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Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation

Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation
Literature review current through: Jan 2024.
This topic last updated: Mar 16, 2023.

INTRODUCTION — Vaginal bleeding is common in the first half of pregnancy. It usually results from disruption of blood vessels in the decidua (ie, pregnancy endometrium) or from a discrete cervical or vaginal lesion. The clinician typically makes a provisional clinical diagnosis based upon the gestational age and the character of bleeding (eg, spotting, light or heavy flow, intermittent or constant, associated with pain or painless). Physical examination and laboratory and/or imaging tests are then used to support or revise the initial diagnosis. Bleeding can be associated with an adverse pregnancy outcome or an ectopic pregnancy, which can be life-threatening.

The evaluation and differential diagnosis of vaginal bleeding in the first half of pregnancy (ie, up to 20 weeks of gestation) are discussed here. The evaluation and differential diagnosis of vaginal bleeding in the second half of pregnancy (ie, 20 weeks or more of gestation) are reviewed separately. (See "Evaluation and differential diagnosis of vaginal bleeding after 20 weeks of gestation".)

INCIDENCE — Vaginal spotting or bleeding occurs in approximately 25 percent of pregnancies in the first trimester (up to 13+6 weeks [ie, 13 weeks plus 6 days of gestation]) [1]. It is much less common in the second trimester (14+0 to 27+6 weeks), occurring in one to two percent of pregnancies [2]. Reported incidence varies widely depending on the definition of bleeding and method of case ascertainment.

EVALUATION

Site — The site of patient evaluation (office versus emergency department) depends upon the volume of bleeding and presence of other symptoms. Patients with heavy bleeding (eg, soaking ≥1 pad/hour for more than two hours, or passing large clots), lightheadedness/syncope, and/or pelvic pain generally warrant prompt evaluation in an emergency department so supportive measures and treatment can be rapidly initiated if the patient is found to be hemodynamically unstable. In hemodynamically unstable patients, two large bore (14 or 16 gauge) peripheral intravenous (IV) catheters are placed for IV fluids, and a hemoglobin/hematocrit level, coagulation studies, and a type and screen or crossmatch are obtained, with transfusion of blood products as needed.

Although patients with severe blood loss (ie, requiring supportive care and rapid treatment) generally have orthostatic changes (systolic blood pressure decline of ≥20 mmHg or diastolic blood pressure decline of ≥10 mmHg or heart rate increase of ≥30 beats/minute present after three minutes of standing, syncope), occasionally young pregnant patients can have massive bleeding without demonstrating orthostasis. Prompt, careful assessment is important to avoid unnecessary delay in the management of such patients.

Goal — The goal of the evaluation is to make a definitive diagnosis when possible and exclude the presence of serious pathology in the remaining cases (algorithm 1). The actual etiology of the bleeding often cannot be determined.

History

Has an intrauterine pregnancy been documented? — Ectopic pregnancy is particularly important to exclude since it can be life-threatening. Thus, the first step in evaluation is to determine whether the patient has had an ultrasound examination and to review the results of that examination. Prior documentation that the pregnancy is in the normal intrauterine location immediately excludes ectopic pregnancy, although the possibility that the prior ultrasound may have missed a heterotopic pregnancy (ie, one intrauterine and one extrauterine pregnancy) or misdiagnosed an interstitial (cornual) ectopic pregnancy as intrauterine should always be considered.

If an intrauterine location of the pregnancy is in doubt, repeat the ultrasound examination. (See 'Ultrasonography' below.)

Are symptoms concerning for ectopic pregnancy or pregnancy loss? — The extent of bleeding should be determined: Is the patient passing blood clots or is the blood soaking through their clothes? Do they feel lightheaded? Do they have significant pelvic pain or cramping? Have they passed any tissue?

If the patient answers yes to any of these questions, then ectopic pregnancy and pregnancy loss (also called miscarriage or spontaneous abortion) are much more likely diagnoses than threatened abortion, implantation bleeding, cervical and vaginal disorders (or ectropion), or cervical insufficiency (in the second trimester). However, the presence of only light, intermittent, painless bleeding does not exclude the possibility of a life-threatening underlying disorder, such as ectopic pregnancy. (See 'Differential diagnosis' below.)

Are there risk factors for ectopic pregnancy or pregnancy loss? — What is the patient's medical history? A past history of ectopic pregnancy or risk factors for ectopic pregnancy (table 1) increase the probability of this disorder, but many patients with ectopic pregnancy have no risk factors. (See 'Ectopic pregnancy' below.)

A history of ≥2 consecutive pregnancy losses or a condition associated with pregnancy loss (eg, chromosomal translocation in either parent, maternal antiphospholipid syndrome, uterine anomaly) increases the likelihood that bleeding is related to pregnancy loss. (See 'Pregnancy loss' below.)

