A Clinical Review of Miscarriage

Written By Danial Mirza

Definition

A miscarriage, known clinically as a spontaneous abortion, is the spontaneous loss of an embryo or fetus from the uterus before it has reached the threshold of viability. For clinical practice within Malaysian government hospitals, this definition is standardized by the Ministry of Health (MOH) as a pregnancy loss occurring before 22 completed weeks of gestation or, if the gestational age is unknown, a fetal weight of less than 500 grams (7). Any pregnancy loss that occurs after this established point of viability is classified as a stillbirth (3).

It is a point of clinical and ethical importance to use the term "miscarriage" when communicating with patients and their families. The medical term "abortion" carries significant social and emotional stigma and can be misinterpreted as an elective procedure, potentially causing unnecessary distress or suggesting blame (1).

Clinical Classifications

The timing of the loss has significant etiological and clinical implications.

  • Early Miscarriage: This refers to a loss that occurs within the first trimester, defined as before 13 completed weeks of gestation. Early miscarriages are exceedingly common, accounting for approximately 80% of all clinically recognized miscarriages. They are most often caused by fetal chromosomal abnormalities (1).

  • Late Miscarriage: This is defined as a pregnancy loss occurring in the second trimester, from 13 weeks up to the 22-week threshold of viability. Late miscarriages are far less common and are more likely to be associated with underlying maternal health conditions, infections, or anatomical abnormalities of the uterus or cervix (1).

  • Recurrent Pregnancy Loss (RPL): This is a distinct clinical entity defined by the experience of three or more consecutive spontaneous miscarriages. However, reflecting a shift towards earlier intervention, many international and local guidelines now recommend initiating investigations after two consecutive losses, particularly if additional risk factors are present, such as advanced maternal age (>35 years), a history of infertility, or a long time to conception (4, 1).

Clinical Subtypes

Accurately classifying the miscarriage subtype is the cornerstone of initial management. The diagnosis is based on a combination of clinical history, the character of vaginal bleeding, the status of the cervical os on speculum examination, and ultrasound findings.

  • Threatened Miscarriage: This is characterized by vaginal bleeding, ranging from light spotting to a heavier flow, that occurs before 22 weeks. The crucial diagnostic feature is a closed, long, and firm cervical os on speculum examination, with an ultrasound confirming a viable, intrauterine pregnancy (i.e., a fetal heartbeat is present). While distressing, it is important to counsel patients that many of these pregnancies continue to term successfully (4).

  • Inevitable Miscarriage: In this scenario, the miscarriage process is considered irreversible. It presents with vaginal bleeding and significant, painful uterine cramping. The defining feature is an open (dilated) cervical os on examination. Products of conception may be visible or palpable at the os but have not yet been passed from the uterus (3).

  • Incomplete Miscarriage: This diagnosis is made when there has been partial expulsion of the products of conception, but some tissue remains within the uterine cavity. Patients typically present with persistent and often heavy vaginal bleeding, significant cramping, and an open cervical os. A study from Hospital Universiti Sains Malaysia (HUSM) identified this as the most common type diagnosed in their hospital setting, highlighting its clinical relevance (16, 18).

  • Complete Miscarriage: This occurs when all products of conception (fetus and placenta) have been completely expelled from the uterus. Following the expulsion, the uterus contracts firmly, the cervical os closes, and the patient's bleeding and pain subside significantly. An ultrasound will confirm an empty uterus with a thin endometrial lining (4).

  • Missed Miscarriage: Also known as a silent miscarriage, this subtype is defined by the in-utero death of the embryo or fetus without the expulsion of any tissue. The cervical os remains closed, and the patient is often asymptomatic, though she may notice a resolution of pregnancy symptoms like nausea. The diagnosis is frequently an incidental finding during a routine antenatal ultrasound that reveals an absence of fetal cardiac activity or an empty gestational sac (anembryonic gestation) (3).

