Han Jae Won, Park Jin Sol, Kim Jong-Seok, Lee Sung Ki
Department of Obstetrics and Gynecology, Konyang University College of Medicine, Daejeon, Republic of Korea.
Myunggok Medical Research Institute, Konyang University College of Medicine, Daejeon, Republic of Korea.
Front Endocrinol (Lausanne). 2025 Jun 4;16:1546602. doi: 10.3389/fendo.2025.1546602. eCollection 2025.
Various causes of recurrent pregnancy loss (RPL) have been identified, but even with a detailed evaluation, almost half of the cases have unidentified etiologies. Immune imbalance is one of the proposed potential etiologies of these idiopathic RPL. To regulate abnormal cellular immunity, intravenous immunoglobulin (IVIG), a type of immunotherapy, is proposed to improve pregnancy outcomes. However, the efficacy of IVIG in RPL is still controversial.
RPL was defined as women with two or more spontaneous abortions and in total, 987 RPL women visited Department of Obstetrics and Gynecology, Konyang University Hospital from January 2007 to December 2020. Only those with a full evaluation and known treatment outcome were included. Idiopathic RPL(n=215) and women with known etiology (n=251) were enrolled. Both the idiopathic and known etiology groups were subsequently stratified into subgroups based on the presence of at least one abnormal cellular immunity (n=100 and n=97, respectively). We investigated the pregnancy outcome by sorting the patients into seven subgroups depending on abnormal cellular immunity including natural killer (NK) cell level, NK cell cytotoxicity and Th1/Th2 ratio.
Patients with older age and higher body mass index had negative effect on pregnancy outcomes whereas the number of previous miscarriages did not show significant difference in pregnancy outcomes. Among all RPL women with at least one abnormal cellular immunity were treated with IVIG and the overall live birth rate (LBR) was 82.7%. The group which did not have IVIG treatment showed an overall LBR of 80.7%. Among the seven groups of idiopathic RPL women with abnormal cellular immunity, the group with both high NK cell level and NK cell cytotoxicity showed the highest LBR, 90.5%, and the group with both high NK cell level and Th1/Th2 ratio showed the lowest LBR, 75%.
IVIG treatment appears to improve LBRs in women with RPL and abnormal cellular immunity. These findings support the potential benefit of IVIG in selected RPL patients with immune imbalances. Further studies are needed to refine patient selection criteria and optimize treatment protocols for improving pregnancy outcomes in this population.
复发性流产（RPL）的病因多种多样，但即便经过详细评估，仍有近半数病例病因不明。免疫失衡是这些不明原因复发性流产潜在的病因之一。为调节异常的细胞免疫，有人提出采用静脉注射免疫球蛋白（IVIG）这种免疫疗法来改善妊娠结局。然而，IVIG治疗复发性流产的疗效仍存在争议。
复发性流产定义为有两次或两次以上自然流产的女性。2007年1月至2020年12月期间，共有987名复发性流产女性前往韩国公州大学医院妇产科就诊。仅纳入那些经过全面评估且已知治疗结果的患者。纳入特发性复发性流产患者（n = 215）和已知病因的患者（n = 251）。随后，根据是否存在至少一种异常细胞免疫，将特发性和已知病因组进一步分层为亚组（分别为n = 100和n = 97）。我们根据包括自然杀伤（NK）细胞水平、NK细胞细胞毒性和Th1/Th2比值在内的异常细胞免疫情况，将患者分为七个亚组，研究其妊娠结局。
年龄较大和体重指数较高的患者对妊娠结局有负面影响，而既往流产次数在妊娠结局方面未显示出显著差异。在所有至少有一种异常细胞免疫的复发性流产女性中，接受IVIG治疗的总体活产率（LBR）为82.7%。未接受IVIG治疗的组总体活产率为80.7%。在七组细胞免疫异常的特发性复发性流产女性中，NK细胞水平和NK细胞细胞毒性均高的组活产率最高，为90.5%，而NK细胞水平和Th1/Th2比值均高的组活产率最低，为75%。
IVIG治疗似乎可提高复发性流产且细胞免疫异常女性的活产率。这些发现支持了IVIG在选定的免疫失衡复发性流产患者中的潜在益处。需要进一步研究以完善患者选择标准，并优化治疗方案，从而改善该人群的妊娠结局。
