GC223 Complications Of Early Pregnancy
Complications of early pregnancy encompass conditions occurring in the first trimester, including miscarriage, ectopic pregnancy, gestational trophoblastic disease, and hyperemesis gravidarum, which can threaten maternal health and pregnancy viability.
Complications of Early Pregnancy
This GC 223 lecture by Dr K Pang covers the spectrum of pathology encountered in the first half of pregnancy — the conditions that every A&E doctor, GP, and O&G trainee must diagnose rapidly because they can be life-threatening. The lecture is organized around three pillars: (1) common presenting complaints, (2) management strategies for each complication, and (3) the emotional/psychiatric impact of early pregnancy loss.
The Big Idea: A woman of reproductive age presenting with vaginal bleeding, abdominal pain, or vomiting needs you to think systematically: Is this a miscarriage? Is this an ectopic pregnancy? Could this be a molar pregnancy? Is she simply experiencing hyperemesis? Each has a different urgency, investigation pathway, and management strategy. Getting the diagnosis wrong — especially missing an ectopic — can kill.
Learning Objectives (from the slide deck) [1]:
- Common presenting complaints of early pregnancy complications
- Outline of management strategy for each condition
- Outline of emotional impact on the couple with early pregnancy losses
Part 1: Common Presenting Complaints
The four cardinal presenting complaints of early pregnancy complications are: nausea and vomiting, vaginal bleeding, abdominal pain, and others (shock, shoulder pain). [1]
- The relationship between hCG and nausea is temporal but not definitively causal. [1]
- hCG peaks at 8–12 weeks → correlates with peak incidence of nausea/vomiting and hyperemesis gravidarum (HG)
- The slide shows a graph with hCG curve overlapping the HG incidence curve, alongside progesterone, TSH, placental weight, and total oestrogens [1]
- What the hormone graph shows: hCG and HG incidence both peak ~9–10 weeks, then fall — temporal overlap that drives the “hCG causes HG” teaching, even though causation remains unproven. [1]
- Mechanism unclear: hCG may directly or indirectly affect brainstem areas controlling nausea (area postrema, nucleus tractus solitarius), but no published data supports a definitive causal relationship [1]
- Other hormones implicated: progesterone (slows GI motility), oestrogens, thyroid hormones (hCG has structural homology with TSH → gestational transient thyrotoxicosis)
Emerging pathway — GDF15–GFRAL axis [1]:
- Recent evidence implicates Growth/Differentiation Factor 15 (GDF15) as a key mediator of NVP/HG
- Pregnancy and a wide range of stressors → ↑ GDF15 → binds GFRAL (Glial-derived neurotrophic factor Family Receptor Alpha-Like) in the area postrema and nucleus of the solitary tract → nausea, vomiting, nutrient deprivation, maternal and fetal adverse events
- This GDF15–GFRAL axis provides a more direct mechanistic link than hCG alone (Liu et al. 2022, Front Med)
Why does hCG cause nausea?
hCG shares a common α-subunit with TSH, FSH, and LH. At very high levels, hCG can cross-react with TSH receptors, stimulating the thyroid gland. This "gestational transient thyrotoxicosis" may contribute to nausea, but the exact mechanism linking hCG to the vomiting centre remains unproven. The temporal correlation is strong but causation is not established.
- Most common reason for A&E attendance in early pregnancy
- Can range from spotting to massive haemorrhage
- Differential diagnosis: threatened/inevitable/incomplete/complete/silent miscarriage, ectopic pregnancy, gestational trophoblastic disease, cervical pathology (ectropion, polyp, carcinoma), implantation bleeding
Causes of abdominal pain in early pregnancy: uterine contraction, distension of the uterine cervix, distension of the fallopian tube (ectopic), and haemoperitoneum. [1]
- Uterine contraction → cramping midline pain, associated with miscarriage
- Cervical distension → occurs when products of conception are trapped in the os (inevitable/incomplete miscarriage); can cause vasovagal shock
- Tubal distension → ectopic pregnancy; pain typically unilateral, may precede rupture
- Haemoperitoneum → diffuse abdominal pain and peritonism from ruptured ectopic
Shock in early pregnancy complications can be hypovolaemic (from bleeding) or vasovagal (from distension of the cervix by tissue mass). [1]
Shoulder pain in early pregnancy = blood irritates diaphragm → stimulates phrenic nerve (C3,4,5) → referred pain to shoulder tip. [1]
What the phrenic diagram shows: C3–C5 → phrenic nerve → diaphragm, with the shoulder tip in the same dermatome — haemoperitoneum from ruptured ectopic can present as “shoulder pain,” not only pelvic pain. [1]
- Shoulder tip pain is a RED FLAG for ruptured ectopic with haemoperitoneum
- The phrenic nerve (C3,4,5 — "C3,4,5 keeps the diaphragm alive") provides sensory innervation to the peritoneum overlying the diaphragm. Blood in the peritoneal cavity irritates this → referred pain felt in the shoulder tip (C4 dermatome)
Exam Trap: Shoulder Pain
The CFB WCS notes explicitly warn: shoulder tip pain is quite non-specific — the patient could simply have MSK pain. But in the context of a positive pregnancy test + vaginal bleeding + abdominal pain, shoulder tip pain strongly suggests ruptured ectopic with haemoperitoneum. Always put it in clinical context. [2]
Additional presenting complaints noted in the CFB WCS [2]:
- Breast tenderness, gastrointestinal symptoms, dizziness/fainting/syncope, urinary symptoms, passage of tissue, rectal pressure or pain on defecation
Part 2: Management Strategies
2A. MISCARRIAGE
Miscarriage: Pregnancy loss at < 24 weeks. WHO definition: "the expulsion from its mother of an embryo or fetus weighing 500g or less, corresponding to a gestational age of up to 20 completed weeks of gestation with no signs of life." [1]
Terminology update (from the slide):
| Previous Term | Recommended Term |
|---|---|
| Incomplete abortion | Incomplete miscarriage |
| Missed abortion | Silent miscarriage |
| Anembryonic pregnancy / Early fetal demise | (subsumed under silent miscarriage) |
High Yield: Use 'miscarriage' not 'abortion'
The lecture explicitly states that "miscarriage" is the preferred term over "spontaneous abortion." This matters clinically (sensitivity to the patient) and in exams (they use "miscarriage" in stems).
