Miscarriage describes the involuntary loss of a pregnancy before 20 weeks of gestation or loss of fetus weighing 500 g or less;r1affects about 10% to 25% of all clinically recognized pregnanciesr1r2r3
Most are sporadic and caused by fetal chromosomal abnormalities (eg, trisomy, monosomy, polyploidy) r2
Most common risk factors are advanced maternal age and prior early pregnancy loss r2
Symptoms of miscarriage typically include vaginal bleeding and uterine cramping
Diagnose pregnancy loss by thorough history and physical examination combined with transvaginal ultrasonography and hCG values r2
Basing diagnosis on single hCG level or ultrasonogram is often unreliable; trending of β-hCG values and examination findings are usually required for accuracy
Administer Rho(D) immunoglobulin to patients who are Rh-negative r1
No medical interventions exist to improve prognosis of threatened miscarriage
Patient may be discharged with patient education if stable; follow-up arrangements for ultrasonography and serial hCG levels are made in conjunction with obstetrician r4
Treatment options for miscarriage (nonviable fetus) include expectant management, medical treatment, and surgical evacuation of uterus
About two-thirds of patients with bleeding will have live fetus on ultrasonographic examination; nearly 85% of these patients go on to deliver live-born infant r1
Recurrent pregnancy loss is defined as 2 or more failed clinical pregnancies r5
Common causes include embryonic chromosomal abnormalities, maternal anatomic abnormalities (eg, septate uterus), luteal phase defects, and antiphospholipid antibodies r6
Diagnostic evaluation for recurrent pregnancy loss can be initiated after 2 failed clinical pregnancies (1 early miscarriage is relatively common) r1
Investigation includes workup for genetic, endocrine, anatomic, and immunologic causes
Treatment of recurrent miscarriage is based on cause, if identified r7
Up to 50% of cases will have no clearly defined cause r1
Most patients with recurrent pregnancy loss will ultimately have successful pregnancy, even without intervention r1r7
Urgent Action
Patients with hemodynamic instability or acute abdomen should be evaluated and treated urgently
Urgently treat patients with early pregnancy loss and hemorrhage, hemodynamic instability, or signs of infection with surgical uterine evacuation
Pitfalls
Ectopic pregnancy is an important consideration in any patient who has abdominal pain or vaginal bleeding and a positive pregnancy test result
Pelvic ultrasonography and serum hCG levels are essential to locate pregnancy r4
Use caution when basing diagnosis of pregnancy loss on a single β-hCG level or ultrasonogram, as single point-in-time measurement is often unreliable
Confirm early pregnancy loss before initiating treatment; failure to do so may have detrimental consequences (eg, interruption of normal pregnancy, pregnancy complications, birth defects) r2
Terminology
Clinical Clarification
Miscarriage describes the involuntary loss of a pregnancy before 20 weeks of gestation or loss of fetus weighing 500 g or less r1
Other terms for miscarriage include spontaneous abortion and early pregnancy loss
Commonly occurring event, affecting about 10% to 25% of all clinically recognized pregnancies r1r2r3
Approximately 80% of losses occur within first trimester, often due to fetal chromosomal abnormalities (about 50%) r2
Recurrent pregnancy loss is defined as 2 or more failed clinical pregnancies r5
Less than about 5% of patients will have 2 consecutive miscarriages, and only 1% of patients will experience 3 or more r3
Classification
Early pregnancy loss: within first 12 6/7 weeks of gestation r2
Denotes nonviable intrauterine pregnancy (gestational sac is empty or contains fetus with no cardiac activity)
Preterm or stillbirth: pregnancy loss after 20 weeks of gestation r1
Point of viability fluctuates
Recurrent pregnancy loss: traditionally defined as 3 or more consecutive spontaneous losses,r1but more recently defined as 2 or more failed clinical pregnanciesr5
Clinical pregnancy is documented by ultrasonography or histopathologic examination r5
Recurrent loss can be further stratified as primary, secondary, or tertiary r7
Primary: patient has never had a viable infant
Secondary: patient previously delivered pregnancy beyond 20 weeks of gestation, with subsequent losses
Tertiary: multiple miscarriages interspersed with viable pregnancies
Most losses in patients with recurrent pregnancy loss occur before 10 weeks of gestation r1
Terms to describe type of abortion by appearance of patient upon presentation (less useful today owing to widespread use of transvaginal ultrasonography in diagnosis of early pregnancy) r1
Threatened abortion: vaginal bleeding in setting of viable intrauterine pregnancy and closed cervical os
Inevitable abortion: open cervical os with no passage of products of conception in setting of either a viable or nonviable intrauterine pregnancy
Incomplete abortion: intrauterine gestation at less than 20 weeks of gestation with open cervical os and partial passage of products of conception
Complete spontaneous abortion: closed cervical os and contracted uterus after passage of all products of conception in setting of intrauterine pregnancy
Missed abortion: nonviable intrauterine pregnancy with gestation less than 20 weeks and closed cervical os
Largely outdated term owing to early, widespread use of transvaginal ultrasonography; delayed diagnosis of fetal demise or anembryonic gestation are rare today
About 25% of clinically pregnant patients experience some vaginal bleeding; up to one-half of patients who have bleeding during early pregnancy will miscarry r1
If present, gentle removal of fetal tissue from cervical os with ring forceps may slow bleeding r4
If products not removed easily with ring forceps, consult gynecologist because cervical ectopic pregnancy is possible, and removal of products can cause severe hemorrhage
Degree of vaginal bleeding
Uterine size and tenderness
Significant tenderness raises concern for ectopic pregnancy or pelvic infection (less common)
Adnexal enlargement
Often unilateral, due to cystic corpus luteum or ectopic pregnancy
Significant tenderness raises concern for ectopic pregnancy or pelvic infection (less common)
Cause of miscarriage is often multifactorial, particularly in recurrent losses
Most common risk factors for early pregnancy loss are advanced maternal age and prior early pregnancy loss r2c19c20
Majority of sporadic losses before 10 weeks of gestation are due to random numeric chromosome errors (eg, trisomy, monosomy, polyploidy) c21
Recurrent pregnancy loss has been associated with several factors, including genetics, age, antiphospholipid syndrome, uterine abnormalities, hormonal or metabolic disorders, infection, autoimmunity, male parameters, and lifestyle issues r6c22c23c24c25c26c27c28c29
Cause for recurrent losses determined in about 50% of cases r1r3
Decreased production of progesterone from corpus luteum (luteal phase deficiency) or inadequate endometrial response to normal levels; may result in inadequate endometrial development to support implanted blastocyst
