Case Report:Successful non-surgical management of a heterotopic abdominal pregnancy following embryo transfer with cryopreserved–thawed embryos

Michael D. Scheiber1 and Marcelle I. Cedars2,3

1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio and 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Campus Box 198, 4200 East 9th Avenue, Denver, CO 80262, USA


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Heterotopic pregnancy is an increasingly common complication of assisted reproductive technology. Abdominal pregnancy is a rare and life-threatening form of ectopic pregnancy that can present as the extrauterine portion of a heterotopic pregnancy. We present the case of a cryopreserved–thawed embryo transfer that resulted in a simultaneous intrauterine and abdominal pregnancy first recognized at 10 weeks gestation. Ultrasound-guided transvaginal injection of potassium chloride into the abdominal pregnancy resulted in asystole and spontaneous resorption of the ectopic fetus, while the intrauterine pregnancy continued and resulted in a liveborn vaginal delivery at full term. Selective embryo reduction using a non-surgical approach in a haemodynamically stable patient can therefore be considered in the management of heterotopic abdominal pregnancy if diagnosed relatively early.

Key words: abdominal pregnancy/cryopreserved embryo transfer/heterotopic pregnancy/in-vitro fertilization/selective embryo reduction


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Ectopic pregnancy is a recognized complication of in-vitro fertilization (IVF) and embryo transfer. Heterotopic pregnancy is defined as the presence of an intrauterine pregnancy (IUP) coexisting with an ectopic pregnancy. Abdominal pregnancies comprise approximately 1% of ectopic pregnancy, but have a maternal mortality almost eight times greater than that of tubal pregnancy (Atrash et al., 1987Go). The first case of an abdominal pregnancy after IVF–embryo transfer was reported in 1988 (Oehninger et al., 1988Go). Since then, several other cases of abdominal pregnancy following IVF–embryo transfer and one case of abdominal pregnancy following cryopreserved–thawed embryo transfer have been reported in the literature (Bassil et al., 1991Go; Fisch et al., 1995Go, 1996Go; del Rosario and El-Roeiy, 1996Go).

Both minimally invasive surgical and non-surgical options for the treatment of tubal ectopic pregnancy have increased dramatically over the last decade. The non-surgical selective reduction of tubal and interstitial heterotopic pregnancies as well as the successful expectant management of tubal heterotopic pregnancies has been reported (Fernandez et al., 1993Go; Baker et al., 1997Go). The treatment for abdominal pregnancy has traditionally been laparotomy, with recent cases of laparoscopic management emerging in the literature. We report the first case of a heterotopic abdominal pregnancy resulting from cryopreserved–thawed embryo transfer as well as the first selective reduction of a heterotopic abdominal pregnancy using the ultrasound-guided transvaginal injection of potassium chloride.


    Case report
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 37 year old gravida 3, para 0 Caucasian female with a 6 year history of infertility resulting from tubal disease, endometriosis, and decreased ovarian reserve presented to our centre for treatment. She was otherwise healthy but had undergone a previous right linear salpingostomy for a spontaneously conceived tubal pregnancy. This conservative surgical approach resulted in a persistent ectopic pregnancy that was successfully treated with a single dose of methotrexate (50 mg/m2). She had also had two spontaneous first trimester losses without complication.

The patient and her husband elected to undergo donor oocyte IVF. The oocyte donor received ovarian stimulation with human urinary gonadotrophins following pituitary down-regulation with gonadotrophin releasing hormone agonist. She received a total of 2700 IU of gonadotrophins, with a peak oestradiol of 3426 pg/ml on the day of HCG (7500 IU i.m.) administration. No pregnancy was achieved with fresh embryo transfer.

