Miscarriage
Miscarriage is the spontaneous loss of a pregnancy before 20 weeks of gestation, most commonly due to chromosomal abnormalities of the embryo or fetus.
Miscarriage (also called spontaneous abortion) is the spontaneous loss of a pregnancy before the fetus reaches viability. By convention, this is defined as pregnancy loss before 24 weeks of gestation (UK/HK definition) or before 20 weeks (US definition) [1][2].
Let's break down the terminology:
- "Mis-carriage" = literally "carrying wrongly" — the pregnancy fails to be carried to term
- The older medical term "abortion" (from Latin abortus = "misborn") technically encompasses both spontaneous and induced pregnancy loss. In clinical practice, we now prefer "miscarriage" for spontaneous loss to avoid confusion and reduce stigma.
Recurrent miscarriage is defined as:
- Loss of ≥2 pregnancies (ESHRE 2017 guideline) [1]
- Loss of ≥3 pregnancies (RCOG Green-top Guideline 2023) [1]
The difference matters practically: ESHRE's lower threshold triggers earlier investigation, which is the approach increasingly adopted in Hong Kong. Know both definitions for exams.
Key Distinction
Do not confuse miscarriage with stillbirth. Stillbirth = loss at ≥24 weeks (UK/HK) or ≥20 weeks and/or ≥500g (some jurisdictions). The gestational age cutoff determines which term applies and has medicolegal implications (stillbirth requires registration; miscarriage does not).
Epidemiology
- Miscarriage is the most common complication of early pregnancy
- Approximately 10–20% of clinically recognised pregnancies end in miscarriage [1][2]
- When including subclinical/biochemical pregnancies (detected only by hCG before ultrasound confirmation), the true rate is estimated at 30–50% of all conceptions — most women never even know they were pregnant
- The vast majority (~80%) of miscarriages occur in the first trimester (< 13 weeks), with a peak at 8–12 weeks [2]
- Affects approximately 1–2% of couples trying to conceive [1]
- Risk of miscarriage increases with number of prior losses:
- After 1 miscarriage: ~20%
- After 2 miscarriages: ~28%
- After 3 miscarriages: ~43%
- Maternal age is one of the strongest independent risk factors:
- < 30 years: ~10–12%
- 35–39 years: ~20%
- 40–44 years: ~40–50%
- ≥ 45 years: ~80%
- Why? Oocyte quality deteriorates with age → increased rates of meiotic non-disjunction → aneuploid embryos → chromosomally abnormal pregnancies that fail early
- The average maternal age at first birth in Hong Kong has risen steadily (now ~32 years), contributing to higher miscarriage rates in the population
- Psychiatric morbidity following miscarriage in Hong Kong: 3 months after miscarriage, 10% of subjects suffered depressive disorder, 1.2% were diagnosed with anxiety disorder not otherwise specified, 0.6% suffered from obsessive compulsive disorder and 0.6% suffered from post-traumatic stress disorder [1]
- Risk factors of depression included younger age, history of infertility and depression (Sham 2010, Gen Hosp Psychiatry 32:284-9) [1]
Exam High Yield
Miscarriage is extremely common. The majority are first-trimester losses due to chromosomal abnormalities. Advanced maternal age is the single biggest risk factor due to oocyte aneuploidy.
Risk Factors
Organised by modifiable vs. non-modifiable, with mechanistic explanation:
| Risk Factor | Mechanism |
|---|---|
| Advanced maternal age (strongest) | ↑ Meiotic non-disjunction → aneuploid embryos (esp. trisomies) |
| Advanced paternal age (> 40y) | ↑ Sperm DNA fragmentation → abnormal embryo development |
| Previous miscarriage | Each prior loss independently increases risk; may reflect underlying undiagnosed cause |
| Genetic factors | Parental balanced translocation, inversions → unbalanced gametes |
| Risk Factor | Mechanism |
|---|---|
| Smoking | Nicotine → vasoconstriction of uteroplacental vessels + carbon monoxide → ↓ O₂ delivery; cadmium → direct embryotoxicity |
| Alcohol | Teratogenic; direct embryotoxicity and impaired implantation |
| High BMI (obesity) | Chronic inflammation, insulin resistance, hormonal imbalance (↑ estrogen from aromatisation) → impaired endometrial receptivity |
| Low BMI / malnutrition | Hypothalamic suppression → inadequate luteal progesterone |
| Caffeine excess ( > 200–300 mg/day) | Vasoconstriction + ↑ catecholamines → uteroplacental insufficiency; caffeine crosses placenta and fetus lacks CYP1A2 to metabolise it |
| Cocaine, recreational drugs | Vasoconstriction → placental abruption / infarction |
| Uterine anomalies | Septate/bicornuate uterus → reduced endometrial blood supply at implantation site; fibroids (esp. submucosal) → distort cavity |
| Cervical insufficiency | Painless cervical dilation → second-trimester loss (discussed under classification) |
| Antiphospholipid syndrome (APLS) | Thrombosis of uteroplacental vasculature + complement-mediated placental injury → ischaemic pregnancy failure [3][4] |
| Thrombophilias | Factor V Leiden, prothrombin G20210A, protein C/S deficiency → placental microthrombosis [3][4] |
| Endocrine disorders | Uncontrolled diabetes mellitus (hyperglycaemia → embryopathy), thyroid disease (hypothyroid → ↓ progesterone support), PCOS (insulin resistance + ↑ LH → impaired endometrial receptivity) |
| Infections | Listeria, Toxoplasma, rubella, CMV, syphilis, malaria → direct fetal/placental infection |
| Environmental exposures | Radiation, organic solvents, heavy metals |
| Psychological stress | ↑ Cortisol → ↑ CRH → ↑ prostaglandins + uterine contractility |
APLS and Miscarriage
Antiphospholipid syndrome is the most important treatable cause of recurrent miscarriage. Think of it whenever you see recurrent pregnancy loss + thrombotic history. It causes both arterial and venous thrombosis plus pregnancy morbidity. Requires TWO positive antibody measurements 12 weeks apart (anti-cardiolipin, lupus anticoagulant, anti-β₂-glycoprotein I) [3][4].
Anatomy and Relevant Functional Considerations
Understanding miscarriage requires understanding the structures that support early pregnancy:
- Myometrium: smooth muscle; must remain quiescent in early pregnancy under the influence of progesterone (which inhibits gap junction formation between myocytes and suppresses prostaglandin synthesis)
- Endometrium → Decidua: after implantation, the endometrium undergoes decidualisation (stromal cells swell with glycogen/lipid, spiral arteries remodel). This provides nutritional support and immune tolerance for the semi-allogeneic embryo
- Cervix: acts as a mechanical barrier; the internal os must remain closed. The cervix is held shut by smooth muscle (internal os) and collagenous connective tissue. Cervical insufficiency (premature softening and dilation) is a cause of second-trimester loss
- Yolk sac: provides nutrition before placenta is established (~weeks 3–10); visible on ultrasound by ~6 weeks → presence confirms a definite intrauterine pregnancy (IUP) [5]
- Embryo/Fetus: cardiac activity usually detectable by 6–7 weeks on transvaginal ultrasound (TVUS) [5]
- Gestational sac: visible by ~5 weeks on TVUS; the double-sac sign (parietal decidua surrounding capsular decidua) indicates IUP [5]
- Trophoblast invasion of spiral arteries is critical: the cytotrophoblast cells invade and remodel the muscular walls of the spiral arteries, converting them from high-resistance, low-flow vessels into low-resistance, high-flow vessels
- Failure of trophoblast invasion → inadequate uteroplacental blood flow → ischaemia → pregnancy failure (this is the shared final common pathway for many causes including APLS, thrombophilias, and pre-eclampsia)
- After ovulation, the corpus luteum in the ovary produces progesterone — the key hormone maintaining early pregnancy
- Progesterone:
- Supports the decidualised endometrium
- Suppresses myometrial contractility
- Modulates immune tolerance at the maternal-fetal interface
- The luteal-placental shift occurs at ~7–10 weeks: the placenta takes over progesterone production. Corpus luteum failure before this shift can cause miscarriage
Etiology and Pathophysiology
This is the most conceptually dense section. We will organise causes systematically and explain the pathophysiology of each.
| Cause | Approximate Frequency | Trimester |
|---|---|---|
| Chromosomal/genetic abnormalities | ~50–60% of sporadic; ~3–5% of recurrent | 1st |
| Idiopathic | ~50% of recurrent | Any |
| Antiphospholipid syndrome | ~15% of recurrent | Any (classically 2nd) |
| Uterine anomalies | ~10–15% of recurrent | 1st or 2nd |
| Endocrine | ~10–15% of recurrent | 1st |
| Thrombophilia (inherited) | ~5–10% of recurrent | 2nd > 1st |
| Cervical insufficiency | Variable | 2nd |
| Infection | Sporadic > recurrent | Any |
This is the single most common cause of sporadic first-trimester miscarriage.
- Mechanism: Errors during meiosis (gamete formation) → aneuploid conceptus → incompatible with life → pregnancy fails
- Most common abnormalities:
- Autosomal trisomy (~50% of chromosomally abnormal miscarriages): esp. trisomy 16 (most common), trisomy 22, trisomy 21
- Monosomy X (45,X / Turner syndrome): ~20%
- Polyploidy (triploidy 69,XXX or tetraploidy 92,XXXX): ~15–20%
- Structural abnormalities: translocations, inversions
- Why first trimester? Severe chromosomal abnormalities are usually lethal early; natural selection eliminates them before the second trimester
- In recurrent miscarriage: ~3–5% of couples have a parental balanced chromosomal rearrangement (e.g., balanced reciprocal translocation, Robertsonian translocation). The parent is phenotypically normal, but gametes may be unbalanced → recurrent aneuploid conceptions
Karyotyping of both parents is recommended in recurrent miscarriage workup to identify balanced translocations.
APLS occurs in ~30% of SLE patients. 2% of population is Ab positive [3].
-
Pathophysiology (multiple mechanisms):
- Thrombosis of uteroplacental vasculature: Antiphospholipid antibodies bind β₂-glycoprotein I on endothelial cells → endothelial activation → upregulation of tissue factor and adhesion molecules → thrombosis of decidual vessels → placental ischaemia and infarction
- Complement activation: Antibody-antigen complexes activate the classical complement pathway → C5a generation → neutrophil recruitment → placental inflammation and damage
- Direct trophoblast toxicity: Anti-β₂GPI antibodies directly bind trophoblast cells → impair invasion, proliferation, and syncytialisation → failed placentation
- Impaired decidualisation: Disruption of endometrial stromal cell differentiation
-
Clinical criteria for APLS (relevant to miscarriage) [3]:
- Recurrent miscarriage — specifically:
- ≥3 consecutive unexplained losses < 10 weeks, OR
- ≥1 morphologically normal fetal loss ≥ 10 weeks, OR
- ≥1 premature delivery < 34 weeks due to eclampsia/severe pre-eclampsia/placental insufficiency
- Recurrent thrombosis: venous (DVT/PE) or arterial (stroke/ACS/PVD) [3]
- Recurrent miscarriage — specifically:
-
Laboratory criteria: Antiphospholipid antibody: lupus anticoagulant (↑APTT, most thrombogenic) > anti-cardiolipin > anti-β₂ glycoprotein (most specific for APLS, but limited sensitivity → only check if the other two are negative) [3]
- Require TWO measurements 12 weeks apart [3]
Why Does Lupus Anticoagulant Cause Thrombosis, Not Bleeding?
This is a classic exam question. Despite its name and despite prolonging the APTT in vitro, lupus anticoagulant is prothrombotic in vivo. In the test tube, LA interferes with the phospholipid-dependent coagulation assay → prolonged APTT. But in the body, the antibodies activate endothelial cells and platelets, upregulate tissue factor, and inhibit natural anticoagulants (protein C pathway, annexin V) → NET PROTHROMBOTIC effect.