Does the patient say that they don't "feel pregnant" anymore? — Patients with a pregnancy loss may notice that symptoms associated with early pregnancy (eg, nausea, breast tenderness, urinary frequency, fatigue) have abated and they do not "feel pregnant" anymore. (See 'Pregnancy loss' below.)

Has the patient had a prior cesarean birth? — In patients with a prior cesarean birth, a subsequent pregnancy may implant in the area of the uterine scar. This is termed cesarean scar pregnancy and can only be diagnosed by ultrasound examination. Diagnosis is important as it is associated with an increased risk of adverse pregnancy outcome. (See 'Cesarean scar pregnancy' below.)

Focused physical examination

Examine any tissue that has been passed — Any tissue the patient has passed vaginally should be examined. Patients may mistake blood clot for the products of conception. Passage of blood clot alone is not diagnostic of any disorder whereas a gestational sac/fetal membranes, fronds indicative of placental villi, or an intact embryo/fetus are diagnostic of a partial or complete pregnancy loss. Products of conception, if present, should be visible upon careful examination. Visualization of villi can be facilitated by rinsing the specimen to clear away blood clot and then floating it in water (picture 1A-B). (See 'Pregnancy loss' below.)

Examine the abdomen — An abdominal examination should be performed before the internal examination. It is best to begin by examining the quadrant of the abdomen where the patient is experiencing the least pain and then moving toward the painful area. Gentle percussion is preferable to deep palpation since it causes less pain and guarding.

Midline pain is more consistent with pregnancy loss, while lateral pain is more consistent with ectopic pregnancy. (See 'Pregnancy loss' below and 'Ectopic pregnancy' below.)

Nongynecologic causes of pain should also be considered. (See "Approach to acute abdominal/pelvic pain in pregnant and postpartum patients", section on 'Medical-surgical causes of acute abdominal pain'.)

Check for embryonic/fetal cardiac activity — Presence of embryonic/fetal cardiac activity is reassuring, as it indicates bleeding is not related to embryonic/fetal demise and highly unlikely to be related to an ectopic pregnancy.

If bedside ultrasound is available, absence of previously documented embryonic/fetal cardiac activity is diagnostic of pregnancy loss. In the absence of a previous ultrasound, pregnancy failure can be diagnosed in the absence of embryonic/fetal cardiac activity when the crown-rump length is ≥7 mm or mean gestational sac diameter is ≥25 mm. Ultrasound diagnosis of pregnancy loss very early in gestation can be complicated and is reviewed in detail separately. (See "Pregnancy loss (miscarriage): Ultrasound diagnosis".)

If the pregnancy is ≥10 to 12 weeks of gestation, a handheld Doppler ultrasound device can be used to check for a fetal heartbeat. The fetal heart rate usually can be easily distinguished from the maternal heart rate since it is typically in the range of 110 to 160 beats per minute; however, the difference in fetal and maternal heart rates can be minimal if the mother has tachycardia and/or the embryo/fetus has bradycardia [3]. Inability to detect fetal heart motion by handheld Doppler device, particularly in the first trimester, may merely reflect the difficulty in blindly finding the location of the embryo/fetus.

Speculum examination

Does the vagina contain tissue or blood clot? — A speculum is inserted into the vagina to assess the volume and source of bleeding. If blood clots, products of conception, or both are present, they can be removed with gauze sponges on a sponge forceps. This tissue is examined for a gestational sac/fetal membranes, fronds indicative of placental villi, or an intact embryo/fetus and, by convention, sent for pathologic examination to confirm the presence of products of conception, which are diagnostic of pregnancy loss, and to exclude gestational trophoblastic disease. (See 'Pregnancy loss' below and 'Gestational trophoblastic disease' below.)

The utility of routine histopathological examination is questionable, as it rarely suggests the underlying cause of the pregnancy failure or establishes a diagnosis of gestational trophoblastic disease [4]. However, pathologists can sometimes diagnose entities that are the probable cause of the loss or associated with recurrent loss. These include massive chronic intervillositis, massive intervillous fibrin deposition, maternal vasculitis, findings suggestive of some fetal chromosomal anomalies (eg, triploidy, some trisomies), and septic abortion.

Can the source of bleeding be seen? — Speculum examination usually confirms that the uterus is the source of bleeding but may reveal a vaginal or cervical source unrelated to pregnancy; in such cases, further evaluation depends upon the nature of the abnormality. (See 'Cervical and vaginal disorders' below and 'Ectropion' below.)

If no blood is seen in the vagina, then the bleeding is either resolved, occurring intermittently, or from a nongenital tract source (eg, hemorrhoids).

