eMedicine Specialties > Obstetrics and Gynecology > General Gynecology

First-Trimester Pregnancy Loss

Elizabeth E Puscheck, MD, Associate Professor, Department of Obstetrics and Gynecology, Wayne State University School of Medicine; In Vitro Fertilization Director, Medical Director, Gynecologic Ultrasound Director, Clinical Endocrine Laboratory Consultant, Department of Obstetrics and Gynecology, University Women's Care
Archana Pradhan, MD, MPH, Staff Physician, Department of Obstetrics and Gynecology, Nassau University Medical Center

Updated: Jun 25, 2006

Introduction

Background

An abortion is the spontaneous or induced loss of an early pregnancy. The period of pregnancy prior to fetal viability outside of the uterus is considered early pregnancy. Most consider early pregnancy to end at 20-24 weeks' gestation. The term miscarriage is used often in the lay language and refers to spontaneous abortion.

Pathophysiology

A spontaneous abortion is a process that can be divided into 4 stages—threatened, inevitable, incomplete, and complete.

Threatened abortion consists of any vaginal bleeding during early pregnancy without cervical dilatation or change in cervical consistency. Usually, no significant pain exists, although mild cramps may occur. More severe cramps may lead to an inevitable abortion.

Threatened abortion is very common in the first trimester; about 25-30% of all pregnancies have some bleeding during the pregnancy. Less than one half proceed to a complete abortion or miscarriage. On examination, blood or brownish discharge may exist in the vagina. The cervix is not tender, and the cervical os is closed. No fetal tissue or membranes have passed. The ultrasound shows a continuing intrauterine pregnancy. If an ultrasound was not performed previously, it is required at this time to rule out an ectopic pregnancy, which could present similarly. If the uterine cavity is empty on ultrasound, obtaining a human chorionic gonadotropin (hCG) level is necessary to determine if the discriminatory zone has been passed.

The discriminatory zone is the level of hCG beyond which an intrauterine pregnancy is consistently visible. The discriminatory zone may vary depending on a number of factors, including hCG assay type and reference calibration standard used, ultrasound equipment resolution, the skill and experience of the sonographer, and patient factors (eg, obesity, leiomyomas, uterine axis, multiple gestations). Also, the discriminatory zone will vary depending on whether the ultrasound is performed abdominally or vaginally. Therefore, having a universal discriminatory zone is difficult, and it optimally should be calculated at each site.

However, some studies recommend that an estimate would be that a gestational sac should be visualized by 5.5 weeks' gestation; a gestational sac should be visualized with an hCG level of 1500-2400 mIU/mL for transvaginal ultrasound or with an hCG level over 3000 mIU/mL for a transabdominal ultrasound. If the hCG level is higher than the discriminatory zone and no gestational sac is visualized in the uterus, then consider that an ectopic pregnancy may be present.

Inevitable abortion is an early pregnancy with vaginal bleeding and dilatation of the cervix. Typically, the vaginal bleeding is worse than with a threatened abortion, and more cramps are present. No tissue has passed yet.

Incomplete abortion is a pregnancy that is associated with vaginal bleeding, dilatation of the cervical canal, and passage of products of conception. Usually, the cramps are intense, and the vaginal bleeding is heavy. Patients describe passage of tissue, or the examiner observes evidence of tissue passage within the vagina. The ultrasound confirms that some of the products of conception are still present in the uterus.

Complete abortion is a completed miscarriage. Typically, a history of vaginal bleeding, abdominal pain, and passage of tissue exists. After the tissue passes, the patient notes that the pain subsides and the vaginal bleeding significantly diminishes. The examination reveals some blood in the vaginal vault; a closed cervical os; and no tenderness of the cervix, uterus, adnexa, or abdomen. The ultrasound demonstrates an empty uterus.

These 4 stages of abortion described above form a continuum. Most studies do not differentiate separately between the epidemiology and pathophysiology of each entity described above.

A fifth term that does not follow the continuum but is important to be aware of is missed abortion. A missed abortion is a nonviable intrauterine pregnancy that has been retained within the uterus without spontaneous abortion. Typically, no symptoms exist besides amenorrhea, and the patient finds out that the pregnancy stopped earlier when a fetal heartbeat is not observed or heard at the appropriate time. An ultrasound usually confirms the diagnosis. No vaginal bleeding, abdominal pain, passage of tissue, or cervical changes are present.

