2. Ectopic Pregnancy Dr. Yasir Katib MBBS, FRCSC, Perinatologist

3. Introduction Ectopic pregnancy occurs when the developing blastocyst becomes implanted at a site other than the endometrium of the uterine cavity Ectopic pregnancy occurs when the developing blastocyst becomes implanted at a site other than the endometrium of the uterine cavity The most common extra-uterine location is the fallopian tube, which accounts for 98% The most common extra-uterine location is the fallopian tube, which accounts for 98%

4. Types of EP

5. Sites of EP Fallopian tube Ampulla Ampulla80% Isthmus Isthmus12% Fimbrial end Fimbrial end5% Cornual & interstitial Cornual & interstitial2% Abdominal1.4% Ovarian0.2% Cervical0.2% Heterotopic Pregnancies: 1 in 30 000

6. Epidemiology 2 nd leading cause of overall maternal mortality in US 2 nd leading cause of overall maternal mortality in US Leading cause of pregnancy-related deaths during T-1 Leading cause of pregnancy-related deaths during T-1 1-2% of all diagnosed pregnancies 1-2% of all diagnosed pregnancies

7. Epidemiology Incidence is  Incidence is   incidence of salpingitis d/t chlamydia or other STI  incidence of salpingitis d/t chlamydia or other STI Improved diagnostic techniques Improved diagnostic techniques  age  age Blacks >non-whites>whites Blacks >non-whites>whites Most occur in multigravid women Most occur in multigravid women > 50% in women with  3 pregnancies > 50% in women with  3 pregnancies 10-15% in nulligravid women 10-15% in nulligravid women

8. Mortality Causes 15% of maternal deaths Causes 15% of maternal deaths Overall risk of death 10X > the risk of childbirth; 50X > risk of legal abortion Overall risk of death 10X > the risk of childbirth; 50X > risk of legal abortion Cause of death due Cause of death due  blood loss (80%)I  infection (3%)  anesthesia (2%) Interstitial & abdominal  5X > risk of death than other sites Interstitial & abdominal  5X > risk of death than other sites

9. Of Historical Note……. 1693 1693 1 st documentation of unruptured ectopic 1 st documentation of unruptured ectopic 1752 1752 Infertility linked to EP Infertility linked to EP mid 19 th century mid 19 th century Path reports stressed pelvic inflammation as cause of EP Path reports stressed pelvic inflammation as cause of EP 1800s 1800s 30 abd operations in (5 women survived) 30 abd operations in (5 women survived) If not treated, 1 out of 3 survived (better!) If not treated, 1 out of 3 survived (better!)

10. Risk Factors for EP Definite (high risk) Definite (high risk) Previous EP Previous EP Any tubal surgery or sterilization procedure Any tubal surgery or sterilization procedure In-utero DES exposure In-utero DES exposure

11. Risk Factors for EP Probable (modrate risk) Probable (modrate risk) PID PID Infertility Infertility “Superovulating agents” “Superovulating agents” Pergonal, Clomiphene citrate Pergonal, Clomiphene citrate Multiple sexual partners Multiple sexual partners Smoking Smoking

12. Risk Factors for EP Uncertain Association (low risk) Uncertain Association (low risk) IUCD IUCD Vaginal douching Vaginal douching Maternal age (extremes) Maternal age (extremes) Use of reproductive techniques Use of reproductive techniques In vitro fertilization In vitro fertilization Gamete intrafallopian transfer Gamete intrafallopian transfer Embryo transfer Embryo transfer

13. Classic TRIAD of EP 1. Delayed menses 2. Irregular vaginal bleeding 3. Abdominal pain Most commonly NOT encountered

14. Symptoms of Ectopic Pregnancy SYMPTOM PTS WITH SYMPTOM Abdominal pain 90-100% Amenorrhea75-95% Vaginal bleeding 50-80% Dizzininess, fainting 20-35% Pregnancy symptoms 10-25% Urge to defecate 5-15% Passage of tissue 5-10%

15. Signs of EP SIGN PTS WITH SIGN Adnexal tenderness 75-90% Abdominal tenderness 80-95% Adnexal mass* 50% Uterine enlargement 20-30% Orthostatic changes 10-15% Fever5-10% * 20% of masses occur on the side opposite the EP.

