1. EARLY PREGNANCY PAIN AND BLEEDING
Part 2: Ectopic Pregnancy

2. Ectopic Pregnancy Definition Pregnancy occurring outside the uterus
Sites
Fallopian tube 93% (ampullary 70%, isthmic 12%, fimbrial 11.1%)
Interstitial 2.4%
Ovarian 3.2%
Abdominal 1.3%
Cervical 1%

3. Ectopic Pregnancy Incidence 1.6% all pregnancies (NSW 1998)
Increasing incidence until about 1992 then plateauing/?falling ( %, %)
?decreased rates associated with contraceptive failures versus no decrease with reproductive failure
Similar rates Western countries

4. Ectopic Pregnancy Age 15-24 years: 0.7% 25-34 years: 1.3%
Mortality
small but 15% all maternal deaths

5. Aetiology
Tubal damage
Change in tubal motility

6. Ectopic Risk factors Pelvic infection Especially chlamydial
45% of patients have evidence of prior salpingitis on pathological specimens
Laparoscopically-proven PID confers a risk of 13% after one episode and 35% after two
Treatment of chlamydia decreases rates

7. Ectopic Risk factors Previous tubal pregnancy
10-25% recurrence after one tubal ectopic

8. Ectopic Risk factors Current IUD
Excellent contraceptive efficacy but prevents implantation in uterus more effectively than in the tube
Copper IUD: 4% of contraceptive failures are ectopics
Progesterone IUD: 17% of contraceptive failures are ectopics
No increased risk once removed

9. Ectopic Risk factors Progesterone hormonal contraceptives
(Likely association)
Mechanism: changes to muscular activity of tube
progesterone IUD
mini-pill (4-10% of contraceptive failures are ectopics)
morning after pill
Implants (30% of contraceptive failures are ectopics)

10. Ectopic Risk factors Infertility
Without treatment – if a woman conceives after >1 year unprotected intercourse she has 2.6 x increased risk
With treatment Surgery such as reversal of sterilisation and tuboplasty Ovulation induction (likely small increase) IVF % all conceptions, 17% increased risk if tubal factor for infertility identified (Why- ?Fluid reflux into tube, ?embryo placed high in uterus)

11. Ectopic Risk factors Other abdominal surgery Ruptured appendix
Other? – not clear

12. Ectopic Risk factors Smoking
> 2 x risk (increased with increased dose)
Nicotine affects tubal motility, ciliary function and blastocyst implantation

13. Ectopic Risk factors Tubal abnormalities
Eg. Salpingitis isthmica nodosa (diverticulae) – abnormal myometrial electrical activity

14. Ectopic Risk factors
In utero diethylstilboestrol (DES) exposure
4-13%

15. Natural history
Tubal abortionspontaneous resolution Expulsion from the fimbrial end of the tube
Involution spontaneous resolution
Rupture (usually about 8 weeks)
Chronic inflammatory mass (uncommon) hCG may be low or absent From bleeding into tubal wall Persistent symptoms, usually requires salpingectomy

16. History Classic triad (50%) Amenorrhoea Vaginal bleeding Pain
Abnormal menstrual pattern
Pain of any sort – unilateral/bilateral, dull/sharp, upper/lower abdomen

17. Examination Vital signs
Abdomen Non-tender to mildly tender Signs of rupture: distension, decreased bowel sounds, peritonism
Cervical motion tenderness
Adnexal mass (50%) – but may be the corpus luteum

18. Investigation hCG positive in virtually all ectopics presenting
Positive in unstable patient
Not rising appropriately
Not falling appropriately
Not seeing an intra-uterine pregnancy at hCG over the discriminatory zone ( on transvaginal scanning)

19. Investigation Ultrasound Transvaginal and transabdominal important
Presence of intrauterine sac virtually excludes ectopic pregnancy
Heterotropic pregnancy 1/30,000 (Increased with IVF/ovulation induction)
Beware pseudogestational sac of ectopic pregnancy (sac-like fluid lucency, probably from bleeding) – ideal to see cardiac activity – yolk sac – double decidual sac sign (concentric echogenic rings)
Doppler ultrasound improves diagnosis

20. Investigation Possible Ultrasound Findings
Absence of intrauterine pregnancy over the hCG discriminatory zone
Adnexal gestation with fetal pole and cardiac activity – 10-17%
Adnexal rings (fluid sacs with thick echogenic rings) – 38%
Complex or solid adnexal rings (DDx corpus luteum, other cysts, pedunculated fibroid)
Intra-abdominal free fluid or cul-de-sac fluid (the latter doesn’t necessarily represent rupture)