Is the internal cervical os dilated?

First trimester – Visualization of the internal cervical os is possible in some cases and if dilated, raises concern that a complete or incomplete pregnancy loss has occurred. Cramping is typically present when the cervix is open. Direct visualization of the gestational sac in a dilated internal cervical os is generally sufficient to conclude that early pregnancy loss is occurring. An open internal cervical os will admit a small instrument, such as a cotton-tipped swab. Ultrasound can provide additional information in these cases, such as whether there are retained products of conception or the unexpected presence of a twin pregnancy with a second viable gestational sac. Therefore, it is prudent to not inform patients that the pregnancy has been lost until ultrasound findings are available and the diagnosis is confirmed. (See 'Pregnancy loss' below.)

A closed internal cervical os is not diagnostic of any pregnancy disorder and can be consistent with ectopic pregnancy, threatened abortion, implantation bleeding, and other intrauterine pathologies. If the internal cervical os appears closed and there are no obvious vaginal or cervical bleeding lesions, the speculum is removed and a bimanual pelvic examination is performed. (See 'Ectopic pregnancy' below and 'Threatened abortion' below and 'Physiologic or implantation bleeding' below and 'Vanishing twin' below.)

In contrast to the internal os, an open external cervical os is usually not helpful diagnostically because it can be a normal finding, especially in parous patients.

Second trimester – A dilated internal cervical os with painful cramps/contractions in the second trimester suggests pregnancy loss. (See 'Pregnancy loss' below.)

By comparison, painless cervical dilation and/or effacement (thinning) in the second trimester suggests cervical insufficiency. The fetal membranes may be prolapsed or ruptured. Uterine cramps/contractions are absent or weak and irregular. (See 'Cervical insufficiency' below.)

Pelvic examination — If findings on speculum examination do not lead to a specific diagnosis, the clinician should determine whether uterine size is appropriate for the estimated gestational age. The size-gestational age correlation is learned by experience and is often described in terms of fruit (eg, 6- to 8-week size = small pear, 8- to 10-week size = orange, 10- to 12-week size = grapefruit). The uterus remains a pelvic organ until approximately 12 weeks of gestation, when it becomes sufficiently large to palpate transabdominally just above the symphysis pubis. The normal uterus is nontender, smooth, and firm.

Uterus large for dates – Uterine size larger than expected for dates suggests a multiple gestation; gestational trophoblastic disease; other uterine pathology (fibroids often cause irregular uterine enlargement and may cause pain/tenderness); or incorrect dating. (See "Twin pregnancy: Overview" and 'Gestational trophoblastic disease' below and "Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and natural history".)

Uterus small for dates – Uterine size smaller than expected for dates suggests loss of an intrauterine pregnancy (see 'Pregnancy loss' below and 'Vanishing twin' below), ectopic pregnancy (see 'Ectopic pregnancy' below), or incorrect dating.

Other findings – With an ectopic pregnancy, findings on pelvic examination may include adnexal, cervical motion, or abdominal tenderness; an adnexal mass; and mild uterine enlargement; however, the physical examination is often unremarkable in a patient with a small, unruptured ectopic pregnancy. (See 'Ectopic pregnancy' below.)

One review of data from observational studies concluded that ultrasound examination and human chorionic gonadotropin (hCG) concentration (both discussed below) could replace pelvic examination in the initial evaluation of patients with early pregnancy bleeding [5]. However, some diagnoses will be missed with this approach (eg, bleeding from cervical or vaginal lesions), this combination of tests may not distinguish between a complete pregnancy loss and an ectopic pregnancy (both will have an empty uterus and positive hCG), and the additional cost of these tests can be avoided in some patients. For example, in bleeding patients in whom sonography has previously confirmed a viable singleton intrauterine pregnancy, another examination is not necessary to exclude ectopic pregnancy or to confirm embryonic/fetal viability if embryonic/fetal heart motion can be detected by a handheld Doppler device. Additionally, there is no value in checking the hCG concentration once the presence of an intrauterine pregnancy has been established sonographically (eg, presence of an intrauterine gestational sac containing a yolk sac or fetus).

Ultrasonography — Ultrasonography is the cornerstone of the evaluation of bleeding in pregnancy. It is most useful in bleeding patients with a positive pregnancy test in whom an intrauterine pregnancy has not been previously confirmed by imaging studies. In these patients, ultrasound examination is performed to determine whether the pregnancy is intrauterine or extrauterine (ectopic) and, if intrauterine, whether embryonic/fetal cardiac activity present. The possibility of heterotopic pregnancy should always be considered. (See 'Heterotopic pregnancy' below.)

