Update on Early Pregnancy Loss Management
May 1, 2018
Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI
Dr. Allen reports she is a Nexplanon trainer for Merck.
Early pregnancy failure typically is defined as an intrauterine pregnancy in the first trimester that is not viable, either because the gestational sac is empty or because the embryo or fetus has no cardiac activity.1 Most commonly, diagnosis is made by ultrasound and the patient may or may not be symptomatic. The Society of Radiologists in Ultrasound issued guidelines in 2013 that proposed conservative radiologic criteria for the diagnosis of early pregnancy failure.2 (See Table 1.) These guidelines are important especially for women whose pregnancies are desired and for women who want to wait for absolute certainty that there has been a failed pregnancy prior to intervention. Otherwise, these guidelines can be interpreted according to individual patient circumstances, which may include wanting a pregnancy termination to avoid unwanted spontaneous passage of pregnancy tissue or the need for an unscheduled visit or procedure.
For women who are stable without hemorrhage or infection, there are three main options for the management of early pregnancy failure: expectant management, medical management with misoprostol, and surgical management. Women’s preferences should guide treatment decisions, given that all three options are medically safe. Factors that patients may consider include shortest time to completion, probability of success, desire to avoid surgery or anesthesia, least amount of pain and bleeding, or number of clinic visits required. Overall, the success rates of each method depend on the time allowed for completion. For expectant management, the success rates also may depend on the type of early pregnancy failure. In one study, by two weeks, 84% of women with an incomplete abortion, 59% of women with an embryonic/fetal demise, and 52% of women with an anembryonic pregnancy had a complete abortion.3 With misoprostol management, authors of a large U.S. randomized, controlled trial reported success rates of 71% by day 3 with 800 mcg of vaginal misoprostol.4 The success rate was increased to 84% when women took a second dose of 800 mcg of vaginal misoprostol, if needed. The ~85% success rate of misoprostol alone (with a second dose) has led investigators to look for agents that may increase completion rates. Given its efficacy in inducing abortion with misoprostol, mifepristone has been researched as a supplementary drug. Preliminary trials have been performed but, to date, evidence is inconclusive.5 We are still waiting for the publication of a large, randomized, controlled trial to settle the issue. Finally, surgical management with manual vacuum aspiration in the office or suction dilation and curettage (D&C) in the operating room is an option, with a success rate of 97%.4
Table 1: Transvaginal Ultrasound Findings Diagnostic of and Suspicious for Pregnancy Failure |
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Findings diagnostic of pregnancy failure |
Findings suspicious for, but not diagnostic of, pregnancy failure |
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Adapted from: Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:1443-1451. |
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If misoprostol management fails, the question for women is whether to pursue expectant management or surgical management. This is highly preference driven, as evidenced by a recent randomized, controlled trial that approached 340 women in this situation and only 59 were willing to be randomized.6 In this Dutch trial, adult women with incomplete abortion after misoprostol treatment were enrolled. The authors excluded women who still had a retained gestational sac for unclear reasons. Perhaps the Dutch practice in that setting is always surgical evacuation, but this was not explained. Incomplete abortion was defined sonographically as visual evidence of retained products of conception or an endometrial stripe thickness of 11 mm or more. It is unclear why this endometrial stripe measurement was chosen. Exclusion criteria included severe vaginal bleeding or abdominal pain requiring immediate surgical intervention, fever, or any contraindications to suction curettage. Women allocated to curettage underwent the procedure within three days. In this study, curettage could include vacuum aspiration or sharp curettage. All women were contacted in two weeks and an ultrasound was performed at six weeks. Success was defined as an empty uterus with endometrial stripe < 10 mm at six weeks or an uneventful clinical course during three months of follow-up if no ultrasound was performed. Secondary outcomes included excessive blood loss (> 500 mL), blood transfusion, antibiotic treatment, and any subsequent surgical intervention. Mean gestational age at misoprostol use was 10 weeks in both arms.
A total of 29/30 (97%) women who underwent surgery compared to 22/29 (76%) women allocated to expectant management had complete abortions (relative risk [RR], 1.3; 95% confidence interval [CI], 1.03-1.6). Equal numbers of women in the two groups experienced a complication (RR, 0.97, 95% CI, 0.21-4.4): three of 30 women in the surgical group (with one post-spinal headache, one Asherman’s syndrome, and one antibiotic treatment) vs. three of 29 in the expectant management group (with two emergency curettages because of excessive blood loss and one antibiotic treatment). Ultimately, four more women in the expectant management group underwent either repeat curettage for persistent vaginal bleeding or hysteroscopy for retained products of conception on ultrasound.
The same authors also offered enrollment in a cohort study to the women who declined randomization.7 A total of 197 women agreed to participate; 132 elected expectant management while 65 chose surgical evacuation. In this cohort, 62/65 (95%) in the curettage arm and 112/132 (85%) in the expectant management arm had complete abortions (RR, 1.12; 95% CI, 1.03-1.23). Complication rates were not significantly different, with 6.2% in the curettage group and 2.3% in the expectant management group (RR, 2.70; 95% CI, 0.6-11.7).7 Overall, the take-home message from both of these studies is that more than three-quarters of women in the expectant management group did not require intervention when they had an “incomplete” abortion after misoprostol treatment for early pregnancy failure. This study aligns with previous studies showing endometrial stripe thickness does not predict the need for intervention and that a thickened endometrial lining after miscarriage can be a normal finding.1 Therefore, clinical signs and symptoms should guide management in this setting, and it is reasonable for women to opt for expectant management as long as they are aware of the small risk of needing surgical evacuation for bleeding.