Frequency

United States

The overall miscarriage rate is reported as 15-20%, which means 15-20% of recognized pregnancies result in miscarriage. The frequency of spontaneous miscarriage increases further with maternal age. With the development of highly sensitive assays for hCG levels, pregnancies can be detected prior to the expected next period. When these highly sensitive hCG assays are used early, the magnitude of pregnancy loss significantly increases to about 60-70%. Late implantation by the conceptus beyond the usual 8-10 days after ovulation also has an increased risk of miscarriage.

About 80% of miscarriages occur within the first trimester. The frequency of miscarriage decreases with an increasing gestational age. Recurrent miscarriage, defined as 2-3 pregnancy losses, affects about 1% of all couples.

International

No significant difference exists between international rates and the rates in the United States.

Mortality/Morbidity

A complete abortion is unlikely to cause any significant risk of mortality unless significant blood loss or infection occurs. Morbidity would be increased if an anemia or infection develops. Patients who are pregnant may bleed quickly and significantly. Distinguishing the causes of bleeding during pregnancy is important.

Threatened abortions usually bleed, a viable intrauterine pregnancy is visible on ultrasound, and the cervical canal is closed. A complete abortion will have a history of bleeding and significant cramping with passage of tissue, followed by a marked reduction in bleeding and resolution of cramping. With a complete abortion, the ultrasound demonstrates an empty uterus and the examination is notable for a closed cervical os. Incomplete or inevitable abortions have bleeding and an open cervical os on examination. The ultrasound may show clots or an intrauterine pregnancy.

These latter 2 conditions (incomplete and inevitable abortions) are a cause for concern when significant bleeding or infection occurs. If a suction dilatation and curettage (D&C) is not performed in a timely manner, significant morbidity and mortality may occur. Retained products of conception also may occur after a spontaneous abortion or after a suction D&C.

Patients with retained products usually return for medical care with symptoms of increased bleeding, increased cramping, and/or infection. Caring for these patients quickly with intravenous antibiotics is important, and, after the antibiotics are administered, then a suction D&C or a repeat suction D&C is performed. These patients will be at risk for developing Asherman syndrome, which consists of adhesions within the uterine cavity. Patients who develop Asherman syndrome may present with amenorrhea or decreased menstrual flow. Asherman syndrome may compromise future fertility. When significant bleeding occurs, fluid management and transfusions may be required while stabilizing the patient prior to a suction D&C.

A complication of D&C is perforation of the uterus, which may be handled by observation. If the patient shows signs of uncontrolled bleeding on ultrasound, then proceeding to a laparoscopy or laparotomy with cauterization of the bleeding area may be necessary. The choice for laparoscopy or laparotomy depends on the stability of the patient. Occasionally, the perforation is in the area of the uterine vessels or other area where the bleeding is difficult to control and a hysterectomy may be necessary. When bleeding is out of control, the patient easily can go into hypovolemic shock or disseminated intravascular coagulopathy (DIC). Both of these situations need prompt attention and treatment.

Race

Complete abortions may occur in any race without distinction.

Sex

Complete abortions only affect females.

Age

Complete abortions only occur in reproductive-aged women unless in vitro fertilization was used with donor eggs in menopausal women. As women mature, the incidence of spontaneous miscarriages increases. Typically, the distribution of miscarriage rates by age occurs as follows: younger than 35 years old, 15% miscarriage rate; 35-39 years old, 20-25% miscarriage rate; 40-42 years old, about 35% miscarriage rate; and older than 42 years old, about 50% miscarriage rate.

Clinical

History

Patients with spontaneous complete abortion usually present with a history of vaginal bleeding, abdominal pain, and passage of tissue. After the tissue passes, the vaginal bleeding and abdominal pain subsides.

