Letrozole add-on in the Treatment of Cesarean Scar Pregnancy

Study Overview
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Brief Summary
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It is hypothesized that the inhibition of estradiol production by letrozole may interfere with physiological effects of progesterone necessary to maintain the pregnancy. There is no reference treatment of cesarean scar pregnancy (CSP) as the limited number of cases precludes the extrapolation of results. In our center we successfully use two-step treatment with methotrexate (MTX) followed by hysteroscopic removal of products of conception (POC). The time in between is needed to achieve a decrease in the trophoblast's vital potential (B-hCG fall) and its vascularization. Additional administration of letrozole could further reduce the vital potential of the pregnancy, eliminating the need for another dose of MTX, resulting in faster healing and lower rate of complications.

Detailed Description
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A prospective cohort study is conducted among women with cesarean scar pregnancy (CSP). Women with increasing B-human chorionic gonadotropin (B-hCG) concentrations are included. Two study arms were planned: women treated with a single dose of 100 mg MTX intravenously and 50 mg MTX in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH) women treated with a single dose of 100 mg MTX intravenously and 50 mg MTX in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH) with additional use of letrozole 5 mg orally (from day 0) for 10 days. Blood parameters (B-hCG, hemoglobin, total blood count, creatinine, urea, alanine/aspartate transaminase, gamma-glutamyltransferase, bilirubin) were tested on days 0,4,7, followed by B-hCG concentration measurement every 7 days until surgery. After obtaining satisfactory decrease in B-hCG and POC vascularization, women underwent hysteroscopic evacuation of POC. Blood loss parameters, frequency of conversion from hysteroscopy to laparoscopy and laparotomy were measured. The women were given the option to choose the treatment used in the study. All enrolled women gave informed written consent to participate in the study.

Official Title
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Evaluation of the Therapeutic Effect of Adding Letrozole to the Protocol of Combined Treatment of Cesarean Scar Pregnancy

Conditions
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Cesarean Scar Pregnancy

Intervention / Treatment
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* Drug: MTX monotherapy
* Drug: MTX + letrozole add-on


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CSP confirmed on pelvic ultrasound consent of the Bioethics Committee for termination of CSP increasing B-hCG concentrations Exclusion Criteria: heterotopic pregnancy decreasing B-hCG concentrations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MTX in monotherapy<br>Combined treatment with MTX followed by hysteroscopic evacuation of POC | Drug: MTX monotherapy<br>* MTX in a single dose of 100 mg intravenously and 50 mg in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH), and subsequent hysteroscopic evacuation of products of conception (POC)<br>|
| Active Comparator: MTX + letrozole add-on<br>Combined treatment with MTX + letrozole add-on followed by hysteroscopic evacuation of POC | Drug: MTX + letrozole add-on<br>* MTX in a single dose of 100 mg intravenously and 50 mg in intra-amniotic injection (day 0), along with 30 mg potassium chloride in case of positive fetal heartbeat (FH) + Letrozole in a daily dose of 5 mg (2 x 2.5 mg) orally for 10 days from day 0, and subsequent hysteroscopic evacuation of products of conception (POC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood loss during the procedure expressed as a decrease in hemoglobin concentration | Decrease in hemoglobin concentration in g/dl on day 1 after the procedure compared to the pre-procedure concentration | up to 6 months | 
| Blood loss volume during the procedure expressed in volume units | The volume of blood lost during the procedure in ml | up to 6 months | 
| Conversion rate from hysteroscopy to laparoscopy or laparotomy due to due to hemorrhage | Percentage (%) of conversion from hysteroscopy to laparoscopy or laparotomy due to hemorrhage | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of treatment on bone marrow function (red blood cells) | Change in red blood count (T/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on bone marrow function (white blood cells) | Change in white blood count (G/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on bone marrow function (platelets) | Change in platelet count (G/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on liver function (serum total bilirubin) | Changes in the concentrations of serum total bilirubin (mg/dl) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on liver function (alanine transaminase) | Changes in the concentrations of alanine transaminase (IU/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on liver function (aspartate transaminase) | Changes in the concentrations of aspartate transaminase (IU/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on liver function (gamma-glutamyltransferase) | Changes in the concentrations of gamma-glutamyltransferase (IU/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on kidneys function (urea) | Changes in the concentrations of serum urea (mmol/l) in the course of treatment (day 0,4,7) | up to 6 months | 
| The effect of treatment on kidneys function (creatinine) | Changes in the concentrations of serum and creatinine (mg/dl) in the course of treatment (day 0,4,7) | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cesarean scar pregnancy, operative hysteroscopy