**4. Discussion**

The treatment of EP with MTX was established in the late 1980s and has become an alternative to surgical intervention. Recently, cost-effectiveness analysis has put a priority on the patient's subsequent fertility, rather than on detection and/or complication rates, as previously reported (7-9). Effort should be made to confirm the diagnosis of ectopic pregnancy definitively before starting MTX treatment; otherwise, complication rates or costs could rise on the contrary. Seror et al reported that MTX treatment appeared to be costeffective in EP cases where the preservation of fertility was important (10). About 40% of women with ectopic pregnancy are treated medically (11), and 90% of them are successfully treated without any surgical intervention at all (12). Medical treatment can be carried out on an outpatient basis, thus making MTX cheaper than the cost of surgical treatment. Surgical intervention is generally adopted when a high possibility of failure and a prolonged time of resolution is predicted. A particularly high serum hCG level or the presence of fetal heart movement results in medical treatment (13).

It is actually difficult to diagnose interstitial pregnancy correctly because of the slight difference between cornual implantation and interstitial pregnancy. Cornual implantation is usually identified in the upper and lateral uterine cavity, whereas interstitial ectopic pregnancy is within the proximal intramural portion of the tube. Therefore, the accurate diagnosis of an interstitial pregnancy requires precise ultrasound imaging (14). Two regimens are commonly used for the administration of MTX (15) (Table 3). The first contains the administration of MTX and leucovorin on alternate days until beta-hCG concentrations begin to drop. This regimen has a success rate of 93%. The second regimen involves the administration of a single dose of MTX, followed by repeated doses every week if beta-hCG concentrations do not fall by 15% within days 4 and 7. It has been reported that at least 13% of women require two doses, and 1% need more than two; however, more than 90% of women who need a second administration avoid surgical intervention (12). The initial level of hCG is the best prognostic indicator of the need for MTX; however, it is still controversial as to what IU should be the cut-point in deciding whether the administration of MTX is necessary. Lipscomb et al. reported that 94% of 350 women whose initial hCG was less than 10,000 IU/ml had success with MTX treatment, therefore suggesting that an initial hCG level greater than 10,000 IU/ml was a factor in the failure of the treatment (12). On the other hand, Gamzu et al. stated that the cut-point to determine the effectiveness of MTX should be lowered to between 2000 mIU/ml and 3000 mIU/ml (16). The hCG incremental rate both before and after MTX represents an independent risk factor for subsequent tubal rupture. Pre-diagnosis concentrations of hCG which increase at least 66% over 48 hours, followed by persistently rising hCG concentrations after treatment with MTX, may lower the threshold for surgical intervention (17).

It is widely accepted that above the discriminatory zone of 1,500 IU/l-2500 IU/l, a normal intrauterine pregnancy (IUP) should be visible via TVU. At our clinic, we consider an initial hCG greater than 1500 IU/ml and an invisible GS clear indicators of a possible ectopic pregnancy, and an elevation of hCG greater than 1.5 times in 48 hours without GS confirms the diagnosis. Orivieto et al. reported that single-dose MTX treatment for EP does not have a negative effect on ovarian function nor on the outcome of following IVF-ICSI (18). Paul et al. reported that when hCG is >4000 IU/ml, the failure rate of MTX treatment is 65% (17). In this study, the MTX-failure rate of 14 cases where initial hCG was >5000 IU/ml was 7.1% (1/14); however, the failure rate of low hCG cases <5000 IU/ml was 16.6%. In tubal pregnancy, EP become less vascularized as it invades the tubal serosa, and tubal rupture is likely to occur, compared with that in interstitial pregnancy, before MTX treatment can solve the EP. Compared with cases of tubal pregnancy, the difficulty in diagnosing interstitial pregnancy is thought to be the reason why hCG levels are higher at the time of confirming the diagnosis. However, in our study, 14 cases consisted of 7 ampullary, 6 interstitial and one cervical pregnancy, indicating that tubal pregnancy does not always rupture in high-hCG cases. Therefore, more study is necessary to determine the cut-off for MTX treatment.

Recently the cost-effectiveness of treatment has been considered in attempts to save on health insurance costs. Seror reported that, although frequent diagnostic ultrasound is necessary, MTX is cost-effective compared with surgical intervention (10). However, subsequent pregnancies should be followed with extreme caution, and elective cesarean section should be considered as an alternative.

In conclusion, a serum hCG level greater than 5,000 IU/ml is not necessarily resistant to MTX treatment, and interstitial pregnancy is a particularly good candidate for conservative treatment, even if initial hCG is higher than 5,000 IU/ml. However, MTX failure and tubal rupture was identified irrespective of an initial hCG level of 800 IU/ml in tubal pregnancy. Emergent access to surgical intervention must be made available. As well, the patient's awareness of risk and her availability for admission and surgery are equally important. Therefore, preparation for surgical intervention for emergent situations, even after conservative treatment is determined, is essential.