• Vaginal bleeding is usually heavy.
  • Quantification of the amount of bleeding is very important because life-threatening hemorrhage may occur. The patient may be able to quantify the number of pads or tampons used over a specified time and qualify the amount that each pad is soaked. This is just an estimate; yet, soaking a pad or more an hour suggests significant and worrisome amounts of bleeding that require prompt attention. These patients should be sent to the emergency department.
  • The presence of blood clots suggests heavy bleeding. The presence of blood clots also may be confused with passage of tissue.
  • Examining the passed material helps clarify whether the material is clot or tissue. If the material is tissue, then the type of abortion may be identified. If the tissue is evaluated and is complete, then a complete abortion is confirmed.
• Abdominal pain is associated with concurrent abortion and resolves with the completion of the abortion.
  • The pain usually is in the suprapubic area, but reports of pain in one or both lower quadrants are not uncommon.
  • The pain may radiate to the lower back, buttocks, genitalia, and perineum.
  • If the pain is occurring only on one side, consider an ectopic pregnancy or a ruptured ovarian cyst as possible causes.
• Consider any reproductive-aged woman presenting with vaginal bleeding to be pregnant until proven otherwise.
• Other symptoms, such as fever or chills, are more characteristic of infection, such as in a septic abortion. Septic abortions need to be treated immediately, otherwise they may be life threatening.

Physical

Patients who are pregnant and bleeding vaginally need immediate evaluation.

• Estimating the patient's hemodynamic stability is the first step.
  • Obtain orthostatic vital signs.
  • Initiate fluid resuscitation early in cases of orthostatic hypotension.
  • Abdominal and pelvic examinations are next.
• The abdominal examination needs to determine whether or not the state of an acute abdomen is present.
  • In a complete abortion, the abdomen is benign, with no distension, no rebound, normal bowel sounds, no hepatosplenomegaly, and mild suprapubic tenderness.
  • Usually, the uterus is either not palpable abdominally or is just slightly above the pubic symphysis in a first-trimester pregnancy loss. The uterus can be enlarged due to other pathology (ie, leiomyomas).
  • If rebound tenderness and/or a distended uterus exist, it is unlikely that a complete abortion has occurred. Assume that an ectopic pregnancy occurred if rebound tenderness is present, and provide the patient with aggressive fluid resuscitation with 2 IV lines and an emergent laparoscopy (if stable enough) or an emergent exploratory laparotomy.
• In the case of a complete abortion, pelvic examination may show some blood on the perineum or vagina but limited active bleeding.
  • The cervix is nontender to minimally tender, and the cervical canal is closed.
  • The uterus is smaller than what is expected for dates, and it is nontender to mildly tender.
  • The adnexa are nontender to mildly tender. Usually, no adnexal masses exist, unless a corpus luteum is still palpable.
  • In summary, the pelvic examination check list includes assessment of the following:
    • Source of bleeding (cervical os)
    • Intensity of bleeding (active, heavy, clots)
    • Any presence or passage of tissue
    • Cervical motion tenderness (increases suspicion for ectopic pregnancy)
    • Cervical os closed for complete or threatened abortion (If it is open, consider inevitable or incomplete abortion.)
    • Uterine size and tenderness
    • Adnexal masses (suspicious for ectopic pregnancy)

Causes

• In the first trimester, embryonic causes of spontaneous abortion are the predominant etiology and account for 80-90% of miscarriages.
• Genetic abnormalities within the embryo (ie, chromosomal abnormalities) are the most common cause of spontaneous abortion and account for 50-65% of all miscarriages.
  • The most common single chromosomal anomaly is 45,X karyotype, with an incidence of 14.6%.
  • Trisomies are the single largest group of chromosomal anomalies and account for approximately one half of all anomalies associated with miscarriage. Trisomy 16 is the most common trisomy found.
  • Approximately 20% of genetic abnormalities are triploidies.
• Teratogenic and mutagenic factors may play a role, but quantification is difficult.
• Maternal causes of spontaneous miscarriage include the following:
  • Genetic: Maternal age is directly related to the aneuploidy risk (>30% in people aged 40 y). Couples with recurrent miscarriages have a 2-3% incidence of a parental chromosomal anomaly (ie, balanced translocation).
  • Structural abnormalities of the reproductive tract include the following:
    • Congenital uterine defects (particularly uterine septum)
    • Fibroids
    • Cervical incompetence
  • Iatrogenic causes (ie, Asherman syndrome)
  • Acute maternal factors include the following:
    • Corpus luteum deficiency
    • Active infection (eg, rubella virus, cytomegalovirus, Listeria infection, toxoplasmosis)
  • Chronic maternal health factors include the following:
    • Polycystic ovary syndrome
    • Poorly controlled diabetes mellitus (A successful pregnancy requires much tighter control.)
    • Renal disease
    • Systemic lupus erythematosus (SLE)
    • Untreated thyroid disease
    • Severe hypertension
    • Antiphospholipid syndrome
  • Exogenous factors include the following:
    • Tobacco
    • Alcohol
    • Cocaine
    • Caffeine (high doses)