This is the highest-yield table from this lecture. The slide builds it incrementally [1]:
| Feature | Threatened | Silent | Incomplete | Inevitable | Complete |
|---|---|---|---|---|---|
| Vaginal bleeding | Yes | May/may not | Yes | Yes | Was present, now stopped |
| Abdominal pain | Nil | Nil | +/- | Yes | Nil |
| Cervical os | Closed | Closed | Open | Open | Closed |
| Uterine size | Corresponding to dates | Small for dates | Small for dates | Corresponding to dates | Small for dates |
| Fetal viability | Alive | No cardiac activity | N/A (products partially expelled) | May still be present initially | N/A (all expelled) |
Why each column matters:
- Threatened: cervix closed, fetus alive → conservative management, may continue normally
- Silent (missed): cervix closed but fetus has died — no pain because the uterus hasn't started contracting to expel. Diagnosed on ultrasound. The old term "missed abortion" = the body "missed" the event
- Incomplete: some products out, some retained → open os, ongoing bleeding, uterus smaller than expected because some tissue has been passed
- Inevitable: cervix open, uterus contracting (pain), products not yet expelled → it is inevitable that this pregnancy will be lost
- Complete: everything has been expelled, cervix closes again, uterus small → but beware: must rule out ectopic pregnancy (the "empty uterus" could mean the pregnancy was never intrauterine!)
Tissue mass distending cervical os should be removed immediately. Verbal consent from patient should be obtained if feasible. [1]
Why? A tissue mass trapped in the os causes cervical distension → vasovagal reflex → bradycardia and hypotension. Removing it immediately relieves the reflex and stops the bleeding. This is a bedside emergency procedure.
Recurrent miscarriage: loss of ≥2 pregnancies (ESHRE 2017) or loss of ≥3 pregnancies (Green-top 2023). [1]
Note the discrepancy — ESHRE uses ≥2, RCOG Green-top uses ≥3. The lecture presents both definitions.
Investigations for recurrent miscarriage [1]:
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) — treatable cause!
- Thyroid function — TSH, anti-TPO (subclinical hypothyroidism or thyroid autoimmunity)
- Karyotyping (parental and/or products of conception — balanced translocation)
- Screening for uterine malformations (e.g., septate uterus — hysteroscopic septum resection may help)
- Thrombophilias for second trimester miscarriage (Factor V Leiden, prothrombin gene mutation, protein C/S deficiency)
Why these specific tests?
- Antiphospholipid syndrome (APS) is the most important treatable cause of recurrent miscarriage — aspirin + LMWH in the next pregnancy significantly improves live birth rates
- Thyroid autoimmunity (even with normal TSH) is associated with increased miscarriage risk
- Parental balanced translocations → unbalanced chromosomal complement in the fetus → miscarriage
- Uterine septum reduces vascularity → implantation failure or early pregnancy loss
- Thrombophilias cause placental micro-thrombosis → especially relevant in second-trimester losses
History: LMP and menstrual history, pregnancy test, vaginal bleeding, abdominal pain, passage of tissue mass, ?planned ?wanted [1]
The last point — whether the pregnancy was planned and wanted — is critical for counselling and emotional support. It also flags potential safeguarding concerns.
Physical examination: general condition, haemodynamic status, ?pallor, abdominal tenderness [1]
Vaginal examination: introitus (?blood stained), vagina (?blood ?tissue mass), cervix (?tissue mass ?os open/closed), uterus (size), fornix [1]
Fornix assessment: check for adnexal masses or tenderness (could suggest ectopic), cervical excitation (ectopic or PID)
Investigations: Hb (also note MCV), Rh factor (no need if known!), pelvic sonogram, tissue mass for histology — ?decidua ?chorionic villi ?fetal parts [1]
Why check MCV? Chronic blood loss → microcytic anaemia; or it may reveal a pre-existing haemoglobinopathy (thalassaemia trait), which is relevant for prenatal counselling in future pregnancies.
Why Rh factor? Rh-negative women need anti-D immunoglobulin to prevent Rh isoimmunisation if they have any bleeding event. "No need if known" saves time and resources.
