Disorders of early pregnancy

Question 1

Define gestational trophoblastic disease.

Answer 1

Excess trophoblastic tissue

Question 2

How do categorise gestational trophoblastic disease?

Answer 2

Premalignant - Can be localised and non-invasive = hyatidiform mole

Malignant - (Gestational trophoblastic neoplasia) - Can have characteristics of malignancy

Question 3

What are the types of hydatidiform moles?

Answer 3

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.

• Karyotype 46 XX (90%), 46XY (10%)
• More common
• 8-20% need chemo

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 (it is a haploid cell). The cell divides and multiplies into a tumour called a partial mole. In a partial mole, some fetal material may form.

• Karyotype 90% 69 XXX, or 69 XXY (10%)
• 0.5% need chemo

Question 4

What are the gestational trophoblastic neoplasias? Describe them.

Answer 4

• Invasive hyaditiform mole (IHM)
  
  • Invades the myometrium, hcg persists, usu after CM
  • Locally invasive, non-metastasising
  • 20% CM
• Choriocarcinoma
  
  • Malignant and metastatic
  • After CM, or normal pregnancy
• Placental site trophoblastic tumours (PTT)
  
  • <1% GTDs
  • Usually after a normal term pregnancy
  • Late presentation 3-4 yrs latter (better prognosis if <2 yrs)
  • Can be slow growing or metastatic. Usually curable
• Epithelioid trophoblastic tumour (ETT)
  
  • very rare

Question 5

How do molar pregnancies present?

Answer 5

Question 6

How are molar pregnancies diagnosed?

Answer 6

• “Snowstorm” appearance of swollen villi with complete moles
• Diagnosis only confirmed histologically
• Serum hCG may be very high

Question 7

What is the immediate management of molar pregnancies?

Answer 7

Complete molar pregnancies are not associated with fetal parts, and therefore, suction removal is the method of choice for uterine removal irrespective of uterine size

1 st line: Suction curettage for partial* molar pregnancies *except when the size of the foetal parts deters the use of suction curettage and then medical evacuation can be used

Anti-D prophylaxis is recommended following removal of a molar pregnancy.

Question 8

What follow-up is required in molar pregnancies?

Answer 8

• For complete molar pregnancy, if hCG has reverted to normal within 56 days of the pregnancy event then follow-up will be for 6 months from the date of uterine removal.
• If hCG has not reverted to normal within 56 days of the pregnancy event then follow-up will be for 6 months from normalisation of the hCG level.
• Follow-up for partial molar pregnancy is concluded once the hCG has returned to normal on two samples, at least 4 weeks apart.
• Women who have not received chemotherapy no longer need to have hCG measured after any subsequent pregnancy event.

Question 9

What should you do if there is a twin pregnancy when there is one non-molar pregnancy and one molar?

Answer 9

Women diagnosed with a combined molar pregnancy and viable twin, or where there is diagnostic doubt, should be referred to a regional fetal medicine centre and GTD centre.

In the situation of a twin pregnancy where there is one viable fetus and the other pregnancy is molar, the woman should be counselled about the potential increased risk of perinatal morbidity and the outcome for GTN.

For twin pregnancies where there is a non-molar pregnancy alongside a molar pregnancy and the woman has decided to terminate the pregnancy (or there has been demise of the coexisting twin) and the size of the fetal parts deters the use of suction curettage, medical removal can be used.

Question 10

What are the RFs for molar pregnancies?

Answer 10

• Asian
• Previous/family hx of molar
• Being very young or very old

Question 11

What advice needs to be given about future pregnancies?

Answer 11

• Future pregnancies

o Do not conceive until F/U complete

o Recommend barrier contraception until hCG normalises

o COCP can be used once hCG normalised

o Avoid IUDs until hCG normalised (risk of uterine perforation)

If receiving chemotherapy, do not conceive for 1 year after completion of treatment → effective contraception is recommended

Question 12

How should you counsel a patient on a molar pregnancy?

Answer 12

Question 13

When does nausea and vomiting tend to occur in pregnancy?

Answer 13

Starts in the first trimester - peaking around 8 - 12 weeks gestation

Question 14

What causes vomiting in pregnancy? What do we worry about if there is excess vomiting?

Answer 14

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 15

What is hyperemesis gravidarum?

Answer 15

Excess vomiting and nausea leading to the rejection of all food and drink.

Question 16

How do we diagnose hyperemesis gravidarum?

Answer 16

Hyperemesis gravidarum is the severe form of nausea and vomiting in pregnancy. 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 17

What tool is used to assess the severity of NVP? What do the scores mean?