Differential Diagnoses

Other Problems to Be Considered

Abortion, incomplete
Abortion, inevitable
Acute appendicitis
Cervical polyps, ectropion, or malignancy
Ovarian torsion
Pregnancy, molar
Pregnancy, subchorionic hemorrhage
Vaginal/vulvar condylomata

Workup

Laboratory Studies

• Complete blood count (CBC) with differential, beta-hCG, blood type and screen (possible crossmatch), possible DIC profile, and urinalysis
  • CBC will help document the amount of blood loss and whether anemia is present. If the hemoglobin and hematocrit are very low and the patient is symptomatic then transfusions would be warranted. The CBC also will provide evidence regarding an infection, which, in the case of infection, would yield an elevated white blood cell count and a left shift on differential.
  • Beta-hCG is important to confirm the pregnancy and distinguish it from dysfunctional uterine bleeding or bleeding from another etiology. The hCG level is also important to help distinguish a complete abortion from a threatened abortion or ectopic pregnancy. If the hCG level is above 1500-2000 mIU/mL, then transvaginal ultrasonography should detect a viable intrauterine pregnancy. A level over 3000 mIU/mL should enable one to visualize a viable intrauterine pregnancy by transabdominal ultrasonography. If the values are so elevated, the cervical canal is closed, and the patient's history is consistent with passing tissue (which a physician has confirmed), then an empty uterus on ultrasonography is consistent with a completed abortion. However, if the hCG level is elevated, no history of passing tissue is present, and the ultrasonography demonstrates an empty uterus, one must assume that an ectopic pregnancy is present until proven otherwise. Low hCG levels (ie, <200 mIU/mL) may make the diagnosis more difficult. Observation and monitoring the hCG levels every few days may be an option if the patient is stable and not complaining of pain. If these low hCG levels plateau and fall, the patient will likely miscarry or have a tubal abortion on her own. However, if the values rise, then follow-up ultrasonography is necessary to determine whether an intrauterine pregnancy or an ectopic pregnancy is present and subsequent appropriate management is necessary. The hCG level should rise about 60% every 2 days during the early first trimester.
  • Blood type and screen (possible crossmatch) is important to determine whether treatment with RhoGAM is appropriate. An Rh-negative woman should receive RhoGAM within 72 hours of miscarriage or ectopic pregnancy to avoid the possibility that the pregnancy has exposed the patient to a positive antigen. If the father of the baby also is Rh negative then the patient can forego the immunoglobulin therapy. It also is important in cases where transfusions are necessary.
  • DIC profile is necessary only in those cases with significant bleeding. The DIC profile usually consists of a platelet count, fibrinogen level, prothrombin time (PT), and activated partial prothrombin time (aPTT). When significant bleeding occurs and the patient is consuming these factors faster then she can make them, then the initiating event needs to be treated (ie, D&C, hysterectomy) and platelets, coagulation factors (usually administered in the form of fresh frozen plasma or cryoprecipitate), or fibrinogen in addition to packed red blood cells may need to be replaced when transfusing a patient. Whole blood may be transfused as another alternative.
  • Urinalysis is important to rule out a urinary tract infection. Pregnant women are prone to urinary tract infections due to the progesterone effect on the smooth muscle of the ureters, which causes mild physiologic hydroureters. A cystitis or renal stone also could be present with bleeding but from a urinary source.

Imaging Studies

• Ultrasound of the pelvis using a vaginal probe to rule out an ectopic pregnancy, retained products of conception, hematometra, or other etiologies: Once the discriminatory level is passed, the ultrasound is fairly reliable. Perform other imaging studies as needed.

Procedures

• If the diagnosis truly is a complete abortion, then no further procedures are needed.

Treatment

Medical Care

A complete abortion usually needs no further treatment, medically or surgically.

With missed, incomplete, or inevitable abortion before 13 weeks' gestation, the standard therapy has been suction D&C. However, at least 2 randomized controlled trials show that misoprostol is an effective medical therapy. In 1 study of incomplete abortion, the subjects were randomized between oral misoprostol (600 mcg) or suction D&C with a 96.3% versus 91.5% success rate in completed abortion with low complications (0.9% for misoprostol) (Weeks, 2005).

