Why is heterotopic pregnancy on the increase?
One reason may be the increase in ectopic pregnancy. Among the factors contributing to the rising incidence of ectopic pregnancy are:
- pelvic adhesive disease
- effects of diethylstilbestrol (DES) on the genital tract
- antibiotic-induced tubal disease
- use of an intrauterine device (IUD)
- voluntary restriction of family size
- iatrogenic curettage of intrauterine pregnancy during surgery for ectopic pregnancy
- pregnancy termination
- history of surgery to treat infertility, ectopic pregnancy, or tubal adhesions
- improvement in the assay used to measure gonadotropin
- improvement in ultrasonography.2-4
A previous ectopic pregnancy is a risk factor for ectopic pregnancy as well as for heterotopic pregnancy.5
Pelvic infection, antibiotic-induced tubal disease, previous ectopic pregnancy, pelvic adhesions, and tubal surgery with cauterization of the tubes and subsequent bowel adhesions distort the fallopian tubes and may render them unable to propel a migrated embryo into the uterine cavity.2,6 Ectopic pregnancy may result from internal migration of a fertilized ovum or transperitoneal migration of sperm.7
DES exposure can distort the uterine cavity.8 Congenital and acquired uterine malformations increase the risk of ectopic pregnancy.3
In addition, ovulation-inducing drugs and ovarian stimulation increase the number of eggs available for conception, with a greater risk of multiple gestation and heterotopic pregnancy.3,9,10
The greatest increase in heterotopic pregnancy has been seen with ART involving the transfer of multiple embryos into the uterus, as well as gamete intrafallopian transfer, also known as GIFT.10,11 When five or more embryos are transferred, the risk of heterotopic pregnancy increases to 1 in 45 pregnancies annually.11 Inadvertent placement of the catheter tip near the tube, excessive force or volume during transfer, and retrograde migration of an embryo because of uterine contraction may also increase the risk of heterotopic pregnancy.8
A heterotopic pregnancy in spontaneous conceptual cycles without ART is relatively rare, even in a woman who has risk factors for ectopic pregnancy.12
How does heterotopic pregnancy develop?
Possibilities include the following, according to Wolf and colleagues:
- fertilization of two ova from a single coitus
- superimposition of an intrauterine pregnancy over an existing ectopic pregnancy (also known as superfetation).13
The appearance of cardiac activity may be discordant in heterotopic pregnancy, according to Hirsh and associates, suggesting that superfetation is indeed a mechanism in its development, with one pregnancy conceived earlier than the other.14
Diagnosis requires a high index of suspicion
The timely detection of heterotopic pregnancy necessitates vigilance.10,15 The TABLE lists signs and symptoms of this condition, which include abdominal pain, an adnexal mass, peritoneal irritation, an enlarged uterus, and absence of vaginal bleeding.6 In contrast to ectopic pregnancy, there is no vaginal bleeding with heterotopic pregnancy because an intact intrauterine pregnancy is present.8
TABLE
Signs and symptoms of heterotopic pregnancy
| Pain after spontaneous or induced abortion |
| Two corpora lutea detected during ultrasonography or laparotomy |
| Persistent Hegar’s sign or Chadwick’s sign after laparotomy for ectopic pregnancy |
| Absence of vaginal bleeding after laparotomy for ectopic pregnancy |
| Lateral location of a gestational sac identified via ultrasonography |
| Fluid in the uterus |
| Discordant appearance of fetal cardiac activity |
| Unpredictable quantitative human chorionic gonadotropin levels |
CASE 2: Ovarian “cyst” turns out to be a gestation
A 28-year-old woman, para 2-0-0-2, visits the emergency department complaining of acute abdominal pain, and is given two diagnoses: urinary tract infection and incomplete abortion at 5 weeks’ gestation. She is treated for the infection and discharged, to be followed up with treatment by her private ObGyn for the incomplete abortion.
Three days later she returns, reporting cramping and increased pain. Ultrasonography reveals intrauterine fetal demise at 8 weeks and 6 days of gestation, along with a hemorrhagic mass in the cul-de-sac—most likely a ruptured hemorrhagic ovarian cyst. Her history includes two cesarean deliveries and treatment with clonidine for hypertension. Her blood pressure is normal, and her abdomen is diffusely tender, with bowel sounds present. The preoperative diagnosis: incomplete abortion and a ruptured hemorrhagic cyst.
During exploratory laparotomy, left salpingo-oophorectomy is performed, and a hemorrhagic ovarian cyst is removed, with evacuation of hemoperitoneum, followed by suction curettage. Almost no tissue is present in the uterine cavity at the time of surgery. The final pathology report determines that the hemorrhagic cyst contained organizing clotted blood with trophoblasts, consistent with ectopic pregnancy. In addition, the uterine contents included scant tissue with hypersecretory endometrium. The physician theorizes that the collapsed gestational sac may have passed out of the patient’s uterus after US or during preoperative preparation.
The patient does well postoperatively and is discharged home.
Should ectopic pregnancy have been suspected earlier?
When a patient experiences pain after spontaneous or induced abortion, ectopic pregnancy should be suspected.2 In addition, women who exhibit signs or symptoms of ectopic pregnancy or continuing pregnancy after an inconclusive or negative US should be assessed thoroughly to exclude ectopic pregnancy.5