Abnormal Menstrual Bleeding Control Of Normal Menstuation PGE2 vasodilation PGF2α vasoconstriction
• Progesterone is necessary to increase arachidonic acid, the precursor to PGF2α.
• With decreased progesterone there is a decreased PGF2α/PGE2 ratio. • Since vasoconstriction is promoted by PGF2α, which is less abundant due to the decrease in progesterone, vasodilation results thereby promoting AUB. Define • Any deviation in normal frequency, duration or amount of menstruation in women of reproductive age.
Normal Menses • Frequency: 21-35 days • Duration: 3-7 days • Volume: 30-80 ml Clinical Types
1. Menorrhagia:
• Cyclic bleeding at normal intervals
• Bleeding is either:
excessive in amount (>80ml) or
duration >7 days / both Causes Of Menorrhagia
Organic: Pelvic Pathology Fibroid uterus Adenomyosis Endometriosis IUCD – in-utero Tb. endometritis – early Ovarian tumour – Granulosa / Theca cell Salpingo-oophoritis, PID Causes Of Menorrhagia
Systemic: • Liver dysfunction • Congestive cardiac failure • Severe hypertension
Endocrine: • Hypothyroidism • Hyperthyroidism – initial stages Causes Of Menorrhagia
Blood dyscrasis:
• ITP • Leukaemia • Von Willerbrand’s disease • Coagulopathy • Severe anaemia Clinical Types
2. Epimenorrhoea / Polymenorrhoea:
• Frequent (<21 days) menstruation,
• at regular intervals.
Frequent cycle + excessive bleeding → Epimenorrhagia Epimenorrhoea / Polymenorrhoea: Causes: 1. Dysfunctional Hypothalamus - Pituitary - Ovarian axis seen at: • extremes of age, • following delivery due to hypersensitivity.
2. PID
3. Endometriosis Clinical Types
3. Metrorrhagia:
• Irregular, acyclical bleeding from the uterus
• Excessive (>80 ml) & / or prolonged menstruation Metrorrhagia Causes:
1. Causes Of Acyclic Bleeding:
Submucous fibroid
Uterine polyp
Ca - cervix & endometrium Metrorrhagia Causes:
2. Causes Of Contact Bleeding:
Ca cervix
Mucous polyp of cervix
Infections of cervix
Cervical endometriosis Metrorrhagia Causes:
3. Causes Of Intermenstrual Bleeding: • Causes of contact bleeding +
Urethral caruncle
Break through bleeding in pill use
IUCD – in – utero
Decubitus ulcer Clinical Types
4. Oligomenorrhea:
• Infrequent uterine bleeding (>35 d)
• Remains constant at that frequency. Causes Of Oligomenorrhea i. Extremes of age – adolescence and pre menopause ii. Weight related obesity iii. Stress and exercise related iv. Endocrine disorders – PCOD, hyperprolactinaemia, hyperthyroidism v. Androgen producing tumours – ovarian / adrenal vi. Tb. Endometritis Clinical Types
5. Hypomenorrhoea:
• When menstrual blood is unduly scanty and lasts for less than 2 days. Causes Of Hypomenorrhoea
1. Genital Tract: Uterine synechiae Tb Endometrial.
2. Endocrinal: Use of OCP Thyroid dysfunction Premenopausal period
3. Systemic: Severe malnutrition Clinical Types
6. DUB Abnormal uterine bleeding for which an organic etiology has been excluded. It is either ovulatory or anovulatory in origin. Classification Of DUB:
I. Ovulatory DUB: a) Functional polymenorrhoea (or) Functional polymenorrhagia b) Functional menorrhagia
– Irregular ripening
– Irregular shedding Classification Of DUB:
2. Anovulatory DUB:
• Metropathia haemorrhagica
• Threshold bleeding Ovulatory DUB
1. Functional Poly / Epimenorrhoea:
• Seen in extremes of age group, following child birth & in PID
• The follicular development is speeded up with resulting shortening of the follicular phase
• Probably due to hyperstimulation of the follicular growth by FSH Ovulatory DUB
2. Functional Menorrhagia: A. Irregular ripening: corpus luteal in-sufficiency • CL does not function properly & inadequate amount of E&P are produced → inadequate to induce proper secretory changes in endometrium, • Because of decreased progesterone → breakthrough bleeding. Ovulatory DUB
2. Functional Menorrhagia: A. Irregular ripening: • There will be break through bleeding or Pre menstrual bleeding • Brownish discharge from GT
E E+P
GF 14th CL Ovulatory DUB
2. Functional Menorrhagia:
B. Irregular shedding: corpus luteal persistency
• CL continues to function and secrete E & P beyond 14 days therefore there is NO drop of E & P levels which is essential for normal menstruation Ovulatory DUB
2. Functional Menorrhagia:
B. Irregular shedding: • Here patient c/o having had normal periods for 4-5 days and then slight bleeding for another 4-5 days → “Prolong bleeding”
E E+P
GF 14th CL Anovulatory Type
1. Metropathia Haemorrhagica: • Seen in extremes of age group • GF continue to grow under the influence of FSH • As there is no LH surge from the anterior pituitary ovulation does not take place Anovulatory Type 1. Metropathia Haemorrhagica: • As the follicles produce E2 unopposed by P→ – Endometrium becomes thick – Myometrium becomes hyperplastic – Due to continued action of E2 & continuous growth of endometrium menstruation does not occur on 28th / 30th day it may be prolonged for 3-4 weeks. Anovulatory Type
2. Threshold bleeding:
• Due to low levels of FSH, GF grows with inadequate production of E2 but enough E2 is produced to induce a certain amount of endometrial growth. Anovulatory Type
2. Threshold bleeding:
• Whenever the E2 levels falls below the threshold level → E2 withdrawal bleeding occurs by the shedding of thin endometrium. • Note: Even this bleeding can be heavy as there is NO action of progesterone on the endometrium. Adolescent Gynecology
Associated Professor Syuzanna Babloyan Department of Ob & Gyn Yerevan State Medical University
Primary Amenorrhea
Dr. Sudha Prasad Professor Unit IV In charge & IVF In-charge Dept. Obstetrics & Gynecology Definition
Absence of menstruation by 16 years of age of age in the presence of normal secondary sexual characteristics or by 14 years in absence of secondary sexual characteristics. Patho-Physiology of Menstruation Hypothalamus
Hypothalamus
Gn-RH ± Ant. pituitary ? – FSH, LH Estrogen Ovaries Progesterone
Uterus
Menses Types of Amenorrhea
• True amenorrhea – Primary – Secondary • Cryptomenorrea or False amenorrhea Causes of Cryptomenorrhea
• Imperforate hymen • Transverse Vaginal septum with functioning uterus • Isolated Vaginal agenesis with functioning uterus • Isolated Cervical agenesis with functioning uterus Clinical Features • Intermittent abdominal pain • - Possible difficulty with micturition • - Possible lower abdominal swelling • Bulging bluish membrane at the introitus or absent • vagina (only dimple)
Etiology of Primary amenorrhea Physiological – Before puberty – Adolescence – Pregnancy – Lactation – Menopause Pathological Amenorrhea – Hypothalamic amenorrhea – Diseases or injury in the region of mid brain – Pituitary amenorrhea – Ovarian amenorrhea – Uterine amenorrhea – Drugs – General constitutional upset and diseases – Environment – Exercise related amenorrhea Hypothalamic amenorrhea
• Disturbance of hypothalamus leading to interference in production of GnRH. • It may interfere with other RH also. • Hence it can cause pituitary infantilism, galactorrhea, stunted growth, obesity or genital hypoplasia. Diseases or injury in the region of mid brain • Encephalitis • Meningitis • Tumors • Fracture of the base of the skull • Psychoses • Emotional upset Pituitary amenorrhea
• Pituitary inability to secrete gonadotropins • Tumors in or near the pituitary gland • Diseases of the anterior pituitary • Pituitary necrosis following massive obstetric hemorrhage is most common cause in women Ovarian Amenorrhea
• Underproduction of estrogen and progesterone • Continuous production of estrogen and progesterone • Overproduction of androgens • Polycystic ovarian syndrome Uterine Amenorrhea
• Congenital absence of uterus – Mullarian duct agenesis • Heavy curettage • Post abortal or peurperal infection • Infection –Tuberculous endometritis • Radiation Drugs • Drugs to cause secondary amenorrhea AMENORRHOEA AN APPROACH FOR DIAGNOSIS
Exclude Pregnancy Exclude Cryptomenorrhea
•HISTORY •PHYSICAL EXAMINATION •ULTRASOUND EXAMINATION Clinical Presentation Four categories of patients are identified 1. Amenorrhea with absent or poor secondary sex 2. Amenorrhea with normal secondary sex characters 3. Amenorrhea with absent uterus and vagina 4. Amenorrhea with signs of androgen excess Amenorrhea with Absent or poor secondary sex Characteristics
Serum FSH level
Low/Normal High
Hypogonadotropic Gonadal dysgenesis hypogonadim Hypogonadotrophic Hypogonadism
Normal hight • Normal external and internal genital organs (infantile) • Low FSH and LH • MRI to R/O intra-cranial pathology. • 30-40% anosmia (kallmann’s syndrome) • May be constitutional delay • Treat according to the cause (HRT), potentially fertile. Gonadal dysgenesis
