Early Pregnancy (Ectopic pregnancy; Molar Pregnancy; Hyperemesis gravid arum)

Question 1

Define what is meant by an ectopic pregnancy [1]

Where is the most common site for an ectopic pregnancy to occur? [1]

Answer 1

An Ectopic Pregnancy occurs when a fertilised ovum implants and matures outside the uterine endometrial cavity

• 97% occur in the fallopian tube with ampulla being the commonest location
• < 2% ovarian
• < 1% cervical
• < 1% abdominal

Question 2

Describe some risk factors for ectopic pregnancy [+]

Answer 2

Previous ectopic

Tubal factors:
- scarring or adhesions from PID
- congenital anomalies,

Tubal surgery:
- salpingectomy
- tubal ligation
- reconstructive surgery

Assisted reproductive technology (ART):
- Fertility treatments, particularly in vitro fertilization (IVF)

Intrauterine device (IUD) use

Smoking

Endometriosis

Question 3

Describe the pathophysiology of ectopic pregnancy [3]

Answer 3

Implantation outside the uterine cavity occurs when the fertilized ovum is unable to reach the endometrial lining due to impaired tubal transport or abnormal embryo-tubal interactions:
- Abnormal embryo migration (disrupted tubal motility, due to factors such as PID, endometriosis, or smoking)
- Impaired tubal environment: Inflammatory processes, including infection or endometriosis, can alter the tubal milieu, promoting ectopic implantation.
- Embryo-tubal interactions: Alterations in the expression of adhesion molecules and chemokines, such as integrins and L-selectin, may affect the embryo-tubal relationship, leading to ectopic pregnancy.

Question 4

Describe the clinical features of ectopic pregnancies [+]

Answer 4

Female with a history of 6-8 weeks amenorrhoea who presents with lower abdominal pain and later develops vaginal bleeding

Constant lower abdominal pain:
- in the right or left iliac fossa
- often FIRST symptom
- pain is constant

Vaginal bleeding:
* usually less than a normal period
* may be dark brown in colour

Recent amenorrhoea
- if longer (e.g. 10 wks) this suggest another causes e.g. inevitable abortion

Cervical motion tenderness (pain when moving the cervix during a bimanual examination)

Dizziness or syncope (blood loss)

Shoulder tip pain(peritonitis)

Question 5

Describe the investigations used for a suspect ectopic pregnancy [3]

Answer 5

A pregnancy test
- Urine bHCG
- Serum bHCG: A single hCG value is not diagnostic, but a slower-than-expected rise or decline in hCG levels may suggest an ectopic pregnancy

Transvaginal US:
- adnexal mass, extrauterine gestational sac, or complex adnexal fluid collection.
- empty uterine cavity and absence of an intrauterine gestational sac

Abdominal US
- should only be used when the patient declines the transvaginal approach

Question 6

Describe how you interpret serum bHCG levels with ectopic pregnancies

Answer 6

If the initial β-HCG level is >1500 iU (discriminatory level)
- & there is no intrauterine pregnancy on transvaginal ultrasound –> consider ectopic pregnancy until proven otherwise

If the initial β-HCG level is < 1500 iU:
- and the patient is stable, a further blood test can be taken 48 hours later
- Viable pregnancy: HCG level would be expected to double every 48 hours.
- Miscarriage: HCG level would be expected to halve every 48 hours

Question 7

What are the three management options for ectopic pregnancy? [3]

Answer 7

Expectant
- watch & see

Medical
- methotrexate

Surgical (laparoscopic)
- Salpingectomy = removal of the fallopian tube affected by the ectopic
- Salpingotomy = affected tube is opened and ectopic is removed. Aims to preserve the tube; considered if the contralateral tube is damaged or there are other fertility concerns

Question 8

Describe the criteria that needs to be met to indicate expectant managment for ectopic pregnancy [5]

Answer 8

• Clinical stable and pain free AND
• Unruptured tubal ectopic pregnancy measuring less than 35mm with no
  visible heartbeat in TVUS AND
• Serum b-hCG levels of ≤1,000 IU/L AND
• Able to return for follow up

Question 9

What is the criteria to meet medical management of EP?

Answer 9

Have no significant pain AND
* Unruptured tubal ectopic pregnancy measuring less than 35mm with no visible heartbeat in TVUS AND
* Serum b -hCG levels of ≤1,500 IU/L AND
* Able to return for follow up

Question 10

What advice should be given to patients who have recieved IM MTX tx for an ectopic pregnancy? [1]

Answer 10

Women treated with methotrexate are advised not to get pregnant for 3 months following treatment. This is because the harmful effects of methotrexate on pregnancy can last this long.