Histology of tissue mass: Confirms intrauterine pregnancy (presence of chorionic villi). If no villi are found, suspect ectopic pregnancy!
HKCOG Guideline Number 10 – Part 1 (March 2004) [1]
| Gestational Age (menstrual) | CRL (mm) | Expected Ultrasound Sign |
|---|---|---|
| 3–4 weeks | — | Thickening of endometrium and decidua |
| 4–5 weeks | — | First appearance of gestational sac |
| 5 weeks | 1–2 | First appearance of yolk sac and embryonic pole |
| 5–6 weeks | 5 | Embryonic cardiac activity |
These milestones help determine whether ultrasound findings are appropriate for gestational age and guide the timing of repeat scans.
Ultrasound milestones: Use transvaginal US preferentially over transabdominal. [1]
Silent miscarriage diagnosis: mean gestational sac diameter ≥25mm with no evidence of embryo or yolk sac; OR CRL ≥7mm with no evidence of cardiac pulsation. [1]
Critical Ultrasound Criteria for Silent Miscarriage
These are the definitive criteria — they mean you can diagnose pregnancy failure without waiting:
- Mean sac diameter ≥ 25mm with no embryo/yolk sac = empty sac = anembryonic pregnancy
- CRL ≥ 7mm with no heartbeat = embryonic/fetal demise
If the measurements are below these thresholds, you CANNOT make the diagnosis on a single scan.
A second scan is needed to make the diagnosis — either a second opinion or a second scan a minimum of 7 days after the first. [1]
Why? To avoid misdiagnosis and inadvertent termination of a viable pregnancy. Early in pregnancy, dating may be slightly off, and an embryo may not yet be visible. The 7-day interval allows time for expected growth.
Gestational sac vs pseudosac: In 10-20% of ectopic pregnancies, endometrial fluid collection surrounded by endometrial tissue may be mistaken as a gestational sac. [1]
How to differentiate:
- True gestational sac: double decidual sign (two echogenic rings — decidua capsularis and decidua parietalis)
- Pseudosac: single layer, centrally positioned, no double ring sign
- Presence of yolk sac = definite intrauterine pregnancy
Incomplete miscarriage on US: thick irregular echoes in the midline of the uterine cavity. If heterogenous shadows with maximum AP diameter ≤15mm, retained products are less likely (RCOG 2006) — beware of limitation. [1]
Complete miscarriage on US: well-defined regular endometrial line. Beware of ectopic pregnancy. [1]
UPT level in urine is very similar to blood. First morning urine has higher hCG concentration. If negative, can rule out pregnancy complication. Cannot differentiate complete and incomplete miscarriage. [1]
Clinical pearl: A negative urine pregnancy test effectively excludes an ongoing pregnancy complication (sensitivity of RightSign test = 10 mIU/mL). But a positive UPT after bleeding doesn't tell you whether products remain — you need ultrasound.
| Type | Management [1] |
|---|---|
| Threatened | Observation. Vaginal micronised progesterone if vaginal bleeding AND ≥1 previous first trimester miscarriage, continued until 16 completed weeks. |
| Silent / Incomplete | Expectant (1-2 weeks), Medical (misoprostol), or Suction evacuation |
| Inevitable | Expectant or Suction evacuation |
| Complete | Reassurance — but beware of ectopic pregnancy |
Progesterone in threatened miscarriage — based on the PRISM trial (2019, NEJM): vaginal micronised progesterone 400mg BD improved live birth rate in women with ≥1 prior miscarriage. The effect was most marked in those with ≥3 prior miscarriages.
An interpregnancy interval (IPI) of < 6 months following miscarriage is not associated with adverse outcomes in the next pregnancy. [1]
- Meta-analysis of 16 studies (1,043,840 women) found IPI < 6 months was associated with reduced risk of further miscarriage (RR 0.82, 95% CI 0.78–0.86) and preterm delivery (RR 0.79, 95% CI 0.75–0.83) (Kangatharan et al., Hum Reprod Update 2017) [1]
- Stillbirth, low birthweight, and pre-eclampsia were not affected by IPI
- This evidence may be used to reassure patients who wish to conceive soon after miscarriage
Misoprostol 800 micrograms vaginally or sublingually. Follow up in Early Pregnancy Assessment Clinic 2 weeks after treatment. [1]
Misoprostol is a prostaglandin E1 analogue → causes uterine contractions and cervical softening → promotes expulsion of retained products. Vaginal and sublingual routes are equally effective; oral route has more GI side effects.
Suction evacuation — indicated when:
- Heavy bleeding requiring urgent intervention
- Patient preference
- Failed medical/expectant management
- Suspected molar pregnancy (sharp curette should NOT be used for molar pregnancy — suction only)
2B. ECTOPIC PREGNANCY
Classic triad: missed period, vaginal bleeding, and abdominal pain. Also: shock, syncope, shoulder pain. Abdominal tenderness with varying degrees of peritonism; cervical excitation. Clinical diagnosis can only be made in half of the patients. [1]
Why can you only clinically diagnose half? Because many ectopic pregnancies present with non-specific symptoms — vague abdominal discomfort, light spotting — mimicking threatened miscarriage, appendicitis, or even normal early pregnancy.
