CASE REPORT fertilization, ovulation, in vitro; pregnancy, heterotopic

Heterotopic Pregnancy After in Vitro Fertilization and Ovulatory Drugs

We report two cases of heterotopic pregnancy in women who were previously infertile. One of these patients conceived with the aid of ovulation stim- ulatory drugs, and the other from in vitro fertilization. In each case an ultra- sound of the pelvis revealed a viable intrauterine pregnancy (twins in one case). Both patients presented in hypovolemic shock and required explorato- ry laparotomy. A t the time of surgery a ruptured ectopic pregnancy with accompanying hemoperitoneum was found in each. Simultaneous ectopic and intrauterine pregnancy, though rare, should be suspected in patients who conceive with the aid of ovulatory drugs or in vitro fertilization. [Snyder T, delCastillo J, Graft J, Hoxsey R, Hefti M: Heterotopic pregnancy after in vitro fertilization and ovulatory drugs. Ann Emerg Med August 1988;17:846-849.]

INTRODUCTION Ectopic pregnancy is defined as implantation of a fertilized ovum in any

site except the uterus. Well-known risk factors for ectopic pregnancy include previous ectopic pregnancy, 1 a history of pelvic inflammatory disease, ~ and an intrauterine device in place.3 A simultaneous ectopic pregnancy and intra- uterine pregnancy is rare, occurring in one in 30,000 pregnancies. 4 In vitro fertilization and ovulation stimulatory drugs are also risk factors for ectopic pregnancy. 1

We describe two cases of simultaneous ectopic pregnancy and intrauterine pregnancy in two women receiving therapy for infertility.

CASE REPORTS Case One

A 26-year-old woman was transported by ambulance after a near-syncopal episode in her physician's office. The patient gave a history of having devel- oped midline lower abdominal pain, of feeling flushed and lightheaded, and of nearly fainting. She was gravida 1 para 0, with a last menstrual period eight weeks earlier. Because of infertility problems, she had received clomiphene citrate 50 mg/day for five days during her last two cycles. There was no other significant medical or surgical history.

Vital signs in the field were blood pressure, 80 palpable; pulse, 70; and respirations, 24 and unlabored. The paramedics started an IV line of 1,000 mL of normal saline and administered a bolus of 200 mL as well as 6 L oxygen by cannula.

Vital signs in the emergency department were blood pressure, 90/70 mm Hg; pulse, 64; respirations, 20; and temperature, 35 C. The patient appeared pale, slightly diaphoretic, and anxious. There was guarding and rebound ten- demess in the fight lower quadrant suprapubic area and left lower quadrant. Bowel sounds were absent. A pelvic examination revealed a long, closed cer- vix and no blood in the vagina. The corpus and adnexae could not be prop- erly assessed because of the patient's pain.

An emergency ultrasound revealed twin gestational sacs with fetuses~ the measurements were compatible with an intrauterine pregnancy of seven to eight weeks (Figure 1). There were cysts on both ovaries and a small amount of free fluid in the pelvis. The fluid was believed to most probably represent rupture of one of the cysts (Figure 2).

Laboratory data showed hemoglobin, 10.6 g%; hematocrit, 31.5%; WBC,

Thomas Snyder, MD* Chicago, Illinois Jorge delCastitlo, MD, FACEP¢ Jeffrey Graft, MD, FACEp1- Rodney Hoxsey, MD, FACOG¢ Marguerita Hefti, MD, FACOG¢ Evanston, Illinois

From the Section of Emergency Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois;* and the Division of Emergency Medicine, Department of Medicine,t and the Department of Obstetrics and Gynecology,¢ Evanston Hospital/McGaw Medical Center of Northwestern University, Evanston, Illinois.

Received for publication February 29, 1988. Accepted for publication April 25, 1988.

Address for reprints: Jorge delCastillo, M D, FACEP % Division of Emergency Medicine, Evanston Hospital, 2650 Ridge Avenue, Evanston, Illinois 60201.

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HETEROTOPIC PREGNANCY Snyder et al

FIGURE 1. Twin intrauterine gesta- tions of seven weeks.

19,700/mm 3, with a differential of 76 segments, 11 bands, ten lymphocytes, three monocytes, and a normal plate- let estimate.

A Foley catheter was inserted and clear yellow urine returned. The pa- tient 's condit ion stabilized with a blood pressure of 100/60 mm Hg and a pulse of 100. A repeat hematocrit was 27%. Blood was sent for type and cross match for four units of packed cells. The diagnosis at this time was probable rupture of an ovarian cyst secondary to c lomiphene hyper- stimulation. The remote possibility of heterotopic pregnancy was also enter- tained.

