Heterotopic pregnancy (HP) is defined as a pregnancy in which one or more embryos is viably implanted in the uterus while the other is implanted elsewhere as an ectopic pregnancy. The frequency of such occurrence is about 1 in 30 000. However, with the increased use of assisted reproductive technology, the rate of occurrence rises to approximately 1 in 100 pregnancies. Interstitial pregnancy, with the incidence of 2%-4% of ectopic pregnancies is one of various difficult situations associated with assisted reproductive technology. Due to the relative rarity of interstitial pregnancy and usually insufficient experience of the operator in the management of interstitial pregnancy, the optimal medical or surgical treatment can be a difficult choice, especially when a live intrauterine fetus coexists.
The traditional treatment for interstitial pregnancy was cornual resection by laparotomy or hysterectomy.1 However, the surgery destroys the integrity of the uterus and affects the result of pregnancy, possibly causing uterine rupture. When coexisting with intrauterine pregnancy, anesthesia and surgery can adversely affect the intrauterine pregnancy. Especially for women who conceived via in vitro fertilization and embryo transfer (IVF-ET), conservative treatment is more desirable. Since the late 1990s, ultrasound-guided transvaginal instillations of methotrexate (MTX), potassium chloride (KC1) and hyperosmolar glucose have been used as a new medical treatment.2 Many studies have reported the successive usage of local aspiration and injection in heterotopic pregnancy.3,4 Although this approach has caused concern due to the highly vascularized tissue involved, as well as the size and activity of the pregnancy, the success rates were high and systemic side effects and complication rates were low.
Since the rupture of interstitial pregnancy can cause fatal intra-abdominal hemorrhage, observation of post-operative complications, assessment of aspiration results, and determination of transfer time to laparoscopic surgery are all very important. However, the assessment of the aspiration efficiency is more difficult due to the complicating intrauterine pregnancy. Serial-hCG level measurements are not useful aids due to the concomitant intrauterine pregnancy (IUP).5 Therefore, ultrasonography should replace serial HCG as the effective tool for assessing the mass in the interstitial portion of oviduct. Due to the rare cases of heterotopic pregnancies, the frequency of changes in the interstitial mass and residual tissue in ultrasound is still unclear. Assessing aspiration results and determining the time to transfer to laparoscopic surgery are both pressing concerns.
We retrospectively evaluated the efficacy of transvaginal ultrasound-guided local aspiration and hyperosmolar glucose instillation in treating five cases of live interstitial pregnancies complicated with live intrauterine pregnancies after IVF-ET. In addition, we carefully observed the changes of the interstitial masses, which we hope will provide insight for similar conditions.
We retrospectively reviewed five live ectopic pregnancies located in the interstitial portion of the fallopian tube, complicated with live intrauterine pregnancies. These cases were treated with aspiration and instillation of hyperosmolar glucose under transvaginal ultrasound-guidance at our center between January 1, 2008 and May 30, 2011. All five cases conceived through IVF-ET. The diagnosis of an interstitial pregnancy is made by visualization of the interstitial line adjoining the gestational sac and the lateral aspect of the uterine cavity and continuation of the myometrial mantle around the ectopic sac with the presence of a bud and cardiac activity.
With the preparation of laparoscopy, the patient was put in a dorso-lithotomy position and a transvaginal ultrasound was performed again to confirm the diagnosis of interstitial pregnancy. A 16G double-lumen needle first penetrated through the myometrium, then entered the interstitial pregnancy sac. Next, aspirate the gemmule embryos and cyst fluid by squirt. Lastly, the position of the needle was adjusted and 0.0015-0.002 L of hyperosmolar glucose was injected into chorionic villi. At the same time, KCl was prepared. If the gemmule embryos cannot be aspirated completely, we suggest inject KCl locally. After a 5-10 minutes observation, we checked the pelvis once again to ensure there was no active bleeding. After the operation, three days of prophylactic antibiotics and five to seven days of luteal supplementation were given to the patients.
