METHODICAL INSTRUCTIONS
for practical lesson
« Endometriosis. Gynaecological diseases of children and teenagers. Abnormalities of location and development of female genital organs. »
MODULE 3: Diseases of the Female Reproductive system. Family planning.
Context module 4: Endocrine disorders the female reproductive system.
I. Scientific and methodical grounds of the theme
Recently the problem of endometriosis has become especially actual due to the increase of frequency of this pathology, implementation of modern diagnostic and therapeutic methods in to practice that’s why the aim of the practical lecture is the study of etiopathogenesis of endometriosis, methods of its diagnostic and treatment
II. Aim:
A student must know:
1. Classification of endometriosis of female genitalia .
2. Main clinic symptoms for endometriosis of female genitalia.
3. Methods of diagnosis of endometriosis of female genitalia.
4. Main principles of therapy of endometriosis of female genitalia.
5. Indications for surgery of endometriosis of female genitalia.
6. Possible developmental anomalies of uterine tubes, ovaries.
7. Clinic, diagnosis and treatment infantilism.
A student should be able to:
1. Collect general and specific gynecologic anamnesis.
2. Make up a plan of examination and treatment of endometriosis.
III. Recommendations to the student
ENDOMETRIOSIS
Endometriosis involves deposits of endometrium outside the uterine cavity. Its manifestations are very variable and often bear no relation to the extent of the disease.
Pathology
The gross appearance shows ectopic deposits which can very in number from a few in one locality to large numbers distributed over the pelvic organs and peritoneum.
The commonest sites of these deposits are:
The commonest appearance of a typical lesion is that of a round protruding vesicle which shows a succession of colours from blue to black to brown. The variation in colour is due to haemorrhage with subsequent breakdown of the haemoglobin. Ultimately the area of haemorrhage heals by the formation of scar tissue. The result is a puckered area on the peritoneum. Commonly however the haemorrhage results in adhesion to surrounding structures. These adhesions are more apt to form between fixed structures such as the broad ligament, ovary, sigmoid colon or the posterior surfaces of the vagina and cervix.
The ectopic deposits of endometrial tissue vary in size from pin-point to 5 mm or more. It is these larger deposits which tend to rupture leading to adhesions. These adhesions over the ovary can lead to the formation of quite large haemorrhagic cysts due to continued bleeding from deposits, the blood being unable to escape. Investigation has shown that many lesions do not have a 'typical' appearance. The following is a list of other appearances which have been described. White, slightly raised opacities due to retro-peritoneal deposits. Red flame-like or vascular swellings, more common in the broad ligament or utero-sacral ligament. Small excrescences like the surface of normal endometrium.
Adhesions under the ovary or between the ovary and the ovarian fossa peritoneum. Cafe-au-lait patches often in the Pouch of Douglas, broad ligament or peritoneal surface of the bladder. Peritoneal defects on utero-sacral ligament or broad ligament. Areas of petechiae or hypervascularisation usually on the bladder and the broad ligament.
Secondary pathology
This is due to the adhesions between the endometriotic deposits and adjacent organs. In long-standing cases the pelvic cavity is obliterated by these adhesions. Retroversion of the uterus can be produced.
Clinical findings
The incidence of endometriosis has been estimated at 3 to 7% of women but the true incidence is unknown. Quite often deposits are found incidentally in women who have no symptoms of endometriosis and are undergoing laparoscopy or laparotomy for some other condition. In addition, as indicated in the section on pathology, many peritoneal changes now known to be due to endometriosis were undiagnosed in the past.
The prevalence of endometriosis peaks between the ages of 30 and 45 years. Since ectopic endometrium is stimulated by the same ovarian steroid hormones as the endometrium lining the uterine cavity, endometriosis is almost never found outside the reproductive years.
Symptomatology
A. Pain affects more than 80% of women with endometriotic deposits. The pain tends to begin premenstrually reaching a peak during menstruation and subsiding slowly.
The character of pain may vary as does its apparent origin. It may be generalised throughout the abdomen and pelvis like the pain of severe dysmenorrhoea. Alternatively, pain may be localised to a particular site within the pelvis. Deep dyspareunia affects around 40% of women with endometriosis.
B. Menstrual disturbance. Menstrual disturbance affects around 20% of women with endometriosis. It may take the form of premenstrual 'spotting', menorrhagia or infrequent periods. Lesions in the wall of the bladder may result in 'menstrual haematuria'.
