Abortion
Synonyms and keywords:Pregnancy loss, miscarriage, spontaneous abortion

# Overview
Abortion is the termination of pregnancy before 20 weeks of gestation, which was first described by an ancient Egyptian medical text as the Ebers Papyrus in 1550 BCE. Abortion is classified as threatened, complete, incomplete, inevitable, septic or missed. Chromosomal abnormalities is the most common cause of sporadic abortion that occur as early as 4-8 weeks gestation, or it could be due to either infectious, immunologic, and environmental factors. Fetal causes of abortion are genetic or chromosomal abnormalities while maternal causes include age, antiphospholipid syndrome, severe hypertension, or systemic lupus erythematosus (SLE). Risk factors for abortion include non-modifiable risk factors like advanced age >35 years and previous pregnancy loss. Modifiable risk factors include obesity, infections, acute and chronic stress, medication and substance use, cocaine, alcohol, tobacco and caffeine. Complications of abortion include infection, post abortion traid, uterine perforation, septic abortion, cervical shock, cervical laceration, and disseminated intravascular coagulation (DIC). The prognosis of abortion depends on the gestational age. The younger the gestational age, the lower the risk of complications.

# Historical Perspective
- Abortion means termination of a pregnancy and it has been known since ancient times.
- Abortion was first described by an ancient Egyptian medical text as the Ebers Papyrus in 1550 BCE, which suggested that an abortion can be induced with the use of a plant-fiber tampon coated with honey and crushed dates.
- During the ancient Egyptian, Persian, and Roman eras, abortion was practiced although it was never explicitly mentioned in any book of the Judeo-Christian Bible.
- In the fourth century BCE, Niddah 23a, a chapter of the Babylonian Talmud, reviews abortion as determining whether a woman is "unclean" and permitting abortion during early pregnancy.
" A woman can only abort something in the shape of a stone, and that can only be described as a lump."
- In 11th century BCE, the Code of Assura, '' a harsh set of laws restricting women in general'' was the earliest legal ban on abortion by forcing the death penalty on married women who obtain abortions without permission of their husbands.
- In the fifth century BCE, the Hippocratic Oath prohibited physicians from inducing elective abortions.
- In the 19th century, surgical abortions became common and Hegar dilator in 1879 invented dilation-and-curettage (D&C).
- On November 18, 1920, the Commissariats of Health and Justice legalized abortion in Soviet hospitals.
- In 1970, Hawaii, New York, Alaska and Washington declared their abortion laws. Hawaii was the first state to legalize abortions and New York allowed abortions up to the 24th week of pregnancy.

# Classification
Abortion can be classified into the following: 

# Pathophysiology
- Chromosomal abnormalities is the most common cause of sporadic abortion that occurs as early as  4-8 weeks gestation, for instance aneuploidy, mosaicism, translocation, inversion, deletion, or fragile sites.
- First-trimester pregnancy loss could be due to either infectious, immunologic, and environmental factors.
- Immunologic factors is not well defined. Several theories suggest that early pregnancy loss could be due to: 
Allogeneic factors.
Lack of the immunological protection of the embryos, such as complement regulatory proteins (eg, mannose-binding lectin, and HLA-DR, HLA-G or HLA-E)
Increased activity of uterine natural killer (uNK) cells.
Alloimmunization to blood group antigen P.
- Allogeneic factors.
- Lack of the immunological protection of the embryos, such as complement regulatory proteins (eg, mannose-binding lectin, and HLA-DR, HLA-G or HLA-E)
- Increased activity of uterine natural killer (uNK) cells.
- Alloimmunization to blood group antigen P.
- Anatomic distortion of uterus may be associated with early or second trimester pregnancy loss, eg: fibroids, polyps, adhesions, or septa depending on the size and position.
- The mechanism of pregnancy loss due to septate uterus is not clearly understood, one theory suggests that poor blood supply to the septum leads to poor implantation.
- FXIII and fibrinogen play an essential role in placental implantation and maintenance of pregnancy, that is why a deficiency of factor XIII (FXIII) and fibrinogen are associated with pregnancy loss.
- It is thought that miscarriage risk is associated with low plasma levels of the hormone kisspeptin.
- The mechanism of abortion in cases of PCOS is unknown, however it could be related to elevated serum luteinizing hormone (LH) levels, high testosterone and androstenedione concentrations or insulin resistance

