Management and obstetric outcomes of 17 heterotopic interstitial pregnancies

Heterotopic interstitial pregnancy, a rare form of pregnancy that involves the coexistence of an ectopic interstitial pregnancy and intrauterine pregnancy, is one of the most life-threatening types of all the ectopic gestations [1]. The calculated incidence is documented to be as high as 1/3600 in pregnancies after assisted reproductive technology (ART) [2].

However, most of these women were asymptomatic or only showed non-specific symptoms such as abdominal pain and vaginal bleeding [3]. The clinicians might not consider the possibility of extrauterine pregnancy in the case of a confirmed intrauterine gestation by ultrasonography. Therefore, the diagnosis of heterotopic interstitial pregnancy is often delayed, even after its rupture [2] and meticulous care is required, especially in the patients with relevant risk factors associated with heterotopic pregnancy such as previous history of ectopic pregnancy, pelvic surgery, or pelvic inflammatory diseases [2, 4].

The treatment of heterotopic interstitial pregnancy aims to preserve the intrauterine pregnancy while removing or interrupting the evolution of the ectopic interstitial pregnancy using a minimally invasive method. The therapeutic modalities include surgical, medical or expectant treatment [2]. However; there is no consensus for the treatment of heterotopic interstitial pregnancy. Therefore, in the present study, we aimed to investigate the therapeutic interventions and corresponding obstetric outcomes of women diagnosed with heterotopic interstitial pregnancy.

Of the total 17 patients, 10 (58.5%) underwent surgical treatment (7 laparoscopic cornual resection, and 3 laparotomy). Laparotomy in those three patients was mainly attributed to poor family economic situation or restriction of laparoscopic operation on weekends or holidays in our institution. However, three cases simultaneously terminated the intrauterine pregnancy by suction evacuation, as they were aware of the risk of uterine rupture later in pregnancy. The median operative time was 45 min (range, 28–135 min) and estimated blood loss in the operation was 175 ml (range, 20–750 ml). Only one case had blood transfusion (2 units of red blood cells) after the operation. The median length of postoperative hospital stay was 2.5 days (range 2–7 days) without any intraoperative and postoperative complications such as miscarriage or uterine rupture. Furthermore, compared with laparotomy, the laparoscopic treatment showed shorter operative time (median 40 vs. 70 min), less blood loss in the operation (150 vs. 400 ml) and shorter hospital stay (2 vs. 4 days), although the difference was not statistically significant (P = 0.11, 0.11 and 0.09 respectively). It was likely due to the small sample size of the study.

After fully informed consent, 4 (23.5%) patients (including 3 with no clinical symptoms and 1 with mild abdominal pain) underwent selective embryo reduction, i.e. aspiration of the ectopic fetal heart and local injection of 10% KCl into the interstitial pregnancy sac under direct transvaginal ultrasound guidance. Expectant management was chosen in the remaining 3 (17.6%) patients with no symptoms or only a small amount of vaginal bleeding (Table 1). Importantly, only a crown rump length or yolk sac was shown in either case, but no fetal cardiac activity in ectopic interstitial gestation was seen by ultrasound scan. All of these 7 patients were followed up closely by weekly clinical and ultrasound assessment. Unfortunately, missed miscarriage of intrauterine gestation at 8 gestational weeks was confirmed in one case with expectant management. However, no surgical treatment was indicated due to persistent existence of ectopic cardiac activity or rupture of interstitial gestation in the other six patients.

In the follow-up study, the three pregnant women, who had simultaneously terminated intrauterine pregnancy, all recovered well after the surgery. In addition, as shown in Table 1, only one of the 14 cases who had an ongoing intrauterine pregnancy was diagnosed with a missed miscarriage at 8 gestational weeks; but the other 13 patients all delivered healthy live babies vaginally or by cesarean section. However, only one case attempted vaginal delivery because the dilatation of cervix was 3 cm when seeing the doctor. The other 12 women all delivered their babies by elective cesarean section due to fears of uterine rupture or cultural factors. It was worthy that no congenital anomalies were reported, and all the infants were in normal growth and development.