Chromosomally incompetent Classic turner’s syndrome (45XO) Turner variants (45XO/46XX), (46X-abnormal X) Mixed gonadal dysgenesis (45XO/46XY) Chromosomally competent 46XX (Pure gonadal dysgenesis) 46XY (Swyer’s syndrome) Turner’s syndrome • Sexual infantilism and short stature. • Associated abnormalities, webbed neck, coarctation of the aorta, high-arched pallate, cubitus valgus, broad shield-like chest with widely spaced nipples, low hairline on the neck, short metacarpal bones and renal anomalies. • High FSH and LH levels. • Bilateral streaked gonads. • Karyotype - 80 % 45, X0 - 20% mosaic forms (46XX/45X0) • Treatment: HRT (Classic 45-XO) Mosaic (46-XX / 45-XO) Ovarian Dysgenesis Amenorrhea with Normal secondary sex Characteristics
FSH, LH, Prolactin, TSH Provera 10 mg PO daily x 5 days
Prolactin + Bleeding No bleeding TSH FSH - Mild hypothalamic dysfunction - PCO ( LH/FSH) Work-up Serum FSH
High Low / normal
Ovarian Hypothalamic-pituitary failure Failure
If < 25 yrs or primary head CT- scan or MRI amenorrhea karyotype If < 35 yrs R/O - Severe hypothalamic autoimmune disease dysfunction - Intracranial pathology ?? Ovarian biopsy Amenorrhea with Utero-Vaginal Absence Karyotype
46-XY 46-XX
. Gonadal regression Andogen Mullarian •. Testicular enzyme Insensitivity Agenesis deficiency (TSF syndrome) (MRKH syndrome) •. Leydig cell agenesis Normal breasts Normal breasts Absent breasts & absent sexual & sexual hairs & sexual hairs hairs Androgen insensitivity Testicular feminization syndrome
• X-linked trait • Absent cytosol receptors • Normal breasts but no sexual hair • Normal looking female external genitalia • Absent uterus and upper vagina • Karyotype 46, XY • Male range testosterone level • Treatment : gonadectomy after puberty + HRT • ? Vaginal creation (dilatation VS Vaginoplasty ) Utero-vaginal Agenesis Mayer-Rokitansky-Kuster-Hauser syndrome
• 15% of primary amenorrhea • Normal breasts and sexual hair development & normal looking external female genitalia • Normal female range testosterone level • Absent uterus and upper vagina & Normal ovaries • Karyotype 46-XX • 15-30% renal, skeletal and middle ear anomalies • Treatment : Vaginal creation (Vaginoplasty)
Amenorrhea
Suzanna R. Babloyan MD, PhD Associated Professor Department of Obstetrics and Gynecology Yerevan State Medical University
Thank you Cervical Intraepithelial Neoplasia Bethesda system classification
Yerevan State Medical University Department of Obstetrics and Gynecology
Associated Prof. Miss Syuzanna Babloyan
Thank you! Chlamydia Trachomatis
Suzanna R. Babloyan MD, PhD
Associated Professor Department of Obstetrics and Gynecology Yerevan State Medical University
Thank you Dysfunctional Uterine Bleeding/ Abnormal Uterine Bleeding
Dr. Sudha Prasad Professor MAMC New Delhi INDIA Normal Menstruation
Duration: 2-7 days Cycle = 23-40 days Amount: Avg. MBL 40 ml ≥ 80 ml - abnormal Definition Abnormal bleeding from the uterus in the absence of any detectable pelvic pathology - tumor, inflammation or pregnancy.
Abnormality in:
Frequency
Amount
Duration
or all three Menorrhagia (Hypermenorrhoea): Cyclical bleeding at normal intervals, which is excessive in amount or duration (5/28 or 8/28)
Polymenorrhoea: Cyclical bleeding at too frequent intervals < 22 days. (5/21)
Polymenorraghia: Cyclical bleeding which is both excessive and too frequent. (9/20-12/20)
Metorrhagia: Acyclical bleeding DUB: Most commonly implies menorrhagia. Etiology
.Purely hormonal .P/V: Essentially normal Incidence: 20-30% women in reproductive age. Pathophysiology
. Local causes in endometrium Altered prostaglandin ratio-
. Increased PGE2 , PGI2 (vasodialators and anti platelet aggregates)
. Decreased PGF2α (vasoconstrictors and platelet aggregates)
. Increased fibrinolytic activity (Tissue Plasminogen activator (TPA) increases).
. Alteration in hypothalamo-pituitary-ovarian axis. Phospholipids
Arachidonic acid Prostaglandin synthetase
Prostaglandin endoperoxidase
Thromboxane PGD PGF2α PGE2 2 Prostacyclin Classifications
Anovulatory (80%) Ovulatory (20%) Puberty Irregular ripening menorrhagia Irregular Metropathia shedding menorrhagica IUCD insertion Premenopausal Following dysfunction sterilization uterine bleeding Anovulatory AUB
Puberty Menorrhagia : Excess estrogen Absent progesterone Premenopausal dysfunction bleeding: R/o Ca endometrium (D&C) Metropathica Haemorrhagia (CGH):
Usually in females>40 yrs (40-45 yrs) Amenorrhoea 6-8 weeks followed by continuous painless bleeding for weeks ovaries are cystic HPE: Myohyperplasia Endometrium: Cystic dialation of glands (Swiss cheese pattern) Absence of secretory hypertrophy Necrotic areas over superficial layers of endometrium. Ovulatory AUB IRREGULAR RIPENING
Deficient corpus luteal function
Inadequate progesterone secretion
Breakthrough bleeding before periods
T/t: Progesterone in premenstrual phase IRREGULAR SHEDDING
Persistent corpus luteum
Prolonged menstruation
Self limiting & spontaneous cure occurs Diagnosis History:- Age, parity and fertility Amount, duration and pattern of uterine bleeding Any symptoms s/o bleeding disorder or myxedema Examination
Evaluate and rule out: Obesity/ signs of androgen excess Thyroid enlargement Galactorrhoea Abdominal and pelvic/ PR examinations Test Indication Urine pregnancy test Pregnancy
CBC Anaemia PT/APTT Coagulopathy (especially in adolescents) Pap smear Cervical cancer TSH Thyroid disease USG Assess endometrium and rule out endometrial carcinoma, endometrial polyp, uterine fibroid. Endometrial sampling Diagnostic Therapeutic in 30%
To exclude organic lesion (Ca Endo, Endo polyp, tubercle endometritis fibroids. To assess final state of endomtrium: Proliferative/ Secretory/ Atrophy/ Irregular ripening/ Irregular shedding Hysteroscopy
Visualises entire uterine cavity Small polyp or submucous fibroids can be identified and treated simultaneously. Management
General Measures: . Menstrual calendar . Oral iron therapy . T/t of secondary disease in present (remove IUCD) MEDICAL NON-HORMONAL HORMONAL . Antifibrinolytics . Progesterone (tranexamic acid) . Oral . Prostaglandin . Intrauterine synthetase . Injectable inhibitors . OCP . NSAID’s . Danazol . Ethamsylate . GnRH analogue Tranexamic acid Antifibrinolytic agent Decrease plasminogen activator Efficacy:- 40-60% reduction of blood loss. Dose: 1 gm 6-8 hrs/day S/E: N/V/D, leg cramps, headache, intracranial thrombosis Ethamsylate
Reduces capillary fragility Dose: 50 mg QID Efficacy: 50% reduction of menstrual blood loss NSAID’s Cyclo-oxygenase inhibitors
Decreases prostaglandin levels
Decreases MBL 25-30% Dose:- 500 mg, 8 hr/day during periods Advantage: . Cheap . Decreases dysmenorrhoea S/E: GI side effect gastritis Hormones (A) PROGESTERONE THERAPY: [MPA, norethistrone] Mechanism: Endometrial thinning Increases PGF2α/ PGE ratio Regimens (oral): (a) D5-D25 in endometrial hyperplasia 6-9 months (b) Luteal phase: D15-D25 for anovulatory cycles. (c) Arrest of hemorrhage: Norethisterone acetate, 20-30 mg daily till bleeding stops, lower dose for 21st day Depo-medroxyprogesterone:- 150 mg I/M 3 monthly Also provides contraception Progestin releasing IUD’s
LNG-IUS (Mirena) Progestasert
. Local endometrial . Needs atophy replacement . 20 microgram/day (5 every year not yrs) convenient .80-90% decreased MBL Advantage (Mirena) . Less S/E . Contraception .As effective as endometrial ablation
S/E:- Intermittent spotting COMBINED ORAL CONTRACEPTION PILL Mechanism
. Endometrial suppression Efficacy:- 30-50% reduction in MBL Advantage
. Contraception
. Dysmenorrhoea SIE: Bloating/ weight gain DANAZOL: . Androgenic action, suppresses endometrium . Reserve drug (when OC’P are contra- indicated) . S/E: Androgenic GnRH Analogue:- . Mechanism: Pituitary down regulation . Advantage: High efficacy . S/E: Cost and has antiestrogenic effects Surgical Management . When medical therapy fails . other associated symptoms persist (a) D & C . Therapeutic- 30-40% . Ding dysplasia or malignancy . Avoided in adolescents (b) ENDOMETRIAL ABLATION Patients who wish to avoid hysterectomy. Patients who are not candidates for major surgery FIRST GENERATION . Laser ablation . Roller ball diathermy SECOND GENERATION . Microwave ablation Hysteroscopic Resection
Thermal uterine TCRE (using ballooning electrocautery loop or ball) to remove endometrium. May reduce the need for hysterectomy by upto 90% Most effective in women over 35 yrs. Hysterectomy
Complete cure Avoidance of long term medical therapy Removal of any missed pathology including unsuspected malignancy
