DÄ internationalArchive46/2021Treatment Options After a Diagnosis of Early Miscarriage: Expectant, Medical, and Surgical

Review article

Treatment Options After a Diagnosis of Early Miscarriage: Expectant, Medical, and Surgical

Dtsch Arztebl Int 2021; 118: 789-94. DOI: 10.3238/arztebl.m2021.0346

Musik, T; Grimm, J; Juhasz-Böss, I; Bäz, E

Background: Approximately 12% of pregnancies end in an early miscarriage (up to week 12  + 0 of pregnancy). Over the past 10 to 15 years, two alternatives to curettage have appeared in the pertinent international treatment guidelines: expectant treatment and medical (drug) treatment. In this review, we discuss the advantages and disadvantages of each of these therapeutic options.

Methods: This review is based on pertinent publications (January 2000 to February 2021) retrieved by a selective search in PubMed, as well as on the guidelines of the American College of Obstetrics and Gynecologists, the Association of the Scientific Medical Societies in Germany, the National Institute for Health and Care Excellence/Royal College of Obstetricians and Gynaecologists, and the International Federation of Gynaecology and Obstetrics.

Results: Three effective and safe treatment options are available after a diagnosis of early miscarriage. Expectant treatment yields success rates of 66–91%, depending on the type of miscarriage. Its complications include hemorrhage requiring blood transfusion in 1–2% of cases. If expectant therapy fails, subsequent treatment with misoprostol or curettage is indicated. Drug therapy with misoprostol yields a complete termination in 81–95% of cases and is thus a valid alternative to expectant therapy, with the advantage of better planning capability. The vaginal application of misoprostol is the most effective means of administration, with the fewest side effects. Curettage is needed in 5–20% of cases. Suctional curettage has a success rate of 97–98%, with an associated anesthesia-related risk of 0.2%, a 0.1% risk of perforation, and a 2–3% rate of repeat curettage.

Conclusion: If there is no acute indication for the surgical treatment of an early miscarriage, the patient can choose among three treatment options. Expectant and medical treatment can be provided on an outpatient basis. Curettage is the treatment of choice in the presence of infection, marked and persistent bleeding, hemodynamic instability, or a pre-existing coagulopathy.

LNSLNS

Early miscarriage up to week 12  + 0 of pregnancy is with 11.9% a common occurrence (1). It is defined as a nonviable, intrauterine pregnancy with an empty gestational sac, an embryo without cardiac activity or a gestational trophoblastic disease with molar placental degeneration. The types of miscarriage requiring treatment include missed miscarriage (fetal death, restrained miscarriage), as well as blighted ovum (empty gestational sac), incomplete miscarriage (incomplete passage of pregnancy tissue) and gestational trophoblastic disease (hydatidiform mole, increased trophoblastic proliferation with molar degeneration). While it is routine for clinicians to be informed of such a finding, it is typically an unexpected and sad outcome of pregnancy for patients. The majority of patients are not aware of how frequent miscarriage is and may develop conditions such as anxiety disorder (30%), depression (10%) and post-traumatic stress syndrome (34%) after pregnancy loss (2).

In 45% (95% confidence interval [38; 52]; 13 studies, 7012 samples) of miscarriages up to 20 weeks of gestation (WG), the pregnancy loss is caused by genetic aberrations (3). The risk of recurrence after one miscarriage is 20%, after two miscarriages 28% (1).

Before treatment of a miscarriage is initiated, it is necessary to prove that the early pregnancy is not intact. An intact (potentially less old) pregnancy, an ectopic pregnancy and a gestational trophoblastic disease (molar placental degeneration) should be ruled out. If the viability of a pregnancy is uncertain, follow-up ultrasound examinations are performed repeatedly and, in required, human chorionic gonadotropin (hCG) levels are monitored.