The other study was a randomized controlled trial with a 3:1 ratio in favor of medical therapy and it included subjects with the following diagnoses: missed abortion (with or without a fetal pole; no fetal heart motion when the fetal pole was present), incomplete abortion, or inevitable abortion. In this study, the initial dose of misoprostol was 800 mcg (4 tab 200 mcg placed vaginally) and the subject was reevaluated on day 3. If the expulsion had not occurred then a second dose of 800 mcg of misoprostol was placed vaginally. The results showed that 71% had completed abortion after the first dose by day 3 and 84% had success with misoprostol by day 8 (95% confidence interval, 81-87%). The risks for bleeding and infection were similar to surgical management (Zhang, 2005).

Medical therapy using misoprostol is an acceptable alternative to surgical therapy for most women based upon these early data.

• In the situation in which a considerable amount of blood loss has occurred, iron therapy or transfusions may be indicated.
• If the diagnosis in not correct, the patient is likely to continue to bleed and cramp for an incomplete or inevitable abortion. In these situations, a suction D&C is indicated. If the patient has any signs of infection, start antibiotics prior to the D&C.
• An ectopic pregnancy may be treated medically or surgically, depending on the clinical scenario.
  • Medical therapy consists of methotrexate, which usually is administered in a dose of 50 mg/m². The effectiveness of medical therapy depends on only applying it to patients who are appropriate candidates based on gestational age, hCG level, ectopic size, patient reliability & compliance, proximity to the office or hospital, and health.
  • Prior to administering the methotrexate, renal and liver function tests are measured and results should be normal. A CBC is warranted, and, if significant anemia exists, then medical therapy is not warranted.
  • The absolute limits for gestational age, hCG level, ectopic size, and the presence or absence of an embryonic heartbeat are debated in the literature. Despite the debate, the factors that decrease the likelihood of success are older gestational age, higher hCG, larger ectopic size, and the presence of a fetal heartbeat.
  • The author likes to use a rule of 3s because it is easy to remember. A patient who is less than 3 weeks from expected menses (7 wk from last menstrual period [LMP]), has an hCG level less than 3000 mIU/mL, and has an ectopic size less than 3 cm has a 95% chance of success with methotrexate. The patient should not have pelvic pain and should have only minimal vaginal bleeding for medical therapy to be considered.
  • On the day of methotrexate injection and on days 4 and 7 after the injection, the hCG level is monitored. A 15% drop in the hCG level is expected between day 4 and day 7. From day 1 to day 4, a rise in the hCG level may occur. If a 15% drop in the hCG level occurs on day 7, then the patient is monitored with weekly hCG levels until the level is less than 5 mIU/mL.
  • Patients may have some cramping or discomfort on the side of the ectopic pregnancy as the hCG declines, but these symptoms should be mild. Typically, patients do not experience bleeding until the hCG level is low.
  • The authors encourage increased fluid intake to avoid some of the adverse effects of methotrexate (mouth sores, renal impairment, etc). However, this dose of methotrexate is much smaller than that used to treat trophoblastic disease, and most patients have very little problems with taking it.
• After methotrexate therapy for an ectopic pregnancy, any plateau or rising of hCG requires evaluation. In some situations, considering a second dose of methotrexate is possible. However, consider surgery as well.
• Any symptoms suggesting ectopic rupture (eg, acute pain, rebound tenderness) should immediately direct the physician to the operating room.
  • Laparoscopy can still be considered if the patient is stable.
  • A linear salpingostomy with excision of the ectopic pregnancy or partial salpingectomy are the possible procedures.
  • If the patient is unstable, the same procedures are performed using a laparotomy.
• For a complete abortion, the medical care is to treat any remaining anemia and to evaluate the blood type and treat the patient with RhoGAM when indicated.
• Prehospital care: Monitor vital signs and provide fluid resuscitation if the patient is hemodynamically stable.
• Emergency department care: If they know what to expect, most patients with complete abortions are not treated in the emergency department. Only those with significant blood loss go to the emergency department.
• Patients with threatened, inevitable, incomplete, and ectopic pregnancies may go to the emergency department.
  • Patients with threatened abortions need an ultrasound to confirm the diagnosis and for reassurance. Usually, no other medical therapy is needed. These patients often are counseled to increase fluid intake, remain at bedrest, or add progesterone supplements. However, none of these treatments have been proven effective in a prospective randomized trial.
  • Abortion, Inevitable, Abortion, Incomplete, and Ectopic Pregnancy are discussed above and in separate articles.