Emergency conditions in gynecology Ectopic pregnancy An ectopic pregnancy is a medical emergency and if not treated properly can lead to the death of the mother. An ectopic pregnancy is a complication of pregnancy in which the fertilized ovum is implanted in any tissue other than the uterine wall. Most ectopic pregnancies occur in the Fallopian tube (so-called tubal pregnancies), but implantation can also occur in the cervix, ovaries, and abdomen. The fetus produces enzymes that allow it to implant in varied types of tissues, and thus an embryo implanted elsewhere than the uterus can cause great tissue damage in its efforts to reach a sufficient supply of blood. Pregnancy can even occur and the tube at the same time (heterotopic pregnancy), but this is rare, about 1/10.000. Risk factors:
• Pelvic inflammatory disease; • Infertility • Tubal surgery • Smoking • Previous ectopic pregnancy • Multiple sexual partners • Current IUD use • Tubal ligation • Previous abortions and so on Cilial damage and tube occlusion
Hair-like cilia located on the internal surface of the Fallopian tubes carry the fertilized egg to the uterus. Damage to the cilia or blockage of the Fallopian tubes is likely to lead to an ectopic pregnancy. Women with pelvic inflammatory disease (PID) have a high occurrence of ectopic pregnancy. This results from the build-up of scar tissue in the Fallopian tubes, causing damage to cilia. If however both tubes were occluded by P1D, pregnancy would not occur and this would be protective against ectopic pregnancy. Tubal surgery for damaged tubes might remove this protection and increase the risk of ectopic pregnancy. Tubal ligation can predispose to ectopic pregnancy. Symptoms
Early symptoms are either absent or subtle. Clinical presentation of ectopic pregnancy occurs at a mean of 7 2 weeks after the last normal menstrual period, with a range of 5 to 8 weeks. Later presentations are more common in communities deprived of modern diagnostic ability. The early signs are:
• Pain in the lower abdomen, and inflammation (Pain may be confused with a strong stomach pain, it may also feel like a strong cramp) • Pain while urinating • Pain and discomfort, usually mild. A corpus luteum on the ovary in a normal pregnancy may give very similar symptoms. • Vaginal bleeding, usually mild. An ectopic pregnancy is usually a failing pregnancy and falling levels of progesterone from the corpus luteum on the ovary cause withdrawal bleeding This can be indistinguishable from an early miscarriage or the ‘implantation bleed’ of a normal early pregnancy. • Pain while having a bowel movement Patients with a late ectopic pregnancy typically experience pain and bleeding. This bleeding will be both vaginal and internal and has two discrete pathophysiologic mechanisms.
• External bleeding is due to the falling progesterone levels. • Internal bleeding (hematoperitoneum) is due to hemorrhage from the affected tube. The differential diagnosis at this point is between miscarriage, ectopic pregnancy, and early normal pregnancy. The presence of a positive pregnancy test virtually rules out pelvic infection as it is rare indeed to find pregnancy with an active Pelvic Inflammatory Disease (PID). The most common misdiagnosis assigned to early ectopic pregnancy is PID. More severe internal bleeding may cause: • Lower back, abdominal, or pelvic pain. • Shoulder pain. This is caused by free blood tracking up the abdominal cavity, and is an ominous sign. • There may be cramping or even tenderness on one side of the pelvis. • The pain is of recent onset, meaning it must be differentiated from cyclical pelvic pain, and is often getting worse. • Ectopic pregnancy can mimic symptoms of other diseases such as appendicitis, other gastrointestinal disorder, problems of the urinary system, as well as pelvic inflammatory disease and other gynaecologic problems. Diagnosis
• An ectopic pregnancy should be considered in any woman with abdominal pain or vaginal bleeding who has a positive pregnancy test.
• An ultrasound showing a gestational sac with fetal heart in the fallopian tube is clear evidence of ectopic pregnancy. An abnormal rise in blood βhCG levels may also indicate an ectopic pregnancy. The threshold of discrimination of intrauterine pregnancy today is around 1500 IU/ml of β- human chorionic gonadotropin (βhCG). A high resolution, vaginal ultrasound scan showing no intrauterine pregnancy is presumptive evidence that an ectopic pregnancy is present if the threshold of discrimination for βhCG has been reached. An empty uterus with levels lower than 1500 IU/ml may be evidence of an ectopic pregnancy, but may also be consistent with an intrauterine pregnancy which is simply too small to be seen on ultrasound. If the diagnosis is uncertain, it may be necessary to wait a few days and repeat the blood work and ultrasound. If the βhCG falls on repeat examination, this strongly suggests,an abortion or rupture. A laparoscope or laparotomy can also be performed to visually confirm an ectopic pregnancy. Often if a tubal abortion has occurred, or a tubal rupture has occurred, it is difficult to find the pregnancy tissue. A laparoscopy in very early ectopic pregnancy rarely shows a normal looking fallopian tube. Two percent of ectopic pregnancies occur in the ovary, cervix or are infraabdominal while a fetus of ectopic pregnancy is typically not viable, very rarely, a live baby has been salvaged from an abdominal pregnancy. In such a situation placenta sits on the intraabdominal organs of the peritoneum and has found sufficient blood supply, such as bowel or misentery. On 19 April 2008 an English woman, Jayne Jones (age 37) who had an ectopic pregnancy attached to the omentum, the fatty covering of her large bowel, gave birth. The baby was delivered by a laparotomy at 28 weeks gestation. The surgery, the first of its kind to be performed in the UK, was successful, and both mother and baby survived. On May 29, 2008 an Australian woman, Meera Thangarajah (age 34), who had an ectopic pregnancy in the ovary, gave birth to a healthy full term 6 pound 3 ounce (2,8 kg) baby girl, Durga, via Caesarean section. She had no problems or complications during the 38 week pregnancy. Heterotopic Pregnancy In rare cases of ectopic pregnancy, there may actually be two fertilized eggs, one outside the uterus and the other inside. This is called a heterotopic pregnancy. Often the intrauterine pregnancy is discovered later than the ectopic, mainly because of the painful, emergency nature of ectopic pregnancies. Since ectopic pregnancies are normally discovered and removed very early in the pregnancy, an ultrasound may not find the additional pregnancy inside the uterus. When hCG levels continue to rise after the removal of the ectopic pregnancy, there is the chance that a pregnancy inside the uterus is still viable. This is normally discovered through an ultrasound. Treatment
• Early treatment of an ectopic pregnancy with the antimetabolite methotrexate has proven to be a viable alternative to surgical treatment since 1993. If administered early in pregnancy, methotrexate can disrupt the growth of the developing embryo cousing the cessation of pregnancy. Surgical treatment
If hemorrhaging has already occurred, surgical intervention may be necessary. Complications
The most common complication is rupture with internal bleeding that leads to shock. Death from rupture is rare in women who have access to modern medical facilities. Infertility occurs in 10-15% of women who have had an ectopic pregnancy. Endometriosis Diagnosis and Treatment
Yerevan State Medical University Department of Ob & Gyn Assoc. Prof. Syuzanna Babloyan
Endometriosis is a disorder in which abnormal growths of tissue, histologically resembling the endometrium, are present in locations other than the uerine lining
Occurin rerely in post-menopausal women
Found almost exclusively in repoductive age 25%-35% women with inferility has endometriosis
Pathogenesis – Unknown The theories include retrograde menstruation with transport of endometrial cells, metaplasia of coelomicepithelium, and hematogenous or lymphatic spread of endometrial cells. Clinical findings dependin on number, sizeand extent f the lesions
Infertility, Dysmenorhea, Dyspareunia are the main presenting complication True complication of endometriosis are: smphysis of uterus with bowel, obstructron of tubes. Endometriosis can cause ovarian torsion or rupture Staging
Stage I- Minimal ( Superficial Endom- 1- 3cm., R. Ovary – less 1cm) Stage II – Mild ( Dep Endo –more than 3cm., R. L. Ovary less than 1cm.) Stage III – Moderate ( Deep Endo - more than 3 cm., L.R. Ovary , Peritoneum more than 1cm) Stage IV – Severe ( Dep Endo – more than 3 cm., Culdesac, Peritoneum, Tubes , R.&L. Ovary more than 2cm)
Thank you !
