Hemorrhage in Early Pregnancy

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Hemorrhage in Early Pregnancy Causes of Bleeding Related to the pregnant state: Abortion (95%), ectopic pregnancy, hydatidiform mole, implantation bleeding. Associated with the pregnant state: Lesions unrelated to pregnancy or aggravated by it (e.g., cervical ectopy, polyp, ruptured varicose veins, malignancy). Spontaneous Abortion (Miscarriage) Definition Expulsion or extraction of an embryo or fetus weighing $\le 500 \, \text{g}$ (not capable of independent survival) or $\approx 22$ weeks gestation. Incidence 10-20% of clinical pregnancies. 75% before 16th week, 80% of these before 12th week. Etiology (Often Complex) Genetic Factors: Majority (50%) of early miscarriages due to chromosomal abnormality. Autosomal trisomy (16) most common (30%). Polyploidy (22%), Monosomy X (20%). Endocrine and Metabolic Factors (10-15%): Luteal phase defect (LPD), deficient progesterone, thyroid abnormalities (hypo/hyperthyroidism, autoantibodies), poorly controlled diabetes. Anatomical Abnormalities (3-38%): Cervicouterine factors: Cervical incompetence (congenital/acquired), congenital uterine malformation (bicornuate/septate uterus), uterine fibroids (submucous variety), intrauterine adhesions (synechiae). Infections (5%): Viral (Rubella, CMV), Parasitic (Toxoplasma, malaria), Bacterial (Ureaplasma, Chlamydia, Brucella). Immunological Disorders (5-10%): Antiphospholipid antibody syndrome (APAS) leading to fetal hypoxia. Immune factors (Th1/Th2 response imbalance). Environmental Factors: Cigarette smoking, alcohol, X-irradiation, antineoplastic drugs, certain chemicals (arsenic, lead). Unexplained (40-60%): Common, often multiple factors, risk increases with maternal age. Mechanism of Miscarriage Before 8 weeks: Ovum expelled intact. Sometimes cervical miscarriage (accommodated in dilated cervical canal). Between 8 and 14 weeks: Fetus expelled, placenta and membranes may be retained or partially separated. Beyond 14th week: Fetus expelled first, then placenta. Types of Miscarriage Types Symptoms Uterine size Cervix (external Os) Ultrasonography Management Threatened Vaginal bleeding, pelvic pain Corresponds to gestational age Closed Fetus alive, retroplacental hemorrhage+ Conservative management Inevitable Vaginal bleeding, pelvic pain (colicky) Same or smaller Open with palpable conceptus Fetus often dead, retroplacental hemorrhage+ Resuscitation, evacuation Complete Expulsion of fleshy mass, subsidence of pain, trace/absent vaginal bleeding Smaller than period of amenorrhea, firmer Closed Empty uterine cavity No active intervention (if empty) Incomplete Expulsion of fleshy mass, persistent pain, persistent vaginal bleeding (heavy) Smaller Open Products of conception partly retained Evacuation of the uterus Missed No fetal cardiac activity, vaginal bleeding (trace/brownish) Smaller Closed Blighted ovum or fetus without cardiac activity Evacuation of the uterus Septic Vaginal discharge (purulent, foul smelling), signs of sepsis Variable, may be larger Open Products of conception retained, foreign body ($\pm$), free fluid in peritoneal cavity/POD Evacuation of the uterus to remove septic focus Threatened Miscarriage Definition Miscarriage process started but recovery is possible. Clinical Features Bleeding per vaginam: Slight, brownish or bright red, usually stops spontaneously. Pain: Usually painless, mild backache or dull lower abdominal pain (after hemorrhage). Pelvic examination: Speculum reveals bleeding from external os. Digital exam reveals closed external os, uterine size corresponds to amenorrhea. Investigations Routine: Blood (Hb, Hct, ABO/Rh), Urine (immunological test not helpful after fetal death). Ultrasonography (TVS): Healthy fetus (gestation sac, yolk sac, cardiac motion) indicates 98% chance of continuation. Anembryonic sac (MSD $\ge 25 \, \text{mm}$ with no embryo) suggests early pregnancy failure. Serum Progesterone: $\ge 25 \, \text{ng/mL}$ indicates viable pregnancy (95%). Serial serum hCG: Helpful for fetal well-being. Rule out ectopic pregnancy. Treatment Rest: Bed rest until bleeding stops (few days). Prolonged restriction not therapeutic. Drugs: Diazepam (5mg BID) for pain. Progesterone may improve outcome (shifts Th1 to Th2). hCG not preferred. Advice on Discharge: Limit activities for 2 weeks, avoid coitus, repeat sonography in 10-14 days. Unfavorable Outcome: Falling serum $\beta$-hCG, decreasing fetal size, irregular gestational sac, fetal bradycardia. Prognosis Unpredictable. In isolated cases: 2/3 continue beyond 28 weeks. 1/3 terminate as inevitable/missed miscarriage. Increased risk of preterm labor, placenta previa, IUGR, fetal anomalies if pregnancy continues. Inevitable Miscarriage Definition Changes have progressed to a state where pregnancy continuation is impossible. Clinical Features Increased vaginal bleeding. Aggravation of colicky lower abdominal pain. Dilated internal os with products of conception felt. Management General Measures: Control excessive bleeding (Methergine 0.2 mg if cervix dilated and uterus $\lt 12$ weeks). Correct blood loss with IV fluids/transfusion. Active Treatment: Before 12 weeks: Dilatation & evacuation (D&E) or suction evacuation followed by curettage. After 12 weeks: Accelerate uterine contraction with oxytocin drip. Manual removal of retained placenta/products, followed by D&E under general anesthesia. Complete Miscarriage Definition Products of conception expelled en masse. Clinical Features History of fleshy mass expulsion. Subsidence of abdominal pain. Vaginal bleeding trace or absent. Internal examination: Uterus smaller and firmer, closed cervical os, trace bleeding. Expelled mass found complete. TVS: Empty uterine cavity. Management Transvaginal sonography: Confirm empty uterus. If not, D&E. Rh-negative women: Administer anti-D gamma globulin (50 $\mu$g for early, 100 $\mu$g for late miscarriage) within 72 hours, unless complete