Answer 17

The PUQE Score - Pregnancy-Unique Quantification of Emesis (PUQE) score.

This gives a score out of 15:

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

Question 18

How should we think of managing NVP and HG?

Answer 18

• Initial management
  
  • Admission?
  • Mild/Moderate/Severe
  • Pharmacological agents
  • Rehydration regime
  • Complementary therapies
• Monitoring and adverse effects
• Further Management
• Discharge and Follow-up
• Counsel on future pregnancies and assess QOL

Question 19

When should inpatient management be considered for NVP and HG?

Answer 19

Inpatient management should be considered if there is at least one of the following:

● continued nausea and vomiting and inability to keep down oral antiemetics

● continued nausea and vomiting associated with ketonuria and/or weight loss (greater than 5% of body weight), despite oral antiemetics

● confirmed or suspected comorbidity (such as urinary tract infection and inability to tolerate oral antibiotics).

Question 20

How should we manage women with mild NVP?

Answer 20

Women with mild NVP should be managed in the community with antiemetics

Ambulatory daycare management should be used for suitable patients when community/primary care measures have failed and where the PUQE score is less than 13.

Question 21

What therapies can be used for NVP?

Answer 21

Combinations of different drugs should be used in women who do not respond to a single antiemetic.

For women with persistent or severe HG, the parenteral or rectal route may be necessary and more effective than an oral regimen.

Women should be asked about previous adverse reactions to antiemetic therapies.

Drug-induced extrapyramidal symptoms and oculogyric crises can occur with the use of phenothiazines and metoclopramide. If this occurs, there should be prompt cessation of the medications.

Clinicians should use antiemetics with which they are familiar and should use drugs from different classes if the first drug is not effective.

Metoclopramide is safe and effective, but because of the risk of extrapyramidal effects it should be used as second-line therapy.

There is evidence that ondansetron is safe and effective, but because data are limited it should be used as second-line therapy.

Question 22

What is the best rehydration regime for ambulatory daycare and inpatient mx?

Answer 22

Normal saline with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration.

Dextrose infusions are not appropriate unless the serum sodium levels are normal and thiamine has been administered.

Question 23

What complementary therapies can be useful?

Answer 23

Ginger may be used by women wishing to avoid antiemetic therapies in mild to moderate NVP.

Women may be reassured that acustimulations are safe in pregnancy. Acupressure may improve NVP.

Question 24

What complications or adverse effects can occur from NVP and HG and what are their preventive/ management strategies?

Answer 24

• Urea and serum electrolyte levels should be checked daily in women requiring intravenous fluids.
• Histamine H2 receptor antagonists or proton pump inhibitors may be used for women developing gastro-oesophageal reflux disease, oesophagitis or gastritis.
• Thiamine supplementation (either oral or intravenous) should be given to all women admitted with prolonged vomiting, especially before administration of dextrose or parenteral nutrition.
• Women admitted with HG should be offered thromboprophylaxis with low-molecular-weight heparin unless there are specific contraindications such as active bleeding.
• Thromboprophylaxis can be discontinued upon discharge. Women with previous or current NVP or HG should consider avoiding iron-containing preparations if these exacerbate the symptoms.

Question 25

What is the further management for HG or NVP?

Answer 25

• In women with severe NVP or HG, input may be required from other professionals, such as midwives, nurses, dieticians, pharmacists, endocrinologists, nutritionists and gastroenterologists, and a mental health team, including a psychiatrist
• When all other medical therapies have failed, enteral or parenteral treatment should be considered with a multidisciplinary approach.
• All therapeutic measures should have been tried before offering termination of a wanted pregnancy

Question 26

What discharge and follow-up arrangements should be implemented?

Answer 26

• Women with NVP and HG should have an individualised management plan in place when they are discharged from hospital.
• Women with severe NVP or HG who have continued symptoms into the late second or the third trimester should be offered serial scans to monitor fetal growth.

Question 27

How should we advise about future pregnancies regarding NVP/HG?

Answer 27

Women with previous HG should be advised that there is a risk of recurrence in future pregnancies.

Early use of lifestyle/dietary modifications and antiemetics that were found to be useful in the index pregnancy is advisable to reduce the risk of NVP and HG in the current pregnancy.

Question 28

What is the effect of NVP and HG on quality of life?