# Causes
Early Pregnancy Loss
Fetal causes:
- Genetic or  chromosomal  abnormalities (45,X karyotype,  Trisomies (Trisomy 16 is the most common), aneuploidy, mosaicism, translocation, inversion, deletion, fragile sites)
- Teratogenic and mutagenic factors.
Maternal causes:
- Genetic: Maternal age is directly related to the aneuploidy risk,
- Parental chromosomal anomaly balanced translocation
- Corpus luteum deficiency
- Active infection such as  rubella virus, cytomegalovirus
- Antiphospholipid syndrome
- Severe hypertension
- Systemic lupus erythematosus (SLE)
- Renal disease
- Poorly controlled diabetes mellitus
- Polycystic ovary syndrome

# Differentiating abortion from other Diseases
Abortion should be differentiated from other causes of bleeding with cramping in early pregnancy:
- Related to Pregnancy
Ectopic pregnancy
Subchorionic hematoma
Hydatidiform mole
- Ectopic pregnancy
- Subchorionic hematoma
- Hydatidiform mole
- Unrelated to pregnancy
Infection (cervicitis)
Polyps
Fibroids
- Infection (cervicitis)
- Polyps
- Fibroids

# Epidemiology and Demographics
- The incidence of abortion worldwide was estimated to be  35 per 1,000 women ages 15 to 44 from 2010 to 2014.
- The rate in resource-rich countries was 27 per 1,000 and in resource-limited countries was 37 per 1,000. The incidence was highest in the Caribbean (65 per 1,000), and the lowest in North America (17 per 1,000). 
- In the United States, one in four women will have an abortion during their reproductive life.
- The incidence of abortion is approximately 31%, the true incidence of abortion is difficult to ascertain, as many losses are not recognized
- The rate of abortion is influenced by maternal age and history of prior pregnancy loss. 15% of women experience sporadic abortion, 2% of pregnant women experience two consecutive abortion and only 0.4 to 1% have three consecutive abortion. 
- The incidence of abortions in the United States were highest in women ages 20 to 24 (19.1 per 1,000 women) and 25 to 29 (18.5 per 1,000 women)
- Most abortions were done in women who were unmarried (85%) and had one or more children (59%).
- Abortion rates in individuals of non-Hispanic White were 38.7, 20.0 for Hispanic, and 7.7 for other races per 1,000 women. 
- In the United States in 2018, 78% of abortions occur at 9 weeks or earlier, 92% at 13 weeks or earlier, and 8% at or after 14 weeks.

# Risk Factors
Non-modifiable risk factors include: 
- Advanced age >35 years, the most significant risk factor because of the associated fetal chromosomal abnormalities.
- Extremes of age
- Advanced paternal age
- Previous pregnancy loss increases the risk of later pregnancy loss.
Modifiable risk factors include:
- Obesity
- Infection (eg: Parvovirus B19 infection,syphilis, cytomegalovirus (CMV) infection)
- Pre-gestational diabetes increases the risk of miscarriage two- to threefold.
- Hyper- and hypothyroidism 
- Acute and chronic stress
- Medication and substance use, examples are NSAIDs (ibuprofen and diclofenac), cocaine, methamphetamines
- Alcohol, tobacco and caffeine

# Screening
There is insufficient evidence to recommend routine screening for abortion.

# Natural History, Complications, and Prognosis
- Complications of spontaneous abortion and therapeutic abortions include the following:
Complications of anesthesia
Post abortion triad (pain, bleeding, low-grade fever) caused by retained products of conception.
Retained products of conception
Uterine perforation
Septic abortion
Cervical shock
Cervical laceration
Disseminated intravascular coagulation (DIC)
- Complications of anesthesia
- Post abortion triad (pain, bleeding, low-grade fever) caused by retained products of conception.
- Retained products of conception
- Uterine perforation
- Septic abortion
- Cervical shock
- Cervical laceration
- Disseminated intravascular coagulation (DIC)
- Prognosis of abortion depends on the gestational age. The younger the gestational age, the lower the risk of complications. The highest risk of death is from a septic abortion; the majority of these cases are a result of illegal abortions in developing countries.

