9/13/23, 12:07 PM Early Pregnancy Loss | ACOG

acog.org ACOG Clinical Obstetrics & Gynecology For Patients Store ACOG Engage Subscribe
 Clinical Guidance Journals & Publications Patient Education Topics  Log In
Search ACOG Clinical

Clinical Guidance Journals & Publications Patient Education Topics 

Early Pregnancy Loss

Practice Bulletin  | Number 200 | November 2018

By reading this page you agree to ACOG's Terms and Conditions. Read terms

View the Practice Advisory and Physician FAQs that have been issued for this document.
 Download PDF

 Figures & Tables

Number 200 (Replaces Practice Bulletin Number 150, May 2015. Reaffirmed 2021)

Committee on Practice Bulletins—Gynecology . This Practice Bulletin was developed by the ACOG Committee on Practice Bulletins—Gynecology in
collaboration with Sarah Prager, MD; Vanessa K. Dalton, MD, MPH; and Rebecca H. Allen, MD, MPH.

INTERIM UPDATE: This Practice Bulletin is updated as highlighted to reflect recent evidence regarding the use of mifepristone combined with misoprostol for
medical management of early pregnancy loss. This Practice Bulletin also includes limited, focused updates to align with Practice Bulletin No. 181, Prevention of
Rh D Alloimmunization .

ABSTRACT: Early pregnancy loss, or loss of an intrauterine pregnancy within the first trimester, is encountered commonly in clinical practice.
Obstetricians and gynecologists should understand the use of various diagnostic tools to differentiate between viable and nonviable
pregnancies and offer the full range of therapeutic options to patients, including expectant, medical, and surgical management. The purpose
of this Practice Bulletin is to review diagnostic approaches and describe options for the management of early pregnancy loss.

Background
Definition

Early pregnancy loss is defined as a nonviable, intrauterine pregnancy with either an empty gestational sac or a gestational sac containing an
embryo or fetus without fetal heart activity within the first 12 6/7 weeks of gestation 1 . In the first trimester, the terms miscarriage,
spontaneous abortion, and early pregnancy loss are used interchangeably, and there is no consensus on terminology in the literature.
However, early pregnancy loss is the term that will be used in this Practice Bulletin.

Incidence

Early pregnancy loss is common, occurring in 10% of all clinically recognized pregnancies 2 3 4 . Approximately 80% of all cases of
pregnancy loss occur within the first trimester 2 3 .

Etiology and Risk Factors

Approximately 50% of all cases of early pregnancy loss are due to fetal chromosomal abnormalities 5 6 . The most common risk factors
identified among women who have experienced early pregnancy loss are advanced maternal age and a prior early pregnancy loss 7 8 .
The frequency of clinically recognized early pregnancy loss for women aged 20–30 years is 9–17%, and this rate increases sharply from 20%
at age 35 years to 40% at age 40 years and 80% at age 45 years 7 . Discussion of the many risk factors thought to be associated with early
pregnancy loss is beyond the scope of this document and is covered in more detail in other publications 6 7 .

Clinical Considerations and Recommendations

What findings can be used to confirm a diagnosis of early pregnancy loss?

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 1/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
Common symptoms of early pregnancy loss, such as vaginal bleeding and uterine cramping, also are common in normal gestation, ectopic
 Clinical Guidance Journals & Publications Patient Education Topics
pregnancy, and molar pregnancy. Before initiating treatment, it is important to distinguish early pregnancy loss from other early pregnancy
complications. Treatment of an early pregnancy loss before confirmed diagnosis can have detrimental consequences, including interruption
of a normal pregnancy, pregnancy complications, or birth defects 9 . Therefore, a thorough evaluation is needed to make a definitive
diagnosis. In combination with a thorough medical history and physical examination, ultrasonography and serum β-hCG testing can be
helpful in making a highly certain diagnosis.

Ultrasonography, if available, is the preferred modality to verify the presence of a viable intrauterine gestation. In some instances, making a
diagnosis of early pregnancy loss is fairly straightforward and requires limited testing or imaging. For example, early pregnancy loss can be
diagnosed with certainty in a woman with an ultrasound-documented intrauterine pregnancy who subsequently presents with reported
significant vaginal bleeding and an empty uterus on ultrasound examination. In other instances, the diagnosis of early pregnancy loss is not
as clear. Depending on the specific clinical circumstances and how much diagnostic certainty the patient desires, a single serum β-hCG test
or ultrasound examination may not be sufficient to confirm the diagnosis of early pregnancy loss.

The use of ultrasound criteria to confirm the diagnosis of early pregnancy loss was initially reported in the early 1990s, shortly after vaginal
ultrasonography became widely available. Based on these early studies, a crown–rump length (CRL) of 5 mm without cardiac activity or an
empty gestational sac measuring 16 mm in mean gestational sac diameter have been used as diagnostic criteria to confirm early pregnancy
loss 10 11 . Recently, two large prospective studies have been used to challenge these cutoffs. In the first study, 1,060 women with
intrauterine pregnancies of uncertain viability were followed up to weeks 11–14 of gestation 12 . In this group of women, 55.4% received a
diagnosis of nonviable gestation during the observation period. A CRL cutoff of 5 mm was associated with an 8.3% false-positive rate for
early pregnancy loss. A CRL cutoff of 5.3 mm was required to achieve a false-positive rate of 0% in this study 12 . Similarly, the authors
reported a 4.4% false-positive rate for early pregnancy loss when using a mean gestational sac diameter cutoff of 16 mm. A mean
gestational sac diameter cutoff of 21 mm (without an embryo and with or without a yolk sac) on the first ultrasound examination was
required to achieve 100% specificity for early pregnancy loss. In a second study of 359 women from the first study group, the authors
concluded that growth rates for the gestational sac (mean gestational sac diameter) and the embryo (CRL) could not predict viability
accurately 13 . However, the authors concluded that if a gestational sac was empty on initial scan, the absence of a visible yolk sac or
embryo on a second scan performed 7 days or more after the first scan was always associated with pregnancy loss 13 .

