Gynae - Early Pregnancy

Question 1

Ectopic Pregnancy

Definition
Risk Factors
Clinical Features
Differential Diagnosis

Answer 1

1. ) Definition - any pregnancy that is implanted at a site outside of the uterine cavity
   - sites: ampulla or isthmus of the fallopian tubes (most common), ovaries, cervix, peritoneal cavity
   - increased risk of rupture in the isthmus
2. ) Risk Factors
   - PMH: previous ectopic, PID and endometriosis due to the formation of adhesions
   - contraception: IUD/IUS, POP and implant due to fallopian tube dysmotility, tubal ligation/occlusion
   - iatrogenic: pelvic surgery (esp tubal), assisted reproduction i.e. embryo transfer in IVF
3. ) Clinical Features
   - lower abdominal or pelvic pain
   - may have vaginal bleeding: the decidual breakdown in the uterine cavity due to suboptimal β-HCG levels
   - brown vaginal discharge (decidual breakdown)
   - there may be a history of amenorrhoea
   - examination: localised abdo tenderness, cervical excitation and/or adnexal tenderness
   - ruptured ectopic: intra-abdominal bleeding, may have shoulder tip pain (blood irritates diaphragm), signs of peritonitis or haemodynamic instability
4. ) Differential Diagnosis
   - miscarriage, ovarian cyst haemorrhage/torsion/rupture
   - appendicitis, diverticulitis, UTI, acute PID

Question 2

Investigations for an Ectopic Pregnancy

Initial Investigations
When Serum β-hCG is > 1500 IU
When Serum β-hCG is < 1500 IU
Other Investigations

Answer 2

1. ) Initial Investigations
   - pregnancy test (urine β-hCG) is the first step, if +ve:
   - pelvic TVUS to find the location of the pregnancy
   - if β-hCG is positive but there is no pregnancy on USS, this is a ‘pregnancy of unknown location’ and a serum β-hCG should be undertaken
2. ) When Serum β-hCG is > 1500 IU
   - this is an ectopic pregnancy until proven otherwise
   - a diagnostic laparoscopy should be offered
3. ) When β-hCG is < 1500 IU - if the patient is stable, a further blood test should be taken 48 hours later:
   - viable pregnancy: β-hCG should double every 48hrs
   - miscarriage: β-hCG should halve every 48hrs
   - if the β-hCG hasn’t either doubled or halved, an ectopic cannot be excluded so the patient should be managed accordingly
4. ) Other Investigations - may be used to rule in/out the other differential diagnoses
   - urinalysis for a UTI

Question 3

Management of an Ectopic Pregnancy

Medical Management
Surgical Management
Conservative/Expectant Management

Answer 3

1. ) Medical Management
   - IM methotrexate to gradually resolve the pregnancy
   - offered to unruptured/stable patients, no heartbeat, and well-controlled pain with β-hCG <1500IU
   - serum β-hCG is monitored to ensure it is declining (>15% on day 4-5), if not, a repeat dose is administered
   - safety netting for symptoms of a ruptured ectopic
   - adv: no surgery, can go home after the injection
   - disadv: treatment can fail, use contraception 3-6mths after (teratogenesis), other side effects inc abdo pain, myelosuppression, renal dysfunction, hepatitis
2. ) Surgical Management
   - offered to patients with severe pain, β-hCG >5000, adnexal mass >35mm or fetal heartbeat is seen on USS
   - laparoscopic salpingectomy: for tubal ectopic
   - salpingotomy can be used if there is damage to the contralateral tube to preserve future fertility, however, there is an increased risk of re-occurrence
   - emergency laparotomy for ruptured ectopic
   - anti-D prophylaxis for all Rh-ve women
   - adv: reassurance as it is definitive/high success rate
   - disadv: general anaesthetic, DVT/PE, bleeding, infection, damage to neighbouring structures
3. ) Conservative Management - watchful waiting of the stable patient, allows the ectopic to resolve naturally
   - not first line, it is only offered to suitable patients:
   - asymptomatic, unruptured embryo, <35mm in size with no heartbeat and a beta-hCG <1000IU and declining
   - serum β-hCG should be checked every 48hrs to ensure it is falling by > 50% until it falls to <5 IU
   - safety netting for symptoms of a ruptured ectopic
   - adv: avoids surgical and medical, can go home
   - disadv: failure or complications necessitating medical or surgical management (25%), rupture of ectopic

