冻融胚胎移植患者血β-hCG水平与妊娠囊大小对早期妊娠结局的影响

Effect of blood β-hCG level and gestational sac size on early pregnancy outcomes in patients with frozen-thawed embryo transfer

摘要

目的 探讨妊娠囊大小和血β-hCG水平对冻融胚胎移植早期妊娠结局的影响。方法 选择2018年8月至2023年8月期间舟山市妇女儿童医院收治的150例冻融胚胎移植患者作为研究组(继续妊娠组68例、早期妊娠终止组82例),76例同期健康孕妇作为对照组,对比两组妊娠囊大小和血β-hCG水平指标.采用平滑曲线拟合冻融胚胎移植早期妊娠发生率与妊娠囊大小及血β-hCG水平的关系;Logistic回归分析妊娠囊大小及血β-hCG水平对冻融胚胎移植患者结局的关联性;受试者工作特征(ROC)曲线及曲线下面积(AUC)评价预测效能;相加及相乘模型评价妊娠囊大小与血β-hCG水平的交互作用。结果 研究组卵黄囊大小异常、绒毛膜下轻度血肿占比、血β-hCG水平高于对照组,卵黄囊变形占比、妊娠囊大小低于对照组,差异均有统计学意义(χ²/t值介于3.720~169.237之间,P＜0.05);与继续妊娠组相比,早期妊娠终止组开始黄体支持前的内膜厚度较薄,阴道流血占比较高,发现胎膜下血肿(SCH)时的妊娠周数较早,妊娠囊较小,血β-hCG水平较高,卵黄囊大小异常、绒毛膜下中度血肿占比较高,差异均有统计学意义(χ²/t值介于2.309~115.951之间,P＜0.05);冻融胚胎移植早期妊娠终止发生率随血β-hCG水平升高而升高,随妊娠囊大小的升高而降低;多因素Logistic回归结果显示妊娠囊大小是冻融胚胎移植患者早期妊娠终止的保护因素(OR值介于0.17~0.73之间,P＜0.05),血β-hCG水平是危险因素(OR值介于1.36~2.19之间,P＜0.05);妊娠囊大小和血β-hCG水平联合预测早期妊娠终止结局的ROC曲线下面积为0.957(95%CI:0.904~0.989),大于独立标志物预测早期妊娠终止结局的效能(P＜0.05);妊娠囊≤1.53cm与血β-hCG水平＞1022.12U/L在冻融胚胎移植患者结局中存在相乘交互作用,两因素共同存在时冻融胚胎移植患者早期妊娠终止率更高(OR＝5.209,95%CI:2.379~7.846)。结论 血β-hCG水平与妊娠囊大小是评估冻融胚胎移植后早期妊娠结局的重要指标.

Abstract

Objective To explore the effects of gestational sac size and blood β-hCG level on the early pregnancy outcomes of frozen-thaw embryo transfer. Methods A total of 150 patients with frozen-thaw embryo transfer admitted to Zhoushan Women and Children Hospital from August 2018 to August 2023 were selected as the study group (68 cases in the continued pregnancy group and 82 cases in the early pregnancy termination group), and 76 healthy pregnant women in the same period were selected as the control group. The gestational sac size and blood β-hCG level indicators were compared between the two groups. The smooth curve was used to fit the relationship between the incidence of early pregnancy in frozen-thaw embryo transfer and the gestational sac size and blood β-hCG level; Logistic regression was used to analyze the association between the gestational sac size and blood β-hCG level on the outcomes of frozen-thaw embryo transfer patients; the receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive efficiency; the additive and multiplicative models were used to evaluate the interaction between the gestational sac size and blood β-hCG level. Results The abnormal yolk sac size, the proportion of mild subchorionic hematoma, and the blood β-hCG level in the study group were higher than those in the control group, while the proportion of yolk sac deformation and the size of gestational sac were lower than those in the control group, and the differences were statistically significant (χ²/t ＝3.720-169.237, P＜0.05). Compared with the continuing pregnancy group, the endometrial thickness before the start of luteal support in the early pregnancy termination group was thinner, the proportion of vaginal bleeding was higher, the gestational week when subchorionic hematoma (SCH) was found was earlier, the gestational sac was smaller, the blood β-hCG level was higher, the abnormal yolk sac size and the proportion of moderate subchorionic hematoma were higher, and the differences were statistically significant (χ²/t ＝2.309-115.951, P ＜0.05). The incidence of early pregnancy termination in embryo transfer increased with the increase of blood β-hCG level and decreased with the increase of gestational sac size. The results of multivariate logistic regression showed that gestational sac size was a protective factor for early pregnancy termination in patients with frozen-thawed embryo transfer (OR＝0.17-0.73, P＜0.05), and blood β-hCG level was a risk factor (OR＝1.36-2.19, P＜0.05). The area under the ROC curve of gestational sac size and blood β-hCG level in jointly predicting the outcome of early pregnancy termination was 0.957 (95%CI:0.904-0.989), which was greater than the efficacy of independent markers in predicting the outcome of early pregnancy termination (P＜0.05). There was a multiplicative interaction between gestational sac ≤1.53cm and blood β-hCG level ＞1022.12U/L in the outcome of frozen-thawed embryo transfer patients. When the two factors coexisted, the early pregnancy termination rate of frozen-thawed embryo transfer patients was higher (OR＝5.209, 95%CI:2.379-7.846). Conclusion The blood β-hCG level and gestational sac size are important indicators for evaluating the early pregnancy outcome after frozen-thaw embryo transfer.