Most common site of tubal ectopic pregnancy is Ampullary (~80%). [1]
Other sites: isthmic (~12%), fimbrial (~5%), interstitial/cornual (~2-3%), and rare: ovarian, cervical, abdominal, caesarean section scar.
The ESHRE working group (2020) classifies early pregnancy location as follows [1]:
- Interstitial, cervical, caesarean scar, and intramural ectopics may be partial or complete
- A pregnancy within the uterine cavity is described as a normally sited (eutopic) pregnancy [1]
Why ampullary? The ampulla is where fertilisation normally occurs. If the fertilised egg is delayed in transit (e.g., by tubal damage), it may implant here. The ampulla has a relatively thin wall → tends to rupture earlier than isthmic ectopics.
Risk factors: previous ectopic pregnancy, tubal damage from infection/surgery, history of infertility, assisted reproduction techniques, increased age, smoking. [1]
| Risk Factor | Why |
|---|---|
| Previous ectopic | Recurrence rate ~10-15%; underlying tubal pathology persists |
| Tubal damage (PID, surgery) | Chlamydial/gonococcal salpingitis → tubal scarring and adhesions → impaired peristalsis [3] |
| Infertility | Often reflects tubal disease |
| ART (IVF) | Embryo transfer may migrate to tubes; higher rate of heterotopic pregnancy |
| Increased age | Cumulative tubal damage, altered tubal motility |
| Smoking | Impairs ciliary function and tubal peristalsis |
From GC 119 [3]: PID complications include ectopic pregnancy and subfertility (tubal obstruction). After 1 episode of PID: 13% infertility; 2 episodes: 36%; 3 episodes: 75%.
Investigations: Hb, Rh, type and screen; a negative pregnancy test effectively rules out ectopic pregnancy; pelvic ultrasound examination; hCG assay; diagnostic laparoscopy; others. [1]
Immediate management [1]:
- Fast (nil by mouth)
- Intravenous line of wide gauge
- Close observation
Why NBM + IV access? If the ectopic ruptures, she needs emergency surgery. You want IV access ready for rapid fluid resuscitation and a fasted patient for safe anaesthesia.
Emergency pathway [1]: If there are symptoms/signs of haemoperitoneum and the patient is haemodynamically unstable → proceed directly to emergency operation (do not delay for further investigations).
Diagnostic findings: adnexal mass moving separately to the ovary ("sliding sign"), comprising a gestational sac containing a yolk sac or fetal pole. [1]
High probability: adnexal mass moving separately to the ovary, with an empty gestational sac ("tubal ring," "bagel sign") or a complex inhomogeneous adnexal mass moving separately to the ovary. [1]
Possible ectopic: empty uterus or a collection of fluid within the uterine cavity (pseudo-sac). Moderate to large amount of free fluid in the peritoneal cavity or Pouch of Douglas. [1]
| USS Finding | Interpretation |
|---|---|
| Adnexal mass with yolk sac/fetal pole | Diagnostic of ectopic |
| "Tubal ring" / "bagel sign" | High probability |
| Empty uterus + positive hCG | Possible ectopic (also: very early IUP, complete miscarriage) |
| Free fluid in POD | Suggests haemoperitoneum → ruptured ectopic |
Decision to intervene should NOT be based solely on a single hCG level. Discriminatory zone is an outdated concept. Repeat assay not earlier than 48 hours. Cannot differentiate different abnormal pregnancy outcomes. [1]
Why is the discriminatory zone outdated? The traditional concept was: "if hCG is above ~1500-2000 IU/L and no IUP is seen on TVUS, it must be ectopic." But this oversimplifies — multiple pregnancies, non-viable IUPs, and lab variability can all confound. The current approach is serial hCG trends + clinical assessment, not a single cutoff.
Normal hCG doubling: In a viable IUP, hCG roughly doubles every 48 hours in early pregnancy. A rise of < 66% (or a plateau/decline) suggests an abnormal pregnancy but doesn't distinguish between failing IUP and ectopic.
After initial hCG, repeat as near as possible to 48 hours later (but no earlier) [1]:
| 48-hour hCG Change | Action |
|---|---|
| > 50% drop | Check urine pregnancy test at EPAC 2 weeks later → if negative: discharge; if positive: check serum hCG and manage accordingly |
| Between 50% decline and 63% rise | Clinical review at EPAC within 24 hours |
| ≥ 63% rise | Repeat TVS 7–14 days later (or earlier if hCG > 1,500 IU/L) |
- If any new or worsening symptoms at any point → clinical review at EPAC within 24 hours [1]
Laparoscopic approach is preferable to an open approach. In haemodynamic instability, should be managed by the most expedient method — in most cases this will be laparotomy. [1]
In the presence of a healthy contralateral tube, there is no clear evidence that salpingotomy should be used (over salpingectomy). [1]
| Procedure | When |
|---|---|
| Laparoscopic salpingectomy | Gold standard for tubal ectopic with healthy contralateral tube |
| Laparoscopic salpingotomy | Consider if contralateral tube is damaged/absent (fertility preservation) |
| Laparotomy | Haemodynamic instability — speed is paramount |
Salpingectomy vs salpingotomy: Salpingectomy (removing the whole tube) is simpler, lower risk of persistent trophoblast, and doesn't clearly reduce future fertility if the other tube is normal. Salpingotomy (incising the tube and removing the ectopic, preserving the tube) risks incomplete removal → persistent ectopic → need for methotrexate or re-operation.