Question 4

Miscarriage

Definition 
Risk Factors
Clinical Features
Investigations
Differential Diagnoses

Answer 4

1. ) Definition - loss of a pregnancy at <24wks
   - early miscarriages (<13wks) are more common
   - miscarriages are common (20-25% of pregnancies)
2. ) Risk Factors
   - maternal age >30-35, maternal or paternal chromosomal abnormalities
   - previous miscarriage, previous uterine surgery
   - smoking, obesity, antiphospholipid syndrome, coagulopathies, uterine anomalies
3. ) Clinical Features
   - many are just found incidentally on ultrasound
   - vaginal bleeding often accompanied by suprapubic, cramping pain (similar to primary dysmenorrhoea)
   - may include passing clots or products of conception
   - excessive bleeding –> haemodynamic instability:
   - dizziness, pallor, and shortness of breath
   - examination: distended/tender abdomen, speculum to see cervical os, POC or local areas of bleeding, bimanual: uterine tenderness, adnexal masses
4. ) Investigations
   - transvaginal USS for definitive diagnosis: no fetal cardiac activity AND
   crown-rump length >7mm OR gestational sac > 25mm
   - if not, can perform a repeat scan in 7 days
   - transabdominal (pelvic) USS can be used if TVUS isn’t acceptable but it is not as accurate
   - serial serum b-HCG if suspecting an ectopic
   - FBC, G+S, Rh- status, CRP and triple swabs if pyrexial
5. ) Differential Diagnoses
   - ectopic pregnancy, cervical/uterine malignancy
   - hydatidiform mole

Question 5

Classifications of Miscarriages

Threatened Miscarriage
Inevitable Miscarriage
Missed Miscarriage
Incomplete Miscarriage
Complete Miscarriage
Septic Miscarriage

Answer 5

1. ) Threatened Miscarriage - basically a false alarm
   - mild bleeding +/- pain with a closed cervix
   - transvaginal USS (TVUS): viable pregnancy
   - reassure, admit/observe if heavy bleeding
2. ) Inevitable Miscarriage
   - heavy (clots) and painful bleeding w/an open cervix
   - TVUS: opened internal cervical os, the fetus may or may not be viable
   - offer conservative/medical/surgical options
   - admit/observe if heavy bleeding
   - likely to proceed to incomplete/complete miscarriage
3. ) Missed Miscarriage
   - asymptomatic or hx of threatened miscarriage, on-going discharge, the uterus is small for dates
   - TVUS: no fetal heart pulsation where CRL is >7mm
   - may want to rescan and a second person to confirm
   - manage medically or surgically, conservatively has lower success rates
4. ) Incomplete Miscarriage
   - products of conception are partially expelled
   - sx of missed miscarriage or bleeding/clots
   - TVUS: retained POC, with A/P endometrial diameter >15mm AND proof there was an intrauterine pregnancy previously present (USS/clinically remove clots)
   - offer conservative/medical/surgical options
5. ) Complete Miscarriage
   - sx of inevitable miscarriage but is now settling/settled
   - TVUS: no POC seen in uterus, endometrium is <15 mm diameter, previous proof of intrauterine pregnancy
   - discharge to GP
6. ) Septic Miscarriage
   - infected POC: fever, rigors, uterine tenderness, bleeding/discharge, pain, ↑WCC, ↑CRP
   - may have features of (in)complete miscarriage
   - medical or surgical management, IV abx and fluids

Question 6

Management of Miscarriage

Conservative Management
Medical Management
Surgical Management

Answer 6

1. ) Conservative Management
   - allows products of conception to pass naturally
   - anti-D prophylaxis if Rh-ve and >12wks for all miscarriages (<12wks if after surgical intervention)
   - adv: remain home, no medication side effects
   - disadv: unpredictable timing, heavy bleeding and pain during passage of POC, can be unsuccessful requiring further intervention and need for transfusion
   - FU: repeat US in 2wks or pregnancy test 3wks later
   - contraindications: infection, high risk of haemorrhage (e.g. coagulopathy, haemodynamic instability)
2. ) Medical Management
   - vaginal misoprostol to expel the contents
   - adv: can be done at home
   - disadv: N+V, heavy bleeding and pain during passage of POC, may need emergency surgical intervention
   - FU: pregnancy test 3 weeks later
3. ) Surgical Management
   - manual vacuum aspiration w/ local anaesthetic if <12wks OR evacuation of retained POC (ERPC)
   - ERPC: same-day procedure under a general, suction tube passed into the cervix to remove the POC
   - indication: haemodynamically unstable, infected tissue, gestational trophoblastic disease
   - adv: planned procedure, asleep during the process
   - disadv: anaesthetic risk, endometritis, haemorrhage, uterine perforation, Asherman’s syndrome, bowel or bladder damage, retained POC

Question 7

Recurrent Miscarriage

Definition
Risk Factors
Investigations
Management

Answer 7

1.) Definition - occurrence of three or more consecutive pregnancies that end in miscarriage before 24weeks

