Novel Insights into Normal Karyotype Miscarriage: Distinctive Patterns and Implications for Diagnosis Based on Next-Generation Sequencing Analysis

Yumene Kubota; Tomoko Ichikawa; Shigeru Matsuda; Yoshimitsu Kuwabara; Shunji Suzuki; Yasuyuki Negishi

doi:10.1002/rmb2.70053

Novel Insights into Normal Karyotype Miscarriage: Distinctive Patterns and Implications for Diagnosis Based on Next-Generation Sequencing Analysis

Reprod Med Biol. 2026 May 11:25:e70053. doi: 10.1002/rmb2.70053. eCollection 2026 Jan-Dec.

Authors

Yumene Kubota¹, Tomoko Ichikawa¹, Shigeru Matsuda¹, Yoshimitsu Kuwabara¹, Shunji Suzuki¹, Yasuyuki Negishi^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology Nippon Medical School Tokyo Japan.
² Department of Microbiology and Immunology Nippon Medical School Tokyo Japan.

Abstract

Purpose: This study aimed to identify the clinical differences between normal and abnormal karyotype miscarriages and evaluate whether clinical findings could predict the presence or absence of chromosomal abnormalities.

Methods: A total of 117 patients with early miscarriage who underwent chorionic villus chromosomal testing using next-generation sequencing were retrospectively analyzed. Clinical findings were compared between the normal (euploid; n = 47) and abnormal karyotype (aneuploid; n = 70) groups.

Results: Normal karyotype miscarriages occurred significantly more often before yolk sac visualization (29.8% vs. 0%, p < 0.0001) and before fetal heartbeat confirmation (51.1% vs. 15.7%, p = 0.0001) than abnormal karyotype miscarriages. The mean crown-rump length was larger in the normal karyotype group (15.3 ± 8.2 mm vs. 11.8 ± 6.8 mm, p = 0.037). Normal karyotype miscarriages exhibited a bimodal distribution in gestational age at miscarriage. In addition, the normal karyotype was associated with a history of two or more biochemical pregnancy losses (21.3% vs. 7.1%, p = 0.045).

Conclusion: Distinct clinical and ultrasonographic patterns were observed in normal and abnormal karyotype miscarriages. These features have limited diagnostic value, and their usefulness in supporting counseling or decision-making is also limited when genetic testing is not available.

Keywords: biochemical pregnancy loss; chromosomal analysis of chorionic villus; early miscarriage; normal karyotype miscarriage; subchorionic hematoma.