Transabdominal ultrasound is performed initially and findings may be diagnostic. At very early gestational ages, transvaginal ultrasound allows for earlier and more reliable detection of an intrauterine or ectopic pregnancy and is more sensitive for detecting embryonic/fetal cardiac activity compared with transabdominal ultrasound, but the latter is useful for assessing free fluid in the abdomen (eg, bleeding from an ectopic pregnancy) and abnormalities beyond the field of view of a high-frequency vaginal probe.

It is important to note that the absence of an intrauterine gestational sac on ultrasound examination is highly suggestive of ectopic pregnancy if more than 5.5 to 6 weeks have elapsed since the first day of the patient's last normal menstrual period (table 2). At earlier gestational ages, however, an intrauterine pregnancy may be present, but not yet identifiable, even by transvaginal ultrasound. In a patient with a positive pregnancy test and a transvaginal ultrasound that shows neither an intrauterine pregnancy nor an ectopic pregnancy (ie, pregnancy of unknown location), serum hCG is tested serially to determine the rate of rise. Ultrasound findings, absolute hCG level, and change in hCG level over time are correlated until a final diagnosis (ie, live intrauterine pregnancy, early pregnancy loss, ectopic pregnancy) is possible. This is described in detail separately. (See "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology" and "Ectopic pregnancy: Clinical manifestations and diagnosis" and "Approach to the patient with pregnancy of unknown location".)

Rarely, ultrasound examination reveals unusual causes of vaginal bleeding, such as gestational trophoblastic disease or loss of one fetus from a multiple gestation. (See 'Gestational trophoblastic disease' below and 'Vanishing twin' below.)

Role of other imaging tests — Magnetic resonance imaging (MRI) is rarely indicated but may be used as a second-line imaging modality for further evaluation of limited and nondiagnostic ultrasound, an unusual ectopic pregnancy, gestational trophoblastic disease, and differentiating causes of severe pelvic pain and adnexal masses.

Computed tomography (CT) may be useful in pregnant patients with trauma or acute nongynecologic pain, for staging of malignancy, or if MRI is not possible and additional information is needed. It is not the preferred modality since it involves use of ionizing radiation, but it can be performed safely and should be used when other imaging modalities do not provide adequate diagnostic information. (See "Diagnostic imaging in pregnant and lactating patients".)

Laboratory tests

Baseline hemoglobin/hematocrit – In hemodynamically stable patients, a baseline hemoglobin/hematocrit measurement can be useful in those with heavy vaginal bleeding, particularly if persistent, since a marked fall in hemoglobin/hematocrit from a previous level or on subsequent testing is consistent with severe bleeding from a pregnancy loss or a ruptured ectopic pregnancy.

Human chorionic gonadotropin (hCG) – Once the presence of an intrauterine pregnancy has been established sonographically, measurement of the hCG level is rarely informative.

Serial measurements of hCG are helpful during the first six weeks of pregnancy if ultrasonography is nondiagnostic (ie, the location of the pregnancy is not known). The pattern of hCG change in very early normal and abnormal pregnancies and its correlation with ultrasound findings is complicated and discussed in detail separately. (See "Approach to the patient with pregnancy of unknown location", section on 'Subsequent testing in selected patients'.)

Other hormone assays (eg, progesterone, estrogen, inhibin A, pregnancy-associated protein-A [PAPP-A]) are less useful than hCG and beyond the scope of this topic.

RhD type – RhD typing should be performed in patients >12 weeks of gestation as anti-D immune globulin is administered to those with uterine bleeding to prevent alloimmunization from concurrent fetomaternal bleeding. Expert opinion varies as to whether RhD typing is needed at ≤12 weeks since anti-D immune globulin is no longer routinely administered to D-negative patients with uterine bleeding at ≤12 weeks. Patient selection for anti-D immune globulin for prophylaxis against alloimmunization is discussed in detail separately. (See "RhD alloimmunization: Prevention in pregnant and postpartum patients", section on 'Indications'.)

DIFFERENTIAL DIAGNOSIS

Common diagnoses with potentially serious consequences

Ectopic pregnancy — Ectopic pregnancy accounts for up to 2 percent all pregnancies. Most patients with a tubal ectopic pregnancy present in the first trimester; presentation after the first trimester increases the chances that the location is nontubal (abdominal, cervical, cesarean scar, or interstitial [cornual]) or heterotopic. (See 'Heterotopic pregnancy' below and 'Cervical pregnancy' below and 'Cesarean scar pregnancy' below and "Abdominal pregnancy".)

Rupture can lead to life-threatening intraabdominal hemorrhage; therefore, the diagnosis of ectopic pregnancy should be suspected in any pregnant patient with vaginal bleeding with or without abdominal pain and no evidence of an intrauterine pregnancy on transvaginal ultrasound.

