{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:21:46Z","timestamp":1792790506807,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003827","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["PD137914"],"award-info":[{"award-number":["PD137914"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003827","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["K132155"],"award-info":[{"award-number":["K132155"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003827","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["7873"],"award-info":[{"award-number":["7873"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Szeged Open Access Fund","award":["PD137914"],"award-info":[{"award-number":["PD137914"]}]},{"name":"University of Szeged Open Access Fund","award":["K132155"],"award-info":[{"award-number":["K132155"]}]},{"name":"University of Szeged Open Access Fund","award":["7873"],"award-info":[{"award-number":["7873"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Thyroid disorders, particularly thyroid autoimmunity, are increasingly prevalent among women of reproductive age and have been linked to fertility outcomes. While current endocrinology guidelines define distinct thyroid-stimulating hormone (TSH) target values for women undergoing assisted reproductive technology (ART), the optimal preconception TSH range for in vitro fertilization (IVF) success remains a topic of debate. Objectives: This study aimed to assess the impact of baseline TSH levels within the recommended normal range on IVF outcomes, specifically clinical pregnancy and live birth rates. Additionally, we assessed the predictive value of procedural and preprocedural factors, including maternal body mass index (BMI) and TSH, using machine learning models. Methods: We conducted a retrospective, single-center cohort study at the Institute of Reproductive Medicine, University of Szeged, involving 996 women who underwent IVF, with or without intracytoplasmic sperm injection. Biometric, medical history, laboratory, and procedural factors were analyzed. Pregnancy and live birth predictions were modeled using support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost) algorithms. The significance of features in the RF and XGBoost models was assessed. Results: SVM models achieved a mean accuracy of 72.26% in predicting pregnancy but were less effective for live birth classification. RF and XGBoost models demonstrated an area under the receiver operating characteristic curve of 0.76 and 0.74 for pregnancy and 0.67 and 0.61, respectively, for live birth. Key predictors included embryo score, maternal age, BMI, and specific hormone levels. Notably, male factors also contributed to outcome prediction. Analysis suggested that variations in maternal TSH within the normal range (0.3\u20134.0 mIU\/L) had no significant impact on IVF success. Conclusions: Our study suggests that preconception TSH levels within the reference range do not significantly influence IVF success, which indirectly supports the validity of the current recommendations on this matter. While machine learning models demonstrated promising predictive performance, larger prospective studies are needed to refine thyroid function targets in ART, with a separate analysis of women with thyroid autoimmunity.<\/jats:p>","DOI":"10.3390\/jcm14134407","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:13:56Z","timestamp":1750407236000},"page":"4407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Influence of Pre-IVF Day 2 TSH Levels on Treatment Success and Obstetric Outcomes: A Retrospective Single-Center Analysis with Machine Learning-Based Data Evaluation"],"prefix":"10.3390","volume":"14","author":[{"given":"Bernadett","family":"N\u00e1dasdi","sequence":"first","affiliation":[{"name":"Department of Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-8226","authenticated-orcid":false,"given":"Viktor","family":"Vedelek","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krist\u00f3f","family":"Bereczki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ty\u00e1s","family":"Bukva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Albert Szent-Gy\u00f6rgyi Medical School, Faculty of Science and Informatics, University of Szeged, 6720 Szeged, Hungary"},{"name":"Department of Pediatrics and Pediatric Health Center, University of Szeged Albert Szent-Gy\u00f6rgyi Health Center, Kor\u00e1nyi Fasor 14-15, 6720 Szeged, Hungary"},{"name":"Laboratory of Microscopic Image Analysis and Machine Learning, Institute of Biochemistry, Biological Research Centre, Hungarian Research Network (HUN-REN), 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-9895","authenticated-orcid":false,"given":"Zoltan","family":"Kozinszky","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"},{"name":"Capio Specialized Center for Gynecology, Solna, 17145 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-4184","authenticated-orcid":false,"given":"Rita","family":"Sinka","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-2118","authenticated-orcid":false,"given":"J\u00e1nos","family":"Z\u00e1dori","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"},{"name":"Institute