Medical therapy should be offered to suitable women. Expectant management is an option for clinically stable women with minimal symptoms and a pregnancy of unknown location. [1]
Medical therapy = Methotrexate (MTX)
- A folate antagonist that inhibits rapidly dividing trophoblastic cells
- Given IM, single dose (50 mg/m²) — may need a second dose
- Criteria for MTX: haemodynamically stable, unruptured, no fetal heartbeat, hCG usually < 5000 IU/L (varies by protocol), patient can comply with follow-up
- Monitor with serial hCG until undetectable
Detailed criteria for medical vs expectant vs surgical management (NICE 126) [1]:
| Management | Criteria |
|---|---|
| Expectant | hCG < 1,500 IU/L; ectopic < 35 mm with no visible heartbeat; clinically stable and pain-free; able to return for follow-up |
| Medical (MTX) | hCG 1,500–5,000 IU/L; no significant pain; unruptured ectopic < 35 mm with no visible heartbeat; no IUP on USS; able to return for follow-up |
| Surgical (laparoscopy) | Ectopic ≥ 35 mm; visible fetal heartbeat; significant pain; unable to follow up; hCG > 5,000 IU/L; or medical treatment declined/unsuitable |
Pre-methotrexate blood tests — treatment is contraindicated if [1]:
- ALT > 2× normal
- Creatinine > 120 µmol/L
- WBC < 3 × 10⁹/L
- Platelets < 100 × 10⁹/L
- hCG > 5,000 IU/L
Expectant management: for pregnancy of unknown location (PUL) when hCG is low and declining spontaneously. Requires close follow-up with serial hCG.
Non-sensitised Rh-negative women should receive anti-D immunoglobulin. [1]
Heterotopic pregnancy: coexistence of an intrauterine and extrauterine gestation. Classical incidence 1 in 30,000. 1-3% following assisted reproduction technique. [1]
Why higher with ART? Multiple embryos may be transferred, and one can implant ectopically while another implants normally. This is why seeing an IUP does NOT completely exclude an ectopic in an IVF patient.
EPAC streamlines management of women with early pregnancy bleeding or pain, reduces the need for admission, needs appointment system, appropriate settings, transvaginal ultrasound, access to laboratory facilities (Rh antibody and hCG). [1]
2C. GESTATIONAL TROPHOBLASTIC DISEASE (GTD)
Premalignant: complete and partial hydatidiform mole. Malignant: invasive mole, choriocarcinoma, placental site trophoblastic tumour (PSTT), epithelioid trophoblastic tumour (ETT). [1]
Gestational trophoblastic neoplasia (GTN): persistence of GTD after primary treatment (persistent elevated hCG). Diagnosis does not require histological confirmation. [1]
| Feature | Complete Mole | Partial Mole |
|---|---|---|
| Karyotype | 46,XX (most) or 46,XY — all paternal | Triploid (69,XXX or 69,XXY) — 2 paternal + 1 maternal |
| Fetus | Absent | May have abnormal fetal tissue |
| Villous swelling | Diffuse, generalized | Focal, patchy |
| Trophoblast proliferation | Marked | Mild-moderate |
| hCG level | Very high (often > 100,000) | Less elevated |
| Risk of GTN | 15-20% | 0.5-5% |
| USS appearance | "Snowstorm" / clusters of grapes | May look like missed miscarriage |
Irregular vaginal bleeding, positive pregnancy test, uterus may be larger than dates, exaggerated pregnancy symptoms, early onset pre-eclampsia, very rarely haemoptysis or seizures (metastasis). [1]
Why larger than dates? Rapidly proliferating trophoblast tissue distends the uterus beyond expected gestational size. The "exaggerated pregnancy symptoms" (severe nausea, hyperemesis) are due to very high hCG levels.
Why early pre-eclampsia? Pre-eclampsia before 20 weeks is very unusual and should raise suspicion for GTD. The abnormal trophoblast triggers the same placental dysfunction pathway that causes pre-eclampsia.
Ultrasound: "snowstorm" appearance (in second trimester); complex, echogenic intrauterine mass containing many small cystic spaces — "clusters of grapes." Theca lutein cysts of ovary. [1]
Theca lutein cysts: Large bilateral ovarian cysts caused by hyperstimulation from very high hCG. They resolve spontaneously after hCG falls.
hCG; CBP, type and screen; suction evacuation; use of oxytocic infusion prior to completion of removal is NOT recommended; +/- Anti-D prophylaxis; monitoring of hCG level after evacuation; chest X-ray and thyroid function test if chest or thyroid symptoms respectively; single or multi-agent chemotherapy if GTN. [1]
Why no oxytocics before completion? Oxytocin causes uterine contractions → may force molar tissue into the venous sinuses of the myometrium → risk of trophoblastic embolism and haemorrhage. Only use after evacuation is complete.
hCG monitoring after evacuation: Serial weekly hCG until normalisation, then monthly for 6 months (complete mole) or 1 month (partial mole, varies by centre). Rising or plateauing hCG = GTN.
