{"paper_id":"d4c75080-597b-4e53-8f91-215c6789d01e","body_text":"Review began\n 01/17/2022 \nReview ended\n 07/16/2022 \nPublished\n 08/12/2022\n© Copyright \n2022\nAbduljabbar et al. This is an open access\narticle distributed under the terms of the\nCreative Commons Attribution License CC-\nBY 4.0., which permits unrestricted use,\ndistribution, and reproduction in any\nmedium, provided the original author and\nsource are credited.\nThe Effect of Autologous Platelet-Rich Plasma\nTreatment on In Vitro\nFertilization/Intracytoplasmic Sperm Injection\nand Its Impact on the Endometrium and Clinical\nPregnancy Rate\nHassan \nS. Abduljabbar \n \n, \nHowida Hashim \n \n, \nHanin H. Abduljabar \n \n, \nAmal A. Elnaeim \n \n, \nNajwan H.\nAbduljabar \n1.\n Obstetrics and Gynecology, Dr. Erfan and Bagedo General Hospital (EBGH), Jeddah, SAU \n2.\n In Vitro Fertilization, Dr.\nErfan and Bagedo General Hospital (EBGH), Jeddah, SAU \n3.\n Obstetrics and Gynecology, King Faisal Specialist Hospital,\nJeddah, SAU\nCorresponding author: \nHassan \nS. Abduljabbar, \nprofaj17@yahoo.com\nAbstract\nBackground\nEndometrial thickness has been identified as a prognostic factor for improving the pregnancy rate for\npatients with female infertility.\nStudy question\nDoes platelet-rich plasma (PRP) treatment affect the endometrial thickness and pregnancy rate after an in\nvitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle?\nAim\nThis study aims to evaluate the effects of autologous PRP treatment on IVF/ICSI, endometrium, and clinical\npregnancy rate.\nMaterials, setting, and methods\nThis is a prospective, non-blind, randomized controlled study. The ethical committee of the Jeddah IVF\nCenter approved the study, and informed written consent was obtained from all patients. We recruited\npatients who consulted at the Jeddah IVF Center from September 2020 to May 2021.\nResults\nA total of 70 patients undergoing IVF/ICSI and embryo transfer (ET) were randomly divided by simple\nrandomization into two groups: those who received PRP treatment after oocyte pickup (OPU) (group A) and\nthose who did not receive PRP treatment (control, group B). The endometrial thickness was measured after\nOPU and before ET. The mean ages of patients in groups A and B were 35.91 ± 4.09 (range: 24-43) and 34.63\n± 4.26 (range: 25-43), respectively, which were not statistically significant (P < 0.223). In the PRP cases, the\ntypes of infertility were primary in 16 (45.7%) and secondary in 19 (54.3%), and the causes of infertility were\nmale factors in 24 (68.6%), unexplained in five (14.3%), ovulatory factor in two (5.6%), endometriosis in two\n(5.6%), tubal factor in one (2.9%), and preimplantation genetic diagnosis (PGD) in one (2.9%). In the control\ngroup, the types of infertility were primary in 14 (40%) and secondary in 21 (60%), and the causes of\ninfertility were male factors in 21 (60%), unexplained in three (8.6%), ovulatory factor in eight (22.9%),\nendometriosis in one (2.8), and PGD in two (5.6%). In our study, we found that the mean endometrial\nthicknesses after OPU were 0.594 ± 0.089 (range: 0.4-0.7) and 0.589 ± 0.090 (range: 0.6-0.9) in the treatment\nand control groups, respectively (odds ratio (OR): 0.005; 95% confidence interval (CI): 0.376-0.047; P <\n0.791). Before ET, the mean endometrial thicknesses were 0.86 ± 0.090 (range: 0.7-0.9) and 0.7464 ± 0.06\n(range: 0.7-1) in groups A and B, respectively, (OR: 0.114; 95% CI: 0.763-0.151; P < 0.001). Of the 35 patients\nin each group, 12 (34.3%) and five (14.3%) had confirmed pregnancies in groups A and B, respectively (OR:\n0.319; 95% CI: 0.099-1.036; P < 0.05), which is statistically significant.\nConclusion\nAutologous PRP treatment in IVF/ICSI improves the endometrial thickness and clinical pregnancy rate.\nCategories:\n Endocrinology/Diabetes/Metabolism, Medical Education, Obstetrics/Gynecology\nKeywords:\n icsi, ivf, prp, endometrial thickness, clinical pregnancy rate\n1\n2\n3\n1\n1\n \n Open Access Original\nArticle\n \nDOI:\n 10.7759/cureus.27913\nHow to cite this article\nAbduljabbar H S, Hashim H, Abduljabar H H, et al. (August 12, 2022) The Effect of Autologous Platelet-Rich Plasma Treatment on In Vitro\nFertilization/Intracytoplasmic Sperm Injection and Its Impact on the Endometrium and Clinical Pregnancy Rate. Cureus 14(8): e27913. \nDOI\n10.7759/cureus.27913\n\nIntroduction\nInfertility is defined as a failure of clinical pregnancy after one year of regular unprotected sexual\nintercourse. Approximately 8%-15% of reproductive-aged couples worldwide suffer from infertility \n[1]\n.