- Factor V Leiden (activated protein C resistance): most common inherited thrombophilia in Caucasians; point mutation in Factor V makes it resistant to inactivation by activated protein C → hypercoagulable state → uteroplacental thrombosis [3][4]
- Prothrombin gene mutation (G20210A): ↑ prothrombin levels → ↑ thrombin generation [3][4]
- Protein C, Protein S, Antithrombin deficiency: loss of natural anticoagulants → unopposed coagulation [3][4]
- These tend to cause second-trimester losses and late pregnancy complications (IUGR, pre-eclampsia, stillbirth) rather than early first-trimester miscarriage
- Thrombophilia screen indications include recurrent miscarriage [3][4]
4. Uterine Causes
- Septate uterus (most common anomaly associated with miscarriage): the septum has poor vascularity → if the embryo implants on the septum, it receives inadequate blood supply → pregnancy failure
- Bicornuate / unicornuate / didelphys uterus: reduced cavity volume + abnormal vasculature
- Mechanism: combination of impaired implantation (poor blood supply) and restricted cavity space → ↑ risk of miscarriage and preterm labour
- Submucosal fibroids: distort the endometrial cavity → mechanical interference with implantation and placentation
- Intrauterine adhesions (Asherman syndrome): post-surgical (e.g., post-D&C) scarring reduces functional endometrial surface area → failed implantation or inadequate decidualisation
- Endometrial polyps: focal space-occupying lesion; controversial direct causation but associated with subfertility
5. Endocrine Causes
- Inadequate progesterone production by the corpus luteum → failure to maintain decidualised endometrium → pregnancy loss
- Why? Progesterone is essential for: (a) endometrial secretory transformation, (b) immune modulation (Th2 shift), (c) myometrial quiescence
- Controversial as a standalone diagnosis, but the concept underpins progesterone supplementation therapy
- Hypothyroidism: thyroid hormones are essential for normal trophoblast development and placental function. Subclinical hypothyroidism and thyroid autoimmunity (anti-TPO antibodies) are both associated with ↑ miscarriage risk
- Hyperthyroidism: uncontrolled → ↑ metabolic demands, possible direct effect on trophoblast
- Mechanism of thyroid autoimmunity: anti-thyroid antibodies may cross-react with placental antigens; also serves as a marker of generalised immune dysregulation
- Poorly controlled diabetes (HbA1c > 8%): hyperglycaemia is directly embryotoxic (↑ oxidative stress, ↑ sorbitol via polyol pathway → osmotic damage to embryonic cells)
- Well-controlled diabetes does NOT significantly increase miscarriage risk — hence the emphasis on preconception glycaemic control
- Multiple proposed mechanisms:
- ↑ LH levels → premature oocyte ageing
- Insulin resistance → hyperinsulinaemia → ↑ PAI-1 → impaired fibrinolysis → uteroplacental thrombosis
- Obesity (common comorbidity) → chronic inflammation
- ↓ Progesterone (anovulatory cycles → luteal insufficiency)
- ↑ Prolactin → suppression of GnRH pulsatility → ↓ FSH/LH → anovulation or inadequate luteal phase
Beyond APLS:
- Alloimmune factors: the maternal immune system must develop tolerance to paternal antigens on the fetus. Failure of this tolerance (e.g., deficiency of blocking antibodies, abnormal NK cell activity) has been proposed but remains controversial and poorly defined
- Natural Killer (NK) cells: elevated uterine NK cell numbers/activity have been associated with recurrent miscarriage in some studies, though the clinical significance and therapeutic implications are debated
- HLA sharing: excessive HLA compatibility between partners was hypothesised to impair maternal immune recognition and tolerance, but evidence is weak
- Sporadic miscarriage: certain infections can cause isolated pregnancy loss
- Listeria monocytogenes: transplacental infection → chorioamnionitis
- Toxoplasma gondii: transplacental → fetal infection
- Rubella, CMV, Parvovirus B19: direct fetal damage
- Treponema pallidum (syphilis): placental vasculitis
- Bacterial vaginosis: associated with second-trimester loss and preterm birth (ascending infection → chorioamnionitis → prostaglandin release → uterine contractions)
- Septic abortion: infection complicating miscarriage (often after retained products or unsafe procedures) — this is a gynaecological emergency [6]
- Infection is generally NOT a major cause of recurrent miscarriage (unless chronic, e.g., chronic endometritis)
- Definition: painless dilation of the cervix, typically in the second trimester, leading to pregnancy loss
- Mechanism: the cervix fails to remain closed under the increasing weight of the growing uterus and amniotic fluid
- Normal cervix: collagen-rich connective tissue provides structural integrity
- Insufficiency: either congenital (↓ collagen content, e.g., Ehlers-Danlos) or acquired (prior cervical surgery — cone biopsy, LLETZ, forced cervical dilation during D&C)
- Presentation: painless cervical dilation → bulging membranes → membrane rupture → delivery of a previable fetus
- Important: this is a second-trimester cause, distinct from the first-trimester causes above
- Sperm DNA fragmentation: oxidative stress, age, smoking, varicocoele → ↑ DNA damage in sperm → abnormal embryo development → early pregnancy failure
- Often overlooked in workup but increasingly recognised
- As detailed under risk factors above: smoking, alcohol, caffeine excess, obesity, recreational drugs, occupational exposures
Classification of Miscarriage
This is clinically the most important framework for approaching a woman presenting with bleeding and/or pain in early pregnancy. The types exist on a clinical spectrum.
| Type | Cervical Os | Bleeding | Pain | Products of Conception | Uterine Size |
|---|---|---|---|---|---|
| Threatened miscarriage | Closed | Mild | Minimal/mild | Retained, fetus viable | Corresponds to dates |
| Inevitable miscarriage | Open | Moderate–heavy | Cramping | Still in utero but passage imminent | Corresponds to dates |
| Incomplete miscarriage | Open | Heavy, may have clots | Cramping | Partially expelled | Smaller than dates |
| Complete miscarriage | Closed (after passage) | Minimal/stopped | Settled | Completely expelled | Smaller than dates |
| Missed miscarriage (silent/delayed) | Closed | Minimal/brown spotting | Minimal | Retained, fetus non-viable (no cardiac activity) | Smaller than dates or static |
| Septic miscarriage | Open or closed | Variable, foul-smelling | Pelvic pain | Infected retained tissue | Tender |
The Critical Exam Question
The key differentiator between threatened and inevitable miscarriage is the state of the cervical os. Closed os + bleeding + viable fetus = threatened. Open os = inevitable. This is the single most important clinical distinction to make on examination.
- Pre-embryonic loss (< 6 weeks): often biochemical pregnancy only (positive hCG, no ultrasound-visible sac)
- Embryonic loss (6–10 weeks): most common timing; embryo visible but fails
- Fetal loss (10–24 weeks): fetus has formed; causes shift from chromosomal to structural/immunological/cervical
- Recurrent miscarriage: ≥2 losses (ESHRE 2017) or ≥3 losses (RCOG Green-top 2023) [1]
- Biochemical pregnancy: positive hCG that falls before ultrasound confirmation of pregnancy
- Anembryonic pregnancy (blighted ovum): gestational sac develops but no embryo forms (empty sac on ultrasound) — this is a subset of missed miscarriage
- Pregnancy of unknown location (PUL): positive hCG but nothing visible on ultrasound — could be very early IUP, ectopic, or resolving pregnancy. Requires serial hCG monitoring.
Clinical Features
| Symptom | Pathophysiological Basis |
|---|---|
| Vaginal bleeding | Disruption of decidual-trophoblastic interface → haemorrhage from exposed decidual vessels. In threatened miscarriage, the bleeding comes from marginal separation of the trophoblast from the decidua — the pregnancy itself may be intact |
| Cramping lower abdominal / suprapubic pain | Myometrial contractions stimulated by prostaglandins (PGE₂, PGF₂α) released from damaged decidual tissue. The uterus contracts to expel the products of conception — similar mechanism to labour. Pain may also arise from cervical dilation |
| Passage of tissue / clots | Physical expulsion of products of conception (gestational sac, placental tissue, embryonic/fetal tissue). Patients may describe passing "grape-like" tissue or recognise fetal parts in later losses |
| Disappearance of pregnancy symptoms | In missed miscarriage: falling hCG levels → regression of hCG-mediated symptoms (nausea, breast tenderness, urinary frequency). Patients may report that their "morning sickness suddenly stopped" |
| Low back pain | Referred pain from uterine contractions via shared sacral nerve root innervation (S2-S4) |
| Dizziness, syncope, weakness | Significant haemorrhage → hypovolaemia → ↓ cardiac output → cerebral hypoperfusion |
| Fever, rigors, malaise | In septic miscarriage: infection of retained products → systemic inflammatory response. Ascending infection → endometritis → parametritis → septicaemia |
| Foul-smelling vaginal discharge | Septic miscarriage: anaerobic bacterial infection of necrotic retained tissue produces malodorous discharge |
| Shoulder tip pain | If concurrent ectopic pregnancy (must always be excluded in early pregnancy bleeding) — diaphragmatic irritation from haemoperitoneum |
Pattern Recognition
- Threatened: light bleeding, closed os, viable fetus — essentially a "warning shot"; ~50% will continue to term
- Inevitable: heavier bleeding + open os — the point of no return
- Incomplete: some tissue passed but some retained → continued bleeding and cramping
- Complete: everything passed → symptoms settling
- Missed: minimal/no symptoms! May present only because dating scan shows no heartbeat or growth has stopped. The "silent" miscarriage. Brown spotting from old blood is typical
- Septic: any of the above + systemic infection signs (fever, tachycardia, tender uterus, offensive discharge)
| Sign | Pathophysiological Basis |
|---|---|
| Vaginal bleeding on speculum examination | Direct visualisation confirms the source of bleeding is from the cervical os (not cervical ectropion, polyp, or vaginal pathology). Blood may be bright red (acute) or brown/dark (old blood, as in missed miscarriage) |
| Cervical os status (closed vs. open) | Closed: threatened or complete or missed. Open: inevitable or incomplete. The internal os dilates in response to prostaglandin-mediated cervical ripening and uterine contractions. In cervical insufficiency, it dilates painlessly |
| Products of conception visible at os | In inevitable/incomplete miscarriage, tissue may be seen protruding through the cervical os. Removing this tissue (with sponge forceps) often provides dramatic relief of pain and bleeding by allowing the uterus to contract down |
| Uterine size discrepancy | Small-for-dates: suggests missed miscarriage (fetus stopped growing), incomplete (partially expelled), or complete (empty). Large-for-dates: consider molar pregnancy or incorrect dates |
| Uterine tenderness | Generalised tenderness: in septic miscarriage, due to endometritis / myometritis. Localised tenderness in adnexae: think ectopic pregnancy |
| Boggy, enlarged uterus | Retained products of conception prevent uterine involution; the myometrium cannot contract effectively around the residual tissue |
| Haemodynamic instability (tachycardia, hypotension, pallor) | Significant blood loss → hypovolaemic shock. Always assess haemodynamic status first! Heavy miscarriage can cause life-threatening haemorrhage, especially incomplete miscarriage with retained tissue preventing uterine contraction |
| Fever ≥ 38°C | In septic miscarriage: endotoxin and cytokine release → hypothalamic temperature reset. Ascending infection pathway: vagina → cervix → endometrium → myometrium → parametrium → peritoneum → systemic sepsis |
| Peritoneal signs | If septic miscarriage progresses to peritonitis; also consider ruptured ectopic pregnancy if peritonism is present with haemodynamic compromise |
Specific Clinical Scenarios by Type
- Mild vaginal bleeding (often brown or light red)
- May have mild lower abdominal discomfort
- Cervical os CLOSED
- Uterus appropriate size for dates
- Fetal cardiac activity PRESENT on ultrasound
- ~50% will continue to deliver; ~50% will progress to miscarriage
- Heavier bleeding with clots
- Significant cramping pain
- Cervical os OPEN — bulging membranes may be visible
- No tissue has yet been completely expelled
- Why is this "inevitable"? Once the cervix opens and membranes rupture, the pregnancy cannot be saved at previable gestational ages
- Continued heavy bleeding and cramping
- Cervical os OPEN
- Some products of conception have been passed (patient may bring tissue in a container)
- Retained tissue prevents effective myometrial contraction → ongoing bleeding (same principle as postpartum haemorrhage from retained placenta)
- Ultrasound: irregular echogenic material in the uterine cavity (retained products)
- Bleeding has settled or is minimal
- Pain has resolved
- Cervical os CLOSED (has closed after all tissue passed)
- Uterus small, firm, well-contracted
- Ultrasound: empty uterine cavity with thin endometrium
- Most common with early pregnancies (< 8 weeks)
- Often asymptomatic or only brown spotting
- Pregnancy symptoms may have disappeared
- Cervical os CLOSED
- Uterine size smaller than expected for dates
- Ultrasound diagnosis:
- Anembryonic pregnancy: gestational sac present but no embryo visible (mean sac diameter ≥ 25 mm with no embryo)
- Embryonic/fetal demise: embryo present but no cardiac activity (CRL ≥ 7 mm with no heartbeat on TVUS)
- Why does the body retain a non-viable pregnancy? The hormonal signals for expulsion (↓ progesterone) may be delayed; the trophoblast may continue producing low levels of hCG for some time even after fetal demise
- Fever, rigors, pelvic pain, offensive vaginal discharge
- Tender uterus on bimanual examination
- May have features of sepsis (tachycardia, hypotension, confusion)
- Risk factors: retained products of conception, prior instrumentation (especially unsafe abortion), prolonged rupture of membranes
- Organisms: commonly polymicrobial — E. coli, Bacteroides, Group B Streptococcus, Clostridium perfringens (can cause gas gangrene and overwhelming sepsis)
- This is a gynaecological emergency [6]
Never Forget — Always Exclude Ectopic Pregnancy!
Any woman of reproductive age presenting with vaginal bleeding and/or abdominal pain MUST have ectopic pregnancy excluded. Ruptured ectopic is life-threatening. Clinical features that should raise suspicion: unilateral adnexal tenderness, peritoneal signs, shoulder tip pain, haemodynamic instability, empty uterus on ultrasound with positive pregnancy test. Ruptured ectopic pregnancy is a cause of haemoperitoneum [7].
Additional Clinical Considerations
- All Rh-negative women presenting with miscarriage (> 12 weeks or requiring surgical intervention) should receive anti-D immunoglobulin to prevent Rh isoimmunisation
- Why? Fetomaternal haemorrhage during miscarriage exposes the Rh-negative mother to Rh-positive fetal red blood cells → maternal immune sensitisation → anti-D antibodies → haemolytic disease of the fetus in subsequent pregnancies
- Complete hydatidiform mole: uterus larger than dates, very high hCG, "snowstorm" appearance on USS, no fetus
- Partial hydatidiform mole: may have a fetus (triploid), uterus size for dates or small
- All products of conception from miscarriage should be sent for histological examination to exclude molar pregnancy
- Miscarriage causes significant grief, anxiety, and depression
- In Hong Kong, 10% of women develop depressive disorder within 3 months post-miscarriage [1]
- Partners also affected
- Sensitive, empathetic communication is essential
- Offer follow-up, counselling, and support resources
High Yield Summary
Definition: Spontaneous pregnancy loss < 24 weeks. Recurrent miscarriage = ≥2 (ESHRE) or ≥3 (RCOG) losses.
Epidemiology: 10–20% of recognised pregnancies; 80% in first trimester; risk increases sharply with maternal age.
Most common cause: Chromosomal abnormalities (~50–60% of sporadic miscarriages), especially autosomal trisomies.
Most important treatable cause of recurrent miscarriage: Antiphospholipid syndrome — causes uteroplacental thrombosis and complement-mediated injury. Diagnose with lupus anticoagulant (most thrombogenic), anti-cardiolipin, anti-β₂GPI × 2 measurements 12 weeks apart.
Classification: Threatened (closed os, viable) → Inevitable (open os) → Incomplete (open os, partial expulsion) → Complete (closed os, all expelled) → Missed (closed os, non-viable, retained) → Septic (infection of retained products = emergency).
Key clinical distinction: Cervical os status differentiates threatened from inevitable miscarriage.
Hong Kong psychiatric morbidity: 10% depression at 3 months post-miscarriage; risk factors include younger age, history of infertility and depression.
Always exclude ectopic pregnancy in any woman with early pregnancy bleeding.
Always send products for histology to exclude molar pregnancy.
Rh-negative women: give anti-D immunoglobulin.
