ectopic pregnancy its clinical features diagnosis and management.

Ectopic pregnancy

1. roll no. - 20040 20043 20044 20046 ECTOPIC PREGNANCY

2. DEFINITION “Any pregnancy where the fertilised ovum gets implanted & develops in a site other than normal uterine cavity”. It represents a serious hazard to a woman’s health and reproductive potential, requiring prompt recognition and early aggressive intervention .

3. Is one in which fertilized ovum is implanted & develops outside normal uterine cavity

4. IMPLANTATIONS SITES EXTRAUTERINE UTERINE OVARIAN ABDOMINAL PRIMARY SECONDARY Intraperitoneal Extraperitoneal Broad Ligament (rare) Cervical <1 Angular Caesarean Cornual TUBAL 95-96% Ampulla 70% Isthmus 25% Interstistial 18% Infundibulum2%

5. Incidence and morbidity Increased PID IUCD Tubal surgeries, and Assisted reproductive techniques (ART). Rate in India – 5.6/10000 deliveries Late marriages and late child bearing -> 2% ART -> 5% Recurrence rate - 15% after 1 st , 25% after 2 ectopics

6. ETIOLOGY : Any factor that causes delayed transport of the fertilised ovum through the tube. Fallopian tube favours implantation in the tubal mucosa itself thus giving rise to a tubal ectopic pregnancy. These factors may be Congenital or Acquired .

7. CONGENITAL Tubal Hypoplasia Tortuosity Congenital diverticuli Accessory ostia Partial stenosis Elongation Intamural polyp Entrap the ovum on its way.

8. Aquired - Pelvic Inflammatory disease (6-10 times) Chlamydia trachomatis is most common Incidence of ectopic pregnancy due to use of contraceptives CuT - 4% Progestasart -17% Minipills -4-10% Norplant -30%

9. Incidence of ectopic pregnancy in tubal sterilization -40% Depends on sterilization technique and age of the patient Bipolar Cauterisation -65% Unipolar Cautery -17% Silicon rubber band -29% Interval Salpingectomy -43% Postpartum Salpingectomy -20% Incidence of ectopic pregnancy in reversal of sterilisation Depends on method of sterilization, Site of tubal occlusion, residual tubal length. Reanastomosis of cauterised tube -15% Reversal of Pomeroy’s - < 3%

10. ETIOLOGY contd. Tubal reconstructive surgery (4-5 times) Assisted Reproductive technique - Ovulation induction, IVF-ET and GIFT (4-7%) - Risk of heterotopic pregnancy(1%) Previous Ectopic Pregnancy - 7-15% chances of repeat ectopic pregnancy

11. Other Risk factors Age 35-45 yrs Previous induced abortion Previous pelvic surgeries Cigarette smoking DES Exposure in Utero Infertility Salpingitis Isthmica Nodosa Genital Tuberculosis Fundal Fibroid & Adenomyosis of tube Transperitoneal migration of ovum

12. Pictures showing TUBAL ABORTION Ruptured ectopic

13. CLINICAL APPROACH Dignosis can be done by history, detail examination and judicious use of investigation. H/o past PID, tubal surgery,current contraceptive measures should be asked Wide spectrum of clinical presentation from asymtomatic pt to others with acute abdomen and in shock.

14. ACUTE ECTOPIC PREGNANCY Classical triad is present in 50% of pt with rupture ectopic. - PAIN:- most constant feature in 95% pt - variable in severity and nature - AMENORRHOEA:- 60-80% of pt - there may be delayed period or slight spotting at the time of expected menses. - VAGINAL BLEEDING: - scanty dark brown Feeling of nausea,vomiting,fainting attack, syncope attack(10%) due to reflex vasomotor disturbance. Abdominal pain most comm. Feature. Shoulder tip pain.

15. O/E:- patient is restless in agony, looks blanched, pale, sweating with cold clammy skin. Features of shock, tachycardia, hypotension. P/A:- abdomen tense, tender mostly in lower abdomen, shifting dullness, rigidity may be present. P/S:- minimal bleeding may be present P/V:- uterus may be bulky, deviated to opposite side, fornix is tender, excitation pain on movement of cervix. POD may be full, uterus floats as if in water.

