{"paper_id":"ee7598ff-3528-4f34-a806-baad0cf11158","body_text":"Endometrium is one of the main factors in implantation and pregnancy. Pregnancy rate\nis increased with growing endometrial thickness. In several studies, the minimum\nendometrium thickness for embryo transfer was reported to be 7 mm ( El-Toukhy  et al. , 2008 ;  Richter  et al. , 2007 ). Several\nmethods are performed for endometrial preparation in frozen-thawed embryo transfer\n(FET) cycles, and there is little consensus on the most effective route. Some FET\ncycles are cancelled due to thin endometrium despite routine treatment, and there is\nno established protocol for this condition. Extended estrogen treatment and adjuvant\ntherapy, such as low dose Aspirin, vaginal Sildenafil, Pentoxifylline and\nintrauterine perfusion with granulocyte-colony stimulating factor (G-CSF) have been\nused for thin endometrium, but there isn't any proved evidence in this treatment\n( Barad  et al. , 2014 ;\n Chang  et al. , 2015 ;  Eftekhar  et al. , 2014 ;  Gleicher  et al. , 2013 ;  Groenewoud  et al. , 2013 ;  Lebovitz & Orvieto, 2014 ;  Xu  et al. , 2015 ).\nIntrauterine infusion of platelet-rich plasma (PRP) is a new approach that has been\nsuggested for the treatment of thin endometrium ( Chang  et al. , 2015 ). PRP is blood plasma prepared from\nfresh whole blood that has been enriched with platelets. It is collected from\nperipheral veins and contains several growth factors such as vascular endothelial\ngrowth factor (VEGF), epidermal growth factor (EGF), platelet derived growth factor\n(PDGF), transforming growth factor (TGF) and other cytokines that stimulate\nproliferation and growth. Recently, PRP has been used in several medical conditions\nin ophthalmology, orthopedics, surgery and wound healing but it's efficacy in\nendometrial growth has not been fully elucidated. The aim of this study was to\nevaluate the effectiveness of intrauterine infusion of PRP in the treatment of thin\nendometrium in FET cycles ( El-Anwar  et\nal. , 2016 ;  Lee  et\nal. , 2016 ;  Maria-Angeliki\n et al. , 2015 ;  Picard\n et al. , 2015 ;  Ronci\n et al. , 2015 ;  Rossi\n et al. , 2016 ;  Sadabad  et al. , 2016 ).\n\nTen patients who had a history of cancelled cycles due to inadequate endometrial\ngrowth (less than 7 mm) in the past FET cycles despite standard treatments, were\nrecruited into the study performed in the IVF center, Taleghani Hospital, Tehran,\nIran from September 2015 to May 2016. All patients signed an informed written\nconsent. The study was approved by the ethical committee of the Shahid Beheshti\nUniversity of Medical Sciences (SBMU) (IR.SBMU.SM.REC.1394.92). Patients'\ncharacteristics and FET outcome data are summarized on  Table 1 .\nPatients' characteristics and FET outcomes\nEndometrial thickness (mm): Before PRP/48 h after first PRP/48h after\nsecond PRP\nDOR: Diminished ovarian reserve\nMiscarriage\nHysteroscopic examination was performed before the cycle, if it had not been done\npreviously. Hormone replacement therapy (HRT) was performed for endometrial\npreparation in all participant: estradiol valerate (Progynova; Bayer Schering\nPharma, France) 6 mg/d was started on the 2 nd  or 3 rd  day of\nthe mensural cycle and it was increased to 8 mg/d on day 9-10 because of inadequate\nendometrial growth (< 7 mm). PRP was performed on day 11-12 in all the patients\ndue to thin endometrium and it was repeated on day 13-14. During the cycle, whenever\nthe endometrial thickness was more than 7 mm, suppository progesterone (Cyclogest;\nActavis, UK limited, England) 400 mg twice-a-day was started and embryo transfer\n(ET) was carried out per embryonic stage. Estradiol valerate and progesterone\nsupplementation were continued for 2 weeks after ET and if the serum βHCG was\npositive, hormone supplementations were continued until 12 weeks of gestation.\nTransvaginal ultrasound was performed by an expert gynecologist with a fellowship in\ninfertility by one machine. Endometrial thickness was measured at the thickest part\nin the longitudinal axis of the uterus.