关键词

超声 / 妊娠囊 / β-hCG / 胚胎移植 / 不良妊娠

Key words

ultrasound / gestational sac / β-hCG / embryo transfer / adverse pregnancy

参考文献

[1] Godiwala P, Makhijani R, Bartolucci A, et al. Pregnancy outcomes after frozen-thawed embryo transfer using letrozole ovulation induction, natural, or programmed cycles[J]. Fertil Steril, 2022, 118(4): 690-698.

[2] 李泽丽, 陈练, 石慧峰, 等. 超声联合磁共振成像检查预测胎盘植入性疾病不良妊娠结局的列线图模型构建[J]. 实用妇产科杂志, 2023, 39(4): 277-281.

[3] Macedo L C G M, Cavagna N M, Dzik A, et al. Oral dydrogesterone in frozen-thawed embryo transfer cycles[J]. Rev Assoc Med Bras, 2022, 68(1): 100-105.

[4] Casper R F. Frozen embryo transfer: evidence-based markers for successful endometrial preparation[J]. Fertil Steril, 2020, 113(2): 248-251.

[5] Chang Y, Shen M, Wang S, et al. Association of embryo transfer type with infertility in endometriosis: a systematic review and meta-analysis[J]. J Assist Reprod Genet, 2022, 39(5): 1033-1043.

[6] Løssl K, Spangmose A L, Asserhøj L L, et al. The future of frozen-thawed embryo transfer in hormone replacement therapy cycles[J]. Curr Opin Obstet Gynecol, 2023, 35(3): 200-209.

[7] Kadour-Peero E, Feferkorn I, Bellemare V, et al. A comparison of frozen-thawed embryo transfer protocols in 2920 single-blastocyst transfers[J]. Arch Gynecol Obstet, 2022, 306(3): 887-892.

[8] Von V F, Conrad K P, Baker V L. Which protocol for frozen-thawed embryo transfer is associated with the best outcomes for the mother and baby? [J]. Fertil Steril, 2021, 115(4): 886-887.

[9] An B G L, Chapman M, Tilia L, et al. Is there an optimal window of time for transferring single frozen-thawed euploid blastocysts? A cohort study of 1170 embryo transfers[J]. Hum Reprod, 2022, 37(12): 2797-2807.

[10] 黄玉林, 李伟清, 利惠婵, 等. 妊娠期肝内胆汁淤积症患者血清25-羟基维生素D3甘胆酸和总胆汁酸水平与不良妊娠结局的关联性研究[J]. 中国临床新医学, 2022, 15(6): 544-548.

[11] Wertheimer A, Hochberg A, Krispin E, et al. Frozen-thawed embryo transfer is an independent risk factor for third stage of labor complications[J]. Arch Gynecol Obstet, 2021, 304(2): 531-537.

[12] Suga N, Oba M S, Kikuchi I, et al. The effects of post-frozen-thawed embryo transfer pregnancy on early fetal development[J]. J Obstet Gynaecol Res, 2022, 48(3): 739-747.

[13] 孔丽娟, 惠品晶, 丁亚芳. 烟雾病颅内外血管的超声血流动力学研究[J]. 中国超声医学杂志, 2021, 37(11): 1201-1204.

[14] Aydin T, Namli K M, Bakirarar B, et al. Comparing the success rate of natural cycle and modified natural cycle protocols for frozen-thawed embryo transfer[J]. Gynecol Endocrinol, 2022, 38(12): 1073-1078.

[15] Xu J J, Chen L, Li C, et al. Effect of embryo cryopreservation duration on pregnancy-related complications and birth weight after frozen-thawed embryo transfer: a retrospective cohort study[J]. J Dev Orig Health Dis, 2022, 13(2): 187-196.

[16] 乔敏霞, 王君, 关三丽, 等. 早期妊娠绒毛膜隆起的妊娠结局及临床转归[J]. 中国妇幼健康研究, 2021, 32(1): 102-105.

[17] Pier B D, Havemann L M, Quaas A M, et al. Frozen-thawed embryo transfers: time to adopt a more “natural” approach? [J]. J Assist Reprod Genet, 2021, 38(8): 1909-1911.

[18] Mitsui T, Mishima S, Ohira A, et al. hCG values and gestational sac size as indicators of successful systemic methotrexate treatment in cesarean scar pregnancy[J]. Taiwan J Obstet Gynecol, 2021, 60(3): 454-457.

[19] Jordans I P M, Verberkt C, De Leeuw R A, et al. Definition and sonographic reporting system for cesarean scar pregnancy in early gestation: modified Delphi method[J]. Ultrasound Obstet Gynecol, 2022, 59(4): 437-449.

[20] 朱亚芳, 谭乳燕, 解左平, 等. 超声联合MRI诊断剖宫产后子宫切口瘢痕处妊娠的价值研究[J]. 中国超声医学杂志, 2021, 37(2): 190-193.