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EARLY PREGNANCY: Biology and Medicine Editor-in-Chief: Eytan R. Barnea MD, FACOG

October 2000
Volume IV, Number 4
ISSN: 1537-6583
Pages: 261-270

First Trimester Diagnosis Of Acardiac Twins

Carolyn B. Coulam, M.D., Glenis Wright

The Center for Human Reproduction, 750 N. Orleans St., Chicago, IL 60610

Short Title: Acardiac Twins

Correspondence: Carolyn B. Coulam, M.D., Tel: (312) 573-1900, Fax: (312) 274-1869

Precis

Primary pathogenesis in acardia is cardiac dysmorphogenesis secondary to reversal of blood flow rather than primary cardiac agenesis.

Abstract

Objective
To describe ultrasonographic findings from 5 to 17 weeks of gestation in monozygotic twin pregnancy resulting in acardia of one twin.

Methods
Transvaginal ultrasonographic examinations were performed using a 7.5 MHz probe at weekly intervals from week 5-11. Uterine artery PI were measured using color Doppler flow.   Embryonic heart rates were determined with M-mode.

Results
A monochorionic gestational sac containing 2 embryos demonstrated embryonic cardiac activity between 5 and 7 weeks. One twin lost cardiac activity at 7 weeks. A diagnosis of acardiac twins was made at 1 weeks when growth of the lower extremities and no development above the thorax as well as reversal of blood flow through the umbilical cord of the acardiac twin was noted by 14 weeks.

Conclusion
Ultrasonographic demonstration of independent embryonic heart rates from 5-6 weeks and reversal of blood flow through the umbilical cord of the acardiac twin suggest that the primary pathogenesis in acardia is cardiac dysmorphogenesis secondary to reversal of blood flow rather than primary cardiac agenesis. Acardiac twins can spontaneously ligate connection with their viable twin. Acardiac twinning is a rare complication of multifetal gestation occurring in 1% of monozygotic twin pregnancies or 1 in 35000 births (1). Acardius, as the name implies, is anomaly in which the heart is absent. Acardius can only occur in multiple gestations since its circulation must be maintained by vascular anastomosis with an accompanying fetus (2). Although little doubt exists that intrauterine growth of the acardiac twin is achieved by the perfusion afforded from the normal co-twin via vessel anastomosis in the placenta, the pathogenesis of acardia has been disputed. Some authors (3-5) have presented evidence supporting the concept that the primary defect is one of cardiac embryogenesis (dysmorphogenesis) and that the vascular anastomosis between the vessels, although necessary for the intrauterine survival of the acardiac twin, is not responsible for the cardiac findings. Others (6-8) believe that the primary cause is an abnormal vascular communication between embryos leading to reversed flow of blood to the hemodynamically disadvantaged or recipient twin, with the resulting secondary atrophy of the heart and dependent organs. Inadequate perfusion of the recipient twin is responsible for the  development of characteristic set of anomalies including acardia and acephalus. The hemodynamically advantaged or pump twin is structurally normal, but is at risk for in utero cardiac failure and without treatment dies on 50% to 75% of cases (9).

Ultrasonography has assumed increasing importance in prenatal diagnosis of congenital anomalies (10). Using this technique, intrauterine diagnosis of acardiac twins has been made as early as 18 weeks of gestation allowing umbilical cord ligation of the acardiac twin at 19 weeks of gestation and uncomplicated birth of abnormal twin at 36 weeks of gestation (11). We now report intrauterine diagnosis of acardiac twins during the first trimester of pregnancy. Unique aspects of the case suggest the pathogenesis of acardia involves arterioarterial anastomosis of placental vessels with retrogade blood flow into the recipient twin and not primary arrest in cardiac development. Further, spontaneous ligation of the vascular connection is documented followed by an uncomplicated delivery of a normal infant at term.