Question 11

What are common AEs of MTX tx for ectopic pregnancy? [4]

Answer 11

• Vaginal bleeding
• Nausea and vomiting
• Abdominal pain
• Stomatitis (inflammation of the mouth)

Question 12

Which patients require surgery for an ectopic pregnancy? [4]

Answer 12

This include those with:
* Pain
* Adnexal mass > 35mm
* Visible heartbeat
* HCG levels > 5000 IU / l

Question 13

Describe the different surgeries used for ectopic pregnancy [2]

Answer 13

Laparoscopic salpingectomy
- is the first-line treatment for ectopic pregnancy.
- This involves a general anaesthetic and key-hole surgery with removal of the affected fallopian tube, along with the ectopic pregnancy inside the tube.

Laparoscopic salpingotomy
- may be used in women at increased risk of infertility due to damage to the other tube.
- The aim is to avoid removing the affected fallopian tube. A cut is made in the fallopian tube, the ectopic pregnancy is removed, and the tube is closed.

Question 14

Answer 14

Question 15

What follow up management do all patients who require a salpignotomy require? [1]

What other management needs to be considered post-ectopic pregnancy? [1]

Answer 15

Patients who have required salpingotomy require weekly b-hCG measurements until negative. Approximately 1 in 5 will need further treatment

Anti-D Rhesus Prophylaxis - Rhesus D negative women may require anti-D rhesus prophylaxis if surgical management and/or repeated, heavy bleeding and/or pain

Question 16

Describe the short term complications of an ectopic pregnancy [2]

Answer 16

Tubal rupture:
- The most severe and life-threatening complication of ectopic pregnancy, tubal rupture occurs when the growing conceptus causes the fallopian tube to burst, leading to severe intraperitoneal haemorrhage.
- Usually occurs between 6-10 weeks gestation. Clinical manifestations include sudden, severe abdominal pain, signs of hypovolemic shock (tachycardia, hypotension, pallor), and peritoneal irritation.
- Prompt surgical intervention is crucial to prevent maternal mortality.

Haemoperitoneum:
- Bleeding into the abdominal cavity from trophoblast invasion.
- Internal bleeding due to ectopic pregnancy can lead to a significant accumulation of blood in the peritoneal cavity, causing hemodynamic instability and potential hypovolemic shock.
- Hemoperitoneum warrants immediate surgical intervention.

Question 17

Describe the intermediate-term complications of an ectopic pregnancy [2]

Answer 17

Persistent trophoblastic tissue:
* Following treatment with methotrexate or surgical management, residual trophoblastic tissue may remain and continue to produce hCG.
* This can necessitate further medical or surgical intervention to ensure complete removal of the ectopic pregnancy
.
Infection:
- Post-surgical infection or an undiagnosed tubo-ovarian abscess may complicate ectopic pregnancy management, requiring antibiotic therapy or additional surgical procedures.

Question 18

Explain the long-term complications of an ectopic pregnancy [3]

Answer 18

Damage to reproductive organs:
- Surgical intervention for ectopic pregnancy, particularly salpingectomy, can impact future fertility.
- Moreover, ectopic pregnancy itself increases the risk of subsequent ectopic pregnancies.

Rh sensitization:
- In Rh-negative women with an ectopic pregnancy, there is a risk of developing Rh isoimmunization.
- Administering Rh immunoglobulin prophylaxis is crucial to prevent complications in future pregnancies.

Question 19

Describe the US findings of an ectopic pregnancy

Answer 19

gestational sac containing a yolk sac or fetal pole may be seen in a fallopian tube
- A mass representing a tubal ectopic pregnancy moves separately to the ovary. The mass may look similar to a corpus luteum; however, a corpus luteum will move with the ovary

Features that may also indicate an ectopic pregnancy are:
* An empty uterus
* Fluid in the uterus, which may be mistaken as a gestational sac (“pseudogestational sac”)

Question 20

Answer 20

A woman who is 8-weeks-pregnant presents with vaginal bleeding and left-sided pelvic pain - ectopic pregnancy

Question 21

Define the following terms:
- hydatidiform mole
- complete mole
- partial mole

Answer 21

A hydatidiform mole:
- is a type of tumour that grows like a pregnancy inside the uterus. This is called a molar pregnancy. There are two types of molar pregnancy: a complete mole and a partial mole.

A complete mole:
- occurs when two sperm cells fertilise an ovum that contains no genetic material (an “empty ovum”).
- These sperm then combine genetic material, and the cells start to divide and grow into a tumour called a complete mole
- No fetal material will form.

