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Definitions for Dating PregnancyConception: 2 weeks after 1st day of last menstrual period (LMP) with a regular 28 day

cycle

Estimated Due Date (EDD): Naegeles rule add 9 months + 7 days to 1st day of LMP. Pregnancy lasts 38wks from conception/40wks from 1st day of LMP

Trimesters:

1st trimester = 1-13wks


2nd trimester = 14-27wks
3rd trimester = 28-40wks

Puerperium:

Delivery > 6wks.


Reversal of the physiological changes of pregnancy

Maternal Physiological Changes During Pregnancy

Cardiovascular and Respiratory Changes

40% increase in plasma volume by 32wks. [RBC] increases by 20%.


40% rise in cardiac output. CO and BP fall if supine due to vena cava compression.
Reduced peripheral venous return causes BP drop in early pregnancy. Return to pre-pregnancy level later.
40% increase in tidal volume.
Haemodilution: overall amount of Hb rises, but concentration falls.
O2 demand increases by 15%.
Increased clotting risk: increased factor VII, VIII, X, and rise in fibrinogen.
Increased RBC mass: protects against the ~0.5L delivery blood loss (1L if twins or CS)

Renal changes

Renal pelvis + ureters dilate (pressure/progesterone): risk of acute pylonephritis.


GFR increases by 50%: reduces plasma urea, creatinine and osmolality.
Increased urinary protein loss. >500mg in 24hrs is abnormal however.

Endocrine changes

Insulin secretion doubles. Physiological glycosuria may occur.


Thyroid binding globulin doubles. T3 + T4 fall slightly. Goitre more common.
Anterior pituitary doubles in size risk of ischaemia in PPH (Sheehans syndrome)
Rise in total and free serum cortisol and urinary free cortisol

Musculoskeletal + skin changes

Joints of the lower back and pelvis soften.


Increased incidence of rashes/epistaxis/hyperpigmentation/spider naevi/erythema

Calcium and phosphate

Increased demand of Ca (especially in 3rd trimester and puerperium) leads to increased gut absorption. Calcium is actively transported across placenta.
Serum Ca + phosphate levels fall (bound to albumin). Ionised Ca remains stable

Liver

Hepatic blood flow unchanged


ALP levels rise by 50% and albumin falls by 10g/L (causes a fall in total protein)

Uterine physiology

Morula becomes blastocyst at the 32 cell stage


Implantation 7-14 days post conception: blastocyst attaches and trophoblast cells invade the endometrium.
Organogenesis: 2-8 wks post conception.
Inner cell mass becomes embryo. Trophectoderm becomes placental trophoblast.
Foetus develops in amniotic cavity, attached to placenta by umbilical cord.
Amnion: membrane lining of cavity, expands as placenta progresses. 2nd layer (chorion) in apposition to the amnion.
Placenta is anchored to maternal decidua.
Intervillous space supplied by maternal spiral arteries.
Cord has 2 arteries (deoxygenated blood from fetus to placenta) + 1 vein (oxygenated blood from placenta to foetus).
Uterus holds 5L at term (500x pre-pregnancy): muscle hypertrophy.
Blood supply from uterine + ovarian arteries.
Cervical mucous plug protects during pregnancy.

Multiple Pregnancy

10X higher risk of stillbirth


50% pre-term
Increased risk of IUGR

Dizygotic = non-identical, duplication of normal processes, dichorionic, diamniotic.

Monozygotic = earlier split, more independent. DCDA <3 days, 4-7days MCDA, >8d MCMA. Requires tertiary centre care if monozygotic!

Risks to mother:

Anaemia
Pre-eclampsia
Hyperemesis
Polyhydramnios
Complicated labour

Risks to developing foetuses:

Congenital abnormalities
Twin-to-twin transfusion
Pre-term delivery
Twin entrapment

More regular antenatal checks are required.

Foetal Growth

Growth governed by intrinsic (maternal height/weight/ethnicity, fetal sex/genes/conditions) and extrinsic (environmental social class, nutrition, maternal disease) factors.

Small for Gestational Age a foetus that has failed to achieve a specific biometric or estimated weight threshold by a specific gestational age may be constitutional or due to intra-uterine growth restriction (IUGR).

Assessments of foetal growth: Biparietal distance, head circumference, abdominal circumference, femur length serial measurements more useful to gauge velocity. Plotted on centiles can show if any dropping
off/lag/acceleration.

Assessment of babys coping: kick charts, CTG, biophysical profile (fetal breathing movements, fetal movements, fetal tone, amniotic fluid volume).

Assessment of babys nutrition: placental assessment appearance, blood flow characteristics via Doppler (umbilical fetus to placenta, uterine mother to placenta). Progressively greater resistance leads to absent or
reversed End Diastolic Flow. (read up on this if youre interested, I wont go into it further!)

Foetal Development

Early Pregnancy

Day 14 = ovulation
Fertilisation occurs commonly in the fallopian tube
Cell division occurs: zygote morula blastocyst as moving to uterine cavity
Day 23 = implantation beginning of fetal-maternal dialogue

When the blastocyst implants production of hCG by the decidua stimulates the ovary to produce progesterone (causes modification of maternal physiology).
hCG levels rapidly rise <10wks. Can be detected in serum/urine 4 weeks after LMP (urine PT +ve when concentration of hCG is 25IU/ml)

Ultrasound

4-5 weeks gestation sac ~6mm


5-6 weeks yolk sac
6 weeks foetal pole ~5mm
7 weeks foetal heart activity
8 weeks limb buds, fetal movements
Foetus should double in size every week until 12 weeks gestation

Stages of Labour
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a womans uterus. The process of normal childbirth is categorized in three stages of
labour: the shortening and dilation of the cervix, descent and birth of the infant, and birth of the placenta.

Stage 1

Onset of regular painful contractions, effacement of the cervix and dilation of the cervical Os to full dilatation.
Latent phase cervix dilates slowly for the first 3 cm may take hours.
Active phase average cervical contraction is 1cm/hr in nulliparous women and 2cm/hr in multiparous women.

Stage 2

From full dilatation of the Os to the birth of the baby.


Passive stage full dilatation head reaches the pelvic floor and women experience a desire to push.
Active stage when mother is pushing, pressure of the head on the pelvic floor produces a desire to bear down and push with contractions.
Stage 3

From the birth of the baby to the expulsion of the placenta & membranes.
Takes around 15 minutes on average
Small amount of blood and the cord lengthens.
Uterine contractions compress blood vessels supporting the placenta which shears away from the wall.

Postpartum Haemorrhage
Primary Postpartum Haemorrhage
Primary postpartum haemorrhage (PPH) is defined as loss of more than 500ml of blood from the genital tract within 24 hours of delivery

PPH can be described as minor or major depending upon the level of blood loss;
Minor PPH involves the loss of of anything up to 1000mls of blood
Major PPH involves the loss of more than 1000mls of blood
Causes
Causes of postpartum haemorrhage include uterine atony, trauma, retained placenta, and coagulopathy. These causes are often referred to as the four Ts Tone (uterine atony)
Trauma (lacerations) Tissue (retained placenta) Thrombin (coagulopathy)2
Uterine atony
Uterine atony is the most common cause of PPH account for around 70% of cases. It occurs due to the uterus losing its muscle tone. As a result it does not contract after delivery and
therefore the uterine vessels are not clamped down on allowing large amounts of bleeding to occur. The uterus can become atonic for a number of reasons such as prolonged labour
(the uterus tires out) or multiple birth (the uterus is large & stretched making it less effective at contracting)
Retained placenta
Retained placenta accounts for around 10% of cases of PPH. It results from either all or part of the placenta been retained within the uterus. This prevents the uterus from contracting
fully and therefore the uterine vessels are not occluded & continue to bleed.
Vaginal or Vulval Lacerations
Vulval & vaginal lacerations account for most of the other 20% of PPH cases. They occur due to the mechanics of birth and can be very severe. They must be monitored for some time
afterwards to ensure no infection develops and proper healing occurs.
Coagulopathy
Around 1% of PPH cases occur as a result of coagulapathy. Common causes of coagulopathy include haemophilia A or B. Its important to rule out coagulopathy as it can result in the
death of a patient if not identified early.
Risk factors
Pregnancy factors
Placenta praevia (15 x risk)
Multiple pregnancy (5 x risk)
Pre-eclampsia (4 x risk)
Previous PPH (3 x risk)
Nulliparity (first childbirth) (3 x risk)

Placental abruption

Delivery factors
Emergency caesarian section (9 x risk)
Retained placenta (5 x risk)
Elective caesarian section (4 x risk)
Mediolateral Episiotomy
Prolonged labour (>12 hours)
Big baby (>4kg)

Maternal factors
Obesity BMI >35 (2 x risk)
Asian ethnicity
Haemophilia (type A or B)
Anaemia (<9g/dl)
Age > 40 years

Symptoms & Signs


Symptoms
Prolonged & worsening vaginal bleeding after delivery
Passing many large clots
Lower abdominal pain
Pelvic pain
Light headedness / Fainting
Shortness of breath

Signs
Pale skin
Tachycardia
Tachypnea
Hypotension
Tender abdomen
Fever
Decreased consciousness

Investigations
Vaginal examination determine source of bleeding
Abdominal examination tender abdomen suggests uterine bleeding
FBC sudden drop in Hb suggests acute blood loss
Clotting prolonged PT & APTT suggest disseminated intravascular coagulation
Blood pressure low BP indicates blood loss
Pulse rate usually tachycardia present due to hypovolaemic shock
Oxygen saturation may be decreased to decreased red blood cells & Hb
Hourly urine output if decreased suggests blood volume loss
ECG
Complications
Hypovolaemic Shock
HELLP Haemolysis, Elevated Liver Enzymes, Low Platelets
Disseminated Intravascular Coagulation due to consumption of clotting factors
Management
Minor PPH
If minor PPH with no clinical signs of shock;
Contact obstetric doctor
Get IV access with two 14 gauge cannulas
Crystalloid infusion
Crossmatch 2 units of blood
BP, Pulse & Oxygen Saturation
FBC
Clotting
Regular clinical monitoring & observation

Major PPH

Contact senior clinical staff


Call Obstetric registrar & alert Consultant
Call Anaesthetic registrar & alert Consultant
Experienced Midwife
Alert consultant haematologist on call
Alert blood transfusion lab
Call porters to transfer specimens & blood products quickly

Airways & Breathing


Check airway if compromised get anaesthetist to secure airway
Give Oxygen at 10/15 L/min
.Circulation
Secure IV access with two 14 gauge cannulas
Blood sample should be taken & sent for;
FBC
Coagulation
U&E
Crossmatch 4 units
Renal & Liver function tests

