Eight studies were compared for the measurement of endometrial thickness before and after PRP infusion in study groups vs. control groups. Clinical pregnancy outcomes are included following PRP treatment.
\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"7780",leadTitle:null,fullTitle:"Ontological Analyses in Science, Technology and Informatics",title:"Ontological Analyses in Science, Technology and Informatics",subtitle:null,reviewType:"peer-reviewed",abstract:"Advance exact science of nowadays inherited the original ontology’s its efforts to systemize and conceptualize. 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She obtained her MSc in Chemical Engineering and in Pharmaceutical Sciences and received her Ph.D. (2013) in Chemical and Biological Engineering from the University of Porto (Portugal). J.A.Loureiro published 34 papers in international peer-review journals (h-index 14).",coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"82791",title:"Dr.",name:"Maria Carmo",middleName:null,surname:"Pereira",slug:"maria-carmo-pereira",fullName:"Maria Carmo Pereira",profilePictureURL:"https://mts.intechopen.com/storage/users/82791/images/system/82791.jpg",biography:"Maria do Carmo Pereira completed the PhD in Chemical Engineering in 1998 at the Universidade do Porto, Faculdade de Engenharia, and a graduation in Chemical Engineering in 1993 at Universidade do Porto, Faculdade de Engenharia, Portugal. She is Assistant Professor at Universidade do Porto, Faculdade de Engenharia and the Group Leader of Supramolecular Assemblies at the Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE). The main research areas that she is working are: i) Nanotechnology and interfacial phenomena; supramolecular interactions including novel nano-engineered biomaterials for therapeutic applications; development of nanostructured electrochemical immunosensors for detection of neurodegenerative diseases; and environment (air quality and atmospheric pollution with emphasis on public and environmental health). During her research career she has authored and co-authored more than 140 articles in peer-reviewed international journals (H-index of 31). She received 10 awards and/or honors.",institutionString:"University of Porto",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Porto",institutionURL:null,country:{name:"Portugal"}}}],coeditorOne:{id:"183036",title:"MSc.",name:"Maria João",middleName:null,surname:"Ramalho",slug:"maria-joao-ramalho",fullName:"Maria João Ramalho",profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:"Maria João Ramalho holds a PhD in Biological and Chemical Engineering. Currently, MJ Ramalho is a researcher at LEPABE (Laboratory for Process Engineering, Environment, Biotechnology and Energy), and a visiting researcher at i3S (Institute for Research and Innovation in Health, University of Porto). Her research interests focuses on the design, optimization, characterization and in vitro evaluation of nanoparticles for the encapsulation of bioactive compounds for several health applications.\r\nHer PhD thesis focused on the development of efficient nanocarriers to deliver drugs to the brain. She is the author of 10 papers in international journals and 2 book chapters.",institutionString:"University of Porto",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Porto",institutionURL:null,country:{name:"Portugal"}}},coeditorTwo:{id:"321636",title:"Dr.",name:"Joana A.",middleName:null,surname:"Loureiro",slug:"joana-a.-loureiro",fullName:"Joana A. Loureiro",profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:"Joana Loureiro is MSc in Chemical Engineering and in Pharmaceutical Sciences and received her PhD (2013) in Chemical and Biological Engineering from the University of Porto (Portugal). She is Researcher at the Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE) and Invited Professor assistant at Universidade do Porto, Faculdade de Engenharia. Her main research areas of interest are: i) nanotechnology and interfacial phenomena; ii) effects of fluorinated systems and peptides on the aggregation of amyloid beta peptide; iii) conformational studies of proteins and peptides self-organized systems and polymer surfaces; and iv) design and production of inorganic and polymeric nano-systems for pharmaceutical and food applications. J.A.Loureiro published 34 papers in international peer review journals (h-index 14).",institutionString:"University of Porto",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Porto",institutionURL:null,country:{name:"Portugal"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"19",title:"Pharmacology, Toxicology and Pharmaceutical Science",slug:"pharmacology-toxicology-and-pharmaceutical-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194667",firstName:"Marijana",lastName:"Francetic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194667/images/4752_n.jpg",email:"marijana@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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\nEvidence shows that PRP infusion directly into the endometrium enhances lining development in patients suffering from chronically refractive or underdeveloped endometrium. Chemical pregnancy in patients that underwent PRP infusion with frozen embryo transfer was 50% (108/216) in comparison to 17.1% (16/93) in patients that did not receive PRP treatment.
\nThe overall objective of this review was to determine if platelet-rich plasma (PRP) infusions are viable alternatives to current treatments for thin endometrial lining, and to distinguish if PRP infusions increase endometrial thickness and implantation in patients that underwent treatment in eight different case studies.
