{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:48:59Z","timestamp":1792547339045,"version":"4.5.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Does intraovarian platelet-rich plasma (PRP) injection increase the number of mature oocytes obtained after controlled ovarian stimulation (COS) in young women with poor ovarian response (POR) undergoing IVF?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Intraovarian PRP injection procedure does not improve mature oocyte yield after COS in women less than 38\u2009years old with an established IVF history of POR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>POR is frequently encountered among the infertile population and the number of women seeking infertility treatment related to POR is increasing. Effective treatment options for this patient population to conceive with autologous oocytes are lacking. Case series and cohort studies suggest that intraovarian PRP injection may improve follicular recruitment in women with premature ovarian insufficiency (POI) and POR, yet robust randomized studies have not been performed to date to determine the clinical utility of this intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This was a multi-center randomized controlled trial (RCT) conducted at university-affiliated reproductive centers in the USA and Turkey, between January 2020 and November 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Patients who met inclusion criteria (&amp;lt;38\u2009years old, two or more prior cycles with &amp;lt;3 oocytes retrieved; and without single gene disorders, prior ovarian surgery, endometriomas, BMI &amp;gt;35\u2009kg\/m2, or severe male factor infertility) were randomized to either the PRP or control group. Patients in both groups subsequently underwent COS, oocyte retrieval, ICSI, preimplantation genetic testing for aneuploidy (PGT-A), and single euploid embryo transfer. Number of metaphase II (MII) oocytes obtained was the primary outcome. Secondary outcomes included ovarian reserve tests (antral follicle count [AFC] and anti-M\u00fcllerian hormone [AMH]), blastocyst and euploid blastocyst yields, and sustained implantation. The study was powered to detect a difference of one mature oocyte obtained at oocyte retrieval.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>In total, 83 patients met inclusion criteria and were randomized to receive autologous intraovarian PRP injection (n\u2009=\u200941) or to no intervention (n\u2009=\u200942). No significant differences were observed in number of MII oocytes retrieved per cycle (2.8\u2009\u00b1\u20092.4 vs 3.1\u2009\u00b1\u20093.3 in PRP vs control, respectively; P\u2009=\u20090.9), blastocysts (1.0\u2009\u00b1\u20091.3 vs 1.3\u2009\u00b1\u20092.1, P\u2009=\u20090.8), or euploid blastocysts (0.8\u2009\u00b1\u20091.1 vs 0.9\u2009\u00b1\u20091.6; P\u2009=\u20090.5). Similarly, no differences were observed in the likelihood of obtaining at least one euploid blastocyst (45% vs 37%, P\u2009=\u20090.4; relative risk [RR], 95% CI\u2009=\u20090.9, 0.6\u20131.2) or the rate of sustained implantation (31% vs 29%, P\u2009=\u20090.9; RR 1.0, 0.7\u20131.3). Posttreatment AFC (7.9\u2009\u00b1\u20094.5 vs 6.8\u2009\u00b1\u20094.8, P\u2009=\u20090.3) and AMH (0.99\u2009\u00b1\u20090.98 vs 0.7\u2009\u00b1\u20090.6, P\u2009=\u20090.2) were also not different between the groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>Results from this RCT may not be generalizable to other PRP preparations owing to heterogeneity and lack of standardization. The control groups did not undergo a sham ovarian injection, which would have been relevant had the results shown benefit of PRP injection. Only patients with POR were included in this study, and these results may not be generalizable to more severe diminution of ovarian reserve, as seen with POI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>The intraovarian PRP injection procedure does not improve mature oocyte yield or other parameters of IVF outcome in women less than 38\u2009years old with an established IVF history of POR. The results from this study do not support the use of intraovarian PRP injection in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>Departmental funds were used and no external funding was requested for this study. ES is a consultant for and receives grant funding from the Foundation for Embryonic Competence. All other authors have no conflict of interest to declare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>Clinicaltrials.gov Registry Identifier: NCT04163640.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION DATE<\/jats:title>\n                    <jats:p>15 November 2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATE OF FIRST PATIENT\u2019S ENROLMENT<\/jats:title>\n                    <jats:p>24 February 2020.