Therapeutic effect of mifepristone combined with misoprostol in early missed miscarriage and prediction of incomplete abortion

Abstract

Objective: To compare the clinical efficacy of mifepristonemisoprostol medical management versus surgical curettage for first-trimester missed miscarriage, and to establish evidence-based sonographic cutoff values predictive of incomplete abortion requiring surgical intervention.

Methods: We retrospectively analyzed a cohort of 702 women diagnosed with first-trimester missed miscarriage between January 2020 and May 2023. Demographic characteristics and ultrasound parameters were systematically recorded. Receiver operating characteristic (ROC) curve analysis was performed to establish optimal sonographic cutoff values for predicting incomplete abortion requiring surgical intervention.

Results: 146 patients received medical treatment (mifepristone and misoprostol) and 556 underwent surgical curettage. At the 1-month follow-up, the medical group showed significantly greater endometrial thickness and longer postoperative bleeding duration than the surgical group (P<0.05). The menstrual volume reduction rate (23.56%) was significantly lower in the medical group than in the surgical group. The incomplete abortion rate was higher in the medical group (17.12%, 25/146) than in the surgical group (2.88%, 16/556). Among the medical group, 14 patients (9.59%) required curettage due to incomplete abortion, while 11 cases resolved spontaneously after prolonged medication. ROC curve analysis identified two cut-off values indicating the need for surgical intervention: endometrial thickness >1.21 cm at 24 h post-medical abortion, and residual mass diameter >0.95 cm at 7 days post-medical abortion.

Conclusions: Medical management of first-trimester missed miscarriage using mifepristone-misoprostol demonstrates comparable efficacy to surgical curettage. An endometrial thickness >1.21 cm at 24 h or residual tissue diameter >0.95 cm at 7 days post-medical abortion should prompt consideration of incomplete abortion.

Keywords

Missed miscarriage / Medication abortion / Incomplete miscarriage / Prediction

Conflict of interest statement

The authors declare no conflicts of interest related to this work.

Funding

This work was supported by National Natural Science Foundation of China (Project approval number 82201825).

Authors’ contributions

Bai Xue conceived and designed the study, developed the methodology, wrote the original draft, and participated in manuscript revision. Li Tianjie performed the formal analysis, created visualizations, curated the data, and acquired funding. Lin Qing supervised the research and managed the project. All authors critically reviewed and approved the final manuscript.

Publisher’s Note

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References

[1] Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, et al. Miscarriage matters: The epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet 2021; 397(10285):1658-1667.

[2] Hardy K, Hardy PJ, Jacobs PA, Lewallen K, Hassold TJ. Temporal changes in chromosome abnormalities in human spontaneous abortions: Results of 40 years of analysis. Am J Med Genet A 2016; 170(10):2671-2680.

[3] Arias-Sosa LA, Acosta ID, Lucena-Quevedo E, Moreno-Ortiz H, Esteban-Pérez C, Forero-Castro M. Genetic and epigenetic variations associated with idiopathic recurrent pregnancy loss. J Assist Reprod Genet 2018; 35(3):355-366.

[4] Jurkovic D, Overton C, Bender-Atik R. Diagnosis and management of first trimester miscarriage. BMJ 2013; 346: f3676. doi: 10.1136/bmj.f3676.

[5] Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. N Engl J Med 2000; 342(13):946-956.

[6] Schreiber CA, Creinin MD, Atrio J, Sonalkar S, Ratcliffe SJ, Barnhart KT. Mifepristone pretreatment for the medical management of early pregnancy loss. N Engl J Med 2018; 378(23):2161-2170.

[7] Neilson JP, Hickey M, Vazquez J. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev 2006; 2006(3): CD002253. doi: 10.1002/14651858.CD002253.pub3.

[8] Higham JM, O’Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97(8):734-739.

[9] Fang J, Xie B, Chen B, Qiao C, Zheng B, Luan X, et al. Biochemical clinical factors associated with missed abortion independent of maternal age: A retrospective study of 795 cases with missed abortion and 694 cases with normal pregnancy. Medicine (Baltimore) 2018; 97(50):e13573.

[10] National Guideline Alliance (UK). Progestogens for preventing miscarriage: Ectopic pregnancy and miscarriage: Diagnosis and initial management: Evidence review C. London: National Institute for Health and Care Excellence (NICE); 2021.

[11] Al-Ma’Ani W, Solomayer EF, Hammadeh M. Expectant versus surgical management of first-trimester miscarriage: A randomised controlled study. Arch Gynecol Obstet 2014, 289(5):1011-1015.

[12] Sotiriadis A, Makrydimas G, Papatheodorou S, Ioannidis JP. Expectant, medical, or surgical management of first-trimester miscarriage: A metaanalysis. Obstet Gynecol 2005; 105(5 Pt 1):1104-1113.

[13] Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: Expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ 2006; 332(7552):1235-1240. doi: 10.1136/bmj.38828.593125.55.

[14] Ehrnstén L, Altman D, Ljungblad A, Kopp Kallner H. Efficacy of mifepristone and misoprostol for medical treatment of missed miscarriage in clinical practice-A cohort study. Acta Obstet Gynecol Scand 2020; 99(4):488-493.

[15] Serdinšek T, Reljič M, Kovač V. Medical management of first trimester missed miscarriage: The efficacy and complication rate. J Obstet Gynaecol 2019; 39(5):647-651.

[16] Bettencourt-Silva B, Rego MT, Miranda C, Cunha AI, Brás F, Lopes-Guerra C, et al. The role of mifepristone on first trimester miscarriage treatment - A double-blind randomized controlled trial - MiFirsT. Eur J Obstet Gynecol Reprod Biol 2023; 289:145-151.

[17] Devall A, Chu J, Beeson L, Hardy P, Cheed V, Sun Y, et al. Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: The MifeMiso RCT. Health Technol Assess 2021; 25(68):1-114. doi: 10.3310/hta25680.

[18] Ghosh J, Papadopoulou A, Devall AJ, Jeffery HC, Beeson LE, Do V, et al. Methods for managing miscarriage: A network meta-analysis. Cochrane Database Syst Rev 2021; 6(6):D12602. doi: 10.1002/14651858.CD012602.pub2.

[19] Petersen SG, Perkins AR, Gibbons KS, Bertolone JI, Mahomed K. The medical management of missed miscarriage: Outcomes from a prospective, single-centre, Australian cohort. Med J Aust 2013; 199(5):341-346.

[20] Odeh M, Tendler R, Kais M, Maximovsky O, Ophir E, Bornstein J. Early pregnancy failure: Factors affecting successful medical treatment. Isr Med Assoc J 2010; 12(6):325-328.

[21] Schreiber CA, Ratcliffe SJ, Quinley KE, Miller C, Sammel MD. Serum biomarkers may help predict successful misoprostol management of early pregnancy failure. Reprod Biol 2015; 15(2):79-85.

[22] Kamaya A, Krishnarao PM, Nayak N, Jeffrey RB, Maturen KE. Clinical and imaging predictors of management in retained products of conception. Abdom Radiol (NY) 2016; 41(12):2429-2434.

[23] Iqbal H, Khan MS, Muneeb A, Mirza WA. Diagnostic accuracy of ultrasound in detecting retained products of conception: A study from a tertiary care hospital in Karachi, Pakistan. Cureus 2018; 10(11):e3564.

[24] Hamel CC, van Wessel S, Carnegy A, Coppus SFPJ, Snijders MPML, Clark J, et al. Diagnostic criteria for retained products of conception-A scoping review. Acta Obstet Gynecol Scand 2021; 100(12):2135-2143.