Human Life Cycle 5 - Endometrium, Labour and Birth

Human Life Cycle 5 - Endometrium, Labour and Birth

Anil Chopra

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

8.  To understand the appearance of the normal cervix

9.  The appearance of the cervix in association with common gynaecological problems

10. To be able to describe the UK cervical screening programme

11. Understand how a cervical smear is taken

12. Understand the role of Human Papilloma Virus in the development of cervical smear abnormalities & cervical cancer

13. Understand the clinical procedure of colposcopy

14. Understand how the cervix is assessed before the onset of labour

15. To be able to describe the process of cervical effacement and dilatation in labour

16. How examination of the cervix is used to assess the progress of labour

17. To understand the mechanism by which the uterus expels the foetus

18. To be able to describe the three stages of labour

19. Understand delivery of the placenta and the mechanisms of haemostasis after delivery

Clinical Aspects of the Endometrium

Fertility: there are a number of endometrial changes that occur before pregnancy, and embryos will only implant when the conditions are favourable – the main reason for IVF failure is implantation failure.

After implantation, under the influence of progesterone the endometrium undergoes decidualisation. If implantation does not occur, the embryo is expelled along with the superficial endometrial lining.

If the mother is not pregnant then the endometrium is shed, and the menstrual discharge is made up of blood and other such secretions. The basal endometrial layer regenerates for next cycle.

Contraception: prevention of embryo implantation by interference with embryological activity.

·  Intrauterine contraceptive devices (IUCR) – this is where a coil (made out of copper, or progesterone-secreting) is inserted into the upper vagina which prevents alters the endometrium (and will not allow it to be favourable to implantation – i.e. these coils will not allow the endometrium to become thick).

·  Combined oral contraceptives and progestogen-only contraceptives affect the endometrium by making it become thin (or will not allow it to become thick) thus making the endometrium not suitable for pregnancy.

·  Post-coital (emergency) contraception. This is otherwise known as the “morning-after pill”. This is where a high dose of progesterone is administered after unprotected sexual intercourse has taken place. The high dose of progesterone will again thin the endometrium making it inhospitable for the embryo to implant. This method of contraception can only have affect if it is administered within 72 hours of intercourse taking place. There is an initial dose which is followed by a second dose taken 12 hours later.

Menorrhagia: heavy and prolonged menstrual periods. It is one of the most common reasons women visit their GPs and gynaecologists.

·  In most cases, women have heavy and regular bleeding, but irregular (anovulatory) bleeding is also common. A majority of cases, have dysfunctional uterine bleeding, not associated with any obvious pelvic or systemic pathology

·  Causes for menorrhagia seem to be linked to local endometrial changes, mainly…

·  Increased prostaglandins – vasodilating à increased bleeding from the spiral arteries in the endometrium.

·  Reduced endothelins – vasoconstricting à increase bleeding as opposed to stopping the bleeding as endothelins would normally do.

Hyperplasia and Endometrial Cancer: excess uncontrolled growth of the endometrial cells which is normally under tight control. It may regress with the administration of progestogens.

·  Normal growth of vascular, stromal and epithelial endometrial cells is tightly controlled.

·  Excess and uncontrolled growth may lead to hyperplasia (pre-cancer).

·  The hyperplasia may regress with administration of progestogens. The abnormal cells which form in association with hyperplasia are called “atypia” and carry a risk of progressing to endometrial cancer.

Endometrial cancer:

·  affects mostly postmenopausal women (in the age range of about 55-65).

·  Most endometrial cancers are adenocarcinomas (with some squamous elements).

·  Commonly the cancer will spread locally (metastasise) and to the pelvic lymph nodes.

·  Endometrial cancer commonly presents with postmenopausal bleeding. About 10% of women with postmenopausal bleeding will have endometrial cancer.

The risk factors for endometrial cancer include:

·  Unopposed oestrogens (mainly oestradiol) – for example in women who have PCOS (polycystic ovary syndrome – remember women with PCOS have high oestrogen levels, and do not have a progesterone-dominant phase in their menstrual cycle).

·  Obesity – this is linked to women who are obese having more circulating oestrogen compounds.

·  Diabetes

·  Never pregnant

Diagnosis of endometrial cancer involves hysteroscopy being performed, and a biopsy of the suspected cancerous endometrium being taken.