May cause early pregnancy loss, typically before the 6th week of gestation
Untreated overt hypothyroidism and subclinical hypothyroidism are associated with increased risk of miscarriage r1
Presence of thyroid autoantibodies (antithyroperoxidase) in pregnant patients—even in those who are euthyroid—may be associated with higher risk of miscarriage and recurrent pregnancy loss r6r9
Maternal hyperthyroidism may be associated with increased risk of early and late pregnancy loss r10
Poorly controlled diabetes is associated with increased risk of early pregnancy loss; there is a direct correlation between hemoglobin A1C and rate of miscarriage r1
Well-controlled diabetes is not a risk factor for recurrent pregnancy loss r3
Insulin resistance is common in patients with recurrent miscarriage and is associated with increased risk of pregnancy loss
Miscarriage, especially recurrent, may be associated with abnormalities in maternal alloimmune response
Maternal immune system normally recognizes paternally derived antigens on embryonic tissues and produces alloantibodies to protect trophoblast from cytotoxic maternal immune response
Possible mechanisms may involve alterations in natural killer cells, regulatory T cells, dendritic cells, plasma cells, and the human leukocyte antigen system r12
Autoimmune disorders
Antiphospholipid syndrome
Characterized by production of moderate to high levels of antiphospholipid antibodies and vascular thrombosis, which may lead to deleterious effects on developing trophoblast r1
May be associated with both early and late pregnancy loss (more common in second and third trimester); however, association remains controversial r1
May lead to thrombus formation in placental microvasculature, with potential for pregnancy loss and other adverse pregnancy outcomes (eg, placental abruption, fetal growth restriction)
Includes factor V Leiden, prothrombin G20210A mutation, and deficiencies in protein C, protein S, and antithrombin III
Numerous infectious pathogens have been identified in cultures of patients with sporadic miscarriages; relationship to recurrent pregnancy loss is less clear r6
Listeria monocytogenes: risk for second trimester miscarriage r1
Chlamydia trachomatis: primary infection associated with pregnancy loss, but not recurrent loss; no evidence that it causes miscarriage in asymptomatic patients r1
Mycoplasma species (Ureaplasma urealyticum, Mycoplasma hominis): most common bacterial species found in cultures from patients with spontaneous miscarriage. There are no randomized placebo-controlled clinical trials to prove causal relationship and that treatment is effective r1
Toxoplasma gondii: may infect embryo and lead to pregnancy loss r1
Many viral agents may cause miscarriage if acquired as primary infection (associated with both first and second trimester loss) r1
Parvovirus B19: may be embryotoxic in first trimester; not cause of recurrent loss
Rubella, varicella, and cytomegalovirus: may cause miscarriage, but not a cause of recurrent loss
HSV in genital tract: primary infection reported to cause miscarriage
No apparent association between HSV-2 infection in pregnancy and fetal death after 16 weeks of gestation
Bacterial vaginosis: risk factor for late miscarriage and preterm birth r1
Adhesions (scarring or synechiae) of the uterine cavity that can lead to partial or complete obliteration of the endometrium; often referred to as Asherman syndromer7
Can result in insufficient endometrium available to support fetal growth
Most frequently results from uterine curettage for pregnancy complications (eg, missed or incomplete abortion) or postpartum complications (eg, hemorrhage, retained placental remnants)
Cervical incompetence (insufficiency; may be congenital or acquiredr1)
Painless dilation of internal cervical os that results in inability of the cervix to maintain pregnancy, leading to prolapse or rupture of fetal membranes and fetal expulsion
Typically occurs during second trimester, rather than first
Acquired: most common; results from surgical trauma to cervix (eg, conization, loop electrosurgical excision procedures, mechanical dilation of cervix, obstetric lacerations)
Congenital: associated with uterine anomalies and congenital defects in cervical tissue
Rarely causes recurrent miscarriage; usually treated after first occurrence of loss
Smoking increases risk of miscarriage in a dose-dependent manner; risk increases with level of smoking activity r1
Smoke contains agents (eg, nicotine, carbon monoxide, mutagens) that harm developing embryo; nicotine is a vasoconstrictor and may reduce blood flow to placenta
Paternal smoking also increases risk; when both parents smoke, rate of miscarriage may increase up to 4-fold r1
Alcohol
Alcohol consumption is a risk factor for miscarriage
Patients who consume alcohol at least 2 days per week have about 2-fold higher risk of miscarriage; those who consume more than 5 drinks per week (on average) have 3-fold higher risk of first trimester miscarriage r1
Cocaine use: associated with increased risk of miscarriage r6
Caffeine
Moderate to heavy caffeine ingestion may be independent risk factor for miscarriage r1
Modest increase in risk associated with more than 300 mg/day of caffeine (equivalent to 3 cups of coffee)
Preconception caffeine consumption is not associated with spontaneous miscarriage
Radiation and magnetic fields
Although high-energy radiation exposure is associated with teratogenic effects and intrauterine growth restriction, no conclusive evidence supports that similar exposure increases risk of miscarriage; presumably, a threshold effect extends from teratogenicity to miscarriage r1
Embryo is most sensitive to lethal effects of radiation during implantation and first few days after, decreases during early embryogenesis, and levels off by term gestation (extrapolated from animal models)
No increased risk of abortion with radiation exposures less than 0.05 Gy r1
Exposures from diagnostic procedures are several-fold less than 0.05 Gy and are unlikely to cause miscarriage, even if administered at time of implantation
Exposure to magnetic fields induced by electric currents has not been associated with significantly higher rate of miscarriage; video display terminals, electric blankets, and power lines are not harmful to pregnancy r1
Patients occupationally exposed to anesthetic gases may be at increased risk for spontaneous abortion
Current practice in hospitals and offices provides adequate scavenging of gases
Occupational exposure to chemotherapeutic agents (eg, nurses, pharmacy technicians) may have increased risk of miscarriage
Heavy metals, lead, cadmium, mercury, and arsenic are embryotoxic
Lead is most common exposure and is associated with miscarriage
Organic solvents (especially those used in computer industry) and organic pesticides may induce miscarriage
Exercise, stress, and depression
Interaction between stress, depression, and pregnancy is complex; relationship with pregnancy loss is equivocal r1
