LCRS: Human Life Cycle

Usama Asif

HUMAN LIFE CYCLE SESSION 5:

The uterus
LECTURE 14:

The endometrium in clinical practice

PROFESSOR JENNY HIGHAM (j.higham@imperial.ac.uk)
Learning objectives
1. To understand how the phases of the endometrium are relevant in clinical medicine
2. To realise the key importance of the endometrium in menstruation & implantation
3. Understand how abnormal growth of the endometrium leads to the clinical problems of hyperplasia &
cancer
4. Comprehend how the endometrium can be manipulated for contraceptive purposes
5. Understand the consequences of destruction of the endometrium
6. Understand how endometrium outside the uterine cavity can lead to the clinical problem of
endometriosis
7. Describe how the endometrium is imaged & sampled in clinical practice
Introduction
- The endometrium is vital to many aspects of life; in clinical practice, the endometrium plays a
huge role in fertility, or the lack of it
- The biological development of the endometrium shows that it is designed to renew itself,
anticipating pregnancy the cyclical endometrial changes will prepare it for implantation and
subsequent pregnancy
o Nowadays, women have more periods than previously i.e. they experience around 400 in
their lifetime vs. 40 for previous generations
o Lactational amenorrhoea is the biggest contraception ever
- The embryo will not implant unless the endometrium is favourable i.e. it is in the so-called
window of implantation the remaining time is a period of
infertility
- Knowing about implantation, we know that we can exploit
this. For example, we exploit the endometrial cycle and its
control in contraception (i.e. where we give exogenous
oestrogen and progesterone, or progesterone only, in order to
make the endometrium unfavourable for sperm, fertilisation
and/or implantation
o It is also exploited when there is a pregnancy scare in
this situation, we cannot inhibit ovulation or gamete
fusion, but we can make the endometrium hostile to
implantation by giving high dose progestogen, or an
IUCD. Note that this is not completely effective, but it
is more effective than doing nothing
- It is also exploited when one wants to conceive, i.e. to induce
ovulation, using IVF and getting the endometrium ready
i.e. certain procedures or treatments will optimise the chance
of success

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Some notes on the menstrual cycle

- Remember that following implantation, under the influence of
progesterone, the endometrium undergoes decidualisation and
gets ready
- If implantation does not occur, the embryo is expelled along with
the superficial endometrial lining this is true of the unfertilised
egg as well
o Essentially, if the woman does not get pregnant the egg is
shed
- This reinitialises the cycle for the next egg. The basal endometrial layer will regenerate and get
ready for the next cycle
- There is remarkably rapid epithelialisation, without scarring, unlike other parts of the body when
they are bled. It is interesting, and there is research being undertaken into this mechanism because,
obviously, this level of healing is useful in other parts of the body
- The (re)growth of the endometrium is tightly controlled
- Quite surprisingly, there is stuff in the period other than blood and it is only 10-70% blood
Hyperplastic endometrium and cancer
- As said above, growth of the endometrium is very tightly controlled, but it can go wrong
- The most common problem is the issue of excess and uncontrolled endometrial growth, leading to
hyperplasia of the endometrial tissue. This can topple into cancer
- The growth of these cells is stimulated under the influence of oestrogens. Under the influence of
progesterones, these cells will stop dividing, but will undergo differential changes to become
more glandular, i.e. secretory this could be useful as high dose progestogens can be used to
potentially treat endometrial hyperplasia, in its early stages
- Abnormal cell forms in association with hyperplasia are called atypia, and carry a risk of
progressing into endometrial cancer
- Endometrial cancer is associated with infrequent ovulation and obesity. It also occurs most
commonly in postmenopausal women over the age of 50
o Obesity is an interesting risk factor, and this is the case because fat tissue releases a weak
oestrogen
- The majority of endometrial cancers are adenocarcinomas, due to the nature of the endometrial
tissue i.e. it is glandular tissue
- It tends to get diagnosed early because one of the presenting symptoms is bleeding after
menopause, which can be alarming it is one of Zolas triggers however, cancer is only a
potential cause. Only 10% turn out to be malignant
- Endometrial cancer is also related to polycystic ovary syndrome
Menorrhagia
- Menorrhagia, i.e. excessive heavy periods is one of the most common reasons for women to
consult their GP and/or their gynaecologist around 15% of
the population have suffered from menorrhagia in their lifetime
o 1 in 7 to 10, i.e. most women are ovulating regularly,
and there is nothing to be found sometimes. This is
called dysfunctional uterine bleeding
- The control mechanisms for menstruation are complex and
understood poorly
- Some people are debilitated by heavy bleeds and a heavy
enough bleed can cause anaemia

