Ch.10 ECTOPIC PREGNANCY

부산백병원 산부인과R2 서영진

Implantation anywhere (normally, endometrial lining of the uterine

cavity)2% in U.S.A

>95% : involve oviductRisk of death ↑, subsequent successful pregnancy↓

but, with earlier diagnosis, maternal survival ↓, reproductive capacity ↓

GENERAL CONSIDERATIONS

Risk factors - prev. tubal surgery - prev. ectopic pregnancy - PID, endometriosis - prev. c/sec - assisted reproduction: GIFT, IVF - failed contraception

EPIDEMIOLOGY - increase fourfold in the U.S.A from 1970 to 1992 - nonwhite, older age - increasing causes 1. Increase STD 2. Earlier diagnosis (before resorb spontaneously) 3. Contraception (failed) 4. Tubal sterilization techniques 5. Assisted reproductive techniques 6. Tubal surgery

Mortality - markly decreased - improved diagnosis & management - but, most common cause of the maternal death in first trimester of the U.S.A

PATHOGENESIS OF ECTOPIC PREGNANCIES

Tubal pregnancy - ampullary > isthmic > interstitial - secondary, tubo-ovarian, tubo-abdiminal, broad-ligament pregnancies develop - fertilized ovum burrows through the epithelium (because, tube lacks a submocosal layer) zygote comes to lie within the muscular wall rapidly proliferating trophoblast invades the subjacent muscuralis maternal blood vessels are opened

Tubal abortion - common in ampulla but rupture is usual in isthmus - if placetal separated completely, all tissues extruded into the pelvic cavity disappear hemorrhage and symptoms - some bleeding: remain the oviduct & PCDS or forming a hematosalpinx

Tubal rupture - the invading, expanding products of conception may rupture the oviduct at any sites - occur in the first few weeks in first trimester (but, interstitial pregnancy usually occur later) - usually, spontaneously rupture (sometimes coitus or bimanual examination) - rarely, undamaged conceptus into the peritoneal cavity lithopedion

# abdominal pregnancy - if the greater portion of the placenta retains its tubal attachment, further development is possible# broad-ligament pregnancy - into a space formed between the folds of the broad ligament# interstitial pregnancy (cornual pregnancy) - 3% of all tubal pregnancy - rupture may not occur until up to 16 weeks - severe hemorrhage (because the inplantation site is located between the ovarian & uterine arteries)

Multifetal ectopic pregnancy # heterotypic ectopic pregnancy - tubal pregnancy + uterine pregnancy - 1/30,000 1/7,000 (assisted reproduction) 1/900 (ovulation induction) - after assisted reproductive technique persistent gonadotropin level after D&C or abortion fundus is larger than menstrual dates more than one corpus luteum ectopic pregnancy without vaginal bleeding USG evidence of intra- and extrauterine pregnancy

# Multifetal tubal pregnancy - same tube or in each tube

CLINICAL FEATURES OF ECTOPIC PREGNANCY

- depend on whether rupture has occurred - usually, not suspect pregnancy thinks that she has a normal pregnancy - in contemporary prectice, symptoms and signs of the ectopic pregnancy are often subtle or even absent

Symptoms and signs - pain : most frequently abdominal and pelvic pain (95%) G-I symptom (80%) dizziness or headache (58%) - abnormal menstruation : amenorrhea (most common) bleeding (true menstruation vs. abnormal) if profused, incomplete abortion > ectopic preg

- abdominal and pelvic tenderness - uterine change : be pushed to one side due to ectopic mass : enlarged uterus (hormonal stimulation) : endometrium is converted to decidua (the decidua without trophoblast suggests ectopic pregnancy but not absolutely) - blood pressure and pulse : early – no change or slightly BP↓ , pulse↓ late – hypovolemic shock (BP↓, pulse ↑)

- pelvic mass : 5-15cm, 20% (bimanual examination) posterior or lateral of uterus soft and elastic : iatrogenic rupture - culdocentesis : identify hemoperitoneum simply : cervix is pulled toward the symphysis pubis 16- or 18- gauze needle through the posterior fornix into the cul-de-sac

Laboratory tests - hemogram : Hb↓,Hct↓.WBC↑ (>30,000 ㎕ ) - chorionic gonadotropin assays : ELISA are sensitive to levels of chorionic gonadotropin of 10 to 20 mIU/mL - serum progesterone level : >25 ㎍ /mL – normal pregnancy (97.5% sensitivity) but, inconclusive

Ultrasound imaging - abdominal sonography : if tubal pregnancy, difficult…. : using abdominal ultrasound until 5 to 6 menstrual weeks or 28 day after timed ovulation - vaginal sonography : earlier and more specific : as early as a week after missed menses : when hCG > 1000 , G-sac is seen half the time : detect adnexal mass, fluid collection of PCDS

DIAGNOSIS OF ECTOPIC PREGNANCY

Multi-modality diagnosis 1. Vaginal sonography 2. Serum -hCG: intiallavel and subsequent level 3. Serum progesterone 4. Uterine curettage 5. Laparoscopy and, less frequently, laparotomy only hemodynamically stable women, with rupture should undergo prompt surgery

# discriminatory -hCG level - failure to visualize a uterine pregnancy by transvaginal ultrasound - empty uterus + >1500 mIU/mL 100% excluding a live uterine pregnancy - mean doubling time for -hCG : 48 hours - if the -hCG level rises inappropriately, plateaus, or exceeds the discriminatory level without evidence of a uterine pregnancy, a live uterine pregnancy can be excluded - biopsy < curettage (sensitivity)

# serum progesterone - its accuracy is crude - if < 5 ng/mL or > 25 ng/mL, neither absolutely refute nor confirm a living uterine pregnancy