# Diagnosis

## Diagnostic Study of Choice
- Ultrasound shows no intrauterine pregnancy or loss of previously seen cardiac activity is diagnostic if the intrauterine pregnancy is confirmed by ultrasound in a previous visit.
- The diagnosis of early pregnancy loss (EPL) occurs if the initial transvaginal ultrasound shows intrauterine pregnancy without fetal cardiac activity and is based on the criteria made by the Society of Radiologists in Ultrasound Multi-specialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy, which include:
A gestational sac 25 mm in mean diameter that does not contain a yolk sac or embryo
An embryo with a crown-rump length (CRL) 7 mm that does not have cardiac activity
After a pelvic ultrasound shows a gestational sac without a yolk sac, absence of an embryo with a heartbeat in 2 weeks
After a pelvic ultrasound shows a gestational sac with a yolk sac, absence of an embryo with a heartbeat in 11 days
Findings that are suspicious for, but not diagnostic of, pregnancy loss include:
CRL <7 mm and no heartbeat.
Mean sac diameter of 16 to 24 mm and no embryo.
Absence of embryo with a heartbeat 7 to 13 days after a scan that showed a gestational sac without a yolk sac
Absence of embryo with a heartbeat 7 to 10 days after a scan that showed a gestational sac  with a yolk sac
Absence of embryo 6 weeks after last menstrual period
Empty amnion (amnion seen adjacent to yolk sac with no visible embryo)
Enlarged yolk sac (>7 mm)
Small gestational sac in relation to the size of the embryo (<5 mm difference between mean sac diameter and CRL)
- A gestational sac 25 mm in mean diameter that does not contain a yolk sac or embryo
- An embryo with a crown-rump length (CRL) 7 mm that does not have cardiac activity
- After a pelvic ultrasound shows a gestational sac without a yolk sac, absence of an embryo with a heartbeat in 2 weeks
- After a pelvic ultrasound shows a gestational sac with a yolk sac, absence of an embryo with a heartbeat in 11 days
- Findings that are suspicious for, but not diagnostic of, pregnancy loss include:
CRL <7 mm and no heartbeat.
Mean sac diameter of 16 to 24 mm and no embryo.
Absence of embryo with a heartbeat 7 to 13 days after a scan that showed a gestational sac without a yolk sac
Absence of embryo with a heartbeat 7 to 10 days after a scan that showed a gestational sac  with a yolk sac
Absence of embryo 6 weeks after last menstrual period
Empty amnion (amnion seen adjacent to yolk sac with no visible embryo)
Enlarged yolk sac (>7 mm)
Small gestational sac in relation to the size of the embryo (<5 mm difference between mean sac diameter and CRL)
- CRL <7 mm and no heartbeat.
- Mean sac diameter of 16 to 24 mm and no embryo.
- Absence of embryo with a heartbeat 7 to 13 days after a scan that showed a gestational sac without a yolk sac
- Absence of embryo with a heartbeat 7 to 10 days after a scan that showed a gestational sac  with a yolk sac
- Absence of embryo 6 weeks after last menstrual period
- Empty amnion (amnion seen adjacent to yolk sac with no visible embryo)
- Enlarged yolk sac (>7 mm)
- Small gestational sac in relation to the size of the embryo (<5 mm difference between mean sac diameter and CRL)

## History and Symptoms
- Constitutional symptoms including  fever or chills, suggesting septic abortion.
- The history should include  when was the date of last menstrual period (LMP), estimated length of gestation, bleeding disorders, previous miscarriage.
- The symptoms that raise suspicion of abortion are:
Vaginal bleeding (the volume of bleeding varies) and suprapubic abdominal cramping (especially during passage of gestational tissue), passage of clot is an important sign.
Loss or reduction of pregnancy symptoms, such as decreased breast tenderness, nausea and vomiting.
- Vaginal bleeding (the volume of bleeding varies) and suprapubic abdominal cramping (especially during passage of gestational tissue), passage of clot is an important sign.
- Loss or reduction of pregnancy symptoms, such as decreased breast tenderness, nausea and vomiting.
- Asymptomatic discovered incidentally or on routine ultrasound in early pregnancy.

## Physical Examination
- Vital signs
Depends on the amount of bleeding, if severe, the patient will be hemodynamically unstable.
- Pelvic examination
Bimanual examination to determine the status of cervix and to estimate the gestational age, adnexal tenderness or masses or cervical motion tenderness to exclude ectopic pregnancy.
Speculum examination to see the source and quantity of bleeding and whether bleeding coming from the cervix and an open cervical os.
Common physical examination findings of threatened miscarriage include vital signs should be within reference ranges, soft and non-tender abdomen, and closed internal cervical os.
Common physical examination findings of incomplete miscarriage include enlarged and soft uterus, dilated and effaced cervix, and products of conception may be partially present in the uterus, at the external os, or may be present in the vagina.
Common physical examination findings of complete miscarriage include a closed cervix, and the uterus should be contracted.
Common physical examination findings of missed miscarriage include normal vital signs, the uterus is small for gestational age, absent fetal heart tones on sonogram and closed cervix.
- Bimanual examination to determine the status of cervix and to estimate the gestational age, adnexal tenderness or masses or cervical motion tenderness to exclude ectopic pregnancy.
- Speculum examination to see the source and quantity of bleeding and whether bleeding coming from the cervix and an open cervical os.
- Common physical examination findings of threatened miscarriage include vital signs should be within reference ranges, soft and non-tender abdomen, and closed internal cervical os.
- Common physical examination findings of incomplete miscarriage include enlarged and soft uterus, dilated and effaced cervix, and products of conception may be partially present in the uterus, at the external os, or may be present in the vagina.
- Common physical examination findings of complete miscarriage include a closed cervix, and the uterus should be contracted.
- Common physical examination findings of missed miscarriage include normal vital signs, the uterus is small for gestational age, absent fetal heart tones on sonogram and closed cervix.

## Laboratory Findings
- Laboratory studies may include the following:
Urine pregnancy test.
Complete blood count with differential, hemoglobin and hematocrit.
Blood type and Rh factor.
- Urine pregnancy test.
- Complete blood count with differential, hemoglobin and hematocrit.
- Blood type and Rh factor.
- Serum hCG and progesterone have limited utility in the diagnostic evaluation of abortion. In general, the diagnosis of pregnancy loss is made by an ultrasound (U/S) once the presence of intrauterine gestational sac is confirmed.
- An intrauterine pregnancy may be seen with (transvaginal ultrasound) (TVUS) at a -hCG level of 1500-2000 IU/L. However, indeterminate pregnancy on TVUS should undergo -hCG level testing and if -hCG  levels 1500, do TVUS again.
- U/S is the most accurate diagnostic modality in the confirmation of a viable pregnancy during the first trimester.
- An empty uterus revealed by U/S in a pregnant woman with positive beta-hCG, suggests a very early pregnancy < 3 wk, a completed miscarriage, or an ectopic pregnancy.

## Electrocardiogram
There are no ECG findings associated with abortion.

## X-ray
There are no x-ray findings associated with abortion.

## Abdominal/ trans-vaginal Ultrasound 
- Findings on an ultrasound suggestive of nonviable pregnancy include gestational sac >25-mm mean sac diameter on transabdominal sonogram; >16-mm MSD on endovaginal sonogram without a detectable embryo, embryo without a heartbeat, hyperechoic material within the uterine cavity.
- An incomplete miscarriage on ultrasound shows gestational sac misshaped or collapsed, an irregular complex mass within the endometrial or cervical canal may be present or echogenic material in the endometrial canal.
- A complete miscarriage may demonstrate an empty uterus noted on transvaginal ultrasound.

## CT scan
There are no CT scan findings associated with abortion. However, a CT scan may be helpful in the diagnosis of complications like uterine rupture.

## MRI
The use of a MRI in maternal emergency obstetric conditions is relatively limited, a MRI has a role where USG is indeterminate, particularly in ectopic pregnancy.

## Other Imaging Findings
There are no other imaging findings associated with abortion.

## Other Diagnostic Studies
There are no other diagnostic studies associated with abortion.

# Treatment

## Expectant management
- Waiting for pregnancy tissue to pass recommended only in the first trimester, after 13 weeks, medication management in a health facility or surgical management should be considered.
- Pain management in the first trimester is typically nonsteroidal anti-inflammatory drugs for pain.
- Follow-up to confirm complete passage of gestational tissue by ultrasound.
- Incomplete uterine emptying still require uterine aspiration.
- Administer RhoGAM to women with Rh-negative and is experiencing vaginal bleeding

## Medical Therapy
- Up to 13 weeks of gestation:
mifepristone followed by misoprostol 24 hours later.
Dose: mifepristone 200 mg orally followed in 24 hours by misoprostol 800 mcg per vagina (typically given as four 200 mcg tablets).
Antibiotics are not recommended for routine medication management of abortion.
Pain management with nonsteroidal anti-inflammatory drug (NSAID) prior to using misoprostol.
Misoprostol alone regemin 800 mcg per vagina (typically four 200 mcg tablets). For patients who do not have complete expulsion after a single dose, a second dose can be given. Between 9 and 12 weeks, the World Health Organization (WHO) recommends an initial 800 mcg dose of misoprostol followed by 400 mcg every three hours until expulsion.
- mifepristone followed by misoprostol 24 hours later.
- Dose: mifepristone 200 mg orally followed in 24 hours by misoprostol 800 mcg per vagina (typically given as four 200 mcg tablets).
- Antibiotics are not recommended for routine medication management of abortion.
- Pain management with nonsteroidal anti-inflammatory drug (NSAID) prior to using misoprostol.
- Misoprostol alone regemin 800 mcg per vagina (typically four 200 mcg tablets). For patients who do not have complete expulsion after a single dose, a second dose can be given. Between 9 and 12 weeks, the World Health Organization (WHO) recommends an initial 800 mcg dose of misoprostol followed by 400 mcg every three hours until expulsion.
- 13 to 20 weeks of gestation
Regardless of the gestational age, medication management of pregnancy loss includes mifepristone and misoprostol. The difference is that the misoprostol dose is often reduced and repeated, and should be done in a health facility.
- Regardless of the gestational age, medication management of pregnancy loss includes mifepristone and misoprostol. The difference is that the misoprostol dose is often reduced and repeated, and should be done in a health facility.

## Surgery
- Surgery evacuation  with sharp curettage or suction curettage is not the first-line treatment option for patients with early pregnancy loss.
- Surgery is usually reserved for patients with either hemorrhage, hemodynamic instability, or signs of infection.
- This is also the preferred method of treatment for women with comorbid conditions such as cardiovascular disease, infection, severe anemia, or bleeding disorders.
- Antibiotic prophylaxis should be given before surgical evacuation

## Primary Prevention
Effective measures for the primary prevention of unsafe abortion include :
- Use of contraception has been shown an effective decrease in the abortion rate.
- Sexual education programs.
- Easy access to contraception.
- Social protection to reduce induced abortion among pregnant women who have been abandoned by their partners, rejected by their families.

## Secondary Prevention
The only way to prevent an unsafe abortion is to provide safe services for termination of pregnancy.