Management of Twin Pregnancies Consisting of a Complete Hydatidiform Mole and Normal Fetus 1 1 Supported in part by the Offield Family Foundation and the Women’s Board of Northwestern Memorial Hospital

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  Management of Twin Pregnancies Consisting of a Complete Hydatidiform Mole and Normal Fetus 1 1 Supported in part by the Offield Family Foundation and the Women’s Board of Northwestern Memorial Hospital
  Management of Twin Pregnancies Consisting of a Complete Hydatidiform Mole and NormalFetus DAVID A. FISHMAN, MD, LUIS A. PADILLA, MD, PACITA KEH, MD,LEEBER COHEN, MD, MARILYNN FREDERIKSEN, MD, AND JOHN R. LURAIN, MD Objective : To report the clinical features, management, andoutcome of twin pregnancies consisting of a complete hyda-tidiform mole and a coexisting normal fetus.  Methods : Between 1966 and 1997, seven women withcomplete hydatidiform mole and coexisting normal fetuswere treated at the John I. Brewer Trophoblastic DiseaseCenter of Northwestern University Medical School. Clinicalfeatures, including presenting symptoms, gestational dates,hCG levels, and complications, as well as route of deliveryor evacuation, pregnancy outcome, genetic analysis, andneed for chemotherapy were assessed. Results : Four women required uterine evacuation before20 weeks’ gestation because of vaginal bleeding or medicalcomplications, one woman required an emergency hysterot-omy because of hemorrhage at 24 weeks, and two womendelivered normal, viable infants at 26 and 34 weeks. Thepathologic diagnosis of complete hydatidiform mole wasconfirmed in each case and the chromosome complementwas 46,XX in all molar gestations. Four of seven womenrequired chemotherapy for treatment of nonmetastatic ges-tational trophoblastic tumors, including both women whodelivered viable infants and two of the five women whosepregnancies were evacuated before 24 weeks’ gestation. Allfour patients were treated with five to seven cycles of a 5-daymethotrexate regimen and achieved complete remission. Conclusion : Patients with a twin pregnancy consisting of acomplete mole and a normal fetus are at increased risk forhemorrhage and medical complications, as well as the de-velopment of persistent gestational trophoblastic tumor.(Obstet Gynecol 1998;91:546–50. © 1998 by The AmericanCollege of Obstetricians and Gynecologists.) The estimated incidence of twin pregnancy consistingof complete hydatidiform mole and coexisting fetus isone in 22,000–100,000 pregnancies. In 1978, the classifi-cation of hydatidiform mole was subdivided into com-plete mole (diploid without fetal parts) and partial mole(triploid with evidence of fetal parts). A twin pregnancyconsisting of a complete hydatidiform mole and acoexisting fetus is distinguished from a partial molarpregnancy because there are two separate concepti: anormal placenta attached to the fetus and a molargestation. We present seven cases of complete molecoexisting with a normal fetus in women treated at the John I. Brewer Trophoblastic Disease Center. The pur-pose of this report is to offer clinical insight into thetreatmentofpatientswhopresentwiththisrarecondition.  Materials and Methods We reviewed the clinical records, pathology reports,and original histologic material of patients with thediagnosis of twin pregnancy consisting of completemole and coexisting fetus treated at the John I. BrewerTrophoblastic Disease Center of Northwestern Univer-sity Medical School between 1966 and 1997. Sevenpatients were identified who had pathologic confirma-tion of the diagnosis of complete hydatidiform moleand coexistent normal fetus, with exclusion of partialhydatidiform mole. The following pretreatment clinicalfeatures were assessed: maternal age at diagnosis, gra-vidity, parity, history of previous hydatidiform mole,uterine size at evacuation, estimated gestational age atdiagnosis, estimated gestational age at evacuation, pre-senting symptoms, and pre-evacuation hCG level. Ul-trasound data were reviewed when available. Chemo-therapy, route of delivery, and pregnancy outcomewere recorded. No patient was lost to follow-up.After either delivery or uterine evacuation, patientswere followed by means of hCG measurements every1–2 weeks until the levels were normal for three con- From the John I. Brewer Trophoblastic Disease Center and theDepartments of Obstetrics and Gynecology and Pathology, Northwest-ern University Medical School, Chicago, Illinois.Supported in part by the Offield Family Foundation and the Women’sBoard of Northwestern Memorial Hospital. 