Case Report
LK was first seen at the Genetics & IVF Institute, Fairfax, Virginia in February, 1999. At that time she presented as a 30 year old nulligravida with a history of regular menses occurring every 28-30 days. She had been trying to achieve desired conception for 15 months without success. Previous evaluation had indicated her husband to be azoospermic with a diagnosis of congenital absence of the vas deferens. Genetic studies revealed that the husband carried the DF508 mutation of the cystic fibrosis gene. The wife was negative for R117H, R347H, D1507, DF508, B542X, G551D, R533X, R560T, R1162X, W1282X, N1303K, 621+1, 711+1, and 1717- 1 mutations of the cystic fibrosis gene. The options of adoption, insemination with donor sperm or in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) were discussed. They wished to proceed with IVF and ICSI with epidymal sperm aspiration.

Ovarian stimulation was accomplished with luteal phase gonadotropin agonist (GnRHa; Lupron, Tap Pharmaceuticals, North Chicago, IL), follicle stimulating hormone (FSH; Metrodin, Serono Laboratories, Inc., Randolph, MA), and human chorionic gonadotropin (hCG). Transvaginal ultrasound guided oocyte retrieval was performed 36 hours after hCG administration and 10 oocytes were retrieved. Five metaphase II oocytes were available for ICSI.

An epididymal sperm aspiration was performed on the husband on the same day as the oocyte retrieval and eight million sperm were obtained. ICSI was performed on five oocytes and the remaining epidymal sperm were frozen in six straws. Two pronuclei were observed in two oocytes 18 hours after injection. Two embryos were replaced in the uterine cavity 48 hours after ICSI. Pregnancy did not result.

A second cycle was done producing 24 oocytes of which ICSI was performed on 14 oocytes using frozen-thawed epididymal sperm. Four embryos resulted and were replaced into the uterine cavity 48 hours after ICSI. The patient did not become pregnant.

A third IVF cycle producing 22 oocytes of which ICSI was performed on 12 oocytes using frozen-thawed epididymal sperm yielded two embryos for transfer. Serum hCG concentration 11 days after ET was 78 mIU/ml and 14 days after ET was 170 mIU/ml. Five weeks after ET transvaginal ultrasonogram revealed a twin gestation. Sac A was 4.0 mm in diameter (consistent with 4 weeks size) and empty with no embryonic structures including yolk sac visualized. Sac B was 12.0 mm in diameter and contained two yolk sacs with two embryonic poles measuring 2.5 mm and 2.1 mm (consistent with 5 weeks gestation) (Table1). Embryonic cardiac activity was seen in both embryonic poles. One week later, at 6 weeks of gestation, sac A was not visualized and sac B had two embryonic poles measuring 2.8 mm and 4.4 mm each with embryonic cardiac activity of 90 and 107 beats/minute, respectively. One week later (at 7 weeks gestation), embryo B1 measured 8.6 mm with cardiac rate of 135 beats/minute and B2 measured 7.2 mm with absent cardiac activity. At 8 weeks gestation, B1 had grown to 17.2 mm and had heart rate of 181 beats/minute. B2 measured 9.2 mm and had no cardiac activity. At 9 weeks of gestation, B1 was 23.9 mm with heart rate of 172 beats/minute and B2 remained 9.5 mm with no cardiac activity. At 11 weeks of gestation, B1 measured 49.1 mm (crown-rump) with fetal cardiac activity of 167 beats/minute. B2 measured 12.8 mm from thorax to foot with no cardiac activity present (Figure 1). The umbilical cords of both twins were visualized with color Doppler and spectral analysis revealing pulsatility index (PI) of 2.67 and resistance index (RI) of 0.94 in B1, and PI of 1.37 and RI of 0.80 in B2. Reversed flow was seen through the umbilical cord of B2 (Figure 2). At 13 weeks, B1 continued normal growth with heart rate of 164 beats/minute. B2 grew to 31.0 mm from thorax to foot. No structures cranial to thorax were visible. Doppler flow through the umbilical cord of B1 had a PI of 1.7 and RI of 0.88. Umbilical blood flow through B2 was visible but not measurable. At 14 weeks, B1 continue to grow at normal rate. Umbilical cord PI was 2.31 and RI 0.92. B2 was resorbing measuring 17.9 mm with no umbilical blood flow. By 20 weeks of gestation, B2 was not seen. B1 continue to grow at normal rate. At 40 weeks of gestation, a 7 lb 8 oz normal healthy male was delivered.