Visualization of an extraovarian adnexal mass containing an empty gestational sac, a complex extraovarian adnexal mass, or intraperitoneal bleeding on transvaginal ultrasound strongly supports the diagnosis of ectopic pregnancy. Visualization of an extrauterine gestational sac with a yolk sac or fetus (with or without a heartbeat) on transvaginal ultrasound is diagnostic. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Transvaginal ultrasound'.)

In the absence of these findings, sonography and human chorionic gonadotropin (hCG) are used until a final diagnosis (ie, live intrauterine pregnancy, early pregnancy loss, ectopic pregnancy) is made. (See "Approach to the patient with pregnancy of unknown location".)

Management of ectopic pregnancy is generally medical (methotrexate therapy) or surgical (see "Ectopic pregnancy: Methotrexate therapy" and "Tubal ectopic pregnancy: Surgical treatment"). Expectant management can be dangerous for the patient, but may be possible in carefully selected patients. (See "Ectopic pregnancy: Expectant management of tubal pregnancy".)

Pregnancy loss — A variety of terms (table 3) are used to describe pregnancy loss. (See "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology".)

Complete pregnancy loss — When a pregnancy loss occurs before 12 weeks of gestation, it is common for the entire contents of the uterus to be expelled, thereby resulting in complete pregnancy loss. If this has occurred, the uterus is small on physical examination and well contracted with an open or closed internal cervical os and the patient may describe diminishing bleeding and pain. Ultrasound will reveal an empty uterus and no extrauterine gestation. The diagnosis is certain if a previous ultrasound examination documented an intrauterine pregnancy. This is important since the uterus may appear empty on ultrasound in a normal pregnancy that is too early to visualize or in an ectopic pregnancy.

In the absence of previous sonographic documentation of an intrauterine pregnancy, other findings that suggest that an empty uterus is due to complete pregnancy loss rather than an ectopic pregnancy or early normal pregnancy are evidence of products of conception in tissue passed vaginally or documentation of falling rather than rising or plateaued hCG levels. If tissue is unavailable or does not show products of conception, then serum hCG levels should be checked and a falling level should be followed serially until the level is undetectable. (See "Approach to the patient with pregnancy of unknown location".)

Incomplete pregnancy loss — The early stage of an incomplete pregnancy loss should be suspected when the internal cervical os is dilated and/or effaced, vaginal bleeding is increasing, and painful uterine cramps/contractions are present. The gestational tissue often can be felt or seen at the dilated and/or effaced internal cervical os on speculum. At a more advanced stage, the gestational sac/fetal membranes may rupture and the embryo/fetus may be passed, but significant amounts of placental tissue can be retained. In such cases the uterine size may be smaller than expected for gestational age and not well contracted. Ultrasound examination showing a focal hyperechoic mass in the endometrium, particularly with evidence of blood flow and enhanced myometrial vascularity by Doppler imaging, supports the diagnosis of retained products of conception.

Management may be expectant, or a medical or surgical intervention to complete the evacuation process can be undertaken. (See "Pregnancy loss (miscarriage): Description of management techniques" and "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care".)

Vanishing twin — Vanishing twin is a type of pregnancy loss. The diagnosis is made when an early ultrasound examination shows a twin (or other multiple) gestation but a subsequent examination shows absence or demise of one twin (or one member of a triplet or higher order multiple gestation). Vanishing twins are often the product of assisted reproduction techniques and can be associated with vaginal bleeding [6]. No intervention is indicated. (See "Assisted reproductive technology: Pregnancy and maternal outcomes", section on 'Early pregnancy loss' and "Twin pregnancy: Overview", section on 'Vanishing twins'.)

Diagnoses identifiable on speculum examination

Cervical insufficiency — The diagnosis of cervical insufficiency is clinical; the classic presentation is cervical dilation and effacement in the second trimester with fetal membranes visible at or beyond the external os in the absence of contractions or with weak irregular contractions that appear inadequate to explain the cervical dilation and effacement. Symptoms include one or more of the following: vaginal fullness or pressure; vaginal spotting or bleeding; an increased volume of watery, mucus or brown vaginal discharge; and mild discomfort in the lower abdomen or back.

Management may involve placement of a cerclage and/or daily administration of vaginal progesterone. (See "Cervical insufficiency".)

Cervical and vaginal disorders — These conditions are diagnosed by visual inspection, with ancillary tests as indicated (eg, wet mount and pH of vaginal discharge, cervical cytology and/or biopsy of mass lesions, ultrasound examination of uterus to detect neoplastic lesions). Even if a lesion appears to be the source bleeding on speculum examination, it is prudent to always consider the possibility of ectopic pregnancy in patients with first-trimester bleeding, especially if associated with pain. (See 'Ectopic pregnancy' above.)