\nPlatelet-rich plasma is prepared from autologous whole blood collected from a patient’s peripheral vein, mixed with an acid citrate dextrose solution A (ACD-A) anticoagulant, and processed to separate platelets from remaining blood components [1]. Platelet-rich plasma is recognized as plasma from autologous blood with 4–5 times the concentration of normal platelet levels; these high concentrations of PRP contain cytokines and growth factors including: vascular endothelial growth factor (VEGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) [2, 3]. Because of the expression of several regenerative growth factors, PRP is being used in several fields of medicine to promote wound regeneration including: arthritis, nerve injury, tendinitis, bone regeneration, cardiac muscle repair, alopecia, and plastic and oral surgery recovery [4, 5]. When the body is injured, a natural healing process occurs that floods the wound site with activated platelets that instantly promote cell regeneration and proliferation. It is theorized that PRP may be used to promote the same growth and proliferation in endometrium that have previous suboptimal growth patterns. Similar research, such as endometrial scratching, has been studied to promote the generation of growth factors to increase implantation; however, the concentration of platelet levels within direct PRP infusion into the endometrium is vastly superior to the natural, localized endometrial healing process that occurs with the scratching method.
\nOther treatment strategies for thin endometrial lining have varied throughout recent years, but have been inclusive of extended use of exogenous estradiol, low-dose aspirin, vitamin E supplementation, and use of granulocyte colony stimulation factor (G-CSF), but not all have been proven effective [6, 7, 8, 9]. The minimal endometrial thickness suggested for successful implantation at embryo transfer is 7 mm [10], however, there are those that argue endometrial lining is a poor indicator for pregnancy outcomes and therefore should not be heavily considered [11]. During typical HRT cycles, estradiol administration is regulated from day 2 or day 3 of an average 28 day cycle and continues until the endometrial lining reaches optimal thickness for transfer (typically >7 mm) at which time progesterone administration then occurs [12]. This model is utilized in IVF clinics globally; however, patients who fail to reach the recommended endometrial thickness often undergo canceled cycles in which they have wasted valuable time, medications, and expenses without receiving an embryo transfer.
\nThin endometrial lining or suboptimal endometrial growth is a problem that affects up to 5% of the patients undergoing IVF treatment [13]. These patients often experience the emotionally and physically traumatizing effects of canceled cycles or repeated implantation failure (RIF). It is proven that growth factors expressed in the endometrium of women with RIF are less than those expressed in normal fertile women [14]. These growth factors can be stimulated by infusion of autologous PRP into the endometrium in conjunction with HRT prior to embryo transfer. However, many factors are involved in successful embryonic implantation, not limited to embryo quality, but also a synchrony between the embryo and the endometrium in addition to any immunological factors [15]. Without optimal endometrial growth, this synchrony becomes far less likely as the endometrium does not express the adequate genes nor growth factors involved in embryonic implantation [16, 17].
\nThrough multiple studies, PRP processing was performed similarly. On the 10th day of HRT, Chang and coworkers drew 15 ml of autologous blood into a tube with 5 ml of Acid Citrate A Anticoagulant (ACD-A) and centrifuged; separating red blood cells, a gel buffy coat, and cellular plasma. The plasma and buffy coat were then transferred to a second tube and centrifuged again, yielding 0.5–1 ml of PRP [18]. Both Zadehmodarres and Nazari and their colleagues drew 17.5 ml of blood on day 9 or 10 of HRT into 2.5 ml of ACD-A and similarly centrifuged twice to obtain 0.5 ml of PRP [19, 20]. Tandulwadkar et al. used 10 ml of autologous blood into an unspecified amount of ACD-A; which was centrifuged sequentially utilizing first a soft spin for 15 minutes, followed by a hard spin for 6 minutes, again yielding between 0.5 and 0.8 ml of PRP [21]. Eftekhar and others used an alternative approach, collecting PRP on the 13th day of HRT by drawing 8.5 ml of peripheral venous blood into a syringe containing 1.5 ml of ACD-A that was then centrifuged for 10 minutes; following first centrifugation, the buffy coat and plasma layer were then removed and centrifuged again, yielding 1.5 ml of PRP [22]. Meanwhile, Hounyoung et al. collected 18 ml of venous blood in a 30 ml syringe prepared with 2 CC of ACD-A and then centrifuged twice to obtain 0.7–1.0 ml of PRP [23]. Nazari and coworkers performed a follow-up study utilizing a double-blinded trial in which 30 patients underwent PRP infusion, prepared in the same manner as the initial pilot study [19], and 30 patients underwent placebo PRP infusions [24]. Chang et al. performed a secondary study as well, involving a larger cohort of patients compared against a control group, and performed PRP collection as previously reported [18, 25]. All studies transfused the PRP into the endometrium using an IUI catheter, and then repeated intravaginal ultrasound 48 hours later to measure endometrial growth; patients who did not reach the desired lining thickness (>7 mm deemed adequate in all studies) were then treated with a second round of PRP infusion [18, 19, 20, 21, 22, 23, 24, 25].
