Successful outcome after serial amnioreductions in triplet fetofetal transfusion syndrome

tion of pregnancy. Physicians should be aware that regardless of the regimen used, failure to achieve termination is a distinct possibility. Additionally, the drugs administered to induce abortion have significant teratogenic potential. Patients should be informed of these possibilities during their initial visit and before administration of abortifacients. The importance of timely follow-up care with physical examination, ultrasonography, or quantitative ␤-human chorionic gonadotropin level determination cannot be overemphasized.8 Such care is essential to avoid cases like the one described in this report. In the event of failure of medical pregnancy termination, the medication(s) can be readministered or if the gestational age is more advanced, a surgical procedure can be performed. Faced with a situation in which the patient changes her mind regarding termination, the physician has an obligation to again discuss the potential teratogenic effects of the agents that were administered. Ultrasonography may aid in this discussion, especially in the second trimester when fetal anatomy can be more clearly delineated. However, as demonstrated by the spectrum of abnormalities associated with methotrexate and other agents, not all effects will be readily shown on ultrasound. A normal ultrasound in this setting does not guarantee that the fetus is free of teratogenic effects from these agents. Physicians and patients using methotrexate for medical termination of pregnancy should be aware of both its limitations and inherent teratogenicity.

REFERENCES 1. Shaw EB, Steinbach HL. Aminopterin-induced fetal malformation: Survival of infant after attempted abortion. Am J Dis Child 1968;115:477–82. 2. Milunsky A, Graef JW, Gaynor MF. Methotrexate-induced congenital malformations. J Pediatr 1968;72:790–5. 3. Bawle EV, Conrad JV, Weiss L. Adult and two children with fetal methotrexate syndrome. Teratology 1998;57: 51–5. 4. Del Campo M, Kosaki K, Bennett FC, Jones KL. Developmental delay in fetal aminopterin/methotrexate syndrome. Teratology 1999;60:10–2. 5. Gonzalez CH, Vargas FR, Perez AB, Kim C, Brunoni D, Marques-Dias MJ, et al. Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Gen 1993;47:59–64. 6. Vargas FR, Schuler-Faccini L, Brunoni D, Kim C, Meloni VF, Sugayama SM, et al. Prenatal exposure to misoprostol and vascular disruption defects: A case control study. Am J Med Genet 2000;95:302–6. 7. Castilla EE, Orioli IM. Teratogenicity of misoprostol: Data from the Latin-American Collaborative Study of Congenital Malformations. Am J Med Genet 1994;51:161–2. 8. Paul M, Schaff E, Nichols M. The roles of clinical assessment, human chorionic gonadotropin assays, and ultrasonography in medical abortion practice. Am J Obstet Gynecol 2000;183:S34–S43.

Successful Outcome After Serial Amnioreductions in Triplet Fetofetal Transfusion Syndrome

CASE: We report one case of triplet fetofetal transfusion syndrome with survival of all three fetuses. Two were donor fetuses, and one was the recipient fetus. Serial amnioreductions were performed at 22, 24, and 26 weeks’ gestation to relieve symptomatic polyhydramnios. Premature rupture of membranes occurred at 27 weeks and cesarean delivery was performed. All three babies were discharged home by 4 months of age, and all had normal neurological development when assessed at 6 months of age.

Wing Cheong Leung, MRCOG, K. Y. Wong, MRCP, K. Y. Leung, MRCOG, C. P. Lee, FRCOG, M. H. Y. Tang, FRCOG, and T. T. Lao, FRCOG Departments of Obstetrics and Gynaecology and Paediatrics, Queen Mary Hospital, University of Hong Kong, Hong Kong, China

BACKGROUND: Triplet fetofetal transfusion is an extremely rare complication with high perinatal mortality. Its rarity does not allow any prospective randomized study on various interventional methods to be conducted. Address reprint requests to: Wing Cheong Leung, Queen Mary Hospital, Department of Obstetrics and Gynaecology, 102, Pokfulam Road, Hong Kong; E-mail: [email protected].

Received April 25, 2002. Received in revised form September 26, 2002. Accepted September 26, 2002.