Severe stress may lead to higher incidence of adverse late pregnancy outcomes but has not been associated with early pregnancy loss; may affect uteroplacental function
Patients who receive counseling for depression associated with recurrent loss seem to have a higher successful pregnancy rate r1
Exercise, employment, and work have no apparent association with miscarriage r1
50% to 60% of miscarriages are due to chromosomal abnormalities r1
Up to 85% of nonviable pregnancies (determined by ultrasonography) demonstrate aneuploidy on pathologic review
Loss at less than 10 weeks of gestation is usually caused by chromosomal abnormality r1
Fetal aneuploidy is the most common cause of miscarriage, with autosomal trisomies accounting for majority of cases (56% trisomic, 20% polyploid, 18% chromosome X monosomies, 4% unbalanced translocationsr1)
May be result of known parental abnormalities or de novo embryonic errors
Recurrent losses in patients younger than 36 years are usually caused by sources other than chromosomal abnormalities r1
Rate of chromosomal abnormalities in aborted fetuses of couples with recurrent pregnancy loss does not differ from matched cohorts in general population
Derangement of organ development (may have chromosomal component) r1
Occurs in 1% to 2% of all miscarriages; incidence increased after induced abortions using nonsterile equipment r1
Most frequent cause is polymicrobial, involving Escherichia coli and other aerobic gram-negative rods; group B β-hemolytic streptococci, anaerobic streptococci, Bacteroides species, and Clostridium perfringens may also be implicated r1
Risk factors and/or associations
Age
More common in patients younger than 18 years and older than 35 years r1c43
Frequency of clinically recognized miscarriage by patient age: r1
20 to 34 years: 9% to 17%
35 to 40 years: 20%
Older than 40 years: 40%
45 years and older: near 80%
Older paternal age
Increasing paternal age is associated with increasing rate of spontaneous abortion r17
May only result in a slight increase in the chance of spontaneous abortion for a specific couple
Independent of maternal age and other factors
Genetics
Miscarriage and aneuploidy
Most sporadic pregnancy losses result from random numeric chromosomal errors (eg, trisomy, monosomy, polyploidy)
Risk of aneuploidy increases with maternal age
Recurrent pregnancy loss
Parental chromosomal disorders (eg, translocations, inversions, rare ring chromosomes, in either parent) r7
Occur in 12% of couples with recurrent pregnancy loss r18
Balanced translocations are most common contributing chromosomal disorder in recurrent losses
Asymmetric inactivation of the X chromosome is more common in patients with recurrent pregnancy loss r18
β-hCG level trending is usually required for accuracy
Obtain transvaginal ultrasonogram in pregnant patients with vaginal bleeding to determine health and location of fetus r19c48
If intrauterine gestation cannot be reliably identified, serial ultrasonographic examinations and β-hCG levels may be required before treatment to rule out possibility of ectopic pregnancy r2
Use caution when basing diagnosis on single level or ultrasonogram, as single point-in-time test results are often unreliable
Determine Rh type; order blood type and antibody screen (if not already tested) r4r20c49c50
Order hemoglobin level to provide baseline measurement and evaluate degree of blood loss with persistent bleeding r4
Septic abortion
Suspect with symptoms of bleeding or spotting and clinical signs of infection during first 20 weeks of pregnancy
Perform CBC, urinalysis, blood chemistry, and electrolyte panel in all patients r1
Obtain blood cultures, chest radiograph, and panels for coagulation and disseminated intravascular coagulation in acutely ill patients
Acquire cervicouterine cultures; Gram stain may provide rapid preliminary analysis r1c51
Recurrent pregnancy loss
Initiate diagnostic evaluation after 2 failed clinical pregnancies r1
Consider evaluation after only 1 second trimester loss as cause is more likely to recur
Evaluation typically involves investigation into genetic, endocrine, metabolic, anatomic, and immunologic causes r3
Patient history often elicits lines of investigation to initiate
Laboratory testing commonly includes measuring levels of TSH, thyroid autoantibodies, prolactin, hemoglobin A1C, and antiphospholipid antibodies r1r3r21c52c53c54c55c56
Recommended to assess for uterine abnormalities, although role in first trimester loss is debatable r3
Additional imaging studies may include hysterosalpingogram, saline sonohysterogram, 3-dimensional ultrasonography, hysteroscopy, or MRI c57c58c59c60
Perform parental karyotype to determine if any balanced structural chromosomal abnormalities exist r1r3
Balanced reciprocal translocations and Robertsonian translocations are observed in 2% to 5% of couples with recurrent miscarriage r3
More controversial studies for the workup of an underlying cause can include: r1
Luteal phase progesterone
Sperm DNA for aneuploidy and fragmentation
HLA typing for alloimmune disorders
Endocervical cultures for infectious agents
Evaluation of specific conditions
Structural issues of cervix or uterus
Preferred imaging options include MRI pelvis, 3-dimensional pelvic ultrasonography, and ultrasound sonohysterography r22
Sonohysterography is a sensitive, specific, and accurate screening tool for assessing abnormalities of uterine cavity; avoids radiation r1
MRI and 3-dimensional ultrasonography can better characterize congenital anomalies as they provide full view of uterus r6r22
The role of fluoroscopy hysterosalpingography is controversial but may be appropriate in some patients r22
Diagnostic hysteroscopy is the gold standard for uterine cavity evaluation but more invasive r6
Intrauterine adhesions may be noted on hysterosalpingogram or sonohysterography; diagnosis best confirmed by hysteroscopy r1
No absolute test for definitive diagnosis of cervical incompetence r1
History of second trimester pregnancy loss without contractions or labor and absence of other clear cause (eg, bleeding, infection, ruptured membranes) aids in diagnosis
Cervix may be noted to be unexpectedly dilated on midtrimester ultrasonography
Sonographic measurements of cervical length can help distinguish patients that may benefit from cervical cerclage r1
Medical conditions
Endocrine causes
Progesterone deficiency (luteal insufficiency)
Difficult to diagnose; measurement of serum progesterone level in luteal phase is unreliable owing to pulsatile nature of release, and endometrial biopsy is of limited value owing to significant inter- and intraobserver variability r1
Luteal phase deficiency has not been proven to be an independent cause of recurrent pregnancy loss r23
Thyroid disease can be initially screened with TSH levels r6r8
TSH measurement alone is sufficient for screening purposes or to exclude hypothyroidism
Obtain serum-free thyroxine with the initial draw if suspicion is strong or if initial TSH level is outside reference range