\nIn the past, IVF clinics allowed for natural cycle frozen embryo transfer in which they permitted endometrial lining to develop on its own, but it resulted in many timing issues with need for frequent monitoring and cancelation due to anovulation and poor development of the endometrium. Today, most clinics have moved fully to HRT protocols that allow for artificial stimulation of the endometrium that can be easily tracked utilizing blood serum and ultrasound assessment to time an embryo transfer concordant with a receptive endometrium. In humans, estrogen stimulates endometrial growth and induces progesterone receptors as it moves naturally through the menstrual cycle. After ovulation, the endometrium is exposed to progesterone which induces morphological and biochemical changes that alter the endometrium from the proliferative phase to the secretory phase [17]. In HRT cycles, estradiol administration (typically Estradiol Valerate) occurs until the lining has reached a thickness of greater than 7 mm, at which time progesterone is then administered for the number of days proportional to the embryo being transferred (i.e., a day 6 blastocyst will receive progesterone for 6 days) and then the embryo is transferred to a supposedly receptive endometrium [26, 27]. In these HRT cycles, patients receive estradiol during the follicular phase that inhibits gonadotropin secretion and prevents follicular development and ovulation. The start of the luteal phase can be exactly pinpointed, as it starts when progesterone is added to estradiol dosages.
\nHRT allows for artificial stimulation of endometrial growth via hormone administration orally, transdermally, intramuscularly, vaginally, subcutaneously, or a combination of both. Most clinics administer estradiol for several days until the endometrial lining has reach a point of optimal growth, at which time they will then administer progesterone to induce the secretory phase of cycle that promotes embryo implantation [21]. Each of the studies examined in this review conducted HRT protocols concordant with physician recommendation as follows:
\nChang et al.: In the pilot study, Estradiol Valerate (E2V) started at 3 mg/d on day 3 of menses and increased every 4 days up to a max of 12 mg/d; and in the cohort study, E2V started at 6 mg/d and subsequently increased to 12 mg/d [18, 25]. The pilot study included five patients suffering from chronically non-responsive thin endometrium (5.9–6.6 mm) who underwent PRP infusion on the 10th day of HRT and lining was measured via transvaginal ultrasound. In the cohort study, platelet-rich plasma infusion was also performed on the 10th day of HRT, and endometrial thickness was measured in both the control group and study group.
\nZadehmodarres et al.: Estradiol Valerate started at 6 mg/d on day 3 of menses, and increased to 8–9 mg/d. Suppository progesterone was started when endometrial thickness reached >7 mm and continued for 2 weeks after ET [19]. PRP infusion was administered on the 11th or 12th day of cycle and assessed 48 hours later.
\nNazari et al.: Estradiol Valerate started on day 2 or 3 of menses at 6 mg/d and was increased to 8 mg/d if lining did not reach >7 mm. When thickness reached 7 mm, progesterone suppositories, 4000 mg, were started twice daily [20, 24]. In the pilot study, 0.5 ml of PRP was infused into the endometrium of patients 48 hours prior to frozen embryo transfer in conjunction with an HRT cycle. In the follow-up RCT, PRP infusion or mock infusion was performed on day 11 or 12 of HRT cycle, modified from the initial pilot study, and lining was measured using transvaginal ultrasonography.
\nTandulwadkar et al.: Estradiol Valerate started at 6–8 mg/d concordant with baseline endometrial vascularity as measured by Power Doppler on day 1 of menses and increased to 12 mg/d if growth was not seen. Transvaginal ultrasounds were performed starting on day 7/8 [21]. Day of PRP infusion was not given in the initial study.
\nEftekhar et al.: In this study, the case group was treated with PRP and increased HRT, and the control group was just treated with increased HRT. For all women, E2V was started at 6 mg/d, then increased to 10 mg/d [22]. PRP infusion occurred on the 13th day of cycle and endometrial lining was measured transvaginally.
\nHounyoung et al.: Patients treated within this study began E2V administration on the second day of menses, starting at 4-6 mg/d and followed by PRP infusion on cycle day 10 [23]. PRP infusion was administered via IUI catheter and repeated 2–3 times in 3 day intervals until optimal endometrial thickness was achieved (>7 mm).
\nEight clinical trials were selected, all of which were inclusive of a total of 346 patients that underwent HRT in conjunction with PRP infusion. Of 346 patients, 313 underwent embryo transfer at either cleavage or blastocyst stage. The remaining 33 patients dropped out of the studies prior to embryo transfer due to persistently poor endometrial development [18, 19, 20, 21, 22, 23, 24, 25].
\nInclusion criteria remained relatively constant through all eight studies. All patients had a history of thin endometrial lining, repeat implantation failure, or two or more canceled cycles due to poor endometrial growth. All patients were between the ages of 18–42 years old and all had a normal BMI of <30%; donor egg cycles were not included due to the potential to skew the results. All patients that underwent embryo transfer post-PRP infusion reached an endometrial thickness of >7 mm, as deemed acceptable by the performing physicians.
\nAll patients with hematological and immunological disorders, hormonal disorders, chromosomal and genetic abnormalities and uterine abnormalities were excluded from the studies. All patients who did not reach optimal endometrial thickness post-PRP infusion were excluded from embryo transfer. Any patient of advanced maternal age (>42 years old) or increased BMI (>30%) was excluded from the studies.