Answer 28

• A woman’s quality of life can be adversely affected by NVP and HG and practitioners should address the severity of a woman’s symptoms in relation to her quality of life and social situation.
• Practitioners should assess a woman’s mental health status during the pregnancy and postnatally and refer for psychological support if necessary.
• Women should be referred to sources of psychosocial support.
• Practitioners should validate the woman’s physical symptoms and psychological distress.
• Women should be advised to rest as required to alleviate symptoms

Question 29

How common is NVP and HG?

Answer 29

NVP affects up to 80% of pregnant women1 and is one of the most common indications for hospital admission among pregnant women, with typical stays of between 3 and 4 days

. HG is the severe form of NVP, which affects about 0.3–3.6% of pregnant women

Question 30

Define termination of pregnancy.

Answer 30

A termination of pregnancy (TOP), or abortion, involves an elective procedure to end a pregnancy.

Question 31

What are the specific criteria for a termination of pregnancy in the majority of cases?

Answer 31

There are specific criteria required to justify the decision to proceed with an abortion. The following is a simplified version of the criteria. An abortion can be performed before 24 weeks if continuing the pregnancy involves greater risk to the physical or mental health of:

• The woman
• Existing children of the family

The threshold for when the risk of continuing the pregnancy outweighs the risk of terminating the pregnancy is a matter of clinical judgement and opinion of the medical practitioners.

Question 32

In what circumstances can a TOP be done at any time?

Answer 32

• Continuing the pregnancy is likely to risk the life of the woman
• Terminating the pregnancy will prevent “grave permanent injury” to the physical or mental health of the woman
• There is “substantial risk” that the child would suffer physical or mental abnormalities making it seriously handicapped

Question 33

What are the legal requirements of a TOP?

Answer 33

• Two registered medical practitioners must sign to agree abortion is indicated
• It must be carried out by a registered medical practitioner in an NHS hospital or approved premise

Question 34

How can a patient access TOP facilities?

Answer 34

• Abortion services can be accessed by self-referral or by GP, GUM or family planning clinic referral.
• Doctors who object to abortions should pass on to another doctor able to make the referral.
• Many abortion services are accessed by self-referral, without the involvement of a GP or other doctor to make the referral.

Question 35

What is Marie Stopes UK?

Answer 35

Marie Stopes UK is a charity that provides abortion services. They offer a remote service for women less than 10 weeks gestation, where consultations are held by telephone and medication are issued remotely to be taken at home.

Question 36

What are the different forms of TOPs?

Answer 36

• Medical - Mifepristone + Misoprostol
• Surgical
  
  • Vacuum + Aspiration
  • Dilatation + Evacuation

Question 37

What does the medical abortion involve? When can it be done?

Answer 37

Mifepristone (oral) followed 24-48 hours later by misoprostol (vaginal, buccal or sublingual)

Suitable at any gestation

Onset of contractions to expel foetus can be painful, simple analgesia recommended

0-9 weeks

o Can be administered at home provided the patient is easy to follow-up and can seek medical attention if necessary

o Bleeding usually follows for up to 2 weeks after abortion

o Recommend urine pregnancy test in 2-3weeks

9+ weeks

o Should be done in a clinical setting (because of increased bleeding and discomfort)

o Repeated doses of misoprostol usually needed every 3 hours until expulsion (MAX:5)

Special Consideration after 21+6 Weeks: feticide (intracardiac KCl injection) should be given to eliminate the possibility of aborted foetus showing any signs of life

Rhesus negative women with a gestational age of 10 weeks or above having a medical TOP should have anti-D prophylaxis.

Question 38

What is Mifepristone and misoprostol?

Answer 38

Mifepristone is an anti-progestogen medication that blocks the action of progesterone, halting the pregnancy and relaxing the cervix.

Misoprostol is a prostaglandin analogue, meaning it binds to prostaglandin receptors and activates them. Prostaglandins soften the cervix and stimulate uterine contractions. From 10 weeks gestation, additional misoprostol doses (e.g. every 3 hours) are required until expulsion.

Question 39

What does vacuum aspiration involve?

Answer 39

Vacuum Aspiration – < 14 weeks

o Involves gently dilating the cervix and using vacuum suction to evacuate the uterus

o Can be performed under local or general anaesthetic
o Cervix is usually pre-treated with misoprostol
o Prophylactic antibiotics (metronidazole) can be given to reduce the risk of infection

Question 40

What does dilatation and evacuation (D&E) involve?

Answer 40

14 to 24 weeks

o Required good cervical dilatation to remove larger foetal parts
o Misoprostol(3 hours pre-surgery) is used to ripen the cervix to allow easier dilatation

o Contents of the uterus extracted using aspiration and other instruments (e.g.forceps)

o Ultrasound is required to confirm evacuation

Question 41

What should women with surgical TOPs get?

