{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:13:07Z","timestamp":1773155587637,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy","award":["7690\/116\/15"],"award-info":[{"award-number":["7690\/116\/15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>\u201cPoor responders\u201d (PR) are an important category of infertile women who experience a modest response to controlled ovarian stimulation. In this study, we evaluated response to growth hormone (GH) administration among PR patient subtypes stratified by follicle stimulation hormone receptor (FSHR) polymorphism (c.2039A &gt; G p.Asn680Ser). We conducted a cohort study of 125 women with poor ovarian response, 58 of whom received GH in addition to the standard treatment, and 67 of whom received the standard treatment only. The Ala307Thr polymorphism genotypes were analyzed using a polymerase chain reaction-restriction fragment length polymorphism method, and the FSHR gene polymorphism was analyzed using a predesigned TaqMan SNP Genotyping Assay (rs6166). A comparative analysis detected statistically significant differences in mean mature follicles (p = 0.0002), metaphase-II oocytes (p = 0.0005), progesterone levels (p = 0.0036), and IGF levels (follicle IGF1, p = 0.0004) between GH-treated and non-GH-treated participants with the FSHR (Ser\/Ser) polymorphism. However, the differences were modest among participants with the other two FSHR polymorphisms (Ser\/Asn and Asn\/Asn). The subcategory of patients with the FSHR Asn680Ser (Ser\/Ser) polymorphism showed a stronger response when GH was added to the IVF protocol.<\/jats:p>","DOI":"10.3390\/diagnostics12102371","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T21:03:10Z","timestamp":1664485390000},"page":"2371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Follicle Stimulating Hormone Receptor (FSHR) Polymorphism on the Efficiency of Co-Treatment with Growth Hormone in a Group of Infertile Women from Romania"],"prefix":"10.3390","volume":"12","author":[{"given":"Mihai","family":"Surcel","sequence":"first","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-141X","authenticated-orcid":false,"given":"Bogdan","family":"Doroftei","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5314-0539","authenticated-orcid":false,"given":"Iulia Adina","family":"Neamtiu","sequence":"additional","affiliation":[{"name":"Health Department, Environmental Health Center, 58 Busuiocului Street, 400240 Cluj-Napoca, Romania"},{"name":"Faculty of Environmental Science and Engineering, Babes-Bolyai University, 30 Fantanele Street, 400294 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Muresan","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Caracostea","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-816X","authenticated-orcid":false,"given":"Iulian","family":"Goidescu","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelina","family":"Staicu","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgiana","family":"Nemeti","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0028-5494","authenticated-orcid":false,"given":"Michael S.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Global and Community Health, George Mason University, 4400 University Drive, MS 5B7, Fairfax, VA 22030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Zlatescu-Marton","sequence":"additional","affiliation":[{"name":"\u201cRegina Maria\u201d Hospital, 29 Dorobantilor Street, 400117 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fendo.2020.00192","article-title":"What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART\/IVF?","volume":"11","author":"Blumenfeld","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Giannelou, P., Simopoulou, M., Grigoriadis, S., Makrakis, E., Kontogeorgi, A., Pantou, A., Galatis, D., Kalampokas, T., Bakas, P., and Bolaris, S. (2020). The Conundrum of Poor Ovarian Response: From Diagnosis to Treatment. Diagnostics, 10.","DOI":"10.3390\/diagnostics10090687"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.rbmo.2017.09.016","article-title":"Insights from Clinical Experience in Treating IVF Poor Responders","volume":"36","author":"Gonda","year":"2018","journal-title":"Reprod. Biomed. Online"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fendo.2018.00461","article-title":"Defining Low Prognosis Patients Undergoing Assisted Reproductive Technology: POSEIDON Criteria\u2014The Why","volume":"9","author":"Esteves","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.12688\/f1000research.10382.1","article-title":"The Novel POSEIDON Stratification of \u2018Low Prognosis Patients in Assisted Reproductive Technology\u2019 and Its Proposed Marker of Successful Outcome","volume":"5","author":"Humaidan","year":"2016","journal-title":"F1000Res"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1530\/REP-09-0567","article-title":"Premature Ovarian Failure","volume":"140","author":"Shelling","year":"2010","journal-title":"Reproduction"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"516","DOI":"10.23736\/S0026-4784.18.04282-X","article-title":"The cAMP\/PKA Pathway: Steroidogenesis of the Antral Follicular Stage","volume":"70","author":"Riccetti","year":"2018","journal-title":"Minerva Ginecol."