*With the exception of programs from the ACCEL series, each of which qualifies for up to 4 Category 1 CME credits.
Volume 60, Issue 05
March 7, 2013
Management of Gestational Trophoblastic Disease Whitney Spannuth Graybill, MD, MS
Extratubal Ectopic Pregnancy Donald L. Fylstra, MD
Insertional Dyspareunia Paul B. Underwood, MD
Presented And Sponsored By The Medical University Of South Carolina, Department Of Obstetrics And Gynecology, College Of Medicine, And Cosponsored By Lowcountry Ahec
The following is an abstracted summary, not a verbatim transcript, of the lectures/discussions on this audio program.
Obstetrics/Gynecology Program Info Accreditation InfoCultural & Linguistic Competency Resources
Pearls from the 43rd Annual OB/GYN Spring Symposium
Presented and sponsored by the Medical University of South Carolina, Department of Obstetrics and Gynecology, College of Medicine, and cosponsored by Lowcountry AHEC
The goals of this program are to improve diagnosis and management of gestational trophoblastic disease, extratubal ectopic pregnancy, and insertional dyspareunia. After hearing and assimilating this program, the clinician will be better able to:
1. Identify patients with high-risk features of gestational trophoblastic disease.
2. Counsel and provide follow-up for a patient with gestational trophoblastic neoplasia.
3. Assess the location of nontubal ectopic pregnancy based on clues provided by the patient’s history and physical findings, and the results of imaging studies.
4. Prepare the patient and operating room staff for delivery of an extratubal ectopic pregnancy.
5. Use history and physical examination to diagnose the cause of insertional dyspareunia.
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Management of Gestational Trophoblastic Disease
Whitney Spannuth Graybill, MD, MS, Assistant Professor of Obstetrics and Gynecology, Medical University of South Carolina, College of Medicine, Charleston
Diagnosis of malignant gestational trophoblastic disease (GTD): requires persistent trophoblastic tissue; persistent disease most often follows molar pregnancy but can occur after any type of gestation; patients with molar pregnancy may develop persistent gestational trophoblastic neoplasia (GTN), invasive mole, or choriocarcinoma; ≈20% of patients develop GTN after evacuation of complete mole; disease limited to uterus in 15% of patients; 5% have metastatic disease at time of diagnosis
Risk factors for postmolar GTN: include theca lutein cyst >6 cm, age >40 yr, excessively enlarged uterus, and initial level of human chorionic gonadotropin (hCG) >100,000 mIU/mL;
Choriocarcinoma: incidence ≈1 in 40,000 pregnancies; 50% of cases follow molar pregnancy, 25% follow spontaneous abortion, and 25% follow term pregnancy
Clinical manifestations: abnormal bleeding; no fetal heart tones; cystic ovarian enlargement; excessively high βhCG; snowstorm pattern on ultrasonography (US); expulsion of hydropic vesicles
Features of mole: partial mole triploid; complete mole diploid; partial mole originates from 2 sperm and one egg, and complete mole from one sperm and no egg; fetus, amnion, focal villous edema, and trophoblastic proliferation present in partial mole; findings in complete mole diffuse; partial mole usually diagnosed as missed abortion; in complete mole, diagnosis often known before evacuation; uterus larger, theca lutein cysts common, and postmolar malignant sequelae present in 15%; signs — most common vaginal bleeding (with complete or partial mole); preeclampsia, hyperemesis, hyperthyroidism, and trophoblastic emboli more common with complete mole
Management: stabilize patient; obtain history and perform physical examination (PE), βhCG level, and radiograph of chest; evacuate by suction curettage; hysterectomy appropriate in patient finished with childbearing; prophylactic methotrexate (MTX) may decrease postmolar GTN, but not recommended; before evacuation, obtain blood count, coagulation parameters, renal and liver function tests, blood type and antibody screen, and thyrotropin level; give Rho(D) immune globulin (HyperRHO, RhoGAM, Rhophylac) if patient Rh negative
Surgical considerations: use 12-mm suction catheter with vacuum pressure 50 to 60 cm Hg; US guidance decreases risk for perforation and ensures evacuation; give oxytocin after cervix dilated; treat emergently; ≈25% of patients with uterine size >14 cm develop anemia, infection, hyperthyroidism, coagulopathy, “waterfall sign” (in which blood gushes out upon cervical dilation); large uterine size also increases risk for embolization, congestive heart failure, thyroid storm, and preeclampsia
Postoperative care: check βhCG weekly until 3 consecutive values normal, then monthly for 6 mo; if level normalizes, risk for postmolar GTN ≈0%; prevent pregnancy for 6 to 12 mo; perform regular PE; risk for future molar pregnancy 1%