16. Differential Diagnosis Complication of IUP Complication of IUP Abortion Abortion Early pregnancy plus uterine fibroid or ovarian tumour Early pregnancy plus uterine fibroid or ovarian tumour Conditions causing acute abd pain Conditions causing acute abd pain Torsion of ovarian tumour, FT, or subserous pedunculated fibroid Torsion of ovarian tumour, FT, or subserous pedunculated fibroid Salpino-oophoritis Salpino-oophoritis Pelvic pain with an IUCD in situ Pelvic pain with an IUCD in situ Appendicitis Appendicitis

17. Differential Dx – cont’d Conditions causing hemoperitoneum Conditions causing hemoperitoneum Ruptured corpus luteum Ruptured corpus luteum Ruptured follicular cyst Ruptured follicular cyst Ruptured endometriotic cyst Ruptured endometriotic cyst Conditions simulating a pelvic hematocele Conditions simulating a pelvic hematocele Retroverted gravid uterus Retroverted gravid uterus Pelvic or tubo-ovarian abcess Pelvic or tubo-ovarian abcess

18. Management of EP Pre-operative diagnostic accuracy of EP based on clinical features alone is notoriously poor: ~50% Pre-operative diagnostic accuracy of EP based on clinical features alone is notoriously poor: ~50% 20% of EP occur as surgical emergencies 20% of EP occur as surgical emergencies Delay is justified only to correct shock Delay is justified only to correct shock

19. Acute Management of EP Remember your ABCs Remember your ABCs Oxygen Oxygen Large bore IV(s)  crystalloids Large bore IV(s)  crystalloids Blood Blood Labs Labs CBC, coagulation studies, T & C CBC, coagulation studies, T & C  -hCG  -hCG

20. Usefulness of Quantitaive  -hCG Assessment of pregnancy viability Assessment of pregnancy viability Serial rise usually indicates a normal pregnancy Serial rise usually indicates a normal pregnancy Correlation with ultrasonography Correlation with ultrasonography With titers > 1500 IU/L, TVUS should ID an IUP With titers > 1500 IU/L, TVUS should ID an IUP With multiple gestation, a gestational sac will not be apparent until titer rises a little higher With multiple gestation, a gestational sac will not be apparent until titer rises a little higher Assessment of treatment results Assessment of treatment results Declining levels are c/w effective medical or surgical Tx; if levels persist  think GTD Declining levels are c/w effective medical or surgical Tx; if levels persist  think GTD

21. The Importance of TVUS Documentation of an intrauterine sac Documentation of an intrauterine sac A viable IUP should be identified when  - hCG > 1500 IU/ml A viable IUP should be identified when  - hCG > 1500 IU/ml Adnexal mass Adnexal mass An EP > 2 cm should be identified An EP > 2 cm should be identified Adnexal cardiac activity Adnexal cardiac activity Detectable when  -hCG is ~ 15 000 – 20 000 Detectable when  -hCG is ~ 15 000 – 20 000

22. U/S – Is it EP or miscarriage?

23. Surgical Management of EP Radical Radical Salpingectomy with/out oophorectomy Salpingectomy with/out oophorectomy Conservative Conservative Salpingotomy Salpingotomy Salpingostomy or segmental resection  does not  repeat EP rate Salpingostomy or segmental resection  does not  repeat EP rate fimbrial evacuation (traumatizes the endosalphinx & is assoc with  rate of recurrent EP (24%) compared with salpingectomy fimbrial evacuation (traumatizes the endosalphinx & is assoc with  rate of recurrent EP (24%) compared with salpingectomy

24. Medical Management of EP Methotrexate (MTX) 1 st used in Japan in 1982 1 st used in Japan in 1982 Antimetabolite that interferes with dihydrofolate reductase Antimetabolite that interferes with dihydrofolate reductase Considered for low  -hCG Considered for low  -hCG Success rate 67%-94% Success rate 67%-94% Indications Indications Hemodynamically stable pt Hemodynamically stable pt good F/U good F/U Recurrent EP following Sx intervention Recurrent EP following Sx intervention