Resuscitation
Position patient in supine position
Keep patient warm bear-hugger
Transfuse blood as soon as possible give 4 units of fresh frozen plasma for every 6 units of blood
.
Until blood is available infuse;
up to 3.5 litres of warmed crystalloid Hartmanns solution
and/or 1-2 litres of colloid as rapidly as required
.
Give platelets if PLT count <50 x 109
Give cryoprecipitate if fibrinogen <1g/L
Stopping the bleeding
In uterine atony try each of the following measures in turn until bleeding stops;
Bimanual uterine compression (rubbing up the fundus) stimulates contractions
Syntocinon 5 units slow IV injection
Ergometrine 0.5mg slow IV injection
Syntocinon infusion 40 units in 500 ml Hartmanns solution at 125 ml/hour
Carboprost 0.25 mg by intramuscular injection every 15 mins (max of 8 doses)
Carboprost intramyometrial 0.5mg
Misoprostol 1000mg rectally

If pharmacological measures fail, surgical treatment should be initiated in the following order;
Intrauterine balloon tamponade blood inside uterus to compress vessels
Haemostatic brace suturing large sutures around uterus to compress it
Bilateral ligation of uterine arteries
Bilateral ligation of internal iliac arteries
If bleeding will not stop hysterectomy must be performed do not hesitate with decision

Intensive monitoring
Patient should be sent to HDU or ICU
Prevention
Active management of the 3rd stage of labour reduces maternal blood loss & chances of PPH
Prophylactic oxytocics should be offered to all women as they reduce chances of PPH by 60%
Low risk vaginal delivery oxytocin 5 or 10 IUs IM injection
Caesarian section oxytocin 5 IU slow intravenous infusion

Secondary Postpartum Haemorrhage


Secondary PPH presents as abnormal bleeding from the genetical tract anytime from 24 hours after delivery until up to 6 weeks postpartum.

Causes
Infection (Endometritis) 1-3% of spontaneous vaginal deliveries
Retained products of conception
Examination

Tachycardia
Fever
Rigors
Tender abdomen (suprapubic)
Fundus may be elevated in cases of retained products

Investigations
FBC low Hb may suggest significant blood loss
MSU could give pain & haematuria which may be confused with PPH
High vaginal swab can confirm presence of infection
USS often can be normal despite retained products been present
Blood cultures may show septicaemia
Management
Speculum examination
Look for signs of inflammation
Rule out lacerations
Identify clots preventing closure of cervical OS
Clots can then be removed at the time
Antibiotics
If antibiotics are indicated combination of ampicillin and metronidazole is appropriate.
If patient has endomyometritis (tender uterus) or sepsis, gentamicin should also be used

Surgery
Surgical measures should be undertaken if there is excessive or continuing bleeding
Regardless of ultrasound findings

The Menstrual Cycle

What is the menstrual cycle?

The menstrual cycle is a complex series of physiological changes occurring in women on a monthly basis. It results in production of an ovum & thickening of the endometrium to allow for implantation if fertilisation should
occur. The menstrual cycle is orchestrated by the endocrine system through the complex interaction of the hypothalamus, pituitary and gonads. The entire cycle lasts around 28 days, with the cycle beginning on the first day
of menstruation & ovulation occurring around day 14.

How is it controlled?

1. The hypothalamus produces Gonadotrophin Releasing Hormone (GnRH)

2. This binds to the pituitary stimulating release of;

Luteinizing hormone (LH)


Follicle Stimulating Hormone (FSH)

3. FSH binds to the ovaries stimulating;

Development of ovarian follicles


Secretion of oestrogen
Secretion of inhibin

The follicle most sensitive to FSH becomes dominant & is known as the Graafian follicle

4. LH binds to the ovaries causing;

Production of oestrogen which is required for ovulation & thickening of the endometrium
Conversion of the Graafian follicle into the progesterone producing corpus luteum
Progesterone causes the endometrium to become receptive to implantation of a fertilised ovum

5. Oestrogen, Progesterone & Inhibin all cause -ve feedback on the pituitary & hypothalamus

6. This results in reduction of GnRH, FSH & LH production

7. In pregnancy GnRH, FSH & LH all remain inhibited, causing cessation of menstruation

Phases of the menstrual cycle

Follicular Phase

1. At the start of the cycle levels of FSH rise causing stimulation of a few ovarian follicles
2. As follicles mature they compete with each other for dominance
3. The 1st follicle to become fully mature will produce large amounts of oestrogen
4. This inhibits the growth of the other competing follicles
5. The 1 follicle reaching full maturity is called the Graafian follicle (oocyte develops within this)
6. The Graafian follicle continues to secrete increasing amounts of oestrogen
.7. Oestrogen causes;
Endometrial thickening
Thinning of cervical mucous to allow easier passage of sperm
.
8. Oestrogen also initially inhibits LH production from the pituitary gland
9. However when the ovum is mature, oestrogen reaches a threshold level which conversely causes a sudden spike in LH around day 12
10. The high amounts of LH cause the membrane of the Graafian follicle to become thinner
11. Within 24-48 hours of the LH surge, the follicle ruptures releasing a secondary oocyte
12. The secondary oocyte quickly matures into an ootid & then into a mature ovum
13. The ovum is then released into the peritoneal space & is taken into the Fallopian tube via fimbriae (finger like projections)
Luteal Phase
14. Once ovulation has occurred the hormones LH & FSH cause the remaining graffian follicle to develop into the corpus luteum
15. The corpus luteum then begins to produce the hormone progesterone
.
16. Increased levels of progesterone result in;
Endometrium becoming receptive to implantation of the blastocyst
Increased production of oestrogen by the adrenal glands
Negative feedback causing decreased LH & FSH (both needed to maintain the corpus luteum)
Increase in the womans basal body temperature
.
17. As the levels of FSH & LH fall, the corpus luteum degenerates
18. This results in progesterone no longer been produced
18. The falling level of progesterone triggers menstruation & the entire cycle starts again
19. However if an ovum is fertilised it produces hCG which is similar in function to LH
20. This prevents degeneration of the corpus luteum (continued production of progesterone)
21. Continued production of progesterone prevents menstruation
22. The placenta eventually takes over the role of the corpus luteum (from 8 weeks)

The Uterine Cycle


The uterus has its own cycle which is driven by the cyclical release of hormones by the ovaries which weve previously talked about. The inside lining of the uterus is known as the
endometrium. The endometrium is the part of the uterus most affected by these changes in hormone levels.

It is composed of 2 layers;

Functional layer this grows thicker in response to oestrogen & is shed during menstruation
Basal layer this forms the foundation from which the functional layer develops it is not shed

Phases of the uterine cycle

The uterine cycle has 3 phases known as the proliferative, secretory & menstrual phases

Proliferative phase

During the proliferative phase the endometrium is exposed to an increase in oestrogen levels caused by FSH & LH stimulating the ovaries. This oestrogen causes repair & growth of the
functional endometrial layer allowing recovery from the recent menstruation & further proliferation of the endometrium.

.Continued exposure to increasing levels of oestrogen causes;

Increased endometrial thickness


Increased vascularity spiral arteries grow into the functional endometrial layer
Development of increased numbers of secretory glands

.Secretory phase

The secretory phase begins once ovulation has occurred

This phase is driven by progesterone produced by the corpus luteum

It results in the endometrial glands beginning to secrete various substances

These secretions make the uterus a more welcoming environment for an embryo to implant

.Menstrual phase

At the end of the luteal phase the corpus luteum degenerates (if no implantation occurs)

The loss of the corpus luteum results in decreased progesterone production

The decreasing levels of progesterone cause the spiral arteries in the functional endometrium to contract

The loss of blood supply causes the functional endometrium to become ischaemic & necrotic

As a result the functional endometrium is shed & exits out through the vagina

This is seen as the 3-5 day period of menstruation a woman experiences each month

Window of fertility
A womans most fertile period is between 5 days before ovulation until 1 to 2 days after

Women can therefore use knowledge of their cycle to improve chances of conception

Women may also monitor symptoms that suggest they are about to ovulate such as;

Basal body temperature measuring it spikes during the LH surge 24-48 hours before ovulation
Thinning of cervical mucous

Symptoms experienced in the menstrual cycle


Abdominal pain & cramps
Heavy vaginal bleeding
Vaginal pain
Nausea
Diarrhoea
Sweating
Fatigue
Irritability
Dysphoria (unhappiness)

Miscarriage (early pregnancy loss)


Miscarriage is the spontaneous loss of an intrauterine pregnancy before 20 weeks gestation (or weighing less than 400g depending on the jurisdiction). It occurs in approximately 1020% of all clinical pregnancies. The risk of miscarriage increases with increasing maternal age; miscarriage occurs in 21% of pregnancies between the age of 35-40 years old and
increases to 41% above the age of 40 years old. Most miscarriages (~80%) are diagnosed between 8-12 weeks, with the risk of miscarriage decreasing as gestational age increases.
Causes of miscarriage
In the first trimester the most common cause of miscarriage is chromosomal abnormality (50-60%):
Autosomal trisomy is the most common abnormality trisomy 16 is the most common trisomy in miscarriage
The most common single chromosomal anomaly is 45X karyotype
Maternal age is related to aneuploidy risk = increasing maternal age increases aneuploidy risk
In the second trimester miscarriage is commonly due to an incompetent cervix:
Important risk factor is previous cervical surgery
Other potential causes of miscarriage include:
Fetal malformations e.g. neural tube defects
Uterine structural abnormalities e.g uterine septum, Ashermans syndrome, fibroids
Chronic maternal health factors:
Thrombophilia
Antiphospholipid syndrome
SLE
PCOS
Poorly controlled diabetes mellitus
Thyroid dysfunction

Active infections including:


Rubella
CMV
Herpes simplex virus
Listeria infection
Toxoplasmosis
Parvovirus B19
Iatrogenic causes:
Amniocentesis
Chorionic villus sampling
Social factors:
Tobacco
Alcohol
Cocaine
Exposure to environmental toxins
Advanced paternal age
Definitions of miscarriage
Miscarriage can be classified according to stage.
Stages
1. Threatened miscarriage