546  0029-7844/98/$19.00  Obstetrics & Gynecology PII S0029-7844(97)00720-5  secutive determinations, then by monthly measure-ments for 6–12 months. The diagnosis of persistentgestational trophoblastic tumor was made when hCGlevels plateaued or increased for two or more consecu-tive determinations. After the diagnosis of gestationaltrophoblastic tumor was made, patients underwent ametastatic evaluation that included physical examina-tion, chest radiograph, and in most cases scans (usuallycomputed tomography) of the head, abdomen, andpelvis. Complete blood cell counts and serum chemistryanalyses were performed, and quantitative serum hCGlevels were measured by radioimmunoassay or en-zyme-linked immunoassay.All patients treated with chemotherapy received0.4 mg/kg (maximum 25 mg) of methotrexate intrave-nously each day for 5 days. This was repeated usuallyevery 14 days (9-day window). Response to therapywas followed by serial serum quantitative hCG levelsobtained before each course of therapy. Complete re-mission was diagnosed after three consecutive weeklyhCG levels were within the normal range. Patientsreceived two additional courses of chemotherapy afterthe first normal hCG level was observed. After remis-sion, hCG levels were determined monthly for 6months, every other month for the next 6 months, andevery 6 months thereafter. Patients were advised not toattempt pregnancy again for 1 year after completingchemotherapy. Combination hormonal contraceptionwas prescribed to avoid pregnancy and LH interferencewith hCG determinations. Results The mean age at diagnosis was 27 years. Four of theseven women were multiparous. No patient used as-sisted reproductive technologies. Five received treat-ment before 24 weeks’ (range 15–23) estimated gesta-tional age (for either hemorrhage, preeclampsia, orhyperthyroidism) and the other two patients ultimatelydelivered viable infants at 26 and 34 weeks’ estimatedgestational age. Serum hCG levels ranged from 8068 to2,400,000 mIU/mL at the time of initial diagnosis andwere not predictive of the need for future chemother-apy.Table 1 shows the therapeutic interventions andclinical outcomes for all patients. Among five requiringintervention before 24 weeks’ estimated gestational age,three underwent dilation and evacuation and two weretreated by hysterotomy. The pathologic diagnosis wasconfirmed in each case and the chromosome comple-ment was 46,XX in all molar gestations. There were nocongenital malformations noted in any of the nonviablefetuses, and each had a 46,XX karyotype.Two women delivered viable infants, one male andone female, without birth defects. Both of these womensubsequently developed persistent gestational tropho- blastic disease with negative metastatic evaluations.Each patient required seven courses of single-agentchemotherapy with methotrexate. Two of the fivewomen undergoing a uterine evacuation required che-motherapy (single-agent methotrexate for five courses).No patient developed disease recurrence or requiredmultiagent chemotherapy to achieve a complete remis-sion. Patient follow-up ranged from 1.5 to 16 years. Todate, three women have attempted and achieved preg-nancy, resulting in four normal infants delivered with-out obstetric or maternal complications. Pathologic re-view of the placentas did not reveal any abnormalities.Figure 1 demonstrates the ultrasound findings of acomplete mole and a coexisting normal pregnancy.Figure 2 is a gross photograph of the twin pregnancydepicted ultrasonographically in Figure 1, demonstrat-ing the normal placenta with fetus attached by theumbilical cord and a coexisting complete mole. Figure3A demonstrates the normal villi of the twin placentaand Figure 3B demonstrates the hydropic villi withcircumferential trophoblastic proliferation of the com-plete mole. Table 1.  Complete Hydatidiform Mole Coexisting With Normal Fetus Caseno.Gestational ageat pregnancytermination (wk)Pregnancyoutcome Chemotherapy Follow-up (y)Subsequentpregnancies1 18 D&E — 16 Vaginal delivery  22 15 Hysterotomy — 16 Cesarean delivery  13 34 Cesarean delivery* MTX 12 Vaginal delivery  24 15 D&E — 4 None5 26 Vaginal delivery* MTX 12 None6 18 D&E MTX 12 None7 23 Hysterotomy MTX 1.5 NoneD&E  dilation and evacuation; MTX  methotrexate.* Viable infants. VOL. 91, NO. 4, APRIL 1998  Fishman et al  Hydatidiform Mole and Normal Fetus  547  Discussion Multiple conception consisting of a complete hydatidi-form mole and a coexisting normal fetus is a rareevent. 1–5 Although the incidence of spontaneous twin-ning in the United States has remained constant (1%),the incidence of multiple gestations ranges from 5–30%with assisted reproductive technologies. 6 The optimalmanagement of complete hydatidiform mole with acoexistent fetus is uncertain, especially when the preg-nancy is desired. The literature to guide clinical deci-sion making is limited; there are few published reports,and most are of single cases, in which a distinction hadnot been established between a partial mole and a twinpregnancy consisting of a complete hydatidiform moleand coexistent normal fetus. 