Discussion

Acardiac anomalies are characterized by the absence of the heart and have been known since 1533, when the condition was first described by Benedetti (12). Theories of origin of acardius have changed throughout the centuries. Prior to the eighteenth century, the anatomic and physiologic relationships of acardiac twins were obscured by superstition and were thought to be due to the disturbed imaginings of expectant mothers (13). During the eighteenth century, the defective germ plasma theory proposing that acardia was determined at the time of conception was introduced (14). During the following century, this concept was refuted by the observations that acardius occurred in monochorial twins of monozygotic origin and that the anastomoses between the vessels of these twins were found to be primarily arterio-arterial so that the circulation in the acardiac twin was reversed making the second twin a parasite of the first (15). The primary etiology was thought to be due to an accidental relationship of the placental vessels. During the twentieth century reports of studies of the embryopathology and embryogenesis of acardiac twins suggested that the primary deficiency is a failure of the heart to develop and that the acardiac twin survives in utero only where there is an anastomosis formed between the vessels of the two umbilical cords (3,4).

Severn (16) showed that the thyroid and liver develop in juxtaposition to the central and caudal areas of fusion of the paired cardiac primordia and appeared developmentally dependent or interdependent on this fusion. He then reported two cases of acardia in which

the absence of the heart was associated with absence of the liver, lungs, thyroid and ventral pancreas (4). Both fetuses were more nearly normal caudally than cephalically. Based upon these findings, the authors conclude3d that the primary defect in acardia was failure of paired structures including cardiac primordia to fuse with consequent failure of development of structures whose origin is associated with the development of the heart. They predicted that the initial defect occurred between the fourth and fifth weeks of gestation, the time during which the paired cardiac primordia normally fuse (12).

The current case provides evidence that refutes the theory that the primary defect in acardia is failure of the heart to develop. Embryonic cardiac activity was documented on two occasions in both twins between 5 and 6 weeks of gestation. Thus the lack of fusion of cardiac primordia between 4 and 5 weeks of gestation cannot be the primary defect. Demonstration of reversed flow of blood through the umbilical vessels of he acardiac twin compared to the normal twin supports the concept that the primary defect is due to abnormal anastomosis of placental vessels is that circulation in the acardiac twin is reversed. Reversal of blood flow into the heart results in failure of subsequent development of the heart and structures cephalad. Pulsed Doppler examination has been previously reported to show reversed flow through the umbilical artery of the acardiac twin later in pregnancy (18).

Twins are born once in approximately 87 births in the United States (19). About 25% of twin pregnancies are monochorionic (19). The proportion of monochorionic placentas with vascular anastomosis has been reported between 20% and 34% (20,21). The most frequent risk associated with monochorionic twinning with vascular anastomosis has been twin-twin transfusion (22). In twin-twin transfusion, one twin pumps blood thorough placental anastomosis to the second twin but receives very little blood in return. The donor twin remains small and anemic while the recipient twin is large and polycythemic. Some authors (23) consider acardius to be a more severe form of feto-fetal transfusion syndrome. However, in twin-twin transfusion syndrome, the vascular malformations are arteriovenous anastomoses (24) in contrast to acardia where the vascular malformations are arterioarterial (6-8). Arterio-arterial anastomoses appear to be a constant feature of monchorionic twin placentation (25). It is this vascular relationship which both causes and supports the acardiac twin. Thus the type of vascular anastomoses determines the type of complications observed in monochorial twinning.

The largest single series of pregnancies complicated by acardiac twinning was reported by Moore in 1999 (9). None of the cases of acardia were diagnosed prior to 22 weeks of gestation. The principal perinatal problems associated with acardiac twinning were congestive heart failure to the pump-twin and preterm delivery. Without treatment, the perinatal mortality of the pump twin is 50% to 75% (9). The therapeutic goal of interrupting the vascular communication between twins has been accomplished by umbilical cord ligation of an acardiac twin through fetoscopy as early as 1 weeks of gestation (11). The current case documents spontaneous ligation of the umbilical cord of an acardiac twin at 14 weeks of gestation before signs of cardiac failure in the pump-twin and hydramnios in the mother. With advances in increased resolution of diagnostic imaging and earlier diagnosis of fetal anomalies, optimal timing of interventional treatment of acardiac twins needs to be defined.