The fetus is threatened (i.e. a miscarriage may happen). There is some vaginal bleeding BUT the cervical os is CLOSED and ultrasound reveals a VIABLE intrauterine pregnancy.
IMPORTANT TO NOTE: 90% of threatened miscarriages will continue to grow to normal gestation.
2. Inevitable miscarriage
The miscarriage is inevitable i.e. a miscarriage is going to happen. There is vaginal bleeding +/- cramping abdominal pain AND the cervical os is OPEN but the products of conception
have not yet passed.
3. Incomplete miscarriage
The miscarriage is incomplete, i.e. currently happening. There is heavy and increased vaginal bleeding, intense lower abdominal pain and passage of some products of conception. On
examination the cervical os is OPEN and there are PRODUCTS OF CONCEPTION present in the canal.
4. Complete miscarriage
The miscarriage is complete. Products of conception have been passed. On examination the cervical os is CLOSED. Ultrasound reveals an EMPTY uterine cavity.
Other types of miscarriage
Missed miscarriage
The miscarriage was missed i.e. a NONVIABLE INTRAUTERINE pregnancy has remained inside the uterus (the fetus has not spontaneously aborted). The patient is amenorrhoeic but
has not had any vaginal bleeding or abdominal pain. On examination there is no passage of tissue and the cervical os is CLOSED. Ultrasound confirms a non-viable intrauterine
pregnancy.
Blighted ovum
Missed miscarriage in which embryonic development stopped before the embryonic pole was visible. The gestational sac may continue to grow.
Septic miscarriage
Miscarriage + sepsis (symptoms of fever / significant abdominal tenderness).
Recurrent miscarriage
Occurrence of 3+ miscarriages.
Clinical assessment
History
Symptoms:
Amenorrhoea
Vaginal bleeding (details regarding quantity and pattern) +/- syncope (indicating significant blood loss)
Cramping abdominal pain
Passage of any fetal tissue
Fever ?septic miscarriage
Menstrual cycle: LMP / cycle length / days bleeding / clots / flooding
If known to be currently pregnant: dating based on LMP / USS results
Past obstetric history:
Outcomes from previous pregnancies and complications
Previous miscarriage or ectopic pregnancy increases the risk
Past gynecological history:
Including cervical / uterine surgery
Risk factors for ectopic pregnancy previous ectopic, previous STI/PID, IUD, previous tubal surgery
Contraception
Pap smears abnormal results LETZ surgery

General medical and surgical history


Family history
Medications / Allergies
Social history: Smoking / Alcohol / Illicit drug use
Important points on examination
Vitals: assessment of haemodynamic stability / pyrexia
Abdominal examination: benign in miscarriage (if rebound tenderness present consider ectopic pregnancy)
Pelvic examination considerations:
Speculum examination
Determine the source of the bleeding
Quantify the bleeding
Is the cervical os open or closed?
Evidence of products of conception in the cervical os
Purulent cervical discharge ? septic miscarriage
Bimanual examination
Uterine size
Cervical motion tenderness (if present increases likelihood of ectopic pregnancy)
Adnexal mass ?ectopic pregnancy
Investigations
Blood tests
Complete blood count with differential.
Quantitative b-hCG:
A single level to assist in USS interpretation (discussed below)
Level may be less than expected for dates in miscarriage (b-hCG doubles every 48 hours reaching 100 000 at 10 weeks, and then plateauing and decreasing to 10 000 at term)
Serial testing every 48 hours showing a falling b-hCG indicates a failing pregnancy (if less than 10 weeks gestation)
If bleeding is significant: group and hold / cross match
Antibody screen: rhesus negative patients will require anti-D
Transvaginal ultrasound

Ensure that the b-hCG level is above that of the discriminatory zone:
The discriminatory zone is the level of serum b-hCG above which the gestational sac is visible on USS
To confirm a pregnancy by transvaginal ultrasound the b-hCG must be above 1500.
This correlates with a gestational age of approximately 5 weeks gestation.
The discriminatory zone for an abdominal ultrasound is 6500.
Five points to check in pregnancy:
Dating
Location: is the pregnancy intrauterine? = important to rule out ectopic pregnancy
Multiple pregnancy
Molar pregnancy = snowstorm appearance
Nonviable pregnancy includes:
Gestation sac > 25mm diameter with no yolk sac or embryo
No cardiac activity: fetal heart rate is typically detected at 5.5 to 6 weeks
Look for retained products of conception (if from the history the miscarriage is incomplete or complete)

Histological examination of any tissue passed vaginally.


Differential diagnosis of early pregnancy bleeding
1) Miscarriage
2) Ectopic pregnancy
3) Molar pregnancy
4) Implantation bleed
5) Genital tract trauma
6) Cervical pathology: ectropion / polyp / malignancy
Management
Management considerations
Emergency
Surgical
Medical
Expectant
Psychological support
In every case:
Is the patient haemodynamically stable?
Rule out ectopic pregnancy
Check rhesus status, if rhesus negative give anti-D

Emergency management (haemodynamically unstable)


The key points in this situation are to make an accurate assessment of the patient, initiate basic resuscitation (ABCD) and inform seniors as soon as possible.
Resuscitation of the patient using the ABCD approach.
Urgent O&G specialist input consultant / registrar input is essential.
Urgent speculum examination to remove POC as clinically indicated:
This may stop the bleeding and restore blood pressure (POC in the cervical os causes cervical dilatation which causes a vasovagal response)
Urgent ultrasound scan: exclude ectopic pregnancy
Anti-D should be considered if the patient is rhesus negative.
Continued bleeding in a haemodynamically unstable patient warrants surgical evacuation.
Surgical evacuation (dilation & curettage)
Dilation and curettage (D&C) refers to the dilation (widening) of the cervix and surgical removal of part of the lining of the uterus and/or contents of the uterus by scraping and scooping
(curettage).

This procedure is indicated in the following situations:


Haemodynamic instability
Excessive bleeding
Infected retained tissue
Suspected molar pregnancy
Unsuccessful expectant or medical management
Risks of the procedure:
Risks of general anaesthesia (e.g. N/V, DVT/PE )
Risks of any operation (e.g. infection, haemorrhage)
Possibility of retained products after operation
Uterine perforation
Cervical tears
Intrauterine adhesions (Ashermans syndrome)
Medical management
Medical management involves the use of a prostaglandin agent to induce uterine contractions and effacement of the cervix (Misoprostol is commonly used).
If haemodynamically stable, women may prefer this option.
It has an 85% success rate.
Risks include:
Bleeding that may continue for up to 3 weeks
Increased pain in association with the bleeding
Infected products of conception
Patient education its essential to inform the patient of the potential risks and explain the need to seek review
Follow up patients are usually followed up approximately 1 week later

Expectant management
Expectant management involves waiting for spontaneous passage of the products of conception, without any medical or surgical intervention.
Risks include:
Bleeding that may continue for several weeks
Increased pain in association with the bleeding
Infected products of conception

Patient education its essential to inform the patient of the potential risks and explain the need to seek review
The patient may require anti-D if they are rhesus negative.
Follow-up review at 7-10 days with ultrasound if continued bleeding, pain or evidence of retained POC on ultrasound discuss further management (suction curettage)

Psychological support
Break bad news appropriately and ensure support.
Provide written information.
Communicate to general practitioner via letter.
Offer referral to relevant healthcare professionals and support groups prior to discharge particularly for counseling/psychological support.
Risk of recurrence
There is no increased risk of having another miscarriage after having one miscarriage (10-20% for the general population).
After two miscarriage the risk of having another miscarriage is 25%.
After three miscarriages the risk is approximately 40%.
Recurrent miscarriages
3+ miscarriages, requires specialist review
There is an underlying cause in 50% of patients.
Causes include:
Increased maternal age
Parental genetic factors (balanced translocations, mosaicism)
Thrombophilic disorders
Endocrine disorders (diabetes mellitus, thyroid disorders, PCOS)
Structural uterine abnormalities
Pertinent features on history:
Menstrual cycle history
Medical Hx: clotting (DVT, PE), endocrinopathy (diabetes mellitus, thyroid dysfunction)
Hx of cervical surgery or uterine instrumentation (cervical incompetence, Ashermans syndrome)
Hx of congenital abnormalities that may be heritable
Detailed family history
Exposure to environmental toxins (e.g. occupational exposures)

Physical examinations should include general physical assessment, any signs of endocrinopathy and any pelvic organ abnormalities.
Investigations:
Cytogenetic analysis performed on the products of conception of the third and any subsequent miscarriages
Parental karyotyping and genetic counseling
Female requires:
Pelvic ultrasound and MRI, sonohysterography, hysteroscopy for further structural evaluation
Thrombophilia screen
Antiphospholipid antibody screen, anticardiolipin antibodies and lupus anticoagulant
Thyroid function: TSH, free T4, thyroid peroxidase antibodies

Ensure adequate psychological support.


The chance of subsequent success of an intrauterine pregnancy is still up to 75%,
The prognosis is improved if one live birth has occurred.

Menorrhagia
Menorrhagia is menstrual blood loss which interferes with the womans physical, emotional, social, and material quality of life, and which can occur alone or in combination with other
symptoms. Any intervention should aim to improve her quality of life.
Causes of Menorrhagia
Dysfunctional uterine bleeding
40 to 60% of those who complain of excessive bleeding have no pathology
This diagnosis should only be given once other common causes have been ruled out
Uterine fibroids
Very common with 25% of women developing at least 1 in their lifetime
Most common in women aged 30-50
They cause increased surface area of endometrium, leading to increased menstrual loss
Pelvic inflammatory disease
Involves inflammation of the uterus, fallopian tubes and/or ovaries
Its most commonly caused by bacterial infections such as:
Gonorrhoea
Chlamydia
Normal vaginal flora organisms
Cervical Cancer
Most common symptom of cervical cancer is abnormal vaginal bleeding
Visualisation of the cervix / SMEAR / Colposcopy should be used to rule out

Endometrial carcinoma
Most common in women over 40
Usually presents with post-menopausal bleeding
Endometrial biopsy should be performed if risk factors for endometrial carcinoma are present
Risk factors
> 45 years old
IMB
PMB
Medical treatment failure
Systemic disease
Hypothyroidism look for other signs of thyroid disease before investigating
Bleeding disorders Haemophilia A or B, Von Willebrands Disease
Investigations
FBC commonest cause of iron deficiency anaemia is menorrhagia
TFTs may detect underlying hypothyroidism only do if suspicious
Ultrasound may allow identification of fibroids or structural abnormalities
Perform an Endometrial biopsy if:
Persistent inter-menstrual bleeding
Age >45
Treatment failure
Management
If history and FBC are reassuring medical treatment should be considered.
Correct iron deficiency with oral iron supplementation
Medical treatment
Mirena (First line)
Coil which also releases progesterone
Keeps endometrial lining thin reducing menstrual loss
Periods often can completely cease
Also works as a contraceptive, so useful for younger women
Should be used for at least 12 months
Side effects
Irregular bleeding (can last up to 6 months)
Breast tenderness
Acne
Amenorrhoea
Uterine perforation at time of insertion (rare)
Tranexamic acid (Second Line)
Plasminogen-activator inhibitor
Prevents the breakdown of thrombosis which normally results in menstruation
It reduces menstrual flow by around 50%
Treatment should be stopped if no improvement is seen within 3 menstrual cycles
Side effects
Indigestion
Diarrhoea
Headaches
Combined Oral Contraceptive (Second Line)
Prevents proliferation of endometrium
Also has the added benefit of acting as a contraceptive
Side effects
Mood changes
Headaches
Nausea
Breast tenderness
DVT
Progestogen (Third line)
Oral e.g. Norethisterone
Taken on day 5-26 of cycle
Results in significant reduction in menstrual blood loss
Injected progestogen also can be used a.k.a. Depot Provera
Surgical Treatment
Endometrial ablation (Novasure)
Involves ablation of the endometrial lining (usually under GA)
Only be given to women with a uterus no bigger than a 10 week pregnancy
A probe is inserted vaginally into the uterus
A wire mesh is then opened up and electrical energy is applied causing
thermal damage to the endometrium
87% of patients have successful reduction in bleeding down to normal levels
Side effects
Vaginal discharge
Dysmenorrhea
Infection (rare)