Answer 41

Rhesus negative women having a surgical TOP should have anti-D prophylaxis. The NICE guidelines (2019) say it should be considered in women less than 10 weeks gestation.

Question 42

What is the post abortion care?

Answer 42

Women may experience vaginal bleeding and abdominal cramps intermittently for up to 2 weeks after the procedure.

A urine pregnancy test is performed 3 weeks after the abortion to confirm it is complete.

Contraception is discussed and started where appropriate. Support and counselling is offered.

Question 43

How should we counsel a patient on TOPs?

Answer 43

Question 44

What are the complications of TOPs?

Answer 44

• Bleeding
• Pain
• Infection
• Failure of the abortion (pregnancy continues)
• Damage to the cervix, uterus or other structures

Question 45

Define ectopic pregnancy.

Answer 45

Ectopic pregnancy is when a pregnancy is implanted outside the uterus.

Question 46

What is the most common site of an ectopic pregnancy?

Answer 46

the fallopian tube but can also implant in the entrance to the fallopian tube (cornual region), ovary, cervix or abdomen.

Question 47

What are the RFs for an ectopic pregnancy?

Answer 47

Certain factors can increase the risk of ectopic pregnancy:

• Previous ectopic pregnancy
• Previous pelvic inflammatory disease
• Previous surgery to the fallopian tubes
• Intrauterine devices (coils)
• Older age
• Smoking

Question 48

How do ectopic pregnancies tend to present?

Answer 48

Ectopic pregnancy typically presents around 6 – 8 weeks gestation.

Have a low threshold for suspecting an ectopic pregnancy, even in atypical presentations. Always ask about the possibility of pregnancy, missed periods and recent unprotected sex in women presenting with lower abdominal pain.

The classic features of an ectopic pregnancy include:

• Missed period
• Constant lower abdominal pain in the right or left iliac fossa
• Vaginal bleeding
• Lower abdominal or pelvic tenderness
• Cervical motion tenderness (pain when moving the cervix during a bimanual examination)

It is also worth asking about:

• Dizziness or syncope (blood loss)
• Shoulder tip pain (peritonitis)

Question 49

How do we investigate a suspected ectopic pregnancy?

Answer 49

A transvaginal ultrasound scan is the investigation of choice

Question 50

What would US findings show in an ectopic pregnancy?

Answer 50

A gestational sac containing a yolk sac or fetal pole may be seen in a fallopian tube.

Sometimes a non-specific mass may be seen in the tube. When a mass containing an empty gestational sac is seen, this may be referred to as the “blob sign”, “bagel sign” or “tubal ring sign” (all referring to the same appearance).

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”)

Green Top:

The following ultrasound criteria may be used for the diagnosis of cervical ectopic pregnancy:

• an empty uterus
• a barrel-shaped cervix
• a gestational sac present below the level of the internal cervical os internal cervical os
• the absence of the sliding sign and blood flow around the gestational sac using Dopplerpler

Question 51

Define pregnancy of unknown location.

Answer 51

A pregnancy of unknown location (PUL) is when the woman has a positive pregnancy test and there is no evidence of pregnancy on the ultrasound scan.

Question 52

What do we measure in the case of a PUL? Why do we do this? What would we expect?

Answer 52

Serum human chorionic gonadotropin (hCG)

The serum hGC level is repeated after 48 hours, to measure the change from baseline.

The developing syncytiotrophoblast of the pregnancy produces hCG. In an intrauterine pregnancy, the hCG will roughly double every 48 hours. This will not be the case in a miscarriage or ectopic pregnancy.

A rise of more than 63% after 48 hours is likely to indicate an intrauterine pregnancy. A repeat ultrasound scan is required after 1 – 2 weeks to confirm an intrauterine pregnancy. A pregnancy should be visible on an ultrasound scan once the hCG level is above 1500 IU / l.

A rise of less than 63% after 48 hours may indicate an ectopic pregnancy. When this happens the patient needs close monitoring and review.

A fall of more than 50% is likely to indicate a miscarriage. A urine pregnancy test should be performed after 2 weeks to confirm the miscarriage is complete.

Monitoring the clinical signs and symptoms is more important than tracking the hCG level, and any change in symptoms needs careful assessment.

Question 53

What should we look for on TVUSS in a PUL?

Answer 53

• Fetal heartbeat = viable intrauterine pregnancy (should become visible once fetal pole >7mm
• If no heartbeat 🡪 measure fetal pole 🡪 >7mm or below re-scan in 7 days
• If no pole 🡪 measure gestational sac 🡪 >25mm (likely miscarriage) or below re-scan in 7 days

Question 54

How do we manage an pregnancy of unknown location?