In the first two cases, after the aspiration, an ultrasound examination was performed every week for the first month. After one month, the ultrasound examination was done four weeks later. During the routine prenatal check-up at twenty to twenty-two weeks of pregnancy, the ultrasound scans the baby as well as the interstitial mass. In the other three patients, ultrasound examination was performed every week in the first two weeks after aspiration to confirm whether the cardiac activity continued. During the first two weeks, we found that the mass kept growing but without a yolk sac. We did nothing for this and just repeated the ultrasound at 10th to 12th, 20th to 22th, and 30th weeks of pregnancy as a routine prenatal check-up.
At the same time, we thoroughly informed the patients and their families of the risk of conservative treatment and the potential complications, such as intra-abdominal hemorrhage and death. We also recommended family members to stay with the patient every hour of the day and informed associated medical staff to open “green channel” for those who suffered from acute abdominal pain.
Gemmule embryos in all 5 cases were aspirated successfully and there was no abdominal hemorrhage, threatened abortion or infection in any of the cases. All the surgeries were performed during 6+5 to 7+4 weeks of pregnancy. The sac of interstitial pregnancy continued to progress after aspiration and stopped growing between 11 to 20 weeks. The bigger diameter of the gestational sac before aspiration was from 0.007 m to 0.025 m. The biggest diameter of the sac after aspiration was from 0.02 to 0.046 cm. By the 30th week of pregnancy, 80% of the interstitial masses had disappeared (Table 1). Four cases have delivered and one is still in on-going pregnancy. All of the four cases underwent cesarean section and there were nothing special detected in the corner of the uterus. In the following section, two cases are presented as examples.
A 29-year-old primigravid woman was admitted to our institution complaining about primary infertility for seven years with a history of tubal adhesiolysis. Frozen embryo transfer (FET) of three embryos was conducted on January 21st, 2008. The serum hCG level was 9000 IU /L (21 days after ET). The B-US (30 days after ET) showed: two intrauterine gestational sacs with positive fetal cardiac activity and a 0.007 m×0.009 m gestational sac with yolk sac and fetal cardiac activity present in the right interstitial part of the fallopian tube. The CRL of the interstitial sac was 0.0061 m and the surrounding blood flow was abundant (Figure 1). Transvaginal ultrasound-guided aspiration of interstitial pregnancy and instillation of 0.0015 L hyperosmolar glucose were performed five days later. The “residual sac” appeared again on ultrasound examination one week after the operation. However, there was no sign of positive fetal cardiac activity or yolk sac (Figure 2). The residual sac grew to its largest size (0.0457 m×0.0364 m) twelve weeks after the operation and subsequently stopped expanding (Figure 3). It then became smaller (0.0406 m × 0.0298 m) fourteen weeks after the operation (Figure 4). The patient delivered her twins successfully through cesarean section after 35 weeks.
A 27 years old primigravid woman presented at our institution with a six-year history of infertility problems. Fresh embryo transfer of two embryos was conducted on October 9th, 2010, and the serum hCG level was 1083U/L (14 days after ET). In addition, B-US (30 days after ET) showed one intrauterine gestational sac with positive fetal cardiac activity and a 0.027 × 0.025 m mass in the right interstitial region with cardiac activity and a CRL of 0.007 m. Transvaginal ultrasound-guided aspiration of interstitial pregnancy and instillation of 0.002 L hyperosmolar glucose (using a 16G needle) were performed. Seventeen weeks after the treatment, ultrasound examination showed the residual interstitial mass, though the yolk sac and cardiac activity were mot detected. The patient delivered a healthy baby successfully after 37 weeks.
With the wide use of assisted reproductive technology, the incidence of serial multiple-pregnancies and heterotopic pregnancies has increased dramatically, presenting a new challenge to clinicians. High-resolution transvaginal ultrasound and multi-Pollock's application of color Doppler ultrasound have made early diagnosis of uncommon ectopic pregnancy possible. Guirgis and Craft recommended arranging a routine high-resolution transvaginal ultrasound between 4-6 weeks after ET, which could lead to an earlier diagnosis of ectopic pregnancy.6 On account of the early detection of heterotopic pregnancy by ultrasound in the 6+5 to 7+4 weeks of pregnancy, all of the five gemmule embryos in these cases were aspirated completely, which relates to the good prognosis.