21. Investigation Chorionic villi in saline test
Useful to distinguish products of intrauterine gestation (chorionic villi) from decidual cast of ectopic pregnancy
Chorionic villi have a lacy frond appearance and float in saline
Tissue should also be sent for histopathology to confirm
Suction curettage may be used to diagnose (hCG <2000, indeterminant ultrasound & <50% rise in hCG over 48 hours)
hCG should fall by >15% within 24 hours of evacuation of normal intrauterine pregnancy

22. Investigation Culdocentesis Aspiration of fluid from cul-de-sac
Positive test if non-clotting blood obtained
70-90% of patients with ectopic pregnancy have a haemoperitoneum
Rarely used now hCG and transvaginal ultrasound available

23. Investigation Laparoscopy Gold standard for diagnosis
Missed in 3-4% (if very small)

24. Management Surgical Laparoscopy vs Laparotomy
Salpingostomy vs Salpingectomy
(Salpingo-oophorectomy)
Medical
Methotrexate
Other (RU-486, KCl, hyperosmolar glucose, prostaglandins). Salpingocentesis
Remember Anti-D in Rh-ve women

25. Management Laparoscopy Shorter hospital stay Less post-operative pain
Less cost
Shorter convalescence
Less blood loss
Less adhesions (but similar tubal patency rates)
Similar: pregnancy rate, persistent trophoblast rate, operating time

26. Management Laparotomy for Haemodynamic instability
Lack of laparoscopic expertise/equipment
Cornual/interstitial pregnancy
Ovarian/abdominal pregnancy
Patient factors eg. Obesity, adhesions

27. Management Salpingectomy vs Salpingostomy Controversial
No difference in future intrauterine pregnancy rates? Some studies suggest difference Not enough evidence yet
Increase in persistent trophoblast rates (failure to remove all tissue) with salpingostomy
No difference in recurrence of ectopic in future
Milking tube Fimbrial – may be effective Ampullary – double recurrence risk

28. Management Salpingo-oophorectomy
No evidence of decreased recurrence rates
Improved intrauterine pregnancy rates with conservation of ovary therefore no longer performed

29. Management Methotrexate
Chemotherapeutic agent which prevents synthesis of DNA (inhibits dehydrofolate reductase)
Much lower doses used for ectopic than malignancy
Use as primary treatment or if plateauing/ inadequately falling hCG after surgical treatment

30. Management Methotrexate Patient Selection Mild/no pain
Haemodynamically stable
Ectopic pregnancy <3cm?
No fetal heart seen
hCG < 2000 ?10000
Compliant/understanding patient

31. Management Methotrexate Baseline LFTs/FBE/UEC/hCG
Dose 50mg/m2 (calculated from height and weight) given IM
Repeat hCG day 4
Repeat LFTs/FBE/UEC/hCG day 7
hCG should fall at least 15% from day 4 to 7 (normal to rise from days 1-4)
Give second dose if inadequate fall
Single dose successful in 91-93% of appropriately chosen patients

32. Management Methotrexate Side Effects <1%
Stomatitis, gastritis, photosensitive rash
Impaired liver or renal function
Pancytopaenia
No evidence of increased malignancy in future
(Contraindications: liver disease, blood dyscrasias, ulcerative colitis, peptic ulcer disease, concomitant infection)
Warn patient re: moderate increase in pain and bleeding first week

33. Management Methotrexate Follow hCG until <2
Surgery if becomes unstable/failed treatment
Intrauterine pregnancy rates post-methotrexate comparable to surgical treatment

34. Follow-up
hCG should be followed weekly to <2 in all patients treated with methotrexate or tube-conserving surgery (salpingostomy). Some would follow patients after salpingectomy also
Patient told no pregnancy 2 months (use barrier method or OC pill). No IUD
Ultrasound at 6 weeks in subsequent pregnancy to ensure intrauterine

35. Future Fertility Overall pregnancy rates after one ectopic:
Intrauterine 50-80%
Ectopic 10-25%
Others infertile

36. Interesting fact
Pregnancy after hysterectomy is possible (tube, cervix)
ALWAYS DO A hCG
ALWAYS THINK OF POSSIBILITY OF ECTOPIC PREGNANCY