Answer 54

Question 55

How should manage an ectopic pregnancy in the GP?

Answer 55

Perform a pregnancy test in all women with abdominal or pelvic pain that may be caused by an ectopic pregnancy. Women with pelvic pain or tenderness and a positive pregnancy test need to be referred to an early pregnancy assessment unit (EPAU) or gynaecology service.

Question 56

What are the different management options of ectopic pegnancies?

Answer 56

There are three options for terminating an ectopic pregnancy:

• Expectant management (awaiting natural termination)
• Medical management (methotrexate)
• Surgical management (salpingectomy or salpingotomy)

Question 57

When is expectant management suitable?

Answer 57

Suitable for patients who are haemodynamically stable and asymptomatic

Can only be done when:

• Follow up is possible to ensure successful termination
• The ectopic is unruptured
• Adnexal mass < 35mm
• No visible heartbeat
• No significant pain
• HCG level < 1500 IU / l

Women with expectant management need careful follow up with close monitoring of hCG levels, and quick and easy access to services if their condition changes.

Question 58

When is medical management suitable for an ectopic pregnancy?

Answer 58

Criteria for methotrexate are the same as expectant management, except:

• HCG level must be < 5000 IU / l
• Confirmed absence of intrauterine pregnancy on ultrasound

Question 59

What does medical management of an ectopic pregnancy entail? What are the common side effects?

Answer 59

Methotrexate is highly teratogenic (harmful to pregnancy). It is given as an intramuscular injection into a buttock. This halts the progress of the pregnancy and results in spontaneous termination.

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.

Common side effects of methotrexate include:

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

Question 60

What is the surgical management of an ectopic pregnancy? When is it appropriate?

Answer 60

Anyone that does not meet the criteria for expectant or medical management requires surgical management. Most patients with an ectopic pregnancy will require surgical management. This include those with:

• Pain
• Adnexal mass > 35mm
• Visible heartbeat
• HCG levels > 5000 IU / l

There are two options for surgical management of ectopic pregnancy:

• Laparoscopic salpingectomy
• Laparoscopic salpingotomy

Question 61

What is the difference between a salpingectomy and a salpingotomy? What are the consequences of each one?

Answer 61

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.

There is an increased risk of failure to remove the ectopic pregnancy with salpingotomy compared with salpingectomy. NICE state up to 1 in 5 women having salpingotomy may need further treatment with methotrexate or salpingectomy.

Question 62

What should be offered to certain women who are having surgical management for the ectopic pregnancy?

Answer 62

Anti-rhesus D prophylaxis is given to rhesus negative women having surgical management of ectopic pregnancy.

Question 63

How should we counsel on management of ectopic pregnancies?

Answer 63

Question 64

Define miscarriage.

Answer 64

Miscarriage is the spontaneous termination of a pregnancy

Question 65

What is the difference between early and late miscarriage?

Answer 65

Early miscarriage is before 12 weeks gestation.

Late miscarriage is between 12 and 24 weeks gestation.

Question 66

What are the types of miscarriage?

Answer 66

• Missed miscarriage
• Threatened miscarriage
• Inevitable miscarriage
• Incomplete miscarriage
• Complete miscarriage

Question 67

Define missed miscarriage. What are the characteristics of this type of miscarriage?

Answer 67

the fetus is no longer alive, but no symptoms have occurred

• Fetus has not developed or has died
• Not recognised until bleeding occurs or USS performed
• Uterus small for dates

Question 68

Define threatened miscarriage. What are the characteristics?

Answer 68

vaginal bleeding with a closed cervix and a fetus that is alive

• Bleeding
• Fetus is still alive
• Uterus is size expected for dates
• Os is closed
• 25% go on to miscarry.

Question 69

Define inevitable miscarriage. What are the characteristics?

Answer 69

vaginal bleeding with an open cervix

• Heavy bleeding
• Fetus may still be alive
• Cervical os open
• Miscarriage imminent

Question 70

Define incomplete miscarriage.

Answer 70

retained products of conception remain in the uterus after the miscarriage

Question 71

Define complete miscarriage. What are the characteristics?

Answer 71

a full miscarriage has occurred, and there are no products of conception left in the uterus

• All fetal tissue has been passed
• Bleeding diminished
• Uterus no longer enlarged
• Os closed

Question 72

What are the causes of miscarriages?