FIBROID UTERUS
Suzanna R. Babloyan MD, PhD Associated Professor Department of Obstetrics and Gynecology Yerevan State Medical University
THANK YOU Gestational trophoblastic disease
Dr. Sudha Prasad Professor Department Obstetrics & Gynecology MAMC New Delhi, India Definition of GTD
Group of diseases Abnormalities of placenta Benign but hyperproliferative H Mole Malignant choriocarcinoma The current WHO classification
Malignant neoplasm of various types of trophoblast Chorio CA PSTT Epitheloid trophoblastic tumors Malformation of chorionic villi that are predisposed to develop Troph.Malignancy H Mole Benign entities which are confused with these lesions Exaggerated placental site Placental site nodule Worldwide varied incidence
course of GTD still remains obscure & confounding Recurrent cases are rare Mostly related to individual pregnancies Incidence of H.Mole in India 1.3 to 12/1000 deliveries Incidence in UK is 1.5/ 1000 live births Choriocarcinoma : 1 case in 50,000 live births The genesis & natural HYDATIDIFORM MOLE
INCIDENCE 1 IN 400 PREG. TIME OF DETECTION 8 – 24 WEEKS CLINICAL PRES. Uterus size>POG in 45% AGE ETHNICITY PREVIOUS H. MOLE REPRODUCTIVE & CONTRACEPTIVE FACTORS CIGARETTE SMOKING BLOOD TYPE NUTRITIONAL FACTORS HERBICIDE EXPOSURE COMPLICATIONS OF MOLAR PREGNANCY Non- neoplastic Neoplastic Endrocinologic Choriocarcinoma Respiratory Cardiogenic non-metastatic Metastatic Hematologic Coagulation abnormalities Low risk lnt. risk Uterine perforation High risk Pelvic sepsis INVESTIGATIONS • FULL BLOOD COUNT TO CHECK FOR ANAEMIA • CLOTTING FUNCTION STUDIES • KFT, LFT • X- RAY CHEST • PRE-EVACUATION SERUM BETA-HCG • T3, T4, IF THERE IS CLINICAL SUSPICION OF THYROTOXICOSIS • USG PELVIS Standard treatment of H.Mole Suction evacuation No medical induction Avoid syntocinon TREATMENT Arrange blood. Suction evacuation if x-ray chest is negative. No medical induction. Hysterectomy if patient wants it. Repeat D & c if irregular bleeding occurs. Histological analysis of evacuated uterine contents. HOW TO SUSPECT INVASIVE MOLE Acute abdominal pain Shock due to Haemoperitoneum. While doing suction evacuation products not retrieved with ease and not proportional to the size of the uterus. Surveillance after molar pregnancy hCG: 48 hr. after evacuation Weekly till 3 normal values Two weekly for 3 months Four weekly for 6-12 months X-Ray chest : Pre or post evacuation Per vaginal examination: To assess adequate uterine involution Advise for contraception FOLLOW UP AFTER TREATMENT OF H.MOLE Weekly serum beta- hcg till normal and then monthly for 6 months to 1 year and 3 monthly for second year. Contraception Physical examination 2-4 weeks after evacuation of mole until remission. Chest film to be repeated if hcg titer plateaus or rises. Chemotherapy started immediately if hcg rises or plateaus during follow-up or metastasis are detected at any time Hcg monitoring after all further pregnancies. Contraception OCP’s after beta hCG has become normal OCP’s have added advantage of suppressing pituitary LH which may interfere with the measurement of low levels hCG in some assays. Study on 10,000 patients by International society for study of trophoblastic disease ----- When OCP’s were used before hCG became normal, it fell slowly and had not reached to normal even 8 weeks after evacuation of mole. If started earlier may stimulate growth of residual tumor, thus increases the chances of receiving chemotherapy. Prophylactic chemotherapy Controversial Can be used in high risk situations Or Follow up is unreliable It has been reported to reduce the risk of PTD to 14% from 47%. Malignant Gestational Trophoblastic Disease Postmolar gestational trophoblastic disease • Non-invasive trophoblastic -Proliferation •Invasive mole -Gestational choriocarcinoma -PSTT GTT is a relatively uncommon condition & that unless affiliated with a T/ t center, most gynecologist never gain sufficient experience to develop the judgment required to individualize therapy appropriately. Despite the excellent prognosis of most cases of GTT, controversy still exists regarding T/ t strategies that will maximize outcome while minimizing morbidity and cost. Centralized referral system England Weston Park hospital ( Shffield) Charing cross hospital ( London) Nine wells hospital ( Dundee) PTD are treated only in first two USA The U.K.Trophoblastic Disease Registration & Surveillance scheme was established in 1973 by RCOG in conjuction with the department of health Persistent trophoblastic disease Evidence of persistent disease unlikely to resolve spontaneously This fundamental definition is generally accepted GTN are rare tumors but highly curable Patients who receive chemotherapy varies greatly 5-6% in Sheffield (UK) 12-15% in Europe 20-30% in North America The current FIGO criteria to diagnose post molar GTD include: – 4 values or more of hCG documenting a plateau (plus, minus 10% of hCG value) over at least 3 weeks: days 1,7,14 and 21. A rise of hCG of 10% or greater for 3 values or longer over at least 2 weeks: days 1,7 and 14 The presence of histologic choriocarcinoma Persistence of hCG 6 months after mole evacuation. CHORIOCARCINOMA • Incidence :1 in 20,000-40,000 pregnancies. • 50% after term delivery • 25% after molar pregnancy • Remainder after other gestational events. Risk of post molar GTD 20-30% after D&C 3-5% after Hysterectomy Most of the recurrences after evacuation are evident within 6 months 3% after partial mole 25% after complete mole 70-90% are invasive mole 10-30% are choriocarcinoma 6-25% have metastatic disease. Data base for evaluation of patients risk for postmolar trophoblastic disease • Chest x-ray • Pre-evacuation hCG titer • Patients age • Previous molar gestation • Uterine gestational size • Gestational age (menstrual dates) • Theca-lutein cysts • Presence of fetus • Medical complications Toxemia Hyperthyroidism Pulmonary insufficiency Invasive mole is the most common form of PTD following a mole. It is probably 6-10 times more common than choriocarcinoma. From clinical stand point of view Difficult to differentiate between Invasive mole & Ch. Carcinoma Both result in elevated hCG & both can give rise to secondary lesions in lung & elsewhere. Not necessary to distinguish for treatment purpose. METASTASIS • Lungs - 80% • Vagina - 30% • Pelvis - 20% • Brain - 10% • Liver - 10% • Rare sites – Spleen, Kidney and GI Tract How to work up? . Full history Imaging Full examination X-Ray chest CT chest Blood tests USG : Abd. & pelvis Endocrine CNS assessment if required Beta hCG TFT Hematology Biochemistry LFT Urate Workup of GTN •Score the disease •Stage the disease Revised FIGO scoring system for GTT Parameter 0 1 2 3 Age(yr) <39 >39 - - Antecedent Mole Abortion Term - pregnancy Interval <4 4 - 6 7-12 >12 Pre T/ t <10 3 10 3-10 4 10 4-10 5 >10 5 hCG Largest 3-4 5 - - tumor(cm) Sites of Lung, Spleen GI T Brain Metastasis Vagina Kidney Liver No. of 0 1 - 4 4 - 8 >8 Metastasis Prior - - Single drug 2 or more Chemo. drugs failed LR 6 or <, HR 7or > Clinical FIGO staging Stage I Stage II Stage III Stage IV EVOLUTION OF STAGING SYSTEM 1976: Hammond’s clinical classification 1983: WHO proposed a modification of prognostic scoring system of Bagshawe 1992: FIGO gave the revised anatomic staging system 2000: Modified WHO prognostic scoring system X-Ray chest / CT chest 29-41% of patients of GTD treated as non- metastatic as per x-ray chest findings, have occult lesions in chest which have been missed by x-ray. CT chest should be done during work up of patient of PTD if x-ray chest is negative, because this will help in deciding the form of chemotherapy. CNS assessment All high risk patients Beta hCG > 50,000 iu/L Patients with 5 or more metastasis visible on a x-ray chest, 8 or more metastasis visible on CT scans of thorax or with single nodule greater than 3 cms. CT head LP- provided there is no clinical evidence of raised intracranial pressure An abnormal CSF-beta hCG is interpreted as one where the ratio with serum beta hCG value is > 1:60 Common problems with hCG determination in trophoblastic disease The USA hCG reference service experience Started in 1998 Measures total hCG concentration by DPC Immulite assay in parallel serum and urine samples False positive results were identified by following criteria: Finding of > 5 fold diff. in serum hCG with alt. immunoassays Prescence of hCG in serum & absence in parallel sample Prescence of urine beta core fragment ( confirmatory criteria) The finding that a heterophilic antibody blocking agent prevented or limited false detection. Serum beta hCG It is a glycoprotein with 5 key variants Regular hCG Hyperglycosylated hCG Nicked hCG hCG missing beta subunit c-terminal peptide Free beta subunit Nicked free beta subunit Urine beta core fragment Unexplained elevated hCG Pregnancy like hCG is produced by scattered differentiated trophoblast cells remaining from evacuation of H.Mole or another source of trophoblast cells, are non-invasive cells, and that because they are slow growing, may not respond to chemotherapy. In patients with persistent low levels of hCG, hyperglocosylated hCG should be done. Level should be < 30% of the total hCG to label it as false positive. Hyperglocosylated hCG is a new