Table_2_Homeostatic Model Assessment for Insulin Resistance Is Associated With Late Miscarriage in Non-Dyslipidemic Women Undergoing Fresh IVF/ICSI Embryo Transfer.docx

ObjectiveTo evaluate the associations between homeostatic model assessment for insulin resistance (HOMA-IR) and pregnancy outcomes in non-dyslipidemic infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).
Materials and MethodsThis is a retrospective study involving 3,615 non-dyslipidemic infertile women who attend to the Reproductive Medicine Center of Xiangya Hospital, Central South University (CSU) between January 2014 and October 2021. Eligible participants were divided into three groups according to the quartiles of HOMA-IR: Group 1 (HOMA-IR <1.46), Group 2 (1.46 to <2.71) and Group 3 (HOMA-IR ≥2.71). Baseline data, clinical characteristics during the assisted reproductive technology (ART) procedure, pregnancy, and neonatal outcomes were compared among the three groups. Subgroup analysis based on presence or absence of the polycystic ovary syndrome (PCOS) status was also performed to analyze the effects of HOMA-IR among non-PCOS populations.
ResultsThe late miscarriage rate and percentage of macrosomia increased with the HOMA-IR group (for late miscarriage rate: 2.23% vs. 3.04% vs. 7.35%, P<0.001; for macrosomia: 0.21% vs. 1.70% vs. 3.23%, P=0.002). Increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.50, 95% CI 1.64-7.47, P=0.001; adjusted OR 3.56, 95% CI 1.56-8.15, P=0.003). In the subgroup analysis, there were 3,165 participants in the non-PCOS group and 450 were assigned to the PCOS group. Late miscarriage rate increased with the HOMA-IR group among non-PCOS populations (2.20% vs. 3.03% vs. 7.67%, P<0.001). Late miscarriage rate of PCOS women were comparable among the three HOMA-IR groups (2.50% vs. 3.06% vs. 5.71%, P=0.634). Among non-PCOS women, increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.71, 95% CI 1.66-8.30, P=0.001; adjusted OR 3.82, 95% CI 1.59-9.17, P=0.003).
ConclusionsLate miscarriage rate and prevalence of macrosomia increased with the HOMA-IR index. Preconception HOMA-IR is an independent risk factor for late miscarriage in normolipidemic women undergoing IVF/ICSI-ET. Controlling insulin resistance before ART might prevent the occurrence of late miscarriage and macrosomia.

研究目的：本研究旨在探讨血脂正常的不孕女性接受体外受精/卵胞浆内单精子注射-胚胎移植（in vitro fertilization/intracytoplasmic sperm injection-embryo transfer, IVF/ICSI-ET）时，胰岛素抵抗稳态模型评估（homeostatic model assessment for insulin resistance, HOMA-IR）与妊娠结局的关联。
材料与方法：本研究为回顾性研究，纳入2014年1月至2021年10月期间于中南大学湘雅医院生殖医学中心（Central South University, CSU）就诊的3615例血脂正常的不孕女性。根据HOMA-IR的四分位数将符合入组标准的受试者分为3组：第1组（HOMA-IR <1.46）、第2组（1.46 ≤ HOMA-IR <2.71）及第3组（HOMA-IR ≥2.71）。比较3组受试者的基线资料、辅助生殖技术（assisted reproductive technology, ART）操作期间的临床特征、妊娠结局及新生儿结局。此外，基于是否合并多囊卵巢综合征（polycystic ovary syndrome, PCOS）进行亚组分析，以探讨HOMA-IR在非多囊卵巢综合征人群中的影响效应。
结果：晚期流产率与巨大儿发生率随HOMA-IR分组升高而逐渐升高：晚期流产率分别为2.23%、3.04%、7.35%（P<0.001）；巨大儿发生率分别为0.21%、1.70%、3.23%（P=0.002）。HOMA-IR升高（HOMA-IR≥2.71）与晚期流产呈正相关（粗比值比（crude OR）=3.50，95%置信区间（95% CI）：1.64~7.47，P=0.001；校正比值比（adjusted OR）=3.56，95%置信区间（95% CI）：1.56~8.15，P=0.003）。亚组分析结果显示，非多囊卵巢综合征组共纳入3165例受试者，多囊卵巢综合征组共450例受试者。在非多囊卵巢综合征人群中，晚期流产率随HOMA-IR分组升高而显著升高（2.20%、3.03%、7.67%，P<0.001）；而多囊卵巢综合征女性的晚期流产率在3个HOMA-IR组间无统计学差异（2.50%、3.06%、5.71%，P=0.634）。在非多囊卵巢综合征女性中，HOMA-IR升高（HOMA-IR≥2.71）与晚期流产呈正相关（粗比值比（crude OR）=3.71，95%置信区间（95% CI）：1.66~8.30，P=0.001；校正比值比（adjusted OR）=3.82，95%置信区间（95% CI）：1.59~9.17，P=0.003）。
结论：晚期流产率与巨大儿发生率随HOMA-IR指数升高而升高。孕前HOMA-IR是接受IVF/ICSI-ET的血脂正常女性发生晚期流产的独立危险因素。在辅助生殖技术前控制胰岛素抵抗，或可预防晚期流产及巨大儿的发生。