Natural cycle cryopreserved–thawed embryo transfer with two cryopreserved–thawed embryos was subsequently performed on cycle day 18. Both embryos had been cryopreserved at the 1-cell stage, were thawed 1 day prior to transfer, and had progressed to the 4-cell stage on the day of transfer. Embryos were transferred in 0.020 ml of human tubal fluid with penicillin and streptomycin (Irvine Scientific, Santa Ana, CA, USA) to ~0.5 cm from the uterine fundus using a Tefcat® (Cook OB/GYN, Spencer, IN, USA) catheter. The cryopreserved–thawed embryo transfer was uncomplicated.

Fourteen days after cryopreserved–thawed embryo transfer serum ß-HCG was 637 mIU/ml, and serum progesterone was 28.8 ng/ml. Twenty-eight days after cryopreserved–thawed embryo transfer a live intrauterine pregnancy with a crown–rump length (CRL) equivalent to 6.4 weeks gestation was visualized on transvaginal ultrasound.

Approximately 8.5 weeks after cryopreserved–thawed embryo transfer the patient presented with severe cramping abdominal pain, tenesmus, and nausea. Transvaginal ultrasound revealed simultaneous live pregnancies, one intrauterine and one presumed abdominal, filling the cul de sac and distinct from the ovaries (see Figure 1Go). The abdominal pregnancy had a CRL consistent with 10 weeks gestation and positive fetal cardiac motion. There was minimal free fluid in the pelvis, and the patient was haemodynamically stable.



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Figure 1. Transvaginal ultrasound image demonstrating intrauterine gestation (top) and coexisting abdominal heterotopic pregnancy (bottom).

 
The strict criteria for the diagnosis of primary abdominal pregnancy were set forth many decades ago (Studdiford, 1942Go) and require: (i) normal tubes and ovaries without evidence of recent or remote injury; (ii) no evidence of a uteroplacental fistula; and (iii) a primary peritoneal implantation site without evidence of secondary implantation after primary tubal nidation. In this case, in order to avoid exposing a pregnant patient and her intrauterine fetus to the risk of an anaesthetic and an operative procedure, the diagnosis of abdominal pregnancy was made only with transvaginal ultrasound. It was the impression of two independent senior ultrasonographers that this was, indeed, an abdominal pregnancy. However, we well recognized the difficulties regarding the diagnosis of an early abdominal pregnancy without surgical exploration.

Two days later, transvaginal selective reduction of the abdominal pregnancy was performed. The patient was sedated with 25 mg of i.v. meperidine and 5 mg i.v. diazepam, and 1 g i.v. cefazolin was administered. Using transvaginal ultrasound guidance, a 16 gauge needle was passed transvaginally into the gestational sac and some of the fluid was withdrawn. Approximately 4 ml of potassium chloride (2 mmol/2 ml) was injected in 0.5 ml increments into the fetal intra-abdominal and intra-cardiac cavities until cardiac asystole was noted. There were no procedural complications.

Serial ultrasound examinations over the next several weeks revealed a gestational sac of decreasing size that eventually underwent cystic degeneration and showed decreasing blood flow by Doppler ultrasound. The intrauterine pregnancy continued to develop normally, and the patient had a spontaneous vaginal delivery of a healthy 2429 g male infant at 39 weeks gestation. Follow-up transvaginal ultrasound in the 8th postpartum week revealed complete resolution of the pelvic mass.


    Discussion
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
The international incidence of heterotopic pregnancy after IVF–embryo transfer approximates to 1%. The Bourn Hall group in the UK reported a 0.75% rate among 2650 clinical pregnancies (Marcus et al., 1995Go) while a multicentre UK study reported a 1.3% rate among 2234 pregnancies (Rizk et al., 1990Go). A Danish series reported a rate of 1.1% among 1171 pregnancies, but these included biochemical pregnancies (Svare et al., 1993Go). An international collaborative patient registry reported a heterotopic pregnancy rate of 0.83% among 601 clinical pregnancies resulting from 2092 gamete intra-Fallopian transfer (GIFT) procedures (Li et al., 1992Go), and a collaborative Australian group reported an incidence of 1% among 1001 clinical pregnancies resulting from GIFT, IVF–embryo transfer or cryopreserved–thawed embryo transfer (Molloy et al., 1990Go).