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Endometriosis
- When the endometrium is in the wrong place, it can be very destructive, i.e. endometriosis
- Endometriosis is a gynaecological medical condition in which cells from the lining of the uterus
(endometrium) appear and flourish outside the uterine cavity, most commonly on the membrane
that lines the abdominal cavity
o Remember that the uterine cavity is lined with endometrial cells, which are under the
influence of female hormones. Endometrial-like cells in areas outside the uterus (i.e. as in
endometriosis) are influenced by hormonal changes and respond in a way that is similar
to the cells found inside the uterus. Symptoms often worsen with the menstrual cycle
- The deposits, as said above, commonly occur in the pelvis i.e. near the Fallopian tubes and the
ovaries
- It occurs due to the migration of these cells to other parts of the body
- Endometriosis is associated with the common and debilitating symptoms of:
o Painful periods i.e. dysmenorrhoea
o Pain with intercourse i.e. dyspareunia
o Infertility
- NB: Adenomyosis is like endometriosis, but is distinct and
refers to the when pockets of the myometrium migrate
into the wall of the uterus
- A chocolate cyst of endometriosis can be seen on
examination. When these cysts bleed and stop repeatedly
in the same area, they leave a gloopy solution
- There is not a strict correlation between the symptoms
all treatments needs to be individualised
- Treating endometriosis involves suppression of the
menstrual cycle using drugs, or surgery to remove the
ectopic endometrium
Imaging and sampling the endometrium
- Imaging is done via ultrasound and sampling via a biopsy
- Ultrasound is a cheap, quick and relatively non-invasive
method of assessing the endometrium
o With ultrasound, one can assess endometrial thickness and the structure of the uterus in
healthy women, youd expect it to be thick during ovulation and thin in menopause etc.
o In premenopausal women, endometrial thickness will vary according to the stage of the
menstrual cycle. In postmenopausal women, the thickness should not exceed 5 mm

Sampling the endometrium is done with various instruments it may be taken in the outpatient
clinic via an endometrial sampler for the investigation of irregular bleeding, thickened
endometrium or if there is suspicion of endometrial cancer

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If needs be, a hysteroscopy might be indicated and it is used to

visualise the endometrium one can see the whole of the uterine
cavity and as the scope progresses in, as it does so, you can assess the
cervix too. A biopsy alone might miss pathology
o It is usually done to investigate persistent irregular or
abnormal menstrual bleeds
o It allows the directed biopsy of abnormal areas
o Magnifies and allows visualisation of the interior
o It can be performed as an outpatient using specially designed
fine instruments
o It is the most accurate imaging method, though not 100%

Amenorrhoea
- Amenorrhoea is when women have absent periods
- It may occur if the regenerative (basal) endometrial layer is destroyed
o It can be done deliberately i.e. induced as treatment, using heat
o The uterine cavity loses the endometrial covering and is replaced by scar tissue. This
results in lighter or no periods
o Hormonal levels will all be normal, and ovulation will still occur
o Id imagine this is therapeutic
Manipulating the endometrium
- The intrauterine system/device, called Mirena and commonly
known as the coil, has influenced gynaecology for two reasons
o There is enough progesterone in the core to slowly leak
out for 5-7 years
o In response to administration of the coil, there is a turn
off and eventual atrophy of the endometrium
o This is useful for two reasons:
It is a very effective contraceptive and is as
effective as sterilisation, but can be reversed
within 30 years
It is a product license for the treatment of menorrhagia (80% less blood loss) with
no need for hysterectomy