\nFive patients were included in the initial pilot study by Chang et al. [18]. 48–72 hours post PRP, all five patients reached a minimum lining of 7 mm (7.0–8.0). All patients underwent frozen embryo transfer, and all five patients were pregnant (5/5) with an ongoing pregnancy rate of 80% (4/5).
\nZadehmodarres and colleagues [19] performed their study on 10 patients with previous canceled cycles due to thin endometrial development, four of which were diagnosed with Asherman’s Syndrome. All 10 patients reached adequate lining thickness for embryo transfer (7.0–7.5). All patients underwent frozen embryo transfer resulting in chemical pregnancy in 50% of patients (5/10) with an ongoing pregnancy rate of 40% (4/10).
\nThe pilot study by Nazari and coworkers [20] was based upon a study group of 20 patients suffering from RIF due to thin endometrial lining. All patients received a blastocyst stage transfer of one to two embryos that were graded morphologically normal. Chemical pregnancy was reported in 90% of patients (18/20) with an ongoing pregnancy rate of 80% (16/20).
\nTandulwadkar et al. [21] assessed not only endometrial thickness, but endometrial vascularity as well post PRP infusion as measured by serial transvaginal ultrasound. Of the 68 patients included in the study, 64 went on to achieve optimal lining thickness for frozen embryo transfer. Average mean lining thickness before PRP infusion was 5 mm, and 7.22 mm after PRP infusion. Of the 64 patients that received a frozen embryo transfer, endometrial vascularity increased in all patients. 60.1% (39/64) reported chemical pregnancy with an ongoing pregnancy rate of 45.3% (26/64).
\nA randomized control trial was performed by Eftekhar and others [22] in which 83 women participated; 40 were allocated to the study group and received PRP infusion, while 43 were placed in the control group and did not receive PRP. Prior to PRP infusion on the 13th day of cycle, there were no significant differences in endometrial lining as measured between the two groups; however, after PRP infusion, significant differences were noted (8.80 vs. 8.04 mm). Of the 40 women in the study group, 7 did not receive an embryo transfer due to persistently thin endometrium, whereas 10 women in the control group were excluded from frozen embryo transfer for the same reason. Thirty-three women in the study group and 33 women in the control group underwent cleavage stage frozen embryo transfer. In the study group, chemical pregnancy was reported in 42.2% (14/33) in comparison to the control group, which recorded chemical pregnancy in only 24.2% (8/33) of patients. Ongoing pregnancy rates were 33.3% (11/33) versus 18.2% (6/33), respectively.
\nHounyoung and colleagues [23] performed a pilot study on 24 patients with a history of refractory endometrium. Of the 24 patients initially included in the study, two patients were canceled, and two were lost to follow-up. Data was collected for the remaining 20 patients, all of whom received a frozen embryo transfer of 2–3 day 3 cleavage stage embryos. Among the study group, a chemical pregnancy rate of 30% (6/20) was reported with an ongoing pregnancy rate of 20% (4/20).
\nAfter an initial pilot study, Nazari et al. [24] performed a follow-up double blinded randomized control trial to validate their previous findings. Sixty patients were selected for inclusion in the study; 30 were randomly assigned to the study group to receive PRP infusion, and 30 were aliquoted to the control group in which a sham-catheter was utilized for mock PRP infusion. In the PRP group, lining increased to 7.21 ± 0.18 mm respectively, and in the mock infusion group, lining reached 5.76 ± 0.97 mm. Of the 30 patients in the study group, all patients received a frozen embryo transfer in comparison to just 6 that reached optimal lining (>7 mm) for frozen embryo transfer in the control group. Chemical pregnancy was recorded in 40% (12/30) of cases in the study group, and in 6.7% (2/30) in the control group. Ongoing pregnancy rate was 33.3% (10/30) in the PRP group, and 3.3% (1/30) in the control group.
\nChang and others [25] performed a follow-up randomized control trial to their initial pilot study as well, assigning 34 patients to the PRP infusion group and 30 patients to the control group, which received only HRT without PRP. In the study group, endometrial thickness reached an average of 7.65 ± 0.22 mm versus 6.52 ± 0.31 mm in the control group. The cycle cancelation rate was 19.0% in the study group, and 41.2% in the control group, which was statistically significant. All patients that reached optimal endometrial thickness received a frozen blastocyst transfer of one or two morphologically good blastocyst stage embryos. In the PRP group, clinical pregnancy was reported as 44.1% (15/34), and 20% (6/30) in the control group.
\nAll patients within study groups that underwent embryo transfer reached optimal lining thickness (>7 mm) after one or multiple rounds of PRP infusion. Patients that underwent PRP infusion in the study groups reached an average endometrial thickness of 7.36 mm with an average increase of 1.68 mm post PRP infusion. In the control groups presented by studies performing RCT, the control patients reached an average endometrial thickness of 6.77 mm with an average increase of 0.91 mm after HRT. Among patients within study groups, the overall chemical pregnancy rate was 50% (108/216) in contrast to 17.1% (16/93) following conventional HRT without PRP infusion.