16. UNRUPTURED ECTOPIC High degree of suspicion & ectopic conscious clinician can diagnose. Diagnosed accidentally in Laparoscopy or Laparotomy C/F – delayed period, spotting with discomfort in lower abdomen. P/A – tenderness in lower abdomen P/V should be done gently uterus is normal size, firm small tender mass may be felt in the fornix Investigations- TVS, radioimmunoassay of β -HCG and Laparoscopy

17. diagnosis Patient with acute ectopic can be diagnosed clinically. Blood should be drawn for Hb %, CBC, blood grouping and cross matching,.Serology and Coagulation profile. Should be catheterized to know urine output. Bed side test :- 1. Urine pregnancy test :- positive in 95% cases. ELISA is sensitive to 10-50 mlU /ml of β hCG and can be detected on 24 th day after LMP. 2. Culdocentesis :- (70-90%) Can be done with 16-18 G lumbar puncture needle through posterior fornix into POD. Positive tap is 0.5ml of non clotting blood.

18. 1. Ultrasonography findings :- a) Transvaginal Sonography (TVS) : Is more sensitive It detect intrauterine gestational sac at 4-5wks and at S- β hCG level as low as 1500 IU/L .

19. Endometrial cavity in usg examination - A trilaminar endometial pattern seen - pseudogestational sac - decidual cyst may be seen PSEUDOSAC – All pregnancies induce an endometrial decidual reaction, and sloughing of the decidua can create an intracavitary fluid collection called a pseudosac Early Gestational Sac Pseudosac Location Eccentrically located Midline within E.cavity Shape Round-shape Irregular Border Double Ring sign Vascularity High Avascular Pattern Peripheral -

20. b) Color Doppler Sonography (TV-CDS): - Improve the accuracy. - Identify the placental shape (ring-of-fire pattern) and blood flow outside the uterine cavity. c) Transabdominal Sonography : - can identify gestational sac at 5-6 wks - S- β hCG level at which intrauterine gestational sac is seen by TAS is 1800 IU/L.

21. USG PICTURE 1.‘Bagel’ sign – Hyperechoic ring around gestational sac in adnexal region 2. ‘Blob’ sign – Seen as small inconglomerate mass next to ovary with no evidence of sac or embryo. 3. Adnexal sac with fetal pole and cardiac activity is most specific. 4. Corpus luteum is useful guide when looking for EP as present in 85% cases in Ipsilateral ovary.

22. Hyperechoic ring around gestational sac in adnexal region

23. Ring sign — a hyperechoic ring around an extrauterine gestational sac.

24. 2. β -HCG Assay- a) Single β -HCG: little value b) Serial β -HCG: is required when result of initial USG is confusing. - When hCG level < 2000 IU/L doubling time help to predict viable Vs nonviable pregnancy. -Rise of β -HCG <66% in 48 hrs indicate ectopic pregnancy or nonviable intrauterine pregnancy . Biochemical pregnancy is applied to those women who have two β -HCG values >10 IU/L

25. 3. Serum Progesterone – level >25 ngm /ml is suggestive of normal intrauterine pregnancy. level <15 ngm /ml is suggestive of ectopic pregnancy. level <5 ngm /ml indicates nonviable pregnancy, irrespective of its location. 4. Diagnostic Laparoscopy (Gold standard)– Can be done only when patient is haemodynamically stable. -It confirms the diagnosis and removal of ectopic mass can be done at the same time.

26. SUSPECTED ECTOPIC PREGNANCY Urine Pregnancy test positive Transvaginal USG IU sac No IU sac Quantitative S-hCG + S progesterone < 66% rise in 48 hr or S progesterone < 5-10 ng/ml D & C Villi present Villi absent Incomplete abortion Laparoscopy >66% rise in 48 hr or S progesterone > 5-10 ng/ml Repeat S-hCG in 48 hrs till USG discrimination zone No sac IU sac Continue to monitor

27. DIFFERENTIAL DIAGNOSIS D/D of Acute Ectopic 1. Rupture corpus luteum of pregnancy 2. Rupture of chocolate cyst 3. Twisted ovarian cyst 4. Torsion / degeneration of pedunculated fibroid 5. Incomplete abortion 6. Acute Appendicitis 7. Perforated peptic ulcer 8. Renal colic 9. Splenic rupture

28. TREATMENT Expectant management Medical management Surgical management Local Systemic (USG or Laparoscopic) salpingocentesis Methotrexate - Potassium chloride - Prostagladin(PGF2 α ) - Hypersmolar glucose Actinomycin D Mifepristone Methotrexate Radical Salpingectomy Conservative Salpingostomy Salpingotomy - Segmental resection Milking or fimbrial expression

29. PRINCIPLE: Resuscitation and Laparotomy /Laparoscopy ANTI SHOCK TREATEMENT: - IV line made patent, crystalloid is started - Blood sample for Hb , blood grouping & cross matching, BT, CT - Folley’s catheterization done - Colloids for volume replacement LAPAROTOMY: Principle is ‘Quick in and Quick out’ - Rapid exploration of abdominal cavity is done - Salpingectomy is the definitive surgery (sent for HP study) - Blood transfusion to be given - Autotransfusion only when donated blood not available.