Chemotherapy for GTN: Single-agent methotrexate for low-risk GTN (FIGO score ≤6); multi-agent (EMA-CO regimen) for high-risk (FIGO score ≥7). Cure rates are excellent (> 95%).
2D. HYPEREMESIS GRAVIDARUM (HG)
Hyperemesis gravidarum: patients with excessive vomiting resulting in admission to hospital. [1]
Clinical triad: > 5% prepregnancy weight loss, dehydration, electrolyte imbalance. [1]
This is the RCOG Green-top Guideline No. 69 (2016) definition.
Windsor definition of HG (2021 consensus) [1]: All of the following criteria are required:
- Symptoms start in early pregnancy before 16 weeks' gestation
- Characterised by severe nausea and/or vomiting
- Inability to eat and/or drink normally
- Strongly limits daily activities
- Signs of dehydration are contributory but not mandatory for the definition
No single biomarker with the ability to identify hyperemesis gravidarum or HG severity. [1]
PUQE-24 score (Pregnancy-Unique Quantification of Emesis) — validated tool to classify NVP severity (RCOG Grade C) [1]:
| PUQE-24 Score | Severity |
|---|---|
| ≤ 6 | Mild |
| 7–12 | Moderate |
| 13–15 | Severe |
The score sums three questions covering duration of nausea, number of vomiting episodes, and number of retching episodes in the last 24 hours (each scored 1–5).
Other causes: multiple pregnancy, gestational trophoblastic disease, hyperthyroidism, upper GI tract disorder, hepatitis, other infection. [1]
Why exclude these? Each requires specific treatment. GTD causes vomiting due to very high hCG. Hyperthyroidism (Graves' disease) needs antithyroid drugs. Upper GI disorders and hepatitis need targeted investigation.
CBP, RFT, LFT, (thyroid function); hCG NOT useful; MSU for routine analysis, microscopy ± culture; pelvic ultrasound; others. [1]
Why is hCG not useful? Because all pregnant women have elevated hCG. It doesn't discriminate HG from normal pregnancy nausea.
Thyroid function and HG — this is a commonly examined concept:
In patients with no prior history of thyroid disease, no evidence of Graves' disease such as goitre, and a self-limited disorder with symptoms of emesis, routine thyroid tests are not needed. Abnormal thyroid tests attributable to gestational transient thyrotoxicosis or HG should be managed with supportive therapy — antithyroid drugs are NOT recommended (Level A, ACOG Practice Bulletin 189). [1]
High Yield: Gestational Transient Thyrotoxicosis
hCG shares structural homology with TSH → at high hCG levels, the TSH receptor is stimulated → suppressed TSH, slightly elevated fT4. This is gestational transient thyrotoxicosis, NOT Graves' disease. It is self-limiting and does NOT require antithyroid drugs. The clue is: no goitre, no ophthalmopathy, no anti-TSH receptor antibodies.
Mallory-Weiss oesophageal tear, Mendelson syndrome, neurological disturbances (Wernicke's encephalopathy, peripheral neuropathy). [1]
| Complication | Mechanism |
|---|---|
| Mallory-Weiss tear | Forceful/repeated vomiting → mucosal tear at gastro-oesophageal junction |
| Mendelson syndrome | Aspiration of gastric contents → chemical pneumonitis |
| Wernicke's encephalopathy | Thiamine (vitamin B1) deficiency from prolonged vomiting + poor intake; classic triad: confusion, ophthalmoplegia, ataxia |
| Peripheral neuropathy | B-vitamin deficiency |
Fast, IV fluid and electrolyte replacement; Antiemetics; Thiamine replacement; Intake and output chart, daily body weight monitoring; Thromboprophylaxis. [1]
Why thromboprophylaxis? Dehydration + pregnancy (hypercoagulable state) → significantly increased VTE risk. LMWH should be considered. [4]
Dietary advice [1]:
- Initially oral fluid intake → followed by small carbohydrate meals → total avoidance of fatty foods
- Avoid offensive foods and odour, eat frequent small meals, low protein/low fat/high carbohydrate, avoid iron supplements, eat whatever pregnancy-safe foods appeal
Dry diet approach [1]:
- Small, frequent meals that are fairly dry and high in easily digested carbohydrates
- Liquids are taken between meals rather than with meals
There is little published evidence regarding the efficacy of dietary changes for prevention or treatment of NVP (ACOG). Eat whatever pregnancy-safe food appeals to them (SOGC 2016). [1]
First-line: H1 receptor antagonists and phenothiazines — safety and efficacy data support their use for NVP and HG (Grade C, RCOG Green-top 69). [1]
Dimenhydrinate (Gravol): H1 antagonist, compatible with pregnancy. Oral or rectal. Caution near birth of premature infants (risk of retrolental fibroplasia). [1]
The ACOG stepped approach (from lecture slide) [1]:
| Step | Drug |
|---|---|
| 1st line | Pyridoxine (vitamin B6) ± doxylamine |
| 2nd line | Dimenhydrinate or promethazine |
| 3rd line | Metoclopramide, ondansetron |
| 4th line | Methylprednisolone (for refractory cases) |
Dimenhydrinate (Gravol): H1 antagonist, compatible with pregnancy. Oral or rectal administration. Caution near birth of premature infants (risk of retrolental fibroplasia). [1]
Thiamine supplementation should be given to ALL women admitted with prolonged vomiting, especially BEFORE administration of dextrose or parenteral nutrition (Grade D, RCOG). [1]
Why thiamine BEFORE dextrose?