Surgical Care

No surgical care is used for complete abortion.

• Inevitable and incomplete abortions are typically treated surgically with suction D&C.
• A septic abortion requires antibiotic therapy prior to a D&C.
• An ectopic pregnancy may be treated medically for the appropriate candidates. The rest require surgery. Surgery for an ectopic pregnancy may consist of either linear salpingostomy or partial or complete salpingectomy via laparoscopy or laparotomy. Although most ectopic pregnancies occur in the fallopian tube, rarely they are located in the ovary and the ovary may need to be removed. An ectopic pregnancy may be found in the abdomen after a tubal abortion has occurred. In this case, the ectopic gestation is removed. If it is adherent to the bowel, then the ectopic gestation is removed as much as possible and follow-up treatment with methotrexate is warranted. In this latter case, the hCG levels need to be monitored until they are less than 5 mIU/mL.
• Whenever the diagnosis is uncertain, it may be appropriate to perform a diagnostic laparoscopy and possible D&C.

Consultations

Consult an obstetrician/gynecologist any time uncertainty about the diagnosis exists and to administer treatment.

Diet

• The patient's diet should be regular if the diagnosis truly is a complete abortion.
• If any uncertainty about the diagnosis exists, keep the patient on nothing by mouth (NPO) until certain that a surgical treatment is not necessary.

Activity

The patient should rest for a few days to 2 weeks for a complete abortion. The rest schedule needs to be adjusted if one of the other diagnoses is correct.

Medication

For a complete abortion, no medication is likely to be needed. Usually, the uterus contracts well after expelling the entire contents and the cervix is closed. The risk for infection is minimal.

Immune globulins

Used to suppress the immune system when the mother is Rh negative.

Rho (D) immune globulin (RhoGAM)

Suppresses immune response of mother who is nonsensitized Rh O (D) negative exposed to Rh O (D) positive blood from the fetus as a result of a fetomaternal hemorrhage, abdominal trauma, amniocentesis, abortion, full-term delivery, or transfusion accident.

Dosing

Adult

<13 weeks' gestation: 50 mcg IM within 72 h of exposure
>13 weeks' gestation: 300 mcg IM

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; patients who have received Rho (D)–positive blood within the last 3 mo

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in thrombocytopenia, bleeding disorders, or IgA deficiency

Ergot alkaloid and derivatives

Occasionally, the uterus does not contract well, and a clot may form in the uterine cavity. If the physician notes a boggy uterus after expulsion of the products of conception, the physician may consider methylergonovine in the appropriate candidate. In most cases in which a clot forms within the uterus, a surgical D&C finally is warranted.

Methylergonovine (Methergine)

Acts directly on uterine smooth muscle, causing a sustained tetanic uterotonic effect that reduces uterine bleeding and shortens the third stage of labor.
Administer IM after a D&C, during puerperium, after delivery of placenta, or after delivering anterior shoulder. Also may be administered IV over no less than 60 sec, but should not be administered routinely because it may provoke hypertension or a stroke. Monitor blood pressure closely when administering IV.

Dosing

Adult

0.2 mg PO tid for 3 d

Pediatric

Not established

Interactions

Concurrent administration of methylergonovine with vasoconstrictors or other ergot alkaloids may produce additive effects

Contraindications

Documented hypersensitivity; glaucoma; Tourette syndrome; anxiety

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established

Precautions

Caution in sepsis, obliterative vascular disease, or hepatic or renal insufficiency

Antineoplastic agent, antimetabolite

These agents inhibit cell growth and proliferation.

Methotrexate (Rheumatrex, Trexall)

Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and embryonic cell reproduction.

Dosing

Adult

50 mg/m² IM once

Pediatric

Not established

Interactions

Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) can increase MTX plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines

Contraindications

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency

Precautions

Pregnancy

X - Contraindicated in pregnancy

Precautions

Has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; fatal reactions reported when administered concurrently with NSAIDs

Prostaglandins

Misoprostol, a prostaglandin agent, has been recently reported as safe and effective medical treatment for missed abortion, inevitable abortion, or incomplete abortion. It is used as off-labeled indication and is not FDA approved for this indication.