30. Laparoscopy Preferred method if haemodynamically stable Tubal Patency no significant difference Followed by similar number of uterine pregnancy Shorter operative time Salpingostomy Less than 2cm size 10-15mm incision

31. MANAGEMENT OF UNRUPTURED ECTOPIC PREGNANCY OPTIONS: - SURGICAL- SURGICALLY ADMINISTERED MEDICAL (SAM) TREATMENT MEDICAL TREATMENT EXPECTANT MANAGEMENT

32. EXPECTANT MANAGEMENT IDENTIFICATION CRITERIA - : 1. Tubal ectopic pregnancies only 2. Haemodynamically stable 3. No rupture or bleeding 4. Adnexal mass of < 3.5 cm without heart beat. 5. Initial β HCG <1000 IU/L and falling in titre (single best) SUCCESS RATE - Upto 60% PROTOCOL: - Hospitalization with strict monitoring of clinical symptom - Daily Hb estimation - Serum β HCG monitoring 3-4 days until it is <10 IU/L - TVS to be done twice a week.

33. CONTD…. Spontaneous resolution occurs in 72%,while 28% will need laparoscopic salpingostomy In spontaneous resolution, it may take 4-67 days (mean 20 days) for the serum HCG to return to non pregnant level. The percentage fall in serum HCG by day 7 is a better indicator than the percentage fall by day 2. Warning: - Tubal pregnancies have been known to rupture even when Serum HCG levels are low.

34. MEDICAL MANAGEMENT Surgery is the mainstay of T/t worldwide Medical M/m may be tried in selected cases CANDIDATES FOR METHOTREXATE (MTX) Unruptured sac < 3.5cm without cardiac activity S- hCG < 10,000 IU/L Persistant Ectopic after conservative surgery PHYSICIAN CHECK LIST CBC, LFT, RFT, S- hCG Transvaginal USG within 48 hrs Obtain informed consent Anti-D Ig if pt is Rh negative

35. CONTD… METHOTREXATE: It can be used as oral,intramuscular ,intravenous usually along with folinic acid. Resolution of tubal pregnancy by systemic administration of Methotrexate was first described by Tanaka et al (1982) Mostly used for early resolution of placental tissue in abdominal pregnancy.Can also be used for tubal pregnancy. Mechanism of action- Methotrexate is a folic acid antagonist that inactivates the enzyme dihydrofolate reductase . Interferes with the DNA synthesis by inhibiting the synthesis of pyrimidines leading to trophoblastic cell death. Auto enzymes and maternal tissues then absorb the trophoblast .

36. Single dose Mtx 50mg/m² IM β HCG levels at days 4 & 7 If difference ≥15% repeat weekly till ≤5IU/ml If difference ˂15% between day 4 & 7 repeat dose & begin D₁ If fetal Cardiac + ve at D ₇ repeat D₁ Mtx Surgical management if β HCG not ↓ or fetal cardiac + ve after 3 doses Two dose on Day 0, 4 Follow-up same as One dose regimen Variable doses Mtx 1gm/ kg IM D ₁₃₅₇ Leucovorin 0.1mg/kg IM D₂₄₆₈ Measure β HCG levels at D ₁₃₅₇ . Continue alternate day regimen until β HCG levels decrease ≥15% in 48hrs, or 4 doses of Mtx given. Then, weekly β HCG levels until <5iu/ml

37. Contd …… Advantages – Minimal Hospitalisation.Usually outdoor treatment Quick recovery 90% success if cases are properly selected Disadvantages- Side effects like GI & Skin Monitoring is essential- Total blood count, LFT & Serum HCG once weekly till it becomes negative

38. SURGICALLY ADMINISTERED MEDICAL Tt (SAM) Aim - trophoblastic destruction without systemic side effects Technique - Injection of trophotoxic substance into the ectopic pregnancy sac or into the affected tube by- Laparoscopy or Ultrasonographically guided Transabdominal ( Porreco , 1992) Transvaginal ( Feichtingar , 1987) With Falloposcopic control (Kiss, 1993)

39. Trophotoxic substances used- Methtrexate ( Pansky , 1989) Potassium Chloride (Robertson, 1987) Mifiprostone (RU 486) PGF2  ( Limblom , 1987) Hyper osmolar glucose solution Actinomycin D Advantage of local MTX : - Increase tissue concentration at local site - Decrease systemic side effects - Decrease hospitalization - Greater preservation of fertility Follow up: - Serum β HCG twice weekly till < 5 IU/L - TVS weekly for 4-6 weeks - HCG after 6 months for tubal patency CONTD…

40. INSTRUCTION TO THE PATIENTS If T/t on outpatient basis rapid transportation should be available Refrain from alcohol, sunlight, multivitamins with folic acid, and sexual intercourse until S-hCG is negative. Report immediately when vaginal bleeding, abdominal pain, dizziness, syncope (mild pain is common called separation pain or resolution pain) Failure of medical therapy require retreatment Chance of tubal rupture in 5-10 % require emergency Laparotomy.