Uterine Artery Embolisation


Uterine artery embolisation is a procedure where an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. Due to collateral
circulation the uterus will not necrose even if both arteries are occluded. This can be used to treat fibroids and reduce heavy menstrual bleeding
Side effects
Persistent vaginal discharge
Post embolisation syndrome nausea, vomiting & fever
Premature ovarian failure (especially in women >45)
Infection (rare)
Hysteroscopic Myomectomy
If a fibroid seems to be a likely cause of menorrhagia then hysteroscopic myomectomy may be considered. It involves insertion of hysteroscope to visualise the endometrium through
the cervix and then surgical removal of fibroids. This can only be done if the fibroids are in a submucosal location.
Side effects
Adhesions
Recurrence of fibroids
Perforation
Infection
Hysterectomy
Vaginal hysterectomy is usually preferred
Abdominal hysterectomy with conservation of ovaries would be the next option
This option would usually only be considered once other methods fail

Side effects
Infection common
Intra-operative haemorrhage
Bladder or bowel damage
Urinary incontinence
Thrombosis DVT / PE

Pre-eclampsia
Pre-eclampsia is a disease of pregnancy involving the development of both hypertension as well as proteinurea. The disease appears to be caused by release of various factors from the
placenta which results in widespread endothelial cell dysfunction & organ damage. Pre-eclampsia can develop anytime from 20 weeks gestation until up to 6 weeks post-partum. The
earlier pre-eclampsia develops the higher the risk of serious complications. The only way to cure pre-eclampsia is to deliver the baby & remove the placenta as this is central to the
disease process. Pre-eclampsia is a major cause of poor pregnancy outcome for both mother & foetus and is associated with significant mortality, therefore early recognition & intensive
management can make a huge difference.
What is the mechanism of Pre-eclampsia?
The most accepted theory currently suggests the following mechanism,;
1. The placenta (trophoblast) does not implant adequately into the uterine wall
2. As a result the blood supply to the placenta is relatively poor
3. This results in under-perfusion of the placenta causing hypoxia of the placental tissue
4. The hypoxic placenta releases inflammatory factors triggering an exaggerated immune response
5. The immune attack results in further release of inflammatory mediators & substances causing v asoconstriction
6. As a result the mothers blood vessels endothelial lining is damaged & peripheral vascular resistance increases
7. Increased peripheral vascular resistance results in the development of hypertension
8. Hypertension causes further damage to blood vessels & major organs including the kidneys, which leak protein as a result
Risk factors
Patient factors
Maternal age >40
Ethnicity african americans have increased risk
Obesity BMI > 35
Family history of pre-eclampsia mother or sister
Pregnancy factors
Previous pre-eclampsia
First pregnancy
Multiple pregnancy
Change of partner
Assisted reproduction techniques
Pre-existing conditions
Obesity
Diabetes mellitus
Chronic hypertension
Chronic renal disease
Thombophillia anti-phospholipid syndrome
Symptoms & Signs
Mild
Hypertension
Significant proteinurea (>0.3g in 24hrs)
Often women are not aware of any symptoms in the early stages
Severe
Severe headache usually frontal
Epigastric pain
Vomiting
Severe oedema face, hands, legs, feet
Papilloedema flashing lights, reduced vision
Reduced foetal movements foetal distress
Intrauterine Growth Restriction
.

HELLP syndrome
HELLP syndrome can develop in severe pre-eclampsia
It is a serious disorder involving the liver & the clotting system
Its main features are;
Haemolysis
Elevated Liver enzymes
Low Platelets
Diagnosis
Both Hypertension & Proteinurea must be present for the diagnosis of Pre-eclampsia to be confirmed
Hypertension
A pregnant women may classed as having hypertension in a number of ways
These include;
140/90mmHg on 2 occasions more than 4 hours apart
Systolic BP of 30mmHg above the booking systolic BP
Diastolic BP of 15-25mmHg above booking diastolic BP
Proteinurea
>0.3g in 24-hrs
This approximates to 1+ or more on a urine dipstick
Investigations
Blood pressure monitoring
Urinalysis protein, microscopy, culture & sensitivities
24 hour urine collection
FBC monitor RBC for drops suggesting haemolysis
LFT monitor liver enzymes for signs of HELLP syndrome
U&E monitor renal function (hypertension can cause renal failure)
Clotting if suspicious of HELLP
Management
Regular monitoring
Regular checking of;
BP hypertension
Urine proteinurea
.
Admission to hospital
Women may need admitting to hospital if they display any of the following;
If BP >170/110mmHg or 140/90mmHg with 2+ proteinurea
Significant symptoms
Abnormal biochemistry/ haematology
Significant proteinurea
Requires antihypertensive treatments
Signs of foetal compromise
Antihypertensives
The aim is to reduce the diastolic BP to <100mmHg
Labetalol oral/IV
Nifedipine oral

Hydralazine IV
Avoid use of Atenolol, ACE Inhibitors or Angiotensin receptor blockers
.
Anti-seizure medication
Given if there is significant risk of eclampsia
Magnesium sulphate IV Membrane stabiliser
It halves the risk of eclampsia!
.
Fluid restriction
Vascular permeability is increased in pre-eclampsia
As a result fluid excess fluid spills into the extravascular compartments
If too much fluid is given it can result in pulmonary oedema
If too little fluid is given it can result in renal failure
Therefore controlling fluid intake reduces risk of fluid overload or depletion
.
Delivery of baby
Delivery is the only cure for pre-eclampsia
However the woman needs to be stable before this can be done
If foetus is <34 weeks then steroids should be given
Delivery can be delayed only if pre-eclampsia is controlled regular monitoring required
Delaying delivery may improve perinatal outcome but increases risk to the mother
A balance must be struck between foetal & maternal wellbeing

Eclampsia
Eclampsia is a life threatening complication of pregnancy which can occur if pre-eclampsia is not controlled & becomes severe. It is characterised by the appearance of tonic clonic
seizures. Eclampsia can cause coma & death in a very short period of time, therefore immediate action should be taken.
Symptoms
Tonic Clonic Seizure:
Sudden loss of consciousness
Tonic Phase body becomes rigid & lasts for 15-20 seconds
Clonic Phase rapid contraction & relaxation of muscles causing forceful jerking of entire body
.
Coma
Death 1 in 50 women will die from eclampsia
.
Effects on the foetus
Foetal distress
Bradycardia
Reduced variability on CTG
.
Placental abruption
High risk of abruption in eclampsia
The foetus becomes hypoxic as a result
Death or serious brain damage can occur
Management
ABC
Place patient on left side avoids aortocaval compression
Secure airway
Give high flow oxygen
.
Antihypertensives
Labetalol, Nifedipine, Hydralazine
Given at higher doses than in routine pre-eclampsia
The aim is to stabilise BP before delivering baby via C-section
.
Magnesium sulphate
Has membrane stabilising effects reducing neuronal excitability
It halves the risk of eclampsia
Also reduces maternal mortality
.
Delivery of baby
C-section is used as it is less demanding on the body & much quicker
Carried out as soon as women is stable
Even if foetus is very premature you have to deliver
Otherwise mother will undergo multiple organ failure & die.

Ovarian Cancer
Ovarian cancer is one of those nightmare cancers: its vague, insidious onset means that it tends not to present until it is too late, and there is currently no effective screening
programme in place to detect it at an earlier stage. Like endometrial cancer, it tends to affect older women and it is vital to consider it a possibility in women over 60 with vague
abdominal or urinary symptoms.
Ovarian cancer tends to present with a pelvic mass, so Ive included a differential diagnosis for this. Ive also described efforts to develop an ovarian screening programme the
UKFOCSS trial is currently underway to investigate its effectiveness.
.
Introduction
Anatomy of the female reproductive system
ANATOMY OF THE OVARIES
the ovaries are a pair of small oval-shaped organs located in the female pelvis. They are the female equivalent of the testes. They function as gonads by producing female germ cells
called ova, and also as endocrine glands which secrete the female sex hormones oestrogen and progesterone.
they lie on either side of the body of the uterus beneath the uterine tubes, within a double-layered sheet of peritoneum called the broad ligament.
they consist of an outer cortex, which contains the ovarian follicles, and an inner medulla containing blood vessels, nerves and lymphatics.
the ovaries are surrounded by a thin fibrous capsule called the tunica albuginea, which is covered externally by a modified layer of peritoneum called the germinal epithelium.
the fimbriae of the uterine tubes drape over the ovaries, and act to catch the ova after they are released and guide them into the uterus.
they are usually located on the lateral wall of the pelvis in a depression known as the ovarian fossa, with the external iliac vessels above, the obturator nerve laterally, and the internal
iliac vessels and ureter running behind them. However, their position can be extremely variable and they tend to move around a lot during and after pregnancy.
they are held in place by ligaments connecting them to other structures the ovarian ligament is continuous with the round ligament and connects them to the uterus, and the
suspensory ligament of the ovary (or infundibulopelvic ligament) is part of the broad ligament which connects them to uterine tubes and the lateral wall of the pelvis, and transmits
the ovarian vessels and nerves.
the ovaries are the only totally intraperitoneal organs in the body this is important as it means that ectopic pregnancies can implant onto abdominal organs, and ovarian cancer can
easily metastasise across the peritoneal cavity (this is known as transcoelomic spread).
PHYSIOLOGY
at birth, the ovaries contain 1-2 million ova, but only about 300-400 will ever undergo maturation
the ovaries usually take it in turns each month to mature and release an ovum (ovulate) during the menstrual cycle the ovum enters the uterine tube, where it can undergo
fertilisation by a sperm and develop into a fetus. If it is not fertilised, it is shed along with the endometrial lining of the uterus.
this process is triggered by the pituitary hormones FSH and LH
the developing ovarian Graafian follicle produces oestrogen, which stimulates the proliferation of the endometrium and changes in cervical mucus which make it more welcoming to
sperm. It also causes a wide variety of systemic effects.
after ovulation has occurred, the corpus luteum produces progesterone which triggers changes in the endometrium to make it more receptive to implantation.
for more detail on the menstrual cycle, see here for the Geeky Medics guide