and invaluable marker for monitoring GTD. Hyperglocosylated hCG is only produced by invasive cytotrophoblast cells. Measurements of this can be used to differentiate invasive and noninvasive disease. Hyperglocosylated hCG test is now commercially available. Principles of treatment In general adequate treatment response is defined by a 50% reduction in beta hCG on weekly serum analysis. The level of beta hCG may reach normal or become undetectable when there is still a residual tumor burden of 10 5- 10 6 cells. Therefore two more courses are given after the normal report of serum beta hCG. Chemotherapy plan Low risk group Salvage of drug resistance in low risk patients High risk group Salvage of drug resistance in high risk patients Treatment of established disease TREATMENT OPTIONS Non-metastatic GTT-Single agent Methotrexate With leucovorin Dactinomycin Etoposide( rarely used) Metastatic good prognosis- GTT- Single agent Methotrexate With leucovorin Dactinomycin Primary hysterectomy followed by single agent chemotherapy if patient has completed her family Primary chemotherapy followed by secondary hysterectomy for persistent uterine disease( must verify that metastatic disease has totally regressed) For refractory disease : MAC –Metho., Actino.,Chlorambucil. SINGLE AGENT CHEMOTHERAPY 1) Methotrexate 20-25 mg IM every day for 5 days (repeat every 7 days if possible) 2) Dactinomycin 10-12 µg/kg IV every day for 5 days (repeat every 7 days if possible) 3) Methotrexate 1 mg/kg IM on days 1, 3, 5, and 7 Folinic acid 0.1 mg/kg IM on days 2, 4, 6, and 8 (repeat every 7 days if possible) 4) Dactinomycin 1.25 mg/m2 I.v. on day 1 every 2 weeks 5-FU 28-30 mg/kg iv. By 8-h infusion daily for 10 days. 5) Methotrexate 30-50 mg/m2 I.m. once weekly 6) Etoposide 200 mg/m2 I. V. daily for 5 days Metastatic poor prognosis EMA-CO P-cisplatin EMA-CE V-vinblastin APE E-etoposide PVB B-bleomycin PEBAd M-methotrexate Ad-adriamycin Ifosfamide+carboplati n+etoposide with A-dactinomycin autologous bone C-Vincristine marrow transplant O-cyclophosmamide EMA-CO Chemotherapy Day 1 EMA: etoposide, 100 mg/m2 IV; and dactomycin 0.5 mg IV; and methotrexate, 100 mg IV push followed by 200 mg/m2 12-h IV. Day 2 EMA: etoposide, 100 mg/m2 IV; dactomycine, 0.5 mg IV, and folinic acid 15 mg IV or PO every 12 h x 4, 24 h after start of methotrexate. Day 8 CO: vincristine, 1 mg/m2 IV and cyclophosphamide, 600 mg/m2 IV Response rate: 84-86% OTHER COMBINATION CHEMOTHERAPY REGIMENS • CHAMOMA • CHAMOCA • EHMMAC • MBP • MAC Treatment of established CNS disease Single cerebral metastasis should be excised prior to chemotherapy Whole brain radiation has no place in routine management but can be used in refractory cases. MTX. 1 gm/m 2 in 2 litres of normal saline infused over 24 hours Folinic acid 15 mg, 6 hourly commencing at the end of MTX infusion 12 doses are given Seven days interval Intrathecal MTX should be continued for 4 injections after CSF serum ratios have become normal. SALVAGE REGIMENS • PEBA: cisplatin, etoposide, bleomycin doxorubicin, • VIP: etoposide, ifosfamide and cisplatin, also ifosfamide alone • Taxanes, platinum an vinca analogues, topisomerase 1 inhibitors When to change chemotherapy • hCG titer has not dropped least by 25% • Titer plateaus • Evidence of new metastasis • Toxicity doesn’t permit adequate dose of chemotherapy. When to stop chemotherapy during treatment period • TLC<3,000 mm3 • Platlet count<100,000/ mm3 • SGOT, SGPT is raised • Severe oral or GI ulceration • Febrile course INDICATIONS FOR SURGERY A. Management of acute complications Gastrointestinal/ urinary tract obstruction lntraperitoneal hemorrhage Raised intracranial pressure lntracranial hemorrhage Hemorrhage from vaginal nodules B. Removal of only known focus of disease Thoracot my and removal of solitary lung nodule Hysterectomy for isolated focus of drug-resistant tumor Localized excision of uterine nodules Craniotomy and excision of cerebral metastases. Role of radio therapy • It decreases tumor vascularity • Stabilizes hemorrhagic complications • 2,000 - 3,000 rads are given over 10 days in combination with chemotherapy in some cases brain and liver metastasis. Results of treatment Disease Remission Non metastatic 100% Good prog. Meta. 100% Poor prog. Meta. 66%. Recurrent GTN All recurrences occur within 36 months of remission 85% before 18 months NM: 2.6% GPMD : 3.7% PPMD : 13%. Secondary tumors Leukaemia Colon cancer Melanoma Breast cancer Subsequent pregnancy H.Mole After hCg normal wait for 6 months can conceive Risk of repeat mole 1/55 Normal pregnancy like any other pregnancy If repeat mole 68-80% will have same histopathology PTD Not to conceive for 1 year after completion of treatment because: Early relapse can be promptly detected Cytotoxic drugs are know teratogens wait for 12 months allows DNA repair apoptosis of the damaged ova in the ovaries Encourage conception in patients in whom CT has been used if they desire so because menopause can be forwarded in this group. Gynecological Diagnosis History: Past history: • Medical and surgical M nesses Personal history: • Diet • bowel and micturition • habits • allergies Marital history: • Sexual intercourse • dyspareunia • contraceptives used • sexual disorders Family history: • diabetes • hypertension • genetic disorders • multiple births • others Menstrual history • Age of menarche • past menstrual cycles • present menstrual cycles • date of the last menstrual period Obstetric history: • Full-term deliverus • preterm deliverius • abortions. Physical examination General examination: • height; • weight; • nutritional status; • oedema; • temp; • pulse, • resp. rate. Systemic examination: • cardiovascular and respiratory system Gynegological examination • examination in situe and spiculum examination • bimanual examination • rectal examination Detailed history and clinical examination often clinch the diagnosis. The investigations also may be necessary to confirm the diagnoses: • Complete blood count • Urinalysis Preoperative investigations • Blood sugar examinations • kidney function tests • liver function tests • Blood test for infeciton • bluding time, clolling time • Blood group and Rh factor • Special tests: like tumor markers • bacherial examinations of the genital tract Special tests Papavicolaou test 1. Normal cytology 2. Inflammatory smear 3. Cervical intraepithelial neoplasma (CIN I) or mild dysplasia 4. CN II; III and carcinoma in situ 5. Malignant cells and tadpole cell with nucliar abnormalities Uterene aspiration cytology • colposcopy (for byopsy will positive pap smiars) • endometrial biopsy • hormonal assays • ultrasonography • hysterosalpinography • CT; MRI • Gynecological endoscopy • aspiration of Pouch of Douglas • Pregnancy test Pediatric gynecology The genital organs of the child are not develop. The ovaries are small and contain only primordial follicles. The ratio of the body of uterus to cervixis 1:1 hypothalamus is insensitive. Avery small amount of oestrogen found in the blood comes from ovary and adrenal gland. Puberty is a change from childhood to adulthood, and imolies physical, biological and psychosexual changes. Normal age of buberty is 13 to 14 years. There are 5 storages of pubertal changes: 1. Physical growth: The growth in the height and weight begins around 10,5 years and is completed by 14. The grows at the rate 5-10 sm per year 2. Development of secondary sex organs, breast development (V statges) 3. Pubic and axillary hair growth 4. Development of overies and the genital organs 5. Growth spurt and menstruation The commonest • The commonest adoliscent gynecological problems are: • Precocious puberty is the apperance of Secondary sexual characters before the age of 8 years and ocurrance of menstruation before 10 years • Necsessary investigations: • Radiography of pituitary fossa • Ultrasound for ovarian tumor • Thyroid funciton tests • Hormonal profile FSH, LH, oestrogen, thyroid • Radiography for line age Delayed puberty When the secondary sexual characters do not appear by the age of 14, and menarche is not established by 16 years of age. Oligomenorrhoea This is mostly due to in adequate maturation of HPO axix and hormonal stimulation. The menstrual cycles are ofthen anovulatory in the first years. Full development results in normal ovulatiry cycles and this will not have any adverse bearing on the girls fertility. The other causes are: stress; anorexia nervosa, hypothyroidism, PCOD. Polymenorrhoea often caused by corpus luteal phase defect Puberty menorrhagia Anovulatory cycles with upopposed oestrogen calulses endometrial hyperplasia and prolonged and at times excessive menstruation. Dysmenorrhoea Primary dysmenorrhoea is characterized by spasmodic pain beginning with the onset of menstruation and lasting 12 to 24 hours, caused by prostaglandin E2 and F2 alphe, with cause vasoconstriction and myometrial contraction. Vaginal discharge Most often is physcological and consist mucoed non-smelling secretion. Infertility Tubal, Ovarian, Uterine, Male Factors Assoc. Prof. Syuzanna Babloyan Yerevan State Medical University Department .of Ob & Gyn Infertility Tube infertility: absence, adhesions, occlusion Uterine factors: absence, adhesions, Asherman