Transvaginal ultrasound-guided fetocide involves transvaginal ultrasound -guided aspiration of the contents in the gestational sac of the ectopic pregnancy and injections of drugs to inhibit the growth of trophoblastic cells. Since the trophoblastic cells are mainly imbedded in the fibrous tissue, it is favorable to slowly and completely absorb the fluid in the gestational sac, and then inject the drugs in villi tissue. 16G-17G double-lumen needles can be used for ectopic pregnancies of about five to seven gestational weeks.
Transvaginal ultrasound-guided fetocide in treating ectopic pregnancy has a long history. Aspiration itself can cause hemorrhage and result in transferring to laparoscopy or laparotomy. We met one case of simple interstitial pregnancy treated by aspiration and severe intra-abdominal hemorrhage resulted, leading to immediate transfer to laparoscopy. In this situation, we found that the needle penetrating through the myometrium can dramatically decrease the risk of hemorrhage. Thus, we only use this technique in cases where the gestational sac is near to the myometrium and the needle can penetrate through the myometrium. Fortunately, none of the cases discussed in this study experienced internal hemorrhage. We believe that this may be due to the fact that the needle induced the muscle fibers to contract and aided in stopping the bleeding. We also found that when there is a muscle layer covering the mass, there is less opportunity of interstitial mass rupture. At the same time, strict aseptic technique and prophylactic antibiotics for three days can decrease the risk of infection and increase the success rate of conservative treatment.
The selection of the drugs for local administration is crucial as well. MTX, prostaglandins, KCl, and hyperosmolar glucose can all be injected locally.7–9 Some authors have reported having no consequent congenital abnormality when they used a small dose of MTX or mixture of MTX and KCl to deal with HP coexisting with intrauterine pregnancy. However, MTX still should not be used in a heterotopic pregnancy because of possible fetal malformation.10 KCI has always been used as a fetocite for multiple-pregnancy. When embryo aspiration fails, injection of KCl can be a good choice. Since there are no cases of aspiration failure in our experiment, the efficiency and security of this method still needs to be determined.
Hyperosmolar glucose helps local dehydration, necrosis of the trophoblastic tissue and resolution of the tubal pregnancy, but does not cause possible fetal malformation. The doses of hyperosmolar glucose need to be carefully considered. High doses will increase the risk of bleeding since the surrounding blood supply of the interstitial part is very rich. In our cases, 0.0015-0.002 L of hyperosmolar glucose was injected locally.
In one of the cases, the bigger diameter of the sac after aspiration was 0.046 m. The size led doctors to be concerned about mass rupture and suggest transfer to surgery. However, the patient refused surgery because of the high risk of abortion associated with surgery in intrauterine twin pregnancies. Fortunately, after 19+3 weeks the sac began to shrink. We suggest that for gemmule embryos that are completely aspirated, if there is no clinical symptom of abdominal pain, ultrasound examination should be performed every week in the first two weeks and then repeated in10th to 12th, 20th to 22th, and 30th weeks of pregnancy along with a routine prenatal check-up. If the patient suffers sudden acute abdominal pain, aggressive surgical intervention should be adopted. At the same time, we must thoroughly inform the patients and their families of the risk of conservative treatment and advise family members to be present for every hour of the day. For those who suffered from acute abdominal pain, the “green channel” was opened for emergency.
After a thorough analysis of these cases, we found that local aspiration and instillation may be an effective method in dealing with live interstitial pregnancy coexisting with a live intrauterine pregnancy. However, more cases are necessary to validate these findings and to prove the security and efficiency of local instillation of hyperosmolar glucose in the treatment of live interstitial pregnancy complicated with live intrauterine pregnancy after IVF-ET.
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Keywords:© 2012 Chinese Medical Association
interstitial pregnancy; heterotopic pregnancy; fetocide; in vitro fertilization; transvaginal ultrasound-guided aspiration