  • Septic Miscarriage: This is not a distinct subtype but a severe, life-threatening complication where any of the above forms of miscarriage (most commonly incomplete or missed) becomes complicated by an intrauterine infection. It is an obstetric emergency characterized by the triad of fever, uterine tenderness, and purulent, foul-smelling vaginal discharge. It can rapidly progress to septic shock and must be managed aggressively with resuscitation, antibiotics, and uterine evacuation (3, 20).

Epidemiology

Miscarriage is the most common complication of early pregnancy. In Malaysia, the clinically recognized incidence is estimated to be between 15% to 20% of all known pregnancies, a figure that aligns with global statistics (1, 24). Worldwide, this translates to an overwhelming 23 million miscarriages each year (25). This number, however, only reflects losses that occur after a pregnancy has been clinically confirmed. The true biological incidence, including very early biochemical losses that occur before a woman may realize she is pregnant, is substantially higher, estimated at 30-50% of all conceptions (1).

Obtaining precise national-level data in Malaysia is challenging due to social sensitivities and potential underreporting. Hospital-based data, such as a study from HUSM showing a miscarriage rate of only 1-2% of pregnancies managed in the hospital, reveals a crucial clinical insight (18). This discrepancy suggests that the vast majority of miscarriages are managed in primary care settings (Klinik Kesihatan, private GPs) or at home without medical intervention. Consequently, patients who present to a hospital's Emergency Department often represent the "tip of the iceberg" and are more likely to have complications such as incomplete miscarriage, severe hemorrhage, or intractable pain requiring hospital-level care.

Etiology

The cause of a miscarriage is often multifactorial, involving a complex interplay of fetal, maternal, and environmental factors. Despite thorough investigation, the cause remains unexplained or "idiopathic" in up to 50% of cases, particularly in recurrent pregnancy loss (23).

  • Fetal Chromosomal Abnormalities: This is, by a significant margin, the single most common cause, accounting for 50-60% of all first-trimester losses (1). These are typically sporadic (random) numerical errors (aneuploidy) arising from non-disjunction during meiosis, rendering the embryo non-viable. Common examples found in miscarriage specimens include autosomal trisomies (e.g., Trisomy 16, 21, 22), Monosomy X (Turner Syndrome), and polyploidy (e.g., triploidy) (4).

  • Maternal Anatomical Factors: Structural abnormalities of the reproductive tract can interfere with implantation or fetal growth.

    • Congenital Uterine Anomalies: Malformations like a septate uterus (most strongly associated with RPL), bicornuate, or unicornuate uterus can lead to loss due to the poor blood supply (vascularization) of the abnormal tissue, creating an inhospitable site for implantation (9).

    • Acquired Uterine Abnormalities: Submucosal fibroids that protrude into the uterine cavity, endometrial polyps, and intrauterine adhesions (Asherman's syndrome, often from previous surgery) can distort the cavity, cause chronic inflammation, or disrupt blood flow to the endometrium (9).

    • Cervical Insufficiency: This is a functional defect characterized by premature, painless dilation and effacement of the cervix, typically leading to a second-trimester loss. It can be congenital or acquired from trauma during previous childbirth or cervical procedures (4).

  • Maternal Endocrine Disorders: A stable hormonal environment is critical for maintaining a pregnancy.

    • Poorly controlled Diabetes Mellitus: Hyperglycemia is directly teratogenic to the developing embryo and causes microvascular damage in the placenta, impairing its function (1).

    • Thyroid disease: Both overt hypothyroidism and hyperthyroidism disrupt the metabolic and hormonal balance required for pregnancy. The presence of thyroid autoantibodies (e.g., anti-TPO), even in women with normal thyroid function (euthyroid), is an independent risk factor for miscarriage (10).

    • Polycystic Ovary Syndrome (PCOS): Women with PCOS have a higher miscarriage rate, thought to be related to hyperinsulinemia, insulin resistance, and elevated androgen levels, which negatively affect oocyte quality and endometrial receptivity (10).