Definitions of persistence or recurrence: 1) >10% increase in hCG level based on 3 values over 2-wk period, or 2) plateau of ±10% over 3-wk period, or 3) persistence of hCG >6 mo after evacuation, or 4) choriocarcinoma; clinical diagnosis of malignant GTN suggested by bleeding for >6 wk after pregnancy, neurologic symptoms, or metastases
Evaluation for metastasis: computed tomography (CT) of chest, abdomen, and pelvis (and head if symptoms or other metastases present); history and PE; determine prognostic score; most common metastatic site lung, followed by vagina, brain, liver, kidney, spleen, and bowel
Staging: International Federation of Gynecology and Obstetrics — stage I disease confined to uterus; stage II extends to genital structures, stage III to lung, and stage IV to other sites; World Health Organization — prognostic score predicts risk for resistance to single-agent chemotherapy; low risk with score 0 to 6 (eg, patient <40 yr of age with antecedent molar pregnancy, pretreatment βhCG <1000 mIU/mL, and metastases limited to lung or vagina; treat with single agent); for score ≥7, use multiagent therapy; National Institutes of Health — high risk if time to treatment >4 mo, pretreatment βhCG level >40,000 mIU/mL, brain or liver metastases present, antecedent term pregnancy, or patient failed on previous chemotherapy; lung or vaginal metastases low risk; all other metastases high risk
Chemotherapy: treat low-risk GTN with MTX or actinomycin D; continue 2 cycles beyond normalization; first agent fails in ≈20% (follow with other agent); institute multiagent therapy in ≈10% who do not respond or develop metastases
Surgical treatment: hysterectomy — chemotherapy still required; use to treat persistent or resistant disease or hemorrhage; repeat evacuation — perform only for residual tissue and persistent bleeding; rate of complete response significantly higher after biweekly intravenous actinomycin D than with weekly intramuscular MTX (70% vs 53%)
Treatment of high-risk GTN: chemotherapy — use etoposide, MTX, actinomycin D, cyclophosphamide (Cytoxan), and vincristine (Oncovin) (EMA/CO); use EMA with cisplatin (EMA/EP) if EMA/CO fails; multimodal — resect metastatic lesions in lung or liver, or use irradiation or intrathecal MTX for brain metastases; hysterectomy — of no benefit; recurrence rate after treatment of high-risk GTN >10% at ≈6 mo
Outcomes: survival ≈100% for nonmetastatic and metastatic low-risk disease and ≥90% for high-risk; recurrence risk 2% to 4% for nonmetastatic and good-prognosis metastatic disease, and slightly higher in other scenarios
Choriocarcinoma: pathologic diagnosis often made by biopsying metastatic disease; systemic metastasis common; treat with multiagent therapy; occurs as primary tumor or after mole
Placental site trophoblastic tumor: intermediate trophoblasts seen on pathologic specimens; follow patient with human placental lactogen, not hCG; risk for metastasis 20%; hysterectomy and pelvic lymphadenectomy required because tumor resistant to chemotherapy; may use adjuvant EMA/EP or EMA/CO; survival rate ≈100% for nonmetastatic and lower for metastatic disease
Phantom hGC: caused by heterophilic antibodies against animal-derived antigens; consider when hCG level 100 to 500 mIU/mL after therapy for GTN; confirm abnormal serum hCG, then test urine (contains no phantom hCG); ensure test can detect low hCG and ask laboratory to use different platform; serial dilution studies produce nonlinear result; laboratory may preabsorb serum to remove antibody
Quiescent disease: caused by inactive noninvasive trophoblasts; usually follows complete mole; typically, hCG level <200 mIU/mL and little or no hyperglycosylated hCG present; hCG levels vary <2-fold over period of ≥3 mo; no tumor seen on imaging; treatment not needed, as most resolve within 6 mo, but follow due to 10% to 20% risk for progression to active disease (higher in choriocarcinoma); in older patients, use oral contraceptive (OC) throughout follow-up testing because developing ovarian failure may cause high luteinizing hormone levels to cross-react with assay
Pituitary hCG: rule out in peri- or postmenopausal woman with persistent low hCG level; normal levels of pituitary hCG ≤32 mIU/mL; recheck after using high-estrogen OC for 3 wk
Extratubal Ectopic Pregnancy
Donald L. Fylstra, MD, Professor of Obstetrics and Gynecology, Medical University of South Carolina, College of Medicine
Overview: 97% of ectopic pregnancies (EP) in fallopian tube; most in ampulla; extratubal EP not necessarily associated with tubal pathology; do not administer MTX unless certain pregnancy ectopic
Isthmic EP: ≤12% of all EP; invasion of muscularis produces symptoms; may use MTX before rupture; segmental resection often required