The incidence of heterotopic interstitial pregnancy has considerably increased, with the widespread use of assisted reproductive technology and the rising frequency of tubal and pelvic inflammatory diseases. However, the optimal management of heterotopic interstitial pregnancy still remains controversial. There are currently limited clinical data or only several case reports in the literature, especially in developing countries. In the present study, we conducted a retrospective review of the therapeutic interventions and further investigated the corresponding obstetric outcomes of all the 17 patients diagnosed with heterotopic interstitial pregnancy over the past five years in our centre.

Previous history of pelvic inflammatory disease, pelvic surgery, and ART are associated with the incidence of heterotopic interstitial pregnancy [2]. Consistent with these studies, we found that all of the 17 pregnant women had been conceived through ART, and 76.5% (13/17) had a history of ectopic pregnancy, pelvic inflammatory disease or surgery. In the present study, neither hypovolemic shock nor maternal death was reported. It seemed that this was not a typical population presenting with ectopic pregnancy. We speculated that it may be related to the fact that all these patients after embryo transfer were provided with detailed health education on red flag symptoms of ectopic pregnancy; and therefore they sought medical advice and received timely professional assessment and treatment.

The feasibility of surgical cornual resection has been demonstrated in treating heterotopic interstitial pregnancy. However, most of these studies were only case reports and mainly conducted in the developed countries or regions [3, 6–10]. Some authors indicated that the long operative time and altered intraperitoneal carbon dioxide environment throughout the laparoscopic operation may involve surgical and anesthetic risk, causing an adverse effect on maternal morbidity and the surviving intrauterine pregnancy [10]. In the present study, we found that all the infants born to the seven pregnant women, who had undergone laparoscopic cornual resection or laparotomy, were in good health and no congenital conformations were reported. In addition, compared with laparotomy, laparoscopic treatment showed the shorter hospital stay, fewer surgical wounds, and reduced use of antibiotics and analgesics. Therefore, laparoscopic cornual resection appears to be a safe and viable treatment option and should be considered, especially in the patients without signs of cornual rupture [11]. The other three women had selected laparotomy only because of poor family economic situation or restriction of laparoscopic operation at night time, weekends or holidays in our institution. We hope that improved access to laparoscopic treatment can be offered in the future.

Surgical cornual resection may increase the risk of delayed haemorrhage and uterine rupture. Compared with surgical treatment, the medical approach is less expensive, less invasive with minimal blood loss and quicker recovery. Therefore, medical embryo reduction of interstitial gestation has been recommended in the patient with hemodynamically stable status [12, 13]. It consists of injecting methotrexate, prostaglandin, or KCL directly into ectopic gestational sac under the guidance of transvaginal ultrasonography. Kim et al. suggested that KCl has reportedly been associated with intrauterine damage, periventricular leukomalacia, and limb anomalies [3]. However, more studies confirmed that no teratogenicity secondary to local injection of KCl was reported [14]. Therefore, selective embryo reduction using local injection of 10% KCl has been performed in four patients after fully informed consent at our centre. To ascertain whether KCl may have adverse effects on the pregnancy outcomes, we further evaluated the infant’s overall health condition during face-to-face interview. No congenital malformation was found, and all the infants were in normal growth and development. Therefore, it indicated that selective embryo reductionby local injection of KCl during the first trimester might be a viable treatment approach.

Expectant management seems to offer a third possible and safe therapeutic alternative [2]. Nevertheless, the current reported clinical studies were limited [15, 16]. In the present study, expectant management had been chosen in three patients (Table 1). Other than a single case of missed miscarriage, an uneventful ongoing pregnancy was documented in the other two cases. Therefore, expectant management might be a viable alternative for the interstitial pregnancy with absence of fetal cardiac activity and limited gestational sac size. Nevertheless, because of the potential risk of continued growth of interstitial gestation and subsequent rupture, cornual gestation and subsequent rupture, serial ultrasound scans and close clinical assessment are necessary [2].

In summary, laparoscopic cornual resection is a feasible approach with favorable surgical and long-term pregnant outcomes. Medical or expectant management may be an efficient treatment alternative for selected symptom-free patient. Although the survival of the intrauterine pregnancy could not always be assured, the prognosis for a woman with heterotopic interstitial pregnancy is generally good.