Answer 72

• isolated non-recurring chromosomal abnormality = 60% ‘one off’ miscarriages
• 3 or more miscarriages - rarer recurrent causes more likely

Question 73

What investigations would we do when suspecting miscarriage?

Answer 73

EPAU

• TVUS (Consider a transabdominal ultrasound scan for women with an enlarged uterus or other pelvic pathology, such as fibroids or an ovarian cyst)
  
  • Inform women that the diagnosis of miscarriage using 1 ultrasound scan cannot be guaranteed to be 100% accurate and there is a small chance that the diagnosis may be incorrect, particularly at very early gestational ages.
  • Determine the viability of an intrauterine pregnancy, first look to identify a fetal heartbeat. If there is no visible heartbeat but there is a visible fetal pole, measure the crown–rump length.
  • Only measure the mean gestational sac diameter if the fetal pole is not visible.
  • If the crown–rump length is less than 7.0 mm with a transvaginal ultrasound scan and there is no visible heartbeat, perform a second scan a minimum of 7 days after the first before making a diagnosis. Further scans may be needed before a diagnosis can be made
  • If the crown–rump length is 7.0 mm or more with a transvaginal ultrasound scan and there is no visible heartbeat:
    
    • seek a second opinion on the viability of the pregnancy and/or
    • perform a second scan a minimum of 7 days after the first before making a diagnosis.
  • If there is no visible heartbeat when the crown–rump length is measured using a transabdominal ultrasound scan:
    
    • record the size of the crown–rump length and
    • perform a second scan a minimum of 14 days after the first before making a diagnosis.
  • If the mean gestational sac diameter is less than 25.0 mm with a transvaginal ultrasound scan and there is no visible fetal pole, perform a second scan a minimum of 7 days after the first before making a diagnosis. Further scans may be needed before a diagnosis can be made.
  • If the mean gestational sac diameter is 25.0 mm or more using a transvaginal ultrasound scan and there is no visible fetal pole
    
    • seek a second opinion on the viability of the pregnancy and/or
    • perform a second scan a minimum of 7 days after the first before making a diagnosis.
  • If there is no visible fetal pole and the mean gestational sac diameter is measured using a transabdominal ultrasound scan:
    
    • record the size of the mean gestational sac diameter and
    • perform a second scan a minimum of 14 days after the first before making a diagnosis.
• Bloods
  
  • hCG levels should be increase 63% in 48h with viable pregnancy
  • Useful to identify viable uterine pregnancy
  • For a woman with a decrease in serum hCG levels greater than 50% after 48 hours:
    
    • inform her that the pregnancy is unlikely to continue but that this is not confirmed and
    • provide her with oral and written information about where she can access support and counselling services;

Question 74

How should we think about the management of a miscarriage?

Answer 74

• Threatened miscarriage
• Expectant
• Medical
• Surgical

Question 75

How do we manage a threatened miscarriage?

Answer 75

Advise a woman with a confirmed intrauterine pregnancy with a fetal heartbeat who presents with vaginal bleeding, but has no history of previous miscarriage, that:

• if her bleeding gets worse, or persists beyond 14 days, she should return for further assessment
• if the bleeding stops, she should start or continue routine antenatal care.

Offer vaginal micronised progesterone 400 mg twice daily to women with an intrauterine pregnancy confirmed by a scan, if they have vaginal bleeding and have previously had a miscarriage.

If a fetal heartbeat is confirmed, continue progesterone until 16 completed weeks of pregnancy.

Question 76

When should we not use expectant management?

Answer 76

Use expectant management for 7 to 14 days as the first-line management strategy for women with a confirmed diagnosis of miscarriage. Explore management options other than expectant management if:

• the woman is at increased risk of haemorrhage (for example, she is in the late first trimester) or
• she has previous adverse and/or traumatic experience associated with pregnancy (for example, stillbirth, miscarriage or antepartum haemorrhage) or
• she is at increased risk from the effects of haemorrhage (for example, if she has coagulopathies or is unable to have a blood transfusion) or
• there is evidence of infection.

Question 77

What do we need to advise about expectant management of a miscarriage?

Answer 77

• Explain what expectant management involves and that most women will need no further treatment. Also provide women with oral and written information about further treatment options.
• If bleeding and pain stops after 7 to 14 days of expectant management, advise the woman to take a urine pregnancy test after 3 weeks, and return for individualised care if it is positive.
• Offer a repeat scan if after the period of expectant management, the bleeding and pain:
  
  • have not started (suggesting that the process of miscarriage has not begun) or
  • are persisting and/or increasing (suggesting incomplete miscarriage).