In most cases, routine, “automatic” surgical treatment of early miscarriage is no longer considered the standard of care (4). Both expectant management and medical (drug) treatment are safe alternatives to curettage. Each of the three treatment options is well accepted by patients (5, 6) and highly effective. However, there are significant differences regarding the treatment process, the duration of treatment and the side effect profile. Consequently, all three treatment options should be discussed in detail, including the respective advantages and disadvantages, with each patient so that the patient can make an informed decision. In March 2021, this topic was for the first time included in the German guideline on induction of labor of the Association of the Scientific Medical Societies in Germany (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften). Some of the recommendations of this guideline differ from the international guidelines.

In this article, we discuss the various methods of treatment and support each of them with evidence which can be used for patient information. We also present the recommendations of various international guidelines and compare them with the recommendations in the AWMF guideline.

Methods

This review is based on pertinent publications (January 2000 to February 2021) retrieved by a selective search in the PubMed database. Publications on the management of miscarriage were included, with a focus on meta-analyses and randomized trials. The following search terms were used: “early pregnancy failure“, “early pregnancy loss“, “missed miscarriage“, “medical therapy of abortion“, “exspectative therapy of abortion“, “miscarriage“, “aspiration abortion“, and “first trimester surgical abortion“. The current guidelines of the American College of Obstetricians and Gynecologists (ACOG), the AWMF, the National Institute for Health and Care Excellence (NICE), and the International Federation of Gynecology and Obstetrics (FIGO) were taken into account in this review.

Expectant management

In the UK NICE guideline, expectant management is—after exclusion of contraindications (Box 1)—recommended as the treatment of choice for the first 7–14 days after diagnosis (7). The success rates of complete passage of pregnancy tissue achieved with expectant management vary with the type of miscarriage and the length of time allowed for watchful waiting. The rate of complete passage of pregnancy tissue within the first two weeks is 70% (314/451 women) and after six weeks 81% (367/451 women) (8). A 2017 Cochrane analysis of incomplete miscarriage found no difference between expectant management and medical treatment regarding the rate of complete passage of pregnancy tissue (mean relative risk [RR] 1.23 [0.72; 2.10]; two studies; 150 women) and the need for surgical intervention (mean RR 0.62; [0.17; 2.26]; two studies; 308 women) (9).The success rate of complete passage of pregnancy tissue decreases in the following order: incomplete miscarriage 91% (201/221 women) > missed miscarriage 76% (105/138) > blighted ovum 66% (61/92) (8) (Table 1). A large meta-analysis published in 2019 (46 studies; 9250 women) described expectant management as the overall least effective strategy compared to medical and surgical management (6).

Exclusion criteria for medical or expectant management
Box 1
Exclusion criteria for medical or expectant management
Overview of various management options for miscarriage
Table 1
Overview of various management options for miscarriage

Expectant management is chosen by patients who do not want to be treated with medication or surgery and feel that this management strategy is the most natural approach and associated with the least iatrogenic interventions. The pregnancy tissue is passed outside the hospital or doctor‘s office. When the bleeding will start and the pregnancy tissue be passed is unpredictable and thus difficult to plan.

Expectant management is acceptable up to a crown-rump length corresponding to week 12  + 0 of pregnancy as long as there is no compelling indication for surgical management (Box 1). Patients who opt for an expectant management approach receive education on the situations in which they should present again at the hospital or doctor‘s office. The patient should be given analgesic medication, such as ibuprofen or metamizole, as needed. In comparison to medical and surgical management, expectant management is associated with an increased risk of bleeding (6) and can in extremely rare cases lead to disseminated intravascular coagulation (dead-fetus syndrome) if the watchful waiting interval is very long (> 8 weeks), extending into the second half of pregnancy (10, 11). The risk of infection does not differ between expectant, medical and surgical management and ranges from 1–3% (9, 12, 13). The patient has to be informed that, should the pregnancy tissue not pass, medical management or curettage are indicated as follow-up treatment. However, most patients (81%; 367/451 women) do not require any further intervention or medication (8). During the period of time until the miscarriage is complete, patients should have gynecological follow-up examinations at least every two weeks (Box 2). The AWMF guidelines does not address the expectant management approach.

Follow-up examinations with expectant and medical management
Box 2
Follow-up examinations with expectant and medical management

Medical (drug) treatment

Medical treatment of miscarriage provides patients with more control over the timing, location and circumstances at the onset of bleeding and passage of pregnancy tissue.