Vaginal laceration (see "Evaluation and management of female lower genital tract trauma")

Vaginal neoplasm (see "Vaginal cancer")

Vaginal warts (see "Condylomata acuminata (anogenital warts) in adults: Epidemiology, pathogenesis, clinical features, and diagnosis")

Vaginal discharge (see "Vaginitis in adults: Initial evaluation")

Cervical polyps, fibroids (see "Benign cervical lesions and congenital anomalies of the cervix")

Mucopurulent cervical discharge or friability at the cervical os (see "Acute cervicitis")

Cervical neoplasm (see "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis")

Management of bleeding related to these conditions depends upon the specific condition. (Refer to individual topic reviews on each disorder).

Ectropion — Cervical ectropion (columnar epithelium exposed to the vaginal milieu by eversion of the endocervix) is a common and normal finding in pregnancy. The exposed columnar epithelium is prone to light bleeding when touched, such as during vaginal intercourse, insertion of a speculum, bimanual examination, or when a cervical specimen is obtained for cytology or culture. No biopsy or intervention is indicated. (See "Benign cervical lesions and congenital anomalies of the cervix", section on 'Ectropion'.)

Diagnoses of exclusion

Threatened abortion — Bleeding related to threatened abortion is the most common nontraumatic cause of first-trimester bleeding (prevalence: 15 to 20 percent of pregnancies). Although bleeding may be heavy, almost all patients remain hemodynamically stable; only an approximate 1 percent of expectantly managed patients require blood transfusion [7].

Threatened abortion is a provisional diagnosis in patients with vaginal bleeding, a closed cervix, and sonographic visualization of an intrauterine pregnancy with detectable embryonic/fetal cardiac activity. The term "threatened" is used to describe these cases because pregnancy loss does not always follow vaginal bleeding, even after repeated episodes or large amounts of bleeding. In fact, 90 to 96 percent of pregnancies with both embryonic/fetal cardiac activity and vaginal bleeding at 7 to 11 weeks of gestation are not lost; the 96 percent ongoing pregnancy rate is associated with bleeding at the later end of this gestational age range [8,9].

Bleeding in threatened abortion is likely due to disruption of decidual vessels at the maternal-fetal interface. These separations generally cannot be visualized by ultrasound, but may sometimes appear as a subchorionic hematoma. Subchorionic hemorrhage or hematoma is associated with increased risk of pregnancy loss, particularly when it amounts to 25 percent or more of the volume of the gestational sac (image 1A-B) [10,11]. There is no clear association between subchorionic hematoma and risk of preterm birth [12].

Management is expectant; available evidence does not support a benefit of progesterone supplementation in patients with threatened abortion and zero or one previous pregnancy loss [13]. The role of progesterone supplementation in recurrent pregnancy loss (two or more failed clinical pregnancies or three consecutive pregnancy losses) is reviewed separately. (See "Recurrent pregnancy loss: Definition and etiology" and "Recurrent pregnancy loss: Evaluation" and "Recurrent pregnancy loss: Management".)

Physiologic or implantation bleeding — This is a diagnosis of exclusion. It is characterized by a small amount of spotting or bleeding approximately 10 to 14 days after fertilization (around the time of the missed menstrual period), and is presumed to be related to implantation of the fertilized egg in the decidua (ie, lining of the uterus) [14], although this hypothesis has been questioned [15]. No intervention is indicated.

Less common disorders

Heterotopic pregnancy — Heterotopic pregnancy (ie, one intrauterine and one extrauterine pregnancy) is rare (1 in 30,000 pregnancies) but the risk is increased in patients who conceived via assisted reproductive technology (ART; 1.5 per 1000 ART pregnancies). The diagnosis is suggested by visualization of both an intrauterine pregnancy and a complex adnexal mass or echogenic fluid in the posterior cul-de-sac. The diagnosis is confirmed when the adnexal mass contains a yolk sac or embryonic/fetal pole. Management is surgical removal of the extrauterine pregnancy. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Heterotopic pregnancy'.)

Cesarean scar pregnancy — Cesarean scar pregnancy occurs from implantation of the pregnancy into either a wedge defect in the lower uterine segment at the site of the hysterotomy for a previous cesarean birth or a microscopic fistula within the hysterotomy scar. As the pregnancy enlarges, vaginal bleeding with or without pain may occur. It occurs in 1 in 2000 pregnancies and accounts for approximately 6 percent of abnormally implanted pregnancies among patients with a prior cesarean birth.

