Abnormal Uterine Bleeding (UAB) In Gynaecological Practice

Abnormal Uterine Bleeding (UAB) In Gynaecological Practice INTRODUCTION Abnormal uterine bleeding (AUB) is a common complaint in gynaecological practice, represents a major proportion of out patients attendence. One, in 20 women in UK consulted their GP for menorrhagia. [1] A menstural cycle of fewer than 21 days or more than 35 days or a menstural flow of less than two days or, more than seven days is considered abnormal. [2] AUB can be categorized as excessive menstural bleeding, irregular, bleeding intermenstural including, postcoital bleeding. [3] Different terms, used to describe AUB are: oligomenorrhea (bleeding occurs at intervals of > 35 days usually caused by, prolonged follicular phase). Polymenorrhagia, (bleeding occurs at intervals of 21 days may be caused by a luteal phase defect). Menorrhagia, (bleeding occurs at normal intervals (21 to 35 days)but with heavy flow (80 ml) or duration (7 days). Menometrorrhagia, (bleeding occurs at regular, non cyclic intervals with heavy flow (80 ml). (2) Abnormal uterine bleeding, includes both DUB bleeding from structural causes. Dysfunctional bleeding can be anovulatory, which is characterized by heavy but regular periods. (I-e, menorrhagia). Structural causes include: fibroids, polyps, endometrial carcinoma pregnancy complications. Abnormal bleeding can also results from contraceptive methods. (4) In peri postmenopause women, it is essential to exclude endometrial carcinoma. In younger women, endometrial hyperplasia anatomical anomalies: such as uterine fibroids, comprise the main pathology. (5) Perimenopause is the period, 2 8 years preceding menopause 1 year after the final menses. (WHO). However, a better practical definition is, the phase preceding the onset of menopause, generally occurring around 40-50 years of age, during which the regular cycle of a women transition to a pattern of irregular cycles. (6) A variety of methods, have been used to investigate patients with AUB, such as, endometrial cytology, transvaginal ultrasound, hysteroscopy, D C and endometrial biopsy . (7) The recommendation regarding, investigation of AUB is that women, over the age of 45, should be investigated with endometrial biopsy. Frequently, this is performed as an inpatient procedure with the biopsy being obtained by uterine curettage (D C). (5)This is the most common procedure used, to evaluate the endometrial cavity of a patient with AUB. (8) However, the value of endometrial curettage is great, in the establishment of histopathologic diagnosis. (6) The operation involves a G. A often a two day stay. Originally, the procedure was thought to have a therapeutic effect or AUB, But studies have failed to support this. This procedure is performed for diagnostic purposes, to exclude endometrial malignancy. (9) REWIEW OF LITERATURE ABNORMAL UTERINE BLEEDING Abnormal uterine bleeding (AUB) is a symptom it is not a disease, but is a common debilitating condition. Dysfunction uterine bleeding (D. U. B) is the diagnosis, given to women with AUB in whom no clear etiology can be identified. [10, 11]. An approach accurate diagnosis depend on recognizing the following types: Menorrhegia: is cyclic bleeding at normal intervals, which is excessive is larger than 7 days o and amount more than 80 ml frrom normal secretory endometrium after normal ovulation is caused by conditions affecting the uterus. (10, 11) Polymenorrhea: is cyclical bleeding which is normal in amount but which occurs at too frequent intervals of Polymenorrhegia: is cyclical bleeding which is both excessive too frequent. Eg: 9/20-12/20. It implies a disturbance in the hypothalamic pituitary ovarian uterine axis. (10) Metrorrhegia: It is bleeding of any amount whch is cyclical which occur irregularly or continuously in between normal cycles. It is caused by benign or malignant growth with ulcration. (10) Dysfunctional Uterine Bleeding continuously occurs at the extreme of reproductive (adolesence perimenopausally). The abnormalities of ovarian activity may be classified as follows. Upto 90% of cases of DUB result form menstrual cycles in which ovulation does not occur (anovulation) (Dodds). The remainder of cases arise from problems associated with ovulation