Active Recall - Miscarriage: Definition, Epidemiology, Etiology and Clinical Features
[1] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p39, p101) [2] Senior notes: Maksim Medicine Notes.pdf [3] Senior notes: Ryan Ho Rheumatology.pdf (p69 – SLE and APLS section); Maksim Medicine Notes.pdf (p317 – APLS diagnostic criteria) [4] Senior notes: Ryan Ho Haemtology.pdf (p136 – Thrombophilia screen); Maksim Medicine Notes.pdf (p165 – Thrombophilia screening) [5] Senior notes: Ryan Ho Radiology.pdf (p35 – Obstetric imaging, signs of IUP) [6] Lecture slides: GCBC-OG-Gyn Emergency_Notes to students_Sep2024.pdf [7] Senior notes: Maksim Surgery Notes.pdf (p177 – Haemoperitoneum, ruptured ectopic pregnancy)
Differential Diagnosis of Miscarriage
The woman presenting with vaginal bleeding and/or lower abdominal pain in early pregnancy is one of the most common and most important clinical scenarios you will encounter. The differential diagnosis is broad and includes life-threatening conditions. Your job is to systematically work through the possibilities, because getting it wrong — particularly missing an ectopic pregnancy — can be fatal.
Let me walk you through how to think about this from first principles.
A woman of reproductive age presents with:
- Vaginal bleeding (PV bleeding), AND/OR
- Lower abdominal / pelvic pain, AND
- A positive pregnancy test (or known pregnancy)
The fundamental question is: What is the location and viability of this pregnancy, and is there an alternative or coexisting pathology?
Organising the Differential Diagnosis
The best way to think about this is to divide differentials into pregnancy-related and non-pregnancy-related causes, then subdivide by anatomical location and urgency.
These are the various types of miscarriage and related intrauterine pregnancy complications:
| Diagnosis | Key Distinguishing Features | Why It Matters |
|---|---|---|
| Threatened miscarriage | PV bleeding, closed cervical os, viable fetus on USS, uterus = dates | ~50% will continue; needs follow-up USS |
| Inevitable miscarriage | PV bleeding, cramping, open cervical os, no tissue passed yet | Cannot be saved; prepare for medical/surgical management |
| Incomplete miscarriage | PV bleeding + tissue passage, open os, retained products on USS | Ongoing bleeding due to retained tissue preventing uterine contraction; may need evacuation |
| Complete miscarriage | Symptoms settling, closed os, empty uterus on USS | Confirm with USS + falling hCG; most common < 8 weeks |
| Missed miscarriage | Minimal symptoms (often no PV bleeding), closed os, non-viable fetus on USS, uterus smaller than dates | Diagnosed after routine scan is booked — i.e. they were meant to be 12 weeks, but now they are 8 weeks in terms of size [1] |
| Septic miscarriage | Fever, offensive discharge, tender uterus, any os status | Gynaecological emergency — sepsis pathway |
| Anembryonic pregnancy | Subset of missed miscarriage; large gestational sac with no embryo | Mean sac diameter ≥ 25 mm with no embryo |
Sequence for Memorisation
Think about it as a sequence [1]: Starting from threatened (mild bleeding, closed os, expected uterine size) → progressing to inevitable (pain, open os, BUT no tissue passage yet, corresponding uterine size) → then incomplete (pain with tissue passage, open os, smaller uterus due to loss of mass) → complete (everything expelled, symptoms settled, closed os). The exception is missed/silent miscarriage, which is the asymptomatic form detected only on routine follow-up ultrasound.
| Diagnosis | Key Distinguishing Features | Why It Matters |
|---|---|---|
| Ectopic pregnancy | Unilateral pelvic/adnexal pain, PV bleeding (often dark/scanty), empty uterus or pseudo-sac on USS, bagel sign or complex inhomogeneous adnexal mass separate to ovary [2], ± shoulder tip pain, ± haemodynamic instability | Life-threatening if ruptured — must always be excluded in ANY woman with early pregnancy bleeding. Ruptured ectopic is a cause of haemoperitoneum [3][4] |
| Heterotopic pregnancy | Coexisting IUP + ectopic; rare spontaneously (~1:30,000) but ↑ with IVF (~1:100) | The presence of an IUP does NOT exclude a concurrent ectopic, especially in IVF pregnancies |
| Pregnancy of unknown location (PUL) | Positive hCG but absent intrauterine pregnancy and no definite USG evidence of ectopic pregnancy [2] | Could be very early IUP, resolving miscarriage, or ectopic — needs serial hCG + repeat USS |
Ectopic Pregnancy — The Diagnosis You Must Not Miss
USG features suggestive of ectopic pregnancy [2]: Bagel sign (hyperechoic ring representing the ectopic gestational sac in the tube) or a complex, inhomogeneous adnexal mass moving separately to the ovary; empty uterus or pseudo-sac (a small fluid collection within the cavity that mimics a gestational sac but lacks the double-decidual sign and yolk sac); moderate to large amount of free fluid in POD suggestive of haemoperitoneum.
| Diagnosis | Key Distinguishing Features | Why It Matters |
|---|---|---|
| Gestational trophoblastic disease (GTD) — molar pregnancy | Molar pregnancy can mimic threatened miscarriage — due to abdominal pain + per-vaginal bleeding [1][5][6]. Very high β-hCG (disproportionate to dates), "snowstorm" appearance on USS (complete mole), uterus large-for-dates, theca lutein cysts, hyperemesis, early pre-eclampsia, hyperthyroidism | Gestational trophoblastic disease is an important differential diagnosis of threatened miscarriage [5][6]. Must send all products of conception for histology to exclude. Malignant potential (choriocarcinoma) |
Why does molar pregnancy cause such high hCG? In a complete mole, the entire conceptus is abnormal trophoblast (46,XX or 46,XY — entirely paternal in origin). Trophoblast is the tissue that produces hCG. More trophoblast = more hCG. The markedly elevated hCG also explains the associated hyperemesis (hCG stimulates the vomiting centre and has TSH-like activity → secondary hyperthyroidism).
Must-Know Lecture Point
Gestational trophoblastic disease is an important differential diagnosis of threatened miscarriage [5][6]. Hyperemesis gravidarum can be life-threatening and it is important to exclude other specific diagnoses [5][6]. Always think of GTD when hCG is disproportionately elevated or the ultrasound findings are atypical.
These conditions can present with PV bleeding and/or pelvic pain and may coexist with early pregnancy or be confused with miscarriage:
| Diagnosis | Key Distinguishing Features | Why It Mimics Miscarriage |
|---|---|---|
| Ruptured ovarian cyst | Sudden unilateral pelvic pain ± PV bleeding, may cause haemoperitoneum | Acute pelvic pain + positive pregnancy test (incidental early IUP) can mimic ectopic or miscarriage |
| Ovarian torsion | Acute severe unilateral colicky pain, nausea/vomiting, enlarged ovary on USS with absent Doppler flow | Pain out of proportion; pregnancy hormones ↑ cyst formation → ↑ torsion risk |
| Ruptured corpus luteum cyst | Right-sided more common (corpus luteum of pregnancy), sudden pain, free fluid on USS | Very common in early pregnancy; can cause significant haemoperitoneum |
| Pelvic inflammatory disease (PID) | Bilateral lower abdominal pain, cervical motion tenderness, vaginal discharge, fever | Rarely coexists with pregnancy but must be considered; ascending infection |
| Cervical pathology (ectropion, polyp, cervicitis, carcinoma) | Bleeding is postcoital or contact-related, cervix abnormal on speculum | Bleeding source is cervix, NOT uterine cavity; pregnancy may be intact |
| Fibroid complications | Red degeneration of fibroid in pregnancy (acute pain over fibroid, low-grade fever, localised tenderness) | Common in pregnancy due to ↑ oestrogen → rapid fibroid growth → outgrows blood supply → necrosis |
These are "medical mimics" — conditions that can present with abdominal pain in early pregnancy and be confused with obstetric emergencies:
| Diagnosis | Key Distinguishing Features | Why It's in the Differential |
|---|---|---|
| Urinary tract infection / pyelonephritis | Dysuria, frequency, loin pain, fever, ↑ WBC in urine | Very common in pregnancy; suprapubic pain may mimic miscarriage |
| Appendicitis | RIF pain (may be higher in pregnancy as caecum displaced), anorexia, nausea, Rovsing sign | Most common non-obstetric surgical emergency in pregnancy; delayed diagnosis → perforation → sepsis |
| Urinary calculus (renal colic) | Severe colicky flank → groin pain, haematuria | Acute abdominal pain in young woman; can be mistaken for ectopic/miscarriage |
| DKA | Known DM or new-onset, abdominal pain, vomiting, Kussmaul breathing, ketotic breath | Most important medical DDx of acute abdomen includes DKA [7][8] |
| Acute MI | Chest/epigastric pain, ECG changes, troponin elevation | Important medical DDx of acute abdomen [7][8]; rare in reproductive age but not impossible |
The approach follows a logical sequence: stabilise → confirm pregnancy → locate pregnancy → assess viability → exclude dangerous mimics.
Need a second scan to make the diagnosis (either a second opinion or a second scan a minimum of 7 days after the first) [9] — this is critical for missed miscarriage. Never diagnose fetal demise on a single scan unless the findings are unequivocal (CRL ≥ 7 mm with no heartbeat), and even then a confirmatory scan is recommended to avoid misdiagnosis.
| Feature | Threatened Miscarriage | Ectopic Pregnancy | Molar Pregnancy | Complete Miscarriage |
|---|---|---|---|---|
| PV bleeding | Light, may be brown | Scanty, dark ("prune juice") | Variable, may pass vesicles | Had heavy bleeding, now settled |
| Pain | Mild/absent | Unilateral, sharp | Cramping | Resolved |
| Cervical os | Closed | Closed | May be open | Closed |
| USS | IUP with fetal heartbeat | Empty uterus ± adnexal mass/free fluid | Snowstorm / cluster of vesicles | Empty uterus, thin endometrium |
| β-hCG | Rising appropriately | Rising suboptimally or plateauing | Disproportionately high | Falling |
| Uterine size | = dates | May be slightly enlarged | Often > dates | < dates |
| Unique features | — | Shoulder tip pain, peritonism | Hyperemesis, hyperthyroidism, theca lutein cysts, early pre-eclampsia | History of tissue passage |
Important Concepts to Understand
From first principles: an ectopic pregnancy (Greek: ek- = out, topos = place → "out of place") is one implanted outside the uterine cavity, most commonly in the fallopian tube (~95%). The tube wall lacks the thick decidualised endometrium and expansile myometrium of the uterus. As the trophoblast invades, it erodes through the thin tubal wall → rupture → massive intra-abdominal haemorrhage → haemorrhagic shock → death if not treated.
Ruptured ectopic pregnancy is listed as a cause of haemoperitoneum [3] and as a life-threatening cause of acute abdomen [8].
- The discriminatory level is the serum β-hCG level above which a viable intrauterine pregnancy should be visible on TVUS
- Generally 1,500–2,000 mIU/mL for TVUS
- If β-hCG is ABOVE this level and the uterus is empty → high suspicion for ectopic (or complete miscarriage with still-elevated hCG, or very early multiple pregnancy)
- If β-hCG is BELOW this level and the uterus is empty → PUL (pregnancy of unknown location) — could be early IUP, ectopic, or resolving miscarriage → serial hCG monitoring
- Normal early IUP: β-hCG approximately doubles every 48 hours (minimum rise ~66% in 48h at low hCG levels, though this varies)
- Failing pregnancy (miscarriage): β-hCG rising suboptimally or falling
- Ectopic pregnancy: β-hCG rising suboptimally (slower than expected) or plateauing — the ectopic trophoblast produces hCG but less efficiently than a normally implanted pregnancy
- Molar pregnancy: β-hCG disproportionately elevated for gestational age
PUL Management Pearl
A pregnancy of unknown location is NOT a diagnosis — it is a description of a clinical situation requiring further investigation. The management is serial β-hCG monitoring (48-hour intervals) combined with clinical assessment and repeat USS. Never assume a PUL is "just an early pregnancy" — it could be an ectopic that hasn't been visualised yet. Management is according to the viability of the pregnancy [2].
This is your practical bedside approach:
-
Speculum examination (do this BEFORE bimanual):
- Look at the cervical os: open or closed? — this is the single most important clinical sign
- Look for products of conception at the os (remove with sponge forceps → relieves pain/bleeding)
- Look for alternative bleeding sources: cervical ectropion, polyp, cervical carcinoma, vaginal laceration
- Look for vesicles (grape-like structures) → molar pregnancy
-
Bimanual examination:
- Uterine size: correlates with dates? Smaller? Larger?
- Uterine tenderness: generalised (septic miscarriage), localised adnexal (ectopic)
- Cervical motion tenderness ("chandelier sign"): strongly suggestive of ectopic pregnancy or PID
- Adnexal mass: tubal ectopic, ovarian cyst, corpus luteum
Exam High Yield: The 'Open Os' Rule
If the cervical os is open and there is active bleeding in confirmed early pregnancy, the diagnosis is either inevitable or incomplete miscarriage. This distinction is clinically made by whether products have been partially passed. Once the os is open, the pregnancy cannot be saved — this determines management. Clinical differentiation for the different types of miscarriage is a key exam skill [9].
Miscarriage is the preferred term as compared to spontaneous abortion [9]. The differential diagnosis of early pregnancy bleeding encompasses:
- Intrauterine pregnancy complications: threatened → inevitable → incomplete → complete → missed → septic miscarriage
- Ectopic pregnancy (must always be excluded — life-threatening)
- Gestational trophoblastic disease (important differential of threatened miscarriage) [5][6]
- Gynaecological causes: cervical pathology, ovarian cyst rupture/torsion, fibroid degeneration, PID
- Non-gynaecological causes: UTI, appendicitis, renal colic, DKA, acute MI [7][8]
Importance of pelvic sonography in the diagnosis [9] — USS (specifically TVUS) is the cornerstone investigation that allows you to locate the pregnancy, assess viability, and exclude ectopic and molar pregnancy.
Best treatment is still evolving [9] — management options (expectant, medical, surgical) will be discussed in the next section.
High Yield Summary
Differential diagnosis of early pregnancy bleeding — the three must-not-miss diagnoses:
- Ectopic pregnancy — can kill within hours if ruptured. Look for empty uterus + adnexal mass + free fluid on USS.
- Gestational trophoblastic disease — can mimic threatened miscarriage. Look for disproportionately high hCG, snowstorm USS, uterus large-for-dates.
