{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T22:11:29Z","timestamp":1769638289766,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T00:00:00Z","timestamp":1675468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>About 60% of cases of recurrent pregnancy loss have unexplained etiology. Immunotherapy for unexplained recurrent pregnancy loss is still unestablished. A 36-year-old woman, not obese, had a stillbirth at 22 gestational weeks and a spontaneous abortion at 8 weeks. She had been examined for recurrent pregnancy loss at previous clinics with no significant findings. When she visited our clinic, a hematologic test showed a Th1\/Th2 ratio imbalance. Ultrasonography, hysteroscopy, and semen analysis showed no abnormalities. She successfully conceived by embryo transfer in hormone replacement therapy cycle. However, she had a miscarriage at 19 weeks. The baby had no deformities, but a chromosomal test was not performed, according to the parents\u2019 will. The placenta pathologically suggested hemoperfusion problems. Her and her husband\u2019s chromosomal tests showed normal karyotypes. Other examinations revealed a repeated Th1\/Th2 ratio imbalance and a high resistance index of uterine radial artery blood flow. She was administered low-dose aspirin, intravenous immunoglobulin, and unfractionated heparin after the second embryo was transferred. Her baby was healthily born by cesarean section at 40 weeks. Intravenous immunoglobulin therapy can be a choice for recurrent miscarriage without risk factors because it has clinically beneficial influences on the patient\u2019s immunological aberration.<\/jats:p>","DOI":"10.3390\/jcm12041250","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T01:35:13Z","timestamp":1675647313000},"page":"1250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Successful Pregnancy and Delivery at Term Following Intravenous Immunoglobulin Therapy with Heparin for Unexplained Recurrent Pregnancy Loss Suspected of Immunological Abnormalities: A Case Report and Brief Literature Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Junichiro","family":"Mitsui","sequence":"first","affiliation":[{"name":"Graduate School of Medical and Dental Sciences, Comprehensive Reproductive Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan"},{"name":"Kameda IVF Clinic Makuhari, Reproductive Medicine, Chiba 261-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3984-975X","authenticated-orcid":false,"given":"Kuniaki","family":"Ota","sequence":"additional","affiliation":[{"name":"Kameda IVF Clinic Makuhari, Reproductive Medicine, Chiba 261-0023, Japan"},{"name":"Fukushima Medical Center for Children and Women, Fukushima Medical University, Fukushima 960-1295, Japan"},{"name":"Department of obstetrics and Gynecology, Tokyo Rosai Hospital, Tokyo 143-0013, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Takayanagi","sequence":"additional","affiliation":[{"name":"Kameda IVF Clinic Makuhari, Reproductive Medicine, Chiba 261-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurie","family":"Nako","sequence":"additional","affiliation":[{"name":"Kameda IVF Clinic Makuhari, Reproductive Medicine, Chiba 261-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Tajima","sequence":"additional","affiliation":[{"name":"Kameda IVF Clinic Makuhari, Reproductive Medicine, Chiba 261-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-7458","authenticated-orcid":false,"given":"Atsushi","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hyogo Medical University, Nishinomiya 663-8131, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-3207","authenticated-orcid":false,"given":"Kiyotaka","family":"Kawai","sequence":"additional","affiliation":[{"name":"Kameda IVF Clinic Makuhari, Reproductive Medicine, Chiba 261-0023, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"ESHRE Guideline Group on RPL, Bender Atik, R., Christiansen, O.B., Elson, J., Kolte, A.M., Lewis, S., Middeldorp, S., Nelen, W., Peramo, B., and Quenby, S. (2018). ESHRE Guideline: Recurrent Pregnancy Loss. Hum. Reprod. Open, 2018, hoy004.","DOI":"10.1093\/hropen\/hoy004"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1053\/j.semperi.2018.12.008","article-title":"Review of Current Guidelines for Recurrent Pregnancy Loss: New Strategies for Optimal Evaluation of Women Who May Be Superfertile","volume":"43","author":"Khalife","year":"2019","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Practice Committee of the American Society for Reproductive Medicine (2012). Evaluation and Treatment of Recurrent Pregnancy Loss: A Committee Opinion. Fertil. Steril., 98, 1103\u20131111.","DOI":"10.1016\/j.fertnstert.2012.06.048"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1111\/jog.12388","article-title":"Management of Recurrent Miscarriage","volume":"40","author":"Ozaki","year":"2014","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jri.2011.03.003","article-title":"Future Directions of Studies for Recurrent Miscarriage Associated with Immune Etiologies","volume":"90","author":"Saito","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.3389\/fimmu.2020.02025","article-title":"T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1\/Th2\/Th9\/Th17\/Th22\/Tfh Cells","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"689019","DOI":"10.3389\/fimmu.2021.689019","article-title":"The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1600-0897.2012.01111.x","article-title":"Does Immunotherapy for Treatment of Reproductive Failure Enhance Live Births?","volume":"67","author":"Coulam","year":"2012","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.it.2017.08.008","article-title":"Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin","volume":"38","author":"Maddur","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13290","DOI":"10.1111\/aji.13290","article-title":"Intralipid Treatment for Women with Reproductive Failures","volume":"85","author":"Coulam","year":"2021","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/intimm\/dxx039","article-title":"IVIG-Mediated Effector Functions in Autoimmune and Inflammatory Diseases","volume":"29","author":"Galeotti","year":"2017","journal-title":"Int. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9428","DOI":"10.1002\/jcp.27627","article-title":"NK Cell Frequency and Cytotoxicity in Correlation to Pregnancy Outcome and Response to IVIG Therapy among Women with Recurrent Pregnancy Loss","volume":"234","author":"Ahmadi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/aji.12442","article-title":"Intravenous Immunoglobulin G Improves Pregnancy Outcome in Women with Recurrent Pregnancy Losses with Cellular Immune Abnormalities","volume":"75","author":"Lee","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_14","first-page":"CD000112","article-title":"Immunotherapy for Recurrent Miscarriage","volume":"2014","author":"Wong","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jri.2019.06.001","article-title":"Treatment with Intravenous Immunoglobulin in Patients with Recurrent Pregnancy Loss: An Update","volume":"133","author":"Christiansen","year":"2019","journal-title":"J. Reprod. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1093\/humrep\/deq179","article-title":"Intravenous Immunoglobulin and Idiopathic Secondary Recurrent Miscarriage: A Multicentered Randomized Placebo-Controlled Trial","volume":"25","author":"Stephenson","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1093\/humrep\/12.11.2388","article-title":"Short-Term Therapy for Recurrent Abortion Using Intravenous Immunoglobulins: Results of a Double-Blind Placebo-Controlled Italian Study","volume":"12","author":"Perino","year":"1997","journal-title":"Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/1471-0528.13192","article-title":"Intravenous Immunoglobulin Treatment for Secondary Recurrent Miscarriage: A Randomised, Double-Blind, Placebo-Controlled Trial","volume":"122","author":"Christiansen","year":"2015","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101527","DOI":"10.1016\/j.eclinm.2022.101527","article-title":"Intravenous Immunoglobulin Treatment in Women with Four or More Recurrent Pregnancy Losses: A Double-Blind, Randomised, Placebo-Controlled Trial","volume":"50","author":"Yamada","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1093\/humrep\/17.3.809","article-title":"A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Immunoglobulin in the Prevention of Recurrent Miscarriage: Evidence for a Therapeutic Effect in Women with Secondary Recurrent Miscarriage","volume":"17","author":"Christiansen","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"512732","DOI":"10.5402\/2012\/512732","article-title":"A High Dose Intravenous Immunoglobulin Therapy for Women with Four or More Recurrent Spontaneous Abortions","volume":"2012","author":"Yamada","year":"2012","journal-title":"ISRN Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13395","DOI":"10.1111\/aji.13395","article-title":"A Systemic Review of Intravenous Immunoglobulin G Treatment in Women with Recurrent Implantation Failures and Recurrent Pregnancy Losses","volume":"85","author":"Saab","year":"2021","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1182\/blood-2014-11-610857","article-title":"Enoxaparin for Prevention of Unexplained Recurrent Miscarriage: A Multicenter Randomized Double-Blind Placebo-Controlled Trial","volume":"125","author":"Pasquier","year":"2015","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"601","DOI":"10.7326\/M14-2062","article-title":"Low-Molecular-Weight Heparin for Women with Unexplained Recurrent Pregnancy Loss: A Multicenter Trial with a Minimization Randomization Scheme","volume":"162","author":"Schleussner","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e13219","DOI":"10.1111\/aji.13219","article-title":"Comparison of Therapeutic Interventions for Recurrent Pregnancy Loss in Association with Antiphospholipid Syndrome: A Systematic Review and Network Meta-Analysis","volume":"83","author":"Liu","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaci.2016.09.023","article-title":"Update on the Use of Immunoglobulin in Human Disease: A Review of Evidence","volume":"139","author":"Perez","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/humrep\/deg156","article-title":"Increased T Helper 1 Cytokine Responses by Circulating T Cells Are Present in Women with Recurrent Pregnancy Losses and in Infertile Women with Multiple Implantation Failures after IVF","volume":"18","author":"Ng","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_28","first-page":"398","article-title":"Determination of Clinical Cellular Immune Markers in Women with Recurrent Pregnancy Loss","volume":"70","author":"Lee","year":"2013","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.biopha.2017.06.001","article-title":"Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss (RPL)","volume":"92","author":"Ahmadi","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Marron, K., and Harrity, C. (2022). Correlation of peripheral blood and endometrial immunophenotyping in ART: Is peripheral blood sampling useful?. J. Assist. Reprod. Genet.","DOI":"10.1007\/s10815-022-02696-6"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1038\/s41598-017-03191-0","article-title":"Human uterine lymphocytes acquire a more experienced and tolerogenic phenotype during pregnancy","volume":"7","author":"Feyaerts","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jri.2016.03.001","article-title":"A shift in the balance of T17 and Treg cells in menstrual blood of women with unexplained recurrent spontaneous abortion","volume":"116","author":"Hosseini","year":"2016","journal-title":"J. Reprod. Immunol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:24:26Z","timestamp":1760120666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,4]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041250"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041250","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,4]]}}}