2. ) Risk Factors
   - advancing maternal age: decline in number and quality of oocytes, father >40 is also a risk factor
   - previous miscarriages, smoking, heavy alcohol intake
3. ) Investigations
   - blood tests: APS antibodies, a thrombophilia screen
   - karyotyping: cytogenetic analysis of POC, parental peripheral blood karyotyping when POC reports an unbalanced structural chromosomal abnormality
   - imaging: pelvic USS to assess uterine anatomy, hysteroscopy, laparoscopy or 3-D pelvic ultrasound for further investigations if suspicious from pelvic USS
4. ) Management - refer to recurrent miscarriage clinic
   - genetic abnormalities: genetic counselling
   - unexplained: offered preimplantation genetic screening with IVF treatment
   - anatomical: no benefit of surgical correction
   - cervical weakness: cervical cerclage (closes cervix) may be indicated, however, there’s a risk of membrane rupture which will stimulate contractions
   - thrombophilia: heparin therapy during pregnancy
   - APS: consider low dose-aspirin + LMWH

Question 8

Causes of Recurrent Miscarriage

Antiphospholipid Syndrome
Genetic Factors
Endocrine Factors
Anatomical Factors
Infective Agents
Inherited Thrombophilias

Answer 8

1.) Antiphospholipid Syndrome - present in 15% of women with recurrent miscarriage

2. ) Genetic Factors
   - parental chromosomal rearrangements: balanced reciprocal or Robertsonian l translocation
   - embryonic chromosomal abnormalities: account for 30–57% of further miscarriages
3. ) Endocrine Factors
   - thyroid disease, diabetes (↑HBA1c at conception is linked w/ ↑risk of miscarriage/fetal malformation)
   - PCOS is also associated with ↑risk of miscarriage
4. ) Anatomical Factors
   - cervical weakness: cervix effaces and dilates before the pregnancy reaches term –> miscarriage
   - acquired uterine abnormalities: fibroids, adhesions
   - genetic uterine: septate, bicornuate, arcuate uterus
5. ) Infective Agents - a rare cause
   - any severe infection (esp w/ pyrexia) causing bacteraemia/viraemia –> sporadic miscarriage
   - BV in T1 is a risk factor for T2 miscarriage
6. ) Inherited Thrombophilia’s - link w/ T2 miscarriage
   - ?due to thrombosis of uteroplacental circulation
   - factor V Leiden, protein C/S and antithrombin III deficiency, prothrombin gene mutation

Question 9

Antiphospholipid Syndrome

Pathophysiology
Clinical Features
Investigations
Management

Answer 9

1. ) Pathophysiology - antiphospholipid antibodies induce a procoagulant state (CLOT syndrome)
   - obstetric complications of APS are due to:
   - inhibition of trophoblastic function and differentiation
   - thrombosis of the uteroplacental vasculature
   - activation of complement pathways
   - can occur in isolation or secondary to autoimmune conditions; such as SLE, RA and systemic sclerosis
2. ) Clinical Features
   - recurrent pregnancy loss: APS is associated w/ pre-eclampsia and intrauterine growth restriction
   - thrombosis formation: arterial/venous/microvascular, less commonly inc PE, MI, retinal thrombosis
   - other manifestations: livedo reticularis, valvular heart disease, renal impairment, thrombocytopenia
   - catastrophic APS is a rare complication w/ formation of microthromboses in multiple organs (50% mortality rate)
3. ) Investigations - blood test for antibodies (needs 2 +ve tests > 12wks apart for 1 of the three antibodies)
   - antibodies: anticardiolipin, lupus anticoagulant, anti-B2-glycoprotein I (binds with cardiolipin)
   - tested for in all women with recurrent miscarriage, atypical vascular thrombosis or recurrent thromboses
   - ≈ 5% of healthy individuals test positive for antibodies
   - diagnosis requires one clinical and laboratory criteria
4. ) Management
   - recurrent pregnancy loss: LMWH and low dose aspirin throughout subsequent pregnancies
   - previous pre-eclampsia or IUGR: low dose aspirin (75mg OD) throughout subsequent pregnancies
   - vascular thrombosis: long-term warfarin, switch to LMWH if the patient is pregnant or is trying to conceive

Question 10

Gestational Trophoblastic Disease (GTD)