- Septic miscarriage — can progress to septic shock. Look for fever, offensive discharge, tender uterus.
Key differentiating tool: Cervical os status (closed = threatened/complete/missed; open = inevitable/incomplete).
Key investigation: Transvaginal USS + serum β-hCG. Need a second scan ≥ 7 days later to confirm missed miscarriage.
Always send products of conception for histology to exclude molar pregnancy.
PUL is not a diagnosis — it requires serial hCG monitoring and repeat USS until the pregnancy is located or resolved.
Active Recall - Differential Diagnosis of Miscarriage
References
[1] Lecture slides: Block C - Complications of Early Pregnancy (CFB WCS in 2023_24).pdf (p14, p87) [2] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p52 — USS features of ectopic) [3] Senior notes: Maksim Surgery Notes.pdf (p177 — Haemoperitoneum, ruptured ectopic pregnancy) [4] Senior notes: Ryan Ho Cardiology.pdf (p227 — DDx of ruptured AAA includes ruptured ectopic) [5] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p111 — Summary: GTD is important DDx of threatened miscarriage) [6] Lecture slides: Block C - Complications of Early Pregnancy (CFB WCS in 2023_24).pdf (p87 — Molar pregnancy can mimic threatened miscarriage) [7] Senior notes: Maksim Medicine Notes.pdf (p119 — DDx of abdominal pain: DKA, MI, Addisonian crisis) [8] Senior notes: Maksim Surgery Notes.pdf (p45 — Life-threatening DDx of acute abdomen) [9] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p26 — second scan rule; p109 — summary)
Diagnosing miscarriage is fundamentally about answering three questions in sequence:
- Is there a pregnancy? (pregnancy test)
- Where is the pregnancy? (ultrasound — intrauterine vs. ectopic vs. unknown location)
- Is the pregnancy viable? (ultrasound criteria + serial hCG)
And then a fourth question that runs in parallel: 4. Is there a dangerous mimic or coexisting pathology? (GTD, sepsis, haemodynamic compromise)
Let me take you through each layer systematically.
Diagnostic Criteria for Miscarriage
A. Ultrasound Diagnostic Criteria (NICE 2023 / RCOG)
These are the definitive criteria for confirming pregnancy failure on transvaginal ultrasound (TVUS). They exist because we must be absolutely certain before diagnosing miscarriage — an error here means potentially terminating a viable pregnancy.
Need a second scan to make the diagnosis (either a second opinion or a second scan a minimum of 7 days after the first) [9].
| Finding | Diagnostic Threshold | Rationale |
|---|---|---|
| Crown-rump length (CRL) with no heartbeat | CRL ≥ 7 mm with no detectable cardiac activity on TVUS | An embryo of this size should have a visible heartbeat. Why 7 mm? Below this, the embryo may be too small for current ultrasound technology to reliably detect cardiac motion — a false-negative heartbeat at < 7 mm could lead to misdiagnosis of a viable pregnancy |
| Mean sac diameter (MSD) with no embryo | MSD ≥ 25 mm with no visible embryo (anembryonic pregnancy) | A gestational sac of this size should contain a visible embryo with yolk sac. Why 25 mm? This is a conservative cutoff with high specificity — below this size, an early but viable embryo might simply not yet be detectable |
The Safety Margin Principle
These cutoffs (CRL ≥ 7 mm, MSD ≥ 25 mm) are deliberately conservative. Older guidelines used smaller cutoffs (CRL ≥ 5 mm, MSD ≥ 20 mm), but case reports of viable pregnancies misdiagnosed as miscarriages led to raising the thresholds. In 2024–2026 practice, if there is ANY doubt, repeat the scan in ≥ 7 days. It is better to delay management by one week than to evacuate a viable pregnancy.
If the findings are below the definitive thresholds, the pregnancy is of uncertain viability and requires follow-up:
| Finding | Action |
|---|---|
| Gestational sac with MSD < 25 mm and no embryo | Repeat TVUS in ≥ 7 days to assess for interval growth and embryo appearance |
| Embryo with CRL < 7 mm and no heartbeat | Repeat TVUS in ≥ 7 days to reassess for cardiac activity |
| Gestational sac with yolk sac but no embryo | Repeat TVUS in ≥ 7–14 days |
| Empty intrauterine sac without yolk sac | Repeat TVUS in ≥ 14 days — very early pregnancy possible |
Why the waiting period? At very early gestational ages (5–6 weeks), a normal pregnancy may not yet show an embryo or heartbeat. The embryo becomes visible at ~6 weeks and the heartbeat at ~6–7 weeks. Rescanning after ≥ 7 days allows enough time for a viable pregnancy to declare itself through growth (the CRL should increase by ~1 mm/day).
This uses the combination of symptoms + speculum findings + ultrasound to classify the type of miscarriage:
| Type | Bleeding | Pain | Cervical Os | USS Findings | β-hCG |
|---|---|---|---|---|---|
| Threatened | Light | Mild/absent | Closed | IUP with fetal heartbeat | Rising appropriately |
| Inevitable | Moderate–heavy | Cramping | Open | IUP, may show low-lying sac, no tissue passed yet | Variable |
| Incomplete | Heavy, clots | Cramping | Open | Retained products of conception (RPOC) — heterogeneous echogenic material in cavity | Falling but still detectable |
| Complete | Settling/stopped | Resolved | Closed | Empty uterine cavity, thin endometrium ( < 15 mm) | Falling towards zero |
| Missed | Minimal/brown | Minimal | Closed | Non-viable IUP (CRL ≥ 7 mm with no heartbeat, OR MSD ≥ 25 mm with no embryo) | Falling or plateauing, low for dates |
| Septic | Variable, offensive | Pelvic pain | Variable | May show RPOC ± fluid collections, ± gas in myometrium (severe) | Variable |
Recurrent miscarriage workup is triggered by ≥2 losses (ESHRE 2017) or ≥3 losses (RCOG Green-top 2023) [1]. The following investigations are directed at identifying treatable underlying causes.
Investigations for recurrent miscarriage [10]:
| Investigation | What It Tests | Rationale |
|---|---|---|
| Antiphospholipid antibodies | Lupus anticoagulant, anti-cardiolipin Ab, anti-β₂GPI Ab | APLS is the most important treatable cause of recurrent miscarriage. Requires two positive results ≥ 12 weeks apart [3][11] |
| Thyroid function — TSH, anti-TPO | Thyroid status and autoimmunity | Hypothyroidism and thyroid autoimmunity both ↑ miscarriage risk. TSH should be < 2.5 mIU/L in first trimester for optimal outcome |
| Karyotyping | Parental peripheral blood karyotype | Identifies balanced translocations / inversions in parents (found in ~3–5% of couples with recurrent loss) → genetic counselling + PGT-SR option |
| Screening for uterine malformations | 3D pelvic USS, saline infusion sonography, hysteroscopy, or MRI | Septate uterus (most common treatable anomaly), submucosal fibroids, intrauterine adhesions |
| Thrombophilias for second trimester miscarriage | Protein C, Protein S, Antithrombin, Factor V Leiden, Prothrombin G20210A | Inherited thrombophilias are particularly associated with second-trimester losses and late pregnancy complications [10][11] |
Timing of Thrombophilia Screening
Do not test at time of VTE event, or while patients are receiving anticoagulants (withhold warfarin × 2 weeks, DOAC × at least 2 days) [11]. Similarly, do not test during pregnancy or the acute postpartum period — pregnancy itself is a hypercoagulable state that can give false results for protein C/S and antithrombin levels.
Diagnostic Algorithm
When the pregnancy cannot be located on ultrasound:
Why 66%? In a normal early intrauterine pregnancy, hCG doubles approximately every 48 hours. The minimum acceptable rise is ~66% (i.e., roughly a doubling). A rise below this is suspicious for a non-viable or ectopic pregnancy, though ~15% of normal IUPs may show a slower initial rise — hence this is a guide, not an absolute rule.
Investigation Modalities
- What it detects: β-hCG in urine (qualitative — positive or negative)
- Sensitivity: detects hCG at ~20–25 mIU/mL → positive from ~4 weeks gestation (roughly the time of the expected period)
- Clinical role: A negative pregnancy test effectively rules out ectopic pregnancy [12]. This is because both intrauterine and ectopic pregnancies produce hCG. If hCG is undetectable, there is no viable trophoblastic tissue.
- Limitation: does not quantify hCG, does not locate the pregnancy, false negatives possible with very dilute urine or very early pregnancy (< 4 weeks)
-
What it measures: exact level of β-hCG in blood (mIU/mL)
-
Clinical roles:
- Single measurement: helps correlate with USS findings (is the hCG above the discriminatory zone where an IUP should be visible?)
- Serial measurements (48h apart): determines the trend — rising (viable IUP), suboptimally rising/plateauing (ectopic or failing), falling (resolving/complete miscarriage)
- Disproportionately high: think molar pregnancy (hCG > 100,000 mIU/mL common in complete mole)
-
The discriminatory zone: the hCG level above which a viable IUP should be visible on TVUS
- TVUS: ~1,500–2,000 mIU/mL (institution-dependent)
- TAS: ~6,500 mIU/mL (less sensitive than TVUS)
- If hCG is above the discriminatory zone and the uterus is empty → high suspicion for ectopic pregnancy (or complete miscarriage with still-elevated hCG, or early multiple pregnancy)
| hCG Trend (48h) | Interpretation |
|---|---|
| Rising ≥ 66% | Likely viable IUP (but does not exclude ectopic) |
| Rising < 66% or plateau | Abnormal pregnancy — ectopic or failing IUP |
| Falling > 50% | Likely resolving (complete miscarriage or resolving ectopic) |
| Falling < 50% | Indeterminate — close follow-up needed |
3. Transvaginal Ultrasound (TVUS)
Importance of pelvic sonography in the diagnosis [9] — this is the single most important investigation in early pregnancy bleeding.
- TVUS is preferred over transabdominal scan (TAS) in early pregnancy because:
- Higher frequency probe (5–10 MHz) → better resolution
- Closer to pelvic organs → earlier detection of intrauterine and ectopic pregnancy
- No need for full bladder
| Gestational Age | Expected TVUS Findings | Source |
|---|---|---|
| ~5 weeks | Gestational sac visible (small anechoic structure in endometrium, double-sac sign: parietal decidua surrounding capsular decidua → indicates IUP) | [5] |
| ~5.5–6 weeks | Yolk sac visible → indicates definite IUP | [5] |
| ~6–7 weeks | Cardiac activity usually identified together with embryo (CRL ~2–5 mm) | [5] |
| 7–12 weeks | Growing embryo/fetus with clearly visible heartbeat, CRL measurable for dating |
| Type | USS Findings |
|---|---|
| Threatened | IUP with fetal heartbeat present. May see subchorionic haematoma (collection of blood between gestational sac and uterine wall — indicates some decidual separation but does not necessarily mean the pregnancy will fail) |
| Inevitable | IUP present but may show low-lying gestational sac near internal os, ± disrupted sac, ± open internal os on USS |
| Incomplete | Heterogeneous echogenic material in uterine cavity (retained products of conception/RPOC). Endometrial thickness > 15 mm is suggestive of significant retained tissue |
| Complete | Empty uterine cavity with thin endometrium (typically < 15 mm). No retained products |
| Missed | Embryo present with no cardiac activity (CRL ≥ 7 mm) OR empty gestational sac (MSD ≥ 25 mm) = anembryonic pregnancy. Confirmed by repeat scan ≥ 7 days later [9] |
| Molar pregnancy | "Snowstorm" appearance (complete mole: diffuse echogenic material with multiple small cystic spaces filling the uterus, no fetus). Partial mole: may have fetal parts + cystic placental changes. May see bilateral theca lutein cysts |
Subchorionic Haematoma
A subchorionic haematoma is a common finding in threatened miscarriage (seen in ~20% of cases). It represents bleeding between the chorion (fetal membranes) and the uterine wall. Small haematomas ( < 20% of gestational sac circumference) generally have a good prognosis. Large haematomas ( > 50% of sac circumference) are associated with increased risk of subsequent miscarriage. The mechanism: partial detachment of the trophoblast from the decidua → exposed decidual vessels bleed into the subchorionic space.
USG features suggestive of ectopic pregnancy [2]:
- Bagel sign (tubal ring: hyperechoic ring in the adnexa representing the ectopic gestational sac)
- Complex, inhomogeneous adnexal mass moving separately to the ovary
- Empty uterus or pseudo-sac (small intracavitary fluid collection without double-decidual sign or yolk sac)
- Moderate to large amount of free fluid in POD suggestive of haemoperitoneum [2]
- Live ectopic (embryo with cardiac activity in adnexa) — rare but pathognomonic
Hb — also note MCV [13]:
- Haemoglobin: assesses degree of blood loss; guides need for transfusion. Active miscarriage can cause significant anaemia
- MCV: why note MCV? A low MCV (microcytic anaemia) may indicate pre-existing iron deficiency, which is very common in women of reproductive age and means even modest blood loss from miscarriage can tip the patient into symptomatic anaemia. This affects management (iron supplementation, lower threshold for transfusion)
- WCC: elevated white cell count raises concern for septic miscarriage or concurrent infection
- Platelets: low platelets may suggest DIC (in septic miscarriage) or underlying thrombocytopenia (e.g., APLS-associated)
Rh factor (no need if known!) [13]:
- Why? Rh-negative women who miscarry (especially > 12 weeks or with surgical intervention) need anti-D immunoglobulin to prevent Rh isoimmunisation
- If the Rh status is already known from previous testing, no need to repeat — but if unknown, it is essential to check
- Group and Screen (also called "Type and Screen"): determines ABO group and screens for atypical red cell antibodies — essential if transfusion may be needed
Hb, Rh, type and screen [12] — these are the baseline bloods for any woman presenting with early pregnancy bleeding.
Tissue mass for histology — ?decidua ?chorionic villi ?fetal parts [13]:
This is a critically important investigation that is often underappreciated. All products of conception should be sent for histological examination.
