Lisa Caronia1 , Rebecca Flyckt1 and Tommaso Falcone1
Cleveland Clinic, Cleveland, OH, USA
Lisa Caronia (Corresponding author)
Ectopic pregnancyIVFAssisted reproductive technology
A 38-year-old primigravida with a 2-year history of primary infertility presented for her first pregnancy ultrasound after in vitro fertilization (IVF) with day 5 embryo transfer (ET). The patient had a history of tubal factor infertility secondary to endometriosis, with left tubal obstruction identified on the initial hysterosalpingogram. She underwent laparoscopic left salpingolysis with hysteroscopic left tubal cannulation and chromopertubation 4 months earlier. Her IVF cycle was uncomplicated and two embryos were transferred on day 5 of development. Two weeks later, she had a positive pregnancy test with serum human chorionic gonadotropin (hCG) of 1238 mU/mL. A second hCG level measured 1 week later was 9870 mU/mL. The patient was scheduled for an ultrasound at 7 weeks gestational age, correlating with approximately 4 weeks after IVF-ET. A transvaginal ultrasound (TVUS) revealed a singleton intrauterine pregnancy, as well as an extrauterine gestational sac with a fetal pole in the left adnexa. The patient’s infertility doctor was notified of the abnormal pregnancy and a decision was made to proceed with laparoscopic removal of the tubal pregnancy .
Diagnosis and Assessment
Our patient has multiple factors which increase the risk of ectopic pregnancy, including history of infertility, tubal surgery, and advancing age. In one study, the authors reported that the risk of ectopic pregnancy among infertile women was double than that in fertile women . Tubal factor infertility, as in this patient’s history, is a predominant risk factor. It could be due to pelvic inflammatory disease, abnormal tubal anatomy, or damage from a previous ectopic pregnancy or surgery. These factors affect the ability of an embryo to successfully migrate to the uterus, increasing the risk of extrauterine implantation. Pregnancies as a result of ovulation-inducing therapies are also associated with increased risk of ectopic pregnancy . It is possible that it is due to changes in tubal transport function; however, multiple confounding variables make a true association difficult to establish. IVF has also been associated with an increased risk of ectopic pregnancy.
The incidence of ectopic pregnancy after IVF was previously reported to be 2–11 %. Recent studies show that the rate is much lower (0.7 %) [1, 3]. Perhaps, it is related to improvements in many aspects of IVF techniques, including ET under ultrasound guidance, practice catheterization, utilization of minimal transfer media, and avoidance of deep catheter insertion. Recent research has also demonstrated that the incidence of ectopic pregnancy is no different in fresh versus frozen IVF-ET cycles, as well as with donor eggs versus standard IVF [4, 5]. Tubal surgery can have a dichotomous impact on ectopic pregnancy occurrence; although tubal surgery is a known risk factor for ectopic, in some cases, tubal surgery may actually help to reduce ectopic risk (e.g., in patients who have a hydrosalpinx removed or a damaged tube repaired or freed from adhesions). Lastly, the risk of ectopic pregnancy progressively increases as women age, with a significantly higher incidence of extrauterine pregnancy in women more than 35 years of age as compared to their younger counterparts .
In fertility population, close monitoring with serial hCG levels and TVUS is standard and can help to detect ectopic pregnancy at an early stage. However, early monitoring increases the likelihood of an initial pregnancy of unknown location diagnosis, which can make proper management decisions challenging. With assisted reproductive technologies (ART) and the increased prevalence of multiple gestations, serial hCG levels may be less helpful, as early rises in hCG measurements may not follow accepted norms.
Heterotopic pregnancy, which classically occurs in 1/30,000 pregnancies , is now on the rise due to the increased use of ART. Current estimates of heterotopic pregnancy are 1 per 4000 pregnancies and can be as high as 1 per 100 to 1 per 1000 pregnancies in women undergoing ovulation induction or IVF [8–10]. Similar to ectopic pregnancy, TVUS has a high sensitivity for heterotopic diagnosis after IVF-ET when performed by an experienced ultrasonographer. Even after seeing an intrauterine pregnancy, one should always examine the adnexas carefully, especially in IVF pregnancy.
The general management principles for ectopic pregnancy also apply to ectopic pregnancy after IVF . However, in the presence of an intrauterine pregnancy, practitioners should choose the treatment for the extrauterine gestation that will pose the least risk to the developing intrauterine fetus. Expectant management is not a feasible strategy, given the inability to reliably monitor with serial hCG levels and TVUS. Methotrexate is not a suitable therapy, as it would be toxic to the viable intrauterine pregnancy. Ultrasound-guided local injection of either hyperosmolar glucose or potassium chloride is an alternative to surgery. There are also several reports in the literature of successful TVUS-guided aspiration of gestational sac content before injection of those agents . This procedure can be performed in the outpatient setting and is of low risk to the concurrent intrauterine pregnancy. It is important to note that local injection of methotrexate is not a suitable agent for heterotopic pregnancy, as it maintains systemic effects . The treatment of choice is laparoscopy with salpingectomy or salpingostomy. It is efficacious and can also be used for patients with hemodynamic instability or signs of tubal rupture . Laparoscopy permits evacuation of the extrauterine pregnancy without disturbing the intrauterine pregnancy. Salpingostomy can be performed for an unruptured ampullary ectopic, whereas salpingectomy may be more suitable if extensive damage of the involved tube is identified intraoperatively and there is a relatively normal-appearing contralateral fallopian tube. Proper preoperative counseling with patients regarding possible intraoperative scenarios is imperative.
The patient underwent a successful laparoscopic salpingostomy without complications. Subsequently, she delivered a full-term male infant by cesarean section . The tubes appeared to be normal at surgery. A hysterosalpingogram 1 year after her delivery was normal, with bilateral spill of contrast material into the abdominal cavity. She then conceived spontaneously 18 months after the birth of her son, delivered at term by repeat cesarean section.
· Infertility, especially tubal factor infertility, is associated with increased risk of ectopic pregnancy.
· Ectopic pregnancy rates are now estimated to be at 0.7 % of all pregnancies achieved through IVF, likely related to improved ET techniques.
· TVUS has a high sensitivity for the diagnosis of ectopic after IVF-ET. Due to the increased risk of multiple pregnancies with ART, serial hCG alone may be difficult to interpret.
· Management strategies of heterotopic pregnancy include laparoscopy as well as ultrasound- guided local injection of hyperosmolar glucose or potassium chloride. Decisions for management should be made on individualized basis dependent upon the clinical context (Fig. 4.1).
Tubal ectopic pregnancy.
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