  • Immunological Factors:

    • Antiphospholipid Syndrome (APS): This is the most important treatable cause of RPL. It is an autoimmune disorder where autoantibodies trigger a hypercoagulable state, leading to thrombosis (blood clots) in the placental microvasculature. This starves the fetus of oxygen and nutrients, leading to its demise (9).

  • Infections: Maternal infections are a significant and preventable cause, responsible for up to 15% of early and as many as 66% of late miscarriages (6). Pathogens can harm the fetus directly, trigger chorioamnionitis (inflammation of the membranes), or induce premature uterine contractions. Well-established links include bacterial vaginosis, TORCH infections (Toxoplasmosis, Rubella, CMV), malaria, and listeriosis (4).

  • Parental and Lifestyle Factors:

    • Advanced Maternal Age (>35 years): This is the single most significant non-chromosomal risk factor. The risk of miscarriage is about 20% at age 35, rises to around 40% by age 40, and can exceed 50% by age 45. This is primarily driven by the age-related decline in oocyte (egg) quality and the corresponding sharp increase in the rate of fetal aneuploidy (10).

    • Advanced Paternal Age (>40 years): An increased risk has been noted for men over 40, likely due to an increased rate of chromosomal abnormalities and DNA fragmentation in sperm (1).

    • Lifestyle: Smoking causes placental vasoconstriction and hypoxia. Heavy alcohol use and illicit drugs like cocaine are directly toxic to the fetus. Obesity (BMI ≥25) and being underweight are linked to hormonal dysregulation and poor oocyte quality. High caffeine intake (>200mg/day) is also associated with an increased risk (1, 6).

Pathophysiology

The underlying mechanism of miscarriage is a direct consequence of its etiology. In cases of fetal aneuploidy, the genetic errors lead to a fundamental failure of normal embryonic development (e.g., failed organogenesis), resulting in developmental arrest, apoptosis, and subsequent recognition by the maternal system as non-viable, triggering uterine contractions and expulsion.

When maternal anatomical defects are the cause, the pathophysiology relates to a hostile uterine environment. A uterine septum or a large submucosal fibroid provides a poorly vascularized surface for implantation, leading to inadequate placentation and early failure. In other cases, these abnormalities physically distort the uterine cavity, preventing the gestational sac from growing normally.

In immunological conditions like Antiphospholipid Syndrome, the mechanism is primarily vascular. The autoantibodies trigger a prothrombotic state, causing widespread microthrombosis in the developing placental vessels. This occludes blood flow, leading to placental insufficiency, infarction, and ultimately, fetal hypoxia and demise.

Finally, infections can lead to miscarriage through several pathways. Some pathogens can cross the placenta and cause direct fetal infection and death. More commonly, infections trigger a potent maternal inflammatory response, leading to the release of prostaglandins and cytokines that stimulate premature uterine contractions and cervical ripening, resulting in the expulsion of the pregnancy.

Clinical Presentation

The classic presentation involves a combination of vaginal bleeding and lower abdominal cramping. A thorough history is key to differentiating the cause and assessing the severity.

Diagnostic Clues

  • Common Symptoms (>50%):

    • Vaginal Bleeding: The hallmark sign. It is crucial to quantify the loss (e.g., number of pads soaked per hour, passage of clots larger than a 50-sen coin). The color can range from brownish (old blood) to bright red (active bleeding) (1, 20).

    • Abdominal/Pelvic Cramping: Typically crampy, central, lower abdominal pain, often described as similar to or worse than menstrual cramps. The severity often correlates with the activity of the miscarriage process (4).

  • Less Common Symptoms (10-50%):

    • Passage of Tissue: Patients may report passing material that looks like large clots or grayish/tan-colored tissue. This represents the products of conception (3).