\nInfertility causes physical, emotional, and social problems in families \n[2]\n. The central issue of in vitro\nfertilization (IVF) treatment is a failure of implantation due to the quality of the embryo or endometrial\nreceptivity. A thin endometrium (defined as an endometrial thickness of <7 mm) on the day of ovulation is\nmost likely to be the cause of failure \n[3]\n.\nOne of the treatments for recurrent implantation failure is platelet-rich plasma (PRP), a concentrated blood\nproduct rich in platelets \n[4,5]\n. In general, whole blood comprises four main components: plasma, platelets,\nred blood cells, and white blood cells. Plasma consists of water, protein, and dissolved salts; more than half\nof the blood volume is plasma, which provides the medium for all other elements transported throughout\nthe body \n[6]\n.\nPRP contains multiple growth factors that typically help the body heal after an injury. Aside from\naccelerating wound healing, PRP also possessed anti-aging properties, which is why it has been used for the\npast 20 years in different areas of medicine \n[7]\n. Platelets (thrombocytes) are not only involved in the clotting\nprocess but also release other substances and growth factors. Red blood cells (erythrocytes) are involved in\noxygen-carbon dioxide exchange, carrying oxygen to tissues and removing carbon dioxide from the\nbody. White blood cells (leukocytes) are primarily responsible for immunity \n[8]\n.\nAlthough persons undergoing PRP treatment can receive PRP from a different person, this is rarely\nperformed as PRP is usually extracted from the same individual that it will be given to. PRP extraction\nconsists of three steps. Step 1 is withdrawing blood from the individual. Step 2 is centrifuging the obtained\nblood for 15 minutes. Step 3 is collecting the plasma (now rich in platelets and devoid of cellular\ncomponents) in preparation for its injection \n[9]\n.\nThe objective of this study was to identify the effect of autologous PRP treatment on IVF/ICSI and on the\nendometrial thickness and clinical pregnancy rate.\nMaterials And Methods\nThis is a prospective, non-blind, randomized controlled study. The ethical committee of the Jeddah IVF\nCenter approved the study (EBGH-002 series of 2020), and informed written consent was obtained from all\npatients. We recruited patients who consulted at the Jeddah IVF Center from September 1, 2020, to May 1,\n2021.\nSample size\nThe sample size was calculated based on the number of patients per six months (200) and the expected 5%\nrepeated failure rate. The final sample size was 70 patients, which was divided into two groups.\nSubjects undergoing IVF/ICSI-frozen embryo transfer (FET) were included in the study if they fulfilled the\nfollowing inclusion criteria: repeated failures, age between 18 and 44 years, type of infertility eligible for\nIVF/ICSI, and endometrial thicknesses between 0.4 and 0.7 cm. Patients younger than 18 and older than 44\nyears, not eligible for IVF/ICS, who have poor embryo quality, who are not suitable for ET, who have an\nendometrial thickness of <0.7 cm, or with a concurrent active infection were excluded from the study.\nThe subjects were randomized into groups A (for PRP) and B (no PRP) via simple random sampling. The\nsubjects’ names were drawn randomly from a pool in which each had an equal probability of being chosen.\nAn experienced gynecologist specializing in infertility performed a transvaginal ultrasound on each subject\nto measure the endometrial thickness using a single machine.\nPRP was prepared via a two-step centrifugation method from autologous blood.\nOn the day of oocyte pickup (OPU), 10-20 mL of peripheral venous blood from each subject was drawn into a\nsyringe that contained 2.5 mL of acid citrate anticoagulant solution (Heraeus Labofuge 400 functional line +\nswinging rotor + four buckets with caps (75008370)) and centrifuged at 1,500 rpm for 10 minutes. The\nobtained plasma was then centrifuged at 3,000 rpm for five minutes to extract the PRP. Then, 0.5 mL of PRP\nwas infused into the uterine cavity of each subject using an intrauterine insemination (IUI) catheter after\nthe OPU.