Comparison of the Effectiveness of Single Dose Metotrexate Protocol and Combined Therapy of Letrazole and Single Dose Metotrexate in the Medical Management of Patients With Ectopic Pregnancy
Abstract
Ektopik gebelikte tek başına tek doz metotreksat tedavisi ile tek doz metotreksat+letrozol tedavisinin başarısını karşılaştırmak, tedavi öncesi ve tedavi sonrası, β-hCG değişiminin, hemogram, biyokimya değerlerinin takibi, rüptüre veya medikal tedavi başarısızlığına bağlı cerrahiye gidişi değerlendirilip, çalışmamızdan elde edilecek bulgular ile erken dönemde kullanılabilecek alternatif tedavi seçeneklerini saptamak, bu tedavi seçenekleri ile maternal morbidite ve mortalitenin azalmasına, fertilitenin korunmasına katkıda bulunmak ve hastaların tedavi uyumlarını arttırıp, tedavi ve yatış maliyetlerini azaltmakır. Materyal – Metod Van Yüzüncü Yıl Üniversitesi Kadın Hastalıkları ve doğum kliniği'nde, Haziran 2021 ve Eylül 2022 tarihleri arasında obstetri ve jinekoloji polikliniklerine başvuran, ektopik gebelik tanısı konulan 60 hasta üzerinde yapılan prospektif bir çalışmadır. Bu amaçla çalışmaya dahil edilen 30 hastaya tek doz metotreksat tedavisi ve 30 hastaya tek doz metotreksat +letrozol tedavisi başlanmıştır. Ektopik gebelik tanısı konulan kişilerin β- HCG, hemogram, biyokimya değerleri bakıldıktan sonra, ciddi veya persistan karın ağrısı olmayan, β- HCG <5000 mIU/ml olan, fetal kardiyak aktivite izlenmeyen, ektopik kitle boyutu 3-4 cm'den küçük olan ve medikal tedaviye kontrendikasyonu olmayan 60 hasta çalışmaya dahil edildi. Çalışmanın sonunda tedavi sonrası kan parametrelerinde bozulma olanlar, rüptüre bağlı cerrahi tedavi gerektiren hastalar, medikal tedaviye yanıt alınamayan hastalar medikal tedaviye başarısızlık olarak değerlendirilmiştir. Bulgular Çalışmaya dahil edilen 60 hasta 2 gruba ayrıldı. Hastalar rastgele olarak sıralandı, tek sayılardaki hastalar yalnız metotreksat (MTX) tedavisi uygulanan (n=30) 1.grup, diğer çift sayılılar MTX+letrozol tedavisi uygulanan (n=30) 2. grup olarak belirlendi. MTX tedavisi uygulanan hasta grubunun yaş ortalaması 32,90±6,09 idi. MTX+letrozol tedavisi uygulanan hasta grubunun yaş ortalaması 29,00±4,73 idi. MTX grubunda β- hCG 7. gün 1010,53±1148,85, MTX+letrozol grubunda 927,50±1049,27 olarak bulundu. MTX+letrozol grubunda daha fazla düşme gözlenmiş olsa da istatistiksel olarak anlamlı bir fark bulunamadı. (p=0,771). MTX uygulanan grupta ALT 1. günde 14,37±4,93; MTX+letrozol uygulanan grupta 20,07±12,36 olarak bulundu aralarındaki fark istatistiki olarak anlamlıydı (p=0,022). MTX uygulanan grupta ALT 7. günde 20,20±19,25; MTX+letrozol uygulanan grupta 37,07±31,59 olarak bulundu aralarındaki fark istatistiksel olarak anlamlı bulundu (p=0,016). MTX uygulanan grupta AST 1. günde 16,60±4,49; MTX+letrozol uygulanan grupta 24,90±11,51 olarak bulundu aralarındaki fark istatistiki olarak anlamlıydı (p=0,001). MTX uygulanan grupta AST 7. günde 20,13±11,08; MTX+letrozol uygulanan grupta 40,37±34,07 olarak bulundu aralarında istatistiksel olarak anlamlı bulundu (p=0,003). MTX tedavisi uygulanan grupta β- hCG4.gün 1471,47±1379,46 ve 7.gün 1010,53±1148,85 olarak bulundu istatistiksel olarak anlamlı fark gözlemlendi (p=0,001). MTX+letrozol tedavisi uygulanan grupta β- hCG4.gün 1656,03±1544,69 ve β- hCG7.gün 927,50±1049,27olarak belirlendi, iki grup arası fark istatistiksel olarak anlamlıydı (p=0,001). Hastaların 4. ve 7. günler arasındaki β-hCG değişim yüzdesi, MTX tedavisi ugulananlarla MTX+letrozol uygulanan gruplar sırasıyla 36,98±25,94 ve 46,07±20,93 olarak bulundu. MTX+letrozol grubunda % bazında anlamlı olarak daha fazla düşme gözlenmiş olsa da istatistiksel olarak anlamlı fark bulunamadı (p=0,141). Yapılan çalışmamızda grup 2 de başlangıç β- hCG değerleri daha yüksek olmasına rağmen takiplerde 4. günden sonraki ölçümlerde daha hızlı ve keskin bir β- hCG düşüşü gözlemlendi. Sonuç MTX+letrozol tedavisinin MTX tedavisi ile aynı başarı oranına sahip olduğu görüldü. Ancak β- hCG değerlerindeki 4 ve 7. Gün düşüş oranlarının istatistiki olarak anlamlı izlenmemesine rağmen letrozol uygulanan grupta yüzdesel olarak daha keskin bir düşüş gözlemlenmiştir. Letrozol kullanılan grupta 7. Günde gözlenen karaciğer enzimlerinde yüksekliğin daha fazla olduğu görüldü ve bu sonuçla kullanılan ilaçların olası toksik etkilerinin göz önünde bulundurulması gerekmektedir.