Testing for thyroid peroxidase antibodies may be warranted r9
Prolactin levels may be measured to detect hyperprolactinemia
Diabetes is diagnosed with laboratory assessment of blood glucose;r7short-term glycemic status can be evaluated by testing hemoglobin A1Cr7d2
Immunologic factors
Alloimmune disorders: testing is not clinically indicated, as there is no current therapy
Antiphospholipid syndrome: diagnosis requires 1 of the following clinical and 1 of the following laboratory criteria to be met: r13
Clinical criteria for laboratory testing of antiphospholipid antibodies:
Vascular thrombosis (arterial, venous, or small vessel) in any tissue or organ, or
Pregnancy morbidity
1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasonogram or direct fetal examination) at or beyond 10th week of gestation, or
1 or more premature births of morphologically normal neonate before 34 weeks of gestation owing to eclampsia, severe preeclampsia, or features consistent with placental insufficiency, or
3 or more unexplained consecutive spontaneous losses before 10th week of pregnancy, with
Laboratory tests, obtained on 2 or more occasions, at least 12 weeks apart
Lupus anticoagulant (ideally performed before treatment with anticoagulants)
Anticardiolipin antibody of immunoglobulin G and/or immunoglobulin M isotype
Anti–β₂-glycoprotein I of immunoglobulin G and/or immunoglobulin M isotype
Celiac disease or gluten intolerance: test patients with personal or family history of celiac disease or gluten intolerance and miscarriage for antigliadin and antiendomysial antibodies r1
Inherited thrombophilias
Routine testing for inherited thrombophilias is not recommended in patients with recurrent pregnancy loss; no clear evidence of association and treatment (eg, heparin) benefit r1
May be useful in patients with personal history of venous thromboembolism in nonrisk setting or with first-degree relative with known or suspected high-risk thrombophilia r3
Infection
Routine testing for infectious agents in patients with recurrent pregnancy loss is not recommended owing to lack of prospective studies linking any agent with loss r1
Some clinicians test patients with recurrent pregnancy loss for common pathogens (eg, Mycoplasma, Ureaplasma, Chlamydia) owing to association with sporadic pregnancy losses and ease of diagnosis r7
Laboratory
Miscarriage (for diagnosis)
β-hCG
Levels should rise predictably in normally developing pregnancy
Minimal increase of 24% in 24 hours and 53% in 48 hours r1
Peak around 100,000 international units at 10 weeks; steepest rate of increase seen within first 6 weeks, followed by slower rise and eventual fall after peak r1
Leukocytosis may be sign of septic abortion
Recurrent pregnancy loss (for evaluation of underlying cause/contributing factor)
TSH
If TSH level is outside reference range (varies by laboratory), follow with assessment of peripheral thyroid hormone levels
Generally (as a simplification) elevated TSH levels may reflect primary hypothyroidism, whereas undetectable TSH levels may reflect hyperthyroidism
Repeat test to confirm result if levels are outside reference range r6
Elevated (positive) thyroperoxidase antibody status is associated with increased likelihood of developing hypothyroidism in gestation r24
Thyroperoxidase antibody positivity was associated with a reduced live birth rate in a large cohort of patients with recurrent pregnancy loss r9
Antiphospholipid antibodies
In addition to clinical features, diagnosis of antiphospholipid syndrome requires the following results confirmed on 2 or more occasions, at least 12 weeks apart: r13
Lupus anticoagulant present in plasma, or
Anticardiolipin antibody (IgG or IgM isotype) in serum or plasma present in medium or high titer (ie, greater than 40 GPL or MPL, or greater than 99th percentile), or
Anti–β₂-glycoprotein I antibody (IgG or IgM isotype) in serum or plasma in titer greater than 99th percentile
Hemoglobin A1C
Elevated levels (especially greater than 8%) are associated with increased risk of miscarriage r6
Prolactin
Elevated levels (hyperprolactinemia) are associated with increased risk of miscarriage r6
If elevated levels are found, pursue further testing to determine underlying cause
Imaging
Transvaginal ultrasonography
Primary imaging modality in evaluating first trimester vaginal bleeding r25
Pregnancy evaluation
Gestational sac is first sonographic evidence of intrauterine pregnancy r25
Small, spherical fluid collection with hyperechoic rim located within endometrium r25
Gestational sacs only 2 to 3 mm in mean sac diameter, corresponding to 4.5 to 5 weeks of gestation, may be seen using high-frequency vaginal transducer r25
Pseudogestational sac (fluid in endometrial cavity) can usually be differentiated from gestational sac based on shape (acute angle at edge), contents (internal echoes), or location (in endometrial cavity) r25
Discriminatory level of hCG: level at which gestational sac should be visualized on transvaginal ultrasonography
β-hCG of 1500 international units (range, 1000-2000 milliunits/mL)r4 traditionally accepted as level at which transvaginal ultrasonography should reveal intrauterine gestational sac; use of this data point is under discussion r1
These values may be too low to exclude a normal intrauterine pregnancy r25
American College of Radiology Appropriateness Criteria state that if there is no transvaginal ultrasonographic evidence of a gestational sac when single serum hCG level is 3000 milliunits/mL or higher, it is unlikely there will be a viable intrauterine pregnancy r25
Yolk sac is first sonographic feature confirming intrauterine pregnancy r25
Thin-walled, spherical structure with anechoic center usually seen within gestational sac greater than 8 mm in mean sac diameter; in some normal pregnancies, gestational sac may be larger before yolk sac visualized
Embryo first appears as thickened, linear echogenic structure at edge of yolk sac r25
Typically seen by 6 weeks of gestational and by the time gestational sac has reached 16 mm mean sac diameter, though it may be larger in some normal pregnancies before it can be visualized
Diagnose a nonviable intrauterine pregnancy if mean sac diameter is 25 mm or more and no embryo is visible with technically adequate transvaginal ultrasonography r25
Only a minority of nonviable pregnancies have diameter this large; criteria are set high to maximize diagnostic certainty and avoid inadvertent harm to viable embryo
Cardiac activity is normally evident in an embryo of any crown-rump length r25
Initial fetal heart rate should be in a range of 80 to 100 beats per minute; will often increase into 180 to 220 beats per minute for first few months, but should return to 110 to 160 beats per minute by 12 weeks r1
Findings suggestive of (but not diagnostic for) pregnancy loss generally require follow-up transvaginal ultrasonography in 7 to 10 days to assess pregnancy viability. These findings include: r26
No heartbeat in embryos with crown-rump length less than 7 mm
Mean sac diameter of 16 to 24 mm and no embryo