syndrome, Polyps, Septum, Tumors, etc. Ovarian factors: Anovulatory , PCOD, Ovarian Tumors, etc. Endometriosis Male factor: (oligospermia, azoospermia) Unknown etiology Infertility Tubal Infertility- 35% all off Infertility 50% of Women Infertility- Tubal Infections, STI,PID, Tuberculosis, etc… 50% other factors: PCOD Endometriosis Uterine Tumors, Abnormalities, etc Thank you! Infertility - primary - secondary - absolute (sterility) - relatively - female - male - combined Female infertility -tuboperitoneal - endocrine - cervical - immunological - concerned with congenital defects in the genital tract - unexplained Diagnosis History (WHO) • obstetric history (outcome and details of every conception, number of living children, obstetric complications, interventions) • duration of infertility • contraceptives used (method(s), duration) • extragenital diseases (diabetes, tuberculosis, thyroid dysfunction, adrenal cortical dysfunction…) • medications • previous abdominal surgery • PID, STD • cervical diseases • presence of galactorrhoea • harmful habits, occupational hazards • hereditary diseases • menstrual history • sexual disorders Examinations • Hight, weight • Skin examination (dry, wet, oily, acne, stria), type of hair distribution, degree of hirsutism (Ferriman-Galwey) • Breast examination (breast development (Tanner), presence of secretion, tumour) • Gynaecological examination Special investigations • STD, vaginal, swab, culture, Pap-test • USI • Cytohormonal evalution (KPI=mature squamous cells / intermediate&basal cells) • Hormonal assays: LH, FSH, PRL, E2, progesterone (Cortizol, TSH, T3, T4, testosterone, DHEA, AKTH - by indications) • Colposcopy, hysteroscopy, laparoscopy • HSG • CT, MRI, USI, mammography • Immunological tests: Postcoital (Huhner's) test (<10sperms – abnormal) Miller-Kurzrok test (semen – mucus contact test) – penetration <3cm - abnormal • Specialists (by indications) • Semen analysis Classiification of anovulation Hypothalamic – pituitarian insufficiency (Hypogonadotropic – ↓FSH, ↓LH, ↓E2) • Kallman's syndrome (hypothalamic hypogonadism) • Simmond's disease, Sheehan's syndrome (pituitarian failure) • hyperprolacinaemia • intracranial tumour, lesion • empty sella syndrome Hypothalamic – pituitarian dysfunction (eugonadotropic) • Stress and drugs • Extreme weight change (anorexia nervosa, bulimia) • PCOS • Vigorous exercise Ovarian failure (hypergonadotropic – ↓E2, ↑LH, ↑FSH) • Gonadal dysgenesis • Resistant ovarian (Savage) syndrom • Premature menopause • Testicular feminizing syndrome • Enzymatic failure • Surgery, radiotherapy • Autoimmune disease • Infections (mumps, tuberculosis, pyogenic infecions) • tumours Adrenal or thyroid diseases In Vitro Fertilization Introduction infertility is the inability of a couple to become pregnant (regardless of cause) after 1 year unprotected sexual Intercourse -using no birth control methods. Infertility affects about 6.1 million people in the United States, about 10% of men and women of reproductive age. New and advanced technologies to help a woman become pregnant include in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other similar, procedures. IVF was used successfully for the first time in the United States in 1981. More than 250 babies have been born since then as a result of using the in vitro fertilization technique, offers infertile couples a chance to have a child who is biologically related to them. With IVF, a method of assisted reproduction, a man's sperm and the woman's egg are combined in a laboratory dish, where fertilization occurs. The resulting embryo is then transferred to the woman's uterus (womb) to implant and develop naturally. Usually, 2-4 embryos are placed in the woman's uterus at one time. Each attempt is called a cycle. The term test tube baby is often used to refer to children conceived with this technique first so- called test tube baby, Louise Brown, reached age 25 years in 2003. She was born in England. Less than 5% of infertile couples actually use IVF. IVF is usually the treatment of choice for woman with blocked, severely damaged, or no fallopian tubes. IVF is also used to oven infertility caused by endometriosis or problems with the man's sperm (such as low spend count). Couples who simply can't conceive and have tried other infertility methods that I not worked for them can also try IVF. Factors to Consider • Age: Women younger than 35 years who do not have problems with their partners' sperm may try IVF. • Multiple births: Generally, in women who use IVF to establish a live birth, about 63% are single babies, 32% are twins, and 5% are triplets or more. • Cost: One cycle of IVF costs an average of $12,400. • Reduced surgery: If a woman has IVF, she may not have to undergo surgery on her fallopian tubes. It is estimated that the IVF technique has reduced such surgeries by half. • Safety: Studies suggest that in vitro fertilization is safe. A recent study covered nearly 1,000 children conceived through these methods in 5 European countries and found that the children, monitored from birth to age 5 years, were healthy as children conceived naturally. However, other studies have found a sl increased risk of genetic disorders in children conceived through assisted reproductive technologies. Technique With in vitro fertilization, eggs are surgically aspirated from the woman's ovary under ultrasound guidance and mixed with sperm outside the body in a laboratory dish. After about 40 hours, the eggs are examined to see if they have become fertilized by the sperm and are dividing into cells. These fertilized eggs (now called embryos) are then placed in the women's uterus, thus bypassing the fallopian tubes where this process normally occurs. IVF is now recognized worldwide as an established treatment for infertility. This is how the procedure takes place: • The woman may be given certain drugs (hormones) to stimulate her ovaries to produce several eggs before the procedure to remove them. • A surgeon then inserts a needle through the vagina into the woman's ovary to remove eggs. This procedure used to be done with laparoscopic surgery, but the needle technique is much less invasive and much easier. General anesthesia is required for this part of the procedure, but the woman may be given some sedative medication. • The fluid removed is examined in the laboratory to make sure eggs are present. • At the same time, the man provides a semen sample. He is asked not to have so intercourse for a few days before the eggs are retrieved from the woman and be he produces a semen sample (usually by masturbation). The sperm are separate from the semen in a laboratory procedure. • The active sperm are combined in the laboratory dish with the eggs. This may be referred to as in vitro fertilization. • About 18 hours after this fertilization procedure, it is possible to determine if the or eggs have been fertilized and have begun to grow as embryos. They are inco and observed over the next 2-3 days or longer. • The doctor then transfers the embryos into the woman's uterus through the cerv with a catheter (a long slender tube). The woman should then remain in a restin position for the next hour or so. • She is given certain hormones for the next 2 weeks. If implantation works (the e eggs attach to the uterine wail and grow), the pregnancy test result is positive. Other assisted reproduction techniques • The following procedures have been used as alternatives to IVF but are not discussed in detail here: • Gamete intrafallopian transfer (GIFT): GIFT is similar to IVF. It is used when a woman has at least one normal Fallopian tube. Eggs are placed in this tube along with a man's sperm to fertilize there. • Zygote intrafallopian transfer (ZIFT): ZIFT is tubal embryo transfer in which a woman's eggs are taken from her ovaries, fertilized in the laboratory, and put back in the fallopian tubes rather than the uterus. • Assisted fertilization techniques when not enough sperm are available or sperm quality is not sufficient to fertilize include the following: – Partial zona dissection – Subzonal sperm injection – Intracytoplasmic sperm injection • Embryo cryopreservation (frozen fertilized egg and sperm) Success Rate Techniques for assessing the viability of an embryo when genetic issues are present are cell biopsy and evaluation and pronuclear biopsy and evaluation. The pregnancy rate by age is similar to that of normally conceived pregnancies: 37% among women younger than 35 years and 28% for those aged 36-39 years. The success rate is about 13% in those older than 40 years. Pregnancy in women older than 44 years is rare. The rate of miscarriages with IVF pregnancies is the same as that with normally conceived pregnancies. Ectopic pregnancy occurs in about 3-5% of cases. An ectopic pregnancy is a serious condition that requires emergency medical care. The embryo is growing outside the uterus and does not survive. Egg and sperm donors Donors may contribute the egg or the sperm (or even a frozen embryo) to an IVF program when a partner is not able to produce the egg or sperm. • Egg donation: Sometimes eggs are used from another woman if the recipient have impaired ovaries or has a genetic disease that could be passed on to her baby, egg