A partial mole:
- occurs when two sperm cells fertilise a normal ovum (containing genetic material) at the same time.
- The new cell now has three sets of chromosomes.
- The cell divides and multiplies into a tumour called a partial mole.
- In a partial mole, some fetal material may form.

Question 22

Molar pregnancy behaves like a normal pregnancy. Periods will stop and the hormonal changes of pregnancy will occur.

There are a few things that can indicate a molar pregnancy versus a normal pregnancy - what are they? [4]

Answer 22

There are a few things that can indicate a molar pregnancy versus a normal pregnancy:
* More severe morning sickness
* Vaginal bleeding
* uterus large for dates
* Abnormally high hCG
* Thyrotoxicosis (hCG can mimic TSH and stimulate the thyroid to produce excess T3 and T4)

Question 23

How do molar pregnancies appear on an US? [1]
How do you confirm? [1]

Answer 23

Made by US (“snowstorm appearance”) and confirmed by histology after uterine evacuation

Question 24

How do you manage molar pregnancies? [3]

Answer 24

• Surgical evacuation of the uterus to remove the mole and histological confirmation
• Referral to to gestational trophoblastic disease centre for management and follow-up (hCG levels are monitored until they return to normal)
• If the mole metastasises, systemic chemotherapy may be required

Question 25

What advice do you give about contraception following complete molar pregnancies? [1]

Answer 25

effective contraception is recommended to avoid pregnancy in the next 12 months

Question 26

When does N&V peak in pregnancy? [1]
What causes N&V? [1]

Answer 26

Nausea and vomiting in pregnancy starts in the first trimester, peaking around 8 – 12 weeks gestation
- The placenta produces human chorionic gonadotropin (hCG) during pregnancy. This hormone is thought to be responsible for nausea and vomiting. Theoretically, higher levels of hCG result in worse symptoms.

Nausea and vomiting are more severe in molar pregnancies and multiple pregnancies due to the higher hCG levels. It also tends to be worse in the first pregnancy and overweight or obese women.

Question 27

What is the difference between N&V and hyperemesis gravidarum? [3]

Answer 27

The RCOG guideline (2016) criteria for diagnosing hyperemesis gravidarum are “protracted” NVP plus:
* More than 5 % weight loss compared with before pregnancy
* Dehydration
* Electrolyte imbalance

Question 28

Which scoring system can be used to assess HG severity? [1]

What are mild, moderate and severe scores? [3]

Answer 28

The severity can be assessed using the Pregnancy-Unique Quantification of Emesis (PUQE) score. This gives a score out of 15:

< 7: Mild
7 – 12: Moderate
> 12: Severe

Question 29

Describe what blood tests might be like for a patient with HG

Answer 29

FBC:
↑ haematocrit – to exclude infections, anaemia
* U&Es: to guide IV fluids and electrolyte replacement (↓or ↑K+,↓Na+, AKI)

In refractory cases OR >1 hospital admission
* LFTs: ↑ transaminases, ↓albumin
* Amylase, bilirubin
* Thyroid profile (hypo or hyperthyroidism)
* Bone profile (Calcium and Phosphate)
* Magnesium
* ABG/VBG (metabolic hypochloremic alkalosis)

Question 30

Describe the mx of mild cases of HG

Answer 30

The following are all first line anti-emetics:
* Prochlorperazine (stemetil)
* Cyclizine
* Doxylamine and pyridoxine
* Promethazine

2nd line:
- Metoclopramide
- Ondansetron

NB: Initially select a 1st line antiemetic - Use a combination of drugs in women who do not respond to a single drug (synergistic effect) – add drugs rather than replacing them

Question 31

Describe the managment of moderate - server HG

Answer 31

IV Fluids
- NaCl or Hartmann’s [avoid glucose containing fluid as they precipitate Wernicke’s encephalopathy] +/- KCl as necessary.

* Anti-emetics IM or IV

• Daily U&Es
• Thiamine supplementation to prevent Wernicke Korsakoff syndrome
  (Thiamine Hydrochloride 25-50mg PO TDS or thiamine 100mg infusion
  weekly)
• Ranitidine or Omeprazole if acid reflux is a problem
• Laxatives as required
• NBM for 24hr then introduce food as tolerated – enteral or parenteral
  nutrition maybe considered in refractory cases
• VTE prophylaxis (TEDS and LMWH)

Question 32

How do you manage future pregnancies if they have previously had severe HG? [2]

Answer 32

Pre-emptive use of doxylamine and pyridoxine to reduce severity of
disease (20/20 mg PO at night should be started when positive pregnancy test)