In 2005, the results of a randomized trial comparing medical management versus curettage were published (14) which led to the inclusion of medical management of miscarriage in international guidelines. In the meantime, medical management has internationally become part of the standard therapy (Table 2). We introduced a misoprostol-based regimen, which is in line with the international guidelines, in the Department of Obstetrics & Gynecology at the Medical Center – University of Freiburg (Box 3). Misoprostol-based treatment strategies have been widely published, and the efficacy of the agent varies by type of miscarriage (6, 9, 14, 15) (Table 1). As with expectant management, the success rate of complete passage of pregnancy tissue in patients with incomplete miscarriage is with 93% (28/30 women) higher with medical management compared to missed miscarriage with 88% (244/278) and blighted ovum with 81% (142/176) (14).

Drug treatment regimen of the Department of Obstetrics & Gynecology at the Medical Center – University of Freiburg for early miscarriage up to 12 + 0 weeks of gestation (WG)
Box 3
Drug treatment regimen of the Department of Obstetrics & Gynecology at the Medical Center – University of Freiburg for early miscarriage up to 12 + 0 weeks of gestation (WG)
Drug treatment regimens of various guidelines
Table 2
Drug treatment regimens of various guidelines

In the international guidelines of ACOG (16), the Royal College of Obstetricians and Gynaecologists (RCOG)/NICE (7) and of FIGO (17), medical management in the first trimenon has been described as a valid alternative to surgical management. Likewise, two Cochrane analyses arrived at the conclusion that medical management is safe and effective and associated with high patient satisfaction (9, 15, 18) (Table 1). In contrast to the ACOG, NICE and FIGO guidelines, the AWMF guideline recommends medical management only up to week 9  + 0 of pregnancy as it less effective compared to surgical treatment (94.6% versus 97.9%) (19).

Misoprostol is the drug of choice. It is a prostaglandin E1 analog and has been approved for the management of gastric ulcer. At the pregnant uterus, it induces contractions of the myometrium as well as softening and dilation of the cervix, regardless of the week of pregnancy. With increasing weeks of pregnancy, the sensitivity of the uterus to misoprostol also increases. Predictive factors for the success of drug treatment with misoprostol include vaginal bleeding, lower abdominal pain and nulliparity (20).

Misoprostol can be administered via the oral, buccal, sublingual, vaginal, and rectal routes. It is more effective—measured as complete passage of pregnancy tissue—with vaginal administration compared to oral administration (RR 3.00; [1.44; 6.24]) (21). In addition, the rate of gastrointestinal side effects is significantly lower with vaginal administration compared to oral administration (12/95 women, 13.6% versus 62/103 women, 65.3%, p<0.01]) (22). The most common side effects of misoprostol are nausea, vomiting, lower abdominal cramping, diarrhea, and fever. With regard to the risk of bleeding, a distinction has to be made between the different types of miscarriage. While 1% of cases (5/488 patients) with blighted ovum or missed miscarriage require blood transfusion because of significant hemorrhage (14), incomplete miscarriage is not associated with an increased bleeding risk (9). There are no consistent recommendations regarding the treatment regimen, but higher doses appear to be more effective compared to lower, repeated single doses. The rate of complete miscarriage is not increased by more than two doses of 800  µg misoprostol (23, 24).

Misoprostol is not approved for the treatment of miscarriage. Thus, the patient should be informed about the established off-label use in writing. A “Dear Doctor Letter (“Rote-Hand-Brief”) of March 2020 advised primarily against the use of misoprostol for the induction of labor (25). An open letter from the major German obstetrics and gynecology societies outlines the different and diverse indications for misoprostol and the need for greater accessibility to misoprostol (26). As it is used off-label, health insurances do not cover the costs of the medication; however, with about 20 cents per tablet, the cost is low.

Bleeding typically starts between 2 and 4 hours of taking misoprostol. It is recommended that the patient takes an analgesic, such as ibuprofen or metamizole, at the same time. Once the bleeding has started, it is usually strong for about two hours, with passing of blood clots and pregnancy tissue. However, if bleeding persists for more than two hours (defined as soaking through >2 large pads in an hour), the patient should go to hospital.