miscarriage before 12 weeks with no instrumentation. Incomplete Miscarriage Definition Part of products of conception retained in uterine cavity. Clinical Features History of fleshy mass expulsion. Continuation of pain. Persistent vaginal bleeding. Internal examination: Uterus smaller, patulous cervical os, varying amount of bleeding. Expelled mass found incomplete. Ultrasonography: Echogenic material within cavity. Complications Profuse bleeding, sepsis, placental polyp. Management Recent cases: Evacuation of retained products of conception (ERPC). Resuscitate patient first. Early abortion: D&E under analgesia/general anesthesia (or MVA). Late abortion: Uterus evacuated under general anesthesia. Products removed by ovum forceps/blunt curette. Histological exam of removed material. Medical management: Misoprostol 200 $\mu$g vaginally every 4 hours. Missed Miscarriage Definition Fetus dead and retained in uterus for variable period; early fetal demise. Pathology Prolonged retention causes maceration/mummification of fetus. Liquor amnii absorbed. Placenta pale, thin, adherent. Pathological process differs before/after 12 weeks. Clinical Features Features of threatened miscarriage followed by: Persistent brownish vaginal discharge. Subsidence of pregnancy symptoms, retrogression of breast changes. Cessation of uterine growth (becomes smaller). Nonaudibility of fetal heart sound (Doppler). Cervix feels firm. Immunological test for pregnancy becomes negative. Real-time ultrasonography: Empty sac or absence of fetal cardiac motion. Complications Same as intrauterine fetal death. Blood coagulation disorders less likely. Management Expectant: Many expel spontaneously. Medical: Prostaglandin E1 (misoprostol) 800 $\mu$g vaginally, repeated after 24 hours if needed. Surgical: Suction evacuation or D&E. Uterus $\gt 12$ weeks: Induction with prostaglandins (misoprostol 200 $\mu$g vaginally every 4 hours, up to 5 doses) or oxytocin (10-20 units in 500 mL NS at 30 drops/min, escalating up to 200 mlU/min). Surgical evacuation often needed post-medical treatment. D&E after cervical ripening (PGE1 or mechanical dilators). Septic Abortion Definition Abortion with clinical evidence of uterine infection. Usually considered septic with fever ($\ge 100.4^\circ F$), offensive/purulent vaginal discharge, and other pelvic infection signs. Incidence About 10% of abortions requiring admission. Majority associated with illegal induced abortion, but can occur after spontaneous abortion. Mode of Infection Usually normal flora of vagina (endogenous) or exogenous. Mixed infection common. Pathology Majority (80%) localized to conceptus. 15% localized endomyometritis or spread to parametrium, tubes, ovaries, pelvic peritoneum. 5% generalized peritonitis/endotoxic shock. Clinical Features Varies with severity. History of unsafe termination often concealed. Sick, anxious, temperature $\gt 38^\circ C$, chills/rigors, persistent tachycardia, hypothermia (endotoxic shock), abdominal/chest pain, tachypnea, impaired mental state, diarrhea/vomiting, renal angle tenderness. Pelvic examination: Offensive, purulent vaginal discharge, uterine tenderness, boggy feel in POD. Clinical Grading Grade I: Infection localized to uterus. Grade II: Infection spreads beyond uterus to parametrium, tubes, ovaries, pelvic peritoneum. Grade III: Generalized peritonitis, endotoxic shock, jaundice, acute renal failure. Investigations Routine: Cervical/high vaginal swab (culture, sensitivity, Gram stain). Blood (Hb, Hct, ABO/Rh, WBC count). Urine analysis/culture. Special: Ultrasonography: Detect retained products, physometra, foreign body, free fluid, pelvic abscess. Blood: Culture (if chills/rigors). Serum electrolytes, CRP, lactate (for endotoxic shock). Coagulation profile. Plain X-ray: Abdomen (bowel injury), Chest (pulmonary complications). Complications Immediate: Hemorrhage, injury (uterus, bowels), spread of infection (peritonitis, endotoxic shock, acute renal failure, atelectasis, ARDS, thrombophlebitis). Increased maternal deaths (20-25%). Remote: Chronic debility, pelvic pain, backache, dyspareunia, ectopic pregnancy, secondary infertility, emotional depression. Prevention Family planning, legalized abortion, postabortion care, antiseptic/aseptic precautions. General Management Hospitalization, isolation. High vaginal/cervical swab for culture/sensitivity. Vaginal examination for abortion process/infection extent. Overall assessment based on clinical grading. Investigation protocols. Principles: Control sepsis, remove infection source, supportive therapy, assess response. Grade I Management Drugs: Antibiotics, prophylactic antigas gangrene/antitetanus serum (if interference history), analgesics, sedatives. Blood transfusion for anemia. Evacuation of uterus: Within 24 hours of antibiotic therapy (if not excessive bleeding). Antibiotic Regimens Broad-spectrum, covering gram-positive/negative, aerobic/anaerobic. Piperacillin-tazobactam or carbapenem + clindamycin (IV). Vancomycin/teicoplanin for MRSA. Gentamycin (3-5 mg/kg single dose) if normal renal function. Co-amoxiclav (not for MRSA, Pseudomonas, ESBL). Metronidazole for anaerobes. Grade II Management Analgesic, ATS, blood transfusion (more often needed). Clinical monitoring: Pulse, respiration, temperature, urinary output, pain, tenderness, mass, CVP. Surgery: Evacuation of uterus: Withhold for $\ge 48$ hours after infection control/localization (except excessive bleeding). Posterior colpotomy: For pelvic abscess in POD. Grade III Management Antibiotics. Clinical monitoring. Supportive therapy: Gastric suction, IV crystalloids for generalized peritonitis. Manage endotoxic shock/renal failure. Guard against organ dysfunction. ICU management needed. Active Surgery (Septic Abortion) Indications: Uterine/bowel injury, pus collection, unresponsive peritonitis/shock, uterus too large for vaginal evacuation. Laparotomy by experienced surgeon. Removal of uterus, adnexa as