such as dysfunction of the corpus luteum or prolonged progesterone secretion. (12) Anovulatory Occasionally anovulatory cycles occur in all women. Upto 90% of cases of D. U. B result from menstural cycles in which ovulation does not occur(anovulation. The remainder of cases arise from problems associated with ovulation such as dysfunction of the corpus luteum or peolonged progesterone secretion. Chronic anovulation in associated with an irregular unpredictable pattern of bleeding ranging from short cycles with scanty bleeding to prolonged period of irregular heavy loss. In anovulatory cycles, the endometrium is unable to produce factors whose sysnthesis is controlled by progesterone, eg. PGF2a (Smith et al, 1982). This may account for the painless bleeding. Anovulatory bleeding may be associated with cystic glandular hyperplasia of the endometrium. This occurs in some older women also in peripubertal girl, where unopposed oestrogen secretion occurs. Endometrial hyperplasia may cause excessive bleeding, anaemia, infertility even endometrial carcinoma. (13) Ovulatory: (idiopathic bleeding) It appears that there are a number of endometrial products, which alters the degree of vadoconstriction thus may effect the volume of menstrual blood loss. In the mid 1970s, a relationship b/w prostaglandins (PG) production menorrhegia was suggested by work showing that total endometrial PG content was proportional to menstrual loss. It appears that a shift in endometrial conversion form the vasoconstrictor PGF20( to the vasodilator PGI2 occurs. Another important factor is endothelin, which is very potent vasoconstricter, produced within the endometrial vessels. Marshs group showed reduced endothelin immunostaining in the endometrium of women with monorrhegia , implicating this peptide in the pathophysiology of increased menstural blood loss. (Marsh 996) (13) Etiology of Abnormal Uterine Bleeding Before Menarche: Malignancy, trauma sexual abuse or assault are potential causes of abnormal uterine bleeding before menarche. Child bearing years: Pregnancy is the first consideration in women of childbearing age who present with AUB. Potential causes of pregnancy related bleeding includes miscarriage, ectopic pregnancy , placenta previa, abrutio placentae trophoblastic disease. Next, iatrogenic causes of AUB should be explored. Bleeding may be induced by medication, including anticogulants, selective serotonin reuptake inhibitors, antipsychotics, cortiosteriods, hormonal medication, tamoxifen (Nolvadex). Herbal substance including ginseng, ginko, soy supplement, may cause menstrual irregularities by altering estrogen levels or clotting parameters. (14), (15) Systemic Disorders: Includes thyroid, hematologic, hepatic, adrenal, pituitary, hypothalamic conditions menstural. Irregularities are associated with both hypothroidism (23. 4% of cases) hyperthyroidism (21. 5% of cases). Coagulation Disorders: Inherited coagulopathy may be the underlying cause of AUB in 18% of white women 7% of black women with menorrhagia. Others causes include polycystic ovary syndrome or diabetes mallitis present with obesity, acne, hirsutism acanthosis nigricans. Genital tract pathology may be associated with intermenstural, postcoital and heavy menstural bleeding, Any history of abnormal Papanicolaou (Pap) smear, sexually transmitted disease, gynaecologic surgery, trauma or sexual abuse should be elicited. Uterine fibroids, endometrial polyps, adenomyosis, endometrial hyperplasia and atypia and endometrial cancer should be excluded. [14, 15] Differential Diagnosis Pregnancy complications: Threatened abortion   Incomplete abortion   Ectopic pregnancy Nonuterine bleeding: Cervical ectropion/erosion   Cervical neoplasia/polyp   Cervical or vaginal trauma   Condylomata   Atrophic vaginitis   Foreign bodies Pelvic inflammatory disease (PID): Endometritis   Tuberculosis Local factors: Endometrial polyps   Endometrial neoplasia   Adenomyosis/endometriosis   Uterine myomata (fibroids)   Intrauterine device (IUD) Uterine sarcoma Coagulation disorders: Thrombocytopenia, platelet disorders   von Willebrand disease   Leukemia   Ingestion of aspirin or anticoagulants   Iatrogenic Causes: Anticoagulants Antipsychotics Corticosteroids Herbal other supplements(ginkgo, soy) Hormone