Comparing the single dose methotrexate treatment and the letrozole + single dose methotrexate treatment success, pretreatment and posttreatment ß-hCG variance, following-up in hemogram and biochemical markers, evaluate the surgical process dependent on rupture and determine the alternative treatment options can be used in the early period with the findings of our study, contribute to the protection of fertility and the decreation of maternal morbidity and mortality with these treatment options, increase treatment compliance of patients and reduce the treatment and hospitalization costs in ectopic pregnancy. Material Method This is a prospective study which is performed on 60 patients diagnosed with ectopic pregnancy who consulted to the obstetry&gynaecology clinic in Van Yuzuncu Yil University between June 2021 and September 2022. The treatment has ben started in 30 of 60 patients included with this purpose with single dose methotrexate treatment, other 30 patients has been started with single dose methotrexate + letrozole. 60 patients were included in study, who had diagnosed with ectopic pregnancy after checking the ß- hCG, hemogram, biochemical markers, with no persistent abdominal pain, no fetal cardiac activity, no contraindication to these medical treatments and ß-hCG value is less than 5000mIU/mL, ectopic mass size is less than 3-4 centimeters. At the end of the study, patients who had deterioration in blood parameters, needed surgical treatment dependent on rupture, could not responding to medical treatments, evaluated as failure. Results 60 patients who included in the study were divided into two groups. Patients were randomly sorted, who had taken the odd numbers, treated with single dose methotrexate (MTX) (n=30), were determined as first group. The other group, who had taken the even numbers and treated with single dose methotrexate (MTX) + letrozole treatment (n=30) were determined as second group. The average age of patients treated with methotrexate, was 32.9 ±6.09. The average age of patients treated with methotrexate + letrozole was 29.00±4.73. The seventh day ß-hCG value was detected as 1010.53±1148.85 in the methotrexate group. It was detected 927.50 ±1049.27 in the methotrexate + letrozole group. Even if more reductions were observed in the second group, MTX+letrozole, it was not remarkable statistically. (p=0.771) The first day ALT value was detected as 14.37±4.93 in the first group, treated with methotrexate. ALT was detected as 20.07±12.36 in the second group, treated with methotrexate + letrozole. The difference between two groups' values were was significant statistically (p=0.022) The seventh day ALT value was detected as 20.20±19.25 in the first group, treated with methotrexate. It was detected as 37.07±31.59 in the second group, treated with methotrexate + letrozole. The difference between two group's values were remarkable statistically (p=0.016) The first day AST value was detected as 16.60±4.49 in the first group , treated with methotrexate. It was detected as 24.90±11.51 in the second group, treated with methotrexate +letrozole. The difference between two group's values were remarkable statistically (p=0.001). The seventh day AST value was detected as 20.13±11.08 in the first group, treated with methotrexate. It was detected as 40.37±34.07 in the second group, treated with methotrexate + letrozole. The difference between two group's values were remarkable statistically (p=0.003). The fourth day ß- hCG value was detected as 1471.47±1379.46 and the seventh day ß-hCG value was detected 1010.53±1148.85 in the first group, treated with methotrexate. The difference between two day's values were remarkable statistically (p=0.001). The fourth day ß- hCG value was detected as 1656.03±1544.69 and the seventh day ß-hCG value was detected as 927.50±1049.27 in the second group, treated with methotrexate + letrozole. The difference between two day's values were remarkable statistically (p=0.001). The ß- hCG change percentage of patients was detected in the first group, treated with methotrexate, as 36.98±25.94 and it was detected in the second group, treated with methotrexate + letrozole, as 46.07±20.93 Even if more decreases were observed on a percentage basis in the second group significantly, the difference between two groups was not remarkable statistically (p=0.141). In our study, even if the initial ß-hCG values were higher in the second group faster and sharper ß-hCG reduction in subsequent values were observed after fourth day checks. Conclusion It was observed that methotrexate treatment and methotrexate + letrozole treatment have the same success rate. But even if the ß-hCG values decline rates were not observed as remarkable on fourth and seventh days statistically a sharper decline were observed at the group treated with methotrexate + letrozole. It has been observed that liver enzymes, evaluated on seventh day, were elevated. With this conclusion it needs to considerate the possible toxic effects of drugs that used.