TERMINOLOGY
ovarian cancer is a malignant neoplasm arising from the tissues of the ovary it is the leading cause of death from gynaecological cancer in the UK
.
Epidemiology
ovarian cancer accounts for 4% of cancers in UK women (about 7000 cases per yer)
it is the fifth most common cancer and causes 5.6% of cancer deaths (about 4000 per year)
there is a lifetime risk of 2.0%, or 1 in 51, for women in the UK
it has a peak incidence in women in their 60s and 70s, and is rare under the age of 40
incidence has decreased over the past 10 years, possibly due to increased use of the OCP
ovarian cancer is almost twice as common in developed countries than in the developing world
.
Aetiology and risk factors
ovarian cancer is believed to result from damage to the ovarian surface epithelium during ovulation
the theory of incessant ovulation basically states that the more a woman ovulates in her lifetime, the higher her risk of ovarian cancer, due to the increased cumulative damage to the
epithelium and the increased risk of mutations during its subsequent repair and regeneration
factors leading to incessant ovulation include early menarche, late menopause, delayed childbearing, nulliparity, use of HRT for >5 years, use of fertility drugs such as clomiphene to
stimulate ovulation, and increasing age
previous ovarian disease, such as ovarian cysts (2-9x risk) or endometriosis (1.5x risk), can increase risk, probably through similar mechanisms
pelvic radiotherapy for previous gynaecological cancers or lymphoma (1-2x risk)
previous breast cancer (2-4x risk) or ovarian cancer (obviously)
smoking is a proven risk factor for some types of ovarian cancer
obesity, diabetes and sedentary lifestyle can also increase risk, especially in younger women
occupational carcinogen exposure asbestos is a known ovarian carcinogen (3-5x risk)
family history is important as several inherited genetic traits can significantly increase risk, for example BRCA1 (46% risk by age 70), BRCA2 (12% risk by age 70) and HNPCC (12%
lifetime risk).
being tall is a risk factor, although no-one really knows why
protective factors include multiparity (>3 pregnancies), breastfeeding, OCP use, hysterectomy, tubal ligation, exercise and aspirin
.
Histopathological types
.
~90% EPITHELIAL OVARIAN TUMOURS
derived from surface coelomic epithelium, generally affect the over 50s
50-80% serous adenocarcinoma
10% endometrioid adenocarcinoma (like endometrial cancer)
3-8% mucinous adenocarcinoma
4-5% clear cell adenocarcinoma
2% other rare types: squamous cell, transitional cell, mixed mesodermal tumour, carcinosarcoma, undifferentiated sarcoma
.
~10% OTHER TYPES
derived from other parts of the ovary, generally affect younger women and progress more quickly and aggressively
1% sex cord stromal tumours granulosa-theca cell, Sertoli-Leydig, gynandroblastoma, lipid cell
1.5% germ cell tumours dysgerminoma, endodermal sinus (yolk sac) tumour, embryonal carcinoma, teratoma, choriocarcinoma, polyembronoma, gonadoblastoma
7% metastases from other sites gastric (Krukenberg tumour), colorectal, breast, endometrial, cervical, lymphoma, leukaemia
.
Symptoms
its insidious onset means that up to 75% of patients present with symptoms of advanced disease due to the mass effects of the tumour
non-specific GI symptoms such as bloating or indigestion (often misdiagnosed as IBS)
gradually increasing abdominal distension (often misdiagnosed as middle-aged spread)
increasing tumour size results in pressure effects causing chronic abdominal, pelvic or back pain, urinary frequency/urgency (pressure on bladder), constipation/altered bowel
habit/bowel obstruction (pressure on bowel), leg swelling and DVT/PE (pressure on pelvic veins)
abnormal vaginal bleeding can also be a symptom
symptoms of metastatic disease include pleural effusion, ascites, weight loss and fatigue
less commonly, sudden torsion, rupture or infection of the tumour in early disease can present with acute abdominal or pelvic pain this is a blessing in disguise as it can lead to early
diagnosis
.
Signs
general examination cachexia, lymphadenopathy, signs of pleural effusion
abdominal examination distension, ascites, palpable pelvic mass, omental cake metastasis
Cusco speculum examination usually normal
bimanual palpation palpable adnexal/pelvic mass which may be fixed and immobile
.
Differential diagnosis pelvic mass
ovarian pathology ovarian cyst/benign tumour, ovarian cancer
tubal pathology tubo-ovarian abscess, tubal malignancy (treat as ovarian)
uterine pathology pregnancy, fibroids/benign tumour, uterine cancer
urological pathology distended bladder, pelvic kidney, transplanted kidney
GI pathology the 6 Fs: fat, fluid, flatus, faeces, fetus, filthy big tumour
other abdominal pathology primary peritoneal cancer, retroperitoneal sarcoma
.
Investigations
Diagnostic tests for women with suspected cancer include:
history and clinical examination including Cusco speculum examination and bimanual palpation
always do a pregnancy test in women of reproductive age
tumour markers are very useful in the diagnosis of ovarian cancer: CA-125 (a coelomic epithelial antigen) is elevated in 90% of cases of advanced disease and 50% of cases of early
disease. It is very sensitive for ovarian cancer but not particularly specific it can also be raised in other gynaecological cancers, GI cancers, benign abdominal and pelvic disorders,
breast cancer and diseases affecting the pleura, pericardium or peritoneum. However, performed in the correct clinical context it can be very informative and should be a standard test
for suspected ovarian cancer.
other tumour markers for specific types of ovarian cancer include CA19-9 (mucinous epithelial), beta-hCG and placental ALP (dysgerminomas, embryonal cancers, choriocarcinoma),
AFP (endodermal sinus/yolk sac tumours), inhibin (granulosa-thecal cell tumours) and LDH (some dysgerminomas) these are usually arranged and interpreted by a specialist gynaeoncologist.
transabdominal +/- transvaginal ultrasound should be performed to assess the mass and check for any metastases
Initial investigations are usually carried out by GPs in primary care, and the risk of malignancy index (RMI) score provides guidance on which patients to refer to gynaecology. It provides
a composite assessment of risk and allows gatekeeping of referrals to specialist centres. It is calculated as menopausal status score x ultrasound assessment score x CA-125 result. A
score of >200 indicates a 75% risk of cancer and should prompt referral to a specialist gynae-oncology centre. A score of <200 represents a 3% risk of cancer and should be monitored
using 4-monthly CA-125 and ultrasound.
.
Staging investigations for patients with a high RMI score include:
blood tests FBC (for anaemia), U+E (for renal function), LFTs (for metastases)
imaging CXR to check for pleural effusion or lung metastases, CT +/- MRI abdomen and pelvis to assess mass, pelvic nodes and any metastases; a PET scan may be required in
advanced disease
invasive tests pleural or ascitic tap may be required if effusion/ascites present
laparoscopy and biopsy is indicated for large cystic lesions or adnexal masses to inform further management
formal surgical staging is usually carried out as part of definitive management described below
.
Ovarian cancers are staged using the International Federation for Gynaecology and Obstetrics (FIGO) system. The TNM system can also be used, but generally gynae-oncologists prefer
to use FIGO.
.
The mortality figures shown are for epithelial ovarian cancers, and the prognosis varies significantly depending on the type of cancer. For example, dysgerminomas have an excellent
cure rate, whereas endodermal sinus (yolk sac) tumours have a very poor prognosis.
.
Management
Surgical management is generally the mainstay of treatment:
exploratory laparotomy for tumour debulking and formal surgical staging
this is a major procedure which generally comprises total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO), infracolic omentectomy, pelvic and para-aortic
lymph node sampling, peritoneal biopsies, multiple pelvic washings, sampling of ascites, inspection and sampling of the underside of the diaphragm, and removal of pretty much
anything else that looks suspicious e.g. bowel, appendix, liver, spleen
maximal cytoreduction (largest residual tumour deposit <2cm) can be achieved in up to 80% of patients and significantly improves survival
a second interval debulking can be carried out after chemotherapy in some cases

This excellent little video from TeamCirisano on YouTube shows the removal of a large cystic ovarian mass at laparotomy. Most of the cyst fluid is drained first to prevent unnecessary
spillage and seeding of cancer cells into the abdominal cavity, then the ovary and tumour are removed.
.
.
Medical therapies are generally used as adjuncts to surgery:
adjuvant chemotherapy is given to all patients >stage Ic, plus anyone stage Ia/Ib with a high grade malignancy. The standard first-line treatment is carboplatin + paclitaxel (response
rate 70-80%). Second-line agents to consider include pegylated liposomal doxorubicin (PLDH) and topotecan. Response to treatment can be monitored using CA-125 levels, which
decrease if treatment is effective and increase if there is a relapse.
intraperitoneal chemotherapy has been shown to improve survival in recent trials
radiotherapy is not really used in the management of ovarian cancer as the tumours tend to be very radioresistant. It is sometimes used in early stage low-bulk disease.
biological immunotherapy is emerging as a potential new treatment specific monoclonal antibodies like bavacizumab (anti-VEGF) and olaparib (anti-PARP) are currently undergoing
trials
advanced metastatic cancer (which is unfortunately very common) requires individualised palliative treatment with tumour debulking, chemoradiotherapy and symptom control
.
Follow-up and prognosis
the overall prognosis is fairly poor (42.9% 5-year survival), but varies significantly depending on the stage and type of cancer (see above)
women who undergo surgery for ovarian cancer are usually followed up and monitored by a specialist gynae-oncology centre, with regular pelvic examinations and CA-125 levels
.
Prevention strategies potential for screening
There are several potential future options for screening for ovarian cancer:
genetic screening can be offered to high-risk women with a significant family history of cancer (e.g. ovarian, endometrial, breast, gastric, colorectal) this generally involves testing for
BRCA1, BRCA2 and/or HNPCC. Patients who test positive for a mutation can be monitored using CA-125 levels and TVUSS, or may choose to undergo prophylactic interventions such as
BSO +/- hysterectomy.
pelvic examination is not a very useful screening tool it would take 10,000 pelvic exams to detect 1 case of early ovarian cancer!
CA-125 (cancer antigen 125) is a glycoprotein shed by epithelial tumours. The normal range is 30-65IU/L. It is a sensitive test for ovarian cancer but not very specific, as it can also be
raised in several other cancers and a range of benign abdominal and pelvic conditions. Despite the high false positive rate, it has been estimated that CA-125 screening could detect
ovarian cancer up to 3 years earlier.
transvaginal ultrasound (TVUSS) is very useful in detecting ovarian cysts and assessing their malignant potential, but requires specialist sonographers and would be expensive to
perform on a population screening basis.
It is clear that a screening programme for ovarian cancer would be greatly valued, as the disease characteristically does not present until it is at an advanced stage. CA-125 and TVUSS
are both sensitive tests, but carry a 2-3% false positive rate in postmenopausal women this is generally considered too high, as it could potentially lead to unnecessary surgical
interventions and cause harm. However, the use of the two tests together would significantly improve the reliability of screening. The UKFOCSS trial is currently underway to assess the
combined effectiveness of CA-125 and TVUSS in screening for ovarian cancer in high-risk patients with a significant family history.