Giving IV dextrose to a thiamine-depleted patient accelerates glucose metabolism, which consumes the remaining thiamine → precipitates Wernicke's encephalopathy. ALWAYS give thiamine first. This is the same principle as in alcoholic patients.
Multivitamin supplementation: Evidence from Emelianova 1999 — women who supplemented with vitamins before 6 weeks of gestation had lower rates of vomiting (40% vs 59%, p=0.002) [1].
The lecture briefly covers legal termination of pregnancy in Hong Kong:
"The continuation of the pregnancy would involve risk to the life of the pregnant woman or of injury to the physical or mental health of the pregnant woman, greater than if the pregnancy were terminated." [1]
This is the legal ground under Hong Kong's Offences Against the Person Ordinance (Cap 212, Section 47A). Termination requires two registered medical practitioners to certify.
Part 3: Emotional Impact of Early Pregnancy Loss
Psychiatric morbidity following miscarriage: 48-51% of women in Western countries develop depressive disorder. In Hong Kong: 12% major depression, 1.3% anxiety disorder at 6 weeks post-miscarriage (Lee 1997). [1]
At 3 months post-miscarriage: 10% depressive disorder, 1.2% anxiety disorder NOS, 0.6% OCD, 0.6% PTSD. Risk factors: younger age, history of infertility and depression (Sham 2010). [1]
Level of distress reduced over time until comparable with controls at 1 year. Initially more distressed patients continued to be distressed throughout the 1-year course (Lok 2010). [1]
Supportive counselling RCT (Kong, Chung & Lok — CUHK, BJOG 2014) [1]:
- 280 women with miscarriage randomised to supportive counselling (at diagnosis + 2 weeks) vs routine care
- No overall difference in psychological distress at 3 months (17.1% vs 24.4%, p = 0.19)
- However, in the subgroup with high baseline distress (GHQ-12 high scorers, n = 152): counselling group had significantly lower distress at 6 weeks (median GHQ 3 vs 4.5, p = 0.04) and 3 months (1 vs 2.5, p = 0.03)
- Conclusion: Routine counselling for all women is not justified, but targeted supportive counselling for women with high initial distress is promising [1]
No difference in psychological outcomes between surgical and medical treatment. More participants with successful medical treatment would choose the same mode. Less satisfied in those with failed medical treatment (Lee 2001). [1]
About 65% believed miscarriage adversely affected their health. > 90% planned to take tonics. 47% of surgical vs 33% of medical group felt surgical evacuation weakened their body. More women in the surgical group felt the intervention damaged the devitalized body (39% vs 21%) (Lee 2001). [1]
This reflects Chinese ethnomedical beliefs about "qi" and the body being weakened by surgical intervention.
Women's negative experiences with healthcare providers: Lack of information, lack of follow-up, insensitivity (comments, terminology), dismissive attitude ("common and routine!"), dishonesty ("nothing wrong"), carelessness (admission to maternity ward), insensitive sonographers, lack of understanding of pregnancy journey. [1]
Communication Matters
Never tell a patient miscarriage is "common and routine." While it occurs in ~15-25% of pregnancies, it is devastating to the individual. Avoid admission to maternity wards. Use appropriate terminology. Offer follow-up. Acknowledge the loss.
1. Miscarriage is the preferred term. Clinical differentiation of types. Importance of pelvic sonography. Best treatment is still evolving. [1]
2. Ectopic pregnancy is an important DDx. Use of algorithm in early diagnosis. Laparoscopic salpingectomy is the gold standard of treatment. Role of Early Pregnancy Assessment Service. [1]
3. GTD is an important DDx of threatened miscarriage. Hyperemesis gravidarum can be life-threatening — important to exclude other diagnoses. [1]
4. Miscarriages are associated with significant psychiatric morbidity though prevalence may be lower in our population. Choice of mode of treatment is affected by ethnomedical beliefs and success rate — should be individualised. Healthcare providers can add to the trauma. [1]
Exam Intelligence
| Trap | Correct Approach |
|---|---|
| Assuming "empty uterus on USS" = complete miscarriage | Always consider ectopic pregnancy — empty uterus + positive hCG = PUL until proven otherwise |
| Using a single hCG level to diagnose ectopic | Discriminatory zone is outdated; need serial hCG + clinical correlation |
| Giving antithyroid drugs for suppressed TSH in HG | This is gestational transient thyrotoxicosis — supportive Rx only, no antithyroid drugs |
| Giving IV dextrose before thiamine in HG | Can precipitate Wernicke's encephalopathy — give thiamine FIRST |
| Confusing salpingectomy with salpingotomy | Salpingectomy = tube removal (gold standard); salpingotomy = tube-sparing incision |
| Not checking Rh status after miscarriage/ectopic | Rh-negative women need anti-D immunoglobulin |
| Using oxytocics during molar evacuation | Oxytocics NOT recommended before completion — risk of trophoblastic embolism |
| Diagnosing silent miscarriage on a single scan | Need second scan ≥7 days later or second opinion |
- Threatened vs inevitable miscarriage: cervix CLOSED vs OPEN
- Silent vs incomplete: both can have no pain, but silent = closed os + no expulsion; incomplete = open os + partial expulsion
- Complete miscarriage vs ectopic: both can show empty uterus — check hCG and consider ectopic!