LCRS: Human Life Cycle

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LECTURE 15:

The cervix
PROFESSOR JENNY HIGHAM (j.higham@imperial.ac.uk)
Learning objectives
1.
2.
3.
4.
5.
6.
7.
8.
9.

To understand the appearance of the normal cervix

The appearance of the cervix in association with common gynaecological problems
To be able to describe the UK cervical screening programme
Understand how a cervical smear is taken
Understand the role of Human Papilloma Virus in the development of cervical smear abnormalities &
cervical cancer
Understand the clinical procedure of colposcopy
Understand how the cervix is assessed before the onset of labour
To be able to describe the process of cervical effacement and dilatation in labour
How examination of the cervix is used to assess the progress of labour
Do you have a normal cervix?
Why have a smear test?
- Cervical screening is ideal for population surveillance to prevent cervical
cancer
- It looks at women at increased risk of cancer, and detecting cells that are on
an abnormal journey
o Acceptable to women
o Accurate test
o Abnormal result detects a readily treatable condition, as opposed to late stage cancer
o Treatment prevents progression of disease from abnormal cells to cancer
o Screening and treatment are costeffective
Cervical screening
- Cervical screening is an automated screening programme. It is primary care centre based and uses
a computerised call and recall programme whereby women at risk are called in, and recalled if
anything comes up
- There are financial incentives for comprehensive screening and there has also been an effect on
mortality and incidence of cervical cancer following the implementation of the screening
programme
o This not only prevents deaths, but also relieves some of the financial burden of treating
women with cervical cancer
The normal cervix
- The squamo-columnarjunction/transformation zone is a very dynamic
(growing, changing, dividing) area where non-keratinising squamous vaginal
epithelium meets the glandular lining of the cervical os (external cervical
opening/orifice)
o The dynamic changes of this zone is affected with age and hormones
o The oestrogen rise in puberty, pregnancy, and whilst on the
contraceptive pill leads to exposure of the glandular tissue
o Post-menopause, there is a fall in oestrogen with a regression in the glandular tissue
o These dynamic changes make it vulnerable

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The view of the cervix is known as ectropion

The cervix is visible with a Cuscoes speculum you rotate the spatula/brush through 360 degree
focus on the SCJ
o You smear on glass slide immediately, and fix the sample with 95% ethyl alcohol or an
aerosol alternative
o Liquid based cytology has improved the sensitivity of smears hugely
o Normal cells have a regular shape with a very small nucleus
o You can also look for nabothian follicles, mucus retention cysts or ovulatory mucus
NB: Screening should start at 25 years, and continue for every three years from the ages of 2549,
every five years from 5064 and only if there are noted abnormalities should the screening be
continued past the age of 65
o The routine screening of less than three years is not cost effective
There is a debate about starting at 25 year evolution to cancer and age of first sex isdecreasing

The abnormal cervix

- Abnormal cervices can result from inflammatory change, infection, human papilloma virus,
cervical intraepithelial neoplasia (CIN) or invasive carcinoma
CIN (cervical intraepithelial neoplasia)
o This is a premalignant and treatable, and
there are three stages of classification:
CIN1 is when there are dysplastic
changes seen that involve a third
of the squamous epithelium
CIN2 is when the lower twothirds are involved
CIN3 is when the entire depth is
involved, but note that the
basement membrane is not
breached
- Cellular changes associated with CIN include:
o Instead of becoming thin and pancake-like, the cells
become plumper and fatter
o The nucleus gets bigger, occupying a greater proportion
of the cell and is disorganised and expands
o To the naked eye, this will look normal. However
cytology will show a mixture of cells with some
dyskaryosis (cellular abnormalities of these cells). The smear will show mild, moderate or
severe dyskaryosis, which will indicate CIN1, CIN2 or CIN3 respectively
- When the cells cross the basement membrane, this is the development to cancer