Cervical Cancer
POST-COITAL BLEEDING IS DUE TO MALIGNANCY UNTIL PROVEN OTHERWISE
.
There are now two cancers that the human race has succeeded in producing effective vaccines against: hepatocellular carcinoma (caused by hepatitis B virus) and more recently
cervical cancer (caused by HPV). Hooray! However, parental controversy surrounding the HPV vaccine and its reduced efficacy in older, sexually active women already exposed to the
virus mean that cervical cancer is something we can unfortunately still expect to encounter for many years to come.
Cervical cancer typically presents with post-coital and/or intermenstrual bleeding, so Ive provided a differential diagnosis for both of these symptoms. Ive also briefly discussed
cervical screening and the HPV vaccine. Its quite a lot of material but its all relevant stuff I hope you find it helpful.
.
Introduction
Anatomy of the female reproductive system
ANATOMY OF THE CERVIX
the cervix is the lower, narrow part (or neck) of the uterus which separates it from the upper part of the vagina. It is about 3cm long and 2.5cm wide. Its physical presence forms a
barrier between the vagina and uterus, and acts as a sphincter which supports the weight of the uterus during pregnancy.
it has an internal os, which opens into the uterus, and an external os which opens into the vagina.
between the internal and external os is the endocervix, which consists of a short narrow canal lined with columnar epithelium which produces several types of cervical mucus. This
canal allows menstrual products to escape the uterus during a period, and allows sperm to enter the uterus to try and find an ovum to fertilise after sex. It also dilates during labour to
allow delivery of the fetus.
the ectocervix is the part which projects into the vagina this is visible on speculum examination and lined with non-keratinised stratified squamous epithelium.
PHYSIOLOGY
the cervix is responsive to the effects of sex hormones: oestrogen causes the cervix to open slightly and the cervical mucus to become thin and receptive to sperm,
whilst progesterone causes the cervix to close and the mucus to thicken to form a plug which blocks off the opening of the uterus.
the area where the endocervix and ectocervix meet is known as the transformation zone (TZ) or squamocolumnar junction. This is where columnar cells of the endocervix undergo
metaplasia and become squamous cells in response to exposure to the harsh acidic environment in the vagina. This is a completely normal physiological process, but it increases the risk
of dysplasia or malignant change occurring in these cells. Most cases of cervical cancer originate in the transformation zone.
women exposed to high levels of oestrogens such as teenagers, pregnant women and those taking the OCP may develop a cervical ectropion. In this, the columnar epithelium of the
endocervix protrudes from the external os, causing the transformation zone to move outwards and producing a red ring on the cervix. It is completely benign, but can cause excessive
discharge or bleeding.
Colposcopic view of the transformation zone (TZ) of the cervix you can see the red columnar epithelium emerging from the external os and the junction where it undergoes squamous
metaplasia (image from Family Practice Notebook http://www.fpnotebook.com)
TERMINOLOGY
cervical cancer is a malignant neoplasm arising from the tissues of the cervix
post-coital bleeding (PCB) is vaginal bleeding occurring immediately after sexual intercourse this has a 6% annual incidence in the UK
intermenstrual bleeding (IMB) is vaginal bleeding (other than postcoital) occurring between periods this has a 17% annual incidence in the UK
.
Epidemiology
cervical cancer accounts for 2% of cancers in UK women (around 3000 cases per year)
it is the twelfth most common cancer, and causes 1% of cancer deaths (about 1000 per year)
there is a lifetime risk of 0.7%, or 1 in 134, for women in the UK
it primarily affects those aged 30-34 (10-15 years after peak incidence of CIN) and the over 80s
incidence has remained stable over the past 10 years
the incidence is much higher in developing countries worldwide, cervical cancer is the second most common cancer in women (around 500,000 cases per year) and the third most
common cause of female mortality (around 274,000 deaths per year)
.
Aetiology and risk factors
the development of cervical cancer is strongly associated with persistent sexually transmitted human papillomavirus (HPV) infection, which interferes with tumour suppressor genes
such as p53 and retinoblastoma to produce viral carcinogenesis
95% of cases are associated with HPV infection, mainly types 16 and 18 and less commonly types 31, 33, 35 and 45
risk factors for exposure to HPV include early first sexual experience, multiple sexual partners (or one promiscuous male partner), history of other STIs, heterosexuality, absence of
barrier contraception and low socio-economic status
immunosuppressed patients are at increased risk such as those with HIV (6x risk), transplant recipients (2x risk) and malnutrition
hormonal factors may have a direct proliferative effect such as early first birth, multiparity and OCP use. Exposure to diethylstilboesterol (which used to be used to prevent
miscarriage) in the womb also increases risk.
smoking reduces cell-mediated immunity and viral clearance
occupational carcinogen exposure tetrachloroethylene is used in dry cleaning/metal degreasing
family history in a first-degree relative confers increased risk, but this is probably due to similar lifestyle factors rather than inherited genetic predisposition.
non-attendance at cervical screening
protective factors include HPV vaccination and attendance at cervical screening
.
Histopathological types
70% squamous cell carcinoma
15% adenocarcinoma
15% mixed pattern

<1% very rare types: neuroendocrine, embryonal rhabdomyosarcoma (sarcoma botryoides), germ cell tumours, clear cell carcinoma, glassy cell carcinoma, lymphoma, leukaemia,
melanoma and metastases from other sites
.
Symptoms
the patient may be completely asymptomatic and cancer may be an incidental finding on cervical smear (severe dyskaryosis or suspicion of invasion) or on samples taken during
treatment for CIN
post-coital bleeding occurs in up to 40% of cases likelihood of cancer is increased if bleeding is profuse or persistent over time, or if it occurs in older women
intermenstrual bleeding
less commonly menorrhagia
increased or altered vaginal discharge some gynaecologists claim this has a characteristic smell
postmenopausal bleeding is a rare symptom in older women <1% of cases will be due to cervical cancer
symptoms of advanced disease include pelvic pain, leg pain and oedema, PR bleeding, altered bowel habit, haematuria, dysuria, urinary frequency, urinary retention, ureteric
obstruction leading to hydronephrosis, fistulae (e.g. vesicovaginal), fatigue and weight loss
symptoms of metastatic disease may include shortness of breath and haemoptysis (lungs), jaundice and abdominal pain (liver), bone pain, hypercalcaemia and pathological fractures
(bones)
.
Signs
general examination findings are usually normal except in advanced disease
abdominal examination may reveal a pelvic mass or craggy hepatomegaly in advanced cases
Cusco speculum examination bleeding, discharge or obvious ulceration/mass
bimanual palpation friable tissue with contact bleeding; obliteration of fornices; roughened, hard, irregular cervix which may be fixed and immobile in locally advanced disease
.
Differential diagnosis postcoital bleeding
trauma
cervical pathology ectropion, cervicitis, cervical or endometrial polyp, cervical cancer
vaginal pathology vaginitis (e.g. severe thrush, atrophic), vaginal cancer
vulval pathology vulval dermatitis, vulval cancer
.
Differential diagnosis intermenstrual bleeding
physiological 1-2% of women have spotting around ovulation, could be due to ectropion
trauma
ovarian pathology oestrogen-secreting ovarian tumours
uterine pathology endometritis/PID, endometrial polyp, endometrial hyperplasia, fibroids, endometrial cancer
cervical pathology cervicitis (e.g. STIs), cervical polyp, cervical cancer
vaginal pathology vaginitis (e.g. severe thrush, atrophic), vaginal cancer
vulval pathology vulval dermatitis, vulval dystrophy, vulval cancer
pregnancy-related early miscarriage, ectopic pregnancy, gestational trophoblastic disease
systemic problem bleeding disorders, metastatic cancer e.g. ovarian, colorectal
iatrogenic trauma, IUCD, progestogens (e.g. POP, Depo-Provera injections), oestrogens (e.g. HRT)
idiopathic dysfunctional uterine bleeding (DUB)
exclude bleeding from somewhere else urethra, bladder, anus, rectum, perineum
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Investigations
IF YOU SUSPECT CANCER, DONT DO A SMEAR SEND THE PATIENT FOR URGENT COLPOSCOPY
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Diagnostic tests for women with suspected cancer include:
history and clinical examination including Cusco speculum examination and bimanual palpation
have a low threshold for performing a pregnancy test
triple swabs to rule out chlamydia and other STIs
colposcopy with punch/loop/cone biopsies of any suspicious areas of the cervix is the key diagnostic test as it allows histological analysis (see the screening section below for details on
how this works)
post-menopausal women may require transvaginal ultrasound scan (TVUSS) and endometrial sampling to rule out endometrial cancer as a cause of bleeding
(Tumour markers are not really used in the diagnosis of cervical cancer CEA, tumour M2-PK and SCC antigen may be raised, but they are associated with many types of cancer so are
not very specific)
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Staging investigations for women with biopsy-confirmed malignancy include:
blood tests FBC (for anaemia), U+E (for renal function), LFTs (for metastases)
imaging CXR for lung metastases, CT abdomen and pelvis for metastases +/- MRI pelvis to show local invasion and pelvic lymph nodes, PET scan may be indicated in advanced disease
cystoscopy to assess bladder invasion
intravenous urogram (IVU) to assess ureteric obstruction
proctoscopy, sigmoidoscopy +/- barium enema to assess rectal compression and invasion
surgical staging may be necessary to provide accurate assessment, as scans can often miss pelvic lymph nodes, and allow tumour debulking this would include an examination under
anaesthetic (EUA) with large loop excision of the transition zone (LLETZ), cystoscopy, hysteroscopy and fractional curettings from the endocervix and endometrium
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Grading how aggressive is it?
Ive had a trawl through Google for useful information about grading of cervical cancers, but havent been able to find much detailed or specific information, which means that it
probably isnt that important compared to staging. Lots of people have tried to develop a special grading system, but none of them have been consistently shown to have a close
correlation with prognosis, so most histopathologists will use a modified version of Broders grading system based on the degree of keratinisation, cellular atypia and mitotic activity of
the cancer cells compared to normal cells:
Grade I well differentiated (good)
Grade II moderately differentiated (OK)
Grade III poorly differentiated (bad)
Grade IV anaplastic (very bad)
Generally, high-grade cancers behave very aggressively but can be very sensitive to chemoradiotherapy. Low-grade cancers grow and spread more slowly but may be less sensitive to
such treatments.
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Staging how far has it spread?
Staging classification uses the International Federation of Gynaecology and Obstetrics (FIGO) system:
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The TNM (tumour nodes metastasis) system can also be used, but generally gynae-oncologists tend to prefer to use FIGO.
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Management
Surgical management depends on the stage of the cancer:
stage 0 (CIN) can be treated colposcopically with LLETZ
stage Ia1 LLETZ or cone biopsy (excision of large cone of cervical tissue under general anaesthetic) can be considered curative if excision margins are clear and preserve fertility;
offer hysterectomy if family is complete
stage Ia2 simple hysterectomy (removal of uterus and cervix) and bilateral pelvic lymph node dissection (BPND)
stage Ib1 radical hysterectomy (removal of uterus, fallopian tubes, cervix, upper vagina and parametrium) and BPND
stage Ib2 and stage IIa radical hysterectomy and BPND can be considered if there is no evidence of lymph node involvement
stage IIb1 or greater in almost all cases, these tumours are considered inoperable. Extremely radical destructive surgery (e.g. pelvic exenteration where all pelvic organs are removed)
may be carried out in small proportion of lymph node-negative cases.
If the patient has not yet completed her family and wishes to preserve her fertility, an alternative to hysterectomy in stage Ia2/Ib1 disease is a procedure called a radical trachelectomy.
In this, most of the cervix and parametrium is removed but the vagina, internal os and uterus are preserved. The internal os is almost completely closed with stitches to allow it to
support a pregnancy. This operation is only a safe option if the cancer is completely removed during the procedure the specimens are checked using frozen section microscopy, and if
the margins are involved, the patient will have to have a hysterectomy to ensure complete excision. If trachelectomy is performed, there is a risk of premature labour and the baby will
have to be delivered by Caesarean section.
This little video from Pedro A Perez-Ponce on YouTube is NOT for the faint-hearted dont let the jazzy Spanish music fool you. It shows a cone biopsy procedure performed
colposcopically using a special diathermy probe. This can be used to treat CIN and early cervical cancer. As you can see, the cone of tissue removed is quite large and extends well into
the endocervical canal. Women who have this procedure are at increased risk of cervical incompetence leading to miscarriage and premature labour.
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Medical therapies may be indicated in more advanced disease:
radiotherapy external beam irradiation and intracavity brachytherapy are usually given after hysterectomy to reduce the risk of recurrence. Radiotherapy is an effective first-line
treatment for inoperable disease, and can also be used to treat recurrences.