needed. Inspection of gut/omentum. Drainage of pus. Unsafe Abortion Termination by unskilled persons or in unsafe environment. Major cause of maternal deaths in developing countries. Recurrent Miscarriage Definition Two or more spontaneous abortions before 20 weeks (ASRM-2013). Earlier: three or more before 24 weeks. Incidence Affects $\approx 1\%$ of reproductive age women. Risk increases with successive abortions ($\gt 30\%$ after 3 losses). Etiology Complex, often obscure. Factors can be recurrent or nonrecurrent. Specific factors for early/late abortion. First Trimester Abortion Genetic factors (3-5%): Parental chromosomal abnormalities (balanced translocation). Endocrine and metabolic: Poorly controlled diabetes, thyroid autoantibodies, luteal phase defect (LPD). Infection: Genital tract infection, bacterial vaginosis. Inherited thrombophilia: Intravascular/placental intervillous thrombosis (Protein C resistance, Factor V Leiden mutation, Protein C/S deficiency, antithrombin III, hyperhomocystinemia, prothrombin gene mutation). Immune factors (10-15%): Autoimmunity (antinuclear antibodies, anti-DNA antibodies, antiphospholipid antibodies). Alloimmunity (Natural killer cells, HLA incompatibility - not considered cause). Unexplained: Majority. Second Trimester Miscarriage Anatomic abnormalities (10-15%): Congenital (Müllerian duct fusion defects: unicorunate, bicornuate, septate, double uterus) or acquired (intrauterine adhesions, uterine fibroids, endometriosis, cervical incompetence). Chronic maternal illness: Uncontrolled diabetes, hemoglobinopathies, chronic renal disease, inflammatory bowel disease, SLE. Infection: Syphilis, toxoplasmosis, listeriosis. Unexplained. Cervical Incompetence Retentive power of cervix impaired (functional/anatomical). Causes: congenital uterine anomalies, acquired (D&C, induced abortion, vaginal delivery, amputation/cone biopsy), multiple gestations, prior preterm birth. Diagnosis of Cervical Incompetence History: Repeated midtrimester painless cervical dilatation/liquor amnii escape/painless expulsion. Internal examination: Interconceptional period (bimanual exam reveals tear/gaping cervix). Investigations: Interconceptional period: Hegar dilator (6-8) passage without resistance. Premenstrual hysterocervicography (funnel-shaped shadow). During pregnancy: Clinical (speculum) reveals painless cervical shortening/dilatation. Sonography (short cervix $\lt 25 \, \text{mm}$, funneling of internal os $\gt 1 \, \text{cm}$, incompetent cervix appears Y-shaped). Investigations for Recurrent Miscarriage Thorough medical, surgical, obstetric history & clinical exam. Diagnostic tests: Blood (glucose, VDRL, thyroid function, ABO/Rh, toxoplasma antibodies). Autoimmune screening (lupus anticoagulant, anticardiolipin antibodies). Serum LH. Ultrasonography (uterine malformation, PCOS, fibroid). Hysterosalpingography (cervical incompetence, synechiae, malformation). Hysteroscopy/laparoscopy. Karyotyping (husband/wife). Endocervical swab (Chlamydia, Mycoplasma, bacterial vaginosis). Treatment (Recurrent Miscarriage) Interconceptional Period Counseling: Success rate high (70%) even after 3 miscarriages. Hysteroscopic resection (uterine septa, synechiae, submucous myomas). Uterine unification operation (metroplasty) for bicornuate uterus. Chromosomal anomalies: Genetic counseling, preimplantation genetic diagnosis (PGD), prenatal diagnosis (CVS, amniocentesis), donor gametes. PCOS: Metformin therapy. During Pregnancy Genital tract infections: Treat appropriately. Reassurance & tender loving care (TLC). Ultrasound: Detect viable pregnancy early. Rest: Adequate rest, avoid strenuous activities, intercourse, travel. Progesterone therapy: Micronized progesterone 100 mg daily (vaginal suppository) from ovulation until 10-12 weeks. Antiphospholipid antibody syndrome (APS): Low-dose aspirin (50 mg/day) and heparin (5000 units SC BID) up to 34 weeks. Cerclage operation: For cervical incompetence. Chromosomal anomaly: Prenatal diagnosis (CVS/amniocentesis). Immunotherapy: Not recommended. Inherited thrombophilias: Antithrombotic therapy (heparin or LMWH) up to 34 weeks. Medical complications: Delay pregnancy until optimally treated. Unexplained: TLC and supportive therapy improve outcome (70%). Management of Cervical Incompetence Cerclage operation: Shirodkar & McDonald procedures (80-90% success). Reinforces weak cervix with nonabsorbable tape. Time of operation: Prophylactic (around 14 weeks or 2 weeks before lowest previous wastage). Emergency (rescue) if cervix dilated/membranes bulging. Case selection: History, physical exam, sonography (short cervical length $\lt 25 \, \text{mm}$, funneling). Fetal growth/anomaly scan. Shirodkar's Operation Steps: Patient in lithotomy, good exposure. Transverse incision anteriorly (below bladder), bladder pushed up. Vertical incision posteriorly. Pass nonabsorbable suture (Mersilene/Ethibond) submucously. Tie suture ends posteriorly (reef knot). Reduce bulging membranes. Repair incisions. McDonald's Operation: Purse-string suture (Mersilene) high up at junction of rugose vaginal epithelium and smooth vaginal part of cervix. Postoperative care: Bed rest (2-3 days). Weekly 17a-hydroxyprogesterone caproate 500 mg IM (if prior preterm delivery). Isoxsuprine (tocolytics) for uterine irritability. Advice on discharge: Antenatal advice, avoid intercourse/rough journey. Report bleeding/pain. Periodic USG of fetus/cervix. Removal of stitch: At 37 weeks or earlier if labor/abortion appears. If not removed, uterine rupture/cervical tear. Contraindications: Intrauterine infection, ruptured membranes, vaginal bleeding, severe uterine irritability, cervical dilatation $\gt 4 \, \text{cm}$, fetal death/defect. Complications: Suture slipping/cutting, chorioamnionitis, membrane rupture, abortion/preterm labor, cervical lacerations/scarring. Abdominal cerclage: Mersilene tape at level of isthmus. Done laparoscopically. Increased complications, subsequent