of Reproductive Medicine, Albert Szent-Gyorgyi Medical School, University of Szeged, 6723 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"V\u00e1gv\u00f6lgyi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S1472-6483(10)60091-0","article-title":"Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue","volume":"18","author":"Aghajanova","year":"2009","journal-title":"Reprod. Biomed. Online"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1007\/s40618-023-02269-z","article-title":"Role of thyroid stimulating hormone in the maintenance and functioning of the human corpus luteum","volume":"47","author":"Taggi","year":"2024","journal-title":"J. Endocrinol. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101378","DOI":"10.1016\/j.beem.2020.101378","article-title":"Impact of thyroid disease on fertility and assisted conception","volume":"34","author":"Unuane","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hu, X., Chen, Y., Shen, Y., Tian, R., Sheng, Y., and Que, H. (2022). Global prevalence and epidemiological trends of Hashimoto\u2019s thyroiditis in adults: A systematic review and meta-analysis. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.1020709"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1210\/jc.2013-2409","article-title":"The incidence and prevalence of thyroid dysfunction in Europe: A meta-analysis","volume":"99","author":"Juan","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.fertnstert.2010.12.004","article-title":"Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization\/intracytoplasmic sperm injection","volume":"95","author":"Kim","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1210\/js.2018-00090","article-title":"Subclinical Hypothyroidism in Women Planning Conception and During Pregnancy: Who Should Be Treated and How?","volume":"2","author":"Maraka","year":"2018","journal-title":"J. Endocr. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1159\/000512790","article-title":"2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction","volume":"9","author":"Poppe","year":"2021","journal-title":"Eur. Thyroid J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"988","DOI":"10.4158\/EP12280.GL","article-title":"Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association","volume":"18","author":"Garber","year":"2012","journal-title":"Endocr. Pract."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1530\/RAF-20-0065","article-title":"Thyroid function and IVF outcome for different indications of subfertility","volume":"2","author":"Aissa","year":"2021","journal-title":"Reprod. Fertil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.diabet.2014.11.009","article-title":"Increased TSH in obesity: Evidence for a BMI-independent association with leptin","volume":"41","author":"Bernard","year":"2015","journal-title":"Diabetes Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1507\/endocrj.EJ19-0441","article-title":"Body mass index (BMI) is associated with serum thyroid-stimulating hormone (TSH) level in infertile women: A cross-sectional study","volume":"67","author":"Dai","year":"2020","journal-title":"Endocr. J."},{"key":"ref_13","unstructured":"National Institute for Health and Care Excellence (2013). Fertility Problems: Assessment and Treatment, NICE. Available online: https:\/\/www.nice.org.uk\/guidance\/cg156."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vedelek, V., Bicskei, P., T\u00e1bi, M., Lajk\u00f3, N., \u00c9kes, C., Bereczki, K., Meixner-Cs\u00e1ti, Z., Sinka, R., V\u00e1gv\u00f6lgyi, A., and Z\u00e1dori, J. (2024). Endometrium development patterns and BMI groups among in vitro fertilization patients; prognostic aspects. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1379109"},{"key":"ref_15","first-page":"128","article-title":"Factors Associated with In Vitro Fertilization Live Birth Outcome: A Comparison of Different Classification Methods","volume":"15","author":"Amini","year":"2021","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_16","unstructured":"World Health Organization (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, WHO. [6th ed.]. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240030787."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.fertnstert.2009.09.009","article-title":"International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009","volume":"92","author":"Adamson","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0020-7292(85)90003-7","article-title":"Sonographic criteria of phasic changes in human endometrial tissue","volume":"23","author":"Sakamoto","year":"1985","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_19","first-page":"5","article-title":"Methods of embryo scoring in in vitro fertilization","volume":"4","author":"Baczkowski","year":"2004","journal-title":"Reprod. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gardner, D.K., Weisssmann, A., Howles, C.M., and Shoham, Z. (2004). Textbook of Assisted Reproductive Techniques: Laboratory and Clinical Perspectives, CRC Press. [2nd ed.].","DOI":"10.3109\/9780203012840"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.fertnstert.2016.11.012","article-title":"Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates","volume":"107","author":"Irani","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_22","unstructured":"Lundberg, S.M., and Lee, S.-I. (2017). A Unified Approach to Interpreting Model Predictions. Advances in Neural Information Processing Systems 30 (NeurIPS 2017), NIPS Foundation."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/j.1467-9868.2007.00646.x","article-title":"Fast Stable Direct Fitting and Smoothness Selection for Generalized Additive Models","volume":"70","author":"Wood","year":"2008","journal-title":"J. R. Stat. Soc. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4103\/jhrs.jhrs_168_21","article-title":"Relationship between Maternal Serum Thyroid-Stimulating Hormone and in vitro Fertilisation-Conceived Pregnancy Outcomes","volume":"15","author":"Coussa","year":"2022","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000357193","article-title":"Association of TSH concentrations and thyroid autoimmunity with IVF outcome in women with TSH concentrations within normal adult range","volume":"77","author":"Mintziori","year":"2014","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"d\u2019Assun\u00e7\u00e3o, V.R.N., Montagna, E., d\u2019Assun\u00e7\u00e3o, L.E.N., Caldas, M.M.P., Christofolini, D.M., Barbosa, C.P., Negreiros, R.A.M., Lagan\u00e0, A.S., de Oliveira, R., and Bianco, B. (2022). Effect of thyroid function on assisted reproduction outcomes in euthyroid infertile women: A single center retrospective data analysis and a systematic review and meta-analysis. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1023635"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00404-022-06683-1","article-title":"Anti-m\u00fcllerian hormone as a predictor for live birth among women undergoing IVF\/ICSI in different age groups: An update of systematic review and meta-analysis","volume":"308","author":"Li","year":"2023","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2147\/tcrm.2006.2.4.355","article-title":"In vitro fertilization (IVF): A review of 3 decades of clinical innovation and technological advancement","volume":"2","author":"Wang","year":"2006","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lantzi, M.A., Papakonstantinou, E., and Vlachakis, D. (2025). Bioinformatic Analysis of Complex In Vitro Fertilization Data and Predictive Model Design Based on Machine Learning: The Age Paradox in Reproductive Health. Biology, 14.","DOI":"10.3390\/biology14050556"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.fertnstert.2020.09.157","article-title":"Artificial intelligence in human in vitro fertilization and embryology","volume":"114","author":"Zaninovic","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.fertnstert.2020.09.159","article-title":"Evaluating predictive models in reproductive medicine","volume":"114","author":"Curchoe","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liu, X., Chen, P., Wang, M., Zhao, W., Jin, L., Shi, J., Mao, Y., Zhang, C., Liang, X., and Huang, R. (2024). Association between pre-gravid body mass index and clinical outcomes in in vitro fertilization: A multicentered retrospective cohort study. BMC Pregnancy Childbirth, 24.","DOI":"10.1186\/s12884-024-06661-2"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Abdala, A., Kalafat, E., Elkhatib, I., Bayram, A., Melado, L., Fatemi, H., and Nogueira, D. (2025). Predictive model for live birth outcomes in single euploid frozen embryo transfers: A comparative analysis of logistic regression and machine learning approaches. J. Assist. Reprod. Genet.","DOI":"10.1007\/s10815-025-03524-3"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, L., Cui, X., Yang, J., Wu, X., and Zhao, G. (2023). Using feature optimization and LightGBM algorithm to predict the clinical pregnancy outcomes after in vitro fertilization. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1305473"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ding, N., Zhang, J., Wang, P., and Wang, F. (2023). A novel machine learning model for predicting clinical pregnancy after laparoscopic tubal anastomosis. BMC Pregnancy Childbirth, 23.","DOI":"10.1186\/s12884-023-05854-5"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1093\/humrep\/dead163","article-title":"Predicting the number of oocytes retrieved from controlled ovarian hyperstimulation with machine learning","volume":"38","author":"Ferrand","year":"2023","journal-title":"Hum. Reprod."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4407\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:55:47Z","timestamp":1760032547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":36,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134407"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134407","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]}}}