chemotherapy when given alongside radiotherapy for inoperable disease, this has been shown to reduce risk of recurrence and death by up to 50%. It can also be used to treat
recurrences. Commonly used drugs are cisplatin +/- topotecan.
advanced metastatic cancer (stage IVb) requires individualised palliative treatment with chemoradiotherapy and symptom control
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Follow-up and prognosis
the overall prognosis is good (66.6% 5-year survival), but varies with the stage of cancer (see above)
women who have conservative treatment of early cervical cancer need to be followed up with regular smears and annual colposcopy to check for recurrence if this is normal after 5
years they can rejoin the normal cervical screening programme
women who have surgery are followed up and monitored by a specialist gynae-oncology centre
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Prevention strategies cervical screening
the NHS cervical screening programme was introduced in 1964 and uses liquid-based cytology to assess the cells of the cervix for premalignant or malignant change
the programme screens 3 million women per year, prevents up to 75% of cervical cancers and is estimated to save 4,500 lives per year in the UK
samples are obtained using a cervical smear test see here for the Geeky Medics OSCE guide
screening is available for women aged 25-65 those aged 25-49 are screened every 3 years, then those aged 50-64 are screened every 5 years
93.5% of adequate smear tests are negative
3.3% show borderline changes requiring a repeat smear in 6 months
in 3.2% of smears, cytology reveals dyskaryosis (abnormalities) in the cells of the cervix, which requires investigation using colposcopy
colposcopy is a procedure during which the cervix is inspected and acetic acid is applied to its surface abnormal cells have increased surface proteins, which are coagulated by the acid
and turn white, producing acetowhite areas which can be biopsied for histological assessment
histology may reveal cervical intraepithelial neoplasia (CIN) this is the term for premalignant, non-invasive neoplastic changes within the cervix, and cannot be diagnosed on a smear
as it requires solid tissue samples
CIN1 usually managed conservatively with 6-monthly colposcopy, LLETZ may be used in some cases e.g. if HPV +ve
CIN2 requires definitive treatment with LLETZ, with 6-monthly follow-up colposcopy
CIN3 requires definitive treatment with LLETZ, with 6-monthly follow-up colposcopy
cGIN (cervical glandular intraepithelial neoplasia) is less common and harder to manage it may indicate neoplasia or adenocarcinoma within the glandular cells of the endocervix or
uterus
HPV DNA testing may be offered to women with borderline smears or mild dyskaryosis to assess cancer risk women who are positive for high-risk types of HPV are more likely to
develop high grade CIN or cancer, whereas lesions associated with a negative HPV test are very unlikely to become cancerous
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Prevention strategies the HPV vaccine
75% of sexually active women are exposed to HPV at some point, but most of them clear the virus
high-risk viral subtypes for cervical cancer include 16, 18, 31, 33, 35 and 45 these are associated with cervical, vaginal, vulval, penile, anal and oropharyngeal cancers
other low-risk viral subtypes, e.g. 6 and 11, may cause genital and anal warts, low-grade CIN and laryngeal papillomatosis
there are two main vaccines available on the current market, Cervarix and Gardasil, both of which are derived from the viral L1 capsid protein and do not contain any genetic material
the vaccination schedule covers all girls aged 12-13 with a course of injections at 0, 1 and 6 months when it was implemented in 2008 there was also a catch-up programme for girls
aged 14-18
the vaccine works best if given before the age of 12 (i.e. before sexual exposure is likely to have occurred), but is licensed for use between the ages of 9 and 26
the vaccination programme is estimated to save about 400 lives per year
CERVARIX (bivalent)
initially used in the UK when vaccination started in 2008 (cheaper)
covers HPV subtypes 16 and 18, which cause 70% of cervical cancers
shows a 66-80% reduction in cases of high-grade CIN and cervical cancer
confers no protection against genital/anal warts or laryngeal papillomatosis
GARDASIL (quadrivalent)
UK screening programme switched to this in September 2012
covers HPV subtypes 16, 18, 6 and 11 and has undergone extensive clinical trials
99% effective if HPV 16 and 18 naive throughout the vaccination process
98% effective if HPV 16 and 18 naive at start of process only
44% effective in all women regardless of HPV status and presence of CIN
confers protection against cervical cancer, other HPV-related cancers, genital and anal warts and laryngeal papillomatosis
The government have yet to make a decision about whether to vaccinate boys as well as girls this would reduce transmission to women and also reduce the incidence of HPV-related
penile, anal and oropharygneal cancers in men. Gardasil is licensed for use in men but is not currently used in the UK.

Endometrial and Uterine Cancer


POSTMENOPAUSAL BLEEDING IS DUE TO MALIGNANCY UNTIL PROVEN OTHERWISE
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Endometrial cancer is a common oestrogen-dependent gynaecological cancer which tends to affect older women. Unlike cervical cancer, it is currently not a screened-for cancer in the
UK, and it is therefore important that doctors maintain a high index of suspicion in order to pick it up as early as possible.
Endometrial cancer typically presents with post-menopausal bleeding, so Ive included a differential diagnosis for this. Ive also outlined potential future screening programmes for
endometrial cancer.
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Anatomy of the female reproductive system
ANATOMY OF THE UTERUS
the uterus (or womb) is a small, hollow muscular organ situated in the female pelvis between the bladder and the rectum. It forms part of the female reproductive system and acts as
the site for fertilisation of an ovum by sperm, and its subsequent implantation and growth into a fetus. It also contracts to expel the fetus during labour.
it has two hollow uterine tubes, which lie in the upper border of the broad ligament and act as a conduit connecting the ovary and peritoneal cavity with the cavity of the uterus. These
guide the passage of the ovum from the ovary to the uterus and are usually the site where fertilisation occurs.
the main part of the uterus is divided into three sections: a fundus lying above the entrance of the uterine tubes, a body lying below the entrance of the tubes, and a lower cervix which
communicates with the upper part of the vagina through a narrow canal.
the wall of the uterus has four distinct layers: the endometrium, myometrium, parametrium and perimetrium (peritoneum)
the endometrium is the thin inner mucous membrane which lines the cavity of the uterus and is shed during the monthly menstrual period. Its high cell turnover makes it the most
common site for cancers of the uterus to develop.
the myometrium is the thick layer of smooth muscle and connective tissue lying beneath the endometrium. It contracts during a period to reduce blood loss (causing cramps) and
during labour to expel the fetus. It often gives rise to benign growths called fibroids (leiomyomas) but rarely undergoes malignant change.
the parametrium is a fibrous fascial layer which lines the outer surface of the upper part of the cervix and separates it from the bladder. It contains the uterine artery and the ovarian
ligament. The parametrium is important, as cervical cancers often spread out to invade it as they grow.
the perimetrium is the membranous layer of visceral peritoneum which lines the outer surface of the whole uterus, apart from a small area anteriorly where it deflects forwards to
cover the bladder.
the visceral peritoneum also forms a large sheet-like fold called the broad ligament which spreads out laterally to connect the uterus to the walls and floor of the pelvis. This contains
the ovarian and uterine arteries and the round ligament.
the uterus is well supported by ligaments which allow it to hold the weight of a pregnancy; these include the levator ani (pelvic floor) and the pubocervical, transverse cervical (or
cardinal), and uterosacral ligaments. If these become lax, the uterus is liable to prolapse.
PHYSIOLOGY
the uterus is extremely responsive to the actions of sex hormones which regulate the changes associated with puberty, the menstrual cycle, pregnancy and menopause
these hormones (especially oestrogens) are implicated in the development of endometrial cancer
oestrogen causes proliferation of the endometrium, with increased vascularity and secretory glands, as well as growth of the uterus during pregnancy
progesterone causes the endometrium to become receptive to implantation of a fertilised ovum. If fertilisation does not take place, a fall in progesterone levels triggers menstruation
and shedding of the thickened endometrial layer.
for more detail on the menstrual cycle, see here for the Geeky Medics guide
TERMINOLOGY
endometrial cancer refers to an oestrogen-dependent malignant neoplasm arising from the endometrium of the uterus
uterine cancer refers to any malignant neoplasm arising from the tissues of the body of the uterus, including the endometrium, myometrium and connective tissues
generally in practice you will notice that the term endometrial cancer is used to refer to cancers of the uterus, as it is by far the most common type
postmenopausal bleeding (PMB) is vaginal bleeding occurring after 12 months of amenorrhoea in a woman of menopausal age or who has experienced the menopause this affects 411% of postmenopausal women and accounts for 5% of all gynaecology outpatient referrals
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Epidemiology
endometrial cancer accounts for 5% of cancers in UK women (around 8000 cases per year)
it is the fourth most common cancer and causes 2.5% of cancer deaths (about 2000 per year)

