Early Pregnancy Loss 

Updated: Jun 08, 2018
Author: Elizabeth E Puscheck, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG 

Overview

Practice Essentials

Early pregnancy loss, or miscarriage, is the loss of a pregnancy before 20 weeks.

In the first trimester, embryonic causes of spontaneous abortion are the predominant etiology and account for 80-90% of miscarriages (see the image below).

Second transvaginal sonogram obtained 1 week after Second transvaginal sonogram obtained 1 week after the initial study fails to demonstrate fetal development. This confirms the diagnosis of an embryonic pregnancy.

Signs and symptoms

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.

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.

Patients who are pregnant and bleeding vaginally need immediate evaluation.

See Clinical Presentation for more detail.

Diagnosis

Examination in women with suspected early pregnancy loss includes the following:

  • Assessment of hemodynamic stability, including vital signs

  • Abdomen: In a complete abortion, the abdomen is benign, with normal bowel sounds, no distention, no rebound, no hepatosplenomegaly, and mild suprapubic tenderness; complete abortion is unlikely if rebound tenderness or a distended abdomen is present— instead, assume ectopic pregnancy (and promptly initiate appropriate therapy)

  • Pelvis: In a complete abortion, some blood may be present on the perineum or vagina, but there is limited active bleeding, no cervical motion tenderness, a closed cervical canal, smaller uterus than expected for dates, uterus and adnexa nontender to mildly tender, no adnexal masses (unless a corpus luteum is still palpable)

The pelvic examination checklist 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)

Testing

Laboratory studies used in the evaluation of early pregnancy loss include the following:

  • Complete blood count with differential

  • levels of beta-human chorionic gonadotropin

  • Blood type and screen (possible crossmatch)

  • Disseminated intravascular coagulopathy profile in women with significant bleeding (platelet count, fibrinogen level, prothrombin time, activated partial prothrombin time)

Urinalysis

Imaging studies

Perform pelvic ultrasonography using a vaginal probe to rule out an ectopic pregnancy, retained products of conception, hematometra, or other etiologies.

Procedures

When the diagnosis is unclear, the following procedures may be performed:

  • Culdocentesis

  • Diagnostic dilation and curettage

See Workup for more detail.

Management

A complete abortion usually needs no further treatment, medically or surgically. With missed, incomplete, or inevitable abortion present before 13 weeks' gestation, treatment may include misoprostol as an alternative to surgery or performance of suction dilation and curettage.

An ectopic pregnancy may be treated medically (methotrexate) or surgically (laparoscopy, laparotomy), depending on the clinical situation.

Pharmacotherapy

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.

The following medications may be used in women with early pregnancy loss:

  • Immune globulins (eg, Rho (D) immune globulin)

  • Ergot alkaloid and derivatives (eg, methylergonovine)

  • Antimetabolite antineoplastic agents (eg, methotrexate)

  • Prostaglandins (eg, misoprostol)

Surgical option

Surgical intervention may include the following:

  • Complete abortion: None

  • Inevitable and incomplete abortions: Suction dilation and curettage

  • Septic abortion: Broad spectrum antibiotic therapy and suction dilation and curettage

  • Ectopic pregnancy: Treat medically for appropriate patients; the rest require surgery such as linear salpingostomy or partial or complete salpingectomy via laparoscopy or laparotomy

  • Unclear diagnosis: Diagnostic suction dilation and curettage with diagnostic laparoscopy

See Treatment and Medication for more detail.

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 weeks' gestation or when the fetus weighs 500 grams. 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. The 4 stages of abortion form a continuum. Most studies do not differentiate separately between the epidemiology and pathophysiology of each entity.

The combination of oxidative stress, a more hypoxic environment, and defective placentation may lead to increased serum ischemia-modified albumin (IMA) concentrations, which in turn, may play a role in the pathophysiology of early pregnancy loss.[1]

Threatened abortion

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. On examination, blood or brownish discharge may be present 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 a normal, singleton, intrauterine pregnancy is consistently visible by ultrasound. The discriminatory zone may vary depending on a number of factors, including the 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.

Some studies recommend 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.[2] Multiple gestations are an exception and can have higher hCG levels earlier in gestation because more hCG is being made by the trophoblasts from the multiple implantations. Thus, the gestational sac(s) may not be visible on ultrasound despite the hCG levels being higher than the discriminatory zone. Even with multiple gestations, the gestational sacs should be visible at a similar gestational age as singleton gestations or about 6 weeks' gestation if the dating is good.