replacement intrauterine devices Oral contraceptive pills Thyroid hormone replacement PATHOPHYSIOLOGY OF ABNORMAL UTERINE BLEEDING: The hallmark of normal menstrual bleeding is the final result of fluctuations in the hypothalamic-Pituitary-Adrenal-Ovarian axis leading to predictable denudation and slough of the endometrium. Hemorrhage followed by prompt hemostasis and repair causes stabilization and regrowth of the endometrium. Physiologically, constant flow levels of estrogen prime the endometrium. Normal secretion of progesterone from the corpus luteum stabilizes the endometrium, decreases vascular fragility and supports the endometrial stroma. Patients with menorrhagia typically have an imbalance of prostaglandins levels and increased fibrinolytic activity . Specifically, women with heavy bleeding often have elevated levels of plasminogen activators compared to those with normal menstruation. [16] An intact coagulation pathway is important in regulation of menstruation. Mensturation disrupts blood vessels and in the face of normal hemostasis, the injured blood vessels are rapidly repaired . Restoration of blood vessels requires successful interaction of platelets and clotting factors. Defficiency of platelets, abnormal platelet function and an intact coagulation pathway may be associated with profound changes in the menstrual ctcle. [16]. Anovulatory D. U. B is usually due to failure of the corpus luteum to sustain the developing endometrium. The decline of inhibin levels and rise in FSH levels reflect the loss of follicular activity and competence as the perimenopausal transition occurs, [16]. Ovulatory D. U. B occurs when ovulatory cycles coexist with intracavitary lesions including polyps, endometrial cancer or fibroids which cause erractic bleeding, [16]. NATURE OF ABNORMAL UTERINE BLEEDING: The studies have shown mean menstrual blood loss to be ~ 30 ml per cycle in most societies, with loss > 60-80 ml per month being associated with an increased tendency towards iron deficiency and anaemia( Hallberg ET AL, 1996 ;Code et al, 1971). An upper limit of 60 ml may be more appropriate clinically. [17]. The duration of normal menstruation also varies greatly, with an average of 5 days and the heaviest loss usually on the first 2 days(Matsumoto at al, 1962 ; Rubin and Crosignani, 1990). Duration of flow is considered abnormal when it lasts 7 days. [17]. Abnormal uterine bleeding may involve any disturbance of regularity, frequency, duration or volume of menstrual flow and the causes may be physiological, pathological or pharmacological (Fraser and Sngertekin, 2000), [17]. MECHANISM S INVOLVED IN AUB: MENORRHAGIA: Menorrhagia is caused by certain pelvic diseases. The mechanisms by which these conditions cause excessive bleeding are poorly understood, but evidence suggest that large , thin walled and fragile surface vessels underlies the menorrhagia occurring with myomata and endometrial carcinoma. This disturbed angiogenesis is most likely a consequence of unco-ordinated release of angiogenic factors from the tumor themselves(Jane and Harris, 1998), s/a VEGF, bFGF, TGF-beta( Stewart and Nowak, 1996)[17]. The mechanism of increased blood loss with copper IUCDs is thought to be due to a combination if increased cytokine- producing endometrial leukocytes ( Sheppard, 1987), increased local fibrinolytic activity and epithelial surface erosion due to contact with the device(Shaw et al, 1979_. Release of PG and activation of mast cells and macrophages may be the underlying mechanisms. [17]. A quantitative reduction in platelets s/a in autoimmune thrombocytopenia or chronic renal failure can lead to increased menstrual loss. DYSFUCTIONAL UTERINE BLEEIDNG: Dysfunctional uterine bleeding accounts for ~50% of all cases of excessive uterine bleeding, 9Barley, 1972)[17] Anovulatory Dysfuctional Uterine Bleeding: The exact mechanisms behind anovulatory bleeding are unknown(Fraser et al, 1996) but it is known that unopposed estrogen can lead to excessive endometrial proliferation and hyperplasia with increased and dilated draining veins and suppression of spiral arterioles ( Beilby et al , 1971). Large thin walled, tortuous, superficial endometrial vessels can often be demonstrated on the surface of hyperplastic