Miscarriage and Recurrent Pregnancy Loss
Sara Seifert
Kristiina Altman
FIRST-TRIMESTER MISCARRIAGE
Miscarriage, or spontaneous abortion, is generally defined as the spontaneous loss of a fetus weighing <500 g or at gestational age (GA) <20 weeks.
Miscarriages are classified according to the GA at which they occur.
Preclinical or biochemical miscarriages happen at or before 5 weeks of gestation.
Clinical miscarriages must have documentation of pregnancy by an appropriate beta-human chorionic gonadotropin (β-hCG) level, ultrasound, or tissue pathology and include the following:
Embryonic miscarriage occurs at 6 to 9 weeks of gestation or crown-rump length (CRL) >5 mm without cardiac activity.
Fetal miscarriage occurs between 10 and 20 weeks of gestation or CRL >30 mm without cardiac activity.
Incidence and Risk
Thirty percent to 40% of all conceptions result in miscarriage.
The risk of preclinical miscarriage is estimated as approximately 25% to 30% in women older than age 35 years.
Ten percent to 15% percent of clinically recognized pregnancies end in first-trimester and early second-trimester losses (<20 weeks of gestation).
Nearly 80% of sporadic losses occur during the first trimester and typically manifest before 12 weeks’ GA.
The risk of miscarriage is 22% to 57% at <6 weeks, 15% at 6 to 10 weeks, and 2% to 3% >10 weeks.
The risk increases significantly with advanced maternal age (AMA) from 8% to 20% in women younger than age 35 years to as high as >50% in those older than age 40 years. This increase is thought to be related to the increased risk of aneuploidic pregnancies in older women.
Although maternal age probably has the greatest impact, several other factors carry an increased risk of sporadic first- or early second-trimester clinical miscarriage. See Table 36-1.
Common causes of sporadic losses include the following:
Chromosomal abnormalities account for approximately 50% of miscarriages.
Incidence is inversely related to GA.
Ninety percent in anembryonic (gestational sac without embryonic structures) products of conception (POCs) (sometimes referred to as “blighted ovum”)
Fifty percent in embryonic abortuses
Thirty percent in fetal abortuses
TABLE 36-1 Risk Factors for Miscarriage
Increasing maternal age (>35 yr old)
History of previous miscarriage
Tobacco
Alcohol
Illicit drug use (e.g., cocaine)
NSAID use
Caffeine (high intake)
Low folate levels/intake
Maternal fever/febrile illness
Maternal obesity
Maternal medical conditions (e.g., diabetes)
NSAID, nonsteroidal anti-inflammatory drug.
Typically autosomal trisomies, monosomies, or polyploidies
Maternal conditions: uterine anomalies, endocrinopathies, autoimmune disease, hypercoagulability, infection, and teratogen exposure
Previous obstetric history: Risk of miscarriage increases from 20% in women with a history of one miscarriage to 43% in women with a history of three or more.
Tobacco: Smoking and exposure to secondhand smoke increase the risk.
Observational and population-based studies have also implicated the following risk factors: alcohol and illicit drug use, nonsteroidal anti-inflammatory drug (NSAID) use, fever, caffeine, obesity, and low folate levels.
Presentation
The hallmark complaint of a pregnant woman experiencing a miscarriage is vaginal bleeding after a missed period, with or without pain.
Of note, 25% of all pregnancies are complicated by bleeding before 20 weeks of gestation. Of these, 12% to 57% end in miscarriage. Several studies have found that spotting or light bleeding does not increase the risk of miscarriage.
The types of spontaneous abortion include the following:
Threatened: often painless, cervix closed, uterine size consistent with GA
Inevitable: painful, cervix open, uterine size consistent with GA
Complete (usually before 12 weeks of gestation): mild pain; cervix closed; uterus small, contracted, and empty
Incomplete (usually after 12 weeks of gestation): painful; cervix open often with tissue in os or vagina; uterus small and not well-contracted, with POCs still in the uterus
Missed (intrauterine fetal demise at <20 weeks of gestation): retained nonviable pregnancy in which the embryo or fetus lacks heartbeat but symptoms of miscarriage have not developed. Also called delayed miscarriage. The patient typically presents due to cessation of the normal symptoms of pregnancy (i.e., nausea, vomiting, breast tenderness) or receives the diagnosis unexpectedly during ultrasound evaluation.