    • Low Back Pain: A dull, persistent ache in the lumbosacral region often accompanies uterine cramping (3).

    • Resolution of Pregnancy Symptoms: A subtle but important sign is the patient's subjective feeling of "no longer being pregnant," with a sudden disappearance of nausea, vomiting, breast tenderness, and fatigue (5).

⚠️ Red Flag Signs & Symptoms

  • Heavy vaginal bleeding (e.g., soaking more than two large sanitary pads per hour for two consecutive hours), suggesting hemorrhage.

  • Signs of hemodynamic instability (tachycardia >100 bpm, hypotension SBP <90 mmHg, dizziness, pallor), indicating significant blood loss.

  • Fever (>38°C), chills, and purulent, foul-smelling vaginal discharge, which are the classic signs of a septic miscarriage.

  • Severe, localized, unilateral abdominal pain or shoulder tip pain (from diaphragmatic irritation by intra-abdominal blood), which are highly suspicious for a ruptured ectopic pregnancy.

Complications

  • Hemorrhage: Profuse bleeding can lead to hypovolemic shock and requires immediate resuscitation and uterine evacuation to control the source (19).

  • Septic Miscarriage: A life-threatening infection of retained products of conception. It can rapidly progress to septic shock, Acute Respiratory Distress Syndrome (ARDS), and Disseminated Intravascular Coagulation (DIC) if not treated aggressively (15).

  • Asherman's Syndrome: Intrauterine adhesions or scarring can develop as a complication of surgical management (particularly vigorous D&C), potentially leading to future infertility or menstrual problems.

  • Psychological Distress: The emotional impact is profound. Grief, anxiety, depression, and even post-traumatic stress disorder (PTSD) are common. This is a significant and often overlooked aspect of morbidity that requires compassionate bereavement care (1).

Prognosis

For a single, sporadic miscarriage, the prognosis for future pregnancies is excellent. The majority of women (>85%) go on to have a successful subsequent pregnancy (33). Even after a threatened miscarriage, a significant proportion of pregnancies continue to term without issue (4). The prognosis worsens with increasing maternal age and with each consecutive loss in cases of RPL. After three consecutive losses, the risk of a further miscarriage can be as high as 40-50%.

Differential Diagnosis

In any woman presenting with first-trimester bleeding and pain, it is crucial to consider and exclude other diagnoses, especially life-threatening ones.

  • Ectopic Pregnancy: This is the most critical differential to exclude in any woman of reproductive age with pain and bleeding. It is suggested by unilateral pelvic pain, adnexal tenderness, or a palpable adnexal mass. An ultrasound showing an empty uterus with a positive pregnancy test, especially when the β-hCG level is above the "discriminatory zone" (>1500-2000 IU/L), is highly suspicious. Sub-optimally rising or plateauing β-hCG levels are a classic feature (46).

  • Molar Pregnancy (Gestational Trophoblastic Disease): Consider this if the uterus is significantly larger than expected for gestational dates or if the patient reports passing "grape-like" vesicles. The diagnosis is strongly supported by extremely high β-hCG levels (often >100,000 IU/L) and a characteristic "snowstorm" or "bunch of grapes" appearance of intrauterine contents on ultrasound, with no viable fetus (19).

  • Implantation Bleeding: This is a diagnosis of exclusion. It is physiological and typically presents as very light, brief spotting ("spotting") that occurs around the time of the expected menses. It is associated with minimal or no pain and a closed cervix on examination (1).

Investigations

Immediate & Bedside Tests

  • Urine Pregnancy Test (UPT): A quick, qualitative confirmation of pregnancy status.

  • Vital Signs Monitoring: Essential to assess for hemodynamic instability (tachycardia, hypotension) or fever, which are red flags for hemorrhage or sepsis, respectively.

Diagnostic Workup

  • First-Line Investigations:

    • Full Blood Count (FBC): This is essential to establish a baseline hemoglobin and hematocrit to objectively assess the degree of blood loss and the potential need for transfusion (the action). It also checks for leukocytosis, which may indicate an underlying infection, raising suspicion for a septic miscarriage (the rationale) (15).

