INTRODUCTION: Embryonic chromosomal abnormalities are the major cause of miscarriage. As a relatively novel genetic screening technology, high-throughput ligation-dependent probe amplification combined with short tandem repeat analysis (HLPA + STR) demonstrates significant clinical advantages, including shorter turnaround time, user-friendly technical workflows, and superior cost-effectiveness. The purpose of this study is to evaluate the frequency and characteristics of fetal chromosomal abnormalities using HLPA + STR in early pregnancy loss (EPL). METHODS: A retrospective analysis was conducted on women who experienced EPL and underwent HLPA + STR. Group differences were compared using χ2 or Fisher's exact test, and multivariate logistic regression analysis was performed to examine the correlation between the fetal cytogenetic results and maternal age, gestational age, and history of miscarriage. RESULTS: In total, 820 (61.75%) cases were detected to be chromosomal abnormalities, including 748 (91.22%) had numerical abnormalities, 59 (7.19%) had structural abnormalities, and 13 (1.59%) had chromosome mosaicism. The most frequent chromosomal abnormality was autosomal trisomy, of which trisomy (T) 16 was the most common, followed by sex chromosome monosomy and triploid. The incidence of fetal chromosomal abnormalities was significantly higher advanced maternal age (AMA) than in non-advanced maternal age (non-AMA) (p < 0.001). The AMA had a 1.93 times higher risk of fetal chromosomal abnormalities compared to the non-AMA (odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.39-2.68; p < 0.001). The risk of fetal chromosomal abnormalities in fetuses with a gestational age > 8 weeks was found to be 1.34 times higher compared to those with a gestational age ≤ 8 weeks (OR, 1.34; 95% CI, 1.07-1.69; p = 0.012). No statistically significant variation in fetal chromosomal abnormalities was observed in the history of miscarriage (p > 0.05). CONCLUSION: In conclusion, our results show that HLPA + STR is an effective strategy for cytogenetic analysis of EPL. In addition, Multivariate analysis identified advanced maternal age and gestational age are independent risk factors for fetal cytogenetic results in EPL, but not related to the history of miscarriage. Therefore, we recommend HLPA + STR as the first-tier screening tool for genetic evaluation in EPL. However, the results of complex abnormalities need to be combined with other techniques.