Abdominal ectopic pregnancy after in vitro fertilization and single embryo transfer: a case report and systematic review

Abdominal ectopic pregnancies comprise less than 1 % of all ectopic pregnancies, yet have a maternal mortality rate eight times greater than tubal ectopic pregnancies [10]. For this reason, early recognition and treatment is crucial in the setting of abdominal ectopic pregnancy. The case presented demonstrates the diagnostic challenge of abdominal ectopic, as the patient’s beta hCG values followed a normal rise and the patient remained asymptomatic up to the point of diagnostic laparoscopy. Transvaginal ultrasound did not visualize the ectopic pregnancy until the beta hCG value was 20,000 pg/mL, which is far beyond the usual discriminatory zone. This atypical presentation of an ectopic pregnancy highlights the need to consider abdominal ectopic pregnancy in the differential of any pregnancy of unknown location after IVF, especially in the setting of non-diagnostic transvaginal ultrasound.

There appears to be an increased rate of ectopic pregnancies after ART when compared to rates in spontaneous pregnancy [11]. As the number of IVF procedures performed continues to rise, the incidence of ectopic and abdominal ectopic pregnancy will likely also rise. While there are still relatively few reported cases of abdominal ectopic pregnancies after IVF, our systematic review demonstrates several trends among reported cases. First, the majority of cases (61 %) report a history of anatomic/structural infertility etiology with history of tubal factor infertility (TFI) (46 %) being the most common. This is consistent with TFI being a known risk factor for ectopic pregnancy following IVF. One study that examined the risk factors for EP following IVF in 712 women reported an odds ratio (OR) of 3.99 (95 % CI: 1.23 to 12.98) for women with TFI compared to those with other infertility causes [12]. In a larger, more recent study of 553,577 ART cycles in the US, among all infertility diagnoses, TFI was the only one significantly associated with increased risk for ectopic pregnancy (adjusted relative risk (RR) 1.25, 95 % CI 1.16–1.35) [13]. In addition, history of tubal ectopic pregnancy was particularly common, being reported in 37 % of the abdominal ectopic cases. This also appears to be consistent with the general ART-associated EP literature. A retrospective study that measured the risk of EP following IVF in 181 women with a previous ectopic demonstrated a 45-fold higher risk of recurrence when compared with 377 women with other causes of infertility. The authors reported that the prevalence of EP was 8.95 % compared with 0.75 % in the control group [14]. History of prior tubal surgery was also particularly common (50 %) among abdominal ectopic cases in our systematic review. A history of tubal/pelvic surgery is another major risk factor for the development of EP following IVF. Odds ratio for developing EP was 8.52 (95 % CI: 5.91–12.27) for prior adnexal surgery, 11.02 (95 % CI: 5.49–22.15) for a previous tubal infertility surgery, 5.16 (95 % CI: 1.25–21.21) for prior surgery for endometriosis and 17.70 (95 % CI: 8.11–38.66) for a previous abdominal/pelvic surgery [12, 15, 16]. Interestingly, bilateral salpingectomy was the most common tubal surgery reported in our case review. While the exact mechanism of abdominal ectopic after bilateral salpingectomy remains unclear, many authors have proposed that it may be due to the development of a micro-fistulous tract after salpingectomy. Uterine perforation during embryo transfer has also been suggested as a mechanism for abdominal ectopic pregnancy, and embryo transfer technique has been related to overall EP risk after IVF. Aspects of the transfer that may increase risk of EP include large volume of transfer media, induction of abnormal uterine contractions, and location of embryo transfer in relation to the uterine fundus [9]. These factors have all been associated with retrograde flow of both transfer media and the embryo toward the fallopian tubes. Many suggestions have been made regarding optimal transfer location within the endometrium, ranging from 5 to 20 mm from the fundal surface, while others recommend “mid-cavity” location to avoid proximity to the fallopian tubes [17‐19].

Other trends identified in our systematic review include >1 embryo transferred (reported in 79 % of cases) and a large number of heterotopic abdominal pregnancy (reported in 46 % of cases). Multiple embryo transfer has always been associated with increased risk of EP with transfer of two or less embryos carrying lower risk than after three or more embryos [20]. In the setting of multiple embryo transfers, identification of an intrauterine pregnancy often leads to delayed diagnosis of abdominal pregnancy in the absence of clinical symptoms. Among the heterotopic cases, 4 reported a 2 week delay in diagnosis of the abdominal ectopic from the time of suspected ectopic, and 5 cases did not identify the abdominal ectopic until beyond the 12th week of pregnancy. Unfortunately, this type of delayed diagnosis has the potential to lead to significantly morbid outcomes. In our review, four cases of viable abdominal pregnancies were identified, which is an extremely rare outcome. Three of these cases were identified at 19 weeks or beyond, and all three had attachment of the abdominal placenta to the peritoneal surface of the uterus without involvement of other abdominal organs. Placental attachment to the uterus has previously been associated with viability of abdominal pregnancies [21], and with a relatively lower risk of bleeding and lower likelihood of fetal growth retardation [22].

Finally, abdominal ectopic pregnancies were far more common in fresh embryo transfer (71 % of cases) than frozen embryo transfer (11 % of cases). This may be due to the fact that frozen embryo transfer has become widely used only recently, and we may begin to see higher frequency with frozen embryo transfers over time. However, several recent studies indicate that ectopic pregnancy rates are higher for fresh as compared to frozen IVF cycles [1, 6].

A limitation of this review is the heterogeneity of reported cases and IVF practices which encompass several decades. Further research focusing on more homogenous population may help in better characterizing this rare IVF complication.