Question 78

When should medical management be offered?

Answer 78

If expectant management is not acceptable or according to patients’ wishes

Question 79

What does medical management of a miscarriage entail?

Answer 79

• Offer vaginal misoprostol for the medical treatment of missed or incomplete miscarriage. (Oral administration is an acceptable alternative if this is the woman’s preference.)
• For women with a missed miscarriage, use a single dose of 800 micrograms of misoprostol.
• If bleeding has not started 24 hours after treatment, she should contact her healthcare professional to determine ongoing individualised care.
• For women with an incomplete miscarriage, use a single dose of 600 micrograms of misoprostol. (800 micrograms can be used as an alternative to allow alignment of treatment protocols for both missed and incomplete miscarriage.)
• Offer all women receiving medical management of miscarriage pain relief and anti-emetics as needed.
• Inform women undergoing medical management of miscarriage about what to expect throughout the process, including the length and extent of bleeding and the potential side effects of treatment including pain, diarrhoea and vomiting.
• Provide women with a urine pregnancy test to carry out at home 3 weeks after medical management of miscarriage unless they experience worsening symptoms, in which case advise them to return to the healthcare professional responsible for providing their medical management.
• Women with a positive urine pregnancy test after 3 weeks must return for a review by a healthcare professional to ensure that there is no molar or ectopic pregnancy.

Question 80

What does the surgical management of a miscarriage entail?

Answer 80

• Where clinically appropriate, offer women undergoing a miscarriage a choice of:
  
  • manual vacuum aspiration under local anaesthetic in an outpatient or clinic setting or
  • surgical management in a theatre under general anaesthetic.
    
    • vaginal misoprostol is often used to ripen the cervix to facilitate cervical dilatation for suction insertion
• Offer anti-D prophylaxis to all rhesus-negative women undergoing surgical management

Manual vacuum aspiration involves a local anaesthetic applied to the cervix. A tube attached to a specially designed syringe is inserted through the cervix into the uterus. The person performing the procedure then manually uses the syringe to aspirate contents of the uterus. To consider manual vacuum aspiration, women must find the process acceptable and be below 10 weeks gestation. It is more appropriate for women that have previously given birth (parous women).

Electric vacuum aspiration is the traditional surgical management of miscarriage. It involves a general anaesthetic. The operation is performed through the vagina and cervix without any incisions. The cervix is gradually widened using dilators, and the products of conception are removed through the cervix using an electric-powered vacuum.

Question 81

How should we counsel patients on miscarriages?

Answer 81

Question 82

Define recurrent miscarriages. How common is it?

Answer 82

Recurrent miscarriage, defined as the loss of three or more consecutive pregnancies. Affects 1% of couples trying to conceive.

Question 83

What are the RFs for recurrent miscarriage?

Answer 83

• Maternal age - Advancing maternal age is associated with a decline in both the number and quality of the remaining oocytes
  
  • 12–19 years, 13%
  • 20–24 years, 11%
  • 25–29 years, 12%
  • 30–34 years, 15%
  • 35–39 years,25
  • 40–44 years,51%;
  • ≥45 years,93%
• Number of previous miscarriages (40% risk after 3 consecutive losses)
• Advanced paternal age

The risk of miscarriage is highest among couples where the woman is ≥35 years of age and the man ≥40 years of age.

Question 84

What are the causes of recurrent miscarriages?

Answer 84

• Idiopathic (particularly in older women)
• Antiphospholipid syndrome
• Hereditary thrombophilias
• Uterine abnormalities
• Genetic factors in parents (e.g. balanced translocations in parental chromosomes)
• Chronic histiocytic intervillositis
• Other chronic diseases such as diabetes, untreated thyroid disease and systemic lupus erythematosus (SLE)

Question 85

What is antiphospholipid syndrome?

Answer 85

Antiphospholipid syndrome refers to the association between antiphospholipid antibodies – lupus anticoagulant, anticardiolipin antibodies and anti-B2 glycoprotein-I antibodies – and adverse pregnancy outcome or vascular thrombosis

Adverse pregnancy outcomes include:

● three or more consecutive miscarriages before 10 weeks of gestation

● one or more morphologically normal fetal losses after the 10th week of gestation

● one or more preterm births before the 34th week of gestation owing to placental disease.

Question 86

Through what mechanism does antiphospholipid antibodies cause pregnancy morbidity?

Answer 86

The mechanisms by which antiphospholipid antibodies cause pregnancy morbidity include inhibition

• of trophoblastic function
• of differentiation, activation of complement pathways at the maternal–fetal interface

resulting in a local inflammatory response and, in later pregnancy, thrombosis of the uteroplacental vasculature.