41. SURGICAL MANAGEMENT OF ECTOPIC Conservative Surgery Can be done Laparoscopically or by microsurgical laparotomy INDICATION: - Patient desires future fertility - Contralateral tube is damaged or surgically removed previously CHOICE OF TECHNIQUE: depends on - Location and size of gestational sac - Condition of tubes - Accessibility

42. VARIOUS CONSERVATIVE SURGERIES 1.Linear Salpingostomy : - Indicated in unruptured ectopic <2cm in ampullary region. - Linear incision given on antimesentric border over the site and product removed by fingers, scalpel handle or gentle suction and irrigation. - Incision line kept open (heals by secondary intention) 2. Linear Salpingotomy : - Incision line is closed in two layers with 7-0 interrupted vicryl sutures. 3. Segmental Resection & Anastomosis: - Indicated in unruptured isthmic pregnancy - End to end anastomosis is done immediately or at later date

43. 4. Milking or fimbrial Expression: - This is ideal in distal ampullary or infundibular pregnancy. - It has got increased risk of persistent ectopic pregnancy. ADVANTAGES OF LAPAROSCOPY - It helps in diagnosis, evaluation, and treatment . - Diagnose other causes of infertility. - Decreased hospitalization, operative time, recovery period, analgesic requirement. Follow up after conservative surgery - With weekly Serum β HCG titre till it is negative. - If titre increases methotrexate can be given.

44. SALPINGECTOMY VS SALPINGOSTOMY / SALPINGOTOMY All tubal pregnancies can be treated by partial or total Salpingectomy Salpingostomy / Salpingotomy is only indicated when : The patient desires to conserve her fertility Patient is haemodinamically stable Tubal pregnancy is accessible Unruptured and < 5Cm. In size Contralateral tube is absent or damaged

45. CONTD…… The choice of surgical treatment does not influence the post treatment fertility, but prior history of infertility is associated with a marked reduction in fertility after treatment.

46. Laparotomy Vs Laparoscopy - Laparoscopy is reserved for pt who are hemodynamically stable. - Ruptured Ectopic does not necessarily require Laparotomy , but if large clots are present Laparotomy should be considered. Reproductive outcome Is similar in pt treated with either Laparoscopy or Laparotomy . Identical rates of 40% of IUP, around 12% risk of recurrent pregnancy with either radical or conservative pregnancy.

47. LAPAROSCOPIC SALPINGECTOMY It is carried out by laparoscopic scissors & diathermy or Endo-loop. After passing a loop of No.1 catgut over the ectopic pregnancy the stitch is tightened and then the tubal pregnancy is cut distal to the loop stitch. The excised tissue is removed by piece meal or in tissue removal bag LAPAROSCOPIC SALPINGOTOMY To reduce blood loss, first 10-40 IU of vasopressin diluted in10 ml of normal saline is injected into the mesosalpinx . Then the tube is opened through an antimesenteric longitudinal incision over the tubal pregnancy by a Co 2 laser (Paulson, 1992) Argon laser ( Keckstein et al; 1992) Laparoscopic scissors and ablating the bleeding points with bipolar diathermy. Fine diathermy knife ( Lundorff , 1992) The tubal pregnancy is then evacuated by suction irrigation.

48. PERSISTENT ECTOPIC PREGNANACY This is a complication of salpingotomy / salpingostomy when residual trophoblast continues to survive because of incomplete evacuation of the ectopic pregnancy. Diagnosis is made because of a raised postoperative β HCG If untreated, can cause life threatening hemorrhage Risk Factor: ( seifer 1997) 1. Early ectopic pregnancy (< 6 wks amenorrhoea ) 2. Smaller size < 2 cm (Incomplete removal) 3. Preoperative high serum β HCG (> 3,000 IU/L) and postoperative Day1 titre is < 50% of preoperative level, is predictor of persistent EP. 4. Implantation medial to the salpingostomy site. Treatment surgery Total or partial salpingectomy Medical (selected Asymptomatic pt) MTX + Leukovorin