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deae093","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T23:33:03Z","timestamp":1713828783000},"page":"1495-1503","source":"Crossref","is-referenced-by-count":39,"title":["Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial"],"prefix":"10.1093","volume":"39","author":[{"given":"Nola S","family":"Herlihy","sequence":"first","affiliation":[{"name":"IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, NJ, USA"},{"name":"Department of Obstetrics & Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadeplhia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigit","family":"Cakiroglu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Acibadem Mehmet Ali Aydinlar University , Istanbul, Turkey"},{"name":"Department of Obstetrics & Gynecology, Acibadem Maslak Hospital Assisted Reproductive Technologies Unit , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Whitehead","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9081-2461","authenticated-orcid":false,"given":"Andres","family":"Reig","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, NJ, USA"},{"name":"Department of Obstetrics & Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadeplhia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulent","family":"Tiras","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Acibadem Mehmet Ali Aydinlar University , Istanbul, Turkey"},{"name":"Department of Obstetrics & Gynecology, Acibadem Maslak Hospital Assisted Reproductive Technologies Unit , Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Richard T","family":"Scott","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, NJ, USA"},{"name":"Department of Obstetrics & Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadeplhia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7464-8203","authenticated-orcid":false,"given":"Emre","family":"Seli","sequence":"additional","affiliation":[{"name":"IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, NJ, USA"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine , New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"2024070305522102200_deae093-B1","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1001\/jama.2021.19415","article-title":"Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial","volume":"326","author":"Bennell","year":"2021","journal-title":"JAMA"},{"key":"2024070305522102200_deae093-B2","doi-asserted-by":"crossref","first-page":"10211","DOI":"10.18632\/aging.103403","article-title":"Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency","volume":"12","author":"Cakiroglu","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"2024070305522102200_deae093-B3","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.18632\/aging.203972","article-title":"Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP)","volume":"14","author":"Cakiroglu","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"2024070305522102200_deae093-B4","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/GCO.0000000000000863","article-title":"Treatment options for endometrial hypoporliferation","volume":"35","author":"Cakirogly","year":"2023","journal-title":"Curr Opin Obstet Gynecol"},{"key":"2024070305522102200_deae093-B5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4103\/0974-2077.150734","article-title":"Principles and methods of preparation of platelet-rich plasma: a review and author\u2019s perspective","volume":"7","author":"Dhurat","year":"2014","journal-title":"J Cutan Aesthet Surg"},{"key":"2024070305522102200_deae093-B6","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fendo.2019.00099","article-title":"A novel predictive model to estimate the number of mature oocytes required for obtaining at least one euploid blastocyst for transfer in couples undergoing in vitro fertilization\/Intracytoplasmic sperm injection: the ART calculator","volume":"10","author":"Esteves","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2024070305522102200_deae093-B7","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1007\/s11033-019-04609-w","article-title":"A report on three live births in women with poor ovarian response following intra-ovarian injection of platelet-rich plasma (PRP)","volume":"46","author":"Farimani","year":"2019","journal-title":"Mol Biol Rep"},{"key":"2024070305522102200_deae093-B8","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1093\/humrep\/der092","article-title":"ESHRE consensus on the definition of \u2018poor response\u2019 to ovarian stimulation for in vitro fertilization: the Bologna criteria","volume":"26","author":"Ferraretti","year":"2011","journal-title":"Hum Reprod"},{"key":"2024070305522102200_deae093-B9","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.fertnstert.2013.11.004","article-title":"The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening","volume":"101","author":"Franasiak","year":"2014","journal-title":"Fertil Steril"},{"key":"2024070305522102200_deae093-B10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/GCO.0000000000000784","article-title":"The use of intraovarian injection of autologous platelet rich plasma (PRP) in patients with poor ovarian response and premature ovarian insufficiency","volume":"34","author":"Herlihy","year":"2022","journal-title":"Curr Opin Obstet Gynecol"},{"key":"2024070305522102200_deae093-B11","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.3390\/ijms21041328","article-title":"Platelet