A follow-up examination is recommended after 7–14 days (Box 2). If the gestational sac is not passed or endometrial thickness is >30 mm on ultrasound, misoprostol dosing can be repeated. In case of unsuccessful medical treatment, curettage is performed.

In recent years, randomized trials assessing the complete passage of pregnancy tissue have shown the superiority of the combination of mifepristone followed by misoprostol compared to misoprostol alone—84% (124/148; CI [77%; 89%]) and 67% (100/149; [59%; 75%]; p = 0.04), respectively (27, 28). This combination treatment is generally recommended, except for the NICE/RCOG guideline.

Surgical management

For decades, curettage was the therapy of choice. The procedure can easily be planed, the patient does not have to consciously deal with the passage of pregnancy tissue and with 98% the chance of success is very high. Curettage continues to be indicated in the presence of signs and symptoms of infection, persistent heavy bleeding or hemodynamic instability and pre-existing coagulopathy as well as on patient request. Likewise, it is the treatment of choice for patients who wish to experience as little bleeding and pain as possible.

Blunt curettage has now been replaced by vacuum aspiration, resulting in decreases in blood loss (mean difference [MD] 17.10  mL; [24.05; 10.15]), pain (RR 0.74; [0.61; 0.90]) and perforation risk (29, 30). In addition, operative time is reduced (MD 1.20 minutes; [−-1.53; −-0.87]). The risk of serious complications is <0.1% (31). Complications include perforation and hemorrhage requiring transfusion (< 0.1%), anesthetic complications (<0.2%) and repeat curettage for residual tissue (1–3%) (14, 31). In a 2008 review, the incidence of recurrent miscarriage was found to be significantly higher in patients with status post curettage for miscarriage compared to medical management of miscarriage (3.6%; 225/6  259 women versus 2.6%; 163/6  172); postpartum hemorrhage also occurred significantly more frequently (4.2%; 44/1  057 versus 2,5%; 27/1  063) (32). Very rare complications of curettage affecting subsequent pregnancies include Asherman’s syndrome with 0.7% (6/844) (33), the slightly increased risk of preterm birth (preterm birth<37 WG: odds ratio [OR] 1.29 [1.17; 1.42], preterm birth<32 WG: OR 1.69 [1.20; 2.38], preterm birth<28 WG: OR 1.68 [1.47; 1.92]) (18), and the placenta accreta spectrum disorders with deep placental invasion abnormalities, as with placenta accreta, increta or percreta (34).

Conclusion for clinical practice

Early miscarriage is a common diagnosis in clinical practice and routinely treated by office-based gynecologists. The devastated patient requires an empathetic, detailed discussion of the various treatment options. Three valid treatment options are available (Table 1). Medical and expectant management can be provided in an office setting. In case of complications or when curettage is indicated, treatment is provided in a hospital or ambulatory surgery center setting.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 21 April 2021, revised version accepted on 23 September 2021

Translated from the original German by Ralf Thoene, MD.

Corresponding author
Dr. med. Thabea Musik
Universitätsklinikum Freiburg, Klinik für Frauenheilkunde
Hugstetterstr. 55, 79106 Freiburg, Germany
thabea.musik@uniklinik-freiburg.de

Cite this as:
Musik T, Grimm J, Juhasz-Böss I, Bäz E: Treatment options after a diagnosis of early miscarriage: expectant, medical, and surgical. Dtsch Arztebl Int 2021; 118: 789–94. DOI: 10.3238/arztebl.m2021.0346

