Address correspondence to Andreas Rempen MD, University Clinic of Obstetrics and Gynecology, Josef-Schneider-Str.4, D-8700 Wurzburg, Germany, Ph: 49-931-201-3621, Fax 49-931-201-3406

Synonyms: None.

Definition: Triplet pregnancy implanted outside the endometrium.

Prevalence: Approximately 1% of ectopic pregnancies are multiple. About 13 reported cases of triplet ectopic gestations.

Etiology: Mechanical obstruction from past inflammation, hormonal deregulation interfering with ovum transport in the tube.

Pathogenesis: Nidation during the passage through the oviduct.

Differential diagnosis: Cystic ovaries, especially after hormonal stimulation; corpora lutea.

Recurrence risk: 0-29% for ectopic pregnancy.

Management: Removal of the gestation, eventually conservative approach in case of unruptured tube.

MESH Triplets, Pregnancy, -Multiple, --Ectopic ICD9 633.1 CDC 651.100

Introduction

The incidence of ectopic pregnancies has increased throughout the world during the last decades. Early diagnosis of the condition is critical to avoid life-threatening bleeding or rupture with irreversible destruction of the tube and subsequent infertility. The introduction of transvaginal sonography allows a detailed visualization of the early first trimester gestation1. Thus, an increase of specific findings also in abnormally located pregnancies has been reported^2,3.

We present the unique occurrence of a tubal triplet pregnancy observed with transvaginal ultrasound in early first trimester after hormonal stimulation.

Case report

A 32-year-old woman presented with intermittent vaginal spotting and pain in the left hypogastrium with a positive pregnancy urine test. This was her first pregnancy, which had been induced elsewhere by gonadotropin stimulation and artificial intrauterine insemination. Gestational age was 28 days post-conception or 42 days (6+0 weeks) post-menstruation. Speculum examination showed uterine bleeding. At pelvic palpation there was marked tenderness and a soft swelling in the region of the left adnexa.

Vaginal sonography revealed a thickened endometrium measuring 15 mm in total anteroposterior width with both layers slightly distended by a thin sonolucent area corresponding to a small amount of blood. The uterine cavity was otherwise empty. In the pouch of Douglas, little free fluid was visible. Apart from the left cystic ovary obviously carrying the corpus luteum, a complex tumor was seen on the left side containing three typical ring structures representing chorionic cavities with a mean diameter of 10, 8 and 5 mm, respectively (fig. 1).

Figure 1: Ectopic triplet pregnancy. Left: Two chorionic cavities each with a visible yolk sac. Right: The third gestational sac close to the other two (not seen in this plane). Arrow: hematoma.

The echo-poor center of each ring was surrounded by an echo-dense rim, respectively, corresponding to the trophoblast which was asymmetrically thickened. One gestational sac contained a yolk sac and a viable embryo with cardiac pulsations of 100 bpm and a length of 5 mm corresponding to 6 weeks menstrual age. The second ring solely revealed a typical yolk sac, measuring 4 mm in diameter. In the third sac no distinct echoes were visible. Adjacent to the three chorionic cavities, there were low-level echo-structures with an inhomogeneous pattern suggesting blood clots. -human chorionic gonadotropin in maternal serum was measured 13,799 mIU/ml (1st International Reference Preparation). This value lies in the range of our reference curve for normal singleton pregnancies with a given age of 6 weeks.

On laparotomy, moderate amount of blood was found in the cul-de- sac. The ampulla of the left tube was distended by a hematoma and the tubal wall showed a small rupture. A partial distal salpingectomy was performed. Both adnexa exhibited thin fibrinous membranes as a sign of past pelvic inflammatory disease. Histological examination identified chorionic villi within the resected tube.

Discussion

Prevalence

Thirteen case reports on ectopic triplet pregnancies have been found^4,5. There are sporadic descriptions of ectopic twin pregnancies diagnosed by sonography6-8, but two triplet tubal gestations were not fully established with sonography before surgery^4,5. In ectopic pregnancies, twins have been observed at a rate of 1:218 (0.5%)⁹, 1:125 (0,8%)⁸ and 1:106 (0.9%)¹⁰. With sophisticated endosonography, it is likely that more multiple ectopics will be detected, resulting in a higher reported frequency. Furthermore, modern infertility therapies, which are associated with greater risks of multiple and ectopic gestations, will probably elevate the overall incidence of multiple ectopic gestations. Thus, in an in vitro fertilization embryo transfer program, a rate of 1 twin per 25 extrauterine pregnancies (4.0%) was seen⁶. The true incidence, however, still remains unknown because many early ectopic pregnancies which resolve spontaneously are not recorded.