CONCLUSION: The option of serial amnioreduction, with the anticipation and preparation for delivery at around 28 weeks, should be seriously considered when triplet fetofetal transfusion syndrome is encountered. (Obstet Gynecol 2003;101:1107–10. © 2003 by The American College of Obstetricians and Gynecologists.)

Triplet fetofetal transfusion is an extremely rare complication with high perinatal mortality in monochorionic and dichorionic triplet pregnancy. A MEDLINE search of the literature from January 1966 to May 2002, using

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Table 1. Summary of the Neonatal Course of the Triplets Triplet A Triplet B Triplet C (donor) (donor) (recipient) Weight (g) At birth On discharge Apgar scores (1 and 5 min) Hemoglobin level at birth Neurological development at 6 mo of age Duration of hospitalization

680 2520 6&7

620 2210 6&8

930 2230 5&7

16.3 g/dL 12.2 g/dL 16.6 g/dL Normal Normal Normal 118 d

103 d

79 d

the terms “fetofetal transfusion” and “triplets,” yielded six reports with a total of only eight cases.1– 6 Here we report the ninth and the only case in the literature with intact survival in all the three affected triplets. CASE The patient, a 33-year-old woman in her first pregnancy, was found to have a naturally occurring, monochorionic, triamniotic triplet pregnancy by ultrasound assessment in the first trimester. On subsequent ultrasound assessment, fetofetal transfusion syndrome with two donor fetuses and one recipient fetus was diagnosed at 20 weeks on the basis of the discordant fetal growth and the oligo-polyhydramnios sequence. The recipient had increased cardiothoracic ratio, but there were no hydropic changes. No gross structural abnormality was found in

any of the three fetuses; however, one of the donors had absent end-diastolic flow (since 20 weeks), whereas the other two fetuses had normal umbilical artery Doppler study. Symptomatic polyhydramnios necessitated serial amnioreductions at 22, 24, and 26 weeks, with the removal of 1600, 2300, and 2600 mL amniotic fluid, respectively. Tocolytic prophylaxis is not routinely used with amnioreduction in our unit. Cytogenetic analysis of the cultured amniocytes showed normal 46,XX karyotype. Despite satisfactory interval growth in all three fetuses, the discordance persisted, and the increased cardiothoracic ratio of the recipient and the absent enddiastolic flow in one of the donors did not improve. One course of betamethasone was given prophylactically at 24 weeks in anticipation of the high chance of preterm delivery. Premature rupture of membranes occurred at 27 weeks, and lower segment cesarean delivery was performed on the same day to minimize the risk of chorioamnionitis, which would further jeopardize the already compromised fetal status. All three neonatal courses were complicated by respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, clinical sepsis, neonatal jaundice, and retinopathy of prematurity. Serial brain ultrasonograms showed minor intraventricular hemorrhage (Papille staging grade I and II). The characteristics of the three triplets are summarized in Table 1. The monochorionic, triamniotic placenta weighed 860 g. Two of the three umbilical cords were velamentously inserted to the placenta. Injection study demon-

Table 2. Clinical Characteristics of the Nine Cases of Triplet Fetofetal Transfusion Reported in the Literature Gestation at diagnosis (wk)

Case no.

Chorionicity

No. of donors

No. of recipients

1. Fisk et al 19902 2. Pons et al 19901 3. Rehan et al 19953

N/A N/A 21

MC DC MC

1 1 1

1 1 1

4. Entazami et al 19974

17

MC

2

1

5. Ling et al 20005

17

DC

1

1

6. Chasen et al 20006 7. Chasen et al 20006 8. Chasen et al 20006

N/A N/A N/A

DC DC DC

1 1 1

1 1 1

9. Present Case

20

MC

2

1

N/A ⫽ information not available; MC ⫽ monochorionic; DC ⫽ dichorionic.