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Human papillomavirus (HPV)

- So far, around 107 different DNA virus types of HPV have been identified and its prevalence may
be as high as 80%
- There are two categories of warts: high risk or lower risk
o High risk warts, classically caused by HPV number 16 and 18, is incorporated into cells,
causing damage and increasing the risk of cervical cancer
- We can type individual HPV to determine whether it is high risk or low risk
- The majority of squamous cancers can be prevented using the vaccine Gardasil there isgood
theoretical success with this, but the effect is not completely known
- Warts can be treated with topical trichloroacetic acid podophyllin, diathermy and cryotherapy
Colposcopy
Indications
- A colposcopy is an image taken of the surface of the cervix using an instrument called a
colposcope. It is used in conjunction with the speculum
- Indications for a colposcopy are:
o Cervical smear suggesting dyskaryosis
o Persistent inflammatory or inadequate smears
o Glandular neoplasia (much less common)
o Abnormal cervix
Procedure
- Colposcopy is an outpatient procedure with a low power binocular microscope (magnifying 6
40x), giving a good view of the transformation zone and vascular patterns
- A camera is attached, so that a complete expanded view can be viewed on a large screen
- Normal vasculature is organised, with large trunks progressing to smaller trunks. Cancer
vasculature is very abnormal and irregular branching
- Weak acetic acid is used on the surface of the cervix. This coagulates nuclear proteins, turning
white in abnormal areas, i.e. highlighting areas of dysplasia
o It is able to do this due to the enlarged disorganised nucleus
- A punch biopsy of these areas can be performed for histological confirmation
- This is an example of see and treat attitude
- Treatment is usually by heat or excision
Treatment
- If one finds CIN1 observe and repeat the colposcopy
- If one finds CIN2/3 one can excise of the transformation zone by an electrical current or laser i.e.
cauterising it
o NB: approximately 30% of CIN3 progresses to invasive disease over 10 years
- Invasive carcinoma (either squamous or adenocarcinoma) require examination under anaesthetic
to decide the stage/spread
o If found early, the cancer can be removed surgically with or without radiotherapy or
chemotherapy
Followup
- See 6-8 months post treatment, usually only performing a smear test
- Redo the colposcope in abnormal smears

LCRS: Human Life Cycle

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LECTURE 16:

Birth
PROFESSOR JENNY HIGHAM (j.higham@imperial.ac.uk)
Learning objectives
1. To understand the mechanism by which the uterus expels the foetus
2. To be able to describe the three stages of labour
3. Understand delivery of the placenta and the mechanisms of haemostasis after delivery
Introduction
- There are three stages of labour
o First stage this occurs from the onset of regular contractions and associated dilatation
andeffacement of the cervix until full dilatation, which is around 10 cm
o Second stage this occurs from full cervical dilatation to the delivery of the baby
o Third stage this occurs when there is the delivery of the placenta and membranes
Birth success
- Labour is very difficult due to the
relative size of the baby head and
the pelvis. Success in birth depends
on:
o The powers strength and
frequency
of
uterine
contractions
o The passenger size and
position of the baby
Initially the baby faces left or right,and then during birth the baby often moves to
face downwards.
A baby that swivels around to lie in a posterior position often lengthens labour
Baby size is mostly determined by proportions of the mother
o The passage especially the bony structures of the pelvis
During pregnancy, joints of the pelvis become softer with tissue, thereby becoming
less rigid. This allows for more flexibility to facilitate birth
First stage of labour
Contractions
- Contractions start at the fundus, or the top of the uterus, where the
myogenic pacemaker is
- The contractions spread downwards, with the intensity greatest at
the top these are therefore termed fundally dominant contractions
- Contraction is followed by relaxation to allow blood flow
- These are very important to progress labour, but this relaxation is
equally important to maintain adequate blood supply to the foetus,
whilst allowing the mother to recover
- The definition of labour is when there is the onset of regular uterine
contractions accompanied by the progressive effacement and
dilatation of the cervix
- Note that it is not entirely clear what initiates human labour, but people have some idea