endometrium(Hamou, 1985) and increased fragility is a probable contribution to increased blood loss. Unopposed estrogen has a direct effect on the uterine blood supply by reducing vascular tone (Fraser at al, 1987) and possibly an indirect effect through inhobiting vasopressin releae( Akerlund et al, 1975) leading to vasodilation and increased blood flow. Unopposed estrogen also stimulates stromal VEGF expression which may contribute to disturbed angiogenesis ( Zhang at al, 1995 ; Smith , 1998). [17]. Ovulatory Dysfunctional Uterine Bleeding: The main defect in ovulatory DUB appears to be in the control of processes involve in the regulation of the volume of blood lost during menstrual breakdown of the endometrium, primarily the processes of vasoconstriction and haemostasis. [17] Endometrial glandular and stromal estrogen and progesterone receptor levels may be increased in the late secretory phase in women suffering from DUB (Gleeson et al, 1993 )[17] There may be some role of endothelins, which increase in at the time of normal menstruation. ( Cameron et al , 1992)[17] Reduced levels of endothelins may lead to an increase in the volume of blood lost. An increase in total PG release and disappropriate rise in PGE2 have been demonstrated in ovulatory DUB (Smith et al, 1981 ). It also has been shown that there is an increase in PGE2 and PGI2 receptors predisposing to vasodilation, in women with menorrhagia ( Adelantado et al, 1988 )[17] Prevention of platelet aggregation by PGI2 release may be an important contributing factor in ovulatory DUB ( Smith et al, 1981 ) as may increased endometrial tPA content, increased local fibrinolytic activity ( Bonner et al, 1983;Casslen et al, 1996;Gleeson et al, 1993 ) and excessive endometrial heparin like activity ( Paton et al , 1980 )[17} Endometrial lysosomal enzyme activity in women with ovulatory DUB is increased, and this activity is also observed in women with menorrhagia secondary to IUCD use (Wang , 1994 ){17 ) Matrix metaloproteinases may be important in contributing to abnormal endometrial breakdown and abnormalities of menstrual bleeding ( Salamonson et al, 2000 ){17, 18 ]. Granulated stromal lymphocytes, macrophages and othe migratory leukocytes may contribute to mechanisms of excessinve loss. [18] In DUB, delayed or incomplete endometrial repair could prolog menstrual bleeding episodes, but nothing is known about such mechanisms. [18] SIGNS AND SYMPTOMS OF ABNORMAL UTERINE BLEEDING: Frequent complaint include: heavy or prolonged menstural flow, social embarrassment, diminished quality of life, sexual compromise and alteration in life style. Pain is not a common presenting symptom unless associated with passage of large blood clots. Prolonged menstrual blood loss can be associated with anaemia. Typical complains of anaemia include fatigue, unusual desire of eating starch or dirt and headaches. Severe anaemia may cause fainting, congestive cardiac failure, exercise induced fatigue, shortness of breath. Hemorrhagic shock death are rare sequelae for DUB. [16] EVALUATION OF AUB IN PERIMENOPAUSAL WOMEN: 1.  History: History focuses on identifying the type of AUB:ovulatory, anovulatory or anatomic in order to guide treatment. Ovulatory bleeding is more common, usually cyclic, and can be associated with mid cycle pain, premenstrual symptoms and dysmenorrhea. Anovulatory bleeding occurs more frequently at the axtremes of reproductive age and in obese women. It is usually irregular and often heavy. Any history of easy bruising and tendency to bleed suggests coagulopathy. History of jaundice and hepatitis gives the evidence of liver sisease. [19] 2. Physical Examination: Physical examination includes looking for evidence of systemic disease. Pelvic and bimanual examination are done to detect disease in the genital tract. Cervical cytology analysis should be current and normal and cervical and vaginal swabs should be assesses to rule out infection. [19] 3. Laboratory tests: Beta subunit human chorionic gonadotropin for pregnancy. Complete blood count with platelet count for coagulopathy LFT, PT for liver disease. TSH for hypothyroidism and hyperthyroidism. Free testosterone for ovarian or adrenal tumor. [19] 4. Assessment of the uterine cavity: The main indications for