Comparing the single dose methotrexate treatment and the letrozole + single dose methotrexate treatment success, pretreatment and posttreatment ß-hCG variance, following-up in hemogram and biochemical markers, evaluate the surgical process dependent on rupture and determine the alternative treatment options can be used in the early period with the findings of our study, contribute to the protection of fertility and the decreation of maternal morbidity and mortality with these treatment options, increase treatment compliance of patients and reduce the treatment and hospitalization costs in ectopic pregnancy. Material Method This is a prospective study which is performed on 60 patients diagnosed with ectopic pregnancy who consulted to the obstetry&gynaecology clinic in Van Yuzuncu Yil University between June 2021 and September 2022. The treatment has ben started in 30 of 60 patients included with this purpose with single dose methotrexate treatment, other 30 patients has been started with single dose methotrexate + letrozole. 60 patients were included in study, who had diagnosed with ectopic pregnancy after checking the ß- hCG, hemogram, biochemical markers, with no persistent abdominal pain, no fetal cardiac activity, no contraindication to these medical treatments and ß-hCG value is less than 5000mIU/mL, ectopic mass size is less than 3-4 centimeters. At the end of the study, patients who had deterioration in blood parameters, needed surgical treatment dependent on rupture, could not responding to medical treatments, evaluated as failure. Results 60 patients who included in the study were divided into two groups. Patients were randomly sorted, who had taken the odd numbers, treated with single dose methotrexate (MTX) (n=30), were determined as first group. The other group, who had taken the even numbers and treated with single dose methotrexate (MTX) + letrozole treatment (n=30) were determined as second group. The average age of patients treated with methotrexate, was 32.9 ±6.09. The average age of patients treated with methotrexate + letrozole was 29.00±4.73. The seventh day ß-hCG value was detected as 1010.53±1148.85 in the methotrexate group. It was detected 927.50 ±1049.27 in the methotrexate + letrozole group. Even if more reductions were observed in the second group, MTX+letrozole, it was not remarkable statistically. (p=0.771) The first day ALT value was detected as 14.37±4.93 in the first group, treated with methotrexate. ALT was detected as 20.07±12.36 in the second group, treated with methotrexate + letrozole. The difference between two groups' values were was significant statistically (p=0.022) The seventh day ALT value was detected as 20.20±19.25 in the first group, treated with methotrexate. It was detected as 37.07±31.59 in the second group, treated with methotrexate + letrozole. The difference between two group's values were remarkable statistically (p=0.016) The first day AST value was detected as 16.60±4.49 in the first group , treated with methotrexate. It was detected as 24.90±11.51 in the second group, treated with methotrexate +letrozole. The difference between two group's values were remarkable statistically (p=0.001). The seventh day AST value was detected as 20.13±11.08 in the first group, treated with methotrexate. It was detected as 40.37±34.07 in the second group, treated with methotrexate + letrozole. The difference between two group's values were remarkable statistically (p=0.003). The fourth day ß- hCG value was detected as 1471.47±1379.46 and the seventh day ß-hCG value was detected 1010.53±1148.85 in the first group, treated with methotrexate. The difference between two day's values were remarkable statistically (p=0.001). The fourth day ß- hCG value was detected as 1656.03±1544.69 and the seventh day ß-hCG value was detected as 927.50±1049.27 in the second group, treated with methotrexate + letrozole. The difference between two day's values were remarkable statistically (p=0.001). The ß- hCG change percentage of patients was detected in the first group, treated with methotrexate, as 36.98±25.94 and it was detected in the second group, treated with methotrexate + letrozole, as 46.07±20.93 Even if more decreases were observed on a percentage basis in the second group significantly, the difference between two groups was not remarkable statistically (p=0.141). In our study, even if the initial ß-hCG values were higher in the second group faster and sharper ß-hCG reduction in subsequent values were observed after fourth day checks. Conclusion It was observed that methotrexate treatment and methotrexate + letrozole treatment have the same success rate. But even if the ß-hCG values decline rates were not observed as remarkable on fourth and seventh days statistically a sharper decline were observed at the group treated with methotrexate + letrozole. It has been observed that liver enzymes, evaluated on seventh day, were elevated. With this conclusion it needs to considerate the possible toxic effects of drugs that used.
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Kadın Hastalıkları ve Doğum, Gebelik, Gebelik-ektopik, Gonadotropinler, Koryonik gonadotropinler, Letrozol, Metotreksat, Obstetrics and Gynecology, Pregnancy, Pregnancy-ectopic, Gonadotropins, Chorionic gonadotropins, Letrozole, Methotrexate
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