Absence of embryo with heartbeat 7 to 13 days after scan showing gestational sac without yolk sac
Absence of embryo with heartbeat 7 to 10 days after scan showing gestational sac with yolk sac
Absence of embryo 6 or more weeks after last menstrual period
Empty amnion (amnion seen adjacent to yolk sac, with no visible embryo)
Enlarged yolk sac (greater than 7 mm)
Small gestational sac relative to size of embryo (less than 5 mm difference between mean sac diameter and crown-rump length)
Criteria for diagnosis of pregnancy loss (by transvaginal ultrasonogram) r25r26
Mean sac diameter of 25 mm or more with no embryo
Crown-rump length of 7 mm or more with no heartbeat
Absence of embryo with heartbeat 2 weeks or more after ultrasonogram showing gestational sac without yolk sac
Absence of embryo with heartbeat 11 days or more after ultrasonogram showing gestational sac with yolk sac, but no embryo
Subchorionic hematoma
Fairly common finding during first trimester; usually small and not considered to substantially increase risk of nonviable pregnancy r25
Visualized as lucency behind brighter placental disk
Large subchorionic hematomas (two-thirds or more of gestational sac circumference) may be associated with increased risk of nonviable pregnancy r25
Cervical evaluation
Typical cervical length is about 3.5 cm or greater r1
Cervical shortening is a marker of preterm birth rather than cervical insufficiency; however, cerclage may be beneficial in patients with short cervix r1
Pregnancy occurring outside the uterine cavity, most commonly in the fallopian tube
Similar to threatened miscarriage in early pregnancy, can present with abdominal or pelvic pain, vaginal bleeding, and history of delayed or absent menses
Consider in any patient who has abdominal pain or vaginal bleeding and a positive pregnancy test result r4
Patients with hemodynamic instability or an acute abdomen are evaluated and treated urgently
Patient may have palpable adnexal mass or suggestive history (eg, ectopic pregnancy, tubal surgery, assisted reproductive techniques, pelvic inflammatory disease, endometriosis, intrauterine device use)
Diagnostic evaluation includes transvaginal ultrasonographic evaluation and hormonal confirmation of pregnancy (eg, serum hCG level) r27
Serial evaluation with transvaginal ultrasonography, serum hCG levels, or both, is often required to confirm diagnosis
Ectopic pregnancy in an unstable patient is a medical emergency and requires prompt surgical intervention
Implantation bleeding
Small amount of bleeding may occur during implantation of blastocyst into endometrium and at the time of first missed menses
Bleeding from implantation is scant, is lighter colored without clots, and lasts only a few hours to a few days, whereas bleeding associated with an impending miscarriage typically turns heavy with a dark color and visible clots r28
If needed, serial serum hCG levels can be used to distinguish between the two
If bleeding is simply due to implantation, β-hCG levels will continue to rise predictably as in a normally developing pregnancy, whereas levels will decline with miscarriage r1
Premalignant form of gestational trophoblastic disease occurring when a nonviable fertilized ovum implants in the uterus and develops into a placenta-derived tumor r29
Similar to threatened miscarriage; characterized by first trimester vaginal bleeding
Differences can include uterine enlargement and level of hCG greater than expected for gestational age
Diagnosis is suspected on basis of initial total serum hCG levels greater than 80,000 milliunits/mL and characteristic ultrasonographic appearance; histopathologic evaluation is required for definitive diagnosis
Collection of blood between chorion and uterine wall formed from bleeding at advancing margin of expanding placenta
Can cause first trimester vaginal bleeding
Small subchorionic hemorrhages are usually asymptomatic
Identified by ultrasonography
Treatment
Goals
Terminate bleeding
Alleviate pain
Complete evacuation of nonviable fetus
Prevent recurrence
Disposition
Admission criteria
Patients with significant hemorrhage, hemodynamic instability, or signs of infection
Recommendations for specialist referral
Refer to obstetrician/gynecologist for evaluation and management
Refer patients with chromosomal abnormalities to genetic counselor
Consider referral to endocrinologist for assistance with managing thyroid disease in pregnancy
Treatment Options
Miscarriage
For patients with severe bleeding or hemodynamic instability, initiate immediate IV fluid resuscitation and/or blood transfusion; prepare for emergent surgery
Threatened miscarriage
Administer Rho(D) immunoglobulin if patient is Rh-negative r1
No medical interventions exist to improve prognosis r1
No benefit to initiating progesterone when patient develops symptoms of threatened abortion; in early gestation (before 7 weeks), low progesterone levels are a result of, not cause of, the abortion r1
Treat cramping with analgesics, if needed
Patient may be discharged with follow-up if stable and if ectopic pregnancy is excluded r4
Timing of follow-up for ultrasonography and serial hCG levels made in conjunction with obstetrician
If intrauterine pregnancy has not been identified, potential for ectopic pregnancy still exists (eg, hCG level too low for sonographic identification or findings do not include fetal pole or yolk sac)
Discharge instructions include return instructions for significant bleeding, signs of hemodynamic instability, or severe pain
Moderate daily activities will not affect pregnancy
Avoid tampons, intercourse, and other activities that could induce uterine infection while patient is bleeding
Instruct patient to bring any tissue passed to provider to be examined for products of conception
Advise patient that miscarriage is common, grieving is normal, and counseling may be beneficial
Reassure patient that they have done nothing to cause miscarriage (eg, minor falls, injuries, stress)
Diagnosed miscarriage (nonviable fetus)
First, confirm early pregnancy loss before initiating treatment; failure to do so may have detrimental consequences (eg, interruption of normal pregnancy, pregnancy complications, birth defects) r2
Treatment options include expectant management, medical treatment, and surgical evacuation of uterus r19
Patient preference guides choice of intervention, established after discussion of various options
No single treatment option is superior to others (provided there are no associated medical complications or symptoms requiring urgent surgical evacuation) r2
A Cochrane review concluded that medical treatment with misoprostol and expectant care are both acceptable alternatives to surgical evacuation, provided sufficient health care services are available to support all approaches r30
All options usually result in complete evacuation of pregnancy tissue and serious complications are rare r2
Administer Rho(D) immunoglobulin to patients who are Rh-negative and not sensitized
Within 72 hours of diagnosis of early pregnancy loss with planned medical or expectant management r2
