Disorders of early pregnancy Flashcards
1
Q
Define gestational trophoblastic disease.
A
Excess trophoblastic tissue
2
Q
How do categorise gestational trophoblastic disease?
A
Premalignant - Can be localised and non-invasive = hyatidiform mole
Malignant - (Gestational trophoblastic neoplasia) - Can have characteristics of malignancy
3
Q
What are the types of hydatidiform moles?
A
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
4
Q
What are the gestational trophoblastic neoplasias? Describe them.
A
- 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
5
Q
How do molar pregnancies present?
A
6
Q
How are molar pregnancies diagnosed?
A
- “Snowstorm” appearance of swollen villi with complete moles
- Diagnosis only confirmed histologically
- Serum hCG may be very high
7
Q
What is the immediate management of molar pregnancies?
A
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.
8
Q
What follow-up is required in molar pregnancies?
A
- 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.
9
Q
What should you do if there is a twin pregnancy when there is one non-molar pregnancy and one molar?
A
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.
10
Q
What are the RFs for molar pregnancies?
A
- Asian
- Previous/family hx of molar
- Being very young or very old
11
Q
What advice needs to be given about future pregnancies?
A
• 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
12
Q
How should you counsel a patient on a molar pregnancy?
A
13
Q
When does nausea and vomiting tend to occur in pregnancy?
A
Starts in the first trimester - peaking around 8 - 12 weeks gestation
14
Q
What causes vomiting in pregnancy? What do we worry about if there is excess vomiting?
A
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.
15
Q
What is hyperemesis gravidarum?
A
Excess vomiting and nausea leading to the rejection of all food and drink.
16
Q
How do we diagnose hyperemesis gravidarum?
A
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
17
Q
What tool is used to assess the severity of NVP? What do the scores mean?
A
The PUQE Score - Pregnancy-Unique Quantification of Emesis (PUQE) score.
This gives a score out of 15:
- < 7: Mild
- 7 – 12: Moderate
- > 12: Severe
18
Q
How should we think of managing NVP and HG?
A
- 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
19
Q
When should inpatient management be considered for NVP and HG?
A
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).
20
Q
How should we manage women with mild NVP?
A
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.
21
Q
What therapies can be used for NVP?
A
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.
22
Q
What is the best rehydration regime for ambulatory daycare and inpatient mx?
A
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.
23
Q
What complementary therapies can be useful?
A
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.
24
Q
What complications or adverse effects can occur from NVP and HG and what are their preventive/ management strategies?
A
- 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.
25
What is the further management for HG or NVP?
* 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
26
What discharge and follow-up arrangements should be implemented?
* 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.
27
How should we advise about future pregnancies regarding NVP/HG?
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.
28
What is the effect of NVP and HG on quality of life?
* 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
29
How common is NVP and HG?
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
30
Define termination of pregnancy.
A termination of pregnancy (***TOP***), or ***abortion***, involves an elective procedure to end a pregnancy.
31
What are the specific criteria for a termination of pregnancy in the majority of cases?
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.
32
In what circumstances can a TOP be done at any time?
* 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
33
What are the legal requirements of a TOP?
* 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
34
How can a patient access TOP facilities?
* 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.
35
What is Marie Stopes UK?
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.
36
What are the different forms of TOPs?
* Medical - Mifepristone + Misoprostol
* Surgical
* Vacuum + Aspiration
* Dilatation + Evacuation
37
What does the medical abortion involve? When can it be done?
**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.
38
What is Mifepristone and misoprostol?
***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.
39
What does vacuum aspiration involve?
**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
40
What does dilatation and evacuation (D&E) involve?
14 to 24 weeks
## Footnote
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
41
What should women with surgical TOPs get?
***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.
42
What is the post abortion care?
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.
43
How should we counsel a patient on TOPs?
44
What are the complications of TOPs?
* Bleeding
* Pain
* Infection
* Failure of the abortion (pregnancy continues)
* Damage to the cervix, uterus or other structures
45
Define ectopic pregnancy.
Ectopic pregnancy is when a pregnancy is implanted outside the uterus.
46
What is the most common site of an ectopic pregnancy?
the fallopian tube but can also implant in the entrance to the fallopian tube (***cornual*** ***region***), ovary, cervix or abdomen.
47
What are the RFs for an ectopic pregnancy?
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
48
How do ectopic pregnancies tend to present?
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)
49
How do we investigate a suspected ectopic pregnancy?
A ***transvaginal ultrasound scan*** is the investigation of choice
50
What would US findings show in an ectopic pregnancy?
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
51
Define pregnancy of unknown location.
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.