Interstitial or cornual EP: 2% to 3% of EP; risk factor bilateral salpingectomies associated with in vitro fertilization; invades uterine wall and becomes surrounded by myometrium; often undetected until second trimester, which creates high risk for maternal mortality; perform early US to diagnose before rupture; look for centrally located pregnancy outside endometrial cavity; myometrial mantle surrounding pregnancy <5-mm thick; echogenic line visible between pregnancy and endometrial cavity; 3-dimensional imaging helpful; difficult to treat laparoscopically; can use MTX; suction curettage with cannulation of tube has been reported; uterine artery embolization (UAE) may be used to control bleeding; subsequent pregnancies require cesarean delivery
Cervical EP: rare; risk factors previous curettage, Asherman syndrome, submucosal leiomyomata, and exposure to diethylstilbestrol; maintain high index of suspicion; do early transvaginal US (TVUS; look for enlarged cervix, dilated canal, amorphous endometrial echoes, and pregnancy below internal os); may present as polypoid structure at os; 3-dimensional imaging may identify location; treat with MTX, UAE, and curettage; if pregnancy ≤12 wk, infiltrate cervix with vasopressin, place high cerclage suture, use suction cannula in canal without dilating cervix, and place 30-mL Foley balloon to tamponade cervical canal for 24 hr
Ovarian EP: diagnosis seldom made preoperatively; ≤3% of EP; Spiegelberg anatomic and pathologic criteria include normal tube on affected side, gestational sac in location of ovary with ligamentous attachment to uterus, and ovarian tissue in EP; may see corpus luteum or mass in ovary, with “ring of fire” on Doppler; at surgery, may see hemorrhagic mass in adnexum (pathologic diagnosis confirms ovarian EP)
Abdominal EP: 1% of EP; usually due to tubal abortion and secondary implantation; Studdiford criteria for primary implantation normal tubes and ovaries, absence of fistula, and early diagnosis that precludes tubal abortion and secondary implantation as mechanism; most common location posterior cul-de-sac; mortality highest of all EP, since diagnosis often difficult to make early; look for small uterus, malpresentation, oligohydramnios, elevated serum α-fetoprotein, and small parts at abdominal wall; timing of placental separation unpredictable, so treat emergently; rate of fetal loss 95%; maternal mortality 18%; when diagnosed in periviable period, involve neonatologist and discuss timing of delivery with patient; leave placenta in situ to prevent severe bleeding; postoperative course frequently complicated; postoperative MTX or embolization of feeding vessels may be required
Cesarean scar EP: frequency (or detection) increasing; enters scar via microscopic tract; look for abnormal presentation; more frequent in pregnancy within 1 yr of cesarean delivery; presents with pain and bleeding; early rupture and hemorrhage may cause loss of uterus or maternal death; diagnose with TVUS (look for empty endometrial cavity, gestational sac in anterior isthmus, and absence of myometrium between pregnancy and bladder); cannot be treated with curettage; hysteroscopic resection has been reported; absorption within scar poor, so if MTX used, inject directly; UAE useful for bleeding but not used as sole treatment for any EP; laparotomy allows uterine repair; laparoscopy possible; treat emergently
Posthysterectomy EP: rarest type; early presentation — sperm in tube when uterus removed; tubal EP occurs after ovulation; often mistaken for normal postoperative symptoms; late presentation — 72% occur after vaginal hysterectomy due to vaginal-peritoneal fistula; prevention — distinguish granulation tissue at vaginal cuff from prolapsed tube; close cuff properly; at laparoscopic hysterectomy, tack peritoneum over cervix
Paul B. Underwood, MD, Professor of Obstetrics and Gynecology, and Associate Dean for Admissions, Medical University of South Carolina, College of Medicine
Prevalence: ≈8% of women seeing gynecologist and one-third of those presenting with sexual problem
Vulvodynia: burns but does not itch; vulva appears normal; patient may have history of yeast infections; use 75 to 100 mg amitriptyline (eg, Elavil, Tryptizol, Tryptomer), beginning with 25 mg at dinnertime; increase by 12.5 mg every 10 to 14 days; taper after ≥1 yr, but 50% require long-term therapy; other treatments — gabapentin (Gralise, Neurontin); sertraline (Lustral, Zoloft); carbamazepine (Carbatrol, Equetro, Tegretol)
Vestibular adenitis: woman with no previous complaints develops pain over ≈3 wk; unable to have intercourse, use tampon, or wear tight clothes due to severe pain; 1- to 2-mm vestibular glands analogous to prostate; use colposcope to view tiny red ulcerations; ulcers, but not surrounding tissue, painful to touch and usually around hymenal ring; excise surgically