Misoprostol (Cytotec)

Prostaglandin agent also categorized as an anti-ulcer (protective) and endocrine metabolic agent. As a prostaglandin agent, misoprostol will increase uterine smooth muscle contractions and soften the cervix to allow passage of products of conception from missed abortion, inevitable abortion, or incomplete abortion. Not FDA approved for medical treatment of these types of abortions; yet, recent literature suggests is that it is safe and effective. Administered orally or vaginally. Comes in 200 mcg tablets.

Dosing

Adult

Dose is with 3-4 tab (600-800 mcg total) vaginally or orally for one dose or repeat dose on day 3

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity to product or components

Precautions

Pregnancy

X - Contraindicated in pregnancy

Precautions

Caution in renal impairment and the elderly;
Adverse reactions include diarrhea 15%,
nausea 7%, cardiovascular (rare), and
hematological anemia (rare)

Follow-up

Further Inpatient Care

• The follow-up should include monitoring hCG levels until the hCG levels are less than 5 mIU/mL. Patients do not need to remain in the hospital during this observation time period.

Further Outpatient Care

• With a complete abortion, measure the hCG level weekly until it is less than 5 mIU/mL in situations in which the products of conception were not evaluated by a physician (eg, the products were flushed down the toilet).
• If the expelled products of conception are evaluated by a physician and confirmed to be intact and truly products of conception (not a clot), performing any further follow-up tests is not necessary.
• Providing reassurance and routine gynecologic care is recommended.
• For ectopic pregnancies, the hCG levels should be monitored as noted above, particularly if medical therapy is performed. If surgical therapy is performed and it is a linear salpingostomy, then the hCG levels should be monitored until they are less than 5 mIU/mL. If a complete salpingectomy is performed and the pathology confirms the ectopic pregnancy, then one may forgo the follow-up for hCG levels.

Deterrence/Prevention

• Contraceptive counseling is warranted. Patients should avoid intercourse or use contraception until the hCG levels have become negative. Patients may wish to continue contraception until they are emotionally ready to try again to become pregnant.

Complications

• Complete abortions may be complicated by infection or accumulation of clot in the uterine cavity without expulsion due to uterine atony. Both of these complications are rare.
• Occasionally, a decidual cast is passed and is mistaken for products of conception. In these cases, an ectopic pregnancy is likely.

Prognosis

• The prognosis is excellent. After one complete abortion, no increased risk exists for another one. Patients need reassurance. Tender loving care is proven effective therapy in one randomized recurrent pregnancy loss trial.

Patient Education

• The patient needs to hear that one miscarriage does not put her at increased risk for another miscarriage. Her next pregnancy is likely to last to term if she is young and has no other risk factors.
• Advise the patient to return to the emergency department if any of the following symptoms occur:
  • Profuse vaginal bleeding
  • Severe pelvic pain
  • Temperature greater than 100°F
• Patients may experience intermittent menstrual-like flow and cramps during the following week. The next menstrual period usually occurs in 4-5 weeks.
• Patients may resume regular activities when able, but they should refrain from intercourse and douching for approximately 2 weeks.
• For excellent patient education resources, visit eMedicine's Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Miscarriage, Abortion, Ectopic Pregnancy, and Dilation and Curettage (D&C).