\nPlatelet-rich plasma infusion is a novel approach to endometrium enhancement. This autologous therapy strives to increase endometrial thickness among patients with histories of canceled cycles and repeat implantation failure due to chronically refractive endometrium. While there is no universally agreed upon treatment for this patient population, the search to find an effective solution for non-reactive endometrial lining should be at the forefront of clinical researchers within the ART industry. Platelet-rich plasma is easily attained, cost-effective, minimally invasive, rich in cytokines and growth factors, and carries very little risk of disease or infection transmission as the patient uses their own blood to attain PRP. Infusion into the endometrium takes place in conjunction with traditional HRT and therefore can be administered during the average cycle while patients are already present for serial ultrasounds and serum hormone level measurements.
\nIn the eight studies discussed above, PRP infusion into the endometrium proved effective when administered on various days of an HRT cycle as well as in variable quantities. While the majority of studies reviewed were clinical applications, which presents a weakness in the data as there was no comparative control group, the randomized controlled trials that were performed offered arguably conclusive, supportive evidence of PRP effectiveness. All the patients that underwent PRP infusion experienced a significantly marked increase in endometrial thickness, allowing for frozen embryo transfer. In the studies that did utilize a study population versus a control population, results among the study participants were significantly improved with greater cycle completion. Although most studies utilized frozen blastocyst transfers, there were some that elected to use frozen cleavage stage embryo transfers, which can also be considered a limiting factor among the data. The studies here agreed upon 7 mm as the minimal lining thickness for embryo implantation success, but some physicians argue that endometrial thickness is a poor marker for transfer outcome. While this argument can be made and supported, as it was by Griesinger and colleagues [11], there is a wide consensus that endometrial thickness does play a vital role in receptivity (Table 1).
\nEight studies were compared for the measurement of endometrial thickness before and after PRP infusion in study groups vs. control groups. Clinical pregnancy outcomes are included following PRP treatment.
The patient populations presented in these studies, including those among the study group and those in the control group, were all patients that had suffered two or more failed previous cycles due to poor lining development. The inclusion criteria for these studies were consistent through all eight trials and provided an unbiased patient group in order to obtain reliable results. The data conclusively shows that endometrial thickness among patients with chronically poor endometrial development is greatly increased with PRP infusion therapy in comparison to traditional HRT alone. The primary outcome of each study was satisfied by the significant increase in endometrial lining development with the secondary satisfaction of improved clinical pregnancy outcomes in the PRP group versus the control group.
\nAnother diagnostic tool to be considered in patients with a history of suboptimal endometrial development and repeat implantation failure is the use of the Endometrial Receptivity Array (ERA). The ERA is a customized array that allows to test for 248 different genes expressed during the endometrial cycle and works concordantly with a computational algorithm that identifies the receptivity status of an endometrial biopsy to diagnose a personalized window of implantation [28]. ERA is performed with a mock embryo transfer cycle. Utilizing the ERA, Ruiz-Alonso and colleagues were able to validate conclusively that 25% of RIF patients had a displaced window of implantation and went on to coin the phrase “personalized embryo transfer” (pET) to increase the chance of a successful pregnancy in women suffering from mistimed endometrial receptivity [29]. Potentially, ERA can be utilized in conjunction with PRP infusion to determine receptivity of the endometrium in PRP patients. In the study by Tandulwadkar et al. [21], not only was lining thickness assessed, but endometrial vascularity was observed as well utilizing 3D Doppler ultrasound. Blood flow to the endometrium as well as the uterine biophysical profile can be measured via a combination between abdominal and transvaginal ultrasound. Greater blood flow to the uterus has been associated with higher implantation rates and can be seen in color utilizing Doppler ultrasound methods [27]. PRP infusion has the potential to increase lining development as well as endometrial vascularity as proven by Tandulwadkar, and future studies should observe an increase in vascularity concordant with lining and uterine biophysical profile. Utilizing the ERA and 3D Doppler system in conjunction with PRP in future studies can be therefore linked to the immune, genetic, and biophysical pathways of the endometrium.
\nWhile the use of PRP infusion into the endometrium to increase lining growth and vascularity is a relatively new area of research, the initial trials show encouraging results. The patients that were included within these studies are patients who had suffered from multiple failed or canceled cycles and would not have received embryo transfers otherwise. In a patient population that has had multiple failures, PRP infusion into the endometrium provides a suitable solution that effectively allows for embryo transfer, giving these patients a chance at pregnancy that they otherwise would not have had utilizing traditional HRT alone. Although the data is still new and there is need for additional research and much larger randomized controlled trials, the initial use of PRP as a universal means of treating poor responders to HRT shows a promising treatment method for the future.
\nThe review of the initial data presented in these eight early studies of PRP infusion into the endometrium in conjunction with traditional HRT reveals statistically significant outcomes. Patients with previous failures that did not reach the minimal lining thickness needed to perform embryo transfer (>7 mm) underwent PRP infusion into the endometrium and reached an average endometrial thickness of 7.36 mm in comparison to the control group, which reached an average of only 6.77 mm. Clinical pregnancy rates within the study group were also significantly higher than the control group, 50% (108/216) versus 17.1% (16/93), respectively. For patients that have had multiple failures and canceled cycles, offering an absolute solution that at minimum guarantees them an embryo transfer can potentially increase the success of frozen embryo transfers in clinics globally, while decreasing patient stress and costs, and reducing the potential for embryo wastage.
