Approach
The critical components of the diagnosis of miscarriage are a detailed history, serial beta hCG titers, and a transvaginal ultrasound scan.
History
Key risk factors include older parental age, uterine malformation, bacterial vaginosis, and thrombophilias. Recent urine pregnancy test results and contraception history should be obtained. The diagnosis of pregnancy may need to be reconfirmed, as some home pregnancy test kits may have questionable sensitivity. A chronological recall of pregnancy events from the outset and a history of postcoital bleeding and recent symptoms may help characterize a possible working diagnosis. Most women suspect that they have lost the pregnancy after expelling an atypical blood clot. An increase in the severity of vaginal bleeding is, however, a poor prognostic sign. In some instances, vaginal bleeding, pelvic discomfort, and early pregnancy symptoms abate after vaginal passage of early pregnancy tissue. This is suggestive of a missed miscarriage.
It is always important to rule out an ectopic pregnancy, especially when pelvic, suprapubic, or inguinal pain is a symptom and is associated with cardiovascular symptoms, fainting attacks, and/or unexplained anemia. Unusually marked symptoms of early pregnancy should alert toward a molar or multiple pregnancy.
Trauma (e.g., motor vehicle accident) is uncommon during pregnancy; however, increased severity of abdominopelvic trauma leads to an increased risk of fetal loss. Caution should be exercised when ascertaining this from the history due to possible medicolegal implications. A cause-effect relationship is unlikely following a recent accidental or intentional suprapubic blunt trauma if there was unproven uterine hypoperfusion or maternal hypotension as a result.[64]
Physical findings
Most women are clinically well but understandably anxious about the possibility of the loss of pregnancy. An ill-looking patient may have had a significant vaginal or intra-abdominal bleed. A cardiovascular examination including assessment of the peripheral perfusion will help identify the pale patient with tachycardia, hypotension, and air hunger indicative of an ectopic pregnancy. Abdominopelvic assessment will reveal the size of a suprapubic mass that may correlate with the gestational age, or draw attention to other coincidental lesions. Examination of the perineum may identify local lesions outside the vagina responsible for the bleeding.
A vaginal speculum examination may reveal early pregnancy tissue in the upper vagina or protruding through the cervical os. It may also reveal lesions such as an ectropion, a cervical polyp, or, very rarely, an unexpected genital tract laceration that may be responsible for the bleeding. Inserting a speculum does not alter the short-term pregnancy outcome, and patients should be reassured that the speculum does not come close to the pregnancy tissue.[65][Figure caption and citation for the preceding image starts]: The natural course of miscarriageFrom: Ankum WM, Wieringa-de Ward M, Bindels PJE. BMJ 2001 Jun 2;322(7298):1343-6. [Citation ends].
Immediate investigations
Transvaginal ultrasound scanning (TVUS):
Key investigation in the diagnosis of miscarriage, provided that the serum beta hCG titer is >1500 mIU/mL.[66][67]
Helps differentiate between a complete or incomplete miscarriage.
Majority of missed miscarriages are encountered unexpectedly during routine or planned TVUS in high-risk patients.
According to the UK National Institute for Heath and Care Excellence (NICE) guideline, a miscarriage should be considered when the gestation sac on TVUS is empty, has a mean diameter of 25 mm or more, and has no visible yolk sac or fetal pole.[68] It is also likely when the crown-rump length of the embryo measures 7 mm or more, with no obvious fetal heart activity.[68][69] A study designed to validate the performance of these cut-off values found that they are not too conservative, but do not take into account gestational age. No advice exists on how to relate gestational age to scan findings and a possible diagnosis of miscarriage.[70] If there is any uncertainty about the viability of a pregnancy, conservative management and ultrasound at least 7 days later are recommended, given the real risk of inadvertent evacuation of a desired pregnancy. It is important to inform women that a diagnosis of miscarriage based on one ultrasound scan is not 100% accurate, and the chance of an incorrect diagnosis is higher at an earlier gestational age.[68]
Guidance from the American College of Obstetricians and Gynecologists advises that an embryo should be visible by transvaginal ultrasonography with a mean gestational sac diameter ≥25 mm. Cardiac motion should be observed when the embryo is ≥7 mm in length. If an embryo less than 7 mm in length is seen without cardiac activity, a subsequent ultrasound examination at a later time may be needed to assess the presence or absence of cardiac activity.[71]
When diagnosing complete miscarriage on an ultrasound scan, in the absence of a previous scan confirming an intrauterine pregnancy, always be aware of the possibility of a pregnancy of unknown location. Advise these women to return for follow‑up (for example, hCG levels, ultrasound scans) until a definitive diagnosis is obtained.[68]
Serum beta hCG titers:
Should be ordered if uncertain about miscarriage status.