52
What do we measure in the case of a PUL? Why do we do this? What would we expect?
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.
53
What should we look for on TVUSS in a PUL?
* **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
54
How do we manage an pregnancy of unknown location?
55
How should manage an ectopic pregnancy in the GP?
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.
56
What are the different management options of ectopic pegnancies?
There are three options for terminating an ectopic pregnancy:
* ***Expectant management*** (awaiting natural termination)
* ***Medical management*** (***methotrexate***)
* ***Surgical management*** (***salpingectomy*** or ***salpingotomy***)
57
When is expectant management suitable?
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.
58
When is medical management suitable for an ectopic pregnancy?
Criteria for ***methotrexate*** are the same as expectant management, except:
* HCG level must be \< 5000 IU / l
* Confirmed absence of intrauterine pregnancy on ultrasound
59
What does medical management of an ectopic pregnancy entail? What are the common side effects?
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
60
What is the surgical management of an ectopic pregnancy? When is it appropriate?
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***
61
What is the difference between a salpingectomy and a salpingotomy? What are the consequences of each one?
***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.
62
What should be offered to certain women who are having surgical management for the ectopic pregnancy?
***Anti-rhesus D prophylaxis*** is given to ***rhesus negative*** women having surgical management of ectopic pregnancy.
63
How should we counsel on management of ectopic pregnancies?
64
Define miscarriage.
Miscarriage is the spontaneous termination of a pregnancy
65
What is the difference between early and late miscarriage?
***Early miscarriage*** is before 12 weeks gestation.
***Late miscarriage*** is between 12 and 24 weeks gestation.
66
What are the types of miscarriage?
* ***Missed miscarriage***
* ***Threatened miscarriage***
* ***Inevitable miscarriage***
* ***Incomplete miscarriage***
* ***Complete miscarriage***
67
Define missed miscarriage. What are the characteristics of this type of miscarriage?
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
68
Define threatened miscarriage. What are the characteristics?
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.
69
# Define inevitable miscarriage. What are the characteristics?
vaginal bleeding with an open cervix
* Heavy bleeding
* Fetus may still be alive
* Cervical os open
* Miscarriage imminent
70
Define incomplete miscarriage.
***retained products of conception*** remain in the uterus after the miscarriage
71
Define complete miscarriage. What are the characteristics?
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
72
What are the causes of miscarriages?
* isolated non-recurring chromosomal abnormality = 60% ‘one off’ miscarriages
* 3 or more miscarriages - rarer recurrent causes more likely
73
What investigations would we do when suspecting miscarriage?
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 day**s 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;
74
How should we think about the management of a miscarriage?
* Threatened miscarriage
* Expectant
* Medical
* Surgical
75
How do we manage a threatened miscarriage?
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.
76
When should we not use expectant management?
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.
77
What do we need to advise about expectant management of a miscarriage?
* 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).
78
When should medical management be offered?
If expectant management is not acceptable or according to patients' wishes
79
What does medical management of a miscarriage entail?
* 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 misoprosto**l. (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.
80
What does the surgical management of a miscarriage entail?
* 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.
81
How should we counsel patients on miscarriages?
82
Define recurrent miscarriages. How common is it?
Recurrent miscarriage, defined as the loss of three or more consecutive pregnancies. Affects 1% of couples trying to conceive.
83
What are the RFs for recurrent miscarriage?
* 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.**
84
What are the causes of recurrent miscarriages?
* ***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***)
85
What is antiphospholipid syndrome?
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.
86
Through what mechanism does antiphospholipid antibodies cause pregnancy morbidity?
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.
87
What uterine abnormalities can cause recurrent miscarriages?
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***
88
What inherited thrombophilic defects play a role in recurrent miscarriage?
* 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.
89
What are the recommended investigations of couples with recurrent first-trimester miscarriage and second-trimester miscarriage?
* 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 i**mmunoglobulin 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.**
90
How should we manage all patients with recurrent miscarriages?
1. Women with recurrent miscarriage should be offered referral to a specialist clinic.
91
How should we manage antiphospholipid syndrome?
* Pregnant women with antiphospholipid syndrome should be considered for treatment with **low-dose aspirin plus heparin** to prevent further miscarriage.
92
How should patients with abnormal karyotypes be managed for recurrent miscarriages?
The finding of an abnormal parental karyotype should prompt referral to a clinical geneticist.
93
How should patients with congenital uterine malformations and cervical weakness be managed for recurrent miscarriages?
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.
94
How should patients with inherited thrombophilias be managed for recurrent miscarriages?
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.
95
What does the PRISM trial suggest?
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.