\nThe author would like to acknowledge and recognize the support of her co-authors and their institutions, the Eastern Virginia Medical School and Ovation Fertility-Newport Beach.
\nThe author declares no conflict of interest.
The nanoparticle includes the particles having size between 1 and 100 nm. These particles have different properties at their atomic level due to their size. This change in properties of nanoparticles is beneficial in many fields [1, 2]. Nanotechnology is one of the most interesting fields for researchers since the last century. Numbers of developments have been made since then in the field of nanotechnology. Nanoparticles can be classified as metal nanoparticles, non-metal ceramic nanoparticles, semiconductor nanoparticles, and a well-known type is carbon nanoparticles [3]. Nanoparticles have those chemical and physical properties which makes them very different from that of the corresponding bulk materials due to their small size and large surface to volume ratio. They attract much attention because of their potential applications in many fields including optics, electrics, magnetism, ceramics, and catalysis [4].
Composites are engineered or naturally occurring solid materials which results when two or more different constituent materials, each having its own significant characteristic (physical or chemical properties) are combined together to create a new substance with superior properties than original materials in a specific finished structure [5, 6]. They are commonly designed to offer wide range of properties and characteristics, some are as follows:
Stiffness and strength
Low coefficient of expansion
Resistance аgаinst fatigue
Ease in manufacturing complex shapes
Simple repair of damaged structures
Resistance to corrosion
Nanocomposites are those composites in which one phase has nanoscale morphology like nanoparticles, nanotubes, or lamellar nanostructure. They have multiphases, so are multiphasic materials, at least of the phases should have dimensions in the range of 10–100 nm. To overcome the limitation of different engineering materials now-a-days, nanocomposites are emerged to provide beneficial alternatives. Nanocomposites can be classified on the basis of their dispersed matrix and dispersed phase materials [7]. With the help of this rapidly expanding field, now-a-days, it has been possible to generate many exciting new materials with novel properties via innovative synthetic approaches. The properties of the so-called found not only depended on the properties of their originals, but also crucially on their interfacial and morphological characteristics. Of course, we cannot ignore the fact that sometimes it also happened that the newly generated property in the material is unknown to the parent constituent materials [8, 9]. Hence, the idea behind nanocomposite is to use building blocks with dimensions in nanometer range to design and create new materials with unprecedented flexibility and improvement in their physical properties.
Nanocomposites are the solid combination of а bulk matrix and nаnodimensionаl phase(s) which differ in properties due to dissimilarities in structure and chemistry. Properties that have indicated substantial improvements:
Mechanical properties (strength, bulk modules, withstands limit, etc.)
Thermal stability
Hinders flame and reduce smoke generations
Permeability of gases, water, and solvents are reduced
More surface appearance
Improved electrical conductivity
Increased chemical resistance
Enhance optical clarity as compared to conventionally filled polymers
Among several nanocomposites, polymer-based nanomaterials are the most leading materials of current research and development. Characteristics like film forming ability, activated functionalities, and dimensional variability provide lots of benefit to polymer-based nanocomposites [10].
The potential risk of nanocomposites commonly occurs majorly in areas like
Risk to health and environment
Molecular manufacturing
Societal risks
Formation of nanocomposite materials:
Nanocomposites can be formed by blending inorganic nanoclusters, fullerenes, clays, metals, oxides, or semiconductors with numerous organic polymers or organic and organometallic compounds, biological molecules, enzymes, and sol-gel derived polymers (Figure 1).
Formation of nanocomposite materials.
Nanocomposite materials that are obtained by the combination of two or more separate building constituents in one material offers unique properties that plausibly arises from their small size, large surface area, and off course from the interfacial interaction between the phases. Their extra ordinary potential have been smoothly utilized to enhance the biological potential of many drugs, biomaterials, catalysts, and also in some high-value added materials [11].
Nanocomposite materials can be classified in the following way based on the presence or absence of polymeric material in the composite.
The nanocomposites in which the compositions do not contain any polymers or polymer-derived materials are called non-polymer-based nanocomposites (Figure 2). Non-polymer-based nanocomposites are also known as inorganic nanocomposites. They can be further classified into metal-based nanocomposites, ceramic-based nanocomposites, and ceramic-ceramic-based nanocomposites [12].
Classification of polymer- and non-polymer-based nanocomposites.
Bimetallic nanoparticles being investigated in detail in the form of either of alloy or core-shell structures due to their improved catalytic properties and advancement in optical properties related to individual and differentiate metals [13]. They can be characterized by:
Super plasticity,
Lower melting points,
Increased strength and hardness,
Improved magnetic properties,
Increased electrical resistivity, etc.
Non-polymer-based nanocomposites can be also classified as: metal/metal nanocomposites, for example Pt-Ru nanocomposites.
