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):

This is the highest-yield table from this lecture. The slide builds it incrementally ^[1]:

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!

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]

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.

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.

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)

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.

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]

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.

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]

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.

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]

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

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]

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]

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%).

Clinical triad: > 5% prepregnancy weight loss, dehydration, electrolyte imbalance. ^[1]

This is the RCOG Green-top Guideline No. 69 (2016) definition.

No single biomarker with the ability to identify hyperemesis gravidarum or HG severity. ^[1]

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]

Mallory-Weiss oesophageal tear, Mendelson syndrome, neurological disturbances (Wernicke's encephalopathy, peripheral neuropathy). ^[1]

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

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]:

Thiamine supplementation should be given to ALL women admitted with prolonged vomiting, especially BEFORE administration of dextrose or parenteral nutrition (Grade D, RCOG). ^[1]

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].