Methotrexate treatment in Ectopic pregnancy

Dinda Fath Faathiren　Zhang Hong

【中圖分类号】R271 【文献标识码】A 【文章编号】1004-7484（2014）03-01084-02

【ABSTRACT】Objectives：Ectopic pregnancy occurs when the embryo fails to implant within the uterine cavity. Methotrexate, a folic acid antagonist has been widely used to treat ectopic pregnancy. The aim of this study is to determine the efficacy of methotrexate treatment for ectopic pregnancies, which will in-turn help us reduce maternal mortality and morbidity .Methods：We studied 150 women with ectopic pregnancies who were treated with methotrexate. Selection criteria included hemodynamically stable women with ?-hcg level of ≤5000 mIU/ml, adnexal mass ≤4 cm, absent cardiac activity and hemoperitoneum less than 100 ml. Pretreatment serum concentrations of human chorionic gonadotropin and progesterone, the size and volume of the gestational mass, and the presence of fluid (presumably blood) in the peritoneal cavity were correlated with the efficacy of therapy, as defined by resolution of the ectopic pregnancy without the need for surgical intervention. Results：There was no relation between the womens age or parity, the size or volume of the conceptus, or the presence of fluid in the peritoneal cavity and the efficacy of treatment. Analysis revealed the pretreatment serum chorionic gonadotropin concentration to be the only factor that contributed to the failure rate. Conclusions：Among women with ectopic pregnancies, a high serum chorionic gonadotropin concentration is the most important factor associated with failure of treatment with methotrexate protocol.

【Keywords】Ectopic pregnancy, Methotrexate, ?-hcg level.

Introductions

Ectopic pregnancy is an acute emergency if not timely diagnosed and treated. Timely diagnosis and appropriate treatment can reduce the risk of maternal mortality and morbidity related to ectopic pregnancy.1It is managed expectantly, medically (with methotrexate) or surgically. Medical management of ectopic pregnancy is generally considered to be less expensive than surgery 2-5. Expectant management is a conservative strategy that involves careful monitoring and assessment to establish whether the ectopic pregnancy will continue to resolve without the need for intervention. The clinical presentation of ectopic pregnancy has changed from a life threatening disease to a more benign condition for which nonsurgical treatment options are available with systemic methotrexate or expectant management. 3Women with a visible ectopic pregnancy and pregnancy of unknown location (PUL) have been offered medical treatment with methotrexate.5 Methotrexate can be administered systemically as a single dose regimen or as multiple dose regimen. Medical management of ectopic pregnancy may be offered to patients with minimal symptoms6. Medical management involves the intramuscular administration of methotrexate, after receiving methotrexate, patients require close monitoring until their serum hCG drops below 5 mIU/l 7.

METHODS

Subjects

Between December 2009 and August 2012, 150 patients of diagnosed ectopic pregnancy treated as in-patients with methotrexate regimen were retrospectively identified from hospital records of the department of Obstetrics and Gynecology, The Second Affiliated Hospital of Suzhou University. The diagnosis of ectopic pregnancy was made using both ultrasound and measurement of ?-hcg. All cases selected for medical management gave their informed written consent before starting the treatment.

The selection criteria for patients suspected to have ectopic pregnancy were as follows: Patients who were hemodynamically stable with beta human chronic gonadotrophin (?-hcg) levels of ≤5000 mIU / ml, adnexal mass ≤4 cm, absent cardiac activity and the presence of hemoperitoneum less than 100 ml. Women treated with MTX were advised to refrain from sexual intercourse until serum hcg was negative, and not to conceive within three months of treatment.

Statistical Method

Using retrospective study, results are given as mean values with 95% confidence intervals or medians with a range. χ2 tests were carried out. p<0.05 was considered to indicate a statistically significant difference, and p<0.01 was considered to indicate a manifest significant difference.