laparotomy for delivery. Alternatives: Bed rest. Progesterone. Vaginal pessary. Induction of Abortion Definition Deliberate termination of pregnancy before fetal viability. Can be legal or illegal. MTP Act (India) Indications Risk to mother's life/grave injury to physical/mental health. Substantial risk of child born with serious physical/mental abnormalities. Pregnancy due to rape. Pregnancy due to contraceptive failure. Practical Indications for MTP To save life of mother (therapeutic): Cardiac diseases (grades III/IV), chronic glomerulonephritis, malignant hypertension, intractable hyperemesis gravidarum, cervical/breast malignancy, diabetes with retinopathy, epilepsy/psychiatric illness. Social indications: To prevent grave injury to physical/mental health (unplanned pregnancy, low socioeconomic status, rape, contraceptive failure). Eugenic: Structural (anencephaly), chromosomal (Down's), genetic (hemophilia) abnormalities. Fetus deformed by teratogenic drugs/radiation exposure. MTP Recommendations Registered medical practitioner (trained/certified). Termination only in authorized centers. Pregnancy in minor/lunatic: Written consent of parents/legal guardian. Termination permitted up to 20 weeks. Beyond 12 weeks: opinion of two practitioners. Abortion confidential, report to Director of Health Services. Methods of Termination of Pregnancy First Trimester (Up to 12 Weeks) Medical: Mifepristone, mifepristone + misoprostol, methotrexate + misoprostol, tamoxifen + misoprostol. Surgical: Menstrual regulation, vacuum aspiration (MVA/EVA), suction evacuation/curettage, D&E (rapid/slow method). First Trimester Medical Methods Mifepristone (RU-486) & Misoprostol: Mifepristone (progesterone antagonist) blocks progesterone. Misoprostol (PGE1) improves efficiency. Effective up to 63 days, highly successful up to 49 days. Protocol: Mifepristone 200 mg orally (Day 1). Misoprostol 400 $\mu$g orally or 800 $\mu$g vaginally (Day 3). Patient observed for 4 hours. Re-examined in 10-14 days. 95% complete abortion. Oral mifepristone 200 mg (1 tab) with vaginal misoprostol 800 $\mu$g (4 tab) after 6-48 hours equally effective. Safe, effective, noninvasive, minimal complications. Methotrexate & Misoprostol: Methotrexate 50 mg/m² IM (before 56 days), followed by misoprostol 800 $\mu$g vaginally 7 days later (may be repeated). Less expensive, but takes longer. Fewer side effects. Contraindications: Mifepristone not for women $\gt 35$ years, heavy smokers, long-term corticosteroid use. First Trimester Surgical Methods Vacuum Aspiration (MVA/EVA): Up to 12 weeks, minimal cervical dilatation. Outpatient procedure using plastic cannula/syringe. Quicker, effective (98-100%), less traumatic. Suction Evacuation/Curettage: Suction machine with cannula. Second Trimester (13-20 Weeks) Prostaglandins: PGE1 (misoprostol), 15 methyl PGF2a (carboprost), PGE2 (dinoprostone) and analogs. Used intravaginally, intramuscularly, or intra-amniotically. Dilation and Evacuation (13-14 weeks). Intrauterine instillation of hyperosmotic solutions: Extra-amniotic (ethacridine lactate, prostaglandins, saline). Intra-amniotic (hypertonic urea, saline). Oxytocin infusion: High dose, with other methods. Hysterotomy (abdominal): Less common. Midtrimester Medical Methods Prostaglandins: Effective, especially in second trimester. Act on cervix/uterus. PGEs preferred (selective action, fewer side effects). Misoprostol (PGE1): 400-800 $\mu$g vaginally every 3-4 hours. Or 600 $\mu$g vaginally then 200 $\mu$g orally every 3 hours. Or 400 $\mu$g sublingually every 3 hours (5 doses). Mean induction-abortion interval 11-12 hours. Mifepristone & prostaglandins: Mifepristone 200 mg orally, then misoprostol 36-48 hours later. 97% success, median induction delivery interval 6.5 hours. Gemeprost (PGE1): 1 mg vaginal pessary every 3-6 hours (5 doses in 24 hours). 90% success. Mean induction-abortion interval 14-18 hours. Dinoprostone (PGE2): 20 mg vaginal suppository every 3-4 hours. With osmotic dilators, mean induction 17 hours. PGF2a (carboprost): 250 $\mu$g IM every 3 hours (10 doses). 90% success in 36 hours. Side effects: nausea, vomiting, diarrhea, pain. Contraindicated in bronchial asthma. Oxytocin: High-dose as single agent (80% effective) or with other methods. Up to 50 milliunits/min or more. Currently high dose (300 units in 500 mL dextrose saline) favored. Midtrimester Surgical Methods D&E (13-15 weeks): Less common. Cervical preparation (laminaria tents, mifepristone, misoprostol) needed. May use USG guidance. Oxytocin infusion helpful. Intrauterine Instillation of Hypertonic Solution (16-20 weeks): Extra-amniotic: 0.1% ethacridine lactate transcervically. Foley's catheter inflation. Intra-amniotic: Hypertonic saline (20%) instilled via abdominal route. Contraindicated in cardiovascular/renal disease, severe anemia. Precautions: ensure needle in amniotic cavity, slow instillation, monitor vitals, stop if adverse symptoms (pain, headache, thirst, tingling). Complications of MTP Immediate: Injury (cervix, uterus), hemorrhage/shock, thrombosis/embolism, postabortal triad (pain, bleeding, low-grade fever). Related to methods: Prostaglandins: Vomiting, diarrhea, fever, uterine pain, cervicouterine injury. Oxytocin: Water intoxication, convulsions. Saline: Hypernatremia, pulmonary edema, endotoxic shock, DIC, renal failure, cerebral hemorrhage. Remote: Gynecological: Menstrual disturbances, chronic pelvic inflammation, infertility (cornual block), scar endometriosis, uterine synechiae. Obstetrical. Ectopic Pregnancy Definition Fertilized ovum implanted and developing outside normal endometrial cavity. Sites of Implantation Tubal (97% - ampulla 55%, isthmus 25%, infundibulum 18%, interstitial 2%), Uterine (1.5% - cornual, cervical, cesarean scar), Ovarian (0.5%), Abdominal (1%). Tubal Pregnancy Increased incidence (1 in 300 to 1 in 150 deliveries) due to PID, tubal plastic operations, ovulation induction, IUD use. Early diagnosis