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References

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2.  Simonds JP, Gowen GA. Fetus amorphus: report of a case. Surg Gynec Obstet 1925; 41: 171-184.

3.  Potter EL. Pathology of the Fetus and Infant. 2^nd ed, Chicgo: Yearbook Medical Publishers, 1961, p. 216.

4.  Severn CB, Holyoke EA. Human acardiac anomalies. Am J Obstet Gynecol 1973; 116: 358-365.

5.  Gewold IH, Freedman RM, Kleinmen CS, Hobbins IC. Prenatal diagnosis of a human pseudoacardiac anomaly. Obstet      Gynecol 1983; 61: 657-662.

6.  Schatz F. Die Gefaessverbindungen der Placentakreistaute einiger Zwillinge, ihre Entwicklung und ihre Folgen. Arch   Gynakol 1897; 53: 144-153.

7.  Napolitani FD, Schreiber I. The acardiac monster. Am J Obstet Gynecol 1960; 80: 582-589.

8.  Benirschke K, Harper VDR. The acardiac anomaly. Teratology 1997; 15: 311-316.

9.  Moore TR, Gale S, Bernirschke K. Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning. Am J Obstet Gynecol 1990; 163: 907-912.

10. Hobbins JC, Grannum PAT, Berkowitz RL, et al. Ultrasound in the diagnosis of congenital anomalies. Am J Obstet Gynecol 1979; 134: 331-336.

11. Quintero RA, Heich H, Puder KS, et al. Brief report: Umbilical cord ligation of an acrdiac twin by fetoscopy at 19 weeks of gestation. N Eng J Med 1994; 330: 469-471.

12. Benedetti A. De Morborum a Capite ad Pedis Signis, Habes Lector Studioso hox Volumine 1553.

13. Wilson EA. Holoacardius. Obstet Gynecol 1972; 40: 740-748.

14. Price B. Primary biasis in twin studies. Am J hum Genet 1950; 293-352.

15. Claudius M. Die Entwicklung der herzlosen Missgeburten, Kill 1859, Schwers.

16. Severn CB. Morphological study of the development of the human liver (developmental of the hepatic diverticulum). Am J Anat 1971; 131: 133-158.

17. Moore KL. The Developing Human: Clinically Oriented Embryology. Second Edition. Philadelphia, Saunders, 1977.

18. Pretorius DH< Leopold GR, Moore TR, Benirschke K, Sivo JJ. Acardiac twin: report of Doppler sonography. J Ultrasound Med 1988; 7: 413-417.

19. Guttmacher AF. Clinical aspects of twin pregnancy. Med Clin North America 1939; 23: 427-439.

20. Maier RF, Bialobrzeski B, Gross A, Vogel M, Dudenhausen W, Obladen M. Acute and chronic fetal hypoxia in monochorionic and dichorionic twins. Obstet Gynecol 1995; 86: 973-977.

21. Pridjian G, Nugent CE, Barr M, Jr. Twin gestation: influence of placentation of fetal growth. Am J Obstet Gynecol 1991; 165: 1394-1401.

22. Shah DM, Chaffin D. Perinatal outcome in very early preterm births with twin-twin transfusion syndrome. Am J Obstet Gynecol 19889; 161: 1111-1113.

23. Eastman NJ, Hellman LM. Williams Obstetrics. New York Meredith Publishing Co. 1971.

24. Naeye RL. Human intrauterine parabiotitc syndrome and its complications. N Eng J Med 1963; 268: 804-809.

25. Bleisch VR. Placental circulation of human twins. Am J Obstet Gynecol 1965; 91: 862-869.

Table 1

Embryonic and fetal lengths and heart rates as well as primary index of umbilical cords in acardiac twins from 5 to 14 weeks of gestation.

Figure 1

Ultrasonogram performed at 11 weeks of gestation of an acardiac twin. Note normal development of lower extremities which in real time were moving and lack of development cephalad to thorax.

Figure 2

Spectral analysis of flow through umbilical vessels of acardiac twins. Note reversed (inverted flow) through the umbilical cord of the acardiac twin (lower panel) compared with the pump twin (upper panel).