A clinician should be concerned about ectopic pregnancy but cannot make the diagnosis of ectopic pregnancy just because the hCG level is higher than the discriminatory zone and the uterus appears empty on ultrasound. Many of these pregnancies are abnormal intrauterine pregnancies as opposed to ectopic. One needs to take into consideration the clinical history, and estimated gestational age by LMP or date of conception, if known. A positive pregnancy test result and an ultrasound that does not reveal the location is known as a pregnancy of unknown location (PUL).[3] Occasionally, a normal intrauterine pregnancy does result. Depending on the clinical scenario, a clinician may choose to observe this patient with serial hCG levels and ultrasonography instead of intervening, or a clinician may need to intervene depending on the situation.

Inevitable abortion

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 cramping is present. No tissue has passed yet. On ultrasound, the products of conception are located in the lower uterine segment or the cervical canal.

Incomplete abortion

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 may describe passage of tissue, or the examiner may observe evidence of tissue passage within the vagina. Ultrasound may show that some of the products of conception are still present in the uterus.

Complete abortion

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.

Missed abortion

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 developing 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.

Etiology

In the first trimester, embryonic causes of spontaneous abortion are the predominant etiology and account for 80-90% of miscarriages (see the image below).

Second transvaginal sonogram obtained 1 week after Second transvaginal sonogram obtained 1 week after the initial study fails to demonstrate fetal development. This confirms the diagnosis of an embryonic pregnancy.

One study suggested that an inflammatory reaction occurs in normal pregnancy and may be disrupted during miscarriage.[4]   

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 also play a role in spontaneous abortion, but quantification is difficult. Iatrogenic causes include Asherman syndrome.

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

Acute maternal factors include the following:

  • Corpus luteum deficiency

  • Active infection (eg, rubella virus, cytomegalovirus, Listeria infection, toxoplasmosis, malaria, brucellosis, human immunodeficiency virus (HIV), dengue fever, influenza, as well as vaginal infection with bacterial vaginosis[5, 6] )

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: A meta-analysis evaluating the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function found a strong link between maternal thyroid autoantibodies and miscarriage and preterm birth.[7]  Evidence suggests that treatment with levothyroxine may attenuate the risks.

  • Severe hypertension

  • Antiphospholipid syndrome

Exogenous factors include the following:

  • Tobacco

  • Alcohol

  • Cocaine

  • Caffeine (high doses)

Independent risk factors for a spontaneous miscarriage include the following[8, 9, 10] :

  • Advanced age

  • Extremes of age

  • Feeling stressed

  • Advanced paternal age

Symptoms of vaginal bleeding but not abdominal pain are associated with increased risk of miscarriage. One paper suggests that miscarriage can occur in about 50% of patients who present with threatened abortion.

Gestational exposure to nonaspirin NSAIDs may increase the risk for miscarriage. Nakhai-Pour et al identified 4705 women who had spontaneous abortions by 20 weeks’ gestation. Each case was matched to 10 control subjects (n=47,050) who did not have a spontaneous abortion. In the women who had a miscarriage, 352 (7.5%) were exposed to a nonaspirin NSAID, whereas NSAID exposure was lower (1213 exposed [2.6%]) in women who did not have a miscarriage.[11]

A study by Hahn et al indicates that obesity increases the likelihood of spontaneous abortion, with the risk being highest in the first two months of pregnancy. The study, of 5132 women, found that compared with women of normal weight, women with a body mass index of 30 or above had a hazard ratio (HR) for spontaneous abortion of 1.34 prior to eight weeks’ gestation, after which it dropped to 1.23. The data also indicated that small stature (height < 166 cm) and a low waist-to-hip ratio are additional risk factors for spontaneous abortion. However, neither waist circumference nor the location of typical weight gain was found to significantly affect the risk.[12]

Select vaginal bacteria may also increase the risk of early pregnancy loss. A multicenter study of 418 pregnant of whom 74 had a miscarriage showed that the greatest risk of miscarriage among young women with high levels of was bacterial vaginosis-associated bacteria 3 (BVAB3).[5]

A Danish nationwide study by Mølgaard-Nielsen et al found that 147 of 3315 women exposed to oral fluconazole in their 7th through 22nd weeks of gestation experienced a spontaneous abortion compared to 563 of the 13,246 unexposed pregnancies.[13, 14]

Nausea and vomiting were associated with a reduced risk for pregnancy loss among women with 1 or 2 prior pregnancy losses in a study by Hinkle et al.[15, 16]

Epidemiology

United States statistics

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 increasing gestational age. Recurrent early pregnancy loss, defined as 2-3 consecutive losses of clinical pregnancies, affects about 1% of all couples.