    • Blood Group and Rh Status: This is mandatory for all pregnant women with bleeding. It identifies Rh-negative women who will require anti-D immunoglobulin (the action) to prevent Rh isoimmunization, which can cause severe hemolytic disease in future pregnancies (the rationale) (12).

    • Serial Quantitative β-hCG: A trend over 48 hours is far more useful than a single value. In a viable pregnancy, the level should roughly double every 48-72 hours. A sub-optimal rise (<53% in 48h) or a plateau is suspicious for an ectopic or non-viable intrauterine pregnancy (the action), helping to differentiate between these critical conditions when ultrasound is inconclusive (the rationale) (46).

  • Gold Standard:

    • Transvaginal Ultrasound (TVS): This is the definitive diagnostic tool in early pregnancy. It provides superior resolution to a transabdominal scan. Its purpose is to confirm the location of the pregnancy (ruling out an ectopic), assess viability by detecting a fetal heartbeat (the action), and help classify the type of miscarriage based on uterine contents and cervical length (the rationale) (13).

Strict Ultrasound Criteria for Diagnosing Pregnancy Loss

To prevent the devastating error of terminating a desired, potentially viable pregnancy, a diagnosis of miscarriage is only definitive if one of the following is observed on TVS (45):

  • Crown-rump length (CRL) ≥ 7 mm with no detectable fetal heartbeat.

  • Mean sac diameter (MSD) ≥ 25 mm with no visible embryo.

  • Absence of an embryo with a heartbeat ≥ 2 weeks after a scan showed a gestational sac without a yolk sac.

  • Absence of an embryo with a heartbeat ≥ 11 days after a scan showed a gestational sac with a yolk sac.

  • If any doubt exists or if findings are suspicious but not diagnostic (e.g., embryonic bradycardia, large yolk sac), a follow-up scan in 7-14 days is mandatory before any irreversible management decisions are made.

Management

Management Principles

Management must be patient-centered, focusing on ensuring clinical safety, providing clear, unbiased information on all options to facilitate true shared decision-making, and offering compassionate psychological and bereavement support.

Acute Stabilisation (The First Hour)

For patients presenting with hemorrhage or suspected sepsis, an ABCDE approach is critical:

  • Airway/Breathing: Assess for patency and administer high-flow oxygen via a non-rebreather mask to maintain SpO2 >94% (the action), which is crucial to prevent tissue hypoxia driven by blood loss or sepsis (the rationale).

  • Circulation: Secure two large-bore (16G or 18G) IV cannulas. Send blood for FBC, Group & Screen, and coagulation profile. Administer a stat fluid bolus of IV Normal Saline or Hartmann's solution, 20mL/kg (the action), to correct hypotension and restore vital organ perfusion (the rationale).

  • Disability: Assess conscious level using GCS. Check blood glucose.

  • Exposure: If sepsis is suspected (fever, uterine tenderness), perform a full examination, take blood cultures, and administer broad-spectrum IV antibiotics immediately (e.g., a combination covering gram-positives, gram-negatives, and anaerobes, as per local hospital guidelines) (the action) to control the infection and prevent progression to septic shock (the rationale).

Definitive Therapy

Threatened Miscarriage

  • The mainstay of care is reassurance and expectant management. Advising strict bed rest is not supported by evidence and is no longer recommended as it does not improve outcomes (46).

  • Progestogen supplementation (e.g., dydrogesterone, micronized progesterone) should be considered only for women presenting with a threatened miscarriage who also have a history of previous miscarriages, as per the 2022 Obstetrical & Gynaecological Society of Malaysia (OGSM) guideline. The benefit is most pronounced in those with ≥3 prior losses (8, 34).