The patient was hospitalized, and a repeat complete blood count was done, showing a hemoglobin of 6 g% and a hematocrit of 18.3%. Blood pres- sure was 120/70 mm Hg, and pulse was 100. The patient was taken to the operating room at that time for an emergency exploratory laparotomy. The findings were fight tubal ectopic gestation at the ampullary- is thmic junction, mpturedi a right ovary with two 3 cm 2 cysts, one hemorrhagic and one corpus luteum; a left tube with laceration of the mesosalpinx near the fimbriae ovarica; a left ovary with cor- pus luteum; and two small cysts mea- suring less than 1 cm each. The uterus was 12-weeks size, consistent with a twin pregnancy of about seven to eight weeks.

Estimated blood loss during surgery was 1,000 mL. The patient required 2,800 mL of crystalloid and 200 mL of hetastarch. In addition, she received four units of packed red blood cells and one unit of flesh frozen plasma.

On the fourth day after surgery, the patient had an expulsion of a clot vag- inally but denied cramping. The spec- imen was examined and appeared to be clot as well as tissue. A pelvic ul- trasound was done on the fifth day, which revealed only the presence of a nonviable sac. A diagnosis of in- complete abortion was made, and the patient was taken to the operating room for a dilatation and curettage. She was discharged on her sixth day (first day after dilatation and curet- tage) in good condition with a hemo- globin of 9.8 g%.

Case T w o Paramedics brought a 35-year-old

TABLE. Risk factors in ectopic pregnancyl.7, 8

Risk Factor Normal

History of tubal ligation

Previous ectopic pregnancy History of pelvic inflammatory disease

Pregnant with intrauterine device in place

DES exposure

In vitro fertilization

Percentage of Pregnancies That Are Ectopic

1.4

15 to 20

15

4 9 to 17

4 t o 5

4 to 11

woman to the ED in Trendelenburg position who complained of abdomi- nal pain and postural weakness. She was gravida 1 para 0 with the last menstrual period eight weeks earlier. She had had in vitro fertilization six weeks earlier. Four embryos had been transferred to her uterus transcer- vically. She was infertile because of a T-shaped uterus that resulted from DES exposure. She had been seen in the ED two days earlier for complaints of scant vaginal bleeding and lower ab-

Annals of Emergency Medicine

dominal pain. Her hemoglobin had been 11.0 g%, and she had been dis- charged with a diagnosis of threatened abortion.

The patient had seen her obstetri- cian the day after her previous ED vis- it, and a pelvic ultrasound then dem- onstrated a viable intrauterine preg- nancy and bilateral enlarged ovaries. She since had experienced progressive bilateral crampy lower abdominal pain along with postural weakness, dizzi- ness, and shoulder pain.

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FIGURE 2. Hyperst imulated ovarian cysts and free intraperitoneal fluid.

At the time of her second ED visit, she had a history of severe vasovagal reactions and attributed her present condition to constipation induced by weekly progesterone injections. She reported continued vaginal spotting and an inability to urinate during the last 24 hours. She denied a history of pelvic inflammatory disease, use of an intrauterine device, or previous ecto- pic pregnancy.

Physical exam ina t i on revealed blood pressure, 84/50 mm Hg; pulse, 92; respirations, 20; and temperature, 37 C. The patient was ashen, in Tren- delenburg position, awake, and alert. Abdomina l e x a m i n a t i o n demon- strated bowel sounds and diffuse ten- demess, especially in the lower quad- rants. Rectal examination revealed no stool but tested heme-positive. The initial impression was that the patient was having a vagal reaction, and an IV line was started. After 1 L lactated Ringer's, the patient's vital signs were pulse, 92, and blood pressure, 135/60 mm Hg. Her color remained poor. The hemoglobin was 6.9 g%. Two units of type-specific blood were ordered and administered while preparations for

an exploratory laparotomy were made. At the time of surgery, 2,300 mL of

flesh and clotted blood were found in the peritoneal cavity. The left fallo- pian tube was actively bleeding and was excised. Pathology later showed an ectopic pregnancy. Both ovaries were hyperstimulated, and the uterus was described as seven- to eight-weeks size. Her course after surgery required the addit ional t ransfusion of four units of blood. The intrauterine preg- nancy survived.

D I S C U S S I O N Ectopic pregnancy is the leading

cause of maternal mortali ty during the first trimester, resulting in 40 to 50 deaths each year in the United States. 5 A report from the Centers for Disease Control for the period of 1980 to 1983 showed a rate of 9.2 ectopic pregnancies per 1,000 pregnancies. 6 Risk factors include previous ectopic pregnancy, pregnancy with an intra- uterine device in place, pregnancy after in vitro fertilization, previous gynecologic surgery, DES exposure, and treatment with ovulatory drugs (Table).

