What is the cause and timeline of a miscarriage?

Causes and Timeline of Miscarriage

Miscarriage occurs primarily due to genetic abnormalities, with fetal chromosomal defects accounting for up to 60% of all miscarriages, while other causes include structural uterine issues, endocrine disorders, immune factors, and thrombophilic conditions. 1, 2

Primary Causes of Miscarriage

Genetic Factors

• Approximately 80% of miscarriages happen within the first 12 weeks of gestation, with over half resulting from genetic defects, usually presenting as abnormal chromosome numbers or gene rearrangements in the embryo 2
• Fetal chromosomal defects account for up to 60% of all miscarriages and are considered non-modifiable factors 1
• Recent research has identified specific gene mutations that may be implicated in both sporadic and recurrent miscarriages 2

Maternal Structural Factors

• Maternal congenital uterine abnormalities affect up to 38% of women with recurrent miscarriage 1
• Short cervix (<25 mm) was previously thought to increase miscarriage risk, but activity restriction is now discouraged as it may actually increase preterm birth rates 1

Endocrine and Metabolic Factors

• Diminished ovarian reserve, characterized by low anti-Müllerian hormone (AMH) levels, is associated with approximately 35% increased relative risk of miscarriage 3
• This translates to about 7% absolute increase in miscarriage risk (e.g., from 20% to 27%) 3
• Insulin resistance and obesity can increase miscarriage risk 1

Thrombophilic Factors

• About 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels 4
• Common thrombophilic conditions include antiphospholipid syndrome (67% of cases), sticky platelet syndrome (21%), and factor V Leiden (7%) 4

Other Risk Factors

• Advanced maternal age (>35 years) and very young maternal age (<20 years) 5
• Advanced paternal age (>40 years) 5
• Very low or very high body mass index 5
• Black ethnicity 5
• Previous miscarriages 5
• Lifestyle factors: smoking, alcohol consumption, stress, working night shifts 5
• Environmental factors: air pollution and exposure to pesticides 5

Timeline and Classification of Miscarriage

Early Pregnancy Loss (EPL)

• EPL is the preferred term for describing a pregnancy that may not progress, is in the process of expulsion, or has incompletely or completely passed 6
• Most miscarriages (80%) occur within the first 12 weeks of gestation 2

Diagnostic Timeline

• Concerning for EPL: Embryonic crown-rump length (CRL) <7 mm with no cardiac activity, mean sac diameter (MSD) 16-24 mm with no embryo, or absence of embryo 7-13 days after visualization of gestational sac 6
• Diagnostic of EPL: CRL ≥7 mm with no cardiac activity, MSD ≥25 mm with no embryo, or absence of embryo ≥14 days after visualization of gestational sac 6

Types of Miscarriage

• Incomplete Miscarriage: presence of intracavitary tissue or persistent gestational sac following pregnancy loss 6
• Complete Miscarriage: no persistent gestational sac or intracavitary tissue following pregnancy loss 6
• Missed Miscarriage (Silent Miscarriage): embryo has died but has not been expelled from the uterus 6
• Anembryonic Pregnancy: gestational sac measuring 25 mm or larger without an embryo 6
• Embryonic Demise: crown-rump length is 7 mm or longer with absence of cardiac activity 6

Poor Prognostic Indicators

• Calcified yolk sac and expanded amnion sign (enlarged amniotic cavity relative to the crown-rump length) 6
• Recurrent miscarriage is a sentinel risk marker for future obstetric complications including preterm birth, fetal growth restriction, placental abruption, and stillbirth 5
• Recurrent miscarriage also predicts longer-term health problems such as cardiovascular disease and venous thromboembolism 5

Management Considerations

• Management options for incomplete miscarriage include expectant management, medical management with misoprostol, or surgical evacuation 6
• Misoprostol should never be used in pregnant women who wish to continue their pregnancy as it can cause abortion, premature birth, or birth defects 7
• Surgical evacuation is preferably performed under ultrasound guidance to reduce the risk of uterine perforation 6
• Histopathologic examination of tissue is recommended to confirm intrauterine pregnancy and rule out gestational trophoblastic disease 6

Psychological Impact

• Miscarriage can lead to significant psychological consequences including increased risk of anxiety, depression, post-traumatic stress disorder, and suicide 5
• The economic cost of miscarriage is substantial, estimated at £471 million per year in the UK 5