reduces maternal deaths. Etiology Salpingitis & PID: 6-10x increased risk (loss of cilia, impaired peristalsis, narrowing lumen, pockets, peritubal adhesions). Chlamydia trachomatis is common cause. Iatrogenic: Contraception failure: IUCD (relative increase in tubal pregnancy, ovarian pregnancy not affected). Progestin-only pill/postcoital estrogen (impaired tubal motility). Sterilization operation: 15-50% chance of ectopic (laparoscopic bipolar coagulation highest). Tubal surgery: Increased risk. Intrapelvic adhesions. ART: 5-7% risk of tubal pregnancy, 1% risk of heterotopic pregnancy. Previous ectopic pregnancy: 10-15% chance of repeat. Developmental defects of tube: Elongation, diverticulum, accessory ostia. Transperitoneal migration of ovum: Contralateral corpus luteum in 10%. Factors facilitating nidation in tube: Early trophoblastic activity, impaired decidual reaction, tubal endometriosis. Morbid Anatomy Changes in tube: Implantation in tube (intercolumnar), minimal decidual change, limited hyperplasia/hypertrophy of muscles, vessel engorgement, blastocyst burrows, pseudocapsule forms, vessels eroded, tube distended/thinned, blood spills from fimbriated end (hemoperitoneum). Tubal rupture. Trophoblast growth inadequate, hCG production inadequate. Changes in uterus: Enlargement, increased vascularity. Decidua develops, but no chorionic villi. Endometrial sloughing (uterine bleeding) if progesterone falls. Decidual cast expelled. Clinical Features of Ectopic Pregnancy Varied features. Three types: acute, unruptured, subacute/chronic. Acute Ectopic Pregnancy (Tubal Rupture/Abortion) Less common ($\approx 30\%$), associated with massive intraperitoneal hemorrhage. Patient profile: Max incidence 20-30 years (peak fertility), nulliparity or long infertility. Mode of onset: Acute, but 1/3 have persistent unilateral uneasiness. Symptoms (Classic Triad): Abdominal pain (100%), amenorrhea (75%), vaginal bleeding (70%). Amenorrhea: Short period (6-8 weeks), or delayed/spotting. Abdominal pain: Acute, agonizing/colicky, or vague soreness. Unilateral/bilateral. Shoulder tip pain ($\approx 25\%$) from hemoperitoneum. Vaginal bleeding: Slight, continuous. Decidual cast expulsion ($\approx 5\%$). Vomiting, fainting attack: Syncopal attack ($\approx 10\%$) due to vasomotor disturbances. Signs: General look: Quiet, conscious, perspires, blanched. Features of shock: Tachycardia, feeble pulse, hypotension, cold clammy extremities. Abdominal examination: Tense, tumid, tender lower abdomen. Shifting dullness. Muscle guard. Pelvic examination: Less informative due to tenderness. Findings: blanched vaginal mucosa, normal/slightly bulky uterus, extreme tenderness on fornix/cervix movement. Floating uterus. Caution: manipulation can precipitate hemorrhage. Unruptured Tubal Ectopic Pregnancy High suspicion needed. High misdiagnosis rate. Include in differential diagnosis for sexually active female with abnormal bleeding/abdominal pain, especially with risk factors. Symptoms: Delayed period/spotting. Unilateral flank uneasiness (continuous/colicky). Signs: Bimanual examination: Soft uterus (early pregnancy). Pulsatile, small, well-circumscribed tender mass felt. Chronic or Old Ectopic Pregnancy Insidious onset. Patient had previous acute pain episodes or chronic features. Difficult to diagnose due to vagaries of clinical features. Confusing features: Absence of amenorrhea/vaginal bleeding, vaginal bleeding followed by pain, normal general condition, bilateral mass on internal exam, history of tubectomy/IUD. Symptoms: Amenorrhea (6-8 weeks). Lower abdominal pain (acute, dull, colicky). Vaginal bleeding (scanty, sanguineous, dark, continuous). Decidual cast. Signs: Ill patient, pallor, persistent high pulse, no shock, slightly elevated temp ($\approx 38^\circ C$). Abdominal examination: Tenderness/muscle guard on affected side. Irregular, tender mass. Cullen's sign (periumbilical bluish discoloration) if hemoperitoneum. Bimanual examination: Painful. Pale vaginal mucosa. Normal/bulky uterus, often incorporated in mass. Extreme tenderness on cervix movement. Ill-defined, boggy, tender mass extending to POD. Mass may push uterus. Diagnosis of Ectopic Pregnancy Acute Ectopic Classic history of acute abdominal catastrophe with fainting/collapse + features of intra-abdominal hemorrhage in reproductive-age woman. No time for investigations beyond Hb, ABO/Rh. Differential diagnoses: Acute appendicitis, ruptured corpus luteum, twisted ovarian tumor, ruptured chocolate cyst, perforated peptic ulcer. Investigations for Tubal Ectopic Pregnancy Blood: Hb, ABO/Rh, WBC count/diff, ESR. Culdocentesis: Simple, safe. Diagnostic alternative if TVS/laparoscopy unavailable. Aspiration of nonclotting blood with Hct $\gt 15\%$ signifies ruptured ectopic. Estimation of $\beta$-hCG: Urine pregnancy test (ELISA) sensitive to 10-50 mIU/mL, positive in 95%. Single estimation less useful than serial. Doubling time in plasma fails. Lower concentration than normal IUP. Sonography (TVS): More informative. Diagnostic features: absence of IUP with positive pregnancy test, fluid (echogenic) in POD, adnexal mass (Blob sign), cardiac motion (rarely), Color Doppler (ring-of-fire pattern). Combination of quantitative $\beta$-hCG & sonography: If $\beta$-hCG $\ge 1500 \, \text{IU/L}$ (TVS) or $\ge 6000 \, \text{IU/L}$ (TAS) with empty uterus, ectopic likely. Failure to double $\beta$-hCG in 48 hours with empty uterus highly suggestive. Laparoscopy: Benefits in confusion with other pelvic lesions. Confirm diagnosis, remove mass, inject chemotherapeutic agents. Risk of false-positive/negative (2-5%). Dilatation & Curettage: Decidua without villi suggestive. Chorionic villi in normal saline (lacy fronds) diagnostic of IUP. Serum progesterone: $\ge 25 \, \text{ng/mL}$ suggests viable IUP; $\lt 5 \, \text{ng/mL}$ suggests ectopic/abnormal IUP. Laparotomy: If in doubt and patient unstable. Differential Diagnosis of Subacute Ectopic