Immediately after surgical management of early pregnancy loss
Treatment alternatives
Expectant management
Option for patients without evidence of infection, hemorrhage, anemia, or bleeding disorder
Data suggest expectant management may be more effective in patients who are symptomatic (tissue is passed, ultrasonogram shows incomplete expulsion) than in those who are asymptomatic r2
In a study comparing expectant management with vaginal misoprostol treatment, expectant management was more likely to be successful in embryonic miscarriage than in anembryonic miscarriage r31
Likelihood of complete expulsion increased with increasing gestational age, increasing crown-rump length, and decreasing gestational sac diameter r31
50% to 70% of patients choose expectant management r1
About 80% of patients successfully achieve complete expulsion given adequate time (up to 8 weeks) r2
25% to 85% of miscarriages spontaneously resolve within 2 weeks, 37% of those within 7 days r1
Counsel patient to expect cramping and moderate to heavy bleeding, and instruct patient on when and whom to call for excessive bleeding r2
Suggested reference for excessive bleeding is soaking of 2 maxi pads per hour for 2 consecutive hours
Compared with surgical treatment, expectant management has higher risk of incomplete miscarriage, bleeding, and need for unplanned (or additional) surgical evacuation of uterus and for transfusion; similar psychological outcomes and risk of infection r32
Counsel patient that surgery may be indicated if complete expulsion is not achieved r2
Medical therapy
Consider for eligible patients who wish to shorten time to complete expulsion and avoid surgical evacuation r2r33
Must be without known or suspected infection, hemorrhage, severe anemia, or bleeding disorder
Typically administered vaginally to expedite expulsion of products of conception
Reduces need for uterine curettage and shortens time to complete expulsion compared with placebo r2
Most patients (80%-90%) completely expel a first trimester loss after 1 or 2 doses r1
71% of patients expel loss by day 3 after single vaginal dose; 84% after second dose of 800 mcg of vaginal misoprostol r34
No baseline clinical characteristics appear to predict treatment success r35
Addition of mifepristone (synthetic steroid) improves treatment efficacy and reduces need for subsequent evacuation r35r36
Consider adding oral dose of mifepristone 24 hours before administering misoprostol (if available) r2r19
Pretreatment with mifepristone before misoprostol was found to be superior to misoprostol alone in managing early pregnancy loss r37r38r39
Counsel patient to expect cramping (potentially severe) and moderate to heavy bleeding, and instruct patient on when and whom to call for excessive bleeding; inform patient that surgery may be indicated if complete expulsion is not achieved r2
Provide adequate analgesia
Administer Rho(D) immunoglobulin to patients who are Rh-negative and not sensitized within 72 hours of first misoprostol dose r2
If misoprostol fails, patient may choose expectant management (in consultation with gynecologist to determine timing) or suction curettage r2
Surgical evacuation of uterus
Treat patients with hemorrhage, hemodynamic instability, or signs of infection urgently with surgical uterine evacuation r2
May be preferable in other situations, such as medical comorbidities (eg, severe anemia, bleeding disorders, cardiovascular disease); may also be preferred by patients who desire an immediate completion with less follow-up r2
Results in faster and more predictable complete evacuation than expectant or medical management; success rate approaches 99% r2
Suction curettage using either electric vacuum apparatus or via manual vacuum aspiration is preferred method r2r19r40
May be performed in outpatient setting using local anesthesia with or without additional sedation
Well tolerated and achieves complete evacuation in the majority of patients r40r41
Sharp curettage adds little once complete suction evacuation of uterus has been performed, and is generally avoided completely owing to lack of any demonstrative benefits and potential for harms (eg, perforations, adhesions)
Administer single preoperative dose of doxycycline to prevent infection r2
If contraception with intrauterine device is desired after miscarriage, it may be placed immediately after surgical treatment (provided septic abortion is not suspected)
After complete passage of pregnancy tissue, recommend patient abstain from vaginal intercourse for 1 to 2 weeks to reduce risk of infection r2
Evaluation of conceptus
Offer cytogenic evaluation of conceptus with recurrent pregnancy loss (3 or more) r1
Miscarriage of aneuploid fetus is more likely to be a random event; may preclude unnecessary further evaluation and suggest greater likelihood of success in future pregnancy
Perform evacuation of uterus within 2 hours of initiation of antibiotics r1
Consider hysterectomy in patients with severe sepsis or if uterus cannot be evacuated through cervix r1
Recurrent pregnancy loss
Treatment is based on cause, if identified, and should be corrected before attempting subsequent pregnancy r7
Treatment of uterine anomalies
Septate uterus
Hysteroscopic septoplasty is treatment of choice; laparotomy reserved for exceptional and complicated anomalies r1r42
Bicornuate uterus
Transfundal metroplasty technique may achieve unification r1
Cervical cerclage (placement of a suture to support and partially occlude cervix) is effective in bicornuate uterus to prevent preterm delivery; also helpful in unicornuate uterus r43
Incompetent cervix
Serial transvaginal ultrasonographic monitoring from 16 weeks of gestation until end of 24 weeks for patients with risk of cervical insufficiency; can avoid placement of history-indicated cerclage in more than one-half of patients r1
Cervical cerclage reduces risk for preterm labor due to cervical insufficiency
Abdominal myomectomy can significantly reduce rate of spontaneous abortion; best indicated for patients with recurrent miscarriage than a single loss r1r42
Hysteroscopic lysis of adhesions; after lysis, a mechanical barrier (eg, balloon catheter) is often placed in cavity for 10 days r1r42
Postoperative administration of high-dose estrogen can promote reepithelialization and reduce risk of recurrent adhesions
Treatment of medical conditions
Endocrine issues
Thyroid disorders
Treat overt hyperthyroidism or hypothyroidism prior to conception r24r42d5
Treatment with levothyroxine may be considered in patients with subclinical hypothyroidism and presence of thyroid autoantibodies r24r44r45d5
Treatment of subclinical hypothyroidism in patients without evidence of thyroid autoimmunity does not appear beneficial r44
In patients treated for hypothyroidism, it is reasonable to adjust levothyroxine dose during pregnancy to target lower half of trimester-specific range for TSH values; requires escalating doses throughout pregnancy under the guidance of endocrinologist r24r46
Hyperprolactinemia
