ALSO  

2006 ALSOâ Syllabus Update

A: First Trimester Pregnancy Complications

Evidence Review Completed May 4, 2006 by Mark Deutchman, MD

Update published:  __________ 2006

Disclosure: this update includes information on a non-FDA approved use of a prescription medication (misoprostol).

Summary of Recommendations SORT A ·            Success of treatment for miscarriage depends on diagnosis. When the woman has an incomplete miscarriage, nonsurgical treatments have a high likelihood of success. When the woman has an embryonic demise or anembryonic pregnancy, misoprostol or surgical treatment are considerably more effective than expectant treatment.1, 2, 3 ·            When the choice is made to treat early pregnancy failure by other than expectant means, MISO vaginally is highly efficacious, safe and well-accepted by women, with fewer gastrointestinal side-effects than the oral route.1, 2, 3

 

Terminology note: The term “blighted ovum” used in the ALSO syllabus is synonymous with “anembryonic pregnancy” used in this update.

Informative clinical trials have been reported comparing management of early pregnancy loss:

• Vaginal misoprostol (MISO) versus surgical management¹. The trial included 652 women with early pregnancy loss (average gestational age 7.2 weeks, range 5-12 weeks). The distribution of diagnoses included:
• 58% embryonic death (missed abortion)
• 36% anembryonic pregnancy
• 6% incomplete or inevitable abortion

Randomization was 3:1 to medical or surgical treatment. Women in the medical group received MISO 800mg vaginally on day 1 and a repeat dose on day 3 if tissue was not yet expelled. The surgical treatment group had either manual vacuum aspiration (MVA) or electric vacuum aspiration (EVA).

• Intravaginal MISO versus expectant treatment². Of 131 eligible women, 104 were randomized to MISO 600mg vaginally or placebo. The distribution of diagnoses included:
• 80% embryonic death or anembryonic pregnancy
• 20% incomplete abortion (average gestational age 10 weeks; range 7-13 weeks).

Follow-up was the next day with a repeat dose if necessary and then again at seven days.

• Oral MISO versus MVA³. This trial included only women with incomplete abortion (average gestational age 9.2 weeks, range 7.2 -11.2 weeks). A cohort of 317 women was randomized to MISO 600mg orally or MVA. Follow-up was at 7 to 14 days.

MISO = misoprostol MVA = manual vacuum extraction EVA = electric vacuum extraction

Secondary findings in these studies include:

• Women treated with MISO have more bleeding but less pain than those treated surgically.
• Women treated expectantly have more outpatient visits than those treated with MISO.
• Surgical treatments are associated with more trauma and infectious complications than MISO treatment.
• MISO administered transvaginally is associated with fewer gastrointestinal side-effects than when given orally.

MISO treatment may be particularly important in resource-limited settings, including developing countries, because it requires no surgical facilities and is inexpensive. An editorial ⁴ urged clinicians to “…improve care for women by substituting a nonsurgical treatment for curettage or aspiration procedures…”, but acknowledges that the use of MISO for this purpose remains an off-label use.

References:

¹ Zhang J, Giles 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. [LOE 1, RCT]

² Bagratee JS, Khullar V, Regan L, et al. A randomized controlled trial comparing medical and expectant management of first trimester miscarriage. Hum Reprod 2004;19:266-271. [LOE 1, RCT]

³ Weeks A, Alia G, Blum J, et al. A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion. Obstet Gynecol 2005;106:540-547. [LOE 1, RCT]

⁴ Winikoff B. Pregnancy failure and misoprostol--time for a change. N Engl J Med 2005;353:834-836. [LOE 3, opinion]