Lichen sclerosus (LS): mostly in postmenopausal women; presents with loss of labia minora and phimosis of clitoris; vulva pale, thin, and tears with stretching; introital stenosis can develop; thin mucosa, keratin, and inflammation seen on biopsy (not needed for diagnosis, but biopsy if ulcers present); only ≈5% of LS progresses to malignancy; treatment — 0.5% clobetasol (Cormax, Temovate); show patient where to apply cream (between labia, around clitoris and urethra, and on perineal body); use twice daily until controlled, then daily; effective in 3 wk; continue use but decrease frequency, if possible; for introital stenosis, perform midline episiotomy and close transversely
Lichen planus: rare; presents with heavy discharge, raw vulva and vagina, superficial ulcers, scarring, vaginal stenosis, and oral ulcers; easily recognizable; use 1% hydrocortisone foam for hemorrhoids (Cortifoam, Proctofoam) in vagina daily; use dilator for vaginal stenosis; tacrolimus (Protopic) also effective; lifelong treatment needed
Rigid hymen: patients report pain since first intercourse; treat surgically; inject with bupivacaine (Marcaine, Sensorcaine) with epinephrine and cut at 2, 4, and 5 o’clock; suture open to prevent recurrence; use same technique for VA
Transverse vaginal band: pain with partial insertion; palpable band forms where embryonic vestibular bulbs meet mullerian ducts; cut band and sew open, or remove band if tight
Urethral diverticulum: pain with partial insertion; palpating tender lump on anterior vaginal wall may expel pus from urethra; distinguish from urethrocele by inserting urethral catheter (catheter can traverse urethrocele, but not diverticulum); open anterior vaginal wall and dissect around cyst; communication with urethra not always in midline, so dissect halfway, then open cyst to see urethral communication and complete dissection; catheterize for 10 days and give antibiotics
Anterior and posterior repairs: avoid making vagina too small; bivalve vagina at 3 and 9 o’clock and place skin graft; if bands present, cut vertically and reapproximate transversely
Vaginismus: possibly not true entity; most women have pathology
Posterior fourchette: for older woman with tears after intercourse, excise affected area of vestibule, then undermine vagina and pull it downward
Drs. Graybill, Fylstra, and Underwood were recorded at the 43rd Annual OB/GYN Spring Symposium, sponsored by Medical University of South Carolina, Department of Obstetrics and Gynecology, College of Medicine, co-sponsored by Lowcountry AHEC, and held April 16-18, 2012, in Charleston, SC. For information on upcoming CME programs presented by Medical University of South Carolina, call 843-876-1925 or visit their website at academicdepartments.musc.edu/cme. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this issue.
ACOG Committee on Gynecologic Practice: ACOG Committee Opinion: Number 345, October 2006: Vulvodynia. Obstet Gynecol. 2006;108(4):1049-52; Alazzam M et al: First-line chemotherapy in low-risk gestational trophoblastic neoplasia. Cochrane Database Syst Rev. 2012;7:CD007102; Alazzam M et al: Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia. Cochrane Database Syst Rev. 2012;12:CD008891; Antosh DD and Gutman RE: Diagnosis and management of female urethral diverticulum. Female Pelvic Med Reconstr Surg. 2011;17(6):264-71; Berkowitz RS and Goldstein DP: Current management of gestational trophoblastic diseases. Gynecol Oncol. 2009;112(3):654-62; Bradford J and Fischer G: Surgical division of labial adhesions in vulvar lichen sclerosus and lichen planus. J Low Genit Tract Dis. 2013;17(1):48-50; Fylstra DL: Ectopic pregnancy not within the (distal) fallopian tube: etiology, diagnosis, and treatment. Am J Obstet Gynecol. 2012;206(4):289-99; Fylstra DL: Ectopic pregnancy after hysterectomy: a review and insight into etiology and prevention. Fertil Steril. 2010;94(2):431-5; Groysman V: Vulvodynia: new concepts and review of the literature. Dermatol Clin. 2010 Oct;28(4):681-96; Cai Z et al: The value of laparoscopy alone or combined with hysteroscopy in the treatment of interstitial pregnancy: analysis of 22 cases. Arch Gynecol Obstet. 2012;285(3):727-32; Chi CC et al: Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus. J Am Acad Dermatol. 2012;67(2):305-12; Gayer G: Images in clinical medicine. Abdominal ectopic pregnancy. N Engl J Med. 2012;367(24):2334; Lurain JR et al: Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia. J Reprod Med. 2012;57(7-8):283-7; Osborne RJ et al: Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol. 2011;29(7):825-31; Simões M et al: Early abdominal pregnancy with an unexpected and misleading location. The ultrasonographic interpretation. Clin Exp Obstet Gynecol. 2012;39(1):115-7; Tommola P et al: Long-term well-being after surgical or conservative treatment of severe vulvar vestibulitis. Acta Obstet Gynecol Scand. 2012;91(9):1086-93; Verma U et al: Conservative management of nontubal ectopic pregnancies. Fertil Steril. 2011;96(6):1391-1395; van Trommel NE et al: The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey. Gynecol Oncol. 2005;99(1):6-13.
Reproduction of this summary in whole or in part in any form or medium without express written permission is prohibited.