A drop in serum hCG concentration of more than 50% after 48 hours with pain and bleeding is suggestive of a failing pregnancy.
A rise in serum hCG of more than 50% over a 48 hour period is suggestive of possible ongoing pregnancy.
A combined assay of serum beta hCG and serum progesterone has been found to have a predictive value of 85.7% for inevitable pregnancy loss.[72] If validated in larger clinical trials, this tool may be useful in triaging patients, planning follow-up, and patient counseling.
Other investigations
Transabdominal scanning (TAS):[68]
May be considered for women with an enlarged uterus or other pelvic pathology (e.g., fibroids or an ovarian cyst) above 8 weeks of gestation.
May also be offered to women for whom a TVUS is not acceptable, with an explanation of its limitations.
In the UK, NICE recommends that if there is no visible heartbeat on TAS, then the crown-rump length needs to be recorded and a second scan should be performed a minimum of 14 days after the first scan before making a diagnosis.
Serum progesterone:
In symptomatic patients with inconclusive ultrasound findings, a single serum progesterone level can be helpful. A titer ranging between 3.2 and 6.0 ng/mL predicts a nonviable pregnancy with a pooled sensitivity of 74.5% and a specificity of 98.4%.[73]
Vaginal swab:
Asymptomatic bacterial vaginosis may play an important role in second-trimester miscarriage.[25][40]
Urine pregnancy test:
A positive urine pregnancy test confirms the pregnancy. If the pregnancy is <6 weeks gestation and the woman is experiencing bleeding, but no pain, and has no risk factors, such as a previous ectopic pregnancy, repeat a urine pregnancy test after 7 to 10 days. A negative pregnancy test means the pregnancy has miscarried. Review the condition of a woman with a further positive pregnancy test.[68]
Rhesus blood group:
Rhesus status is determined during routine screening in early pregnancy. It identifies whether the Rh-negative blood group is present in the mother, which indicates the need for Rho (D) immune globulin administration.
Complete blood count:
May indicate degree of blood loss and probable need to transfuse.
Scoring tool to predict the viability of a pregnancy:
The use of a simple scoring tool to predict the viability of a pregnancy, and whether it is likely to proceed beyond the first trimester, has been proposed.[74] The factors scored in this tool are:
the presence of fetal cardiac activity on ultrasound scan
the size of the yolk sac
the maternal age
the gestational age
the bleeding score; and
mean gestational sac diameter.
When applied to 1435 patients, the scoring tool performed with a sensitivity of 92% and a specificity of 73%.
Investigations for recurrent miscarriage
The majority of recurrent miscarriages are unexplained. Investigations that may be considered in patients include:[3][75]
Lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2 glycoprotein I antibodies for antiphospholipid syndrome
Pelvic ultrasound to identify congenital or acquired uterine structural abnormalities
Cytogenetic analysis should be performed on products of conception of the third and subsequent consecutive miscarriage(s). Parental peripheral blood karyotyping of both partners should be performed in couples with recurrent miscarriages where testing of products of conception reports an unbalanced structural chromosomal abnormality.[76]
Do not test for inherited thrombophilias including methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage as robust data linking MTHFR polymorphisms or other common inherited thrombophilias and recurrent pregnancy loss are lacking.[77][78][79]
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