25. Methotrexate – cont’d Contraindications Contraindications Evidence of rupture Evidence of rupture Serum  -hCG > 5 000 IU/L (varies) Serum  -hCG > 5 000 IU/L (varies) FH detected on U/S FH detected on U/S Adnexal mass> 3.5 cm on U/S Adnexal mass> 3.5 cm on U/S Unreliable pt Unreliable pt F/U unavailable F/U unavailable Laparoscopy required to make dx Laparoscopy required to make dx Solid adnexal masses (germ cell tumour) Solid adnexal masses (germ cell tumour) Free fluid > 30ml Free fluid > 30ml

26. Methotrexate Protocol Exclude contraindications as well as Exclude contraindications as well as No evidence of renal, liver, or hematopoietic disease (Bilirubin, AST,ALT, urea, Cr, CBC) No evidence of renal, liver, or hematopoietic disease (Bilirubin, AST,ALT, urea, Cr, CBC) Informed consent Informed consent 5% risk of hematoperitoneum 2° to rupture of EP following MTX 5% risk of hematoperitoneum 2° to rupture of EP following MTX MTX 50mg/m² body surface area (~1mg/kg) given IV or IM MTX 50mg/m² body surface area (~1mg/kg) given IV or IM

27. Methotrexate Protocol – cont’d Pt F/U Pt F/U repeat serum quantitative  -hCG in 3-4 days, 7days, then weekly until < 10 IU/L repeat serum quantitative  -hCG in 3-4 days, 7days, then weekly until < 10 IU/L If > day-4 level at day-7  repeat MTX If > day-4 level at day-7  repeat MTX If  -hCG fails to fall by at least 25%/week at any time  repeat dose If  -hCG fails to fall by at least 25%/week at any time  repeat dose U/S not required routinely U/S not required routinely Pt should avoid Pt should avoid Alcohol use, sexual I/C, oral folic acid (until HCG levels are neg) Alcohol use, sexual I/C, oral folic acid (until HCG levels are neg)

28. Methotrexate Protocol – cont’d What to expect What to expect Majority experience some degree of abd pain (occurs in ~ 50% at day-6) Majority experience some degree of abd pain (occurs in ~ 50% at day-6) Shedding of a decidual cast Shedding of a decidual cast Moderate vaginal bleeding Moderate vaginal bleeding Side effects (usually at higher doses) Side effects (usually at higher doses) Impaired liver function, bone marrow suppression, neutropenia, stomatitis, hematosalpinx Impaired liver function, bone marrow suppression, neutropenia, stomatitis, hematosalpinx

29. Expectant Mx of EP Anticipates spontaneous regression of EP Anticipates spontaneous regression of EP Occurs in ~ 57% Occurs in ~ 57% Symptoms, HCG titers, & U/S findings followed Symptoms, HCG titers, & U/S findings followed Risk of tubal rupture is 10% if HCG levels < 1000 Risk of tubal rupture is 10% if HCG levels < 1000 Criteria include Criteria include Sonographic diameter < 3cm Sonographic diameter < 3cm Initial  -hCG < 1 000 IU/ml, no  in 2-day period, subsequent levels  Initial  -hCG < 1 000 IU/ml, no  in 2-day period, subsequent levels  asymptomatic asymptomatic

30. Future Fertility following EP Subsequent conception rate is ~ 60% Subsequent conception rate is ~ 60% Incidence of recurrent EP is 15% Incidence of recurrent EP is 15% Other factors influencing include: Other factors influencing include: Age, parity, history of infertility, evidence of contralateral tubal disease, ruptured EP, IUCD use, salpingitis Age, parity, history of infertility, evidence of contralateral tubal disease, ruptured EP, IUCD use, salpingitis No difference b/t laparoscopy vs laparotomy No difference b/t laparoscopy vs laparotomy

31. Prevention of EP Treat salpingitis early & correctly Treat salpingitis early & correctly MTX management lowers rate of subsequent EP MTX management lowers rate of subsequent EP Risk of EP is  with all methods of contraception, except progesterone containing IUCDs Risk of EP is  with all methods of contraception, except progesterone containing IUCDs Remember Rh Sensitization Remember Rh Sensitization Rhogam for the Rh-neg woman Rhogam for the Rh-neg woman