- What to look for:
- Decidua: confirms the tissue is from an intrauterine pregnancy site (but decidual reaction alone can also occur with ectopic pregnancy)
- Chorionic villi: the definitive histological confirmation that the tissue is from a pregnancy. Presence of chorionic villi in uterine curettings confirms intrauterine pregnancy and effectively excludes ectopic
- Fetal parts: confirms embryonic/fetal tissue
- Hydropic villi / trophoblastic proliferation: suggests molar pregnancy — this is why histology is essential. You cannot diagnose GTD without it
Why Histology Is Non-Negotiable
Gestational trophoblastic disease is an important differential diagnosis of threatened miscarriage [5][6]. Molar pregnancy can be missed clinically and even on ultrasound (especially partial moles). The ONLY way to definitively exclude it is histological examination of products of conception. Missing a molar pregnancy means missing surveillance for gestational trophoblastic neoplasia (GTN), which includes the potentially fatal choriocarcinoma. Always send tissue for histology.
7. Investigations for Recurrent Miscarriage
These are performed after ≥2 losses (ESHRE) or ≥3 losses (RCOG) and are directed at identifying treatable causes [1][10]:
| Investigation | What It Tests | Key Findings and Interpretation |
|---|---|---|
| Antiphospholipid antibodies [10] | Lupus anticoagulant (LA), anti-cardiolipin IgG/IgM, anti-β₂GPI IgG/IgM | Positive on ≥2 occasions at least 12 weeks apart confirms APLS [3]. LA: detected by DRVVT/KCT (functional assay); aCL/anti-β₂GPI: by ELISA, must be moderate-to-high titre ( > 40 units or > 99th percentile). LA is the most thrombogenic. Anti-β₂GPI is the most specific but has limited sensitivity [3] |
| TSH + anti-TPO [10] | Thyroid function and autoimmunity | TSH > 2.5 mIU/L in first trimester associated with ↑ miscarriage risk. Anti-TPO positivity is an independent risk factor for miscarriage even with normal TSH (marker of immune dysregulation + subclinical thyroid insufficiency under pregnancy stress) |
| Parental karyotype [10] | Chromosomal structure of both parents | ~3–5% of couples with recurrent miscarriage carry a balanced translocation or inversion. The carrier is phenotypically normal but produces unbalanced gametes → recurrent aneuploid conceptions. Enables genetic counselling and consideration of PGT-SR (preimplantation genetic testing for structural rearrangements) with IVF |
| Screening for uterine malformations [10] | Uterine cavity anatomy | 3D USS / saline infusion sonohysterography (SIS): first-line; can distinguish septate (most common, treatable by hysteroscopic septoplasty) from bicornuate uterus. Hysteroscopy: gold standard for intracavitary assessment (polyps, fibroids, adhesions, septa). MRI pelvis: gold standard for external uterine contour (distinguishes septate from bicornuate) |
| Thrombophilia screen [10][11] | Inherited thrombophilias | Protein C, Protein S, Activated Protein C Resistance (APCR), Anti-thrombin (AT), Factor V Leiden PCR, Prothrombin G20210A mutation [11]. Indicated particularly for second-trimester miscarriage [10]. Testing timing: ≥2 weeks after stopping anticoagulation, not during acute thrombotic event [11] |
| Investigation | Rationale |
|---|---|
| Fasting glucose / HbA1c | Screen for diabetes mellitus (poorly controlled DM is embryotoxic) |
| Prolactin | Hyperprolactinaemia → anovulation/luteal insufficiency |
| Products of conception karyotype | Cytogenetic analysis of miscarriage tissue determines if the loss was due to aneuploidy (no further workup needed for that loss) vs. chromosomally normal embryo (more concerning for a maternal/paternal cause) |
| Pelvic USS / 3D USS | Baseline assessment of uterine anatomy (as above) |
| Endometrial biopsy | In selected cases: chronic endometritis (CD138+ plasma cells), luteal phase assessment |
| Anti-nuclear antibodies (ANA) | Screen for SLE / connective tissue disease if clinical suspicion [3] |
| Progesterone level (mid-luteal) | Assesses corpus luteum function (luteal phase deficiency); level > 30 nmol/L suggests adequate luteal function |
Approach to Recurrent Miscarriage Workup — The Mnemonic 'TULIPS'
A useful mnemonic for investigations in recurrent miscarriage:
- T = Thyroid (TSH + anti-TPO)
- U = Uterine anatomy (3D USS / hysteroscopy / MRI)
- L = Lupus anticoagulant + antiphospholipid antibodies
- I = Inherited thrombophilia (Protein C/S, Factor V Leiden, etc.)
- P = Parental karyotype
- S = Sugar (fasting glucose / HbA1c)
| Investigation | When to Order | What It Tells You |
|---|---|---|
| Coagulation screen (PT, APTT, fibrinogen) | Suspected DIC (septic miscarriage, massive haemorrhage) | Full-house clotting: ↓platelets, ↑PT/APTT, ↑D-dimer, ↓fibrinogen [14] suggests DIC — obstetric causes include septic abortion, amniotic fluid embolism [14] |
| Blood cultures | Fever, suspected septic miscarriage | Identify causative organism, guide antibiotic therapy |
| C-reactive protein (CRP) | Suspected infection | Non-specific inflammatory marker; markedly elevated in septic miscarriage |
| Renal function, electrolytes | Significant haemorrhage, sepsis, or prolonged vomiting | Assess for AKI (hypovolaemia or sepsis), electrolyte derangement |
| Liver function tests | Suspected HELLP (rare at < 24 weeks), DIC, sepsis | ↑AST/ALT, ↑LDH suggest haemolysis or hepatic involvement |
| Diagnostic laparoscopy [12] | Suspected ectopic pregnancy when USS is inconclusive and clinical concern is high | Direct visualisation of tubes and pelvis; both diagnostic and therapeutic (can perform salpingectomy/salpingotomy) |
Integration: Putting It All Together
When a woman presents with bleeding/pain in early pregnancy, the initial investigations are:
Investigations for acute miscarriage presentation [12][13]:
- Hb — also note MCV [13]
- Rh factor (no need if known!) [13]
- Pelvic sonogram [13] — TVUS preferred
- Tissue mass for histology — ?decidua ?chorionic villi ?fetal parts [13]
- Urine pregnancy test (if pregnancy not yet confirmed)
- Serum β-hCG (if PUL, if USS inconclusive, or to correlate with USS findings)
- Type and screen [12] (if significant bleeding or intervention planned)
After ≥2 losses (ESHRE) or ≥3 losses (RCOG) [1]:
Investigations for recurrent miscarriage [10]:
- Antiphospholipid antibodies (LA, aCL, anti-β₂GPI)
- Thyroid function — TSH, anti-TPO
- Karyotyping (parental)
- Screening for uterine malformations (3D USS / hysteroscopy / MRI)
- Thrombophilias for second trimester miscarriage (Protein C/S, AT, Factor V Leiden, Prothrombin G20210A)
Plus additional investigations as clinically indicated: fasting glucose, prolactin, POC karyotype, endometrial biopsy.
High Yield Summary
Ultrasound Diagnostic Criteria for Missed Miscarriage (must memorise):
- CRL ≥ 7 mm with no cardiac activity → confirmed fetal demise
- MSD ≥ 25 mm with no embryo → confirmed anembryonic pregnancy
- Always confirm with a repeat scan ≥ 7 days later or a second opinion
Discriminatory zone for β-hCG:
- TVUS: 1,500–2,000 mIU/mL → IUP should be visible above this level
- If uterus is empty above discriminatory zone → suspect ectopic
Acute investigations: Hb (+ MCV), Rh factor, pelvic sonogram, tissue for histology, serum β-hCG
Recurrent miscarriage investigations (TULIPS): Thyroid (TSH + anti-TPO), Uterine anatomy, Lupus anticoagulant + aPL antibodies, Inherited thrombophilias, Parental karyotype, Sugar (glucose/HbA1c)
Histology of products is essential — to confirm intrauterine pregnancy (chorionic villi) and exclude molar pregnancy
APLS diagnosis requires two positive antibody tests ≥ 12 weeks apart (LA, aCL, or anti-β₂GPI at moderate-to-high titre)
Active Recall - Diagnosis and Investigations of Miscarriage
[1] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p39 — recurrent miscarriage definitions) [2] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p52 — USS features of ectopic pregnancy) [3] Senior notes: Ryan Ho Rheumatology.pdf (p73 — Revised Sapporo criteria for APLS) [5] Senior notes: Ryan Ho Radiology.pdf (p35 — Obstetric imaging, signs of IUP) [6] Lecture slides: Block C - Complications of Early Pregnancy (CFB WCS in 2023_24).pdf (p87 — Molar pregnancy mimics threatened miscarriage) [9] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p26 — second scan rule; p109 — summary) [10] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p40 — Investigations for recurrent miscarriage) [11] Senior notes: Ryan Ho Haemtology.pdf (p136 — Thrombophilia screen indications and tests); Senior notes: Maksim Medicine Notes.pdf (p165 — Thrombophilia screening) [12] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p44 — Investigations for ectopic pregnancy) [13] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p22 — Investigations for miscarriage) [14] Senior notes: Ryan Ho Haemtology.pdf (p136–137 — DIC pathogenesis and causes)
The management of miscarriage follows a tiered approach: first stabilise the patient, then choose the appropriate management strategy based on the type of miscarriage, clinical stability, patient preference, and individual circumstances. The key principle is that best treatment is still evolving [9] — and in 2025–2026, there is a strong emphasis on patient-centred, individualised care with shared decision-making.
Choice of mode of treatments is affected by ethnomedical beliefs, success rate and should be individualized [15][16].
Let me walk you through this systematically.
General Principles
Before any specific management, every woman presenting with miscarriage needs:
- ABCs: Airway, Breathing, Circulation — assess haemodynamic status first
- IV access: two large-bore cannulae if significant bleeding
- Bloods: FBC (Hb + MCV), Group and Rh, crossmatch if heavy bleeding
- Fluid resuscitation: crystalloid (normal saline or Hartmann's) if hypovolaemic
- Blood transfusion: if Hb critically low or ongoing massive haemorrhage
- Anti-D immunoglobulin: for all Rh-negative women (especially > 12 weeks gestation or if surgical intervention performed)
- Analgesia: paracetamol ± NSAIDs (safe once miscarriage is inevitable/confirmed; avoid in threatened miscarriage where fetus is viable as prostaglandin inhibition is theoretically concerning). Opioids for severe pain.
Miscarriages is associated with significant psychiatric morbidity although the prevalence may be lower in our population [15][16].
Healthcare providers can add to the trauma [15][16] — this is a crucial and often overlooked point. How you communicate matters enormously:
- Use sensitive, empathetic language
- Avoid phrases like "at least you know you can get pregnant" or "it was nature's way"
- Acknowledge the loss; offer follow-up, counselling referral, and support group information
- Provide written information (many hospitals have patient information sheets for expectant, medical, and surgical management of miscarriage) [15]
- In Hong Kong, 10% develop depressive disorder within 3 months post-miscarriage [1]
For most types of miscarriage (excluding threatened and complete), there are three management strategies:
| Strategy | Description | When Preferred |
|---|---|---|
| Expectant ("watch and wait") | Allow the body to expel the pregnancy tissue naturally | Patient preference, stable condition, small amount of retained tissue |
| Medical (misoprostol) | Pharmacological induction of uterine contractions to expel tissue | Patient preference, wants to avoid surgery, no contraindications |
| Surgical (suction evacuation) | Physical removal of products of conception under anaesthesia | Heavy bleeding, haemodynamic instability, patient preference, failed expectant/medical management, suspected GTD, septic miscarriage |
Management by Type of Miscarriage
Management: threatened — observation [17].
Rationale: The pregnancy is still viable (closed os, fetal heartbeat present). There is no intervention that can "fix" the situation if the pregnancy is going to fail, but ~50% will continue to term. The key is supportive care and monitoring.
Specific management:
- Rest and reassurance: advise the patient to avoid strenuous activity (though there is no strong evidence that bed rest prevents miscarriage)
- Avoid intercourse: theoretical concern about mechanical disruption, though evidence is limited
- Follow-up USS: in 1–2 weeks to confirm ongoing viability and growth
- Vaginal micronised progesterone is prescribed to women who have vaginal bleeding and have one or more previous first trimester miscarriage and continued till 16 completed weeks of gestation [17]
Progesterone in Threatened Miscarriage — The PRISM Trial
The landmark PRISM trial (2019, NEJM) showed that vaginal micronised progesterone (400 mg twice daily) improved live birth rates in women with threatened miscarriage who had a history of ≥1 prior miscarriage. The benefit was most pronounced in women with ≥3 prior miscarriages. The mechanism: progesterone supports the decidualised endometrium, suppresses myometrial contractility (by reducing gap junction formation and prostaglandin receptor expression), and promotes immune tolerance (Th2 shift) at the maternal-fetal interface. Continued till 16 completed weeks of gestation — this covers the period until the placenta has fully taken over progesterone production (the luteo-placental shift is complete by ~10–12 weeks, but the 16-week cutoff provides a safety margin) [17].
Who does NOT get progesterone? Women with threatened miscarriage who have no prior history of miscarriage — the PRISM trial showed no significant benefit in this group.
B. Missed Miscarriage (Silent Miscarriage) and Incomplete Miscarriage
Silent or incomplete miscarriage — basically expectant for 1–2 weeks, if stable; medical administration of misoprostol; suction evacuation for really bad bleeding [15].
These two types are grouped together because the management options are identical — all three strategies (expectant, medical, surgical) are available.
- What it involves: waiting for the body to spontaneously expel the pregnancy tissue, typically 1–2 weeks [15][18]
- Success rate: ~50% for missed miscarriage within 2 weeks; higher (~80%) for incomplete miscarriage (because some tissue has already been expelled)
- Monitoring: advise the patient to return if bleeding becomes very heavy (soaking > 2 pads per hour for > 2 hours), if she develops fever, or if pain becomes unbearable
- Follow-up: Follow up in Early Pregnancy Assessment Clinic 2 weeks after to confirm complete expulsion (repeat USS + urine hCG)
- When to convert to medical/surgical: if tissue not expelled within 2 weeks, or if complications arise (heavy bleeding, infection)
Why does expectant management work? Once the embryo dies, hCG levels fall → progesterone support withdraws → decidual necrosis → prostaglandin release → myometrial contractions → expulsion. The body's own mechanisms eventually clear the tissue, but this can take time.