Patients may be concerned with the effects on future fertility of the three different management options. There has been a historical concern regarding surgical treatment potentially leading to procedural complications and subsequent Asherman’s syndrome (intrauterine adhesions). In one specialized clinic in Vancouver, British Columbia, 884 women were evaluated for early pregnancy failure between July 2011 and December 2012.8 Of these women, 210 chose misoprostol, 191 chose manual vacuum aspiration in the office under local anesthesia, 406 chose suction D&C under IV moderate sedation in an ambulatory surgical center, and 77 underwent suction D&C under general anesthesia in the hospital operating room. Afterward, six women contacted the clinic complaining of amenorrhea more than eight weeks postoperatively. All six women had undergone sharp curettage at the time of their suction D&C under IV or general anesthesia, which was practiced routinely at the clinic. Three of these women also had repeat procedures for retained products of conception that also included sharp curettage. All six were revealed to have intrauterine adhesions on hysteroscopy consistent with Asherman’s syndrome. There were no cases reported after manual vacuum aspiration that did not include sharp curettage. The authors decided to stop using sharp curettage routinely with suction D&C procedures. This corresponds to standard practice in the United States.1
Although there are limitations to the data, including no active follow-up on all the patients, the results are intriguing. The true incidence of intrauterine adhesions after suction D&C is unknown, as women can be asymptomatic, but one can imagine that sharp curettage may be more likely to injure the basal layer of the endometrium compared to suction alone and it is not really necessary to ensure complete evacuation. One systematic review reported a pooled prevalence of intrauterine adhesions on hysteroscopy of 19% (95% CI, 12.8-27.5%) after suction D&C for early pregnancy failure.9 The majority of the intrauterine adhesions were classified as mild (58%), followed by moderate (28.2%) and severe (13.7%). The authors did not report whether sharp curettage was used, and the clinical relevance of these intrauterine adhesions is unknown. The authors of this systematic review found no studies reporting on the link between intrauterine adhesions and long-term reproductive outcome after miscarriage.
Meanwhile, several studies have shown similar pregnancy outcomes subsequent to expectant, medical, or surgical management of early pregnancy failure.1 For example, pregnancy outcomes were ascertained in the same population of Dutch women who participated in the randomized trial and cohort study evaluating curettage vs. expectant management for women who had incomplete abortion after misoprostol treatment of early pregnancy failure.10 Of the 211 women in both studies with follow-up data, 198 had tried to conceive after early pregnancy failure. Of these, 73 had received curettage and 125 were managed expectantly. In the curettage group, 69 women conceived (92%) compared to 120 (96%) of the expectant management group (P = 0.34). The mean time to pregnancy was 32 weeks for women in the curettage group and 29 weeks for women in the expectant management group (nonsignificant).
In sum, we can reassure women that there is very low risk that any treatment will affect future fertility, so this should not be a deciding factor in the decision-making process. Rather, women should choose the option that feels most comfortable to them and fits into their lifestyles.
REFERENCES
- The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol 2015;125:1258-1267.
- Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:1443-1451.
- Luise C, Jermy K, May C, et al. Outcome of expectant management of spontaneous first trimester miscarriage: Observational study. BMJ 2002;324:873-875.
- Zhang J, Gilles JM, Barnhart K, et al. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005;353:761-769.
- Van den Berg J, Gordon BB, Snijders MP, et al. The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: A systematic review of the literature. Eur J Obstet Gynecol Reprod Biol 2015;195:18-26.
- Lemmers M, Verschoor MA, Oude Rengerink K, et al. MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A randomized controlled trial. Hum Reprod 2016;31:2421-2427.
- Lemmers M, Verschoor MAC, Oude Rengerink K, et al. MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A cohort study. Eur J Obstet Gynecol Reprod Biol 2017;211:83-89.
- Gilman Barber, Rhone SA, Fluker MR. Curettage and Asherman’s Syndrome — Lessons to (re-) learn? J Obstet Gynaecol Can 2014;36:997-1001.
- Hooker AB, Lemmers M, Thurkow AL, et al. Systematic review and meta-analysis of intrauterine adhesions after miscarriage: Prevalence, risk factors and long-term reproductive outcome. Hum Reprod Update 2014;20:262-278.
- Lemmers M, Verschoor MAC, Overwater K, et al. Fertility and obstetric outcomes after curettage versus expectant management in randomized and non-randomized women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage. Eur J Obstet Gynecol Reprod Biol 2017;211:78-82.
Early pregnancy failure typically is defined as an intrauterine pregnancy in the first trimester that is not viable, either because the gestational sac is empty or because the embryo or fetus has no cardiac activity. This article will discus the main options for the management of early pregnancy failure: expectant management, medical management with misoprostol, and surgical management. Women’s preferences should guide treatment decisions, given that all three options are medically safe.
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