The vast majority of heterotopic pregnancies following assisted reproductive technology procedures involves simultaneous intrauterine and tubal ectopic pregnancies. Reports of abdominal pregnancies are rare but increasing with the widespread use of assisted reproduction procedures. Even salpingectomy does not eliminate the risk of abdominal pregnancy with IVF–embryo transfer, as cases have been reported following bilateral salpingectomy (Fisch et al., 1996Go).

Several aetiological mechanisms have been suggested to contribute to the relatively high rate of heterotopic pregnancy resulting from assisted reproduction procedures. These include the transfer of excessive numbers of embryos (Tummon et al., 1994Go), the uterine location of embryo transfer, accidental direct injection of embryos into the Fallopian tube, retrograde passage of embryos into the tube due to hydrostatic forces, the volume of transfer medium (Botta et al., 1995Go), and the extremely rare possibility of uterine perforation during embryo transfer (Oehninger et al., 1988Go; Marcus et al., 1995Go).

The management of heterotopic pregnancy remains controversial. Laparoscopy may be invaluable in both the diagnosis and treatment (Louis-Sylvestre et al., 1997Go). As shown by these authors, many patients are minimally symptomatic and careful ultrasound survey of the pelvis is required even in the face of a documented intrauterine pregnancy (IUP) following assisted reproduction. Surgical therapy has been the traditional mainstay, but involves surgical and anaesthetic risks to both the mother and the intrauterine pregnancy. Louis-Sylvestre et al. (1997) noted a 40% loss of viable IUP after laparoscopy. The known high risk of surgical treatment with an abdominal pregnancy further complicated this particular patient's course. Recently, the non-surgical management of heterotopic pregnancy has gained popularity. The medical armamentarium is somewhat more limited with heterotopic pregnancy than with simple ectopic pregnancy due to concerns over maintaining the intrauterine pregnancy. Methotrexate and RU486 with their potential adverse effects on the intrauterine gestation and prostaglandins with their potential effect on uterine contractility are not options in the treatment of ongoing heterotopic pregnancy.

The injection of potassium chloride to selectively reduce multiple intrauterine gestations has been widely used. More recently this approach has been used to manage heterotopic pregnancy. The successful non-surgical management of six cases of heterotopic pregnancy using either potassium chloride injection into the tubal ectopic pregnancy or expectant management has been reported (Fernandez et al., 1993Go). Wright et al. (Wright et al., 1996Go) also reported the selective embryo reduction of the tubal gestation of a heterotopic pregnancy resulting from IVF–embryo transfer, but this resulted in a haematosalpinx requiring minilaparotomy and salpingectomy. The successful resolution of three interstitial heterotopic pregnancies, two of which resulted from IVF–embryo transfer, with the transvaginal administration of potassium chloride was reported (Benifla et al., 1996Go). However, two of the three ongoing pregnancies resulted in miscarriage.

The treatment of abdominal pregnancy traditionally necessitated laparotomy. However, several authors (Ben-Rafael et al., 1995Go; del Rosario and El-Roeiy, 1996Go) have recently described the laparoscopic management of abdominal pregnancy. To the best of our knowledge, this is the first case report describing the use of potassium chloride to selectively terminate an abdominal heterotopic pregnancy resulting from IVF–cryopreserved–thawed embryo transfer.

We conclude that heterotopic pregnancy occurs in approximately 1% of pregnancies achieved through the use of assisted reproduction. Although a small number of these will be abdominal heterotopic pregnancy, we have shown that a non-surgical approach can be used safely and effectively to manage these patients if they are clinically stable and the abdominal pregnancy is recognized relatively early in gestation.


    Notes
 
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    References
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Atrash, H.K., Friede, A. and Hogue, C.J.R. (1987) Abdominal pregnancy in the United States: frequency and maternal mortality. Obstet. Gynecol., 69, 333–337.[Abstract]

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Submitted on June 18, 1998; accepted on January 27, 1999.





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