C. Infertility. Endometriosis is found more commonly in women undergoing investigation for infertility than in the 'normal' population. It is not clear which condition arises first. Approximately 30% of patients with endometriosis complain of infertility. When endometriosis is extensive, and both fallopian tubes are occluded, the mechanism by which endometriosis prevents conception is obvious. However, milder forms of endometriosis are also associated with subfertility, and here the pathophysiology is less clear. The most likely mechanism appears to be that immunological factors within the peritoneal cavity inhibit normal gamete function, thus reducing fertilisation rates.
Physical examination
Endometriosis cannot be diagnosed by physical examination alone. However, enlargement of the ovaries, fixed retroversion of the uterus and tender nodules within the pelvis may each raise the suspicion of the disease. Endometriosis should always be considered when patients have symptoms referable to the pelvic cavity.
Laparoscopy
Laparoscopic examination is the only way of making a positive diagnosis. The lesions can be seen and their number and location estimated. Endometriosis of long standing may be very difficult to diagnose due to obliteration of the pelvic cavity by adhesions. Histological confirmation must be obtained if feasible.
Imaging techniques
Ultrasound, computerised tomography and magnetic resonance imaging may suggest the presence of endometriosis (e.g. by the demonstration of a particular type of ovarian cyst) but are by themselves insufficiently reliable to make the diagnosis.
Differential diagnosis
Due to the mixture of symptoms and the variation in appearance of the pelvic structures, conditions such as pelvic inflammatory disease and tumours of the ovary and bowel must be considered and eliminated.
Histogenesis. There are three theories.
Retrograde spill of menstrual debris through the tubes. Retrograde menstruation takes place in most women, but it is unclear why some women should develop endometriosis while others are unaffected.
Metaplasia of embryonic cells. These are derived from the primitive coelom and may remain in and around the pelvis and differentiate into Mullerian duct tissue.
Emboli of endometrial tissue may travel by lymphatics or blood vessels and become established in various sites.
The first of these theories is most favoured.
TREATMENT. Medical treatment. Any treatment must be aimed at treating symptoms. Since ovarian hormones are responsible for growth and activity in endometrium many medical therapies are designed to reduce ovarian steroid production or oppose their action.
1. Progestogens
Progestogens in a relatively high dose (e.g. medroxyprogesterone acetate 10 mg tid) induce decidualisation, and sometimes resorption of ectopic endometrium. Side effects include weight gain, bloating and irregular vaginal bleeding.
2. Combined contraceptive pill
The combined oral contraceptive pill also induces decidualisation of ectopic endometrium. It may be given continuously for up to 3 months.
3. Danazol
Danazol is a steroid hormone closely related to testosterone, which inhibits pituitary gonadotrophins, is anti-oestrogenic, anti-progestational, slightly androgenic and anabolic. The dose of danazol given can be titrated to the patient's symptoms up to a maximum of 800 mg daily. If danazol can be tolerated, symptoms and objective signs of disease can be alleviated in the majority of patients. However, androgenic side effects including amenorrhoea, weight gain, acne, hirsutism and deepening of the voice may limit acceptability of the drug.
4. Gestrinone
Gestrinone is a derivative of 19-nortestosterone. It has slight androgenic activity and is markedly anti-oestrogenic and anti-progestogenic. It interacts with the pituitary steroid receptors and decreases gonadotrophic secretion resulting in diminished follicular growth and anovulation. A bi-weekly oral dose of 2.5 to 5.0mg for 6 months induces amenorrhoea, disappearance of pain and regression of the endometrial deposits. Side effects include weight gain, acne, seborrhoea and mild hirsutism.
Gonadotrophic releasing hormone analogues (GnRH analogue)
GnRH analogues are administered by depot injection or nasal spray. Their mode of action is shown above. Although these drugs are generally effective in treating symptoms, menopausal side effects, in particular bone loss, may preclude long term use. In the future, use of 'add back' regimens which include small supplementary doses of oestrogen may prove to be effective in treating the symptoms of endometriosis without the complications of total oestrogen deprivation.
Conclusion
As with medical therapies for other conditions, the optimum treatment is dictated by the side effect profile which is most acceptable to the patient. None of the drug treatments described will prevent recurrence of endometriosis once therapy has been stopped, although there may be a period of some months between stopping treatment and the re-emergence of symptoms. No medical treatment has been shown to improve subsequent fertility. Notwithstanding, none of the above, with the exception of the combined pill, is a proper contraceptive agent and patients should be advised to use barrier contraception to avoid the potential teratogenic effects of drugs such as danazol if they are at risk" of becoming pregnant.