What is it?
Risk Factors
Clinical Features
Investigations
Management

Answer 10

1. ) What is it? - describes a group of pregnancy-related tumours, can be divided into 2 main groups:
   - pre-malignant (more common): molar pregnancies
   - malignant (rarer): invasive mole, choriocarcinoma, placental trophoblastic site tumour and epithelioid trophoblastic tumour
2. ) Risk Factors
   - maternal age <20 or >35, use of oral contraceptive
   - previous GTD, previous miscarriage
3. ) Clinical Features
   - vaginal bleeding and abdo pain early in pregnancy
   - examination: soft and boggy uterus larger than expected for gestation ( ‘large for dates’), molar vesicles can shed PV
   - if undiagnosed, later symptoms can cause:
   - hyperemesis and gestational thyrotoxicosis due to high β-hCG levels, anaemia, uterus
4. ) Investigations
   - USS: complete mole has a granular or ‘snowstorm’ appearance with a central heterogeneous mass and surrounding multiple cystic areas/vesicles (solid collection of echoes with numerous small anechoic spaces which resembles a bunch of grapes)
   - histological examination of POC: done post-treatment and on non-viable pregnancies to confirm/get the definitive diagnosis
   - serum β-hCG: markedly elevated at diagnosis, urine β-hCG in cases of persistent post-partum bleeding
   - TFTs: raised T4/T3, low TSH (b-hCG mimics TSH)
   - staging CT/MRI/pelvic US in metastatic spread
5. ) Management
   - refer to a GTD centre for FU and future pregnancies
   - suction curettage for non viable molar pregnancies
   - medical evacuation if the partial mole is of greater gestation, theoretical risk of embolisation of the trophoblastic tissue if oxytocic agents are used
   - anti-D post-evacuation if the mother is Rh-ve
   - may need chemo after evac if β-hCG doesn’t fall,
   - other types of GTD: refer to specialist GTD centre, chemotherapy +/- surgery is the mainstay of treatment

Question 11

Types of Gestational Trophoblastic Disease (GTD)

Partial Molar Pregnancy
Complete Molar Pregnancy
Choriocarcinoma
Placental Site Trophoblastic Tumour 
Epithelioid Trophoblastic Tumour

Answer 11

1. ) Partial Molar Pregnancy
   - one ovum w/ 23 chromosomes is fertilised by 2 sperms so there are 69 chromosomes (triploidy)
   - this can exist with a viable fetus if the fetus has a normal karyotype (46) and triploidy is at the placenta
   - usually benign but can be malignant (invasive mole):
   - invades into the myometrium and around the body
2. ) Complete Molar Pregnancy
   - an ovum without any chromosomes is fertilised by one sperm which duplicates (or 2 sperms)
   - causes 46 chromosomes of paternal origin alone
   - can also become an invasive mole
3. ) Choriocarcinoma
   - malignancy of the trophoblastic cells of the placenta
   - commonly co-exists with a molar pregnancy, however it would not present until AFTER the pregnancy
   - characteristically metastasises to the lungs
4. ) Placental Site Trophoblastic Tumour
   - malignancy of the intermediate trophoblasts (normal function is to anchor the placenta to the uterus)
   - commonly occurs after a normal pregnancy but can also occur after a molar pregnancy or miscarriage
5. ) Epithelioid Trophoblastic Tumour
   - malignancy of the trophoblastic placental cells so can be very difficult to distinguish from a choriocarcinoma
   - mimics the cytological features of an SCC

Question 12

Termination of Pregnancy (Abortion)

Legal Requirements
Medical Abortion
Surgical Abortion
Post-Abortion Care

Answer 12

1. ) Legal Requirements
   - TOP can be performed <24 weeks if the pregnancy poses a greater risk to the physical or mental health of the woman or the existing children of the family
   - TOP can be performed >24 weeks if it will prevent “grave permanent injury” to the woman (inc mental) or there is “substantial risk” that the child would be physically or mentally handicapped
   - two registered NHS medical practitioners must sign to agree abortion is indicated
2. ) Medical Abortion
   - most appropriate earlier in pregnancy, but can be used at any gestation. It involves two treatments:
   - mifepristone (anti-progestogen) and misoprostol (prostaglandin analogue) 1-2 days later
   - from 10wks, additional misoprostol doses (e.g. every 3 hours) are required until expulsion
   - anti-D prophylaxis for Rh-ve women >10wks
3. ) Surgical Abortion
   - done under GA or LA +/- sedation
   - cervical priming: softening and dilating the cervix with misoprostol, mifepristone or osmotic dilators
   - there are two options for surgical abortion:
   - suction of the contents of the uterus (<14 weeks)
   - evacuation using forceps (between 14 and 24 weeks)
   - anti-D prophylaxis in all Rh-ve women inc <10wks
4. ) Post-Abortion Care
   - may experience vaginal bleeding and abdominal cramps intermittently for up to 2wks post-procedure
   - urine pregnancy test is done 3wks after to confirm it is complete, if still positive, repeat after another week
   - complications: bleeding, pain, infection, failure of the abortion, damage to structures (e.g. cervix or uterus)