Very limited data suggest that a trial of bromocriptine can normalize prolactin levels before pregnancy in patients with history of 2 or more pregnancy losses, which may improve rate of successful pregnancy r47
Abnormal glucose metabolism
Optimize glycemic control in patients with diabetes r48d6
Role of metformin is uncertain
Has not been shown to reduce risk of sporadic miscarriage in patients with polycystic ovarian syndrome r42r44
When used to treat polycystic ovary syndrome and induce ovulation, metformin should be discontinued by the end of the first trimester r48
Some evidence suggests may reduce risk of recurrent miscarriage r7
Obesity
Encourage weight loss in patients with elevated BMI r42
Immunologic factors
Alloimmune disorders
There are no current immunotherapies available for patients with recurrent miscarriages r1
A Cochrane review concluded that paternal cell immunization, third-party donor leukocytes, trophoblast membranes, and IV immunoglobulin provide no significant beneficial effect over placebo in improving live birth rate r49
Antiphospholipid syndrome
Treat patients with documented antiphospholipid syndrome with daily low-dose aspirin (81 mg) and prophylactic low-molecular-weight heparin or unfractionated heparin; initiate with positive pregnancy test result r42r45r50
Shown to decrease pregnancy loss and increase live birth rate; however, evidence of benefit is of low certainty r51
Continue for minimum of 6 weeks postpartum (to minimize risk of maternal thromboembolism) r13
Antepartum prophylactic use of anticoagulants, aspirin, or both has not been proved to reduce risk of early pregnancy loss;r2 however, low-molecular-weight heparin is often used to prevent complications, owing to the absence of other effective treatmentsr52r53
Infection
Empiric antibiotic treatment of infectious agents in patients with recurrent pregnancy loss is not indicated, owing to lack of prospective studies linking any agent with recurrent loss r1
If acute infection is identified, initiate appropriate antibiotic therapy in both parents r7
Several options are available to detect genetic abnormality in offspring when 1 partner carries a structural genetic abnormality: r1r3
Chorionic villus sampling
Amniocentesis
In vitro fertilization with preimplantation genetic testing r1
Allows for diagnosis of specific translocations and transfer of only unaffected embryos; success rate of live births compared with natural conception and observation remains lower
Routine preimplantation genetic testing is not currently recommended for couples with recurrent pregnancy loss and structural genetic abnormality (eg, deletions, duplications, translocations)
No identifiable cause
Accounts for about 50% of patients with recurrent pregnancy loss r1
Consider administration of exogenous progesterone in early pregnancy to patients with 3 or more unexplained consecutive miscarriages; not recommended in patients with sporadic miscarriage r1
There is evidence that supplementation with synthetic progestogens may prevent miscarriage in subsequent pregnancies in patients with history of unexplained recurrent miscarriages r54r55r56
Counseling and emotional support during early pregnancy has been shown to increase live birth rate in couples with unexplained recurrent miscarriage r1
Aspirin, with or without heparin, has no established role in preventing unexplained recurrent pregnancy loss r57
One study showed low-dose aspirin was associated with fewer pregnancy losses among patients who had experienced 1 to 2 prior losses when initiated prior to conception and continued throughout pregnancy r58
Immunomodulatory therapies, such as corticosteroids, intravenous immunoglobulin, alogeneic lymphocyte transfer, lipid infusions, or tumor necrosis factor-α blockers, may be considered in the context of clinical studies r12
Vaginal route preferred to maintain steady serum levels and to avoid gastrointestinal adverse effects.
Misoprostol Oral tablet; Adult females: As an alternative to traditional management, such as surgical or expectant management, misoprostol has shown efficacy and safety in women <= 13 weeks gestation with indicators of pregnancy failure. 800 mcg intravaginally (placed into the posterior vaginal fornix) on day 1, followed by a repeat dose on day 3 if expulsion incomplete. Follow by vacuum aspiration on day 8 if expulsion still incomplete.
Mifepristone Oral tablet [Pregnancy Termination]; Adult and Adolescent pregnant females through 70 days (10 weeks) gestation: On day 1, administer one 200 mg mifepristone tablet PO as a single dose. Between 24 to 48 hours later, administer misoprostol 800 mcg buccally; the patient should place two 200 mcg misoprostol tablets in each cheek pouch for 30 minutes and then swallow any remnants with water or another liquid. Expulsion typically occurs within 2 to 24 hours. Patients should be given emergency healthcare contact numbers and a follow-up visit should occur approximately 7 to 14 days after mifepristone administration. If complete expulsion has not occurred, but the pregnancy is not ongoing, may give additional misoprostol 800 mcg buccally, then another visit approximately 7 days later.
For loss of pregnancy during first trimester (12 weeks of gestation or less) r4
Rho(D) Immune Globulin (Human) Solution for injection; Adult and adolescent females: 50 mcg (250 International Units) IM as soon as possible. Give within 3 hours of spontaneous or surgical removal of aborted tissues, if possible, and within 72 hours of exposure.
Rho(D) Immune Globulin (Human) Solution for injection; Adult and adolescent females: 300 mcg (1,500 International Units) IM as soon as possible and within 72 hours of the event.
Consider in patients who have had 3 or more consecutive miscarriages. r1
Available as vaginal suppository (50-100 mg twice dailyr7) to begin 3 days after ovulation and continued throughout first trimester. r1
Vaginal suppository
Progesterone Vaginal insert; Adult females: 100 mg PV 2 to 3 times per day starting the day after oocyte retrieval and continuing for up to 10 weeks total duration. In women 35 years and older, the appropriate dosage for efficacy has not been definitively determined.
For prophylaxis in antiphospholipid syndrome; initiated with positive pregnancy test result.
Heparin Sodium (Porcine) Solution for injection; Adult females: Usually 5000 to 10,000 units by subcutaneous injection every 12 hours given along with aspirin 81 mg PO daily. r1
For normalization of prolactin levels before pregnancy in patients with history of 2 or more pregnancy losses. r6
Bromocriptine Mesylate Oral tablet; Adults and Adolescents 16 years and older: Initially, 1.25 mg to 2.5 mg PO daily with food, with titration of 2.5 mg/day PO at 2 to 7 day intervals as needed until the desired therapeutic response occurs; individualize. In amenorrheic or infertile patients without demonstrably elevated serum prolactin levels, the usual dose is 2.5 mg PO twice daily (with food). Usual dosage range: 2.5 mg to 15 mg/day PO, in divided doses. Max: 30 mg/day PO, in divided doses, may be necessary for some patients.