### **5. References**

214 Ectopic Pregnancy – Modern Diagnosis and Management

The treatment of EP with MTX was established in the late 1980s and has become an alternative to surgical intervention. Recently, cost-effectiveness analysis has put a priority on the patient's subsequent fertility, rather than on detection and/or complication rates, as previously reported (7-9). Effort should be made to confirm the diagnosis of ectopic pregnancy definitively before starting MTX treatment; otherwise, complication rates or costs could rise on the contrary. Seror et al reported that MTX treatment appeared to be costeffective in EP cases where the preservation of fertility was important (10). About 40% of women with ectopic pregnancy are treated medically (11), and 90% of them are successfully treated without any surgical intervention at all (12). Medical treatment can be carried out on an outpatient basis, thus making MTX cheaper than the cost of surgical treatment. Surgical intervention is generally adopted when a high possibility of failure and a prolonged time of resolution is predicted. A particularly high serum hCG level or the presence of fetal heart

It is actually difficult to diagnose interstitial pregnancy correctly because of the slight difference between cornual implantation and interstitial pregnancy. Cornual implantation is usually identified in the upper and lateral uterine cavity, whereas interstitial ectopic pregnancy is within the proximal intramural portion of the tube. Therefore, the accurate diagnosis of an interstitial pregnancy requires precise ultrasound imaging (14). Two regimens are commonly used for the administration of MTX (15) (Table 3). The first contains the administration of MTX and leucovorin on alternate days until beta-hCG concentrations begin to drop. This regimen has a success rate of 93%. The second regimen involves the administration of a single dose of MTX, followed by repeated doses every week if beta-hCG concentrations do not fall by 15% within days 4 and 7. It has been reported that at least 13% of women require two doses, and 1% need more than two; however, more than 90% of

Fig. 3. Time-course of serum hCG level in Case II

movement results in medical treatment (13).

**4. Discussion** 

[1] Satoe Fujiwara, Yoshiki Yamashita, Sachiko Kawabe, Hideki Kamegai, Yoshito Terai, Masahide Ohmichi. A case of a methotrexate-resistant ectopic pregnancy in which

**13** 

*Taiwan* 

**The Treatment of Ectopic Pregnancy with** 

**Laparoscopy-Assisted Local Injection of** 

*1Department of Obstetrics and Gynecology, Taipei Medical University* 

*2Department of Obstetrics and Gynecology, Taipei Veterans General* 

*3Graduate Institute of Medical Sciences, Taipei Medical University, Taipei* 

Ching-Hui Chen1, Peng-Hui Wang2, Li-Hsuan Chiu3 and Wei-Min Liu1\*

Laparoscopy-assisted local injection of chemotherapeutic agents is not yet considered as a standard treatment for ectopic pregnancy. Herein, we demonstrated cases of cesarean scar pregnancy and ovarian ectopic pregnancy successfully treated with trans-vaginal sonography-guided local injection of etoposide. Furthermore, we evaluated the efficacy of laparoscopic local injection of etoposide compared with methotrexate on tubal pregnancy treatment. With the aid of laparoscopic injection, local etoposide treatment offers a precise localization and minimally invasive approach to the management of ectopic pregnancies. Compared to the conventional way to treat ectopic pregnancy using methotrexate, local injection of etoposide is considered to be a high-success rate, low-risk, and less-limitation

option for such types of ectopic pregnancies with careful selection of cases.

ectopic pregnancy (Lurie, 1992; Te Linde, Rock, & Thompson, 1997).

**2. Current opinion and therapeutic strategy on ectopic pregnancies** 

Ectopic pregnancy is a complication of pregnancy in which the fetus implants outside the endometrial cavity, which ultimately ends in death of the fetus. It constitutes 1.6% of all pregnancies (Lurie, 1992). Most ectopic pregnancies are located in the fallopian tube, but the implantation can also occur in the cervix, ovaries, abdomen, and even cesarean scars. Ectopic pregnancy is usually not viable. If left untreated, half of ectopic pregnancies will resolve without treatment and presents as the tubal abortions. Ectopic pregnancies are considered as a dangerous health problem for women of childbearing age because of the internal bleeding as a common complication. In fact, maternal mortality is 0.14% in cases of

Within various forms of ectopic pregnancies, cesarean scar pregnancy is a rare form of ectopic implantation. The pathogenesis is thought to be a normal fertilization followed by implantation at the ecchymotic lesion site which is bulging from the uterine wall at the

**1. Introduction** 

 \*

Corresponding Author

**Chemotherapeutic Agents** 

*Hospital and Taipei Medical University, Taipei* 

*Hospital and National Yang-Ming University, Taipei* 

dactinomycin was effective as a second-line chemotherapy. Fertil Steril 2009;91:929. e13-15.