Contraindications to expectant management:
- Haemodynamic instability / heavy uncontrolled bleeding
- Evidence of infection (septic miscarriage)
- Patient unable or unwilling to wait / return for follow-up
- Suspected molar pregnancy (need tissue for histology urgently)
Misoprostol 800 micrograms is taken vaginally or sublingually [19].
-
What is misoprostol? A synthetic prostaglandin E1 (PGE₁) analogue
- "Miso-" = from misoprostol, a prostaglandin analogue; "-prostol" from prostaglandin
- Mechanism: binds to EP2/EP3 prostaglandin receptors on myometrial cells → increases intracellular calcium → stimulates myometrial contractions; also ripens and softens the cervix (collagenase activation + increased water content in cervical stroma)
-
Regimen: Misoprostol 800 micrograms vaginally or sublingually [19]
- Can repeat dose after 48 hours if no response
- Some protocols add oral mifepristone (200 mg) 24–48 hours before misoprostol (mifepristone is an anti-progesterone → sensitises the uterus to prostaglandins → increases misoprostol efficacy from ~70% to ~85%)
-
Success rate: ~80–85% complete expulsion within 1–2 weeks (higher with mifepristone pretreatment)
-
Follow up in Early Pregnancy Assessment Clinic 2 weeks after treatment [19]
-
Side effects: cramping abdominal pain (expected — the drug is working), nausea, vomiting, diarrhoea (prostaglandin effect on GI smooth muscle), fever/chills (transient, prostaglandin-mediated pyrexia via hypothalamic PGE₂)
-
Contraindications to misoprostol:
- Known allergy to prostaglandins
- Suspected ectopic pregnancy (will not treat ectopic; delays definitive management)
- Haemodynamic instability (needs surgical management)
- Suspected molar pregnancy (need tissue for histology + risk of trophoblastic embolisation)
- Intrauterine device (IUD) in situ (remove first)
- Previous caesarean section / uterine surgery — relative contraindication (risk of uterine rupture, though very low in early pregnancy)
-
What it involves: suction evacuation — removal of products of conception by vacuum aspiration under anaesthesia (general or local/conscious sedation)
- Also called "evacuation of retained products of conception (ERPC)" or "suction curettage" or "manual vacuum aspiration (MVA)"
- Why suction, not sharp curettage? Suction is safer — lower risk of uterine perforation and Asherman syndrome (intrauterine adhesions) compared to sharp metal curettage. Sharp curettage is now largely obsolete for first-trimester evacuation
-
Indications:
- Suction evacuation for really bad bleeding [15] — haemodynamic instability, heavy uncontrolled bleeding
- Failed expectant or medical management
- Patient preference (some women prefer the certainty and speed of surgical completion)
- Suspected molar pregnancy (need complete tissue for histology)
- Septic miscarriage (urgent evacuation + antibiotics)
- Confirmed incomplete miscarriage with significant retained products
-
Success rate: > 95% complete evacuation in a single procedure
-
Procedure:
- Pre-operative cervical priming (misoprostol 400 mcg vaginal or sublingual 2–3h before, or osmotic dilator) → softens cervix → reduces risk of cervical trauma
- Anaesthesia (GA or local + sedation)
- Gentle cervical dilation (if needed)
- Suction catheter inserted → negative pressure applied → products aspirated
- All tissue sent for histology (to confirm pregnancy tissue and exclude GTD)
-
Complications (important — see Complications section for detail):
- Uterine perforation (~0.1–0.5%)
- Cervical trauma
- Incomplete evacuation / retained products
- Intrauterine adhesions (Asherman syndrome) — from aggressive curettage
- Infection (endometritis)
- Haemorrhage
-
Contraindications:
- Undiagnosed pregnancy of unknown location (must locate pregnancy first — evacuating the uterus when there is an ectopic will not treat the ectopic and delays diagnosis)
- Cervical stenosis (relative — requires careful dilation)
- Coagulopathy (correct first)
Practical Decision-Making
In practice, the choice between expectant, medical, and surgical management is a shared decision between the clinician and the patient. Factors that influence the choice:
- Patient preference (some women want to avoid surgery; others want it "over and done with")
- Gestational age (earlier gestations more amenable to expectant/medical; later first-trimester losses may benefit from surgical)
- Amount of retained tissue on USS
- Clinical stability (unstable = surgical)
- Cultural/ethnomedical beliefs — particularly relevant in Hong Kong where some patients may prefer one approach based on cultural attitudes [15][16]
- Access to follow-up (expectant/medical require reliable follow-up; if patient lives remotely or cannot return easily, surgical may be preferable)
Inevitable — basically expectant, if stable; suction evacuation for really bad bleeding [15][18].
- The pregnancy is already failing (open os), so the goal is to facilitate safe and complete passage of tissue
- Expectant: if bleeding is manageable and the patient is stable, allow natural expulsion
- Medical (misoprostol): can be used to accelerate expulsion if expectant management is too slow
- Surgical (suction evacuation): for really bad bleeding [15] or if the patient is haemodynamically unstable
Practical tip: If products of conception are visible at the cervical os during speculum examination, gently remove them with sponge forceps (ring forceps). This is both diagnostic (sends tissue for histology) and therapeutic — removing tissue from the os relieves the vasovagal response (cervical stimulation → vagus nerve activation → bradycardia and hypotension) and allows the uterus to contract, reducing bleeding.
Complete miscarriage — don't need to do anything, ask patient to come back after 3 weeks → do a urine hCG, to rule out ectopic pregnancy [15].
- No active intervention needed: all tissue has been expelled, bleeding and pain have settled
- But beware: beware of ectopic pregnancy [18] — a "complete miscarriage" could actually be a decidual cast (decidualised endometrium shed from the uterus in response to falling hCG from an ectopic pregnancy, mimicking passage of pregnancy tissue)
- Follow-up: urine pregnancy test at 3 weeks — should be negative. If still positive → suspect:
- Retained products of conception (not truly complete)
- Ectopic pregnancy
- Gestational trophoblastic disease
- Send any passed tissue for histology to confirm chorionic villi (confirms intrauterine pregnancy)
The 'Complete Miscarriage' Trap
Never assume a miscarriage is "complete" based on symptoms alone. A decidual cast from an ectopic pregnancy can look exactly like expelled products of conception to the patient. Always: (1) confirm with USS showing empty uterus + thin endometrium, (2) send tissue for histology (looking for chorionic villi), (3) follow up with urine hCG at 3 weeks [15][18].
This is a gynaecological emergency requiring immediate action:
- Resuscitation: IV access, fluids, oxygen, catheterise (monitor urine output)
- Bloods: FBC, coagulation screen (rule out DIC), blood cultures (× 2 sets), CRP, lactate, renal/liver function
- Broad-spectrum IV antibiotics: start immediately, do NOT wait for culture results
- Typical regimen: IV amoxicillin + IV metronidazole + IV gentamicin (covers Gram-positives, anaerobes, and Gram-negatives)
- Alternative: IV co-amoxiclav + IV gentamicin; or piperacillin-tazobactam
- Why metronidazole? Anaerobic organisms (Bacteroides, Clostridium) are common in pelvic sepsis from retained necrotic tissue — metronidazole targets anaerobes specifically
- Urgent surgical evacuation: once antibiotics are started and the patient is stabilised (ideally within hours, not days). Leaving infected retained products in situ is like leaving an abscess undrained — the source of sepsis must be removed
- Senior involvement: early escalation to consultant. If deteriorating → ITU referral, consider sepsis pathway (Surviving Sepsis guidelines)
- Watch for DIC: obstetric causes of DIC include septic abortion, amniotic fluid embolism, abruptio placentae [14]
Recurrent miscarriage — loss of ≥2 pregnancies (ESHRE 2017), loss of ≥3 pregnancies (Green-top 2023) [1].
Management of recurrent pregnancy loss — Clinical SOP, Division of Reproductive Medicine [1].
The management depends on the identified underlying cause:
| Cause | Management | Rationale |
|---|---|---|
| Antiphospholipid syndrome | Low-dose aspirin (75 mg daily) from positive pregnancy test + prophylactic LMWH (e.g., enoxaparin 40 mg SC daily) throughout pregnancy until 6 weeks postpartum | Aspirin inhibits platelet aggregation (blocks thromboxane A₂ via COX-1 inhibition); LMWH provides anticoagulation to prevent uteroplacental thrombosis. This combination reduces miscarriage rate from ~80% to ~20–30% in APLS — one of the most dramatic treatment effects in obstetric medicine [3] |
| Inherited thrombophilia (with 2nd-trimester loss) | Consider prophylactic LMWH in pregnancy + aspirin; refer to haematology | Evidence less strong than for APLS, but thromboprophylaxis is rational given the pathophysiology of uteroplacental microthrombosis [11] |
| Parental balanced translocation | Genetic counselling; options include natural conception with prenatal diagnosis (CVS/amniocentesis for fetal karyotype), or IVF with preimplantation genetic testing for structural rearrangements (PGT-SR) | PGT-SR allows selection of embryos with balanced/normal chromosome complement before transfer, avoiding recurrent aneuploid conceptions |
| Uterine septum | Hysteroscopic septoplasty (resection of the septum) | Removes the poorly vascularised septum that causes implantation failure. Improves live birth rate from ~30% to ~70% in observational studies |
| Submucosal fibroids | Hysteroscopic myomectomy | Removes the fibroid that distorts the endometrial cavity and impairs implantation |
| Intrauterine adhesions | Hysteroscopic adhesiolysis ± intrauterine balloon/IUD stent ± oestrogen therapy post-procedure | Restores the endometrial cavity; oestrogen promotes endometrial regeneration over the denuded surfaces |
| Cervical insufficiency | Cervical cerclage (McDonald or Shirodkar) at 12–14 weeks in subsequent pregnancies; or vaginal progesterone | Cerclage = a suture placed around the cervix to mechanically hold it closed, compensating for the structural weakness. "Cerclage" from French cercler = to encircle |
| Hypothyroidism | Levothyroxine to achieve TSH < 2.5 mIU/L in first trimester | Restores adequate thyroid hormone levels for normal trophoblast development and placental function |
| Thyroid autoimmunity (euthyroid) | Consider levothyroxine supplementation (controversial but increasingly supported) | Even with normal TSH, thyroid reserve may be insufficient under the increased demands of pregnancy; anti-TPO may indicate subclinical insufficiency |
| Diabetes mellitus | Preconception optimisation: target HbA1c < 6.5% (48 mmol/mol) before conception; tight glycaemic control throughout pregnancy | Hyperglycaemia is directly embryotoxic; good control reduces miscarriage rate to near-background levels |
| Idiopathic recurrent miscarriage (no cause found — ~50%) | Supportive care, progesterone supplementation (vaginal micronised progesterone 400 mg BD from positive test until 16 weeks), TLC (tender loving care) clinic follow-up | The PRISM trial showed benefit of progesterone in women with recurrent miscarriage and threatened bleeding. Supportive care in dedicated early pregnancy clinics with frequent USS follow-up has been shown to improve live birth rates (from ~30% to ~70%) — likely through reducing stress/cortisol |
Anticoagulation in Pregnancy — Important Drug Considerations
Warfarin crosses the placenta → risk of fetal ICH and teratogenicity [20] (warfarin embryopathy: nasal hypoplasia, stippled epiphyses — most dangerous in weeks 6–12). Therefore:
- LMWH is the anticoagulant of choice in pregnancy — does not cross the placenta (large molecular weight), predictable pharmacokinetics
- Antiphospholipid syndrome: heparin followed by indefinite warfarin [20] — meaning LMWH during pregnancy, then switch to warfarin postpartum for lifelong anticoagulation (since APLS is a lifelong thrombotic condition)
- Switch to LMWH when 1st trimester (↓ teratogenicity) and > 36 weeks (avoid PPH) → cover up to 6 weeks postpartum (highest risk as blood returns from uterus) [20]
This algorithm applies when the pregnancy cannot be located on USS:
Workflow for a positive urine hCG test [15]:
hCG more than 50% drop in a repeat test > 48 hours → suggestive of possible miscarriage → do another urine pregnancy test after 2 weeks [15].
hCG more than 63% rise in 48 hours → suggestive of a continuing pregnancy → ask lady to come back for a trans-vaginal USG 1–2 weeks later [15].
hCG between a 50% decline, and a 63% rise in 48 hours → this is the level we are most unsure of, especially if ultrasound does not show an intrauterine pregnancy → could suggest ectopic pregnancy, pregnancy of unknown location [15].
Special Considerations
| Scenario | Anti-D Required? |
|---|---|
| Threatened miscarriage < 12 weeks, no intervention | Not routinely (unless heavy/repeated bleeding or intervention performed) — NICE 2021 guidance; however practice varies |
| Any miscarriage ≥ 12 weeks (all Rh-negative women) | Yes — 250 IU anti-D IM within 72 hours |
| Surgical evacuation at any gestation (Rh-negative) | Yes |
| Ectopic pregnancy (Rh-negative) | Yes |
Why 72 hours? Anti-D must be given before the maternal immune system has time to mount a primary immune response to the Rh-positive fetal red cells. The window is approximately 72 hours after fetomaternal haemorrhage.
- Ovulation can occur as early as 2 weeks after miscarriage
- If the patient does not wish to conceive immediately, contraception should be discussed and offered
- There is no need to wait before trying to conceive again (the old advice of "wait 3 months" is not evidence-based) — WHO and NICE recommend trying whenever the couple feels emotionally ready
Tissue mass for histology — ?decidua ?chorionic villi ?fetal parts [13]:
- Confirms intrauterine pregnancy
- Excludes gestational trophoblastic disease (GTD)
- In recurrent miscarriage: cytogenetic analysis of products helps determine if the loss was aneuploid (reassuring — likely sporadic) or euploid (more concerning — suggests underlying maternal/paternal cause)
| Type | 1st Line | 2nd Line | Urgent/Emergency |
|---|---|---|---|
| Threatened | Observation + vaginal micronised progesterone (if ≥1 prior miscarriage, continue to 16 weeks) [17] | Follow-up USS | — |
| Missed / Incomplete | Expectant 1–2 weeks [15][18] | Misoprostol 800 mcg vaginally or sublingually [19] | Suction evacuation (heavy bleeding, failed medical, suspected GTD) [15][18] |
| Inevitable | Expectant [15][18] | Medical (misoprostol) | Suction evacuation (heavy bleeding) [15][18] |
| Complete | No treatment; urine hCG at 3 weeks; beware ectopic [15][18] | — | — |
| Septic | IV antibiotics + urgent suction evacuation | — | Always emergency management |
| Recurrent | Investigate and treat underlying cause [1][10] | Progesterone supplementation, supportive care | — |
High Yield Summary
Three management options for missed/incomplete/inevitable miscarriage: Expectant (1–2 weeks), Medical (misoprostol 800 mcg vaginally or sublingually), Surgical (suction evacuation).