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose correctly may occur in this situation. A presumed completed abortion may be an ectopic pregnancy with passage of clot where the clot was thought to be tissue. Missing an ectopic pregnancy can be a life-threatening situation. Be careful. If uncertainty exists regarding whether the passed tissue is tissue or a clot, have a pathologist evaluate it prior to sending the patient out.
• If a suction D&C is performed, then a known complication in a small percentage of cases is Asherman syndrome or intrauterine synechiae. This situation may cause amenorrhea, infertility, or miscarriage in these patients in the future. Be gentle with the sharp curettage after the suction, and, if there is difficulty, ultrasound guidance may be helpful. Do not forget that bleeding may be occurring due to DIC, which will not respond to a D&C but needs the missing factors replaced.
• Perforation of the uterus may occur if a suction D&C is performed. Pregnant uteri are softer than the unpregnant state, and it is easier to perforate. Uterine perforation may occlude itself naturally because the uterus is a muscle that can undergo contraction and place its own pressure on the site until the bleeding stops. However, uncontrolled internal bleeding from a uterine perforation may require additional surgery, either a laparoscopy or laparotomy to control the bleeding. Occasionally, a hysterectomy may be the last resort to control the bleeding, which would eliminate the patient's ability to conceive in the future. Unrecognized uterine perforations may lead to significant internal bleeding that could be a life threat. Observe patients closely after a D&C and listen when patients complain of unusual symptoms (eg, shoulder pain, unexpectedly significant abdominal pain).
• Misdiagnosis of an early intrauterine pregnancy for an ectopic pregnancy and administering methotrexate inappropriately may occur if the physician is not familiar with the laboratory and ultrasound department's discriminatory zone. Thinking about the patient's history and physical examination, differential diagnosis (including multiple gestations), the accuracy of the gestational age, the hCG level (and pattern of hCG levels if checked every 2 d), and ultrasonographic findings is very important to make an appropriate diagnosis. This is an area of rapidly growing malpractice in obstetrics and gynecology.
• Misdiagnosis of an ectopic pregnancy as an incomplete or inevitable abortion can be a problem. In these cases, it is important to follow up on the pathology findings from the suction D&C. If one is uncertain, ask pathology to evaluate the specimen while one is still in the operating room and proceed to laparoscopy if no chorionic villi are found in the suction D&C specimen.

References

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7. Hurd WW, Whitfield RR, Randolph JF Jr, et al. Expectant management versus elective curettage for the treatment of spontaneous abortion. Fertil Steril. Oct 1997;68(4):601-6. [Medline].

8. Jurkovic D, Ross JA, Nicolaides KH. Expectant management of missed miscarriage. Br J Obstet Gynaecol. Jun 1998;105(6):670-1. [Medline].

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Keywords

first-trimester pregnancy loss, miscarriage, spontaneous abortion, abortion, pregnancy loss, voluntary pregnancy termination, pregnancy termination, induced pregnancy termination, pregnancy complications, spontaneous complete abortion, ectopic pregnancy, incomplete abortion, inevitable abortion

Contributor Information and Disclosures

Author

Elizabeth E Puscheck, MD, Associate Professor, Department of Obstetrics and Gynecology, Wayne State University School of Medicine; In Vitro Fertilization Director, Medical Director, Gynecologic Ultrasound Director, Clinical Endocrine Laboratory Consultant, Department of Obstetrics and Gynecology, University Women's Care
Elizabeth E Puscheck, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Endocrine Society, International Society for Clinical Densitometry, North American Menopause Society, Sigma Xi, Society for Assisted Reproductive Technologies, and Society of Reproductive Surgeons
Disclosure: Ferring Grant/research funds Other

Coauthor(s)

Archana Pradhan, MD, MPH, Staff Physician, Department of Obstetrics and Gynecology, Nassau University Medical Center
Disclosure: Nothing to disclose.

Medical Editor

Suzanne R Trupin, MD, Clinical Professor of Obstetrics and Gynecology, University of Illinois College of Medicine-Champaign; CEO and Owner, Women's Health Practice; CEO and Owner, Hada Cosmetic Medicine and Midwest Surgical Center
Suzanne R Trupin, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, Association of Reproductive Health Professionals, International Society for Clinical Densitometry, and North American Menopause Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard S Legro, MD, Professor, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Pennsylvania State University College of Medicine; Consulting Staff, Milton S Hershey Medical Center
Richard S Legro, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Endocrine Society, Phi Beta Kappa, and Society of Reproductive Surgeons
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Assumption Community Hospital
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Lee P Shulman, MD, Professor of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University; Chief, Division of Reproductive Genetics, Department of Obstetrics and Gynecology, Prentice Women's Hospital, Northwestern Memorial Hospital
Lee P Shulman, MD is a member of the following medical societies: American College of Medical Genetics, American College of Obstetricians and Gynecologists, American Medical Association, American Society for Reproductive Medicine, American Society of Human Genetics, Association of Reproductive Health Professionals, Central Association of Obstetricians and Gynecologists, Chicago Medical Society, Illinois State Medical Society, North American Society for Pediatric and Adolescent Gynecology, Phi Beta Kappa, Society for Gynecologic Investigation, Society for Maternal-Fetal Medicine, and Tennessee Medical Association
Disclosure: Nothing to disclose.

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