49. OVARIAN ECTOPIC PREGNANCY Incidence: 1:40,000 Risk factor: - IUCD - Endometriosis on surface of ovary Course: C/F are same as tubal pregnancy ruptures within 2-3 wks Diagnosis: On Laparotomy Spiegelberg’s Criteria 1. Ipsilateral tube is intact and separate from sac 2. Sac occupies the position of the ovary 3. Connected to uterus by ovarian ligament 4. Ovarian tissue found on its wall on HP study M/M Ruptured Laparotomy Oophorectomy Unruptured Ovarian wedge resection Ovarian Cystectomy

50. ABDOMINAL PREGNANCY Incidence: Rarest MMR : 7-8 times > tubal ectopic 90 times > Intrauterine pregnancy H/O : - Irregular bleeding, spotting - Nausea, vomiting, flatulence, constipation, diarrhoea , abdominal pain. - Fetal movement may be painful and high in the abdomen O/E : - Abnormal fetal position, easy in palpating fetal parts. - uterus palpated separate from sac - no uterine contraction after oxytocin infusion

51. CERVICAL PREGNANCY Implantation occurs in cervical canal at or below internal Os. Incidence: 1 in 18,000 RISK FACTORS : - Previous induced abortion - Previous caesarean delivery - Asherman’s syndrome - IVF - DES exposure - Leiomyoma

52. Diagnosis: CLINICAL CRITERIA : Paulman & McEllin 1. Uterine bleeding, no cramping, following amenorrhoea 2. Cervix distended,thin walled,soft consistency 3. Enlarged uterine fundus may be palpated. 4. Internal Os is closed 5. External Os is partially opened USG CRITERIA : American Journal of O&G 1. Echo-free uterine cavity/ pseudo-gestational sac 2. Decidual reaction 3. Hourglass uterus with ballooned cervical canal 4. Gestational sac in endocervix 5. Closed internal Os 6. Placental tissue in Cx canal

53. HISTOPATHOLOGIC CRITERIA Rubin’s : 1. Cervical glands present opposite to placenta 2. Placental attachment to the cervix must be below the entrance of uterine vessels . 3. Fetal element absent from corpus uteri. D/d : Carcinoma Cx Cervical submucous fibroid Trophoblastic tumour Placenta previa

54. TREATMENT Surgical Mainstay therapy in past Radical surgery Hysterectomy Conservative D & C (risk of torrential bleeding) Cerclage Bernstein ≈ Mc Donald’s Wharton ≈ Shirodkar’s Transvaginal ligation of Cx branch of uterine artery - Angiographic uterine A embolisation Intracervical vasopressin inj Foley’s catheter as tamponade Medical Recently proposed Single or Combination OR Adjunct to surgery Methotrexate Actinomycin KCl Etoposide

55. CORNUAL PREGNANCY SITE: Implantation occurs in rudimentary horn of Bicornuate uterus COURSE : Rupture of horn occurs by 12-20 wks D/D : 1. Interstitial tubal pregnancy 2. Painful leiomyoma along with pregnancy 3. Ovarian tumor with pregnancy 4. Asymmetrical enlargement of uterus. Implantation into cornu of normal uterus is sometime called Angular pregnancy . TREATEMENT: - Affected cornu with pregnancy is removed - Hysterectomy - Hysteroscopically guided suction curettage if communication with Cx is patent

56. HETEROTYPIC PREGNANCY Co-existing intrauterine and extra uterine pregnancies More likely: a) Ass. reproductive technique b) Rising HCG titre after D & C c) More than 1 corpus luteum at laparotomy M/M : Depends on the site. Ectopic site may be removed with continuation of IU pregnancy ( Rh Immunoglobulin: dose of 50 μ gm is sufficient to prevent sensitization.)

57. INTERSTITAL PREGNANCY (2%) It ruptures late at 3-4 months gestation. Fatal rupture – severe bleeding as both uterine & ovarian artery supply. Early & Unruptured – Local or IM MTX with followup Cornual resection by Laparotomy may be done. There is high risk of uterine rupture in subsequent pregnancy. Rupture – Hysterectomy is indicated

58. CAESAREAN SCAR ECTOPIC PREGNANCY Recently reported USG slows on empty uterine cavity and gestational sac attached low to the lower segment caesarean scar. C/F : similar to threatened or inevitable abortion Diagnosis : Doppler imaging confirms Management: Methotrexate injection Hysterectomy in a multiparous women. In young pt resection & suturing of scar may be done (high risk of rupture).

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