Threatened miscarriage: Observation. Vaginal micronised progesterone if ≥1 prior miscarriage, continued until 16 weeks gestation.
Complete miscarriage: No active treatment, but follow up with urine hCG at 3 weeks to rule out ectopic pregnancy. Send tissue for histology.
Septic miscarriage: Emergency — IV antibiotics (amoxicillin + metronidazole + gentamicin) + urgent surgical evacuation.
Misoprostol: PGE₁ analogue, 800 mcg vaginally/sublingually. Follow-up in EPAC at 2 weeks.
Recurrent miscarriage — APLS treatment: Low-dose aspirin + prophylactic LMWH throughout pregnancy (reduces miscarriage from ~80% to ~20–30%).
Anticoagulation in pregnancy: LMWH is the drug of choice (warfarin is teratogenic and crosses placenta).
Always send products for histology to confirm IUP and exclude molar pregnancy.
Patient-centred care: Choice of treatment should be individualised based on clinical stability, patient preference, ethnomedical beliefs, and success rates. Healthcare providers can add to the trauma — communicate sensitively.
Active Recall - Management of Miscarriage
[1] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p39 — recurrent miscarriage definitions and management) [3] Senior notes: Maksim Medicine Notes.pdf (p317 — APLS diagnostic criteria and management); Senior notes: Ryan Ho Rheumatology.pdf (p73 — Revised Sapporo criteria) [9] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p109 — summary: best treatment is still evolving) [10] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p40 — investigations for recurrent miscarriage) [11] Senior notes: Ryan Ho Haemtology.pdf (p136 — thrombophilia screening) [13] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p22 — investigations: tissue for histology) [14] Senior notes: Ryan Ho Haemtology.pdf (p136–137 — DIC causes including obstetric) [15] Lecture slides: Block C - Complications of Early Pregnancy (CFB WCS in 2023_24).pdf (p29 — management of miscarriage types; p49 — hCG workflow; p88 — psychiatric morbidity and individualised treatment) [16] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p112 — psychiatric morbidity, ethnomedical beliefs, healthcare providers can add to trauma) [17] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p35 — threatened miscarriage: observation + progesterone) [18] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p36 — management of silent, incomplete, inevitable, complete) [19] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p37 — misoprostol 800 mcg vaginal or sublingual, EPAC follow-up 2 weeks) [20] Senior notes: Ryan Ho Haemtology.pdf (p132 — anticoagulation in pregnancy, warfarin teratogenicity, LMWH preference, APLS management)
Complications of miscarriage can be divided into immediate/acute (occurring during or shortly after the miscarriage event), subacute (days to weeks later), and long-term (weeks to months or permanently). We also need to consider complications of the management itself (expectant, medical, and surgical), and the profound psychological impact that the lecture slides emphasise repeatedly.
Let me work through each systematically, explaining the pathophysiology from first principles.
A. Immediate / Acute Complications
The most common acute complication of miscarriage.
- Mechanism: When the products of conception partially separate from the decidua, the exposed spiral arteries bleed. Unlike postpartum haemorrhage where the uterus can contract around the empty cavity to compress vessels ("living ligature"), in incomplete miscarriage the retained tissue prevents effective myometrial contraction → persistent bleeding from open sinusoidal vessels
- When it is worst: Incomplete miscarriage is the highest-risk type — some tissue has been expelled (disrupting the decidual-trophoblastic interface) but retained fragments prop open the uterine cavity and prevent the myometrium from clamping down
- Severity spectrum: ranges from mild ongoing spotting to massive, life-threatening haemorrhage requiring emergency surgical evacuation and blood transfusion
- Risk factors for severe haemorrhage: advanced gestational age at miscarriage (larger placental bed), uterine atony, coagulopathy (e.g., DIC), cervical or uterine laceration (especially with surgical management)
- Management:
- IV access, fluid resuscitation, crossmatch blood
- Bimanual compression of the uterus
- Remove products at the cervical os with sponge forceps (allows uterus to contract)
- Uterotonic agents: IV oxytocin (stimulates myometrial contractions), ergometrine (sustained uterine contraction via direct smooth muscle action — contraindicated in hypertension), misoprostol (PGE₁ analogue)
- Suction evacuation if retained products are the cause [15][18]
- Rarely: uterine artery embolisation, intrauterine balloon tamponade, hysterectomy (last resort for uncontrollable haemorrhage)
- Mechanism: A consequence of massive haemorrhage → ↓ intravascular volume → ↓ venous return → ↓ cardiac output → ↓ organ perfusion → multi-organ failure if uncorrected
- Clinical features: tachycardia (earliest sign — compensatory sympathetic response), hypotension (late sign — indicates significant volume depletion > 30%), pallor, cold clammy peripheries, confusion, oliguria
- Why does tachycardia precede hypotension? The baroreceptor reflex detects ↓ blood pressure → activates sympathetic nervous system → ↑ heart rate and ↑ peripheral vasoconstriction to maintain blood pressure. Blood pressure is maintained ("compensated shock") until the compensatory mechanisms are overwhelmed → then sudden decompensation with frank hypotension
- Mechanism: Products of conception lodged in the cervical canal stimulate the vagus nerve (the cervix has rich parasympathetic innervation). This triggers a profound vasovagal response → bradycardia + vasodilation → hypotension → syncope/collapse
- Key distinction from hypovolaemic shock: cervical shock causes bradycardia (parasympathetic), whereas hypovolaemic shock causes tachycardia (sympathetic). This distinction is critical at the bedside
- Management: Remove the products from the cervical os with sponge forceps → the vasovagal trigger is removed → haemodynamics rapidly improve. IV atropine (muscarinic antagonist, blocks vagal tone) if severe bradycardia persists. IV fluids to support blood pressure
Cervical Shock vs. Hypovolaemic Shock
Both present with hypotension and collapse, but the management is different:
- Cervical shock: bradycardia + hypotension → remove tissue from os + atropine
- Hypovolaemic shock: tachycardia + hypotension → fluid resuscitation + surgical evacuation + blood transfusion
Misidentifying cervical shock as hypovolaemic shock (or vice versa) leads to incorrect and potentially harmful treatment. Always check the pulse rate.
B. Infective Complications
- Mechanism: Retained products of conception are an ideal culture medium — warm, moist, necrotic tissue with excellent blood supply. Bacteria ascend from the vagina and cervix → colonise the retained tissue → endometritis → myometritis → parametritis → peritonitis → septicaemia
- Common organisms: Polymicrobial — E. coli (Gram-negative), Bacteroides fragilis (anaerobe), Group B Streptococcus (Gram-positive), Clostridium perfringens (anaerobe — produces gas gangrene, toxin-mediated haemolysis, can be rapidly fatal)
- Risk factors: incomplete evacuation, prolonged retained products, instrumentation (especially non-sterile), prolonged rupture of membranes, immunosuppression
- Clinical features: fever ≥ 38°C, rigors, offensive vaginal discharge, pelvic pain, tender uterus on bimanual examination, tachycardia, hypotension (if septic shock)
- Complications of sepsis itself:
- Septic shock: vasodilatory shock → distributive circulatory failure → multi-organ dysfunction
- Disseminated intravascular coagulation (DIC): obstetric causes of DIC include septic abortion, amniotic fluid embolism, abruptio placentae, HELLP syndrome [14]. In sepsis, bacterial endotoxins activate tissue factor → widespread intravascular coagulation → consumption of clotting factors and platelets → paradoxical bleeding + microvascular thrombosis
- Pelvic abscess: walled-off collection of pus in the pouch of Douglas or adnexae
- Peritonitis: generalised peritoneal inflammation from spreading infection
- Septic thrombophlebitis: infection of pelvic veins → potential for septic pulmonary emboli
- Mechanism: Infection of the endometrium following miscarriage (either spontaneous or post-surgical)
- Clinical features: persistent low-grade fever, ongoing pelvic pain, offensive lochia/discharge, uterine tenderness
- Important: if post-surgical, usually presents 2–7 days after evacuation
- Management: oral antibiotics (doxycycline + metronidazole) for mild cases; IV antibiotics for severe cases; consider re-evacuation if retained products are the nidus of infection
C. Complications of Surgical Management
- Mechanism: During suction evacuation or curettage, an instrument (dilator, curette, or suction cannula) passes through the myometrial wall. The uterus in early pregnancy is soft and engorged → ↑ risk of perforation
- Incidence: ~0.1–0.5% of surgical evacuations
- Risk factors: retroverted uterus (the instrument follows the wrong curvature), previous caesarean section (scar is thinner), cervical stenosis (excessive force required), operator inexperience
- How it presents: sudden loss of resistance during the procedure, instrument goes "too far," sudden onset of severe abdominal pain post-procedure, signs of intra-abdominal bleeding or bowel injury
- Complications of perforation: haemoperitoneum (injury to uterine/ovarian vessels), bowel injury (especially if perforated fundus is near bowel loops), bladder injury
- Management: if suspected → stop the procedure → observe with serial vitals and USS → if haemodynamically stable, may be managed conservatively (small perforations often heal spontaneously) → if unstable or evidence of visceral injury → diagnostic laparoscopy or laparotomy
- Mechanism: forceful dilation of the cervix (especially if not adequately primed) can tear the cervical tissue
- Consequence: acute bleeding from the laceration site; long-term risk of cervical insufficiency in future pregnancies (weakened cervical structure → painless dilation in second trimester)
- Prevention: pre-operative cervical priming with misoprostol or osmotic dilators
- Mechanism: failure to completely remove all products during surgical evacuation
- Clinical features: persistent or recurrent bleeding, ongoing pelvic pain, risk of secondary infection
- Diagnosis: USS showing heterogeneous echogenic material in the uterine cavity; ± positive hCG
- Management: repeat evacuation (suction) or medical management (misoprostol)
- Incidence: ~2–5% of surgical evacuations
- Mechanism: aggressive or repeated curettage of the endometrium damages the basal layer (stratum basalis) → exposure of the underlying myometrium → fibrosis → adhesion formation between opposing uterine walls
- Why does this matter? Adhesions reduce the functional endometrial surface area → impaired implantation in future pregnancies → secondary infertility, recurrent miscarriage, menstrual abnormalities (hypomenorrhoea, amenorrhoea if severe)
- Prevention: prefer suction evacuation over sharp curettage; avoid excessive instrumentation; gentle technique
- Diagnosis: hysteroscopy (gold standard), saline infusion sonography, or hysterosalpingogram
- Treatment: hysteroscopic adhesiolysis (division of adhesions under direct vision) + post-operative intrauterine balloon stent + oestrogen therapy to promote re-epithelialisation
Asherman Syndrome — The Iatrogenic Complication to Know
Asherman syndrome is the most important long-term complication of uterine instrumentation. It is entirely iatrogenic (caused by the treatment itself). The risk is highest with sharp curettage (which scrapes the basal endometrium) and lowest with suction evacuation (which is less traumatic to the basal layer). This is why modern practice strongly favours suction over sharp curettage. The condition name comes from Joseph Asherman, an Israeli gynaecologist who described it in 1948.
D. Complications of Medical Management
- Incidence: ~15–20% of cases treated with misoprostol alone (lower if mifepristone pretreatment is used)
- What it means: products of conception are not completely expelled after medical treatment
- Management: offer repeat misoprostol dose or surgical evacuation
- Follow up in Early Pregnancy Assessment Clinic 2 weeks after treatment [19] — this follow-up is specifically designed to detect failed medical management
- Pain: significant cramping abdominal pain (expected — prostaglandin-mediated uterine contractions). Manage with paracetamol + codeine; NSAIDs are also effective once miscarriage is confirmed
- GI side effects: nausea, vomiting, diarrhoea — prostaglandin PGE₁ acts on GI smooth muscle receptors (same reason misoprostol was originally developed as a gastroprotective agent — at lower doses, it inhibits gastric acid secretion and promotes mucus production; at higher doses, the systemic prostaglandin effect causes GI side effects)
- Fever/chills: transient prostaglandin-mediated pyrexia (PGE₂ acting on the hypothalamic thermoregulatory centre) — typically resolves within hours; distinguish from infection-related fever (which is persistent and associated with other sepsis features)
E. Long-Term / Late Complications
- Mechanism: if an Rh-negative mother carries an Rh-positive fetus, fetomaternal haemorrhage during miscarriage allows fetal Rh-positive red blood cells to enter the maternal circulation → maternal immune system produces anti-D IgG antibodies → in subsequent Rh-positive pregnancies, these IgG antibodies cross the placenta → attack fetal red blood cells → haemolytic disease of the fetus and newborn (HDFN): fetal anaemia, hydrops fetalis, kernicterus, intrauterine death
- Prevention: anti-D immunoglobulin to all Rh-negative women (within 72 hours of the miscarriage event, especially if ≥ 12 weeks or surgical intervention)
- Why within 72 hours? Must be given before the maternal primary immune response is mounted (which takes ~72 hours). Anti-D works by coating any fetal Rh-positive cells in the maternal circulation, marking them for destruction by the reticuloendothelial system before the maternal B cells can recognise them and produce their own anti-D
- After a single miscarriage: fertility is generally not impaired; the prognosis for next pregnancy is good (~80–85% live birth rate)
- After recurrent miscarriage: depends on underlying cause — if treatable (APLS, uterine septum, thyroid disease), outcomes improve significantly with appropriate management
- After surgical complications: Asherman syndrome → subfertility (as above); cervical damage → cervical insufficiency in future pregnancies
- Psychological impact on fertility: anxiety and fear about trying again can delay conception; supportive care and early pregnancy assessment clinics improve outcomes
- If products of conception are not sent for histology, a molar pregnancy can be missed → subsequent development of gestational trophoblastic neoplasia (GTN), including invasive mole and choriocarcinoma
- Choriocarcinoma is a highly malignant but curable cancer (> 95% cure rate with chemotherapy if detected) — but if undiagnosed, it metastasises rapidly (lungs, brain, liver) and can be fatal
- Prevention: tissue mass for histology — ?decidua ?chorionic villi ?fetal parts [13] — histology should be performed on all evacuated or passed products of conception
F. Psychological and Psychiatric Complications
This is heavily emphasised in the lecture slides and is an important and frequently examined area.