},{"key":"ref_8","first-page":"30","article-title":"The role of high follicular levels of angiotensin ii and vascular endothelial growth factor in anticipating the development of severe ovarian hyperstimulation syndrome in patients with prophylactic cabergoline therapy undergoing an in vitro fertilization procedure","volume":"16","author":"Surcel","year":"2020","journal-title":"Acta Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1210\/en.2008-0850","article-title":"Role of the Phosphatidylinositol-3-Kinase and Extracellular Regulated Kinase Pathways in the Induction of Hypoxia-Inducible Factor (HIF)-1 Activity and the HIF-1 Target Vascular Endothelial Growth Factor in Ovarian Granulosa Cells in Response to Follicle-Stimulating Hormone","volume":"150","author":"Alam","year":"2009","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ircmb.2018.02.001","article-title":"Follicle-Stimulating Hormone Receptor: Advances and Remaining Challenges","volume":"Volume 338","author":"Landomiel","year":"2018","journal-title":"International Review of Cell and Molecular Biology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1210\/jc.2014-1139","article-title":"IGF1R Signaling Is Necessary for FSH-Induced Activation of AKT and Differentiation of Human Cumulus Granulosa Cells","volume":"99","author":"Baumgarten","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1210\/me.2007-0020","article-title":"Follicle-Stimulating Hormone Induces Multiple Signaling Cascades: Evidence That Activation of Rous Sarcoma Oncogene, RAS, and the Epidermal Growth Factor Receptor Are Critical for Granulosa Cell Differentiation","volume":"21","author":"Wayne","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19431","DOI":"10.1074\/jbc.M401235200","article-title":"Follicle-Stimulating Hormone Activation of Hypoxia-Inducible Factor-1 by the Phosphatidylinositol 3-Kinase\/AKT\/Ras Homolog Enriched in Brain (Rheb)\/Mammalian Target of Rapamycin (MTOR) Pathway Is Necessary for Induction of Select Protein Markers of Follicular Differentiation","volume":"279","author":"Alam","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1007\/s10815-021-02276-0","article-title":"Variants Ala307Ala and Ser680Ser of 307 and 680 FSHr Polymorphisms Negatively Influence on Assisted Reproductive Techniques Outcome and Determine High Probability of Non-Pregnancy in Caucasian Patients","volume":"38","author":"Montoro","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/cen.12573","article-title":"The Ser680Asn Polymorphism in the Follicle-Stimulating Hormone Receptor Gene Is Associated with the Ovarian Response in Controlled Ovarian Hyperstimulation","volume":"82","author":"Huang","year":"2015","journal-title":"Clin. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1177\/1933719116630419","article-title":"In Estimated Good Prognosis Patients Could Unexpected \u201cHyporesponse\u201d to Controlled Ovarian Stimulation Be Related to Genetic Polymorphisms of FSH Receptor?","volume":"23","author":"Alviggi","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"797365","DOI":"10.3389\/fendo.2021.797365","article-title":"Effect of Genetic Variants of Gonadotropins and Their Receptors on Ovarian Stimulation Outcomes: A Delphi Consensus","volume":"12","author":"Conforti","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4103\/0974-1208.86089","article-title":"Investigating the Association between Polymorphism of Follicle-Stimulating Hormone Receptor Gene and Ovarian Response in Controlled Ovarian Hyperstimulation","volume":"4","author":"Sheikhha","year":"2011","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1186\/s13048-014-0122-2","article-title":"Evaluating Influence of the Genotypes in the Follicle-Stimulating Hormone Receptor (FSHR) Ser680Asn (Rs6166) Polymorphism on Poor and Hyper-Responders to Ovarian Stimulation: A Meta-Analysis","volume":"7","author":"Pabalan","year":"2014","journal-title":"J. Ovarian Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.ymgme.2011.04.005","article-title":"Influence of Follicle-Stimulating Hormone Receptor (FSHR) Ser680Asn Polymorphism on Ovarian Function and in-Vitro Fertilization Outcome: A Meta-Analysis","volume":"103","author":"Yao","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.fertnstert.2012.08.037","article-title":"A Common Asn680Ser Polymorphism in the Follicle-Stimulating Hormone Receptor Gene Is Not Associated with Ovarian Response to Gonadotropin Stimulation in Patients Undergoing in Vitro Fertilization","volume":"99","author":"Mohiyiddeen","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.fertnstert.2012.02.012","article-title":"Assessment of FSHR Variants and Antim\u00fcllerian Hormone in Infertility Patients with a Reduced Ovarian Response to Gonadotropin Stimulation","volume":"97","author":"Binder","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/humrep\/dev342","article-title":"Combined Assessment of Polymorphisms in the LHCGR and FSHR Genes Predict Chance of Pregnancy after in Vitro Fertilization","volume":"31","author":"Lindgren","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1093\/humrep\/deab068","article-title":"The Effect of Polymorphisms in FSHR and FSHB Genes on Ovarian Response: A Prospective Multicenter Multinational Study in Europe and Asia","volume":"36","author":"Polyzos","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_25","first-page":"CD000099","article-title":"Growth Hormone for in Vitro Fertilization","volume":"1","author":"Duffy","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/humupd\/dmp026","article-title":"Addition