assessment of the uterine cavity is to exclude pathology, most often seen in women over 45 years of age with anovulatory cycles. [19] A wide variety of methods are available for endometrial assessment including: Ultrasonography Endometrial Biopsy Hystroscopy Dilatation and curettage Sonohysterography Hysterosalpingography 1. Ultrasonography: Ultrasonography to look for ovarian or uterine disease. Transvaginal ultrasound is 80% sensitive and 69% specific for fibroids and polyps and is superior to transabdominal ultrasound. If possible, transvaginal ultrasound should be performed on days 4-6 of the menstrual cycle. [19] 2. Endometrial Biopsy: Endometrial biopsy is a simple office procedure that can be done by family physicians, [19]despite its convenience , cost effectiveness and safety, it is a blind endometrial sampling procedure. [20]It is a useful method to exclude malignancy in perimenopausal women. The annual incidence of endometrial cancer is 19. 5 per 100, 000 women. One in 4 cases of endometrial carcinoma occurs before menopause, so biopsy should be considered for high risk premenopausal patients, even in the presence of fibroids. Endometrial biopsy produces an adequate sample more that 85% of the time and detects 87-96% of endometrial carcinoma. [19] 3. Hysteroscopy: Hysteroscopy permits direct visualization of the cercical canal and uterine cavity, enabling observation of intrauterine abnormalities. Hysteroscopy is considered an accurate gold standard in uterine cavity evaluation. Despite the lack of adequate information about the diagnostic accuracy, it is used in many studies with and without endometrial sampling as a reference standard, [21] Hysteroscopy was reported to have sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 94. 2, 88. 8, 96. 3 and 83. 1% respectively, in predicting normal or abnormal endometrial histopathology (Garuti et al, 2001). The highest accuracy of hysteroscopy was in diagnosing endometrial polyps, where as the worst result was in estimating hyperplasia. In a recent study the sensitivity and PPV of hysteroscopy without endometrial biopsy in diagnosing endometrial carcinoma was only 58. 8 and 20. 8 % respectively (Lo and Yuyen, 2000 ). There, since the incidence of focal lesions in patients with AUB is 46-74% (Nagele et al, 1996;Pal et al, 1997 ), it seems that the most cost effective approach is to proceed with hysteroscopy complemented by endometrial biopsy, early in the assessment of AUB. [22] 4. Dilatation Curettage: Dilatation is a common surgical procedure done on women to scrape and collect the tissue from inside the uterus. Dilatation is a widening of the cervical passage. This is done using smoothy conical and tapered, graduated metal rods of various sizes and these appropriately called the dilators, which dilates the tight cervical passage slowly. Curettage is the second part of the procedure and is done to scrape the inside contents of the uterus. For this, a sharp spoon like instrument called curette is used. The procedure is usually performed under general anaesthesia. [23, 24, 25] Indications:[23, 24, 25]s Dialtation and curettage may be done as a diagnostic or a therapeutic procedure. Diagnostic: Diagnose conditions by collecting tissue samples for biopsy. To diagnose endometrial cancer. To investigate the causes of infertility. To investigate the cause of abnormal bleeding in postmenopausal women taking HRT. Therapeutic: Treat intermenstural bleeding To remove polyps in the endometrial or inner lining of the uterus. To treat irregular and heavy bleeding. To remove an embedded IUD used for contraception. To perform abortion in the early stages of pregnancy. To evacuate spontaneous abortion product. [23, 24, 25] Preoperative procedure: It is recommended that the patient take nothing by mouth, for at least 6 hours. Pain killers and antibiotics may be prescribed before the procedure. A sedative may be useful to relieve the anxirty of srgery. The genital area may be shaved and prepared for the surgery. An enema may be administered to clear the bowels. [23] Anaesthesia: General Anaesthesia: Most D Cs are done under general anaesthesia. The procedure is normally very short and the general anesthetic can be quickly reversed, with the patient going home soon