Tubal passage control after methotrexate treatment in ectopic pregnancies

J Clin Exp Invest www.clinexpinvest.org Vol 2, No 4, December 2011 Yazışma Adresi /Correspondence: Dr. Neval Yaman Görük Ümraniye Eğit. ve Araş. Hast. Kadın Hast. ve Doğum Kliniği, Ümraniye, İstanbul E-mail: neval-yaman81@hotmail.com Geliş Tarihi / Received: 15.10.2011, Kabul Tarihi / Accepted: 04.12.2011 Copyright © Klinik ve Deneysel Araştırmalar Dergisi 2011, Her hakkı saklıdır / All rights reserved Klinik ve Deneysel Araştırmalar Dergisi / 2011; 2 (4): 400-403 Journal of Clinical and Experimental Investigations doi: 10.5799/ahinjs.01.2011.04.0080


INTRODUCTION
The ectopic pregnancy is defined as the settlement of fertilized ovum outside the uterus, frequently at fallopian tubes. 1 Together with the fact that abnormal localization is at fallopian tube at 90%, more rarely abdominal, cervical, ovarian, interstitial, in-traligamentous, heterotopic, multiple ectopic pregnancies can be observed. 2The ectopic pregnancy is an important reason for maternal mortality and morbidity.However, by early establishment of ectopic pregnancy diagnosis with the help of contemporary diagnostic methods, the treatment modalities which are more conservative than before can be applied.
For this aim, the more frequently used agent has become methotrexate (MTX).As the experiences obtained with the medical treatment flourish, single dose treatment regimens have appeared for simplifying the treatment, increasing the harmony, decreasing the side effects and costs. 3e reproductive result after the ectopic pregnancy is generally evaluated with the determination of tubal opening with histerosalpingography (HSG), future pregnancy and ectopic pregnancy's relapse rate.In this study, the ipsilateral tubal passage control has been done in cases treated with MTX, and their results have been evaluated.

Totally 30 cases which have been given medical treatment due to ectopic pregnancy diagnosis in a
Training and Research Hospital Clinic of Obstetrics and Gynecology have been included to study content.To the patients, the ectopic pregnancy diagnosis has been established by applying anamnesis, gynecological examination, physical examination, pregnancy test, ultrasonography (USG) and dilatation and curettage (D&C).All patients have been informed about their statuses, the risks that they have been told.To the patients in which findings in favors of rupture has not been determined and which have been stabile hemodynamically, the information on the treatment protocol has been given and their consents have been obtained and single dose MTX treatment has been started.From all patients, before starting the treatment, serum BhCG, full blood count, kidney and liver function tests have been requested.The serum beta human chorionic gonadotropin values and USG findings have been recorded.Then, MTX 50 mg/ m 2 dose has been made as i.m.At the 4 th day of the treatment, the serum BhCG values have been repeated.The increases in the serum BhCG concentration between the 1 st and 4 th days have been accepted as normal.Between the 4 th and 7 th day, in the patients in whose serum BhCG concentration there is 15% decrease, the single dose MTX treatment has been accepted as adequate.Then, till the levels have become indeterminable, the weekly BhCG follow-ups have been realized.However, to the patients in which any increase in the serum BhCG concentration after this or a decrease under 15% at the 7 th day, the treatment protocol has been repeated.
The patients benefiting from the MTX treatment have been called for control after 6 months after their serum BhCG levels have reached to negative values.The gynaecological examination and transvaginal USG have been realized.Their USG findings have been recorded.The patients requesting the evaluation of the oviducts opening at the side where the ectopic pregnancy develops have been informed about this issue.In the direction of the patients' preferences, the ipsilateral tubal passage controls have been made in 18 of them with diagnostic laparoscopy and in 9 of them with HSG.
When HSG is imaged, 10ml iodine has been given inside from cervix with hysterography tool in a way not passing the pressure of 180 mm Hg to the patient in dorsolithotomy position in the sterile environment.Meanwhile, the patient has been brought to the neutral position, two units of spot film have been imaged, and the tubal opening has been controlled.
To the cases to which the diagnostic laparoscopy will be applied, information regarding the interventions to be applied and their complications have been given and their approvals have been obtained.The cases have been given the dorsolithotomy position under the general anaesthesia and the bladder has been emptied with sterile foley catheter.The venter dermis, vulva and vagina have been cleaned with povidone iodine.The uterus elevator has been placed to cervix.The verres injection has been entered while the patients have been at neutral position.After the confirmation of peritoneal entrance, the abdomen has been inflated with carbon dioxide gas till the pressure of 15 mmHg.After the trochar insertion, the patient has been brought to trendelenburg position and the operation has been started.Uterus, oviducts, ovaries has been panoramically evaluated.50 ml methylene blue has been given inside from cervix with rubin tube placed as transvaginal and it has been observed whether transmission from oviducts is available or not.
The treatment results of these patients whose tubal opening control has been realized with diagnostic laparoscopy and HSG have been examined and evaluated prospectively.