The sonographic findings in cesarean scar pregnancy are an empty uterus with clearly visualized endometrium; empty cervical canal; a gestational sac implanted in the lower anterior uterine segment at the presumed site of cesarean incision scar; a triangular (at ≤8 weeks of gestation) or rounded or oval (at >8 weeks of gestation) gestational sac that fills the shallow area representing a healed hysterotomy site; a prominent or rich vascular pattern at or in the area of a cesarean scar; an embryonic or fetal pole, yolk sac, or both with or without fetal cardiac activity; and thin or absent myometrium between the gestational sac and the bladder [16]. All of these findings may not be present. Histologic confirmation is not required for diagnosis.

Hemodynamically unstable patients require surgery. For hemodynamically stable patients, the optimal management (ie, surgical or medical termination, expectant management) is unclear. (See "Cesarean scar pregnancy".)

Rare disorders

Cervical pregnancy — Cervical pregnancy is a rare form of ectopic pregnancy in which the pregnancy implants in the lining of the endocervical canal. Vaginal bleeding is the most common symptom and is often painless and profuse, resulting in hemodynamic instability. It may be misdiagnosed as an incomplete pregnancy loss.

The sonographic criteria for diagnosis of a cervical pregnancy are a gestational sac or placenta within the cervix (typically with embryonic/fetal cardiac activity or blood flow to the sac), visualization of an endometrial stripe and absence of an intrauterine pregnancy, and an hourglass (figure of eight) shaped uterus with ballooned cervical canal. Histologic confirmation is not required for diagnosis.

Because cervical pregnancy is rare, there are no established criteria for candidates for medical versus surgical treatment. A combination of methods may be required. (See "Cervical pregnancy: Diagnosis and management".)

Gestational trophoblastic disease

Hydatidiform mole — Patients with a molar pregnancy typically present with a positive pregnancy test and signs and symptoms consistent with early pregnancy or early pregnancy complications (bleeding, pelvic discomfort, hyperemesis gravidarum). Molar pregnancy may be suspected based on unusually high hCG levels and, less commonly, uterine size that is large for dates.

Sonographic features suggestive of a complete mole include a central intrauterine heterogeneous mass with numerous discrete anechoic spaces (snowstorm appearance), absence of a fetus, and absence of amniotic fluid.

Surgical removal of the hydatidiform mole is the central component of treatment. (See "Hydatidiform mole: Epidemiology, clinical features, and diagnosis" and "Hydatidiform mole: Treatment and follow-up".)

Choriocarcinoma — Choriocarcinoma is a rare cause of uterine bleeding. A history of a molar pregnancy is the most important risk factor, but it can occur after any type of antecedent pregnancy (spontaneous or induced abortion, preterm or term birth) and rarely occurs coexistent with a normal intrauterine pregnancy. Antepartum vaginal bleeding is the most common presenting symptom and can occur in any trimester. Bleeding may result from vaginal metastases or from the intrauterine tumor. Other symptoms that have been reported include respiratory symptoms from lung metastases, neurologic symptoms from brain metastases, and acute abdominal pain from bleeding intraabdominal metastases [17,18].

The diagnosis should be considered after other more common causes of antepartum bleeding have been excluded and especially in patients with respiratory or neurologic symptoms. Gestational trophoblastic neoplasia is a clinical diagnosis based upon elevation of serum hCG, after a nonmolar pregnancy and after other etiologies of an elevated hCG have been excluded. On ultrasound, choriocarcinoma appears as a mass enlarging the uterus, with a heterogeneous appearance that correlates with areas of necrosis and hemorrhage. The tumor is usually markedly hypervascular on color Doppler and may extend into the parametrium.

Chemotherapy is the major treatment modality. (See "Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk stratification" and "Initial management of high-risk gestational trophoblastic neoplasia".)

PROGNOSIS — In ongoing pregnancies, studies consistently show an association between first-trimester uterine bleeding and adverse outcome later in pregnancy (eg, pregnancy loss, preterm birth, preterm prelabor rupture of membranes, fetal growth restriction) [15,19-32]. The prognosis is most favorable when bleeding is light and limited to early pregnancy (ie, less than 6 weeks of gestation) [15,27] and worsens when bleeding is heavy or extends into the second trimester [22-26].

For most patients with ongoing pregnancies, no effective interventions are available, but they can be reassured of the relatively low likelihood of adverse outcome. For example:

In a series of 550 patients followed prospectively from the time of their positive pregnancy test, 117 (21 percent) had bleeding prior to 20 weeks of gestation and 67 miscarried (12 percent, or approximately one-half of those with bleeding) [32]. Fourteen of 18 pregnancies with heavy bleeding (eg, clots) and moderate pain miscarried (78 percent).