donor may be anonymous or known (such as a younger relative for an older woman or a designated donor). Ideally, the donor should be aged 21-30 years, donor's eggs are removed the same way they are with IVF. The recipient takes increasing doses of estrogen to synchronize her hormone levels in preparation for embryo transfer. Both the donor and recipient should talk with a counselor about psychological aspects of this procedure. Everyone signs a consent form to cover legal issues of such a donation. Success rates for this type of donation are high than the rates with conventional IVF. The rate of multiple pregnancy is high, so doctors try to transfer only 2 embryos at one time. Sperm donation: This can be routinely done for women whose male partners had impaired sperm or low sperm counts. Donation may be anonymous from a sperm bank. In some cases, a male partner may "bank" sperm if he anticipates problem with chemotherapy or other medical conditions that may affect his sperm later in. Embryo donation: Receiving a donor embryo (usually from a frozen embryo create in the laboratory from another couple) is the earliest form of adoption. The donor couple must sign an advance directive regarding embryo ownership and dispose Those directives should include statements regarding (1) embryo donation to are couple, (2) donation of the embryos for research, or (3) disposition of the embryo after thawing. Ovarian Induction YEREVAN STATE MEDICAL UNIVERSITY Department of Obstetrics and Gynecology Associated Prof. Syuzanna Babloyan PELVIC INFECTION CLASSIFICATION Pelvic inflammatory disease • Acute salpingitis • IUD related pelvic cellulitis • Tubo-ovarian abscess • Pelvic abscess Puerperal infections • C-section & delivery Postoperative • Parametritis • Vaginal cuff abscess • Tubo-ovarian abscess Abortion associated • Post abortion cellulitis • Incomplete septic abortion Secondary • Appendicitis, diverticulitis, tuberculosis “Pelvic inflammatory disease” is a general term for acute, subacute, recurrent or chronic infection of oviducts and ovaries, often with involvement of adjacent tissues PATHWAYS OF DISSEMINATION • Intraabdominal spread • Lymphatic spread • Hematogenous spread ACUTE SALPINGITIS • Lower abdominal and pelvic pain • Sensation of pelvic pressure • Tenderness on uterus movement • Inflammatory mass • Nausea, vomiting, headache • Vaginal discharge • Fever • Leukocytotosis with left shift • Pathological smear RECCURENT OR CHRONIC PELVIC INFECTION • History of acute pelvic infection • Recurrent episodes • Chronic pelvic pain • Generalized pelvic tenderness • Thickening of adnexal tissues • Infertility PELVIC ABSCESS (cul-de-sac) • All above mentioned • Fluctuant mass filling cul-de-sac • Painful defecation • Severe back pain • Rectal pain TUBO-OVARIAN ABSCESS • History of pelvic infection • Lower abdominal and pelvic pain • Tenderness on uterus movement • Adnexal mass, extremely tender • Nausea, vomiting, headache • Rebound tenderness in lower quadrants • Fever POSTOPERATIVE PELVIC INFECTION • Cuff induration • Infected cuff hematoma • Salpingitis • Pelvic cellulitis • Pelvic tromboflebitis • Tubo-ovarian abscess POSTOPERATIVE PELVIC INFECTION • Recent pelvic surgery • Pelvic or low abdominal pain or pressure • Fever and tachycardia • Purulent, foul discharge • Malaise, chills, etc. • Vaginal cuff tenderness • Cellulitis or abscess ACUTE ABDOMEN IS AN ANY INTRA-ABDOMINAL EMERGENCY REQUIRING AN “ACUTE” MEDICAL DECISION ACUTE ABDOMEN • Acute onset of severe abdominal pain • Signs of peritonitis with guarding and rebound tenderness • Nausea and vomiting • Elevated WBC count (inflammation) • Fever (occasionally) • Anemia or hypovolemic shock (bleeding) • Possible complications of pregnancy DIFFERENTIAL EVALUATION OF FLUID OBTAINED BY CULDOCENTESIS BLOOD Ruptured ectopic pregnancy, hemorrhage from cyst, retrograde menstruation, rupture of spleen or liver, gastrointestinal bleeding, acute salpingitis PUS Ruptured tubo-ovarian abscess, uterine abscess with myoma, pelvic abscess, ruptured appendix or diverticular abscess CLOUDY Pelvic peritonitis, twisted adnexal cyst, appendicitis, pancreatitis, echinococcosis, etc. DIFFERENTIAL DIAGNOSIS OF ACUTE ABDOMEN CBC urine culdocentesis fever nausea Ruptured Hematocrit Red blood Blood, non- No Unusual ectopic low after cells rare clotting pregnancy treatment of sample, high hypovolemia hematocrit Salpingitis Rising white White Cloudy, many Yes Gradual blood cell blood cells WBC onset with count occasionally ileus present Hemorrhagic Hematocrit Normal Blood, low No Rare ovarian cyst may be low hematocrit after treatment of hypovolemia Torsion of Normal Normal Minimal clear No Rare adnexa fluid Degenerating Normal or Normal Normal clear Yes Rare myoma elevated fluid /No white blood cell count An extrauterine pregnancy (ectopic pregnancy, heterotopic pregnancy, eccyesis) is one in which a fertilized ovum implants in an area other than the uterine cavity RISK FACTORS FOR ECTOPIC PREGNANCY • Pelvic inflammatory disease • History of prior ectopic pregnancy • History of tubal surgery and conception after tubal ligation • Use of fertility drugs or assisted reproductive technology • Use of an progesterone IUD • Increasing age • Smoking • Other ECTOPIC PREGNANCY • Abdominal pain • Amenorrhea • Vaginal bleeding 40-50% • Abdominal tenderness 75% • Palpable adnexal mass 50% • Positive hCG • nausea, breast fullness, fatigue, low abdominal pain, heavy cramping, shoulder pain, recent dyspareunia CLASSIFICATION • TUBAL - isthmic, ampullary,fimbrial, interstitial, bilateral, distal with segmental abs. of tube • UTERINE – cornual, angular, in a uterine diverticulum, in a uterine sacculation, in a rudimentary horn, intramural • CERVICAL • INTRALIGAMENTOUS • OVARIAN – tubo-ovarian, abdomino-ovarian (secondary abdominal pregnancy) • ABDOMINAL – primary, secondary, abdomino- ovarian, tuboabdominal • ASSOCIATED WITH HYSTERECTOMY • COMBINED WITH I/U PREGNANCY ECTOPIC PREGNANCY LOCATION 80% 2% 12% 0.2% 5% 0.6% 0.2% Etiology A. Tubal Factors B. Zygote Abnormalities C. Ovarian Factors D. Exogenous Hormones E. Other Factors Adnexal Torsion • Complete or incomplete rotation of the ovary on its vascular pedicle • Leads to arterial, venous, or lymphatic occusion • Can cause massive congestion of ovarian parenchyma and subsequent hemorrhagic infarction Secondary Amenorrhea Dr. Sudha Prasad Professor & IVF Coordinator Department Obstetrics & Gynecology MAMC New Delhi Definition Absence of menstruation for 3 normal menstrual cycles or no menstruation for six months in a previously menstruating women of reproductive age. Etiology of Secondary Amenorrhea Physiological – Pregnancy – Lactation – Menopause Pathological Amenorrhea – Hypothalamic amenorrhea – Diseases or injury in the region of mid brain – Pituitary amenorrhea – Ovarian amenorrhea – Uterine amenorrhea – Drugs – General constitutional upset and diseases – Environment – Exercise related amenorrhea PathoHypothalamus-Physiology of Menstruation Hypothalamus Gn-RH ± Ant. pituitary ? – FSH, LH Estrogen Ovaries Progesterone Uterus Menses Pathophysiology of Amenorrhea • Inadequate hormonal stimulation of the endomerium Anovulatory amenorrhea - Euestrogenic - Hypoestrogenic • Inability of endometrium to respond to hormones “Ovulatory amenorrhea” - Damaged endometrium ( e.g Asherman’s syndrome) Hypothalamic amenorrhea • Disturbance of hypothalamus leading to interference in production of GnRH. • It may interfere with other RH also esp. undereating or overeating leading to obesity or wasting. • Hence it can cause pituitary infantilism, galactorrhea, stunted growth, obesity or genital hypoplasia. Disease or Injury in the region of the mid brain • Encephalitis • Meningitis • Tumors • Fractures of the base of the skull Cerebral Cortex • Psychoses • Emotional upsets and stresses • Pseudocysis • Anorexia nervosa • Polycystic ovarian syndrome Drugs • Drugs to cause secondary amenorrhea by lowering PIF: – Phenothiazine derivatives – Reserpine – Ganglion blocking agents – Chemotherapeutic agents: Alkylating agents – Estrogen progesterone pills Pituitary amenorrhea • Pituitary inability to secrete gonadotropins • Tumors in or near the pituitary gland • Diseases of the anterior pituitary • Pituitary necrosis following massive obstetric hemorrhage is most common cause in women Sheehan’s syndrome • Pituitary inability to secrete gonadotropins • Pituitary necrosis following massive obstetric hemorrhage is most common cause in women • Diagnosis : History and ↓ E2, FSH, LH + other pituitary deficiencies Treatment : Replacement of deficient hormones Premature ovarian failure • 10% of secondary amenorrhea • Serum estradiol < 50 pg/ml and FSH > 40 IU/ml on repeated occasions. • Few cases reported, where therapy resulted in ovulation. • High dose estrogen or HMG or immuno therapy may reverse autoimmue ovarian failure. • Rarely spont. ovulation (resistant ovaries) Euestrogenic Anovulatory Amenorrhea Normal androgens High androgens • Hypothalamic-pituitary • PCOS dysfunction (stress, • Musculinizing ovarian weight loss or gain, tumour exercise, pseudocyesis) • Cushing’s syndrome • Hyperprolactinemia • Congenital adrenal • Feminizing ovarian hyperplasia (late onset) tumour • Non-gonadal endocrine disease (thyroid, adrenal) • Systemic illness Hypoestrogenic Anovulatory Amenorrhea Normal androgens High androgens - Hypothalamic-pituitary failure - Severe dysfunction - Musculinizing ovarian tumour - Neoplastic,destructive, - Cushing’s syndrome infiltrative, infectious & trumatic conditions - Congenital adrenal hyperplasia involving hypothalamus or (late onset) pituitary - Ovarian failure - Gonadal dysgenesis - Premature ovarian failure - Enzyme defect - Resistant ovaries - Radiotherapy, chemotherapy Polycystic ovary syndrome • The most common cause of chronic anovulation • Hyperandrogenism ; LH/FSH ratio • Insulin resistance is a major biochemical feature ( blood insulin level hyperandrogenism ) • Long term risks: Obesity, hirsuitism, infertility, type 2 diabetes, dyslipidemia, cardiovasular risks, endometrial hyperplasia and cancer. • Treatment depends on the needs of the patient and preventing long term health problems. Metabolism of estradiol Acetate Cholesterol Pregnenolone Progesterone 17 hydroxy Pregnendiole 17 Hydroxy progesterone Dehydro-epi- androstenedione (DHA) Androstenedione Testosterone Estrone Estradiol Presentation • Common in 2nd and 3rd decades. • History of amenorrhea or oligomenorrhea. • Hirsuitism } • Obesity } Hyperandrogenism • Acne } • Infertility due to anovulation. • Hyperinsulinemia Risk Factors Prone for: – Endometrial carcinoma – Breast carcinoma – Cardiovascular disease – Type II diabetes mallitus Non-dysgenesis ovarian failure • Steroidogenic enzyme defects (17- hydroxylase) • Ovarian resistance syndrome • Autoimmune oophoritis • Postinfection (eg. Mumps) • Postoopherectomy • Postradiation • Postchemotherapy Amenorrhea Signs of androgen excess Testosterone, DHEAS, FSH, and LH TEST. >200 ng/dL DHEAS >700 mug/dL DHEAS 500-700 mug/dL U/S ? MRI or CT ↑Serum 17-OH Progesterone level Ovarian Adrenal Or adrenal hyperfunction Late CAH tumor Lower elevations PCOS (High LH / FSH) Weight-related amenorrhoea Anorexia Nervosa • 1o or 2o Amenorrhea is often first sign • A body mass index (BMI) <17 kg/m² menstrual irregularity and amenorrhea • Hypothalamic suppression • Abnormal body image, intense fear of weight gain, often strenuous exercise • Mean age onset 13-14 yrs (range 10-21 yrs) • Low estradiol risk of osteoporosis • Bulemics less commonly have amenorrhea due to fluctuations in body wt, but any disordered eating pattern (crash diets) can cause menstrual irregularity. • Treatment : ↑ body wt. (Psychiatrist referral) Exercise-associated amenorrhoea • Common in women who participate in sports (e.g. competitive athletes, ballet dancers) • Eating disorders have a higher prevalence in female athletes than non-athletes • Hypothalamic disorder caused by abnormal gonadotrophin-releasing hormone pulsatility, resulting in impaired gonadotrophin levels, particularly LH, and subsequently low oestrogen levels Contraception related amenorrhea • Post-pill amenorrhea is not an entity • Depot medroxy-progesterone acetate Up to 80 % of women will have amenorrhea after 1 year of use. It is reversible (oestrogen deficiency) • A minority of women taking the progestogen-only pill may have reversible long term amenorrhea due to complete suppression of ovulation Late onset congenital adrenal hyperplasia • Autosomal recessive trait • Most common form is due to 21-hydroxylase deficiency • Mild forms Closely resemble PCO • Severe forms show Signs of severe androgen excess • High 17-OH-progesterone blood level • Treatment : cortisol replacement and ? Corrective surgery Cushing’s syndrome • Clinical suspicion : Hirsutism, truncal obesity, purple striae, BP • If Suspicion is high : dexamethasone suppression test (1 mg PO 11 pm ) and serum cortisol level done at 8 am : < 5 µg/ dl excludes cushing’s • 24 hours total urine free cortisol level to confirm diagnosis • 2 forms ; adrenal tumour or ACTH hypersecretion (pituitary or ectopic site) Normal FSH, LH; E&P challenge test-ve amenorrhea trumatica Asherman’s syndrome • History of pregnancy associated D&C • Rarely after CS , myomectomy T.B endometritis, Diagnosis : HSG or hysteroscopy Treatment : lysis of adhesions; D&C or hysterescopy + estrogen therapy ( ? IUCD or catheter) Uterine Amenorrhea • Infection: – Post abortal or peurperal infection – Infection –Tuberculous endometritis • Inflammation • Heavy curettage • Radiation Asherman’s syndrome Gonorrhoea Neisseria gonorrhoea – gram- negative diplococcus, localized intracellularly Transmission - sexual - perinatal Incidence – 0.02 - 0.2% of gynecological pathology Pathology – columnar epithelium of • Bartholin’s gland • Urethra • Endocervix • Fallopian tubes • Rectum • Pharynx Symptoms • Local signs • Tubo-ovarian abscess, pelvic abscess, adhesions, hyperpolymenorrhoea • Arthritis • Septicemia • Skin lesions • Infertility • Ectopic pregnancy • Conjunctivitis of newborn • Fitz-Hugh-Curtis Syndrome • >70% asymptomatic cases Treatment • Penicillin – drug of choice • Amoxycillin • Spectinomycin (penicillinase producing N.g.) • Cephalosporins • Tetracyclines • Surgery • Treatment of sexual partner (s) Trichomoniasis Most common STD Trichomonas Vaginalis – motile anaerobic protozoah Symptoms • Typical discharge – profuse, thin, frothy, greenish yellow • Pruritus, vulvitis • “Strawberry vagina” • Urinary symptoms • 20% asymptomatic cases Therapy Drugs of choice – 5 – Nitroimidazole derivates • Metronidazole – 2.0g (single oral doze) • Tinidazole – 2.0g • Necessary treatment of sexual partner Chlamidia Classification - Chlamydia trachomatis (ophtalmitis, lymphogranuloma venereum (LGV), urogenital infection, arthritis) - Chlamydia pneumoniae - Chlamydia psittaci (atypic pneumonia, zooinfection) Chlamydia trachomatis Gram-negative bacteria, obligate intracellular parasite. Deseases, caused by Chlamydia trachomatis • urethritis • cervicitis • endrometritis • salpingitis • peritonitis • perihepatitis (Fitz-Hugh-Curtis syndrome) • conjunctivitis • arthritis • skin lesions • Reiter syndrome Complications of pregnancy and labour • Preterm labour, IUGR • Pregnancy heamorrhage • Puerperal endometritis • Conjunctivitis, pneumonia, genital infections of newborn Symptoms – 90% - asymptomatically or scanty symptoms – vaginal discharge – DUB – postcoital haemorrhage – dysuria – infertility – lower abdominal pain – ectopic pregnancy Treatment • Doxycycline • Tetracycline • Azithromycin • Erithromycin • Amoxycillin Candidiasis •Candida albicans (>90%) •Candida tropicalis, C crusei, C glabrata… - fungal infection Predisposing factors • Pregnancy • Diabetes • Hormonal contraception • Use of antibiotics Symptoms • Pruritis • Profuse curdy discharge • Vulvitis • Dysuria • Dyspareunia Herpes genitalis • Herpes genitalis – DNA viral infection •Herpes simplex type–2 - 70-80% •Herpes simplex type–1 - 20-30% • 80-90% of adults are seropositive 70-80% - HSV-1 20-30% - HSV-2 Herpes genitalis Reccurent indection Primary (reactivation of (ekzogenous) endogenous herpes infection) Symptoms ~ 50% - asymptomatic Primary infection • oedema, hyperemy of vulva • vesicular skin lesions (bilateral) • vesicles persist about 3 weeks • erosion of vesicles → painful ulcers →healing without scarring • inguinal lymphadenopathy • general symptoms Reccurent infection • is less severe and lasts shorter • prodromal syndromes (itching, paraesthesia) • possible alteration of localization of skin lesions • psychoemotional, sexual disturbances • dysuria • (reccurent) loss of pregnancy Treatment primary recurrent (first episode) •prevention of reccurence •antiviral drugs (per os, IV, (suppressive therapy) locally) • immunotherapy •analgetics •antiviral drugs •desensitation •sedatation •vitamins HPV Human papilloma virus (HPV) DNA virus Classification HPV High onkogen types low onkogen types (HPV – type 16,18) (HPV – type 6,11) •CIN-I – 50% (are positive for •condiloma acuminata HPV) •1% of sexually active •CIN-II – 75% women •CIN-III – 95% •cervical cancer – 98% Tuberculosis Mycobacterium tuberculosis>90% Mycobacterium bovis • Localization – intracellular Genital tuberculosis commonly is secondary focus of infection Primary focus • lungs~90% • Lymph nodes • Urinary tract • Bones and joints Spreading of infection • blood stream • direct spread (peritoneum, bowels, lymph(mesenteric nodes) • ascending way (very rare) Pathology Fallopian tube • Tuberculous endosalpingitis • Tuberculous exosalpingitis • Interstitial tuberculous salpingitis Uterus (in 70%-80% cases) • pyometra • Asherman syndrome Cervix • ulcer • papillary erosion Vulva, vagina • ulcer • elephantiasis – like vulva Symptoms • ~10% - asymptomatic cases • Infertility • Menorrhagia • Amenorrhoea • Lower abdominal pain • Vaginal discharge • Abdominal mass • Dyspareunia • Repeated PID • Fistula Diagnosis • histopathological examination (typical giant cells with caseation) • tissue culture (D&C, first day menstrual fluid, suction lavage of endometrii), PCR – test • hysterosalpingogram (if diagnosis is known – contraindicated) • USI • laparoscopy • Mantoux test • biopsy Treatment • antitubercular drugs: Isoniazid + Rifampicin + Ethambutol • surgery VULVOVAGINITIS Suzanna R. Babloyan MD, PhD Associated Professor Department of Obstetrics and Gynecology Yerevan State Medical University Thank you