Risk factors

Independent risk factors for a spontaneous miscarriage include advanced age, extremes of age, feeling stressed, and advanced paternal age.[8, 9, 10]  Symptoms of vaginal bleeding but not abdominal pain are associated with increased risk of miscarriage. One paper suggests that miscarriage can occur in about 50% of patients who present with threatened abortion.

International statistics

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

Race-, sex-, and age-related demographics

Early pregnancy loss may occur in any race without distinction.

Early pregnancy loss only affects females.

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.

Women who conceive using donor eggs have miscarriage rates that are similar to the egg donor's age and not the recipient's age. This information is well documented on the CDC's Assisted Reproductive Technology Web site, and it indicates that miscarriages are increased significantly due to aging oocytes rather than due to the aging uterus.

Prognosis

The prognosis for early pregnancy loss is excellent. After one complete abortion, no increased risk exists for another one. Patients need reassurance. "Tender loving care" with subsequent pregnancies is proven effective therapy in some studies.[17, 18, 19]  This approach includes early quantitative hCG levels and ultrasounds weekly, after the hCG threshold is reached, with more frequent visits available if needed for reassurance.

Morbidity/mortality

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

Incomplete and inevitable abortions are a cause for concern when significant bleeding or infection occurs. If treatment is not performed in a timely manner, significant morbidity and mortality may occur. Retained products of conception 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 is performed. These patients are 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, then proceeding to a laparoscopy or laparotomy to control the bleeding 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 or uterine artery embolization may be necessary. When bleeding is severe, the patient can easily go into hypovolemic shock or disseminated intravascular coagulopathy (DIC). Both of these situations need prompt attention and treatment.

Surveillance data suggest that spontaneous miscarriages and induced abortions accounted for about 4% of pregnancy-related deaths in the United States.[20]

A prospective survey study by Farren et al that included 186 women reported that of those in the early pregnancy loss group who responded after 1 month, 28% met the criteria for PTSD and 32% for anxiety. Of those in the early pregnancy loss group that responded after 3 months, 38% met criteria for PTSD and 20% for anxiety.[21]

Complications

In a long-term study of more than 1 million women, researchers found an association between pregnancy loss and an increased risk of subsequently developing atherosclerosis, particularly among women younger than 35 years.[22, 23]  Women who had miscarriages had a 13% increased risk of subsequent myocardial infarction, a 16% increased risk of cerebrovascular infarction, and a 20% increased risk of renovascular hypertension relative to women who had not had miscarriages. The effect on adverse outcomes appeared to be cumulative, with each additional miscarriage increasing the risk of myocardial infarction (by 9%), cerebral infarction (by 13%), and renovascular hypertension (by 19%).[22, 23]

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.

 

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 patient education resources, see the Pregnancy Center, as well as Miscarriage, Abortion, Ectopic Pregnancy, and Dilation and Curettage (D&C).

 

Presentation

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.

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.

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 appears 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.

Physical

Patients who are pregnant and bleeding vaginally need immediate evaluation.

Estimating the patient's hemodynamic stability is the first step, as follows:

  • Obtain orthostatic vital signs.

  • Initiate fluid resuscitation early in cases of orthostatic hypotension.

  • Abdominal and pelvic examinations are next.

The abdominal examination helps determine whether or not the state of an acute abdomen is present. Note the following:

  • 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 (eg, leiomyomas).

  • If rebound tenderness or a distended abdomen is present, a complete abortion is unlikely. Assume instead that an ectopic pregnancy is present and if rebound tenderness is present, then provide the patient with aggressive fluid resuscitation with 2 IV lines, quantitative hCG, stat ultrasound (if stable enough) and an emergent laparoscopy or an emergent exploratory laparotomy.

In the case of a complete abortion, pelvic examination may show some blood on the perineum or vagina but there is limited active bleeding. Note the following:

  • Cervical motion tenderness does not exist.

  • The cervical canal is closed.

  • The uterus is smaller than 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)

 

DDx

Diagnostic Considerations

Important considerations

Failure to diagnose correctly may occur in early pregnancy loss.. A presumed completed abortion may be an ectopic pregnancy with passage of clot in which the clot was thought to be tissue. Use caution, as missing an ectopic pregnancy can be a life-threatening situation. If uncertainty exists regarding whether the passed material 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 requires replacement of the missing factors.

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 ultrasonography 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.