- GTD vs threatened miscarriage: uterus larger than dates, very high hCG, snowstorm USS, theca lutein cysts
- HG vs morning sickness: HG requires hospitalisation, has > 5% weight loss, dehydration, electrolyte imbalance
- GC 119 [3]: PID → tubal damage → ectopic pregnancy risk. Chlamydia is the most common cause of tubal factor infertility.
- GC 115 [9]: Medical problems complicating pregnancy — diabetes increases miscarriage risk; pre-eclampsia can present early in molar pregnancy.
- CFB Fertility Regulation [10]: Methods of contraception; legal grounds for termination of pregnancy in Hong Kong.
- GC 113 [11]: Pre-marital/pre-pregnancy counselling — Rh status screening, rubella immunity, carrier screening for thalassaemia — all relevant to preventing complications in early pregnancy.
- Ryan Ho Radiology [12]: Ectopic pregnancy site 75-80% ampulla; presentation mimics appendicitis; TVUS for diagnosis; serial β-hCG; diagnostic laparoscopy is gold standard but invasive.
- DVT in pregnancy [4]: Pregnancy = hypercoagulable state. HG with dehydration further increases VTE risk → thromboprophylaxis is part of HG management.
High Yield Summary
-
Miscarriage
- Preferred term over "abortion."
- Classified by pain, cervical os status, and uterine size.
- USS criteria for silent miscarriage: mean sac diameter ≥25mm with no embryo/yolk sac, OR CRL ≥7mm with no heartbeat.
- Always need a SECOND scan ≥7 days later.
- Management: observation (threatened + progesterone if prior miscarriage), expectant/medical/surgical (silent/incomplete).
- Check Rh status.
- Recurrent miscarriage investigations: antiphospholipid antibodies, TSH/anti-TPO, karyotype, uterine malformation screening, thrombophilia screen for 2nd trimester losses.
-
Ectopic
- Classic triad (often incomplete clinically).
- Most common site = ampulla (~80%).
- Negative pregnancy test rules it out.
- USS: adnexal mass separate from ovary.
- Don't rely on single hCG or discriminatory zone.
- Gold standard Rx = laparoscopic salpingectomy.
- Laparotomy if unstable.
- MTX for suitable stable patients.
- Anti-D for Rh-negative.
- Heterotopic 1:30,000 (higher with ART).
-
GTD
- Complete vs partial mole. Snowstorm USS, very high hCG, uterus larger than dates. Suction evacuation (no oxytocics before completion). Monitor hCG post-evacuation. GTN if hCG persists/rises → chemotherapy.
-
Hyperemesis gravidarum
- Clinical triad: > 5% weight loss + dehydration + electrolyte imbalance.
- Exclude GTD, multiple pregnancy, thyrotoxicosis (gestational transient thyrotoxicosis is NOT Graves' — no antithyroid drugs).
- Ix: CBP, RFT, LFT, TFT, MSU, USS.
- Rx: IV fluids, thiamine BEFORE dextrose, antiemetics (H1 antagonists first-line), thromboprophylaxis, dietary modification.
-
Emotional impact
- 10-12% major depression post-miscarriage in HK. Be sensitive. Don't dismiss. Don't admit to maternity ward. Individualise treatment choice. Healthcare providers can add to trauma.
Active Recall - Complications of Early Pregnancy
[1] Lecture slides: GC 223. Complications of Early Pregnancy.pdf [2] Lecture slides: Block C - Complications of Early Pregnancy (CFB WCS in 2023_24).pdf [3] Lecture slides: GC 119. Vaginal discharge obstetric and gynaecological infections.pdf (Complications - late section) [4] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf (Pregnancy and estrogen associated VTE section) [9] Lecture slides: GC 115. I am pregnant medical problems complicating pregnancy.pdf [10] Lecture slides: CFB (OG03) Fertility Regulation.pdf [11] Lecture slides: GC 113. Can we get married Pre-marital, pre-pregnancy and pre-natal counselling.pdf [12] Senior notes: Ryan Ho Radiology.pdf (Obstetric Imaging section)
GC222 I Want To Donate My Organs
A UK General Medical Council guidance topic addressing the principles and processes by which individuals can express their wish to donate organs after death, including consent, registration, and the roles of healthcare professionals in facilitating organ donation.
GC224 Hypertension And Pregnancy
Hypertension in pregnancy encompasses a spectrum of blood pressure disorders—including chronic hypertension, gestational hypertension, preeclampsia, and eclampsia—that can lead to significant maternal and fetal morbidity if not promptly identified and managed.