In a prospective series in which all subjects (n >16,500) had a viable pregnancy at enrollment at 10 to 14 weeks, the frequency of preterm birth in those with no, light, or heavy first-trimester bleeding was approximately 6, 9, and 14 percent, respectively, and the frequency of pregnancy loss before 24 weeks of gestation was 0.4, 1, and 2 percent, respectively [22]. A limitation of this series is that patients were enrolled late in the first trimester and with sonographically confirmed embryonic/fetal cardiac activity, thus those with very early bleeding and pregnancy loss had already been excluded.

Bed rest is unnecessary and will not improve outcome. Rarely, patients with a history of recurrent pregnancy loss may benefit from vaginal progesterone therapy. This is controversial and these patients are discussed separately. (See "Recurrent pregnancy loss: Management", section on 'Progesterone'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obstetric hemorrhage".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Bleeding in early pregnancy (The Basics)")

SUMMARY AND RECOMMENDATIONS

General principles – Vaginal bleeding is a common event in early pregnancy, especially the first trimester; the source is virtually never from the embryo/fetus. A provisional clinical diagnosis of the cause is based on the patient's gestational age and character of the bleeding (eg, light or heavy, associated with pain or painless). Physical examination and laboratory and/or imaging tests are then used to support or revise the initial diagnosis. The goal of the evaluation is to make a definitive diagnosis when possible and exclude the presence of serious pathology in the remaining cases (algorithm 1) (See 'Introduction' above and 'Incidence' above and 'Goal' above.)

Etiology – Vaginal bleeding in the first half of pregnancy may be related to:

Ectopic pregnancy (See 'Ectopic pregnancy' above.)

Pregnancy loss (See 'Pregnancy loss' above.)

Threatened abortion (See 'Threatened abortion' above.)

Cervical, vaginal, or uterine pathology (See 'Cervical and vaginal disorders' above and 'Ectropion' above and 'Cervical insufficiency' above and 'Cervical pregnancy' above and 'Gestational trophoblastic disease' above.)

Physiologic bleeding (ie, related to implantation of the pregnancy) (See 'Physiologic or implantation bleeding' above.)

Diagnostic evaluation – Evaluation consists of a focused history and physical examination (bimanual and speculum), and often ultrasound examination (algorithm 1). (See 'Evaluation' above.)

Exclude ectopic pregnancy – An important goal in the evaluation of patients with bleeding in early pregnancy is to rule out the possibility of ectopic pregnancy, since ruptured ectopic pregnancy can result in severe hemorrhage and death. Sonographic confirmation of an intrauterine pregnancy excludes ectopic pregnancy, except in rare cases of heterotopic pregnancy, which should be considered, especially in patients who conceive by assisted reproductive technology (ART). (See 'Evaluation' above and 'Ectopic pregnancy' above and 'Heterotopic pregnancy' above.)

Examine any tissue that has been passed – Products of conception, if present in tissue the patient has passed vaginally, should be visible upon careful examination and are diagnostic of a partial or complete pregnancy loss. Visualization of villi can be facilitated by rinsing the specimen to clear away blood clot and then floating it in water (picture 1A-B). (See 'Focused physical examination' above and 'Speculum examination' above and 'Pregnancy loss' above.)

Check for embryonic/fetal cardiac activity – Handheld Doppler or ultrasound confirmation of embryonic/fetal cardiac activity is reassuring, as it indicates bleeding is not related to embryonic/fetal demise. (See 'Check for embryonic/fetal cardiac activity' above and 'Ultrasonography' above.)

Examine the vagina and cervix – Speculum examination usually confirms that the uterus is the source of bleeding but may reveal a vaginal or cervical source unrelated to pregnancy; in such cases, further evaluation depends upon the nature of the abnormality. If no blood is seen in the vagina, then the bleeding is either resolved, occurring intermittently, or from a nongenital tract source (eg, hemorrhoids). (See 'Speculum examination' above and 'Pelvic examination' above and 'Diagnoses identifiable on speculum examination' above.)

Direct visualization of the gestational sac in a dilated internal cervical os in a patient with bleeding and/or pain is generally sufficient to conclude that pregnancy loss is occurring. In contrast, in the second trimester, cervical dilation and/or effacement (possibly with prolapsed fetal membranes) that is painless or associated with only mild discomfort in the lower abdomen or back suggests cervical insufficiency. (See 'Speculum examination' above and 'Cervical insufficiency' above.)

Diagnoses of exclusion – Threatened abortion and implantation bleeding are diagnoses of exclusion in patients with vaginal bleeding, a closed cervix, and sonographic visualization of an intrauterine pregnancy with detectable embryonic/fetal cardiac activity. (See 'Threatened abortion' above and 'Physiologic or implantation bleeding' above.)

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References

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