1–5,7–9 Advances in ultra-sonography and cytogenetics now permit earlier ante-natal detection and may allow a distinction betweencomplete and partial moles.The diagnosis of multiple gestation with molar preg-nancy and coexisting fetus can be established by afirst-trimester abdominal ultrasound. 3,4 However, anearly ultrasound is less able accurately to detect thisrareentitythanitistodetectacompleteorpartialmolargestation. 3–5 In 1994, Steller et al 3,4 reported that 68% of patients with hydatidiform mole and coexisting fetuswere diagnosed correctly by abdominal ultrasound. Inour patient population, only three of seven womenwere diagnosed correctly by abdominal ultrasonogra-phy. Misinterpretations were attributed to abnormalplacentation, hematoma formation, or placental tumors.Prenatal diagnosis enables the physician to distin-guish between chromosomally normal, potentially via- ble fetuses and triploid nonviable fetuses. Previousstudies 5 have suggested using fetal and pregnancycriteria as well as performing cytogenetic analysis tohelp determine which pregnancies could be continuedwith the expectation of a normal fetal outcome.The risk for a gestational trophoblastic tumor has been reported to be significantly higher for twin preg-nancies with a hydatidiform mole than for single molargestations (56 versus 20%). 1–5 Steller et al 3,4 reportedthat persistent disease developed in 12 (55%) of 22patients following pregnancies composed of completemole and coexisting fetuses, compared with only ten(14%) of 71 patients following a singleton molar gesta-tion. They noted that all patients with metastatic diseasehad lung metastases and that one patient also had avaginal metastatic lesion. Eight of 12 patients requiringchemotherapy needed multiagent therapy to achieveremission. Miller et al 5 reported that three of fourpatients with coexisting hydatidiform mole and normalfetus ultimately required chemotherapy; the exceptionwas the patient who delivered a viable infant.We 10,11 reported previously that 19% of patients witha molar gestation were found to develop postmolargestational trophoblastic disease requiring chemother-apy. In our experience with twin pregnancies involvinga complete hydatidiform mole and a coexisting fetus,four (57%) of seven patients required single-agentmethotrexate chemotherapy to achieve complete remis-sion. The two women who delivered normal viableinfants required seven courses to achieve completeremission, compared with five courses for the twowomen requiring uterine evacuation. Notably, womenwith postmolar trophoblastic tumors average fivecourses of single-agent chemotherapy to achieve com-plete remission, in the experience of the John I. BrewerTrophoblastic Disease Center. 12 Three women undergo-ing uterine evacuation before 24 weeks’ gestation didnot require subsequent chemotherapy for postmolartrophoblastic tumor, and all have remained withoutevidence of recurrent disease. Our experience agreeswith the existing literature 1–5 in that women withcomplete molar gestation and coexisting fetus develop Figure 1.  Twin pregnancy with coexisting complete hydatidiformmole as visualized by abdominal ultrasound. Figure 2.  Photograph of the gross specimen visualized previously inFigure 1 and depicting a normal placenta with fetus attached byumbilical cord and an abnormal placenta of a hydatidiform mole. 548 Fishman et al  Hydatidiform Mole and Normal Fetus Obstetrics & Gynecology  persistent trophoblastic tumor more frequently thanthose with molar gestations alone; however, all of ourpatients responded to the 5-day methotrexate regimen,and none required multiagent chemotherapy.Information regarding the antenatal management of multiple gestation consisting of coexisting fetus andcomplete molar pregnancy is limited. Only five surviv-ing fetuses have been reported from 22 pregnancies.Our study found two fetal survivors in seven pregnan-cies; therefore, to date a total of seven fetal survivorshave been documented from 29 pregnancies (24%). Of note, both women in our study delivered prematurelysecondary to preterm labor. These infants were bornwithout congenital abnormalities and presently arealive and well. To date, three of our patients haveattempted and achieved subsequent pregnancies, re-sulting in four normal infants. These pregnancies werefull-term and uncomplicated and occurred 16–90months after completion of therapy.Patients with complete hydatidiform mole and coex-isting normal fetus who desire continuation of preg-nancy must be cautioned about the potential for severemedical complications, such as hemorrhage, pre-eclampsia, and