concentrates in musculoskeletal medicine","volume":"21","author":"Mariani","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024070305522102200_deae093-B12","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s10815-020-01710-z","article-title":"The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a nonrandomized interventional study","volume":"37","author":"Melo","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"2024070305522102200_deae093-B13","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1093\/humrep\/dey238","article-title":"Diminished ovarian reserve and poor response to stimulation in patients &lt;38 years old: a quantitative but not qualitative reduction in performance","volume":"33","author":"Morin","year":"2018","journal-title":"Hum Reprod"},{"key":"2024070305522102200_deae093-B14","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1177\/0963689719859539","article-title":"A case series on natural conceptions resulting in ongoing pregnancies in menopausal and prematurely menopausal women following platelet-rich plasma treatment","volume":"28","author":"Pantos","year":"2019","journal-title":"Cell Transplant"},{"key":"2024070305522102200_deae093-B15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.fertnstert.2020.07.002","article-title":"Rate of true recurrent implantation failure is low: results of three successive frozen euploid single embryo transfers","volume":"115","author":"Pirtea","year":"2021","journal-title":"Fertil Steril"},{"key":"2024070305522102200_deae093-B16","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1016\/j.fertnstert.2016.02.005","article-title":"A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept","volume":"105","author":"POSEIDON Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number)","year":"2016","journal-title":"Fertil Steril"},{"key":"2024070305522102200_deae093-B17","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.fertnstert.2023.05.007","article-title":"Bologna vs. POSEIDON criteria as predictors of the likelihood of obtaining at least one euploid embryo in poor ovarian response: an analysis of 6,889 cycles","volume":"120","author":"Reig","year":"2023","journal-title":"Fertil Steril"},{"key":"2024070305522102200_deae093-B18","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/GCO.0000000000000703","article-title":"Emerging follicular activation strategies to treat women with poor ovarian response and primary ovarian insufficiency","volume":"33","author":"Reig","year":"2021","journal-title":"Curr Opin Obstet Gynecol"},{"key":"2024070305522102200_deae093-B19","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1056\/NEJMc1402340","article-title":"Platelet-rich plasma injections in acute muscle injury","volume":"370","author":"Reurink","year":"2014","journal-title":"N Engl J Med"},{"key":"2024070305522102200_deae093-B20","volume-title":"Assisted Reproductive Technology Success Rates. National Summary and Fertility Clinic Reports","author":"SART","year":"2014"},{"key":"2024070305522102200_deae093-B21","volume-title":"Assisted Reproductive Technology Success Rates. National Summary and Fertility Clinic Reports","author":"SART","year":"2018"},{"key":"2024070305522102200_deae093-B22","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.3390\/jcm9061809","article-title":"Reactivating ovarian function through autologous platelet-rich plasma intraovarian infusion: pilot data on premature ovarian insufficiency, perimenopausal, menopausal, and poor responder women","volume":"9","author":"Sfakianoudis","year":"2020","journal-title":"J Clin Med"},{"key":"2024070305522102200_deae093-B23","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1080\/09513590.2018.1445219","article-title":"First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma","volume":"34","author":"Sills","year":"2018","journal-title":"Gynecol Endocrinol"},{"key":"2024070305522102200_deae093-B24","doi-asserted-by":"crossref","first-page":"hoaa009","DOI":"10.1093\/hropen\/hoaa009","article-title":"ESHRE guideline: ovarian stimulation for IVF\/ICSI(dagger)","volume":"2020","author":"The Eshre Guideline Group On Ovarian Stimulation","year":"2020","journal-title":"Hum Reprod Open"},{"key":"2024070305522102200_deae093-B25","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.fertnstert.2020.07.052","article-title":"A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy","volume":"115","author":"Tiegs","year":"2021","journal-title":"Fertil Steril"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/39\/7\/1495\/58383994\/deae093.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/39\/7\/1495\/58383994\/deae093.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T01:54:44Z","timestamp":1719971684000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/39\/7\/1495\/7667973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":25,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,5,9]]},"published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deae093","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,5,9]]}}}