\nIn each group, we analyzed the following variables: age in years, type of infertility (primary or secondary),\ncausative factor in males, unexplained, ovulatory factor, endometriosis, and tubal factor. Finally, after\npreimplantation genetic diagnosis, the two groups were compared.\nWe identified the number of embryos and the day of transfer (day 3 or day 5), and depending on embryo\n2022 Abduljabbar et al. Cureus 14(8): e27913. DOI 10.7759/cureus.27913\n2\n of \n5\n\nquality, endometrial thickness after OPU and just before the ET were measured. Then, clinical pregnancy is\nconsidered positive when patients had a positive beta-hCG test result.\nThe primary outcome was the endometrial thickness, and the secondary outcome was clinical pregnancy as\ndetermined by a positive serum beta-hCG test result.\nStatistical analysis\nThe paired sample t-test and chi-square test were used for statistical analysis, and cross-tabulation was\nperformed using the SPSS version 22 software (IBM Corp., Armonk, NY, USA). P < 0.05 was considered\nstatistically significant.\nResults\nA total of 70 patients undergoing IVF/ICSI and ET were randomly divided by simple randomization into\ngroup A, in which the subjects received PRP after OPU, and group B, in which the subjects did not receive\nPRP.\nThe mean ages of the subjects in groups A and B were 35.91 ± 4.49 years (range: 24-43 years) and 34.63 ±\n4.26 years (range: 25-43 years), respectively, with the difference not reaching statistical significance (P <\n0.2243). The types and causes of infertility are shown in Table \n1\n.\nVariable\nPRP cases (n = 35)\nControl (n = 35)\nOdds ratio (lower-upper)\nP-value\nMean age (years) (range)\n35.91 ± 4.49 (24-43)\n34.63 ± 4.26 (25-43)\n1.05 (-0.82-3.37)\n0.223\nInfertility\n \n \n1.263 (0.49-3.26)\n0.405\nPrimary (%)\n16 (45.7)\n14 (40)\nSecondary (%)\n19 (54.3)\n21 (60)\nReason for infertility\n \n \n \n0.383\nMale factor (%)\n24 (68.6)\n21 (60)\nUnexplained (%)\n5 (14.3)\n3 (8.6)\nOvulatory factor\n2 (5.6)\n8 (22.9)\nEndometriosis (%)\n2 (5.6)\n1 (2.8)\nTubal factor (%)\n1 (2.9)\n0 (0)\nPGD (%)\n1 (2.9)\n2 (5.6)\nNumber of embryos\n \n \n \n0.861\n1 (%)\n10 (28.6)\n8 (22.9)\n2 (%)\n11 (31.4)\n12 (34.3)\n3 (%)\n14 (40)\n15 (42.9)\nDay of transfer\n \n \n \n0.5\nDay 3 (%)\n5 (14.3)\n4 (11.4)\n \nDay 5 (%)\n30 (85.7)\n31 (88.6)\n1.29 (0.32-5.28)\nTABLE\n 1: Patient characteristics\nPRP: platelet-rich plasma; PGD: preimplantation genetic diagnosis\nThe mean endometrial thicknesses in groups A and B after OPU were 0.59 ± 0.089 (range: 0.4-0.7) and 0.58 ±\n0.090 (range: 0.4-0.7), respectively (odds ratio (OR): 0.005; 95% confidence interval (CI): 0.0376-0.047; P <\n0.791). It is not statistically significant. Before ET, the mean endometrial thicknesses in groups A and B were\n0.86 ± 0.0.90 (range: 0.7-0.9) and 075. ± 0.07 (range: 0.7-1.0), respectively (OR: 0.114; 95% Cl: 0.0763-0.151;\nP < 0.001). In the 35 patients in each group, 12 and five had confirmed pregnancies in groups A and B,\n2022 Abduljabbar et al. Cureus 14(8): e27913. DOI 10.7759/cureus.27913\n3\n of \n5\n\nrespectively (Table \n2\n).\n \nPRP cases (n = 35)\nControl (n = 35)\nOdds ratio (lower-upper)\nP-value\nEndometrial thickness after OPU (mean (range))\n0.59 ± 0.089 (0.4-0.7)\n0.58 ± 0.09 (0.4-0.7)\n0.005 (0.0376-0.047)\n0.791\nEndometrial thickness before ET (mean (range))\n0.86 ± 0.09 (0.7-0.9)\n0.75 ± 0.07 (0.7-1.0)\n0.114 (0.0763-0.151)\n0.0001\nPregnancy (yes/no) (%)\n12 (34.3%)/23 (65.7%)\n5 (14.3%)/30 (85.7%)\n0.319 (0.099-1.036)\n0.05\nTABLE\n 2: Endometrial thickness and pregnancy rate in the PRP and control groups\nNumber (%)\nOPU: oocyte pickup; ET: embryo transfer\nDiscussion\nIntrauterine PRP infusion is used to treat the endometrium. PRP is rich in platelets; it is derived from blood\nplasma, which is prepared from fresh whole blood. PRP therapy may potentially improve a thin endometrium\nthat is unresponsive to conventional treatment and represents a new method for the thin endometrium with\npoor response.\nIt has been reported that PRP promotes endometrial growth and improves pregnancy outcomes in patients\nwith a thin endometrium \n[10]\n. Do we know the suitable endometrial thickness for conceiving? The\nendometrial thickness is positively correlated with the number of pregnancy losses and live births in IVF.\nHence, to increase the chances of live birth and minimize pregnancy loss, the optimal endometrial thickness\nshould be >7 mm \n[11]\n.\nThe adverse effects of PRP therapy include pain at the injection site, infection, allergic reaction, hematoma,\nand skin discoloration \n[12]\n.