of Growth Hormone to Gonadotrophins in Ovarian Stimulation of Poor Responders Treated by In-Vitro Fertilization: A Systematic Review and Meta-Analysis","volume":"15","author":"Kolibianakis","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"519572","DOI":"10.3389\/fendo.2020.519572","article-title":"The Effect of GH Administration on Oocyte and Zygote Quality in Young Women with Repeated Implantation Failure After IVF","volume":"11","author":"Tesarik","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, J., Chen, Q., Wang, J., Huang, G., and Ye, H. (2020). Does Growth Hormone Supplementation Improve Oocyte Competence and IVF Outcomes in Patients with Poor Embryonic Development? A Randomized Controlled Trial. BMC Pregnancy Childbirth, 20.","DOI":"10.1186\/s12884-020-03004-9"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.tjog.2017.10.018","article-title":"Effects of Growth Hormone plus Gonadotropins on Controlled Ovarian Stimulation in Infertile Women of Advanced Age, Poor Responders, and Previous in Vitro Fertilization Failure Patients","volume":"56","author":"Ho","year":"2017","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234014","DOI":"10.1155\/2014\/234014","article-title":"Growth Hormone and Reproduction: A Review of Endocrine and Autocrine\/Paracrine Interactions","volume":"2014","author":"Hull","year":"2014","journal-title":"Int. J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1530\/REP-14-0494","article-title":"A Direct Action for GH in Improvement of Oocyte Quality in Poor-Responder Patients","volume":"149","author":"Weall","year":"2015","journal-title":"Reproduction"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.tvjl.2004.05.014","article-title":"Control of Reproductive Processes by Growth Hormone: Extra- and Intracellular Mechanisms","volume":"170","author":"Sirotkin","year":"2005","journal-title":"Vet. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.fertnstert.2018.08.018","article-title":"Growth Hormone during in Vitro Fertilization in Older Women Modulates the Density of Receptors in Granulosa Cells, with Improved Pregnancy Outcomes","volume":"110","author":"Regan","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ghir.2015.09.002","article-title":"Growth Hormone Signaling Pathways","volume":"28","author":"Schwartz","year":"2016","journal-title":"Growth Horm. IGF Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ijgo.2015.10.020","article-title":"The Effects of Growth Hormone on Clinical Outcomes after Frozen-Thawed Embryo Transfer","volume":"133","author":"Hong","year":"2016","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/14647273.2020.1805517","article-title":"Performance of Ovarian Response Prediction Index (ORPI) in Predicting Ovarian Response and Livebirth in the in-Vitro Fertilisation Cycle Using a Standard Stimulation with Corifollitropin Alpha in a GnRH Antagonist Protocol","volume":"25","author":"Ng","year":"2022","journal-title":"Hum. Fertil."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/01443615.2016.1225025","article-title":"Predictive Values of Anti-M\u00fcllerian Hormone, Antral Follicle Count and Ovarian Response Prediction Index (ORPI) for Assisted Reproductive Technology Outcomes","volume":"37","author":"Ashrafi","year":"2017","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/09513590.2020.1786509","article-title":"Are Ovarian Reserve Tests Reliable in Predicting Ovarian Response? Results from a Prospective, Cross-Sectional, Single-Center Analysis","volume":"37","author":"Peluso","year":"2021","journal-title":"Gynecol. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s00404-018-4906-2","article-title":"Are We Choosing the Correct FSH Starting Dose during Controlled Ovarian Stimulation for Intrauterine Insemination Cycles? Potential Application of a Nomogram Based on Woman\u2019s Age and Markers of Ovarian Reserve","volume":"298","author":"Garzon","year":"2018","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_40","first-page":"CD012693","article-title":"Individualised Gonadotropin Dose Selection Using Markers of Ovarian Reserve for Women Undergoing in Vitro Fertilisation plus Intracytoplasmic Sperm Injection (IVF\/ICSI)","volume":"2","author":"Lensen","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"263349412199942","DOI":"10.1177\/2633494121999420","article-title":"Human Growth Hormone Use in Poor Ovarian Response\u2014Caution and Opportunities","volume":"15","author":"Norman","year":"2021","journal-title":"Ther. Adv. Reprod. Health"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3389\/fendo.2020.00105","article-title":"Management Strategies for POSEIDON Group 2","volume":"11","author":"Sunkara","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.fertnstert.2016.01.022","article-title":"Regimen of Ovarian Stimulation Affects Oocyte and Therefore Embryo Quality","volume":"105","author":"Bosch","year":"2016","journal-title":"Fertil. Steril."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/10\/2371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:41:56Z","timestamp":1760143316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/10\/2371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":43,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["diagnostics12102371"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12102371","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]}}}