:27-30. Available from: https://www.tofjonline.org/text.asp?2021/4/1/27/332638
| Introduction|| |
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., Numerous factors have an important role in implantation failure. These include mechanical, inflammatory, and systemic factors. 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. Various methods have been used for the treatment and management of RIFs such as hysteroscopy, endometrial stimulation, immunotherapy,,, growth hormone, aspirin and heparin treatment,, infusion of intralipid solution, endometrial scratching, pre-implantation genetic screening, blastocyte transfer, zygote intrafallopian transfer, salpingectomy, and autologous endometrial cell co-culture. 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. Despite many studies on the therapeutic effects of PRP in various medical fields, there are limited reports in the field of gynecology.,, In this study, we investigated the effect of intrauterine infusion of PRP on the pregnancy outcome in women with RIF.
| Patients and methods|| |
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|| |
A total of 17 patients with RIF history were recruited.
Patients characteristics are shown in [Table 1].
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|| |
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%, for cleavage stage and 25.4 till 21.2% for blastocyte transfer., 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. Cytokines are important for the early stages of embryo implantation. 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.
Previous studies proved that PRP could be used for the management of various medical disorders., But with our current knowledge, there are few studies on the effect of PRP on pregnancy outcome in women with RIFs. Farimani et al. 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. 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. 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. 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|| |
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.
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
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.
BashiriA, Halper KI, Orvieto R. Recurrent implantation failure—Update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018;16:121.
Fox C, Morin S, Jeong JW, Scott RT Jr, Lessey BA. Local and systemic factors and implantation: What is the evidence? Fertil Steril 2016;105:873-84.
Arefi S, Soltanghoraee H, Zarnani A, Sadeghpour Tabaei A, GhafarriNovin M, Zeraati H, et al
. Repeated IVF/ICSI-ETs failures and impact of hysteroscopy. Iranian J Reprod Med 2008;6:19-24.
Friedler S, Margalioth EJ, Kafka I, Yaffe H. Treatable uterine cause for in-vitro
fertilisation failures. Lancet 1993;341:1213.
Coulam CB, Krysa LW, Bustillo M. Intravenous immunoglobulin for in-vitro
fertilization failure. Hum Reprod 1994;9:2265-9.
Elram T, Simon A, Israel S, Revel A, Shveiky D, Laufer N. Treatment of recurrent IVF failure and human leukocyte antigen similarity by intravenous immunoglobulin. Reprod Biomed Online 2005;11:745-9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
GiudiceLC. Growth factors and growth modulators in human uterine endometrium: Their potential relevance to reproductive medicine. Fertil Steril 1994;61:1-17.
Dimitriadis E, White CA, Jones RL, Salamonsen LA. Cytokines, chemokines and growth factors in endometrium related to implantation. Hum Reprod Update 2005;11:613-30.
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.
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.
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.
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.