Septic: painful, purulent discharge; cervix open; cervical motion tenderness; tender uterus; constitutional symptoms (e.g., fever, malaise); tachycardia; and/or tachypnea. The infectious source is often Staphylococcus aureus. Septic miscarriage is frequently a complication of unsafe induced abortion as opposed to the sequela of spontaneous loss.
Assessment
The differential diagnosis for early pregnancy bleeding includes the following:
Physiologic
Ectopic pregnancy
Gestational trophoblastic disease
Anatomic pathology of the vagina, cervix, or uterus
The gold standard for diagnosis is imaging, usually with transvaginal ultrasound. This modality is especially useful in differentiating intrauterine and ectopic pregnancies.
Viability can be determined through the appearance of a gestational and/or yolk sac and with measurement of the CRL. A gestational sac should be visible at β-hCG levels of 1,000 to 2,000 mIU/mL (˜5 weeks of gestation) depending on ultrasound equipment and radiologist, but the detection level may be higher in patients with difficult anatomy (e.g., morbid obesity, multiple fibroids, deeply retroflexed uterus). Newer research is elucidating the lowest discriminatory levels with modern ultrasound equipment and the 99% probability levels for visualizing a gestational sac (390 to 3,510 mIU/mL), a yolk sac (1,094 to 17,716 mIU/mL), and a fetal pole (1,394 to 47,685 mIU/mL).
In diagnosing a missed clinical miscarriage, the operator can use several sonographic criteria: (a) absence of fetal cardiac activity with a CRL >5 mm and/or (b) absence of a fetal pole in the presence of a mean sac diameter of >18 mm transvaginally or >25 mm transabdominally.
The early presence of fetal cardiac activity in women of AMA is not necessarily reassuring. One series demonstrated an increased risk of miscarriage from 4% in women younger than age 35 years to 29% in women older than age 40 years.
Evaluation also includes a complete blood, a type and screen, serum progesterone, and serial quantitative β-hCG measurements. The last is most useful in conjunction with imaging. In normal pregnancies, β-hCG levels usually rise 55% to 66% in 48 hours. The measurements should be done in the same laboratory due to intraassay variations. Occasionally, a slower rise may be seen in normal pregnancies.
Management and Complications
If bleeding is minimal or symptoms have resolved, a threatened miscarriage can be managed expectantly. Bed rest or progesterone treatment does not prevent miscarriage.
Similarly, complete abortions often require no intervention other than evaluation of passed tissue to confirm POCs. In such cases or with expectant management, patients should be advised to bring the POC to the hospital for evaluation.
Miscarriage has a 1.5% to 2% risk of alloimmunization. Given the minimal risks of anti-D immune globulin (RhoGAM) administration compared to the potential benefits, any Rh (D)-negative woman who experiences a spontaneous loss or has a threatened miscarriage should receive it.
Incomplete, inevitable, or missed miscarriages can be managed expectantly, medically, or surgically. These three outcomes have been extensively studied. Selecting an option is based on a combination of patient wishes, stability, and stage of miscarriage.
TABLE 36-2 Options for Medical Treatment of Miscarriage | ||||||||||||
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Expectant Management
Expectant management is an ideal option for women who present during the first trimester, are clinically stable, and would prefer no intervention.
The success is greatest in incomplete (91%) compared to missed (76%) or preclinical (66%) miscarriages. The average time to miscarriage completion is 2 to 4 weeks.
Surgical or medical intervention is indicated if expectant management fails.
Medical Management
Medical management is an effective method for women who decline surgery or expectant management (Table 36-2).
The World Health Organization recommends either 800 µg vaginal or 600 µg sublingual misoprostol, to be repeated after 3 days. This results in a completion rate of 79% by 7 days and 87% by 30 days. Cramping and bleeding typically occur within 2 to 6 hours of administration. Pretreatment with Tylenol and NSAIDs is helpful. Of note, the oral route tends to cause more undesirable side effects, such as uterine cramping and gastrointestinal symptoms.
Several trials have included the combination of a progesterone antagonist (mifepristone) and misoprostol. The U.S. Food and Drug Administration-approved regimen includes 600 mg mifepristone and 48 hours later 400 µg misoprostol orally, with 92% efficacy. An alternative recommendation (200 mg mifepristone orally with 800 µg misoprostol per vagina) appears to have greater efficacy (95% to 99%) as well as fewer side effects and lower cost.
Follow-Up
A follow-up ultrasound should show the absence of POCs, and serum β-hCG level should drop 80% 1 week following the passage of tissue. It is prudent to follow β-hCG levels to zero if an intrauterine pregnancy (IUP) was not documented.
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