hyperthyroidism, that may necessitateprompt pregnancy termination. Although a variety of surgical methods are safe and effective in evacuating amultiple conception with a fetus and coexisting molargestation, dilation and evacuation is recommendedeven when the pregnancy is beyond 20 weeks’ gesta-tion. The intervention should be performed in theoperating room with anesthesia and an awareness of the potential for excessive blood loss, pulmonary insuf-ficiency due to fluid overload or trophoblastic emboli-zation, and symptoms associated with very high hCGlevels, such as hyperthyroidism and thyroid storm. If hygroscopic cervical dilators are used, care should beexercised because a significant uterine hemorrhagecould be induced. Rapidly performing the dilation andsuction evacuation helps decrease blood loss, but acces-sory use of uterotonic agents such as oxytocin near thecompletion of evacuation should be considered as well.In our series, those patients who had surgical evacua-tion of the uterine contents did not have significantrelated morbidity. One patient with preexisting Gravesdisease required medical intervention for stabilizationof her clinically worsening hyperthyroidism.Patients also should be advised about the significantrisk of developing persistent gestational trophoblastictumor requiring chemotherapy. It is not clear whetherthe higher likelihood of evolution into persistent dis-ease is due to more aggressive biologic behavior of theabnormal trophoblastic tissue in coexisting twin gesta-tions or merely to delayed diagnosis. Based on ourexperience and on published reports, approximately40–57% of these patients will require chemotherapy.Fortunately, to date all patients treated at the John I.Brewer Trophoblastic Disease Center have achievedand maintained a complete remission even after subse-quent pregnancies. References 1. Vejerslev LO. Clinical management and diagnostic possibilities inhydatidiform mole with coexistent fetus. Obstet Gynecol Surv1991;46:577–88.2. Jones WB, Lauersen NH. Hydatidiform mole with coexistent fetus.Am J Obstet Gynecol 1975;122:267–72.3. Steller MA, Genest DR, Bernstein MR, Lage JM, Goldstein DP,Berkowitz RS. Natural history of twin pregnancy with completehydatidiform mole and coexisting fetus. Obstet Gynecol 1994;83:35–42.4. Steller MA, Genest DR, Bernstein MR, Lage JM, Goldstein DP,Berkowitz RS. Clinical features of multiple conception with partialor complete molar pregnancy and coexisting fetuses. J Reprod Med1994;39:147–54.5. Miller D, Jackson R, Ehlen T, McMurtrie E. Complete hydatidiformmole coexistent with a twin live fetus: Clinical course of four caseswith complete cytogenetic analysis. Gynecol Oncol 1993;50:119–23.6. Assisted reproductive technology in the United States and Canada: Figure 3.  Photomicrographs comparing histologic appearance of a normal twin placenta with regular chorionic villi (A) with that of a completemole with gigantic hydropic villi with cisterna together with circumferential trophoblastic proliferation (B) (H&E,  40). VOL. 91, NO. 4, APRIL 1998  Fishman et al  Hydatidiform Mole and Normal Fetus  549  1994resultsgeneratedfromtheAmericanSocietyforReproductiveMedicine/Society for Assisted Reproductive Technology Registry.Fertil Steril 1996;66:697–705.7. Zbella EA, Vermesh M, Deppe G, Friberg J. Coexistent completehydatidiform mole and fetus after therapy with human meno-pausal gonadotropin. J Reprod Med 1984;29:760–2.8. Omichi MO, Tasaka K, Suehara N, Miyake A, Tanizawa O.Hydatidiform mole in a triplet pregnancy following gonadotropintherapy. Acta Obstet Gynecol Scand 1986;65:523–4.9. Jinno M, Ubukata Y, Hanyu I, Satou M, Yoshimura Y, NakamuraY. Hydatidiform mole with a surviving coexistent fetus followingin-vitro fertilization. Hum Reprod 1994;9:1770–2.10. Lurain JR, Brewer JI, Torok EE, Halpern B. The natural history of hydatidiform mole after primary evacuation. Am J Obstet Gynecol1983;145:591–5.11. Murad TM, Longley JV, Lurain JR, Brewer JI. Hydatidiform mole:Clinicopathologic associations with the development of postevacu-ation trophoblastic disease. Int J Gynecol Obstet 1990;32:359–67.12. Lurain JR, Elfstrand EP. Single-agent methotrexate chemotherapyfor the treatment of nonmetastatic gestational trophoblastic tu-mors. Am J Obstet Gynecol 1995;172:574–9. Address reprint requests to: David A. Fishman, MDPrentice Women’s Hospital333 East Superior Street, Suite 420Chicago, IL 60611E-mail: Received October 9, 1997.Received in revised form December 3, 1997. Accepted December 18, 1997. Copyright © 1998 by The American College of Obstetricians andGynecologists. Published by Elsevier Science Inc. 550 Fishman et al  Hydatidiform Mole and Normal Fetus Obstetrics & Gynecology
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