Ceramic-based nanocomposites are defined as ceramic composites with more than one solid phase, in which at least one of the phases has dimensions in the nanoscale range (<50–100 nm). In these types of composites, both the phases have combined magnetic, chemical, optical, and mechanical properties, for example hydroxyapatite/titania nanocomposites [14, 15, 16].
These can be characterized by:
Better toughness
Increased ductility
Increased strength and hardness
The non-polymer-based nanocomposites can be also classified as ceramic/ceramic nanocomposites which can be used in the area of artificial joint implants for fracture failures and it could promptly reduce the cost of surgery and would extend the mobility of the patient. The life spam would increase by 30 years, if the use of zirconia-toughened alumina nanocomposite implants is used effectively. The other example of ceramic/ceramic nanocomposites are calcium sulfate-biomimetic apatite nanocomposites [17].
The most promising prospects of both metal-based nanocomposites and ceramic-based nanocomposites are in the application of areas in dentistry in which the non-polymer-based nanocomposites or the inorganic materials that is metal or ceramics such as calcium phosphate, hydroxyapatite, and bioactive glass nanoparticles are very advantageous in alveolar bone regeneration and enamel substitution [18].
The polymer or copolymer which contains nanoparticles or nanofillers dispersed in the polymer matrix is termed as poly nanocomposites. One dimension (1D) must be lying in the range of 1–50 nm and these possess several shapes like as platelets, fibers, spheroids, etc. Poly nanocomposites are in the category of multiphase systems such as, MPS namely composites, blends, and foams which can absorb about 95% of the production of plastics. So, these systems need controlled mixing, the achieved dispersion should be stable, dispersed phase should be oriented, and the compounding strategies which are involved for all MPS, which includes poly nanocomposites (PNC) is almost same [19].
Polymer nanocomposites are proposed as a class of materials with unique properties but, the most challenging property of PNCs is the complex interfacial areas in between the polymer matrices because of this small scale large specific area is created that highlight the importance of polymer-nanoparticle interactions. So, to achieve properties, such as, mechanical, thermal, optical, and electric, we need to analyze the intercalation process among the nanoparticles and polymer bases [20].
Polymer nanocomposites are known to be a class of reinforced polymer with a very low, i.e., less than about 5% of nanometric clay particles. These substances gained huge attention simultaneously from both the academic institution as well as from industrial sectors commonly in the area of nanocomposites. This is actually due to their drastically enhanced or improved thermal, mechanical as well as the barrier properties as compared to the micro- and also the conventional composites. These materials can be differentiated notably by: improved fire resistance and thermal stability, improved barrier properties, and increased recyclability [21].
However, despite of having so many advantages, it is still very much difficult to prepare a uniform dispersion between the filler and the matrix, as shown in Figure 3. Hence, unlikely, it reflects the lower mechanical as well as thermal properties in the produced nanocomposites.
Uniform dispersion between the filler and matrix in nanocomposites.
Figure 4 shows the various uses of polymer nanocomposites irrespective of the nature of the field used. By the hydrolysis of tetraethyl-ortho-silicate, the hybrids made of poly rubber (dimethyl siloxane) and nanosilica can be given a specific shape like objects, such as golf balls (Figure 5). Many number of polymer nanocomposites for example, rubber, propylene, styrene butadiene rubber, and ethylene vinyl acetate are used in barrier applications.
Various uses of polymer nanocomposites.
Rubbery hybrids with different shapes.
They can act as a tremendous barrier for chemicals like toluene, sulfuric acid, and hydrochloric acid as well as for several gases such as, carbon dioxide, oxygen, and nitrogen [22, 23]. They are also utilized in chemical protective and surgical gloves as they have excellent solvent barrier properties in order for avoiding contamination from medicine.
Polymer nanocomposites are also used in food packaging, and the particular examples for food packaging includes processed cheese, meat, and dairy products also the medical containers for carrying blood collection tubes, baby pacifiers, and drinking water bottles. To enhance the barrier, mechanical properties and the life of the product clay-based polymer nanocomposites are been used in plastic bottles [24]. Nanocomposites are also incorporated for beer bottle manufacture, so as to reduce many problems like biological and non-biological aspects, beer colloids instability, oxygen permeation, and change in taste due to light exposure. The double core Wilson tennis ball is the most recently commercialized sports goods (Figure 6), in which the coating of clay nanocomposites is done in order to maintain the internal pressure for a long period of time and also the core is coated by butyl rubber clay nanocomposite which doubled the shell life and acts a gas barrier.
The core of this Wilson tennis ball is covered by a polymer-clay nanocomposite coating.
In today’s time, the biggest milestone is the incorporation or application of polymer/clay nanocomposites in the field of electronics and automobile sectors. Specifically to decrease the solvent transmission through polymers like elastomers, poly urethane, is the most impressive ability nanoclay incorporation. The poly nanocomposites help in the reduction of weight and processing cost so that they used by tire companies which are the major driving force for their usage. It is the naturally obtained materials which possesses low density. When the clay incorporated tires are compared with the ordinary ones then it is found that they have excellent mechanical properties and also improved gas barrier performance for tubeless tires uses [25]. Mostly for automobile tire manufacturing, styrene butadiene and natural rubber nanocomposites are preferred the most. It is due to their improved thermal properties and abrasion resistance that contribute to the long life of the tires. They have great applications in solar cells, transistors, battery manufacturing, etc.