Nondrug and supportive care
Follow-up care after early pregnancy loss
Essential part of care for patients with miscarriage
Discuss and implement plans for future pregnancy
Delaying conception after early pregnancy loss has no significant evidence for decreasing risk of subsequent miscarriage r1r2
If contraception is desired and appropriate, hormone-based contraception may be initiated immediately after completion of early miscarriage r2
Encourage patients to stop smoking and refrain from drinking alcohol during pregnancy
Recommend limiting caffeine intake to patients who become pregnant r1
Avoid contact with environmental toxins (eg, anesthetic gases and chemotherapeutic agents for hospital personnel, organic solvents, organic pesticides, heavy metals, lead, cadmium, mercury, arsenic)
For patients with elevated lead levels, treat with chelation therapy before pregnancy; can be used during pregnancy as well r1
Recommend weight reduction in obese patients
Encourage counseling for depression associated with recurrent loss
Emotional/psychological care
Ask patient open-ended questions about experience and thoughts to assess mood and status r1
Anger or difficulty with health care system during time of miscarriage: managing these frustrations can improve future interactions and may decrease risk of depression after loss
Guilt: many patients feel the loss was something they caused by some action they performed; reassure that exercise, intercourse, and dietary indiscretions do not cause miscarriage r7
Grieving and depression: grieving may cause physical symptoms of depression (eg, fatigue, anorexia, sleeplessness, headache, back pain); depression can affect up to 30% of patients after miscarriage r1
Advise patients to return if symptoms occur
Depression may be treated with counseling and antidepressant therapy
For couples with recurrent pregnancy loss, explanation and appropriate emotional support are important aspects of treatment c72
Consider testing for cause after 2 or more miscarriages;r1unexplained reproductive failure can lead to anger, guilt, and depressionr7
Antenatal counseling and psychological support are shown to increase success rates for couples with recurrent pregnancy loss r7
History of second trimester pregnancy loss without contractions or labor and absence of other clear cause (eg, bleeding, infection, ruptured membranes)
Elective placement at 12 to 14 weeks of gestation is recommended
Consider in patients with singleton pregnancy, history of spontaneous preterm birth at less than 34 weeks of gestation, and cervical length less than 25 mm before 24 weeks of gestation
Examination-indicated cerclage (emergency or rescue cerclage) r1
Cervical dilation found on digital or speculum examination at less than 24 weeks of gestation
Cervical lacerations with hemorrhage, if labor occurs
Interpretation of results
Fetal survival rates increase from 20% to 80% with cerclage when strict criteria are used to diagnose cervical incompetence (only slight increase if criteria are less certain) r1
Follow-up depends on diagnosis and specific approach to management taken
Monitor patients at risk for cervical insufficiency with serial ultrasonographic examination from 16 weeks of gestation to end of 24 weeks r1
Patients treated with expectant or medical management for miscarriage require follow-up within 1 to 2 weeks to establish that passage of tissue is complete r2
Ultrasonography is typically used to document absence of (and presumed passage of) gestational sac previously seen
Endometrial thickness less than 30 mm is also a commonly used criterion to indicate complete expulsion of pregnancy tissue; however, in asymptomatic patients, there is no evidence of increased morbidity if endometrium is thicker r2
Surgical intervention is not required in asymptomatic patients with thickened endometrial stripe after treatment of early pregnancy loss
Consider patient-reported symptoms, such as passage of tissue and resolution of vaginal bleeding and pelvic cramping
Standardized follow-up phone calls, urine pregnancy tests, or serial quantitative β-hCG values may also be useful, especially for patients with limited access to ultrasonographic evaluations r2
Reversion to negative pregnancy test result may take several weeks r4
Insufficient studies exist to provide meaningful guidance for using these approaches
For patients treated for hypothyroidism during pregnancy, obtain thyroid function tests 30 to 40 days after initial normalization of TSH level (to less than 2.5 milliunits/L), then every 4 to 6 weeks after r46
In patients with thyroid autoimmunity who are euthyroid in early pregnancy, monitor every 4 to 6 weeks for TSH level elevation owing to higher risk for developing hypothyroidism r24
Complications and Prognosis
Complications
Physical
Uterine retention of aborted fetus beyond 5 weeks can be associated with consumptive coagulability and hypofibrinogenemia r1c76c77
Often associated with emotional and psychological morbidity c81
Includes increased risk of anxiety, depression, posttraumatic stress disorder, and suicide r62
Couples experiencing miscarriage have increased risk for relationship failure compared with couples with live births r1
Prognosis
Miscarriage
Bleeding may occur in 30% to 40% of pregnancies during the first 20 weeks of gestation; about 50% of these will ultimately result in miscarriage r1
Patients who do not miscarry are slightly more apt to deliver preterm or have fetal anomalies
About two-thirds of patients with bleeding will have live fetus on ultrasonographic examination; nearly 85% of these patients go on to deliver live-born infant r1
Rate of loss by fetal development on ultrasonogram r1
Gestational sac visualized:11.5%
Embryonic cardiac activity at 6 weeks: 6% to 8%
Cardiac activity persistent at 8 to 12 weeks: 2% to 3%
Septic abortion fatality rate is 0.4 to 0.6 per 100,000 spontaneous abortions r1
Most patients will have successful pregnancy after a miscarriage, even without intervention r1
If no cause for recurrent loss is identified after complete evaluation, 65% of patients have successful subsequent pregnancy r7
Patients with recurrent losses who seek treatment have good prognosis; over 80% of patients younger than 30 years and 60% to 70% of patients aged 31 to 40 years achieve successful pregnancy within 5 years of first visit to physicianr1
Miscarriage, especially recurrent miscarriage, indicates risk for obstetric complications, such as preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies r62
Miscarriage may be a marker for future maternal illness; recurrent pregnancy loss in particular is associated with an increased risk of premature mortality, mainly from cardiovascular disease r63
Screening and Prevention
Prevention
There are no effective interventions to prevent early pregnancy loss r2
Bed rest, pelvic rest, vitamin supplementation, uterine relaxants, and β-hCG have not been proved to prevent miscarriage
Patients who have experienced 3 or more prior pregnancy losses may benefit from progesterone therapy in first trimester r2c82
Decreasing risk for miscarriage
Treatment is based on cause, if identified, and should be corrected before attempting subsequent pregnancy; for example: r7
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