afterwards. Spinal Anaesthesia: The advantage of spinal anaesthesia is that the patient is awake but at the same time does not have any sensation below the waist. It avoids all the complications of general anaesthesia. Local Anaesthesia: Occasionally, D C s are done under local anaesthesia, if the patient is not ready for general or spinal anaesthesia. [23, 25] Procedure: The vagina and cervix are cleaned with an antibacterial solution that may be iodine or alcohol based. The cervix is visualized using an instrument that is locatedin the vagina called the speculum. Lights are so adjusted to visualize the cervix so that its upper lip can be grasped with a special curved forceps called the Vulsellum. This helps both in stabilizing and bringing the cervix down towards the vaginal opening to ease with rest of the procedure. Dilatation is next done using sequential metal round tapered dilators and the opening to the uterus is gradually widened to about the size of a large pencil. Once this dilatation has been completed, the curette is inserted into the uterine cavity and is used to gently scrape the lining of the uterus. When the surgeon feels the gritty layer of cells just above the muscle of the uterus, then he/she knows that the scrapping has gone deep enough to sample the tissue adequately. This scrapping is done throughout the uterus and the tissue is sent to histopathologist. [23, 24, 25, 26] Post operative care: There may be mild abdominal discomfort after a dilatation and curettage, if pain is severe, consult a doctor. Medication should be taken as advised by doctor. Ensure to take antibiotics. Avoid the use of any contraceptive device or sexual intercourse for a week. Use sanitary napkins during this time period. If there are any signs of infection s/a fever , pain or discharge, consult the doctor immediately. [23, 24, 25] Contraindications: If a patient is too ill to undergo surgery. If the patient is unable to move her legs apart, s/a with severe arthritis in the hips. If the patient has problem with clotting mechanism of the body. [23] Complications: Complications are usually rare: Anaesthetic Complications: Reactions to anaesthetic medications. Breathing difficulties. Surgical Complications: Perforation of the uterus. Laceration of the cervix. Scarring of the endometrium. Infection of the uterus or other pelvic organs. Hemorrhage. [23, 24, 25] 5. SONOHYSTEROGRAPHY: Sonohysterography is being used more frequently for evaluation of women with many gynaecologic conditions. In 1992, it is reported the use of sonohysterography for detecting endometrial polyp in 14 of 148 infertility patients. In 13 of the women, polyps were asymptomatic. [27]This procedure is to be done by use of saline infused through a catheter into the endometrial cavity provides slight distention and separation of cavity walls, allowing the better visualization of uterine cavity. [28] Sonohysterography not only aids in diagnosis of intrauterine pathology but also in decision regarding surgical versus medical management of patients and and directs the approach and instrumentation required when surgical treatment is warranted. [28] It can be performed in any phase of cycle but the best time is during the first phase of the cycle especially when the indication is sterility or thickened endometrium at transvaginal sonography. [28] 6. HYSTEROSALPINGOGRAPHY: Hysterosalpingography requires the use of radiations and iodinated contrast material. It is expensive and provides indirect information about the uterine cavity. One can delineate fibroids and polyps but cannot comment on endometrial thickness. [28] 7. MEGNETIC RESONANCE IMAGING: Magnetic resonance imaging , an expensive modality provides excellent images of the uterus and myometrial pathology disrupting the endometrium, however, intracavitary lesions are not well demonstrated. [28] EMBRYOLOGY OF THE FEMALE GENITAL SYETEM Although genetic sex is determined at fertilization, gender is not apparent until approximately the 12th week of embryonic life. By the 6th week embryonic life, both male and female embryos start to develop the following structures on either side of the midline. :[29, 30] Genital ridge (proliferation of coelomic epithelium ) Mesonephric (wolffian )duct (lateral to the