Non-Viable Miscarriage (Incomplete, Missed)

Three equivalent management pathways should be discussed with the patient, respecting her autonomy:

  1. Expectant Management: Awaiting spontaneous passage of tissue without intervention. A key Malaysian study from the University of Malaya Medical Centre (UMMC) found a success rate of 85.3% by 5 weeks with high patient satisfaction and no major complications (53). This is a safe and effective first-line option for clinically stable women who are well-informed about what to expect.

  2. Medical Management: Using medication to induce uterine contractions and expulsion. The standard regimen is Misoprostol, a prostaglandin E1 analogue. A typical dose is 800mcg administered vaginally, which can be repeated if necessary. Protocols are available in the Malaysian MOH Handbook (55). This avoids surgery but can cause significant, predictable cramping and bleeding at home.

  3. Surgical Management: Physical removal of tissue from the uterus. Manual vacuum aspiration (MVA) under local anesthesia or suction aspiration under general anesthesia are the preferred methods as they are associated with less blood loss and lower risk of uterine perforation than traditional sharp dilatation and curettage (D&C). This is the quickest resolution and is the required treatment for hemorrhage, sepsis, or when other methods fail (14).

Supportive & Symptomatic Care

  • Analgesia: Proactively offer adequate pain relief (e.g., NSAIDs like mefenamic acid, or paracetamol) to all patients to ensure their comfort throughout the process.

  • Anti-D Immunoglobulin: This is a mandatory and critical preventative intervention for all non-sensitized Rh-negative women. The Malaysian MOH guideline specifies a dose of 250 IU IM for losses before 20 weeks of gestation, to be given within 72 hours of the sensitizing event (the miscarriage) (7).

Key Nursing & Monitoring Instructions

  • Strict input/output chart monitoring, with close tracking of pad usage for patients with ongoing bleeding.

  • Hourly vital signs for any patient who is hemodynamically unstable or at risk.

  • Inform medical staff immediately if systolic BP drops below 90 mmHg, heart rate rises above 110 bpm, temperature spikes >38°C, or urine output is <0.5mL/kg/hr.

Long-Term Plan & Patient Education

  • Advise patients that a normal menstrual cycle typically resumes within 4 to 6 weeks. Bleeding after the miscarriage can last for 1-2 weeks, gradually lightening (3).

  • Discuss future family planning and contraception. For those who wish to delay another pregnancy, contraception can be initiated immediately.

  • For those desiring another pregnancy, it is vital to reassure them that a single miscarriage is usually a random event. Medically, it is safe to try to conceive again as soon as they feel physically and emotionally ready, though many advise waiting for one normal menstrual cycle to aid in dating the next pregnancy (50).

  • Provide compassionate bereavement support. Acknowledge the loss as real, validate their grief, and refer to hospital counselors or community-based support groups as needed. This is a critical and often neglected component of care (7).

When to Escalate

Call Your Senior (MO/Specialist) if:

  • The patient is hemodynamically unstable (tachycardic, hypotensive) and not responding to initial fluid resuscitation.

  • There are clear signs of sepsis (fever, rigors, uterine tenderness), as this requires urgent senior input for management, including timely uterine evacuation.

  • The diagnosis is uncertain, particularly if an ectopic pregnancy cannot be confidently excluded by ultrasound and β-hCG trends.

  • The patient has exceptionally heavy bleeding requiring consideration for blood transfusion or emergency surgical intervention.

  • The patient has a known significant comorbidity (e.g., heart disease, bleeding disorder).

Referral Criteria

  • Refer to the Psychology or Medical Social Work department for all patients who express significant emotional distress, anxiety, or grief.

  • Refer patients who meet the criteria for Recurrent Pregnancy Loss (≥2-3 consecutive losses) to a specialist O&G or Reproductive Medicine clinic for a comprehensive etiological workup.

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Danial Mirza
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Oligohydramnios: A Clinical Review
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Polyhydramnios: A Clinical Review