there is a lifetime risk of 2.35%, or 1 in 43, for women in the UK


it usually affects women in their 50s, 60s and 70s, and is rare in those aged under 40
incidence is increasing, probably due to increasing population age, obesity and use of HRT
it is the most commonly diagnosed gynaecological cancer in developed countries incidence is significantly lower in developing countries, where cervical cancer is far more common
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Aetiology and risk factors
endometrial cancer is believed to result from the stimulation of excess endometrial proliferation by prolonged exposure to unopposed oestrogens which are, for whatever reason, not
being modified and controlled by the effects of progesterone
endogenous oestrogen exposure contributing factors include early menarche, late menopause, delayed childbearing, nulliparity (2-3x risk), obesity (2-3x risk), PCOS, diabetes mellitus
(1.5x risk), metabolic syndrome, anovulatory menstrual cycles (means patient lacks luteal phase progesterone), and oestrogen-secreting tumours e.g. granulosa-thecal cell ovarian
tumours (10x risk)
exogenous oestrogen exposure can result from use of oestrogen-only HRT (1.5x risk), tamoxifen (3x risk) or tibolone (1.8x risk)
sedentary lifestyle has been shown to increase risk
family history is important as inherited genetic traits, such as hereditary non-polyposis colon cancer (HNPCC lifetime risk 40-60%) and PTEN, can confer significantly increased risk
protective factors include parity, OCP use, exercise, smoking, aspirin and drinking coffee
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Histopathological types
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TYPE I ENDOMETRIOID HISTOLOGY (75-80%)
this typically occurs in pre- and perimenopausal women
it may be preceded by premalignant atypical endometrial hyperplasia (EH)
it is associated with oestrogen exposure, a low grade and a favourable prognosis
75% endometrioid adenocarcinoma, which has squamous (aka adenosquamous), villoglandular, secretory and ciliated cell variants
5% mucinous adenocarcinoma
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TYPE II NON-ENDOMETRIOID HISTOLOGY (~20%)
this occurs more frequently in postmenopausal women
it may be preceded by premalignant endometrial intraepithelial carcinoma (EIC)
it has little association with oestrogen exposure and tends to be high grade and more aggressive
5-10% serous carcinoma
1-5% clear cell carcinoma
~10% mixed adenocarcinoma
<1% very rare types: squamous cell carcinoma, neuroendocrine tumours (large cell and small cell), transitional cell carcinoma, undifferentiated carcinoma, metastases from other sites
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UTERINE SARCOMAS (<5%)
these are tumours arising from the myometrium and connective tissues of the uterus
this is a rare diagnosis with an aggressive clinical course and a poor prognosis
2% leiomyosarcoma
1% carcinosarcoma (aka mixed mesodermal Mullerian tumour)
<1% endometrial stromal carcinoma
<1% very rare types: fibrosarcoma, adenosarcoma, undifferentiated sarcoma, metastases
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Symptoms
postmenopausal bleeding is the classical presenting symptom 8-10% will have endometrial cancer, ~30% will have endometrial hyperplasia (of which ~5% will be atypical), ~10% will
have endometrial polyps and the remaining 50% will have endometrial atrophy due to menopause
likelihood of cancer is increased if bleeding is profuse or persistent over time, particularly if it occurs in an older woman
in pre- or perimenopausal women (20-25% of cases), symptoms can include intermenstrual bleeding or menorrhagia
increased vaginal discharge
pyometra (a collection of pus in the uterine cavity) is a less common but important symptom 50% of postmenopausal women with pyometra will have an underlying malignancy
rarely (1% of cases), it may be an incidental finding on a cervical smear
symptoms of advanced disease include pelvic pain, pelvic mass, leg swelling, haematuria, PR bleeding, weight loss and fatigue
symptoms of metastatic disease may include cough, shortness of breath or haemoptysis (lungs), abdominal pain and jaundice (liver) bone pain, hypercalcaemia and pathological
fractures (bones)
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Signs
general examination findings are usually normal except in advanced disease
abdominal examination may reveal a pelvic mass in advanced cases
Cusco speculum examination is usually normal; very rarely cancer may be visible in the cervix
bimanual palpation is usually normal, but the uterus may be enlarged or immobile in locally advanced disease
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Differential diagnosis postmenopausal bleeding
trauma
ovarian pathology oestrogen-secreting ovarian tumours e.g. granulosa-thecal cell
uterine pathology endometrial atrophy, endometritis/PID, endometrial polyps, endometrial hyperplasia, endometrial cancer
cervical pathology cervicitis, cervical polyps, cervical cancer
vaginal pathology vaginitis (e.g. severe thrush, atrophic), vaginal cancer
vulval pathology vulval dermatitis, vulval dystrophy, vulval cancer
systemic problem bleeding disorders, metastatic cancer e.g. ovarian, colorectal
iatrogenic trauma, oestrogens e.g. HRT
exclude bleeding from somewhere else e.g. urethra, bladder, rectum, anus or perineum 0.7% of patients with postmenopausal vaginal bleeding will actually have bladder cancer
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Investigations
Diagnostic tests for women with suspected cancer include:
history and clinical examination including Cusco speculum examination and bimanual palpation
it is always worth performing a cervical smear while youre down there if the patient is due one, but if there is any suspicion of cervical cancer she should be referred for urgent
colposcopy
transvaginal ultrasound (TVUSS) to measure endometrial thickness >5mm is worrying (7.3% risk of cancer), but remember in younger women the endometrium may be up to 12mm
thick if they are about to have their period
endometrial sampling should be performed in all women over 40 and those with worrying features; this can either be done as a Pipelle biopsy or a formal hysteroscopy
outpatient Pipelle biopsy is easily performed in clinic, but it only samples about 4% of the endometrial surface and is performed blindly, so the abnormal area could easily be missed
hysteroscopy and curettage biopsy is performed as an inpatient under general anaesthetic this allows visualisation of the endometrium and sampling of most of its surface, but
carries an anaesthetic risk and is more lengthy and expensive to perform
Most gynaecology units now have a one-stop clinic for 2 week wait endometrial cancer referrals this usually comprises TVUSS on arrival, followed by assessment by a doctor and
further investigations (Pipelle biopsy or hysteroscopy) as required.
(Tumour markers are not really used in the diagnosis of endometrial cancer CA-125 may be raised, but is much more strongly associated with ovarian cancer and is also associated with
other cancers)
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Staging investigations for women with biopsy-confirmed malignancy include:
blood tests FBC (for anaemia), U+E (for renal function), LFTs (for metastases)
pre-operative assessment G&S, ECG, CXR
surgical staging is the gold standard for staging of endometrial cancer it allows removal of the tumour at the same time as gathering required samples for histopathological
assessment
imaging is rarely required if surgical staging is carried out, but in certain cases of advanced disease or where the diagnosis is uncertain, imaging could involve MRI pelvis to assess local
invasion and pelvic lymph nodes +/- CT abdomen and pelvis or PET scan for metastases
invasive tests such as cystoscopy, proctosigmoidoscopy and barium enema are generally not required but could be used to assess the extent of invasion in locally advanced disease
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Grading how aggressive is it?
Endometrial cancer is graded using the FIGO grading system:
G1 5% or less of a non-squamous or non-morular solid growth pattern (good)
G2 6-50% of a non-squamous or non-morular solid growth pattern (OK)
G3 >50% of a non-squamous or non-morular solid growth pattern (bad)
Grading is used alongside staging to provide an estimate of the patients prognosis. Survival is roughly halved with a grade 3 (high grade) malignancy.
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Staging how far has it spread?
Endometrial cancer is staged by the International Federation of Gynaecology and Obstetrics (FIGO) system. The TNM system can also be used, but generally gynae-oncologists prefer to
use FIGO.

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Uterine sarcomas each have their own different FIGO staging systems, and carry a much poorer overall prognosis. With both endometrial and uterine cancers, prognosis depends on
grade as well as stage.
Management
Surgical management is the mainstay of treatment, and allows formal surgical staging as well as removal of the tumour:
stage I total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO)
stage II exploratory laparotomy and surgical staging with radical hysterectomy, bilateral pelvic lymph node dissection (BPND) +/- para-aortic lymph node clearance, pelvic and
peritoneal washings for cytology and omental sampling if indicated
stage III/IV exploratory laparotomy with maximal tumour debulking and full surgical staging as above
laparoscopic hysterectomy is becoming more popular, and studies have shown equivalent survival rates and better post-operative recovery in early stage disease
Medical therapies are used alongside surgery in more advanced disease:
radiotherapy external beam irradiation and/or intracavity brachytherapy are given post-operatively to women with stage Ib grade 3 disease, and stage II-IV disease of any grade
the PORTEC trial showed that adjuvant radiotherapy reduces the risk of local pelvic recurrence, but confers no survival advantages to women with disease severity less than stage Ib
grade 3. Radical radiotherapy can also be used effectively to treat local recurrences (50% response rate), and as a primary treatment in frail patients unsuitable for major surgery.
chemotherapy can be used in stage III/IV disease, but response rates in endometrial cancer tend to be poor. Commonly used drugs include doxorubicin, paclitaxel and
carboplatin/cisplatin.
hormonal therapies such as tamoxifen and progestogens can be used in advanced or recurrent disease, with a reasonable response rate (15-30%). They can also be used for palliation
of symptoms such as excessive bleeding.
advanced metastatic cancer (stage IVb) requires individualised palliative treatment with tumour debulking, chemoradiotherapy and symptom control.
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Follow-up and prognosis
the overall prognosis is good (77.3% 5-year survival) but varies significantly depending on the stage, grade and type of cancer (see above)
women who undergo surgery for endometrial cancer are generally followed up and monitored by a specialist gynae-oncology centre
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Prevention strategies potential for screening
There are several potential future options for screening for endometrial cancer:
genetic screening can be offered to high-risk women with a significant family history of cancer (e.g. endometrial, ovarian, breast, GI, urothelial) this generally involves testing for
HNPCC and PTEN. Patients who test positive for a mutation can be monitored using TVUSS and endometrial sampling, or may choose to undergo prophylactic interventions such as
hysterectomy.
cervical screening contributes slightly to screening for endometrial cancer 1% of cases are incidental findings on smear tests.
transvaginal ultrasound (TVUSS) can be used to assess endometrial thickness if >5mm there is a 7.3% likelihood of cancer, if <5mm there is a 2% likelihood of cancer.
endometrial sampling using Pipelle biopsy is an easy way to screen for premalignant and malignant changes endometrial hyperplasia represents a high risk of malignancy and is easily
treatable once diagnosed.
However, none of these methods have been shown by studies to reduce mortality from endometrial cancer. It is also arguable that as both endometrial hyperplasia and endometrial
cancer tend to present early with postmenopausal bleeding, and have an excellent prognosis when diagnosed at an early stage, the need for a population screening programme is less
compelling when compared to something like ovarian cancer, which has few symptoms and tends to present late with a poor prognosis.
Currently screening is only recommended in women with a proven genetic predisposition to endometrial cancer.

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