Heterotopic pregnancies are extremely rare forms of ectopic pregnancy in gynecology. However, in recent years the incidence rate has increased to 1% with widespread use of ART . HP is a life-threatening condition which have a maternal mortality rate eight times greater than tubal ectopic pregnancies . For this reason, early recognition and treatment is critical to improving the prognosis. Clinical features associated with HP vary widely among individuals. Some patients were asymptomatic and others may experience acute abdominal pain, pelvic hemorrhage and hypovolemic shock. The present study suggested no significant difference between the HP and IUP with aspect to blood level of β-hCG. β-hCG is usually low in ectopic pregnancies. However, it’s probably unhelpful in diagnosis of heterotopic pregnancy, for they might indicate normal ranges in patients with HP. Transvaginal ultrasound provides a very important tool for the diagnosis of HP. However, the simultaneously presented concurrent intrauterine sac and bilaterally hyperstimulated ovaries greatly increased the difficulty in diagnosis. Given the above, diagnosis of HP is a major predicament for clinicians.
Many studies have shed light on the risk factors of HP over the past few years, with the hope of a clinical prediction model for it . In our study, history of multiple abortions, tubal infertility, previous ectopic pregnancies and multiple embryo-transfer were associated with an increased incidence of HP following IVF treatment. Thus, HP should always be involved in differential diagnosis in symptomatic patients with risk factors suggested above. Furthermore, outpatient follow-up should be performed more frequently in patients with multiple embryo transfer, even though an intrauterine gestational sac is visible on ultrasound. A history of salpingitis and gross tubal damage in patients acts as a potential pathological mechanism of ectopic pregnancies following IVF and in natural conceptions . The results are consistent with the present study which has shown that patients with history of tubal damage ( salpingitis and previous ectopic pregnancies ) are associated with increased rate of HP. A possible explanation is that altered tubal anatomy and function due to tubal damage may alter the mechanism of tubal transport and signaling molecules in tubal microenvironment which prevents embryonic implantation in the oviduct . Compared with other indications for IVF treatment, tubal indications is a major risk for HP in the current study. The same results were also presented in Li’s study . The probable explanation of tubal pregnancies in those patients was that the embryos migrated into the oviduct after uterine placement,but the damaged tubal failed to transport the embryos back into the uterine.
The distance from the tip of transfer catheter to uterine fundus has also been evaluated as a potential risk factor for development of HP . In our center, distance of air bubble to fundus was controlled in 15–20 millimetres range, and the data suggested no significant difference between HP and IUP (17.55 ± 1.80 mm vs. 17.32 ± 1.75 mm, p = 0.55). The result was consistent with study by Friedman et al. which reported that air bubble position too close to the fundus (10 mm) probably ended in a tubal pregnancy while a distance of 15–20 millimetres would achieved a higher rate of embryo implantation . That is a possible explanation for the comparable data on distance of air bubble to fundus between the two groups in our center. The results of this study showed that multiple-embryo transfer was a risk factor associated with increased incidence of HP ( OR 0.300,95% CI 0.092–0.983; P = 0.037). This finding confirms and expands that of a previous study which believed that the diagnosis of HP must be considered in patients with two or more embryos transferred in a cycle . Therefore, selective single-embryo transfer probably is a preferred choice for a decreased risk of HP. Overall, in the present study, we found some factors from the cause of infertility, specific characteristics of IVF and embryo-transfer techniques which increased the risk of HP following embryo transfer. Patients treated with IVF-ET should have more frequent ultrasound examinations early in pregnancy, for delay in diagnosis of HP is more common than ectopic pregnancy. Therefore, it’s important to increase clinicians’ awareness of HP though an intrauterine pregnancy is present, especially in patients with risk factors given above.
Surgery is still the most frequently chosen method of treatment with HP. The surgical approaches are laparotomy and laparoscopy. The efficacy and safety of laparoscopic surgery during pregnancy is well certificated. It shows superiority over laparotomy approaches in postoperative recovery and subsequent reproductive outcomes . In the present study, 20 (80%) patients were treated by laparoscopy. The surgical procedures were slightly modified, avoiding both excessive manipulation and cannulation due to co-exsistance of the gestational sac in uterine. Among the 25 patients, 24 (96%) underwent salpingectomy. A possible explanation is that, compared with salpingostomy, salpingectomy gives the competitive advantages of shortening the operation time, decreasing rates of persistent trophoblast, reducing intraoperative stimulation of uterine and avoiding the possibility of another ectopic pregnancy. For the patients urgently needing a child, salpingectomy was acceptable if compensated by a higher survival rate of the intrauterine pregnancy following surgical treatment.
In the present study, the survival factors of intrauterine pregnancy following surgical treatment of HP were analyzed. We found that shorter operative duration, smaller size of the ectopic mass were associated with more chance to survive for the coexistent intrauterine pregnancy, and the prognosis would be better if ectopic pregnancies were in the ampulla of fallopian tube. As noted above, the factors are somewhat interrelated: a smaller size and ampulla located pregnancy involves a more simple surgical procedure and shorter duration of operation (salpingectomy), less manipulation of the uterus and surgical complications, which are key points for a better reproductive outcome. This finding is consistent with previous research , which suggests that salpingectomy may be a preferred choice in women with HP following IVF-embryo transfer.
In the current study, 3 patients had severe abdominal pain and massive pelvic hemorrhage due to tubal rupture. As a result, only one of them (33.3%) had the chance for an ongoing pregnancy after emergency surgery. Delayed diagnosis of HP in patients with a visible intrauterine pregnancy is life-threatening. It must be emphasized that for women treated with IVF-ET, even if an intrauterine gestational sac is confirmed, a high index of suspicion for HP is required, especially for these high-risk patients.