\nOur study aimed to analyze the effect of intrauterine PRP therapy in subjects undergoing IVF/ICSI or FET\ncycles. The effect of PRP treatment on endometrial thickness and clinical pregnancy was determined and\nrecorded. In our study, we found that the mean endometrial thicknesses after OPU were 0.594 ± 0.089 and\n0.589 ± 0.090 in the treatment and control groups, respectively; the difference between groups was not\nstatistically significant (P < 0.791). Meanwhile, the mean endometrial thicknesses before ET were 0.86 ±\n0.094 and 0.746 ± 0.066 in the treatment and control groups, respectively; the difference was statistically\nsignificant (P < 0.0001). The effectiveness of intrauterine\n \nPRP treatment in improving a thin endometrium\nwas studied in the trial, and the results show that PRP treatment results in thicker endometrium in patients\nwith a thin endometrium that is refractory to treatment \n[13]\n. PRP treatment also enhances the growth of\nendometrium and pregnancy outcomes in women with a thin endometrium \n[14]\n. Evaluation of the\neffectiveness of PRP in treating a thin endometrium was tried, and it was found to improve endometria. In\naddition, PRP treatment also improved implantation, pregnancy, and live birth rates of subjects with a thin\nendometrium \n[15]\n.\nIn infertile women with a history of failed implantation, intrauterine PRP infusion before frozen ET was\nfound to have no significant effect on pregnancy \n[16]\n. A prospective cohort with a large number of patients\nis necessary to explore the underlying mechanisms responsible for PRP’s beneficial effects and further\ninvestigate the benefits of PRP treatment in women with a thin endometrium who have undergone frozen\nET (FET). Chang et al. found that PRP improves endometrial proliferation, embryo implantation rate, and\nclinical pregnancy rate in women with a thin endometrium after FET \n[10]\n.\nConclusions\nAutologous PRP treatment in IVF/ICSI improves the endometrium and clinical pregnancy rate. Although\nthere is increasing evidence suggesting the possible benefit of PRP treatment on the endometrium of\ninfertile women, the mechanism is not very clear and needs further explication. Further, careful studies,\nespecially RCTs, on larger scales are required, and follow-ups on long-term health and complications are\nneeded.\nAdditional Information\nDisclosures\nHuman subjects:\n Consent was obtained or waived by all participants in this study. The Jeddah Fertility\n2022 Abduljabbar et al. Cureus 14(8): e27913. DOI 10.7759/cureus.27913\n4\n of \n5\n\nResearch Ethical Committee issued approval number EBGH-002 series 2020. The Ethical Committee of the\nJeddah IVF Center approved the study, and all patients signed informed written consent. \nAnimal subjects:\nAll authors have confirmed that this study did not involve animal subjects or tissue. \nConflicts of interest:\nIn compliance with the ICMJE uniform disclosure form, all authors declare the following: \nPayment/services\ninfo:\n All authors have declared that no financial support was received from any organization for the\nsubmitted work. \nFinancial relationships:\n All authors have declared that they have no financial\nrelationships at present or within the previous three years with any organizations that might have an\ninterest in the submitted work. \nOther relationships:\n All authors have declared that there are no other\nrelationships or activities that could appear to have influenced the submitted work.\nAcknowledgements\nWe want to express our heartfelt appreciation to all medical staff in the operating room. We would also like\nto express our gratitude to all those who helped us during the writing of this manuscript (Dr. Ahmed A.J. and\nMiss N. Jardah) and appreciation to all the reviewers and editors for their views and ideas.\nReferences\n1\n. \nVander Borght M, Wyns C: \nFertility and infertility: definition and epidemiology\n. Clin Biochem. 2018, 62:2-\n10. \n10.1016/j.clinbiochem.2018.03.012\n2\n. \nPolisseni F, Carvalho MA, Pannain GD, Souza LC, Oliveira VA: \nThe search for assisted reproduction: profile\nof patients seen in the fertility outpatient clinic of a public hospital\n. JBRA Assist Reprod. 2020, 24:305-9.\n10.5935/1518-0557.20200008\n3\n. \nMahajan N, Sharma S: \nThe endometrium in assisted reproductive technology: how thin is thin?\n. 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