EARLY PREGNANCY PAIN AND BLEEDING Part 2: Ectopic Pregnancy

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%

Ectopic Pregnancy Incidence 1.6% all pregnancies (NSW 1998) Increasing incidence until about 1992 then plateauing/?falling (1970 0.3%, 1992 1.7%) ?decreased rates associated with contraceptive failures versus no decrease with reproductive failure Similar rates Western countries

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

Aetiology Tubal damage Change in tubal motility

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

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

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

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)

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 - 2-8% all conceptions, 17% increased risk if tubal factor for infertility identified (Why- ?Fluid reflux into tube, ?embryo placed high in uterus)

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

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

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

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

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

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

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

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 (1000-2000 on transvaginal scanning)

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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