\nPRP was prepared from autologous blood using a two-step centrifuge process. On the\n9 th  or 10 th  day of the mensural cycle, 17.5 ml of\nperipheral venous blood was drawn in the syringe that contained 2.5 ml of Acid\nCitrate A Anticoagulant solution (ACD-A) (Arya Mabna Tashkhis, Iran) and centrifuged\nimmediately at 1200 rpm for 12 min to separate the red blood cells. The plasma was\ncentrifuged again at 3300 rpm for 7 min to obtain the PRP. Then, 0.5 ml of PRP was\ninfused into the uterine cavity with the IUI catheter (Takwin, Iran).\nThe primary outcome was endometrial expansion and the secondary outcomes were\nchemical and clinical pregnancies, determined by positive serum βHCG, 2 weeks\nafter ET and the presence of fetal hear beat in the transvaginal ultrasound 5 weeks\nafter ET.\n\nA total of 10 patients with a history of FET cancellation due to thin endometrium\nwere recruited into the study. Uterine cavity abnormalities were not detected before\nstarting the cycle. Four participants had a past of therapeutic resectoscopic\nhysteroscopy due to Asherman's syndrome and myoma. All the participants needed PRP\nin the treatment cycles due to inadequate endometrium growth. Endometrial thickness\nincreased at 48 h after the first PRP and reached more than 7 mm after the second\nPRP in all patients. Embryo transfer was then carried out for all of them. Five\npatients were pregnant and in four of them the pregnancy progressed normally.\n\nPRP is autologous blood plasma that has been enriched with platelets at about 4-5\ntimes more than the circulating blood. PRP can stimulate proliferation and\nregeneration with a large amount of growth factors and cytokines, including PDGF,\nTGF, VGEF, EGF, fibroblast growth factor (FGF), insulin-like growth factor I, II\n(IGF I, II), interleukin 8 (IL-8) and connective tissue growth factor (CTGF).\nCurrently, PRP infusion is being increasingly used in several fields in medicine\nsuch as nerve injury, osteoarthritis, chronic tendinitis, bone repair and\nregeneration, cardiac muscles, alopecia, plastic surgery and oral surgery, but there\nis limited experience in gynecology and obstetrics ( Alcaraz  et al. , 2015 ;  Borrione  et al. , 2010 ;  Patel  et al. , 2016 ;  Yu\n et al. , 2011 ).\nFor the first time, Chang reported the efficacy of intrauterine infusion of PRP for\nendometrial growth in women with thin endometrium. In that trial, PRP was infused in\n5 women with inadequate endometrium who had poor response to conventional therapy\nduring the FET cycle. The proper response to treatment was reported in all of them,\nand normal pregnancy was reported in 4 women ( Chang\n et al. , 2015 ).\nAdequate endometrial thickness is a main factor for implantation and pregnancy. Women\nwith persistent thin endometrium often do not undergo embryo transfer. Several\nmethods have been described for endometrial preparation but there is not any\ndefinitive method yet. In recent years, intrauterine infusion of G-CSF has been\nstudied but inconsistent results have been reported. Some researchers reported that\nG-CSF favors endometrial growth and pregnancy. G-CSF is a cytokine that stimulates\nneutrophilic granulocyte differentiation and proliferation, it may induce\nendometrium proliferation and growth, thus improve pregnancy outcome. According to\nthis hypothesis, local infusion of PRP that contains several growth factors and\ncytokines may improve endometrial growth and receptivity. PRP is collected from\nautologous blood sample, so in comparison to G-CSF, PRP is more accessible and\naffordable ( Gleicher  et al. ,\n2011 ;  Lucena & Moreno-Ortiz,\n2013 ).\nThe results of our pilot study revealed the efficacy of PRP on endometrial growth.\nAdequate endometrial growth was found in all the participants after two PRP\ninfusions in all patients who had a history of cycle cancellation due to thin\nendometrium. At the present, there is limited evidence in this regard. Hence, we\nsuggest further clinical trials in this context. PRP is a safe procedure, with\nminimal risks of transmission of infectious disease and immunological reactions\nsince it is made from autologous blood samples.\n\nAccording to this study, it seems that PRP was effective for endometrial growth in\npatients with thin endometrium.","source_license":"CC-BY-4.0","license_restricted":false}