Pregnancy Incomplete abortion: Bleeding before pain, no fainting, bright red bleeding, good general condition, no hemoperitoneum. Salpingitis: History of similar attacks, burning pain, amenorrhea absent (slight bleeding), fever, tossing in bed, flushed face, bilateral tenderness/mass, leukocytosis. Appendicitis: Pain/tenderness at McBurney's point, muscle guard/rigidity, negative pelvic findings. Twisted ovarian tumor: History of swelling, no fainting, vaginal bleeding (confusing), unaffected general condition, cystic mass separate from uterus. Ruptured chocolate cyst. Ruptured corpus luteum (pregnancy test negative). Management of Ectopic Pregnancy Evolved from radical surgery to conservative medical/surgical. Individualized treatment. Acute Ectopic Principle: Resuscitation and laparotomy. Antishock treatment: Ringer's solution. Blood transfusion (after clamps occlude vessels). Volume replacement with colloids. Laparotomy: Indications: hemodynamically unstable, laparoscopy contraindicated, evidence of rupture. Principle: 'quick in quick out'. Surgical procedures: Salpingectomy (remove tube) or salpingostomy (linear incision, remove products, leave incision open). Rh-negative women: Anti-D immunoglobulin. Management of Unruptured Tubal Pregnancy Expectant: Observation, hoping for spontaneous resolution. Medical: Systemic: Methotrexate (MTX) 50 mg/m² IM (single dose). Monitoring serum $\beta$-hCG (D4, D7). Second dose if decline $\lt 15\%$. Direct local: MTX, potassium chloride. Conservative surgery: Laparoscopic or microsurgical. Indications: Not fulfilling medical criteria, $\beta$-hCG not decreasing, persistent fetal cardiac activity. Linear salpingotomy: Longitudinal incision over ectopic, remove products, leave incision open (heals by secondary intention). Segmental resection: For isthmic pregnancy. End-to-end anastomosis. Fimbrial expression: For distal ampullary pregnancy. Salpingectomy: If tube damaged, contralateral tube normal, future fertility not desired. Post-treatment monitoring: Weekly $\beta$-hCG until $\lt 5.0 \, \text{mIU/mL}$. Persistent ectopic pregnancy (10-15%): Due to incomplete trophoblast removal. Higher after fimbrial expression and if initial $\beta$-hCG $\gt 3000 \, \text{IU/L}$. Prophylactic single dose MTX resolves. Rh-negative women: Anti-D gammaglobulin (50 $\mu$g if $\lt 12$ weeks; 300 $\mu$g if $\gt 12$ weeks) post-op. Prognosis of Tubal Pregnancy Maternal mortality reduced (0.05%). Recurrence risk 1 in 10. Fertility not adversely affected if no history of subfertility. Expectant/medical management better than salpingectomy. Prevention of Recurrence Subsequent IUP incidence 60-70% after conservative surgery. Subsequent ectopic 10-20%. Successful conception $\approx 60\%$. Interstitial Pregnancy Rarest tubal pregnancy. Thick, vascular musculature allows longer growth (12-14 weeks). Termination usually by rupture (massive intraperitoneal hemorrhage). Abortion through uterine cavity rarely. USG Diagnostic Criteria Empty uterine cavity. Gestation sac located laterally in intramural part of tube, surrounded by thin myometrium ($\lt 5 \, \text{mm}$). "Interstitial line sign" (echogenic line from central uterine cavity to interstitial sac). Management Expectant: Serum $\beta$-hCG low or falling. Medical: Patient hemodynamically stable, MTX (systemic/local). Surgical: Cornual resection (laparoscopy preferred). Hysterectomy common. Abdominal Pregnancy Primary Fertilized ovum implantation on peritoneum. Rare. Studdiford's criteria: normal tubes/ovaries, no uteroperitoneal fistula, pregnancy exclusively on peritoneal surface, young enough to exclude secondary implantation. Secondary More common. Primary sites: tube, ovary, uterus. Conceptus escapes through rent. Incidence 1 in 3,000. Rising with ART. Symptoms History of disturbed tubal pregnancy (pain, vaginal bleeding). Exaggerated minor ailments of IUP (nausea, vomiting, constipation, pain, increased fetal movements). Signs in Advanced Pregnancy Uterine contour not well-defined, no Braxton-Hicks contraction. Fetal parts easily felt. Persistent abnormal attitude/position. High fetal position (intraperitoneal), low (intraligamentary). Internal Examination Uterus difficult to separate from abdominal mass, enlarged (12-16 weeks) but not typically soft, displaced. Imaging Studies (USG Diagnostic Criteria for Early Pregnancy) Empty uterine cavity. Gestational sac surrounded by bowel loops, separated by peritoneum. Fluctuation of sac. MRI helpful for diagnosis/placenta localization. Diagnosis Rarity, variegated clinical pictures. High index of suspicion, elevated $\beta$-hCG, USG/MRI. Highly suggestive features for late cases: failed induction for IUFD, no uterine contraction with oxytocin. Surest evidence: laparotomy. Management Early pregnancy: Laparoscopic removal. Systemic MTX with USG-guided feticide. Advanced pregnancy: Urgent laparotomy. Risks: hemorrhage, IUFD, fetal malformation, neonatal loss. Continuation only in exceptional circumstances. Patient hospitalized. Laparotomy: Remove entire sac-fetus-placenta-membranes. If placenta adherent to vital organs, remove fetus and leave placenta (monitor $\beta$-hCG). MTX as adjunct. Prognosis Maternal mortality $\lt 5\%$, morbidity high. Perinatal mortality $\approx 90\%$. Fetal malformation $\approx 50\%$. Ovarian Pregnancy Spiegelberg's Criteria Tube on affected side intact. Gestation sac in ovarian position. Gestation sac connected to uterus by ovarian ligament. Ovarian tissue on sac wall (histology). USG Diagnostic Criteria Empty uterine cavity. Wide echogenic ring with anechoic area on ovary. Gestation sac/embryo seen. Negative "sliding organ sign". Treatment Options Surgical: Laparoscopic removal (conceptus, enucleation, wedge resection). Oophorectomy if excessive bleeding or ovarian pathology. Medical: Systemic MTX (if high surgical risk, persistent GTN). Cornual Pregnancy Pregnancy in rudimentary horn of bicornuate uterus. Prevalence 1 in 76,000. Horn