Pathogenesis

Mechanically obstructed tubes due to antecedent of inflammatory disease or hormonally influenced retardation of tubal passage may serve as predisposing factors for the pathological implantation of extrauterine pregnancies¹¹. In multiple tubal pregnancy, early twinning causing a larger cell mass and thus a delayed transport in the damaged tube was presumed to contribute to the ectopic nidation⁸.

Sonographic diagnosis

Sonographic criteria of ectopic pregnancy comprise lack of gestational structures within the uterine cavity, fluid in the cul-de-sac and adnexal mass. Strong evidence of ectopic pregnancy is given if an embryo with cardiac activity or the yolk sac is seen outside the endometrium. A thick-walled but empty ring structure within the adnexal region is suspicious of ectopic gestation if it is clearly shown to be separate from the ovary for corpus luteum cysts may give a similar appearance. In our case, the relatively high -hCG level which was found to be in the normal range (though it is known to be decreased in most ectopic pregnancies¹²) gave further evidence of multiple gestation. The discordant sizes of the three gestational sacs with demonstrable embryonic heart action in only one instance may be explained by individual variation of cleavage rates of the cells and thus growth of the embryos, or by developmental failure of one or both smaller sacs according to the phenomenon known as the "vanishing twin" in intrauterine gestation.

Management

Therapy of choice is surgical removal of pregnancy through laparoscopy or laparotomy either with preservation of the tube or salpingectomy depending on the individual situation. Conservative management may be possible prior to tubal rupture4. Reported recurrence risks for ectopic pregnancy range between 0 and 29%, depending on the population examined13.

References

1. Rempen A: Vaginale Sonographie im ersten Trimenon. I.Qualitative Parameter. Z Geburtsh Perinat 195:114-122, 1991.

2. Kivikoski AI, Martin CM, Smeltzer JS: Transabdominal and transvaginal ultrasonography in the diagnosis of ectopic pregnancy: A comparative study. Am J Obstet Gynecol 163:123- 128, 1990.

3. Rempen A: Vaginal sonography in ectopic pregnancy. J Ultrasound Med 7:381-387, 1988.

4. Frishman GN, Steinhoff MM, Luciano AA: Triplet tubal pregnancy treated by outpatient laparoscopic salpingostomy. Fertil Steril 54:934-935, 1990.

5. Wrfel W, Krsmann G, Rothenaicher M, et al: Tripel-EUG nach in-vitro-Fertilisation und Embryotransfer. Geburtsh Frauenheilk 49:592-594, 1989.

6. Rizk B, Morcos S, Avery S, et al: Rare ectopic pregnancies after in-vitro fertilization: one unilateral twin and four bilateral tubal pregnancies. Hum Reprod 5:1025-1028, 1990 .

7. Sheerer DM, Liberto L, Woods JR: Preoperative sonographic diagnosis of a unilateral tubal twin gestation with documented fetal heart activity. J Ultrasound Med 9:729-731, 1990.

8. Ash KM, Lyons EA, Levi CS, Lindsay DJ: Endovaginal sonographic diagnosis of ectopic twin gestation. J Ultrasound Med

10:497- 500, 1991.

9. Breen JL: A 21 year survey of 654 ectopic pregnancies. Am J Obstet Gynecol 106:1004-1019, 1970.

10. Rempen A, Feige A: Der Stellenwert der Sonographie bei Extrauteringravidt. Z Geburtsh Perinat 188:279-284, 1984.

11. Bronson RA: Pathophysiology in the development of ectopic pregnancy. In: DeCherney AH (ed):Ectopic pregnancy. Aspen Publishers, Rockville, p 53-64, 1986.

12. Confino E, Demir RH, Friberg J, et al: The predictive value of beta subunit levels in pregnancies achieved by in vitro fertilization and embryo transfer: an international collaborative study. Fertil Steril 45:526-531, 1986.

13 Leach RE, SJ Ory: Modern management of ectopic pregnancy. J Reprod Med 34:324-338, 1989.