Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes
Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigate...
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| description | Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7-10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66-0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management. |
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CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7-10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66-0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0136172</identifier><identifier>PMID: 26288130</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis ; Apoptosis ; Biochemistry, Molecular Biology ; Bioindicators ; Biomarkers ; Biomarkers - analysis ; Cell-Free System - chemistry ; Deoxyribonucleic acid ; Disorders ; DNA ; DNA - analysis ; Female ; Fertilization ; Fertilization in vitro ; Fertilization in Vitro - methods ; Fluids ; Follicular fluid ; Follicular Fluid - chemistry ; Genomics ; Gonadotropins ; Gynecology and obstetrics ; Hostages ; Human health and pathology ; Humans ; In vitro fertilization ; Infertility ; Infertility, Female - metabolism ; Infertility, Female - therapy ; Life Sciences ; Medicine ; Menstruation ; Multivariate analysis ; Obstetrics ; Ovarian Reserve ; Ovulation Induction - methods ; Patients ; Pituitary (anterior) ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - metabolism ; Pregnancy ; Pregnancy Outcome ; Prognosis ; Prospective Studies ; Quality ; Sperm Injections, Intracytoplasmic ; Stimulation ; Womens health ; Young Adult</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0136172-e0136172</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Traver et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>2015 Traver et al 2015 Traver et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c792t-b78788442c553e46001be6752b086c14ba32f361dc6c64074644e7e0ee31e6353</citedby><cites>FETCH-LOGICAL-c792t-b78788442c553e46001be6752b086c14ba32f361dc6c64074644e7e0ee31e6353</cites><orcidid>0000-0002-1786-0088</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545729/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545729/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26288130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01913394$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Polejaeva, Irina</contributor><creatorcontrib>Traver, Sabine</creatorcontrib><creatorcontrib>Scalici, Elodie</creatorcontrib><creatorcontrib>Mullet, Tiffany</creatorcontrib><creatorcontrib>Molinari, Nicolas</creatorcontrib><creatorcontrib>Vincens, Claire</creatorcontrib><creatorcontrib>Anahory, Tal</creatorcontrib><creatorcontrib>Hamamah, Samir</creatorcontrib><title>Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7-10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66-0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management.</description><subject>Adult</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biochemistry, Molecular Biology</subject><subject>Bioindicators</subject><subject>Biomarkers</subject><subject>Biomarkers - analysis</subject><subject>Cell-Free System - chemistry</subject><subject>Deoxyribonucleic acid</subject><subject>Disorders</subject><subject>DNA</subject><subject>DNA - analysis</subject><subject>Female</subject><subject>Fertilization</subject><subject>Fertilization in vitro</subject><subject>Fertilization in Vitro - methods</subject><subject>Fluids</subject><subject>Follicular fluid</subject><subject>Follicular Fluid - chemistry</subject><subject>Genomics</subject><subject>Gonadotropins</subject><subject>Gynecology and obstetrics</subject><subject>Hostages</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>In vitro fertilization</subject><subject>Infertility</subject><subject>Infertility, Female - 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metabolism</topic><topic>Pregnancy</topic><topic>Pregnancy Outcome</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Quality</topic><topic>Sperm Injections, Intracytoplasmic</topic><topic>Stimulation</topic><topic>Womens health</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Traver, Sabine</creatorcontrib><creatorcontrib>Scalici, Elodie</creatorcontrib><creatorcontrib>Mullet, Tiffany</creatorcontrib><creatorcontrib>Molinari, Nicolas</creatorcontrib><creatorcontrib>Vincens, Claire</creatorcontrib><creatorcontrib>Anahory, Tal</creatorcontrib><creatorcontrib>Hamamah, Samir</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Traver, Sabine</au><au>Scalici, Elodie</au><au>Mullet, Tiffany</au><au>Molinari, Nicolas</au><au>Vincens, Claire</au><au>Anahory, Tal</au><au>Hamamah, Samir</au><au>Polejaeva, Irina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-19</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0136172</spage><epage>e0136172</epage><pages>e0136172-e0136172</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7-10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66-0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26288130</pmid><doi>10.1371/journal.pone.0136172</doi><tpages>e0136172</tpages><orcidid>https://orcid.org/0000-0002-1786-0088</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-08, Vol.10 (8), p.e0136172-e0136172 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1708482713 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Analysis Apoptosis Biochemistry, Molecular Biology Bioindicators Biomarkers Biomarkers - analysis Cell-Free System - chemistry Deoxyribonucleic acid Disorders DNA DNA - analysis Female Fertilization Fertilization in vitro Fertilization in Vitro - methods Fluids Follicular fluid Follicular Fluid - chemistry Genomics Gonadotropins Gynecology and obstetrics Hostages Human health and pathology Humans In vitro fertilization Infertility Infertility, Female - metabolism Infertility, Female - therapy Life Sciences Medicine Menstruation Multivariate analysis Obstetrics Ovarian Reserve Ovulation Induction - methods Patients Pituitary (anterior) Polycystic ovary syndrome Polycystic Ovary Syndrome - metabolism Pregnancy Pregnancy Outcome Prognosis Prospective Studies Quality Sperm Injections, Intracytoplasmic Stimulation Womens health Young Adult |
| title | Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T22%3A41%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cell-free%20DNA%20in%20Human%20Follicular%20Microenvironment:%20New%20Prognostic%20Biomarker%20to%20Predict%20in%20vitro%20Fertilization%20Outcomes&rft.jtitle=PloS%20one&rft.au=Traver,%20Sabine&rft.date=2015-08-19&rft.volume=10&rft.issue=8&rft.spage=e0136172&rft.epage=e0136172&rft.pages=e0136172-e0136172&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0136172&rft_dat=%3Cgale_plos_%3EA426228485%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1708482713&rft_id=info:pmid/26288130&rft_galeid=A426228485&rft_doaj_id=oai_doaj_org_article_e7da582f10a04a3487d1d330d3d33c6e&rfr_iscdi=true |