Other problems to be considered

Other conditions to consider in patients with early pregnancy loss include:

  • Abortion, incomplete

  • Abortion, inevitable

  • Acute appendicitis

  • Cervical polyps, ectropion, or malignancy

  • Ovarian torsion

  • Pregnancy, molar

  • Pregnancy, subchorionic hemorrhage

  • Vaginal/vulvar condylomata

Differential Diagnoses

 

Workup

Laboratory Studies

Complete blood count (CBC) with differential

A 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

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 at least 53% every 2 days during the early first trimester.[24]

Blood type and screen

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 is also Rh negative then the patient can forego the immunoglobulin therapy. It is also important in cases where transfusions are necessary.

Possible DIC profile

A 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

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

Ultrasonography of the pelvis using a vaginal probe should be performed 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 as long as it is taken within the clinical scenario.

Guidelines for assessing prenatal viability

In October 2013, the Society of Radiologists in Ultrasound published new guidelines on using ultrasonography to assess prenatal viability.[25, 26] The guidelines are designed to help avoid the possibility of physicians causing inadvertent harm to a potentially normal pregnancy.

Diagnostic criteria for nonviability include the following:

  • A crown–rump length of ≥7 mm and no heartbeat

  • A mean sac diameter of ≥25 mm and the absence of an embryo

  • The absence of an embryo with heartbeat ≥2 weeks following a scan that showed a gestational sac with no yolk sac

  • The absence of an embryo with heartbeat ≥11 days following a scan that showed a gestational sac with a yolk sac

Findings that are suspicious for, but not diagnostic of, a pregnancy failure include the following:

  • A crown–rump length of < 7 mm and no heartbeat

  • A mean sac diameter of 16–24 mm and the absence of an embryo

  • The absence of an embryo with heartbeat 7–13 days following a scan that showed a gestational sac with no yolk sac

  • The absence of an embryo with heartbeat 7–10 days following a scan that showed a gestational sac with a yolk sac

  • The absence of an embryo ≥6 wk after the last menstrual period

  • An empty amnion

  • An enlarged yolk sac (>7 mm)

  • A small gestational sac in relation to the embryo size (< 5 mm difference between the mean sac diameter and the crown–rump length)

Presence of one or more of these findings should prompt further investigation into the pregnancy's viability.

Procedures

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

If the diagnosis is unclear and there is fluid in the cul de sac, then a culdocentesis can be performed. This procedure is one where a needle with 10-20 mL syringe attached is placed into the posterior cul de sac through the vagina and the fluid is aspirated. If the fluid consists of nonclotting blood, then a ruptured ectopic pregnancy must be considered. This technique is not used often.

Alternatively, if the diagnosis is unclear, but normal early pregnancy has been excluded, a diagnostic D&C may be performed. In this situation, the specimen is sent for pathologic evaluation and, if chorionic villi are found, then an intrauterine pregnancy demise is confirmed. No further treatment is needed beyond the suction D&C. However, if no chorionic villi are found, then one needs to presume that an ectopic pregnancy is present and initiate appropriate treatment.

Pathology results from specimen sent from an early pregnancy (either from D&C for incomplete abortion or from ectopic pregnancy) should reveal chorionic villi.

 

Treatment

Medical Care

A complete abortion usually needs no further treatment, medically or surgically. Patients do not need to remain in the hospital when a diagnosis of complete abortion is made; these patients are usually sent home. However, if there are concerns about significant blood loss, then the patient may need to stay for 24-hour observation and receive blood transfusions. If there are concerns regarding significant infection, IV antibiotic therapy may be needed for a short time until fever/symptoms resolve.

With missed, incomplete, or inevitable abortion present 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 alternative medical therapy. In one study of incomplete abortion, the patients were randomized between oral misoprostol (600 mcg) or suction D&C, with success rates at 96.3% and 91.5%, respectively. The complication rate is low (0.9% for misoprostol).[27]

The other study was a randomized controlled trial with a 3:1 randomization to medical therapy versus D&C. 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 study 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 those of surgical management.

Medical therapy using misoprostol is an acceptable alternative to surgical therapy for most women based upon these early data. The patient should be counseled regarding the risks and benefits of both. The advantages of medical therapy is that no surgical procedures are needed if it is successful. Passage of tissue should happen within a few days of receiving medical therapy. If it is not successful, then a surgical approach may follow. The risks for medical therapy include bleeding, infection, possible incomplete abortion, and possible failure of the medication to work. The advantage of a suction D&C is that the procedure is scheduled and occurs at a known time. The risks of a D&C include bleeding, infection, possible perforation of the uterus (as noted in Surgical Care), and possible Asherman syndrome after the procedure.