usually not communicating with uterine cavity. Fertilization then implantation. General/local reactions intensified. Termination by rupture inevitable (12-20 weeks) with massive intraperitoneal hemorrhage. USG Diagnostic Criteria Single interstitial portion of tube in main uterine body visible. GS mobile, separate from uterus. GS/products surrounded by myometrium. Vascular pedicle connecting GS to unicornuate uterus. Often misdiagnosed as fibroid/ovarian tumor. Surgery involves removal of rudimentary horn. Cervical Pregnancy Rare (1 in 16,000). Implantation in cervical canal. Trophoblast erosion causes thinning/distension. Confused with cervical abortion. Bleeding painless. Uterine body above distended cervix. Intractable bleeding raises suspicion. High morbidity/mortality. USG Diagnostic Criteria Empty uterine cavity. Cervix barrel shaped. GS below internal os. Absence of "sliding sign". Increased blood flow around GS. Clinical Diagnostic Criteria (Rubin-1983) Soft, enlarged cervix (equal/larger than fundus). Uterine bleeding after amenorrhea, no cramping pain. Products confined/attached to endocervix. Closed internal os, partially opened external os. Management Medical: Systemic MTX, local injection with KCl. Surgical: If bleeding life-threatening. D&C (with/without adjunctive methods). Uterine artery ligation/embolization (UAE). Hysteroscopic resection with UAE. Hysterectomy. Criteria for Successful Conservative Management Pregnancy $\lt 12$ weeks. No fetal cardiac activity. Low serum $\beta$-hCG levels. Pregnancy of Unknown Location (PUL) No sign of intra/extrauterine pregnancy or retained products with positive pregnancy test. Cesarean Scar Pregnancy Implantation into myometrial defect at site of previous uterine scar. Prevalence 1 in 2500-3000. Outcome: viable pregnancy or miscarriage within scar. USG Diagnostic Criteria Empty uterine cavity. GS/solid mass of trophoblast cells anteriorly at level of internal os, embedded in niche scar. Thin/absent myometrium layer. Distinct vascular flow. Closed endocervical canal. Yolk sac, embryo, cardiac activity may be seen. Negative 'slide organs' sign. MRI needed if USG inconclusive. Serum $\beta$-hCG for management. Types Type 1 (Endogenic - growing towards uterine cavity). Type 2 (Exogenic - growing outwards, high risk of rupture/hemorrhage). Treatment Options Surgical more effective than medical. Live birth reported (rare). Medical: MTX (systemic/local). Surgical: S/E or excision by open, laparoscopic, hysteroscopic. Additional hemostatic measures (Foley catheter, UAE, hysterectomy). Pregnancy of Uncertain Viability Intrauterine gestation sac ($\lt 20 \, \text{mm}$), no yolk sac/fetus, no fetal echo $\lt 6 \, \text{mm}$ CR length, no fetal activity. Repeat scan in 1 week to confirm/refute viability. Heterotopic Pregnancy Incidence 1 in 8,000. More common after ART. IUP co-existent with tubal/cervical/ovarian pregnancy. Diagnosis difficult. USG Diagnostic Criteria IUP + co-existing ectopic. Higher than expected $\beta$-hCG. Persistently raised $\beta$-hCG after miscarriage/termination. Management IUP considered in management. Medical: MTX (if IUP nonviable, patient does not wish to continue). Gestational Trophoblastic Disease (GTD) Definition Spectrum of proliferative trophoblast abnormalities associated with pregnancy. Persistent GTD (persistently raised $\beta$-hCG) is gestational trophoblastic neoplasia (GTN). Classification Extensive, confusing. Morphological less important as management is medical. Follow-up depends on hCG. Immunohistochemical/molecular studies important. Conventional histological classification: hydatidiform mole (complete/partial), invasive mole, choriocarcinoma, PSTT. Modified WHO (1998) classification for metastatic disease (low-risk/high-risk). Non-gestational trophoblastic disease: primary choriocarcinoma of ovary. Hydatidiform Mole (Vesicular Mole) Definition Abnormal placental condition with degenerative/proliferative changes in young chorionic villi. Formation of small cysts. Benign neoplasia of chorion with malignant potential. Incidence Wide geographical/ethnic variation. India: 1 in 400. Etiology Related to ovular defect. Prevalence highest in teenage/over 35 years. Varies with race/ethnic origin. Faulty nutrition (low protein/animal fat, low carotene). Disturbed maternal immune mechanisms. Cytogenetic abnormality (complete moles: 46XX karyotype, paternal origin). Higher paternal:maternal chromosome ratio. History of prior hydatidiform mole increases recurrence risk. Pathology Principally chorion disease. Death of ovum/failure of embryo essential for complete mole. Secretion from hyperplastic cells + transferred substances from maternal blood accumulate in villi stroma. Villi distended into vesicles. Vesicle fluid is interstitial fluid, rich in hCG. Naked eye appearance: Mass filling uterus (multiple chains/clusters of cysts). No embryo/amniotic sac. Hemorrhage in decidual space. Microscopic appearance: Edematous villi, trophoblast proliferation, absence of blood vessels in villi. Ovarian changes: Bilateral lutein cysts ($\approx 50\%$) due to excessive hCG. Regress spontaneously. Clinical Features Prevalent in teenaged/elderly, high parity. Amenorrhea 8-12 weeks. Symptoms: Vaginal bleeding: Most common (90%). Mimics incomplete/threatened abortion. Blood mixed with gelatinous fluid ('white currant in red currant juice'). Lower abdominal pain: Due to overstretching, concealed hemorrhage, perforation (invasive mole), infection, uterine contractions. Constitutional symptoms: Patient sick without apparent reason. Excessive vomiting ($\approx 15\%$) due to excess hCG. Breathlessness ($\approx 2\%$) due to pulmonary embolization. Thyrotoxic features ($\approx 2\%$). Expulsion of grape-like vesicles: Diagnostic. $\approx 50\%$ not suspected until expelled. No quickening. Signs: Early pregnancy features. Patient looks more ill than accounted for. Pallor (disproportionate to blood loss) due to concealed