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Cervical changes
- The cervix needs to undergo some changes in order to prepare itself for birth
- For example, it needs to undergo effacement this
is where the cervix gets thin and flat
o It transforms from a long firm (3 cm)
cylinder to a flat structure
o Once it is very thin, the cervix can move
away to allow passage of the baby
o These changes result from fluid in hydrophilic mucopolysaccharides between the collagen
mesh ripening
o Prostaglandins inhibit collagen synthesis and encourage collagen breakdown
- The cervix also needs to undergo dilatationi.e. the cervix needs to open, progressing from 0 to 10
cm

Descent and foetal passage

- As the foetus is ready to be delivered, the uterine muscle starts to undergo contractions
accompanied with partial etraction/shortening
o Gradually, the muscles are shortened and the capacity of the
uterus decreases, therefore the baby has no option but to
descend
- It is the later that maternal effort of pushing the baby through the
vagina that it is necessary to complete birth
- At the pelvic inlet, there is greater space laterally, therefore the
baby tends to look sideways
- The only structure here is the sigmoid colon, which, when empty,
provides increased space as the baby presses on it, it will
sometimes cause the contents of the colon to empty
- At the pelvic outlet, there is more space anteroposterioly, therefore
the baby tends to do a quarter turn
- The pubic symphysis tends to be flexible to provide more space for
end delivery
- Finally, the baby undergoes restitution to become more comfortable.
- If there is not enough space at final delivery, and episiotomy (see to the
right) can be used to increase the diameter of the passage for the foetus
to pass through
- This procedure is much safer than a tear. This increases the soft tissue
space

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Abnormal births
- The majority of births are normal, but sometimes, assistance is needed for foetal or maternal
reasons
- Forceps or a ventouse i.e. a suction cup, are used to assist delivery
Caesarean sections
- Caesarean sections are required for 20% of all births, with rates rising in recent years
- Many women opt for a Caesarean birth, as it is planned and predictable
- In cases of a breech baby, i.e. when the baby exits the mother feet first, instead of head first, and
this is dangerous. This is indicative of a Caesarean section too
The third stage of labour
- This is the delivery of placenta and membranes associated with it. The ejection of these structures
is helped by uterine contractions and gentle cord traction
- The vascular placental bed in the inner wall of the uterus is then left exposed
- The average blood loss during this stage is 300 ml, but haemorrhage is a real risk, occurring in 5%
of cases
- However, diet, increased clotting ability etc. have been developed to try and reduce this risk.
Other things to reduce the risk of haemorrhage include:
o Increased maternal coagulating ability during pregnancy
o Increase in circulating blood volume
o Contracting down of uterine muscle fibres to
close vessels
o Contraction helped by drugs oxytocin and
ergometrine syntometrine. These have had a
worldwide impact on reducing maternal deaths
Oxytocin
is
short
acting,
with
ergometrine
giving
a
sustained
contraction
o Bimanual compression can also be used its
pretty grim, where you fist the woman with one
hand and push down at the fundus with the
other see image to the right
Timings
- The first stage lasts 5-16+ hours
o From the onset of regular contractions and associated dilatation and effacement ofthe
cervix until full dilatation i.e. 10 cm
o With increasing numbers of pregnancies, this time reduces
- The second stage lasts 30 minutes to two hours, with active pushing by the mother for an hour
o This is from full cervical dilatation to the delivery of the baby
- The third stage lasts 10-30 minutesand involves the delivery of the placenta and membranes