Treatment – total hysterectomy, and removal of tubes and ovaries, lymph node biopsy, and radiotherapy for positive nodes

Endometriosis: a condition in which the cells of the endometrium are found growing outside the endometrium.

v  The endometrium is unique in its cyclical regenerative process.

v  It occurs most commonly in the pelvis, but can occur elsewhere.

v  Endometriosis is thought to be a result of “retrograde-menstruation” – this is where menstruation does not occur through the vagina; instead the menstrual matter migrates down the fallopian tubes and implants.

v  Endometriosis is associated with several common and debilitating symptoms. The most common include:

o  Infertility.

o  Painful periods [dysmenorrhoea]

o  Pain with intercourse [dyspareunia]

o  Infertility

o  Menstrual irregularity.

o  Menorrhagia.

o  Adenomyosis – this is where endometrium deposits are found in the uterine muscle. It causes a lot of pain (especially during menstruation) and can also cause the uterus to be enlarged.

Treatment involves surgical removal of the endometriosis material: conservative (i.e. removing only the ectopic material and perhaps affected areas of the endometrium) or hysterectomy. The alternative to this is suppression with drugs

Amenorrhoea: the absence of periods. This occurs when the regenerative basal layer of the endometrium is destroyed. This may be accidental, such as at the time of uterine evacuation after a miscarriage or deliberate, using heat (Endometrial ablation). Uterine cavity looses endometrial covering and is replaced by scar tissue. Hormone levels are usually still normal and ovulation can still occur.

Tests and Investigations

Ultrasound:

·  probably the most commonly used means of imaging the endometrium. It is a cheap, quick and relatively non-invasive.

·  It allows you to assess the endometrial thickness (in postmenopausal women – should not exceed 5mm) and intrauterine and intramural structures.

·  Saline can be used to outline intrauterine pathology

·  In premenopausal women, endometrial thickness will vary according to the stage of the menstrual cycle

Endometrial biopsies:

·  These may be taken in an outpatient clinic for a number of reasons, such as; investigation of irregular bleeding, investigation of a thickened endometrium, if there is a history of hyperplasia and/or atypia, and if there is a high suspicion of endometrial cancer.

·  This type of biopsy will be a “blind biopsy”, that is it doesn’t sample all of the endometrium, and as a result, biopsy alone often misses endometrial pathology. Therefore hysteroscopy is recommended in women who require endometrial biopsies to be taken.

Hysteroscopy:

·  offers both a diagnostic and surgical means of investigating and operating on the endometrium.

·  Hysteroscopy allows you to view the endometrium directly and in real-time, and the whole endometrial cavity can be seen.

·  It allows direct biopsy of any suspicious or definitely abnormal areas.

·  Can asses suitability of the pathology for removal (for example, a simple ovarian cyst can be identified as that and therefore can be removed without the need for MRI imaging etc.).

·  This procedure can be performed in the outpatient clinic using local anaesthetic.

·  It is the most accurate imaging technique available at present (but is still not 100% accurate).

·  It is an invasive, very expensive and time-consuming procedure, and so cannot be performed as routinely as ultrasound though it is clearly a better technique than ultrasound.

·  Unfortunately, hysteroscopy magnifies and distorts the image seen, and so does not give a “true-picture” of the endometrium.

·  Surgeons use a 30° “scope” to allow visualisation of the anterior and posterior walls of the endometrial cavity.

·  Surgical uses:

o  destroy the endometrium to achieve amenorrhoea (heat – electrical, fluid or microwave).

o  It can also be used to remove an intrauterine pathology, such as a submucous fibroid, or polyps in the endometrial cavity.

The Cervix

Cervical Cancer Smears

Cervical screening has brought down the incidence of cervical cancer. It is a general screening tests that is widely accepted by women, accurate, reliable, and cost effective. Abnormal results can result in early treatment which can result in prevention of disease progression. It is based in primary care (hospitals) and is a computerised “call and recall” system is now in place.

Guidelines:

25 First invitation

25-49 3 yearly

50-64 5 yearly

65+ Only if not since 50 or recently abnormal

Screening has reduced the risk of dying from cervical cancer by 75% in the UK and the number of women needing radical surgery has been reduced.

Anatomy of the Cervix

The cervical “os” is the opening of the cervix onto the vagina. The point at which the cells of the vaginal epithelium meet the glandular cells of the cervix is known as the transition zone. The position of the transition zone changes with age and hormone levels.