The most important modifying property of surfaces is coating. So, many methods and strategies are tried by the researchers to improve the surface properties of several products. The properties such as, excellent resistance for chemicals, better barrier properties, super hydrophobicity, and corrosion resistance are exhibited by nanoclay incorporated thermoset polymer nanocoatings [18]. The process parameters, such as dipping time, nature of surfactant, temperature, etc., determine the coating thickness. The thermoset polymer nanocoatings which are incorporated clay and nanosilver could improve the antibacterial properties and is used in medical sectors.
The name “Bi-nanocomposites” is given as they are characterized as natural nanocomposite. To understand their essential roles in biological systems, their structures and properties are studied by biologists. Bio-nanocomposites are designed originally and are present to fulfill the needs of life and to meet surrounding environmental conditions so they can guarantee the living of the associated species. Natural materials are different in terms of structure and compositions but the design of bio-nanocomposites require biological molecules to consider them as synthetic building blocks, which is far more distant from the context of their own natural function. They are made of biopolymers and inorganic solids which has the dimension in the range of 1–100 nm. Due to their multidimensional properties such as antimicrobial activity, biocompatibility, and biodegradability they have several numbers of applications. The effective outcome of growing needs of bio-based polymers is the drastic reduction in the usage of fossil fuels. Bio-nanocomposites have easily replaced conventional non-biodegradable petroleum-based plastic as they are light weight and eco-friendly; they have become a sustainable that is future lasting material for use in high performance applications. As they are biocompatible, it makes them beneficial for biomedical applications and also makes them suitable for cosmetics and biotechnology applications. They have dominant significance in the future as green sustainable materials [26]. Bio-nanocomposites will act as substituents for the currently used petroleum-based polymers.
Bio-nanocomposites are used in cosmetics industries and also in the fabrication of implants, scaffolds, diagnostics, and biomedical devices.
They are also very beneficial as catalysts, contact lenses, and gas-separation membranes.
In the treatment of osteomyelitis, by the regeneration of tissue biopolymer-based nanocomposite is applicable.
Artificial bone implants involves nanostructured organic/inorganic nanocomposites which are useful in managing load-bearing bone grafts.
Using live cells of functionalized particles, controlled electrophoretic assembly of bioinorganic composite materials is done.
They are largely applicable in diagnostic, drug delivery, and tissue generation.
In industries, they are used as actuators. They are also used in the manufacturing of compostable bags as they are eco-friendly.
Nanocomposites have been growing with a speedy rate so as their large number of applications. In the next 10 years, the worldwide production will exceed 600,000 tons in the following regions:
Superior strength fibers and films
UV protection gels
Drug delivery systems
New fire retardant materials
Anti-corrosion barrier coatings
Lubricant and stretch paints
Nanocomposites have also attracted the field of automotive and industrial applications by doing enhancements in especially the mechanical properties. They can be used or applied in the various vehicles types like engine covers, door covers, and timing belt covers. Other applications are usage as blades for vacuum cleaners, mower hood, covers for mobile phones, etc.
Modification of surface properties of nanoparticles by treating them with green agents for specific applications having specific improved microstructural properties like improved exfoliation, compatibility, and also thermal stability.
Advance optimization of the polymerization conditions during the preparation of the nanocomposites in order to get maximum output with minimal cost.
Detailed study on the effect of composition of the nanocomposites to build up the developed microstructures during the preparation activities.
Preparation of nanocomposites as well as their blends by using the materials like polymer blends along with the melt blending technologies. Hence, the advantages of the properties of the individual material as well as their coaction can be developed.
Using nanocomposites to make flexible batteries: “А nanocomposite of cellulous materials and nanotubes could be used to make а conductive paper. When this conductive paper is soaked in an electrolyte, а flexible battery is formed.”
With the rapid development of nanotechnology in the past few years, the study of the nanocomposites has been increasingly become important in the development of new materials for advanced applications. To fulfill the growing needs of multifunctional materials, nanocomposites are the right choice as these are not only the versatile class of materials, but also have a high level of integrated association. It is a multidisciplinary field which includes the knowledge of scientific background as well as technological aspects to create macroscopic engineered materials obtained through nanolevel structures. These materials are suitable materials to meet the emerging demands arising from scientific and technologic advances. Outstanding potentials of nanocomposites can be exemplified by the massive investments from many companies and governments throughout the world. As a result, nanocomposites are expected to generate a great impact in world economy and business. The important aspects is that it provides plausible benefit to many of our industrial sector like electronics and electrical industry, chemical industry, transportation sectors, health care organizations, and above an all the protection of the environment. Hence, these are expected to have high impact on making the environment cleaner, greener, and safer in the coming years.
The author is very much thankful to the faculty members of AIAS, Amity University, Uttar Pradesh for providing necessary facilities and their constant encouragement to complete the above assessment.
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