Surgical treatment
Where infertility is not a problem radical surgery to remove both ovaries is said to be a lasting cure for endometriosis, since it removes the oestrogenic stimulus to endometrial growth. In many cases the patient wishes relief from pain but also desires to retain the possibility of future pregnancy. In these circumstances only conservative surgery can be employed.
The intentions in conservative surgery are:
· To ablate as many endometrial deposits in the pelvic cavity as possible.
· To restructure the pelvic anatomy by destroying adhesions which interfere with ovarian and tubal function.
· To destroy endometrial deposits in the ovaries.
· To deal with sensory nerve pathways.
In view of the many vital structures such as the bladder, rectum, colon and ureters in close proximity to each other, conventional open surgery is not always feasible. Laser surgery under laparoscopy, with its almost microscopic accuracy, may be employed. Endometrial deposits and adhesions can be vaporised easily without damaging tissue outside a radius of a fraction of a millimetre from the target. Similarly the laser destruction of ovarian lesions can be carried out without destroying any of the functional tissue.
The question of dealing with sensory nerve pathways is difficult to answer. Severe pain is a feature of a number of gynaecological conditions, especially those related to malignancy. Elsewhere in this book operative techniques are described which involve interfering with sensory conductivity centrally, i.e. at the spinal cord level. Recently, a local operative procedure, paracervical uterine denervation, has been recommended. This consists of vaporising the utero-sacral ligaments by laser at their attachment to the posterior aspect of the cervix where the sensory fibres emerge from the uterus. Two difficulties are associated with this procedure. First, the ureters must be avoided and, secondly, veins lying lateral to the ligaments must not be injured. Unfortunately severe pain is often associated with severe endometriosis and adhesions may make the operation very difficult.
Reports in the literature record complete relief from pain in 50% of patients followed for more than a year and another 41% obtained moderate relief.
IV. Control questions and tasks
1. Frequency of endometriosis pathology.
2. Classification of endometriosis.
3. Laboratory methods of endometriosis diagnosis.
4. Conservative methods of treatment.
5. Surgical methods of treatment.
V. List of recommended literature
1. Danforth’s Obstetric and gynaecology.-Seventh edition.-1994.-P.845-853
2. Gynecology.-Stephan Khmil, Zina Kuchma, Lesya Romanchuk.-2003.-P.263-267
3. Gynaecology illustrated. David McKay Hart, Jane Norman.-Fifth Edition.-2000.-P.122-128
DEVELOPMENT OF FEMALE GENITALIA IN PRENATAL PERIOD
On the 3-4th weeks of embryo development on internal surface of primary kidney a gonad germ is generated. Primary gonad has an indifferent structure (identical for both genders) and consists of celomic epithelium cells (external layer), mesenchyme (internal medullar layer) and gamete cells — gonocytes. Sexual differentiation of indifferent glands is induced by sexual chromosomes. Y-chromosome presence determines testicle development, and X-chromosome presence determines ovarian development.
External genitals of fetus also goes through the different stages of development. They are germinated on the 6-7th weeks of the development in the form of genital prominence and urethral fissure, bordered by urethral and labioscrotal folds.
Forming of masculine sexual glands begins from the 7th week, and masculine genitals — from the 8th week of fetal development.
Differentiation of female reproductive system takes place in later terms. Forming of female-type gonads begins from 8-10th week of pregnancy. Presence of 2 X-chromosomes in a zygote is necessary for ovarian development. A gene inducing ovarian development is localized in long shoulder of X-chromosome. Under its influence gonocytes are transformed into ovogonies, then — into ovocytes, around which the primary granulous cells are generated from mesenchymal cells. They are situated in the cortex of sexual gland and intensively reproduce themselves by means of mitotic division. On the 5th month of embryonal development a number of primary follicles reaches 4 mln., till the birth time of a girl their amount is reduced to 1 mln. The ovary is morphologically formed.
Internal genitalia — uterine tubes, body, uterine cervix, upper 1/3 of vagina are formed from paramesonephral ducts. Process starts on the 5-6th and finishes to 18th week of pregnancy. From upper one-third of paramesonephral ducts uterine tubes are formed. Lower and middle parts uniting together form a body and uterine cervix. Lower department of paramesonephral ducts forms the upper one-third of vagina, lower 2/3 are formed from urino-genital sinus
Common organ cavity is formed to 21-22 week of gestation. The rest of mesonephral channels are preserved as paraovophorone, epiovophorone and Gartner's passages on the lateral walls of vagina. External female genitals are formed since the 17th week of gestation. At first major labia are formed from labioscrotal folds, from urethral folds minor labia are generated. Clitoris is formed from genital prominence