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Leung et al

Triplet Fetofetal Transfusion Syndrome

OBSTETRICS & GYNECOLOGY

strated vascular communications between the donor compartments and the recipient compartment. COMMENT There was a very high perinatal mortality rate in the eight previously reported cases of triplets with fetofetal transfusion syndrome.1– 6 Of the 17 fetuses involved in the fetofetal transfusion, only two survived. Furthermore, one of the two surviving fetuses had periventricular leukomalacia and neurological impairment.4 The clinical characteristics of these eight cases, together with that of our case, are in Table 2. The presence of hydrops of the recipient and absence of umbilical artery enddiastolic flow in one of the twins have been found to be poor prognostic signs in twin–twin transfusion syndrome.7 The former sign seemed to have the same predictive value in triplet fetofetal transfusion, whereas the latter sign was often not available and could not be evaluated. The outcomes of these nine cases suggest that, irrespective of whether an expectant approach or active intervention was adopted, it was unlikely for triplet pregnancies complicated by fetofetal transfusion to go beyond 28 weeks’ gestation. It is thus necessary to make the necessary preparations for the delivery in a tertiary center with adequate neonatal intensive care support. Before our case, antenatal therapeutic intervention in the form of serial amnioreductions was performed in three of the eight cases, and none of the six affected fetuses survived. Our case is the only one in the literature with successful outcome in all three triplets affected by fetofe-

Hydrops present

Umbilical artery end-diagnostic flow

Yes (recipient) N/A Yes (recipient)

Absent (donor and recipient) N/A N/A

Yes (recipient)

N/A

No

N/A

N/A N/A N/A

N/A N/A N/A

No

Absent (one donor)

VOL. 101, NO. 5, PART 2, MAY 2003

tal transfusion. We also found out that all of the five survivals (Table 2) occurred in monochorionic rather than dichorionic triplet pregnancies. This phenomenon may not be genuine, as the number of cases is too small; however, one possible hypothesis is that, with three fetuses involved in the fetofetal transfusion process rather than two, the hemodynamic disturbance to each involved fetus would be shared with the other two, and this might constitute a survival benefit. As proposed by van Gemert and colleagues8 amnioreduction in twin–twin transfusion syndrome decreases the amniotic fluid pressure of polyhydramnios, which in turn increases the transplacental fluid flow from mother to the fetuses. This flow increases the donor and recipient’s blood volumes, mean arterial pressures, urine production, and thus their amniotic fluid volumes; however, if the net fetofetal transfusion from donor to recipient increases to a greater degree than the fetal growth of the donor, its blood volume, mean arterial pressure, and urine production decrease. The oligo-polyhydramnios sequence recurs, requiring the next amnioreduction. The same mechanism probably applies in the case of triplet fetofetal transfusion; however, amnioreduction is at best a temporary treatment and does not correct the underlying problem. The more definitive treatment is fetoscopic laser occlusion of the placental vascular anastomoses, which is suggested to be superior to amnioreduction in the management of severe, early-onset twin– twin transfusion syndrome8; however, it has never been described in triplet fetofetal transfusion. The presence of

In utero treatment

Gestation at delivery (wk)

Perinatal outcome of fetuses involved in fetofetal transfusion

Nil Nil Indomethacin plus five amnioreductions (23–26 wk) Digoxin

26 N/A 27

Stillbirth ⫻ 2 Stillbirth ⫻ 2 Early neonatal death ⫻ 2

27

Three amnioreductions (17–20 wk) Nil Nil Serial amnioreductions

28

Stillbirth ⫻ 1 (one donor); the other donor survived with normal development; the recipient survived but with neurological impairment Early neonatal death ⫻ 2

Three amnioreductions (22–26 wk)

27

20 22 32

Leung et al

Termination of pregnancy Termination of pregnancy Donor died in utero at 22 wk; selective feticide of recipient at 23 wk All three survived with normal neurological development at 6 mo of age

Triplet Fetofetal Transfusion Syndrome

1109

more than one donor or recipient would complicate the fetoscopic operation, because the placental vascular anastomoses between each set of donor and recipient have to be occluded. As a result, the procedure-related risks, including membrane rupture and miscarriage, would increase. Thus the role of laser therapy, and its merits when compared with amnioreduction, in the management of fetofetal transfusion syndrome in higherorder multiple pregnancies is yet to be established. The rarity of triplet fetofetal transfusion syndrome does not allow any prospective, randomized study on various interventional methods to be conducted. Nevertheless, the option of serial amnioreduction, with the anticipation and preparation for delivery at around 28 weeks, should be seriously considered when such a case is encountered.

3.

4.

5.

6.

7.

neonatal criteria apply in utero? Arch Dis Child 1990;65: 657–61. Rehan VK, Menticoglou SM, Seshia MMK, Bowman JM. Fetofetal transfusion in triplets. Arch Dis Child 1995;73: F41–F43. Entezami M, Runkel S, Becker R, Weitzel HK, Arabin B. Feto-feto-fetal triplet transfusion syndrome (FFFTS). J Maternal Fetal Med 1997;6:334–7. Ling PY, Leo MV, Rodis JF, Campbell WA. Amnioreduction in triplet fetofetal transfusion. Obstet Gynecol 2000;96: 843. Chasen ST, Al-Kouatly HB, Ballabh P, Skupski DW, Chervenak FA. Outcome of dichorionic triplet pregnancies. Am J Obstet Gynecol 2002;186:765–7. Mari G, Detti L, Oz U, Abuhamad AZ. Long-term outcome in twin-twin transfusion syndrome treated with serial aggressive amnioreduction. Am J Obstet Gynecol 2000; 183:211–7. van Gemert MJ, Umur A, Tijssen JG, Ross MG. Twin-twin transfusion syndrome: Etiology, severity and rational management. Curr Opin Obstet Gynecol 2001;13:193–206.

REFERENCES 1. Pons JC, Olivennes F, Fernandez H, Ramdin I, Mayenga JM, Bessis R, et al. Transfusion syndrome in a triplet pregnancy. Acta Genet Med Gemellol 1990;39:389–93. 2. Fisk NM, Borrell A, Hubinont C, Tannirandorn Y, Nicolini U, Rodeck CH. Fetofetal transfusion syndrome: Do the

8.

Trial of Labor in Women With Transverse Vaginal Septa

selected cases. (Obstet Gynecol 2003;101:1110 –2. © 2003 by The American College of Obstetricians and Gynecologists.)

Elizabeth N. Blanton, MD, and Dwight J. Rouse, MD

A transverse vaginal septum is a rare congenital anomaly of the reproductive tract thought to arise from defective canalization of the vagina. Here, we describe the management and outcomes of two gravidas with transverse vaginal septa first diagnosed during pregnancy, and review the obstetric literature pertinent to this condition. The literature was searched via MEDLINE (1966 –2002) using key words “pregnancy” or “delivery” and “transverse” and “septum,” coupled with a search of the retrieved bibliographies.

Center for Research on Women’s Health, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama

BACKGROUND: Transverse vaginal septa are rare anomalies that may be first diagnosed during pregnancy. Management options including elective cesarean delivery, incision before labor, and a trial of labor have been proposed. CASES: Two patients with transverse vaginal septa were allowed a trial of labor. The septa were incised in active labor, resulting in vaginal delivery with no related complications. CONCLUSION: Allowing a trial of labor despite a transverse vaginal septum is a reasonable management option in Reprints are not available. Address correspondence to: Dwight J. Rouse, MD, University of Alabama at Birmingham, Department of Obstetrics and Gynecology, OHB 457, 619 19th Street South, Birmingham, AL 35249-7333; E-mail: [email protected]. DJR was financially supported by a Mid-Career Investigator Award from the National Institute of Child Health & Human Development (1-K24HD0137501). 1110

Received May 15, 2002. Received in revised form June 29, 2002. Accepted August 1, 2002.

CASE 1 A young nullipara presented with what appeared to be a blind vaginal pouch at 28 weeks’ gestation. She gave a history of having undergone minor vaginal surgery at the time of menarche. Ultrasound demonstrated an intrauterine gestation and normally appearing cervix behind a transverse vaginal septum (Figure 1). No clear septal opening could be visualized. Antepartum resection was considered but was not performed because of concerns of excessive vascularity. It was decided to allow a trial of labor. She presented with painful regular contractions at 384⁄7 weeks. A pinpoint opening was visible

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