Based on these studies, the Society of Radiologists in Ultrasound Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and
Exclusion of a Viable Intrauterine Pregnancy created guidelines that are considerably more conservative than past recommendations and
also have stricter cutoffs than the studies on which they are based 14 Table 1 . The authors of the guidelines report that the stricter cutoffs
are needed to account for interobserver variability; however, this already was accounted for in the original study through its use of multiple
ultrasonographers 12 15 . Other important limitations in the development of these guidelines should be recognized. For example, there were
few cases at or near the measurements ultimately identified as decision boundaries. Similarly, the time between observing a gestational sac
and expecting to see a yolk sac or embryo was increased from 7 days or more in the clinical study 13 to 14 days in the guidelines 14 . The
basis of this recommendation is unclear.

Obstetrician–gynecologists caring for women experiencing possible early pregnancy loss should consider other clinical factors when
interpreting the Society of Radiologists in Ultrasound guidelines, including the woman’s desire to continue the pregnancy; her willingness to
postpone intervention to achieve 100% certainty of pregnancy loss; and the potential consequences of waiting for intervention, including
unwanted spontaneous passage of pregnancy tissue, the need for an unscheduled visit or procedure, and patient anxiety. It is important to
include the patient in the diagnostic process and to individualize these guidelines to patient circumstances.

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 2/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
Criteria that are considered suggestive, but not diagnostic, of early pregnancy loss are listed in Table 1 14 . Slow fetal heart rate (less than
 Clinical Guidance Journals & Publications Patient Education Topics
100 beats per minute at 5–7 weeks of gestation) 16 and subchorionic hemorrhage also have been shown to be associated with early
pregnancy loss but should not be used to make a definitive diagnosis 17 . These findings warrant further evaluation in 7–10 days 14 .

In cases in which an intrauterine gestation cannot be identified with reasonable certainty, serial serum β-hCG measurements and ultrasound
examinations may be required before treatment to rule out the possibility of an ectopic pregnancy. A detailed description of the
recommended approach to ectopic pregnancy diagnosis and management is available in Practice Bulletin Number 193, Tubal Ectopic
Pregnancy 18 .

What are the management options for early pregnancy loss?

Accepted treatment options for early pregnancy loss include expectant management, medical treatment, or surgical evacuation. Although
these options differ significantly in process, all have been shown to be reasonably effective and accepted by patients. In women without
medical complications or symptoms requiring urgent surgical evacuation, treatment plans can safely accommodate patient treatment
preferences. There is no evidence that any approach results in different long-term outcomes. Patients should be counseled about the risks
and benefits of each option. The following discussion applies to symptomatic and asymptomatic patients.

Expectant Management

Because of a lack of safety studies of expectant management in the second trimester and concerns about hemorrhage, expectant
management generally should be limited to gestations within the first trimester. With adequate time (up to 8 weeks), expectant management
is successful in achieving complete expulsion in approximately 80% of women 19 . Limited data suggest that expectant management may
be more effective in symptomatic women (those who report tissue passage or have ultrasound findings consistent with incomplete
expulsion) than in asymptomatic women 20 21 . Furthermore, studies that included women with incomplete early pregnancy loss tend to
report higher success rates than those that included only women with missed or anembryonic pregnancy loss 22 .

Patients undergoing expectant management may experience moderate-to-heavy bleeding and cramping. Educational materials instructing
the patient on when and who to call for excessive bleeding and prescriptions for pain medications should be provided. It also is important to
counsel patients that surgery may be needed if complete expulsion is not achieved. Studies among women with early pregnancy loss
typically have used ultrasound criteria, patient-reported symptoms, or both, to confirm complete passage of gestational tissue. Although
there is no consensus in the literature, a commonly used criterion for complete expulsion of pregnancy tissue is the absence of a gestational
sac and an endometrial thickness of less than 30 mm 23 . However, there is no evidence that morbidity is increased in asymptomatic women
with a thicker endometrial measurement 24 . Surgical intervention is not required in asymptomatic women with a thickened endometrial
stripe after treatment for early pregnancy loss. Thus, the use of ultrasound examination for any diagnostic purpose other than documenting
the absence of the gestational sac is not recommended. Other follow-up approaches, such as standardized follow-up phone calls, urine
pregnancy tests, or serial quantitative serum β-hCG measurements, may be useful, especially for women with limited access to follow-up
ultrasound examination 25 . However, these approaches have not been studied sufficiently among women with early pregnancy loss to
provide meaningful guidance.

Medical Management

Medical management for early pregnancy loss can be considered in women without infection, hemorrhage, severe anemia, or bleeding
disorders who want to shorten the time to complete expulsion but prefer to avoid surgical evacuation. Compared with expectant
management, medical management of early pregnancy loss decreases the time to expulsion and increases the rate of complete expulsion
without the need for surgical intervention 26 .

Misoprostol-based regimens have been extensively studied for the medical management of early pregnancy loss 26 . Most studies suggest
that a larger dose of misoprostol is more effective than a smaller dose, and vaginal or sublingual administration is more effective than oral
administration, although the sublingual route is associated with more cases of diarrhea 26 . The largest randomized controlled trial
conducted in the United States demonstrated complete expulsion by day 3 in 71% of women with first-trimester pregnancy loss after one
dose of 800 micrograms of vaginal misoprostol 23 . The success rate was increased to 84% after a second dose of 800 micrograms of
vaginal misoprostol was administered if needed. Therefore, in patients for whom medical management of early pregnancy loss is indicated,
initial treatment using 800 micrograms of vaginal misoprostol is recommended, with a repeat dose as needed Box 1 .

Box 1.

Protocol for the Medical Management of Early Pregnancy Loss

• Misoprostol 800 micrograms vaginally, with one repeat dose as needed, no earlier than 3 hours after the first dose and typically within 7 days if
there is no response to the first dose*

• A dose of mifepristone (200 mg orally) 24 hours before misoprostol administration should be considered when mifepristone is available.†

• Prescriptions for pain medications should be provided to the patient.

• Women who are Rh(D) negative and unsensitized should receive Rh(D)-immune globulin within 72 hours of the first misoprostol administration.

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 3/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG


• Follow-up to document the complete passage of tissue can be accomplished by ultrasound examination, typically within 7–14 days. Serial serum β-
Clinical Guidance Journals & Publications Patient Education Topics
hCG measurements may be used instead in settings where ultrasonography is unavailable. Patient-reported symptoms also should be considered
when determining whether complete expulsion has occurred.

• If medical management fails, the patient may opt for expectant management, for a time determined by the woman and her obstetrician–
gynecologist or other gynecologic provider, or suction curettage.

*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. National Institute of Child Health Human Development (NICHD) Management of Early Pregnancy Failure Trial.
N Engl J Med 2005;353:761–9.

†
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;378:2161–70.

The addition of a dose of mifepristone (200 mg orally) 24 hours before misoprostol administration may significantly improve treatment
efficacy and should be considered when mifepristone is available Box 1 . Although initial studies were unclear about the benefit of
mifepristone for the management of early pregnancy loss 27 , a 2018 randomized controlled trial showed that a combined mifepristone–
misoprostol regimen was superior to misoprostol alone for the management of early pregnancy loss 28 . Among 300 women undergoing
medical management for early pregnancy loss, those who received mifepristone (200 mg orally) followed by misoprostol (800 micrograms
vaginally) 24 hours later had significantly increased rates of complete expulsion (relative risk [RR], 1.25; 95% CI, 1.09–1.43) compared with
women who received misoprostol alone (800 micrograms vaginally) 28 . The mifepristone–misoprostol regimen also was associated with a
decreased risk of surgical intervention with uterine aspiration to complete treatment (RR, 0.37; 95% CI, 0.21–0.68). Reports of bleeding
intensity and pain as well as other adverse effects were generally similar for the two treatment groups, and the occurrence of serious
adverse events was rare among all participants. These results are consistent with the demonstrated efficacy and safety of the mifepristone–
misoprostol combined regimen for medication-induced abortion 29 30 . Currently, the availability of mifepristone is limited by U.S. Food and
Drug Administration Risk Evaluation and Mitigation Strategy restrictions 31 . The American College of Obstetricians and Gynecologists
supports improving access to mifepristone for reproductive health indications 32 .

A 2013 Cochrane review of limited evidence concluded that among women with incomplete pregnancy loss (ie, incomplete tissue passage),
the addition of misoprostol does not clearly result in higher rates of complete evacuation when compared with expectant management (at
7–10 days, success rates were 80–81% versus 52–85%, respectively) 33 . Therefore, at this time, there is insufficient evidence to support or
refute the use of misoprostol among women with incomplete pregnancy loss.

As with expectant management of early pregnancy loss, women opting for medical treatment should be counseled on what to expect while
they pass pregnancy tissue, provided information on when to call regarding bleeding, and given prescriptions for pain medications.
Counseling should emphasize that the woman is likely to have bleeding that is heavier than menses (and potentially accompanied by severe
cramping). The woman should understand how much bleeding is considered too much. An easy reference for the patient to use is the
soaking of two maxi pads per hour for 2 consecutive hours 34 . The patient should be advised to call her obstetrician–gynecologist or other
gynecologic provider if she experiences this level of bleeding. As with expectant management, it also is important to counsel patients that
surgery may be needed if medical management does not achieve complete expulsion.

Follow-up typically includes confirmation of complete expulsion by ultrasound examination, but serial serum β-hCG measurement may be
used instead in settings where ultrasonography is unavailable. Patient-reported symptoms also should be considered when determining
whether complete expulsion has occurred.

Surgical Management

Surgical uterine evacuation has long been the traditional approach for women presenting with early pregnancy loss and retained tissue.
Women who present with hemorrhage, hemodynamic instability, or signs of infection should be treated urgently with surgical uterine
evacuation. Surgical evacuation also might be preferable in other situations, including the presence of medical comorbidities such as severe
anemia, bleeding disorders, or cardiovascular disease. Many women prefer surgical evacuation to expectant or medical treatment because it
provides more immediate completion of the process with less follow-up.

In the past, uterine evacuation often was performed with sharp curettage alone. However, studies show that the use of suction curettage is
superior to the use of sharp curettage alone 35 36 . Furthermore, the routine use of sharp curettage along with suction curettage in the first
trimester does not provide any additional benefit as long as the obstetrician–gynecologist or other gynecologic provider is confident that the
uterus is empty. Suction curettage also can be performed in an office setting with an electric vacuum source or manual vacuum aspirator,
under local anesthesia with or without the addition of sedation 37 38 . Surgical management in the office setting offers significant cost
savings compared with the same procedure performed in the operating room 38 39 40 . Patients often choose management in the office
setting for its convenience and scheduling availability 38 .

How do the different management options for early pregnancy loss compare in effectiveness and risk of complications?

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 4/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
Studies have demonstrated that expectant, medical, and surgical management of early pregnancy loss all result in complete evacuation of
 Clinical Guidance Journals & Publications Patient Education Topics
pregnancy tissue in most patients, and serious complications are rare. As a primary approach, surgical evacuation results in faster and more
predictable complete evacuation 22 . The success of surgical uterine evacuation of early pregnancy loss approaches 99% 23 . The largest
U.S. trial reported that success rates after medical management of anembryonic gestations (81%) was lower than with embryonic or fetal
death (88%) or incomplete or inevitable early pregnancy loss (93%) 23 . However, a subsequent multivariable analysis of the same data
revealed that only active bleeding and nulliparity were strong predictors of success 41 . Therefore, medical management is a reasonable
option for any pregnancy failure type.

Overall, serious complications after early pregnancy loss treatment are rare and are comparable across treatment types. Clinically important
intrauterine adhesion formation is a rare complication after surgical evacuation. Hemorrhage and infection can occur with all of the
treatment approaches. In the Management of Early Pregnancy Failure Trial, women randomized to the misoprostol group were significantly
more likely to have a decrease in their hemoglobin levels greater than or equal to 3 g/dL than women in the vacuum aspiration group 23 42 .
However, rates of hemorrhage-related hospitalization with or without transfusion are similar between treatment approaches (0.5–1%) 23

43 . Pelvic infection also can occur after any type of early pregnancy loss treatment. One systematic review concluded that although
infection rates appeared lower among those undergoing expectant management than among those undergoing surgical evacuation (RR,
0.29; 95% CI, 0.09–0.97), the overall rates of infection were low (1–2%) 43 . Because neither approach was clearly superior, the reviewers
concluded that patient preference should guide choice of intervention 43 .

The risk of infection after suction curettage for missed early pregnancy loss should be similar to that after suction curettage for induced
abortion. Therefore, despite the lack of data, antibiotic prophylaxis also should be considered for patients with early pregnancy loss 44 45 .
The use of a single preoperative dose of doxycycline is recommended to prevent infection after surgical management of early pregnancy
loss. Some experts have recommended administration of a single 200-mg dose of doxycycline 1 hour before surgical management of early
pregnancy loss to prevent postoperative infection. The use of antibiotics based only on the diagnosis of incomplete early pregnancy loss has
not been found to reduce infectious complications as long as unsafe induced abortion is not suspected 46 . The benefit of antibiotic
prophylaxis for the medical management of early pregnancy loss is unknown.

How do the different treatment approaches to early pregnancy loss differ with respect to cost?

Studies have consistently shown that surgical management in an operating room is more costly than expectant or medical management 47

48 . However, surgical management in an office setting can be more effective and less costly than medical management when performed
without general anesthesia and in circumstances in which numerous office visits are likely or there is a low chance of success with medical
management or expectant management 49 . Findings from studies comparing the cost-effectiveness of medical and expectant
management schemes are inconsistent. However, a U.S. analysis of all three management approaches concluded that medical management
with misoprostol was the most cost-effective intervention 48 . One limitation of the available studies on cost of early pregnancy loss care is
that none of these studies can adequately consider clinical nuances or patient treatment preferences, which can affect patient adherence to
the primary treatment regimen and, subsequently, the effectiveness of that treatment. For instance, in one observational study, the
effectiveness of medical management of early pregnancy loss was far lower than rates reported in randomized clinical trials, which was due
in large part to patients’ unwillingness to complete the treatment regimen 50 .

How should patients be counseled regarding interpregnancy interval after early pregnancy loss?

There are no quality data to support delaying conception after early pregnancy loss to prevent subsequent early pregnancy loss or other
pregnancy complications. Small observational studies show no benefit to delayed conception after early pregnancy loss 51 52 . Abstaining
from vaginal intercourse for 1–2 weeks after complete passage of pregnancy tissue generally is recommended to reduce the risk of
infection, but this is not an evidence-based recommendation.

How should patients be counseled regarding the use of contraception after early pregnancy loss?

Women who desire contraception may initiate hormonal contraception use immediately after completion of early pregnancy loss 53 . There
are no contraindications to the placement of an intrauterine device immediately after surgical treatment of early pregnancy loss as long as
septic abortion is not suspected 53 . The expulsion rate with immediate intrauterine device insertion after suction curettage in the first
trimester is not clinically significantly different than placement 2–6 weeks postoperatively (5% versus 2.7% at 6 months) 54 .

How should patients be counseled regarding prevention of alloimmunization after early pregnancy loss?

Although the risk of alloimmunization is low, the consequences can be significant, and administration of Rh D immune globulin should be
considered in cases of early pregnancy loss, especially those that are later in the first trimester. If given, a dose of at least 50 micrograms
should be administered. Because of the higher risk of alloimmunization, Rh D-negative women who have surgical management of early
pregnancy loss should receive Rh D immune globulin prophylaxis 55 .

What type of workup is needed after early pregnancy loss?

No workup generally is recommended until after the second consecutive clinical early pregnancy loss 7 . Maternal or fetal chromosomal
analyses or testing for inherited thrombophilias are not recommended routinely after one early pregnancy loss. Although thrombophilias
commonly are thought of as causes of early pregnancy loss, only antiphospholipid syndrome consistently has been shown to be significantly
associated with early pregnancy loss 56 57 . In addition, the use of anticoagulants, aspirin, or both, has not been shown to reduce the risk of
early pregnancy loss in women with thrombophilias except in women with antiphospholipid syndrome 58 59 .

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 5/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
Are there any effective interventions to prevent early pregnancy loss?
 Clinical Guidance Journals & Publications Patient Education Topics

There are no effective interventions to prevent early pregnancy loss. Therapies that have historically been recommended, such as pelvic rest,
vitamins, uterine relaxants, and administration of β-hCG, have not been proved to prevent early pregnancy loss 60 61 62 . Likewise, bed rest
should not be recommended for the prevention of early pregnancy loss 63 . A 2008 Cochrane review found no effect of prophylactic
progesterone administration (oral, intramuscular, or vaginal) in the prevention of early pregnancy loss 64 . For threatened early pregnancy
loss, the use of progestins is controversial, and conclusive evidence supporting their use is lacking 65 . Women who have experienced at
least three prior pregnancy losses, however, may benefit from progesterone therapy in the first trimester 7 .