A study by Schreiber et al that included 300 women who had an early pregnancy loss and received pretreatment with oral 200 mg of mifepristone followed by vaginal 800 μg of misoprostol (mifepristone-pretreatment group), or vaginal 800 μg of misoprostol alone (misoprostol-alone group) reported that 83.8% of the mifepristone-pretreatment group had complete expulsion after one dose of misoprostol compared to 67.1% in the misoprostol-alone group.[48]

In patients with recurrent pregnancy loss (≥2 miscarriages) and cellur immunity anomalies (eg, elevated natural killer cell levels or cytotoxicity and increased T-helper cell 1  (Th1) to Th2 ratio), intravenous immunoglobulin (IVIG) may improve pregnancy outcomes.[29]

In a murine model, combined therapy with sildenafil and heparin prevented fetal loss, which may have implications in the management of women with impending pregnancy loss or for prevention in women with a history of recurrent miscarriages.[30]

Large blood loss

In the situation in which a considerable amount of blood loss has occurred, aggressive hydration, iron therapy or transfusions may be indicated.

Misdiagnosis

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, if possible, without significantly delaying the suction D&C.

Ectopic pregnancy

An ectopic pregnancy may be treated medically or surgically, depending on the clinical scenario. Treatment guidelines for ectopic pregnancy are available from the American College of Obstetricians and Gynecologists.[31] (See Ectopic Pregnancy for further information.)

Note the following:

  • Medical therapy consists of methotrexate, which is usually administered in a dose of 50 mg/m2. The maximum dose is 100 mg. 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 and 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 3's 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. An increase beyond these parameters for gestational age, hCG level, or ectopic size, or presence of a fetal heart motion on ultrasound significantly decreases the success of this medical approach. 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.[31] From day 1 to day 4, a rise in the hCG level may occur. If a 15% or more drop in the hCG level occurs from day 4 to 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 (eg, mouth sores, renal impairment). 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.

Plateau or rising hCG after methotrexate therapy

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, surgery should be considered as well.

Potential ectopic rupture

Any symptoms suggesting ectopic rupture (eg, acute pain, rebound tenderness) should immediately direct the physician to the operating room. NOoe the following:

  • 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.

Complete abortion

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 patients know what to expect, most 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 ultrasonographic evaluation to confirm the diagnosis and for reassurance.

A possible treatment for threatened miscarriage is the use of progestogen. In 4 randomized studies involving 421 women that compared the use of progestogen in the treatment of threatened miscarriage with either placebo or no treatment, limited evidence suggests that the use of progestogen can reduce the rate of spontaneous miscarriage. Treatment with progestogens did not increase the occurrence of congenital abnormalities in the newborns, and the women did not have any significant difference in incidence of pregnancy-induced hypertension nor antepartum hemorrhage. Further larger studies are warranted for stronger conclusions.[32]

Abortion, Inevitable, Abortion, Incomplete, and Ectopic Pregnancy are discussed above and in separate articles.

Consultations

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

Diet and activity

The patient's diet should be regular if the diagnosis truly is a complete abortion. If any uncertainty about the diagnosis exists, restrict oral intake until certain that surgical treatment is not necessary.

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.

Surgical Care

Note the following:

  • No surgical care is used for complete abortion.

  • Inevitable and incomplete abortions are typically treated surgically with suction D&C.

  • A septic abortion requires broad spectrum antibiotic therapy prior to a suction D&C, if possible without delaying the D&C.

  • If a boggy uterus is noted with active bleeding during a D&C, then methylergonovine maleate (Methergine) (0.2 mg IM) may be given to contract the uterus. This will also decrease the likelihood that clots will be retained in the uterus.

  • 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. For more information, see Medscape Reference article Ectopic Pregnancy.

  • Whenever the diagnosis is uncertain, a diagnostic suction D&C with a diagnostic laparoscopy may be appropriate.

 

Medication

Medication Summary

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

Class Summary

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.

Ergot alkaloid and derivatives

Class Summary

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.

Antineoplastic Agent, Antimetabolite

Class Summary

These agents inhibit cell growth and proliferation.

Methotrexate (Rheumatrex, Trexall)

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

Prostaglandins

Class Summary

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.

 

Follow-up

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.

Psychological counseling or grief counseling should be offered for those with early pregnancy loss. Support groups can also be helpful.[33]