Psychiatric morbidity following miscarriages: a prevalence study of Chinese women in Hong Kong [21]:
- 48–51% of women in Western countries developed depressive disorder
- 150 subjects interviewed
- 12% had major depression and 1.3% had anxiety disorder 6 weeks after the miscarriage (Lee 1997, J Affect Disord 43:63-8) [21]
Psychiatric morbidity following miscarriage in Hong Kong [1]:
- 3 months after miscarriage, 10% of subjects suffered depressive disorder, 1.2% were diagnosed with anxiety disorder not otherwise specified, 0.6% suffered from obsessive compulsive disorder and 0.6% suffered from post-traumatic stress disorder
- Risk factors of depression included younger age, history of infertility and depression (Sham 2010, Gen Hosp Psychiatry 32:284-9) [1]
Miscarriages is associated with significant psychiatric morbidity although the prevalence may be lower in our population [15][16].
Spectrum of psychological complications:
| Complication | Prevalence | Pathogenesis / Mechanism |
|---|---|---|
| Grief reaction | Nearly universal | Loss of a wanted pregnancy = bereavement. The grief may be disproportionate to the gestational age because many parents have already formed an attachment to the imagined child. Grief is often disenfranchised (society minimises the loss — "it was only early") |
| Depressive disorder | 10–12% at 6 weeks to 3 months [1][21] | Biological: abrupt hormonal changes (↓ hCG, ↓ progesterone, ↓ oestrogen) affect serotonergic pathways. Psychological: loss, guilt, self-blame, perceived failure. Social: lack of recognition/support |
| Anxiety disorders | ~1.2–1.3% [1][21] | Fear of recurrence, health anxiety, generalised worry. May be exacerbated by previous infertility history |
| Post-traumatic stress disorder | ~0.6% [1] | The miscarriage event (especially if traumatic — heavy bleeding, emergency surgery, haemorrhagic shock) can be experienced as a traumatic event fulfilling PTSD criteria |
| Obsessive compulsive disorder | ~0.6% [1] | Intrusive thoughts related to pregnancy, compulsive checking behaviours |
| Relationship strain | Common but variable | Partners may grieve differently; communication difficulties; sexual avoidance due to fear of another pregnancy |
Healthcare providers can add to the trauma [15][16] — insensitive comments, dismissive attitudes, lack of follow-up, rushed consultations, and failure to acknowledge the loss all worsen the psychological impact.
Clinical Pearl: What Healthcare Providers Should Do
Six domains of care identified from research [22]:
- Staff care: train healthcare providers in sensitive communication
- Assessment: screen for psychological distress (PHQ-9, GAD-7) at follow-up visits
- Information: provide written information about miscarriage, what to expect, and where to find support
- Phone follow-up: contact the patient within 1–2 weeks after discharge
- Risk assessment: identify women at high risk for psychiatric morbidity (younger age, history of infertility, history of depression) [1]
- Care during subsequent pregnancies: early reassurance scans, dedicated early pregnancy clinic follow-up, psychological support
- Partners (particularly male partners) are often overlooked — they experience grief too but may feel pressure to "be strong"
- No formal medical follow-up is typically offered to partners
- Consider offering couples counselling or directing to support groups
G. Obstetric Complications in Subsequent Pregnancies
- After 1 miscarriage: ~20% risk of another
- After 2 miscarriages: ~28%
- After 3 miscarriages: ~43%
- The risk is cumulative and increases with advancing maternal age
- If the cervix was traumatised during surgical evacuation (forceful dilation), there is a risk of cervical insufficiency in subsequent pregnancies → painless second-trimester dilation → previable delivery
- Prevented by gentle technique, adequate cervical priming, and awareness of the risk
- Repeated uterine instrumentation may damage the endometrium → abnormal placentation in future pregnancies (placenta praevia, placenta accreta spectrum) — though the risk increase from D&C alone is small compared to caesarean section
| Category | Complication | Mechanism | Prevention/Management |
|---|---|---|---|
| Acute | Haemorrhage | RPOC prevents uterine contraction; open decidual vessels | Surgical evacuation, uterotonics, transfusion |
| Acute | Hypovolaemic shock | Massive blood loss → ↓ circulating volume | Fluid resuscitation, blood products, surgical control |
| Acute | Cervical shock | Products at os → vagal stimulation → bradycardia | Remove products from os; atropine if needed |
| Infective | Septic miscarriage / endometritis | Infected retained products → ascending infection | IV antibiotics + urgent evacuation |
| Infective | DIC | Sepsis → tissue factor release → consumption coagulopathy | Treat underlying sepsis; supportive (FFP, platelets, cryoprecipitate) |
| Surgical | Uterine perforation | Instrument passes through myometrium | Careful technique; laparoscopy/laparotomy if visceral injury |
| Surgical | Asherman syndrome | Aggressive curettage damages stratum basalis → fibrosis | Use suction not sharp curettage; hysteroscopic adhesiolysis if occurs |
| Surgical | Cervical trauma | Forceful dilation → cervical laceration | Cervical priming; gentle dilation |
| Medical | Failed medical Mx | Incomplete expulsion of products | Repeat misoprostol or surgical evacuation |
| Long-term | Rh isoimmunisation | Fetomaternal haemorrhage in Rh-negative mother | Anti-D immunoglobulin within 72 hours |
| Long-term | Missed GTD | Products not sent for histology | Always send tissue for histology |
| Psychological | Depression, anxiety, PTSD, OCD | Hormonal, psychological, and social factors | Screening, sensitive care, follow-up, counselling |
| Obstetric | Recurrent miscarriage | Depends on underlying cause | Investigate and treat after ≥2–3 losses |
High Yield Summary
Most common acute complication: Haemorrhage (especially incomplete miscarriage — retained products prevent uterine contraction).
Cervical shock vs. hypovolaemic shock: Cervical shock = bradycardia (vagal) → remove products from os + atropine. Hypovolaemic shock = tachycardia (sympathetic) → fluids + transfusion + surgical evacuation.
Septic miscarriage: Retained infected products → ascending polymicrobial infection → can progress to DIC, septic shock, peritonitis. Treat with IV antibiotics + urgent evacuation.
Asherman syndrome: Most important iatrogenic long-term complication of surgical evacuation. Caused by aggressive curettage damaging the endometrial basal layer → intrauterine adhesions → infertility, amenorrhoea. Prevention: use suction, not sharp curettage.
Rh isoimmunisation: Prevent with anti-D immunoglobulin in all Rh-negative women within 72 hours.
Always send products for histology to exclude molar pregnancy (GTD).
Psychiatric morbidity (Hong Kong data): 10–12% depression at 6 weeks to 3 months; 0.6% PTSD; 0.6% OCD. Risk factors: younger age, infertility history, prior depression. Healthcare providers can add to the trauma — communicate sensitively.
Active Recall - Complications of Miscarriage
[1] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p101 — psychiatric morbidity 3 months post-miscarriage, Sham 2010) [13] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p22 — tissue mass for histology) [14] Senior notes: Ryan Ho Haemtology.pdf (p136–137 — DIC causes including obstetric: septic abortion, amniotic fluid embolism, abruptio placentae) [15] Lecture slides: Block C - Complications of Early Pregnancy (CFB WCS in 2023_24).pdf (p29 — management; p88 — psychiatric morbidity, ethnomedical beliefs, healthcare providers can add to trauma) [16] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p112 — psychiatric morbidity, choice of treatment individualised, healthcare providers can add to trauma) [18] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p36 — management of miscarriage types: complete — beware ectopic) [19] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p37 — misoprostol 800 mcg, EPAC follow-up 2 weeks) [21] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p100 — psychiatric morbidity prevalence study: 12% major depression at 6 weeks, Lee 1997) [22] Lecture slides: GC 223. Complications of Early Pregnancy.pdf (p105 — hospital-based interventions following miscarriage: six domains of service delivery)
High Yield Summary
Definition: Spontaneous pregnancy loss < 24 weeks. Recurrent miscarriage = ≥2 (ESHRE) or ≥3 (RCOG) losses.
Epidemiology: 10–20% of recognised pregnancies; 80% in first trimester; risk increases sharply with maternal age.
Most common cause: Chromosomal abnormalities (~50–60% of sporadic miscarriages), especially autosomal trisomies.
Most important treatable cause of recurrent miscarriage: Antiphospholipid syndrome — causes uteroplacental thrombosis and complement-mediated injury. Diagnose with lupus anticoagulant (most thrombogenic), anti-cardiolipin, anti-β₂GPI × 2 measurements 12 weeks apart.
Classification: Threatened (closed os, viable) → Inevitable (open os) → Incomplete (open os, partial expulsion) → Complete (closed os, all expelled) → Missed (closed os, non-viable, retained) → Septic (infection of retained products = emergency).
Key clinical distinction: Cervical os status differentiates threatened from inevitable miscarriage.
Hong Kong psychiatric morbidity: 10% depression at 3 months post-miscarriage; risk factors include younger age, history of infertility and depression.
Always exclude ectopic pregnancy in any woman with early pregnancy bleeding.
Always send products for histology to exclude molar pregnancy.
Rh-negative women: give anti-D immunoglobulin.
High Yield Summary
Differential diagnosis of early pregnancy bleeding — the three must-not-miss diagnoses:
- Ectopic pregnancy — can kill within hours if ruptured. Look for empty uterus + adnexal mass + free fluid on USS.
- Gestational trophoblastic disease — can mimic threatened miscarriage. Look for disproportionately high hCG, snowstorm USS, uterus large-for-dates.
- Septic miscarriage — can progress to septic shock. Look for fever, offensive discharge, tender uterus.
Key differentiating tool: Cervical os status (closed = threatened/complete/missed; open = inevitable/incomplete).
Key investigation: Transvaginal USS + serum β-hCG. Need a second scan ≥ 7 days later to confirm missed miscarriage.
Always send products of conception for histology to exclude molar pregnancy.
PUL is not a diagnosis — it requires serial hCG monitoring and repeat USS until the pregnancy is located or resolved.
High Yield Summary
Ultrasound Diagnostic Criteria for Missed Miscarriage (must memorise):
- CRL ≥ 7 mm with no cardiac activity → confirmed fetal demise
- MSD ≥ 25 mm with no embryo → confirmed anembryonic pregnancy
- Always confirm with a repeat scan ≥ 7 days later or a second opinion
Discriminatory zone for β-hCG:
- TVUS: 1,500–2,000 mIU/mL → IUP should be visible above this level
- If uterus is empty above discriminatory zone → suspect ectopic
Acute investigations: Hb (+ MCV), Rh factor, pelvic sonogram, tissue for histology, serum β-hCG
Recurrent miscarriage investigations (TULIPS): Thyroid (TSH + anti-TPO), Uterine anatomy, Lupus anticoagulant + aPL antibodies, Inherited thrombophilias, Parental karyotype, Sugar (glucose/HbA1c)
Histology of products is essential — to confirm intrauterine pregnancy (chorionic villi) and exclude molar pregnancy
APLS diagnosis requires two positive antibody tests ≥ 12 weeks apart (LA, aCL, or anti-β₂GPI at moderate-to-high titre)
High Yield Summary
Three management options for missed/incomplete/inevitable miscarriage: Expectant (1–2 weeks), Medical (misoprostol 800 mcg vaginally or sublingually), Surgical (suction evacuation).
Threatened miscarriage: Observation. Vaginal micronised progesterone if ≥1 prior miscarriage, continued until 16 weeks gestation.
Complete miscarriage: No active treatment, but follow up with urine hCG at 3 weeks to rule out ectopic pregnancy. Send tissue for histology.
Septic miscarriage: Emergency — IV antibiotics (amoxicillin + metronidazole + gentamicin) + urgent surgical evacuation.
Misoprostol: PGE₁ analogue, 800 mcg vaginally/sublingually. Follow-up in EPAC at 2 weeks.
Recurrent miscarriage — APLS treatment: Low-dose aspirin + prophylactic LMWH throughout pregnancy (reduces miscarriage from ~80% to ~20–30%).
Anticoagulation in pregnancy: LMWH is the drug of choice (warfarin is teratogenic and crosses placenta).
Always send products for histology to confirm IUP and exclude molar pregnancy.
Patient-centred care: Choice of treatment should be individualised based on clinical stability, patient preference, ethnomedical beliefs, and success rates. Healthcare providers can add to the trauma — communicate sensitively.
High Yield Summary
Most common acute complication: Haemorrhage (especially incomplete miscarriage — retained products prevent uterine contraction).
Cervical shock vs. hypovolaemic shock: Cervical shock = bradycardia (vagal) → remove products from os + atropine. Hypovolaemic shock = tachycardia (sympathetic) → fluids + transfusion + surgical evacuation.
Septic miscarriage: Retained infected products → ascending polymicrobial infection → can progress to DIC, septic shock, peritonitis. Treat with IV antibiotics + urgent evacuation.
Asherman syndrome: Most important iatrogenic long-term complication of surgical evacuation. Caused by aggressive curettage damaging the endometrial basal layer → intrauterine adhesions → infertility, amenorrhoea. Prevention: use suction, not sharp curettage.
Rh isoimmunisation: Prevent with anti-D immunoglobulin in all Rh-negative women within 72 hours.
Always send products for histology to exclude molar pregnancy (GTD).
Psychiatric morbidity (Hong Kong data): 10–12% depression at 6 weeks to 3 months; 0.6% PTSD; 0.6% OCD. Risk factors: younger age, infertility history, prior depression. Healthcare providers can add to the trauma — communicate sensitively.
Endometriosis
Endometriosis is a chronic gynecological condition in which endometrial-like tissue grows outside the uterine cavity, commonly on the ovaries, fallopian tubes, and pelvic peritoneum, causing inflammation, pain, and potential infertility.
Ectopic Pregnancy
An ectopic pregnancy is the implantation and development of a fertilized ovum outside the uterine cavity, most commonly in the fallopian tube, posing a risk of life-threatening hemorrhage if rupture occurs.