Statistical analysis
For statistical analyses, NCSS (

RESULTS
The average age of the cases was 30.63±4.36 years.Twelve of the cases (40%) have experienced surgery previously.While 20 of the cases (66.7%) have not used contraception method, 6 of the cases (20%) use intrauterine device, 2 of the cases (6.7%) use tubal ligation and 1 of the cases (3.3%) uses depo-provera and oral contraceptives.
As the cases' BhCG levels change between 160 IU/L and 10910 IU/L, its average is 2387±2500 IU/L.As the MTX doses that they have used change between 50 mg and 100 mg, its average is 67.7±13.5 mg.
While the bulk dimension of 6 of the cases (20%) is below 4 cm, 24 of them (80%) is between 4 cm and 5.5 cm.Four of the cases (13.3%) received additional dose MTX.No significant difference was found in BhCG levels of the cases who received additional dose MTX and who not received (p>0.05).Also no significant relationship was found between additional MTX treatment and bulk dimension (p>0.05)(Table1).It has been found that tubal passage of 22 of 27 cases (81.5%) was open while tubal passage control was performed and 5 of them (18.5%) were closed.No significant difference was found in BhCG levels of the cases with open or closed tubal passage (p>0.05).Also, there was no significant relationship between tubal passage opening and bulk dimension (p>0.05)(Table 2).

DISCUSSION
In the past ten years, the ectopic pregnancy incidence has increased dramatically.The increase in the sexual inherited disease risk, ovulation induction, assisted reproductive techniques, tubal sterilization and more accurate diagnosis methods used in the diagnosis make think that the ectopic pregnancy incidence increases in fact. 4e anamnesis and physical examination determine the patients under risk and increase the possibility of determining the non-ruptured ectopic pregnancies.In the normal pregnancies, when Transvaginal USG and b-HCG levels go over 1000-1500 IU/L, gestational sac can be observed. 5In 90% of the ectopic pregnancies, the evidences regarding the extrauterine pregnancy can be determined.The determination of yolk salk, embryo, cardiac activity together with a gestational sac outside uterus make the establishment of ectopic pregnancy diagnosis and require emergency action. 6ovall et al. have published the results of MTX treatment in 100 patients and 50 of the 100 cases had diagnosis with laparoscopy and 50 of them with non-laparoscopy algorithm.Full resolution has realized in 96 patients between 14-92 days.In four patients, due to tubal rupture, laparotomy has been required; in one case, at a late period such as 23 rd day of the MTX application, a rupture has occurred.In five patients, fetal cardiac activity has been observed and in all of these, the treatment has become successful.In 49 of 58 patients (84%) to whom the HSG is applied in the advanced followup, it has been shown that the ipsilateral oviducts are open. 7 study of Hajenius et al. have reported single sided tubal opening rate after the medical treatment of the ectopic pregnancy has been compared with the conservative laparoscopic treatment.The tubal opening rate at the ipsilateral side after medical treatment has been similar to the conservative laparoscopic treatment (linear salpingotomy) and between 60%-85%. 8ito et al. have evaluated tubal transmission prospectively with HSG in the ectopic pregnancy cases to which conservative method has been applied as a follow-up or methotrexate treatment in 2005.It has been found that the cases having starting BhCG value>5000 IU/L have 12 times more risk for oviducts obstruction.However, no relation has been determined between the obstruction and ectopic pregnancy bulk size. 9 this study, 6 months after the medical treatment, in 27 cases, tubal opening control has been made.It has been researched whether ipsilateral oviducts are open or not with HSG.In a similar way to the rates in the literature, it has been found that 22 of the cases (81.5%) has open similar sided oviducts and 5 of them (18.5%) has been closed.Between serum BhCG levels of the cases with open tubal passage and the cases with closed ones when they get diagnosis, a statistically significant difference was not found (Table 2).However, while the average BhCG value of the cases whose ipsilateral tubal passages are observed open is 922 IU/ ml, the average BhCG value has been found as 4354 IU/ ml in the cases whose similar sided tubal passages are closed.We think, if the patient number being increased, a statistically significant difference can be obtained.
In conclusion, it has been suggested that, the aim at the ectopic pregnancy treatment is to pro-tect the fertility rather than saving life.With this aim, MTX has been researched very commonly and it is at the first rank among the methods, which are alternative to the surgery treatment.The medical treatment decreases the morbidity belonging to the anaesthesia and surgery.The success rate and the future reproduction performance are similar to the ones to whom the surgery treatment has been applied.
Software (Utah, USA) program has been used.While evaluating the study data, in addition to the descriptive statistical methods (Mean, Standard deviation, frequency), Mann Whitney U test of the quantitative data has been used.In the comparison of the qualitative data, Fisher's Exact Chi-Square test has been used.The statistically significance has been accepted at the level of p<0.05.

Table 1 .
Dilatation and curettage, bulk size, additional treatment, laparotomy and tubal passage control

Table 2 .
The evaluation of tubal passage control