Question 87

What uterine abnormalities can cause recurrent miscarriages?

Answer 87

Several uterine abnormalities can cause recurrent miscarriages:

• Uterine septum (a partition through the uterus)
• Unicornuate uterus (single-horned uterus)
• Bicornuate uterus (heart-shaped uterus)
• Didelphic uterus (double uterus)
• Cervical insufficiency
• Fibroids

Question 88

What inherited thrombophilic defects play a role in recurrent miscarriage?

Answer 88

• Both inherited and acquired thrombophilias, including activated protein C resistance (most commonly due to factor V Leiden mutation),deficiencies of protein C/S and antithrombin III, hyperhomocysteinaemia and prothrombin gene mutation, are established causes of systemic thrombosis.
• In addition, inherited thrombophilias have been implicated as a possible cause in recurrent miscarriage and late pregnancy complications with the presumed mechanism being thrombosis of the uteroplacental circulation.

Question 89

What are the recommended investigations of couples with recurrent first-trimester miscarriage and second-trimester miscarriage?

Answer 89

• ANTIPHOSPHOLIPID SYNDROME
• All women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriage should be screened before pregnancy for antiphospholipid antibodies.
  
  • To diagnose antiphospholipid syndrome it is mandatory that the woman has two positive tests at least 12 weeks apart for either lupus anticoagulant or anticardiolipin antibodies of immunoglobulin G and/or immunoglobulin M class present in a medium or high titre over 40 g/l or ml/l,or above the 99th percentile).
• KARYOTYPING
  
  • Cytogenetic analysis should be performed on products of conception of the third and subsequent consecutive miscarriage(s).
  • Parental peripheral blood karyotyping of both partners should be performed in couples with recurrent miscarriage where testing of products of conception reports an unbalanced structural chromosomal abnormality
• ANATOMICAL FACTORS
  
  • All women with recurrent first-trimester miscarriage and all women with one or more second-trimester miscarriages should have a pelvic ultrasound to assess uterine anatomy.
  • Suspected uterine anomalies may require further investigations to confirm the diagnosis, using hysteroscopy, laparoscopy or three-dimensional pelvic ultrasound.
• THROMBOPHILIAS
  
  • Women with second-trimester miscarriage should be screened for inherited thrombophilias including factor V Leiden, factor II (prothrombin) gene mutation and protein S.

Question 90

How should we manage all patients with recurrent miscarriages?

Answer 90

1. Women with recurrent miscarriage should be offered referral to a specialist clinic.

Question 91

How should we manage antiphospholipid syndrome?

Answer 91

• Pregnant women with antiphospholipid syndrome should be considered for treatment with low-dose aspirin plus heparin to prevent further miscarriage.

Question 92

How should patients with abnormal karyotypes be managed for recurrent miscarriages?

Answer 92

The finding of an abnormal parental karyotype should prompt referral to a clinical geneticist.

Question 93

How should patients with congenital uterine malformations and cervical weakness be managed for recurrent miscarriages?

Answer 93

There is insufficient evidence to assess the effect of uterine septum resection in women with recurrent miscarriage and uterine septum to prevent further miscarriage

• Cervical cerclage is associated with potential hazards related to the surgery and the risk of stimulating uterine contractions and hence should be considered only in women who are likely to benefit.
• Women with a history of second-trimester miscarriage and suspected cervical weakness who have not undergone a history-indicated cerclage may be offered serial cervical sonographic surveillance.
• In women with a singleton pregnancy and a history of one second-trimester miscarriage attributable to cervical factors, an ultrasound-indicated cerclage should be offered if a cervical length of 25 mm or less is detected by transvaginal scan before 24 weeks of gestation.

Question 94

How should patients with inherited thrombophilias be managed for recurrent miscarriages?

Answer 94

There is insufficient evidence to evaluate the effect of heparin in pregnancy to prevent a miscarriage in women with recurrent first-trimester miscarriage associated with inherited thrombophilia.

Heparin therapy during pregnancy may improve the live birth rate of women with second-trimester miscarriage associated with inherited thrombophilias.

Question 95

What does the PRISM trial suggest?

Answer 95

There is new evidence from the PRISM trial that suggests a benefit to using vaginal progesterone pessaries during early pregnancy for women with recurrent miscarriages presenting with bleeding.

This may become part of guidelines in the future. At present, the RCOG guidelines on recurrent miscarriage (2011) state there is insufficient evidence for progesterone supplementation.