Study Protocol

Women with ectopic pregnancies were considered candidates for methotrexate treatment if they were hemodynamically stable; did not have free fluid (presumably blood) outside the pelvic cavity on transvaginal ultrasonography; did not desire surgical therapy; and did not have hepatic, hematologic, or renal disease. For the women enrolled in the study, the size of the gestational mass, as determined by transvaginal ultrasonography, had to be 4 cm or less. The women received methotrexate. Serum chorionic gonadotropin was measured the day followed. If serum concentrations of chorionic gonadotropin had not decreased then the ectopic pregnancy was treated surgically.Serial measurement of serum ?-hcg and early ultrasound examination have allowed detection of early and unruptured tubal ectopic pregnancies, 1,4

Criteria of successful

After conservative treatment, clinical symptoms disappeared; ?-hcg was dropped to a normal level; the diameter of ectopic pregnancy mass was decreased by more than 0,5 cm and gestational sac was decreased by more than 50% in diameter or even totally disappeared.

Criteria of failure

Conservative treatment had to be taken over by surgical treatment due to intra-abdominal hemorrhage induced by the occurrence of abdominal pain or intensified abdominal pain after treatment; ?-hcg did not present obvious decrease, or present continuous increase; ectopic pregnancy mass failed to exhibit diminishing tendency.

Toxic side effects of drug treatment

Scale division of toxic side effects was based on the criteria enacted by WHO concerning acute and sub-acute scales of cytotoxic drugs (Postovsky and Ben Arush, 2005).

Results

The patients who received methotrexate were monitored carefully to ensure complete resolution of the ectopic gestation using serial assessment of hCG levels every 4–7 days until hCG <5 IU/L. We defined treatment failure as those women in whom the physician responsible for the care opted for surgical management after methotrexate treatment. This was either due to failure of the hCG to fall, symptoms such as significant pain or clinical features of possible tubal rupture or intraperitoneal haemorrhage.

In this study, the mean age was 30 years ranging between 15-45 years (p=0.355). The success rate of MTX decreased as maternal age increased.

The mean gestation age at diagnosis was 4.3 weeks .The success rate of MTX decreased with increasing gestational age. Adnexal mass ranged from 2-4 cm. In patients with adnexal mass more than 4 cm, the success rate was less (p=0.132). The highest success rate of MTX was among patients with pregnancy of unknown location, followed by women with 2-3 cm adnexal mass. There was no marked difference in the site of ectopic gestation.

The average value of ?-hcg on day 1 in patients treated with single dose of MTX was 1234 (range 109-5269) and those treated with two doses or more was 1319.20 (range 865-6885). Time of resolution for ectopic pregnancy was defined as the total number of days from the beginning of treatment until β-hcg level became negative (<5mIU/ml).

Conclusion

Methotrexate has proven to be an effective medical management for ectopic pregnancies in a society where tubal conservation is of utmost importance. It is less invasive, less expensive and can be given on an outpatient basis and does not need expertise like laparoscopy. Future reproductive expectations are better with methotrexate with higher intrauterine pregnancy rates and lower ectopic rates subsequently. However the risk of tubal rupture after medical treatment combined with a prolonged follow up for an ectopic pregnancy to resolve requires outpatient monitoring for rupture and methotrexate side effects making compliance important in patient selection.The predictors of success in our study are the ?-hcg level?and adnexal mass less than 4 cm. Single dose methotrexate offers a safe and effective non-surgical method of treating selected patients and one important advantage of medical therapy is the potential for considerable savings in treatment costs.

Ectopic pregnancy is a common and serious problem with both high morbidity and maternal mortality. We can diagnose ectopic pregnancy earlier than the clinic signs will be present and this will give us the possibility to apply the best treatment with fewer complications. Quantity β-hCG measure, ultrasound examination, D & C inform us for the diagnosis of ectopic pregnancy and surgical treatment can be avoided.

MTX is recommended for all women without hemodinamic problems, unruptured pregnancy and not high β- hCG level (β-hCG < 5000 mlU/mL) It is confirmed that the reduce rate of 15% of β-hCG in the fourth day after application of MTX is a success guide. It is recommended to apply measure of β-hCG levels after laparoscopic salpingostomy. We need to do more improvement in our ectopic pregnancy treatment protocol even we have good application and results from present experience.

References

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