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Department of Obstetrics & Gynecology at the Medical Center – University of Freiburg, Freiburg, Germany: Dr. med. Thabea Musik, Dr. med. Juliane Grimm, Prof. Dr. med. Ingolf Juhasz-Böss, Dr. med. Elke Bäz
Exclusion criteria for medical or expectant management
Box 1
Exclusion criteria for medical or expectant management
Follow-up examinations with expectant and medical management
Box 2
Follow-up examinations with expectant and medical management
Drug treatment regimen of the Department of Obstetrics & Gynecology at the Medical Center – University of Freiburg for early miscarriage up to 12 + 0 weeks of gestation (WG)
Box 3
Drug treatment regimen of the Department of Obstetrics & Gynecology at the Medical Center – University of Freiburg for early miscarriage up to 12 + 0 weeks of gestation (WG)
Overview of various management options for miscarriage
Table 1
Overview of various management options for miscarriage
Drug treatment regimens of various guidelines
Table 2
Drug treatment regimens of various guidelines
1.Magnus MC, Wilcox AJ, Morken NH, Weinberg CR, Håberg SE: Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ 2019; 364: l869 CrossRef MEDLINE PubMed Central
2.Farren J, Jalmbrant M, Falconieri N, et al.: Differences in post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy between women and their partners: multicenter prospective cohort study. Ultrasound Obstet Gynecol 2021; 57: 141–8 CrossRef MEDLINE
3.van den Berg MM, van Maarle MC, van Wely M, Goddijn M: Genetics of early miscarriage. Biochim Biophys Acta 2012; 1822: 1951–9 CrossRef MEDLINE
4.Harris LH, Dalton VK, Johnson TR: Surgical management of early pregnancy failure: history, politics, and safe, cost-effective care. Am J Obstet Gynecol 2007; 196: 445 e1–5 CrossRef MEDLINE
5.Kong GW, Lok IH, Yiu AK, Hui AS, Lai BP, Chung TK: Clinical and psychological impact after surgical, medical or expectant management of first-trimester miscarriage—a randomised controlled trial. Aust N Z J Obstet Gynaecol 2013; 53: 170–7 CrossRef MEDLINE
6.Al Wattar BH, Murugesu N, Tobias A, Zamora J, Khan KS: Management of first-trimester miscarriage: a systematic review and network meta-analysis. Hum Reprod Update 2019; 25: 362–74 CrossRef MEDLINE
7.National Institute for Health and Care Excellence (NICE): NICE guideline. Ectopic pregnancy and miscarriage: diagnosis and initial management. 2019. www.nice.org.uk/guidance/ng126 (last accessed on 19 September 2021).
8.Luise C, Jermy K, May C, Costello G, Collins WP, Bourne TH: Outcome of expectant management of spontaneous first trimester miscarriage: observational study. BMJ 2002; 324: 873–5 CrossRef MEDLINE PubMed Central
9.Kim C, Barnard S, Neilson JP, Hickey M, Vazquez JC, Dou L: Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev 2017; 1: Cd007223 CrossRef MEDLINE PubMed Central
10.Erez O, Mastrolia SA, Thachil J: Disseminated intravascular coagulation in pregnancy: insights in pathophysiology, diagnosis and management. Am J Obstet Gynecol 2015; 213: 452–63 CrossRef MEDLINE
11.Lurie S, Feinstein M, Mamet Y: Disseminated intravascular coagulopathy in pregnancy: thorough comprehension of etiology and management reduces obstetricians’ stress. Arch Gynecol Obstet 2000; 263: 126–30 CrossRef MEDLINE
12.Wu HL, Marwah S, Wang P, Wang QM, Chen XW: Misoprostol for medical treatment of missed abortion: a systematic review and network meta-analysis. Sci Rep 2017; 7: 1664 CrossRef MEDLINE PubMed Central
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: 1235–40 CrossRef MEDLINE PubMed Central
14.Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C, Frederick MM: A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005; 353: 761–9 CrossRef MEDLINE
15.Kulier R, Kapp N, Gülmezoglu AM, Hofmeyr GJ, Cheng L, Campana A: Medical methods for first trimester abortion. Cochrane Database Syst Rev 2011; 2011: Cd002855 CrossRef MEDLINE PubMed Central
16.American College of Obstetricians and Gynecologists: ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002; 78: 179–90.
17.International Federation of Gynecology and Obstetrics (FIGO): Misoprostol-only recommended regimens 2017. www.mhtf.org/2017/06/29/new-figo-guidelines-for-misoprostol-use (last accessed on 19 September 2021).
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