Summary of Recommendations and Conclusions

The following recommendation and conclusion are based on good and consistent scientific evidence (Level A):

• In patients for whom medical management of early pregnancy loss is indicated, initial treatment using 800 micrograms of vaginal
misoprostol is recommended, with a repeat dose as needed. The addition of a dose of mifepristone (200 mg orally) 24 hours before
misoprostol administration may significantly improve treatment efficacy and should be considered when mifepristone is available.

• The use of anticoagulants, aspirin, or both, has not been shown to reduce the risk of early pregnancy loss in women with thrombophilias
except in women with antiphospholipid syndrome.

The following recommendations are based on limited or inconsistent scientific evidence (Level B):

• Ultrasonography, if available, is the preferred modality to verify the presence of a viable intrauterine gestation.

• Surgical intervention is not required in asymptomatic women with a thickened endometrial stripe after treatment for early pregnancy loss.

• The routine use of sharp curettage along with suction curettage in the first trimester does not provide any additional benefit as long as the
obstetrician–gynecologist or other gynecologic provider is confident that the uterus is empty.

The following recommendations are based primarily on consensus and expert opinion (Level C):

• Accepted treatment options for early pregnancy loss include expectant management, medical treatment, or surgical evacuation. In women
without medical complications or symptoms requiring urgent surgical evacuation, treatment plans can safely accommodate patient
treatment preferences.

• The use of a single preoperative dose of doxycycline is recommended to prevent infection after surgical management of early pregnancy
loss.

• Although the risk of alloimmunization is low, the consequences can be significant, and administration of Rh D immune globulin should be
considered in cases of early pregnancy loss, especially those that are later in the first trimester.

• Because of the higher risk of alloimmunization, Rh D-negative women who have surgical management of early pregnancy loss should
receive Rh D immune globulin prophylaxis.

References
1. National Institute for Health and Clinical Excellence . Ectopic pregnancy and miscarriage: diagnosis and initial management in early pregnancy
of ectopic pregnancy and miscarriage. NICE Clinical Guideline 154 . Manchester (UK) : NICE ; 2012 . Available at:
http://www.nice.org.uk/guidance/cg154/resources/guidance-ectopic-pregnancy-and-miscarriage-pdf . Retrieved January 20, 2015. (Level III)
Article Locations:

2. Wilcox AJ , Weinberg CR , O’Connor JF , Baird DD , Schlatterer JP , Canfield RE , et al . Incidence of early loss of pregnancy . N Engl J Med 1988 ;
319 : 189 – 94 . (Level II-3)
Article Locations:

3. Wang X , Chen C , Wang L , Chen D , Guang W , French J . Conception, early pregnancy loss, and time to clinical pregnancy: a population-based
prospective study . Fertil Steril 2003 ; 79 : 577 – 84 . (Level II-2)
Article Locations:

4. Zinaman MJ , Clegg ED , Brown CC , O’Connor J , Selevan SG . Estimates of human fertility and pregnancy loss . Fertil Steril 1996 ; 65 : 503 – 9 .
(Level II-3)
Article Locations:

5. Stephenson MD , Awartani KA , Robinson WP . Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control
study . Hum Reprod 2002 ; 17 : 446 – 51 . (Level II-2)
Article Locations:

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 6/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
6. Alijotas-Reig J , Garrido-Gimenez C . Current concepts and new trends in the diagnosis and management of recurrent miscarriage . Obstet
 Clinical Guidance Journals & Publications Patient Education Topics
Gynecol Surv 2013 ; 68 : 445 – 66 . (Level III)
Article Locations:

7. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Practice Committee of the American Society for Reproductive
Medicine . Fertil Steril 2012 ; 98 : 1103 – 11 . (Level III)
Article Locations:

8. Nybo Andersen AM , Wohlfahrt J , Christens P , Olsen J , Melbye M . Maternal age and fetal loss: population based register linkage study . BMJ
2000 ; 320 : 1708 – 12 . (Level II-3)
Article Locations:

9. Barnhart KT . Early pregnancy failure: beware of the pitfalls of modern management . Fertil Steril 2012 ; 98 : 1061 – 5 . (Level III)
Article Locations:

10. Brown DL , Emerson DS , Felker RE , Cartier MS , Smith WC . Diagnosis of early embryonic demise by endovaginal sonography . J Ultrasound
Med 1990 ; 9 : 631 – 6 . (Level III)
Article Locations:

11. Pennell RG , Needleman L , Pajak T , Baltarowich O , Vilaro M , Goldberg BB , et al . Prospective comparison of vaginal and abdominal sonogra-
phy in normal early pregnancy . J Ultrasound Med 1991 ; 10 : 63 – 7 . (Level II-3)
Article Locations:

12. Abdallah Y , Daemen A , Kirk E , Pexsters A , Naji O , Stalder C , et al . Limitations of current definitions of miscarriage using mean gestational
sac diameter and crown-rump length measurements: a multicenter observational study . Ultrasound Obstet Gynecol 2011 ; 38 : 497 – 502 .
(Level II-3)
Article Locations:

13. Abdallah Y , Daemen A , Guha S , Syed S , Naji O , Pexsters A , et al . Gestational sac and embryonic growth are not useful as criteria to define
miscarriage: a multicenter observational study . Ultrasound Obstet Gynecol 2011 ; 38 : 503 – 9 . (Level II-3)
Article Locations:

14. Doubilet PM , Benson CB , Bourne T , Blaivas M , Barnhart KT , Benacerraf BR , et al . Diagnostic criteria for nonviable pregnancy early in the first
trimester. Society of Radiologists in Ultrasound Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable
Intrauterine Pregnancy . N Engl J Med 2013 ; 369 : 1443 – 51 . (Level III)
Article Locations:

15. Pexsters A , Luts J , Van Schoubroeck D , Bottomley C , Van Calster B , Van Huffel S , et al . Clinical implications of intra- and interobserver repro-
ducibility of transvaginal sonographic measurement of gestational sac and crown-rump length at 6-9 weeks’ gestation . Ultrasound Obstet
Gynecol 2011 ; 38 : 510 – 5 . (Level II-3)
Article Locations:

16. Doubilet PM , Benson CB , Chow JS . Long-term prognosis of pregnancies complicated by slow embryonic heart rates in the early first trimester
. J Ultrasound Med 1999 ; 18 : 537 – 41 . (Level II-3)
Article Locations:

17. Tuuli MG , Norman SM , Odibo AO , Macones GA , Cahill AG . Perinatal outcomes in women with subchorionic hematoma: a systematic review
and meta-analysis . Obstet Gynecol 2011 ; 117 : 1205 – 12 . (Meta-analysis)
Article Locations:

18. Tubal ectopic pregnancy. ACOG Practice Bulletin No. 193. American College of Obstetricians and Gynecologists . Obstet Gynecol 2018 ; 131 :
e91 – 103 . (Level III)
Article Locations:

19. 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 . (Level III)
Article Locations:

20. Bagratee JS , Khullar V , Regan L , Moodley J , Kagoro H . A randomized controlled trial comparing medical and expectant management of first
trimester miscarriage . Hum Reprod 2004 ; 19 : 266 – 71 . (Level I)
Article Locations:

21. Ngai SW , Chan YM , Tang OS , Ho PC . Vaginal misoprostol as medical treatment for first trimester spontaneous miscarriage . Hum Reprod
2001 ; 16 : 1493 – 6 . (Level I)
Article Locations:

22. Sotiriadis A , Makrydimas G , Papatheodorou S , Ioannidis JP . Expectant, medical, or surgical management of first-trimester miscarriage: a
meta-analysis . Obstet Gynecol 2005 ; 105 : 1104 – 13 . (Meta-analysis)
Article Locations:

23. 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. National Institute of Child Health Human Development (NICHD) Management of Early Pregnancy
Failure Trial . N Engl J Med 2005 ; 353 : 761 – 9 . (Level I)
Article Locations:

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 7/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
24. Creinin MD , Harwood B , Guido RS , Fox MC , Zhang J . Endometrial thickness after misoprostol use for early pregnancy failure. NICHD
 Clinical Guidance Journals & Publications Patient Education Topics
Management of Early Pregnancy Failure Trial . Int J Gynaecol Obstet 2004 ; 86 : 22 – 6 . (Level III)
Article Locations:

25. Grossman D , Grindlay K . Alternatives to ultrasound for follow-up after medication abortion: a systematic review . Contraception 2011 ; 83 : 504
– 10 . (Level III)
Article Locations:

26. Neilson JP , Hickey M , Vazquez JC . Medical treatment for early fetal death (less than 24 weeks) . Cochrane Database of Systematic Reviews
2006, Issue 3. Art. No.: CD002253. DOI: 10.1002/14651858.CD002253.pub3 . (Meta-analysis)
Article Locations:

27. van den Berg J , Gordon BB , Snijders MP , Vandenbussche FP , Coppus SF . The added value of mifepristone to non-surgical treatment regi-
mens 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 . (Systematic Review)
Article Locations:

28. 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 : 2161 – 70 . (Level I)
Article Locations:

29. Kulier R , Kapp N , Gülmezoglu AM , Hofmeyr GJ , Cheng L , Campana A . Medical methods for first trimester abortion . Cochrane Database of
Systematic Reviews 2011, Issue 11. Art. No.: CD002855. (Systematic Review)
Article Locations:

30. Medical management of first-trimester abortion. Practice Bulletin No. 143. American College of Obstetricians and Gynecologists . Obstet
Gynecol 2014 ; 123 : 676 – 92 . (Level III)
Article Locations:

31. U.S. Food and Drug Administration . Mifeprex (mifepristone) information. Postmarket drug safety information for patients and providers . Silver
Spring (MD) : FDA ; 2018 . (Level III)
Article Locations:

32. American College of Obstetricians and Gynecologists . Improving access to mifepristone for reproductive health indications. Position
Statement . Washington, DC : American College of Obstetricians and Gynecologists ; 2018 . (Level III)
Article Locations:

33. Neilson JP , Gyte GM , Hickey M , Vazquez JC , Dou L . Medical treatments for incomplete miscarriage . Cochrane Database of Systematic
Reviews 2013, Issue 3. Art. No.: CD007223. DOI: 10.1002/14651858.CD007223.pub3 . (Meta-analysis)
Article Locations:

34. Paul M , Lichtenberg ES , Borgatta L , Grimes DA , Stubblefield PG , Creinin MD , editors. Management of unintended and abnormal pregnancy:
comprehensive abortion care . Hoboken (NJ) : Wiley-Blackwell ; 2009 . (Level III)
Article Locations:

35. Tunçalp Ö , Gülmezoglu AM , Souza JP . Surgical procedures for evacuating incomplete miscarriage . Cochrane Database of Systematic
Reviews 2010, Issue 9. Art. No.: CD001993. DOI: 10.1002/14651858.CD001993.pub2 . (Meta-analysis)
Article Locations:

36. Rogo K . Improving technologies to reduce abortion-related morbidity and mortality . Int J Gynaecol Obstet 2004 ; 85 ( suppl 1 ): S73 – 82 .
(Level III)
Article Locations:

37. Goldberg AB , Dean G , Kang MS , Youssof S , Darney PD . Manual versus electric vacuum aspiration for early first-trimester abortion: a con-
trolled study of complication rates . Obstet Gynecol 2004 ; 103 : 101 – 7 . (Level II-3)
Article Locations:

38. Dalton VK , Harris L , Weisman CS , Guire K , Castleman L , Lebovic D . Patient preferences, satisfaction, and resource use in office evacuation of
early pregnancy failure . Obstet Gynecol 2006 ; 108 : 103 – 10 . (Level II-3)
Article Locations:

39. Blumenthal PD , Remsburg RE . A time and cost analysis of the management of incomplete abortion with manual vacuum aspiration . Int J
Gynaecol Obstet 1994 ; 45 : 261 – 7 . (Level III)
Article Locations:

40. Choobun T , Khanuengkitkong S , Pinjaroen S . A comparative study of cost of care and duration of management for first-trimester abortion with
manual vacuum aspiration (MVA) and sharp curettage . Arch Gynecol Obstet 2012 ; 286 : 1161 – 4 . (Level II-3)
Article Locations:

41. Creinin MD , Huang X , Westhoff C , Barnhart K , Gilles JM , Zhang J . Factors related to successful misoprostol treatment for early pregnancy
failure. National Institute of Child Health and Human Development Management of Early Pregnancy Failure Trial . Obstet Gynecol 2006 ; 107 :
901 – 7 . (Level II-2)
Article Locations:

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 8/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
42. Davis AR , Hendlish SK , Westhoff C , Frederick MM , Zhang J , Gilles JM , et al . Bleeding patterns after misoprostol vs surgical treatment of
 Clinical Guidance Journals & Publications Patient Education Topics
early pregnancy failure: results from a randomized trial. National Institute of Child Health and Human Development Management of Early
Pregnancy Failure Trial . Am J Obstet Gynecol 2007 ; 196 : 31.e1 – 31.e7 . (Level I)
Article Locations:

43. Nanda K , Lopez LM , Grimes DA , Peloggia A , Nanda G . Expectant care versus surgical treatment for miscarriage . Cochrane Database of
Systematic Reviews 2012, Issue 3. Art. No.: CD003518. DOI: 10.1002/14651858.CD003518.pub3 . (Meta-analysis)
Article Locations:

44. Achilles SL , Reeves MF . Prevention of infection after induced abortion: release date October 2010: SFP guideline 20102. Society of Family
Planning . Contraception 2011 ; 83 : 295 – 309 . (Level III)
Article Locations:

45. Sawaya GF , Grady D , Kerlikowske K , Grimes DA . Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a
meta-analysis . Obstet Gynecol 1996 ; 87 : 884 – 90 . (Meta-analysis)
Article Locations:

46. Prieto JA , Eriksen NL , Blanco JD . A randomized trial of prophylactic doxycycline for curettage in incomplete abortion . Obstet Gynecol 1995 ;
85 : 692 – 6 . (Level I)
Article Locations:

47. Petrou S , McIntosh E . Women’s preferences for attributes of first-trimester miscarriage management: a stated preference discrete-choice ex-
periment . Value Health 2009 ; 12 : 551 – 9 . (Level III)
Article Locations:

48. You JH , Chung TK . Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis . Hum
Reprod 2005 ; 20 : 2873 – 8 . (Level III)
Article Locations:

49. Rausch M , Lorch S , Chung K , Frederick M , Zhang J , Barnhart K . A cost-effectiveness analysis of surgical versus medical management of
early pregnancy loss . Fertil Steril 2012 ; 97 : 355 – 60 . (Level III)
Article Locations:

50. Colleselli V , Schreiber CA , D’Costa E , Mangesius S , Wildt L , Seeber BE . Medical management of early pregnancy failure (EPF): a retrospective
analysis of a combined protocol of mifepristone and misoprostol used in clinical practice . Arch Gynecol Obstet 2014 ; 289 : 1341 – 5 . (Level II-
3)
Article Locations:

51. Vlaanderen W , Fabriek LM , van Tuyll van Serooskerken C . Abortion risk and pregnancy interval . Acta Obstet Gynecol Scand 1988 ; 67 : 139 –
40 . (Level II-3)
Article Locations:

52. Goldstein RR , Croughan MS , Robertson PA . Neonatal outcomes in immediate versus delayed conceptions after spontaneous abortion: a retro-
spective case series . Am J Obstet Gynecol 2002 ; 186 : 1230 – 4 ; discussion 1234–6. (Level III)
Article Locations:

53. U.S. medical eligibility criteria for contraceptive use, 2010. Centers for Disease Control and Prevention (CDC) . MMWR Recomm Rep 2010 ; 59 (
RR-4 ): 1 – 86 . (Level III)
Article Locations:

54. Bednarek PH , Creinin MD , Reeves MF , Cwiak C , Espey E , Jensen JT . Immediate versus delayed IUD insertion after uterine aspiration. Post-
Aspiration IUD Randomization (PAIR) Study Trial Group . N Engl J Med 2011 ; 364 : 2208 – 17 . (Level I)
Article Locations:

55. Prevention of Rh D alloimmunization. Practice Bulletin No. 181. American College of Obstetricians and Gynecologists . Obstet Gynecol 2017 ;
130 : e57 – 70 . (Level III)
Article Locations:

56. McNamee K , Dawood F , Farquharson R . Recurrent miscarriage and thrombophilia: an update . Curr Opin Obstet Gynecol 2012 ; 24 : 229 – 34 .
(Level III)
Article Locations:

57. McNamee K , Dawood F , Farquharson RG . Thrombophilia and early pregnancy loss . Best Pract Res Clin Obstet Gynaecol 2012 ; 26 : 91 – 102 .
(Level III)
Article Locations:

58. Empson MB , Lassere M , Craig JC , Scott JR . Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoag-
ulant . Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD002859. DOI: 10.1002/14651858.CD002859.pub2 . (Meta-analysis)
Article Locations:

59. de Jong PG , Kaandorp S , Di Nisio M , Goddijn M , Middeldorp S . Aspirin and/or heparin for women with unexplained recurrent miscarriage with
or without inherited thrombophilia . Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD004734. DOI:
10.1002/14651858.CD004734.pub4 . (Meta-analysis)
Article Locations:

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 9/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
60. Rumbold A , Middleton P , Pan N , Crowther CA . Vitamin supplementation for preventing miscarriage . Cochrane Database of Systematic
 Clinical Guidance Journals & Publications Patient Education Topics
Reviews 2011, Issue 1. Art. No.: CD004073. DOI: 10.1002/14651858.CD004073.pub3 . (Meta-analysis)
Article Locations:

61. Lede RL , Duley L . Uterine muscle relaxant drugs for threatened miscarriage . Cochrane Database of Systematic Reviews 2005, Issue 3. Art.
No.: CD002857. DOI: 10.1002/14651858.CD002857.pub2 . (Meta-analysis)
Article Locations:

62. Devaseelan P , Fogarty PP , Regan L . Human chorionic gonadotrophin for threatened miscarriage . Cochrane Database of Systematic Reviews
2010, Issue 5. Art. No.: CD007422. DOI: 10.1002/14651858.CD007422.pub2 . (Meta-analysis)
Article Locations:

63. Aleman A , Althabe F , Belizán JM , Bergel E . Bed rest during pregnancy for preventing miscarriage . Cochrane Database of Systematic Reviews
2005, Issue 2. Art. No.: CD003576. DOI: 10.1002/14651858.CD003576.pub2 . (Meta-analysis)
Article Locations:

64. Haas DM , Ramsey PS . Progestogen for preventing miscarriage . Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.:
CD003511. DOI: 10.1002/14651858.CD003511.pub3 . (Meta-analysis)
Article Locations:

65. Wahabi HA , Fayed AA , Esmaeil SA , Al Zeidan RA . Progestogen for treating threatened miscarriage . Cochrane Database of Systematic
Reviews 2011, Issue 12. Art. No.: CD005943. DOI: 10.1002/14651858.CD005943.pub4 . (Meta-analysis)
Article Locations:

The MEDLINE database, the Cochrane Library, and the American College of Obstetricians and Gynecologists’ own internal resources and documents
were used to conduct a literature search to locate relevant articles published between January 2000–July 2014. The search was restricted to articles
published in the English language. Priority was given to articles reporting results of original research, although review articles and commentaries also
were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document.
Guidelines published by organizations or institutions such as the National Institutes of Health and the American College of Obstetricians and
Gynecologists were reviewed, and additional studies were located by reviewing bibliographies of identified articles. When reliable research was not
available, expert opinions from obstetrician–gynecologists were used.

Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive Services Task Force:

• I Evidence obtained from at least one properly designed randomized controlled trial.

• II-1 Evidence obtained from well-designed controlled trials without randomization.

• II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

• II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be
regarded as this type of evidence.

• III Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Based on the highest level of evidence found in the data, recommendations are provided and graded according to the following categories:

Level A—Recommendations are based on good and consistent scientific evidence.

Level B—Recommendations are based on limited or inconsistent scientific evidence.

Level C—Recommendations are based primarily on consensus and expert opinion.

Published online on August 29, 2018.

Copyright 2018 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a
retrieval system, posted on the Internet, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior
written permission from the publisher.

Requests for authorization to make photocopies should be directed to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400.

American College of Obstetricians and Gynecologists 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920

Early pregnancy loss. ACOG Practice Bulletin No. 200. American College of Obstetricians and Gynecologists. Obstet Gynecol 2018;132:e197–207.

This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary.
This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It is not intended
to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the reasonable judgment of
the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or
technology. The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its publications may not reflect the most
recent evidence. Any updates to this document can be found on www.acog.org or by calling the ACOG Resource Center.

While ACOG makes every effort to present accurate and reliable information, this publication is provided “as” is without any warranty of accuracy, reliability, or
otherwise, either express or implied. ACOG does not guarantee, warrant, or endorse the products or services of any firm, organization, or person. Neither ACOG
nor its officers, directors, members, employees, or agents will be liable for any loss, damage, or claim with respect to any liabilities, including direct, special,
indirect, or consequential damages, incurred in connection with this publication or reliance on the information presented.

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 10/11
9/13/23, 12:07 PM Early Pregnancy Loss | ACOG
All ACOG committee members and authors have submitted a conflict of interest disclosure statement related to this published product. Any potential conflicts
 Clinical Guidance Journals & Publications Patient Education Topics
have been considered and managed in accordance with ACOG’s Conflict of Interest Disclosure Policy. The ACOG policies can be found on acog.org . For
products jointly developed with other organizations, conflict of interest disclosures by representatives of the other organizations are addressed by those
organizations. The American College of Obstetricians and Gynecologists has neither solicited nor accepted any commercial involvement in the development of
the content of this published product.

Topics Blood proteins Combined oral contraceptives Diagnostic imaging Hormonal methods Immunoglobulins Immunoproteins

Induced abortion Intrauterine devices Intrauterine systems LARC Medicated intrauterine devices Misoprostol

Obstetrical and gynecological diagnostic techniques Obstetric surgical procedures Oral contraceptives Pregnancy complications

Prenatal diagnosis Prenatal ultrasonography Prostaglandins Spontaneous abortion Ultrasonography

American College of Obstetricians and Gynecologists Copyright 2023. All rights reserved.
409 12th Street SW, Washington, DC 20024-2188 Privacy Statement | Terms and Conditions of Use

https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/11/early-pregnancy-loss 11/11