genital ridge ). Paramesonephric ( mullerian ) duct which consists of: Upper vertical part lateral to the wolffian duct. Middle horizontal part crosses in front of the wolffian duct ( both upper and middle parts form the fallopian tubes ). Lower vertical part fuses with the similar part of the opposite side to form the uteri-vaginal canal (the upper part forms the body and cervix of the uterus while the lower part forms the upper 4/5 of the vagina ). The lower 1/5 of the vagina develops from the sino-vaginal bulbs in the posterior wall of the uro-genital sinus. [29] Origin and derivatives of the Mullerian Ducts: Mullerian ducts persists, in females to develop into the fallopian tubes, the uterus and part of the vagina. [31]. Mullarian duct grows , at first it is solid, but later it becomes canalized. It deviates more and more medially till it meets its fellow of the opposite side. The septum between the two mullerian ducts disappear. The proximal parts of the mullerian ducts form the fallopian tubes, while the distal parts meet together to form the body and cervix of the uterus and the upper 4/5th of the vagina. The stroma and muscles develop from the surrounding mesoderm. The fusion of the two mullerian ducts brings together two peritoneal folds which become the broad ligaments. [29] Ovary: Development of the ovary passes into three phases: Migration of the germ cells from the yolk sac to the posterior body wall at level of 10th thoracic level to enter the genital ridge The germ cells differentiate into oogonia then primaryoocytes and become arrested until puberty. Descent of the ovary to reach the pelvis along a ligamentous cord called the gubernaculums that is attached inferiorlyot the inguinal region. The gubernaculums becomes incorporated into the uterine wall at the point of entry of the fallopian tube and persists in the adult as the ovarian ligaments and the round ligament. [29] External Genitalia: Clitoris develops from the genital tubercle (by slight elongation ). Labia minora develops from the genital folds (by remaining separate ) Labia majora develop from the genital swelings (by enlarging greatly ). Vestibule develops from the lower most part of the urogenital sinus. [29]. ANATOMY AND HISTOLOGY OF FEMALE GENITAL TRACT Uterus: The uterus is a fibromuscular organ and is a hollow and pear shaped highly vascular organ present in the pelvis between the bladder and the rectum. It is about 8 cm long and 5 am broad, within which fetal development occurs. Uterus is usually divided into a lower cervix and an upper corpus of uterine body. 1. Cervix; The cervix is narrow region at the bottom of the uterus that leads to the vagina. It has a convex round surface with a circular or slit like opening (the external os ) into the endocervical canal, ehich is approximately 2 -3 cm in length and opens proximally into the endometrial cavity at the internal os. [30, 32, 33] Histologically, the cervical mucosa generally contains both stratified squamous  epithelium (exocervix) and mucus secreting columnar epithelium (endocervix). The mucus secreting glands are confined to the endocervix. The area where the two types of epithelia meet is called the squamocolumnar junction. [30, 34]. Cervical mucus secreted by the mucosa layer of the cervical canal serves to protect against bacteria entering the uterus from the vagina . [33]. In the cervix, the stroma is firmer, more fibrous and less cellular. [34] 2. Uterine Corpus: The body of the uterus varies in size. At birth , the cervix and corpus are approximately equal in size, in the adult women, the corpus has grown to 2-3 times the size of the cervix. The uterine corpus is divided into different regions: Isthmus: where the endocervicla canal opens into the endometrial cavity. Uterine cornu: Funnel shaped area on each side of the upper uterine body receives the insertion of the fallopian tubes. Fundus: The portion of uterus above uterine cornu. [30] Histologically, the wall of the uterus consists of the following three layers: Perimetrium: It is serous membrane that covers the outside of the uterus. Myometrium: It consists of several layers of smooth muscles and imparts the bulk of the uterine wall. Contractions of these muscles during childbirth help to force the fetus out o