We emphasize that infertility treat- ment is a risk factor for ectopic preg- nancy and may predispose for simul- taneous ec topic and in t rau te r ine pregnancies.

Infertility affects 15% of couples. 9 More than one-third of infertility is related to fallopian tube dysfunction. 9 This may result from pelvic inflam- matory disease, previous ectopic preg- nancy, failed tubal reconstruction, or congenital malformation from DES exposure.

The main indication for in vitro fer- t i l i za t ion is tubal dysfunc t ion , lo Other indications include oligosper- mia, cervical or immunologic prob- lems, endometriosis, and unexplained infertility, lo Egg development is usu- ally enhanced by ovulation stimulato- ry agents.lO Before ovulation, the eggs are recovered laparoscopically and in- cubated. The man's sperm is added, and fertilization is accomplished in vitro. The fertilized eggs are further incubated, and from one to six are transferred to the uterus. The patient then is started on progesterone supple- ments. The presence of viable preg- nancy is determined ten days later by serum B-HCG. A viable intrauterine pregnancy can usually be d~termined by ultrasound five weeks after concep- tion or seven weeks after the patient's last menstrual period. The patient then receives routine prenatal care.

Simultaneous intrauterine pregnan- cy and ectopic pregnancy have been reported to occur in one in 30,000 pregnancies. 4 The use of ovulation in- duction alone and in conjunction with in vitro fertilization may raise this in- cidence. 4 There have been reports of simultaneous ectopic and intrauterine pregnancies after in vitro fertilization, and two cases after the use of ovula- tion induction agents alone have been reported.4,11

There are several explanations for this phenomenon. With both infer- tility treatments, mult iple ova are available for fertilization or are fertil- ized and placed in the uterus. All of the risk factors for ectopic pregnancy have in common fallopian tube abnor- malities. These abnormalit ies may have been caused by infection, con- genital defect, surgery, or damage by previous ectopic pregnancy. The com- bination of tubal pathology and multi- ple ova may increase the risk of simul-

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HETEROTOPIC PREGNANCY Snyder et al

taneous ectopic and intrauterine pregnancy.

The incidence of heterotopic preg- nancy seems to be increasing because of the more frequent use of ovulatory drugs and in vi tro fertilization. Our patients' conditions were the products of each of these modalities with re- sulting heterotopic pregnancies.

SUMMARY Ectopic pregnancy must be sus-

pected in women who have conceived with the aid of ovulatory drugs (clomiphene citrate or menotropins} or in v i t ro fertilization. An intra- uterine pregnancy by ultrasound does not rule out a heterotopic multiple

g e s t a t i o n in s u c h p a t i e n t s .

REFERENCES 1. Weckstein L: Clinical diagnosis of ectopic pregnancy. Clin Obs te t Gynecol 1987;30: 236-244.

2. Westrom L: Effect of acute pelvic inflam- matory disease on fertility. Am J Obstet Gyne- col 1975~121:707.

3. Siegler AM, Wang C8, Westoff C: Manage- ment of unruptured tubal pregnancy. Obstet Gynecol Surv I981;36:599.

4. Sondheimer SJ, Turek RW, Blasco L, et ah Si- mul taneous ectopic pregnancy with intra- uterine twin gestations after in vitro fertiliza- tion and embryo transfer. Fertii Steril 1985; 43:313-316.

5. Dorfman SF: Epidemiology of ectopic preg- nancy. Clin Obstet Gynecol 1987;30:173-I80.

6. Centers for Disease Control: Ectopic preg- nancy - - United States, 1981 to 1983. MMWR 1986;35:334.

7. Martinez F, Trounson A: An analysis of fac- tors associated with ectopic pregnancy in a human in vitro fertilization program. Fertil Steril 1986;45:79-87.

8. Lopata A: Concepts in human in vitro fertii- ization and embryo transfer. Fertil Steril 1983; 40:289.

9. Rivlin M, Morrison JC, Bates GW: Manual of ! Clinical Problems in Obstetrics and Gyne- cology. Boston, Little, Brown and Co, 1982, p 8-12, 305-319.

I0. Garcia JE: In vitro fertilization. Obstet Gynecol Annu 1985;14:45-72.

11. Berger MJ, Taymor ML: Simultaneous intra- uterine and twin pregnancies following ovula- tion induction. Am J Obste t GynecoI 1972; 113:812-813.

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