hemorrhage/iron deficiency. Pre-eclampsia ($\approx 50\%$). Uterus larger than dates ($\approx 50\%$). Uterine enlargement due to exuberant vesicles/concealed hemorrhage. Uterus firm elastic (doughy). No fetal parts/movements. No fetal heart sound. Vaginal examination: No internal ballottement. Unilateral/bilateral ovarian enlargement (theca lutein cyst) ($\approx 25-50\%$). Vesicles in vaginal discharge pathognomonic. If cervical os open, blood clot or vesicles felt. Investigations Full blood count, ABO/Rh. Hepatic, renal, thyroid function tests. Sonography: 'Snowstorm' appearance (characteristic). Rule out missed abortion, partial mole, degenerated fibroid. Doppler USG, sonography of liver/kidneys/spleen. Quantitative $\beta$-hCG: High titer in urine (positive pregnancy test diluted). Normal pregnancy $\beta$-hCG peaks at 10-14 weeks, rarely $\gt 100,000 \, \text{mIU/mL}$. Molar pregnancy often $\gt 100,000 \, \text{mIU/mL}$. Plain X-ray abdomen: If uterus $\gt 16$ weeks, negative fetal shadow helpful. Chest X-ray for pulmonary embolization. CT/MRI not routinely recommended. Definitive diagnosis: Histological examination. Differential Diagnosis Often confused with threatened abortion, fibroid/ovarian tumor with pregnancy, multiple pregnancy. $\beta$-hCG and USG are diagnostic. Complications of Molar Pregnancy Immediate: Hemorrhage & shock: Vesicle separation, concealed/revealed. Massive intraperitoneal hemorrhage (perforating mole). Atonic uterus, uterine injury during evacuation. Sepsis: No protective membranes, vaginal organisms, degenerated vesicles/blood, increased operative interference. Perforation of uterus: Perforating mole. D&E/curettage. Pre-eclampsia, eclampsia. Coagulation failure (pulmonary embolization of trophoblastic cells). Late: Choriocarcinoma (2-10%). Risk factors: age $\ge 40$ or $\lt 20$, parity $\ge 3$, $\beta$-hCG $\gt 100,000 \, \text{mIU/mL}$, uterine size $\gt 20$ weeks, previous mole, theca lutein cysts $\gt 6 \, \text{cm}$. Prognosis Immediate risk diminished due to early diagnosis/treatment. 15-20% complete moles progress to persistent GTN. $\approx 5\%$ develop metastatic disease. Recurrence risk 1-4%. Improved prognosis due to high-risk factor recognition, careful $\beta$-hCG follow-up, cytotoxic drugs. Management (Hydatidiform Mole) Early diagnosis by USG/hCG. Principles: Suction evacuation (SE), supportive therapy, counseling for follow-up. Supportive Therapy: IV fluids, blood transfusion, parenteral antibiotics. Definitive Management (SE): Safe, rapid, effective. Even up to 28 weeks. Cervix favorable: SE (negative pressure 200-250 mmHg). Or D&E. Monitor. Use oxytocin (not routine due to embolization risk). Digital exploration/ovum forceps. Cervix tubular/closed: Slow dilatation (laminaria tent). Or misoprostol 400 $\mu$g. Hysterectomy: For age $\gt 35$, family completed, uncontrolled hemorrhage/perforation. Reduces GTN risk 5-fold. Hysterotomy: Rarely done. Curettage post-SE: Not routine. In selected cases with persistent bleeding/GTN. Gentle curettage 5-7 days post-SE. Remove necrosed decidua/vesicles. Histology. Follow-up (Mandatory for $\ge 1$ year) Objective: diagnose persistent trophoblastic disease (PTD). $\beta$-hCG should regress to normal within 3 months. Intervals: Weekly $\beta$-hCG until negative (4-8 weeks). If negative for 56 days, monthly for 6 months. Protocols: History, clinical exam, hCG assay. Methods: Enquire symptoms (bleeding, cough, breathlessness, hemoptysis). Abdominovaginal exam (involution of uterus, ovarian size, malignant deposit). Investigations (hCG in urine/serum). Prophylactic Chemotherapy Not routine (toxic drugs, ovarian failure). Used if $\beta$-hCG fails to normalize/re-elevates, postevacuation hemorrhage, inadequate follow-up, metastasis, high-risk factors. Regimes: Methotrexate or Actinomycin D. Contraceptive Advice Not pregnant for $\ge 1$ year. Rise in hCG causes confusion with fresh pregnancy/PTD. With TVS, pregnancy can be diagnosed early. May be pregnant after 6 months if $\beta$-hCG negative. Delayed up to 1-2 years for GTN/metastasis. IUD contraindicated. Combined oral pills used after $\beta$-hCG normal. Injection DMPA or barrier methods can be used. Partial or Incomplete Mole Chorionic villi affection focal. Fetus or amniotic sac present. Karyotype triploid (69XXY/69XYY). Dilated villi, trophoblast hyperplasia, fetal blood vessels with RBCs. Fetus dies early or born growth retarded. Clinical picture similar to complete mole or threatened/missed abortion. $\beta$-hCG not markedly raised. Uterus not usually large for dates. Low malignant potential. Terminate if fetus not alive. If alive, warn patient of risks. Twin Pregnancy - Coexistent Molar Pregnancy & Normal Fetus Rare (1 in 22,000 to 1 in 1,00,000). Medical complications (hyperthyroidism, PIH, hemorrhage) increased. Increased risk of postmolar GTN/metastatic disease. Placental Site Trophoblastic Tumor (PSTT) Rare. Syncytiotrophoblastic cells generally absent. Persistent low $\beta$-hCG. Arises from intermediate trophoblasts. Vaginal bleeding. Local invasion. Not responsive to chemotherapy. Hysterectomy preferred. Persistent Gestational Trophoblastic Neoplasia (GTN) Definition Persistence of trophoblast activity after initial treatment. Follows hydatidiform mole, invasive mole, choriocarcinoma, PSTT. Can be benign or malignant. If after nonmolar pregnancy, always choriocarcinoma. Overall incidence after complete hydatidiform moles 15-20%. Diagnosis Postevacuation follow-up. Features: continued vaginal bleeding, persistent theca lutein cysts, soft/enlarged uterus, $\beta$-hCG fails to normalize/plateaus/re-elevates. Exclude metastasis (X-ray, CT, MRI). Pathologically: invasive mole, choriocarcinoma, PSTT. Treatment Classified low/high-risk (WHO prognostic scoring). Low-risk: single-agent chemotherapy (MTX). High-risk: combination chemotherapy (EMA-CO). Hysterectomy for women $\ge 40$ years/family completed. Regular follow-up essential.