Surgical diagnosis - laparoscopy :direct visualization of the fallopian tube, pelvis

- laparotomy :hemodynamically unstable

TREATMENT AND PROGNOSIS

- importantly, early diagnosis→early medical Tx (more cost-effective than surgical therapy)

Anti-D immunoglobulin - D-negative women who are not sensitized D- antigen should be given anti-D immunoglibulin

Surgical management - laparoscopy > laparotomy (if stable) - salpingostomy : < 2cm incision, distal third of tube small bleeding – electrocautery incision is left unsutured - salpingotomy : incision is closed with Vicryl 7-0 - salpingectomy : tubal resection (wedge of the outer third of the interstitial portion)

- segmental resection and anastomosis : an unruptured isthmic pregnancy : prevent scarring and narrowing of the small isthmic lumen - persistent trophoblast : increase the risk 1. small preg < 2 cm 2. early preg < 42 menstrual days 3. β-hCG > 3000 mIU/mL 4. implantation medial to the salpingostomy site

: incomplete remove of trophoblast 5~10% of salpigostomies : post op #1 → β-hCG value is less than 50% of preop. value

Medical management # systemic methotrexate - folic acid antagonist effective against rapidly proliferating trophoblast - contraindication : active bleeding, >4cm, breast feeding, alcoholic, immunodeficiency, lever or renal ds, peptic ulcer - success rate ↑ : < GA 6 weeks, <3.5cm, -hCG<15,000 mIU/mL fetus is dead

<patient selection> - must be hemodymamically stable - fails 5~10% ( higher : > 6weeks, >4cm) require treatment : other medical or surgical if outpatient, rapid transportation signs of rupture must be reported promptly until resolved, sexual intercourse(X), alcohol(X) folic acid, vitamins (X)

table 10-3

<monitoring toxicity> - liver involve, stomatitis, gastroenteritis BM depression, pneumonitis, alopecia - resolved by 3~4 days after methotrexate was stop <monitoring efficacy of therapy>

<persistent ectopic pregnancy> - requires additional methotrexate or surgery - separation pain : mild and relieved by nonnarcotic analgesics but, worrisome pain : Hb, β-hCG follow up, USG

Other treatment - direct injection : various cytotoxic drugs laparoscopy or transvaginally by culdocentesis - oral methotrexate therapy : two devided doses 2 hours apart for total dose of 60 mg/ ㎡ : lower success rate

- expectant management : spontaneous resolution : 1. Decreasing serial -hCG levels 2. Tubal pregnancies only 3. No evidence of bleeding or rupture 4. Ectopic mass < 3.5cm : more likely if initial -hCG < 1000mlU/mL

ABDOMINAL PREGNANCY

- follow early rupture or abortion of a tubal pregnancy into the peritoneal cavity - placenta : after penetrating the oviduct and maintains its tubal attachment, gradually encroaches upon and implants in neigh- boring serosa fetus : continues to growth within peritoneal cavity

Diagnosis - difficult , because early rupture or abortion of a tibal pregnancy is the usual antecedent - nausea, vomiting, flatulence, constipation, diarrhea, abdominal pain - palpable fetal position : close to the examining fingers (thin, multiparous) - cervix : usually displaced - fetal head : vaginal fornix

# laboratory tests : unexplained transient anemia after initial tubal rupture or abortion : unexplained increase AFP value # sonography : oligohydramnios is common but nonspecific : fetal head lie adjacent to maternal bladder with no interposed uterine tissue # MRI, CT

Fetal outcome - surviving fetuses may be abnormal - fetal deformation : cranial asymmetry various joint abnormalities fetal malformation: limb deficiency CNS anomalies

Management - risk for sudden and life-threatening bleeding : in-hospital management generally, termination - suppuration, mummification, calcification adipocere : yellowish, greasy mass - surgery : bleeding due to the lack of constriction of vessels after placental separation (adequate blood supply, monitoring) laparotomy : vertical midline incision

# management of the placenta - avoid unnecessary exploration of other organ must be safety removed - if possible, blood vessel supplying the placenta should be ligated first - if leaving placenta : long-term sequelae (infection) resorption (>5years) - methotrexate use is controversal

# arterial catheterization and embolization - preoperatively - lifesaving in massive pelvic hemorrhage

# maternal prognosis - higher than normal pregnancy - reduced by preoperative planning

OVARIAN PREGNANCY

- rare - IUD user - similar to tubal pregnancy - rupture at early period

Diagnosis - serious bleeding : 1/3 - vaginal ultrasound

Treatment - surgical : wedge resection, cystectomy, ovariectomy - methotrexate in unruptured state

CERVICAL PREGNANCY

- rare form (1 in 18,000 pregnancies) - increasing : assisted reproduction (in vitro fertilization, embryo transfer) - typically, trophoblast erodes endocervix - 90% : painless bleeding 1/3 : massive bleeding 1/4 : abdominal pain - identification : clinical suspicion + sonography

Surgical management - in past : hysterectomy (but, urinary tract injury↑, because the enlarged barrel-shaped cervix) - Cerclage : similar to a McDonald cerclage Shirodkar cerclage - Curettage and Tamponade : hemostatic cervical suture at 3 and 9 o’ clock suction curettage, then foley catheter(30cc) vaginal packing tightly

- Arterial embolization : preoperative arterial embolization : laparoscopic uterine artery ligation + hysteroscopic endocervical resection

Medical management - to avoid the risk of uncontrolled hemorrhage - chemotherapy is the first choice in stable women (methotrexate and other drug) - other method (not systemically) : directly into the gestational sac intra-amnionically

OTHER SITES OF ECTOPIC PREGNANCY

- Splenic pregnancy - hepatic pregnancy - retroperitoneal pregnancy - diaphragmatic pregnancy - cesarean scar pregnancy