Abnormalities

There are a number of different abnormalities that can occur in the cervix:

•  Inflammatory change

•  Infection

•  HPV – human papilloma [or wart] virus – often no frank “wart”

•  Cervical intraepithelial neoplasia (CIN) [cannot be seen by the naked eye]

•  Invasive carcinoma

There are 3 stages of a pre-malignant tumour:

•  CIN1 = dysplastic changes involving one third of squamous epithelium

•  CIN2 = lower two thirds involved

•  CIN3 = entire depth involved.

CIN = Cervical-Intra-epithelial Neoplasia

At these stages, the basement membrane has not been breached and the condition is still treatable.

Human Papillomavirus

There are over 107 different types of Papillomavirus identified. It is thought to be associated with the increased risk of development of cervical cancer. The type of HPV can be determined by liquid based cytology and patients found to have high risk types are advised for smears and biopsies. There is now a vaccine available.

A common technique used to view the transformation zones is the colposcopy:

•  Outpatient procedure

•  Good view of Transformation Zone & vascular patterns

•  3% acetic acid – coagulates nuclear proteins and turn white in abnormal areas

•  Highlight areas of dysplasia

•  Punch biopsy for histological confirmation

Indications for colposcopy

·  cervical smear suggesting dyskaryosis

·  persistant inflammatory or inadequate smears

·  glandular neoplasia (much less common)

·  abnormal cervix

The treatments for neoplasia depend on progression of the disease. If CIN 1 is observed, then watchful waiting is adopted. If CIN 2 or 3 is the diagnosis, then the neoplastic cells are excised.

Treatment

·  CIN 1 – body can correct it

·  CIN 2+3 – excision TZ by LLETZ (burn off TZ), laser cone biopsy

·  ~35% CIN 3 progress to invasive disease over 10 yrs.

·  Invasive carcinoma (squamous or adeno-): examination under anaesthetic to decide stage/spread, if early can remove surgically +/- radiotherapy or chemotherapy

·  See 6-8 months post treatment

·  Smear tests alone not usually enough

·  Re-colposcope if smear is abnormal

·  CIN 1 – routine smears after 2 yrs of negative smears

·  CIN or worse – annual smears for at least 10 yrs.

Cervix in Labour

There are 3 stages to labour:

First stage – lasts 5-16 hrs

•  From the onset of regular contractions and associated dilatation and effacement of the cervix until full dilatation [10cm].

•  Because uterine muscles are arranged in spirals from the top to the bottom of the uterus, a contraction will cuase these muscles to contract causing shortening of the upper segment and drawing upwards of the lower segment, in a gradual expulsive motion. This draws the cervix up over the baby's head

Second stage – lasts 30mins – 2hrs

•  From full cervical dilatation to delivery of the baby

Third stage – lasts 10-30mins

•  Delivery of the placenta and membranes

Success of a birth depends on the

-  “powers” – strength and frequency of uterine contractions

-  “passenger” - size & position of the baby

-  “passage” – especially the bony structure of the pelvis

Contractions start at the top (fundus – intensity is greatest at the top) and continue sequentially downward. They are followed by relaxation to allow for blood flow (during contraction, the squeezing means poor blood flow to the uterus). Too many contractions à hyperstimulation à reduced blood flow.

The process of labour is defined as the onset of regular uterine contractions accompanied by the progressive effacement and dilatation of the cervix.

Effacement: the changing of shape of the cervix so that it becomes thin and flat before and during early labour.

•  Cervix transforms from a long firm approx. 3 cm long cylinder, to a flat structure

•  Contractions pull up and soften cervix.

•  Changes result from fluid in hydrophilic muco-polysaccharides between the collagen mesh “ripening”

•  Prostaglandins inhibit collagen synthesis and encourage collagen breakdown

Birth and Descent of Foetus

The erect posture causes the weight of the abdominal contents to thrust on the pelvic floor, a complex structure which must not only support this weight but allow three channels to pass through it: the urethra, the vagina and the rectum. The relatively large head and shoulders require a specific sequence of manoeuvres to occur for the bony head and shoulders to pass through the bony ring of the pelvis. If these manoeuvres fail, the progress of labour is arrested. All changes in the soft tissues of the cervix and the birth canal are entirely dependent on the successful completion of these six maneuvers: