Letrozole in Tubal Ectopic Pregnancy
Letrozole in Tubal Ectopic Pregnancy
Tubal ectopic pregnancies are abnormal pregnancies in the Fallopian tube, rather than in the
 womb. They occurred in around 1-2% of all pregnancies. Methotrexate (MTX) given by the
 intramuscular route i.e. systemic, a commonly used drug for cancer , was a widely used
 alternative for management for unruptured tubal ectopic pregnancies and was recommended as
 first line treatment for selected women.

 Letrozole, aromatase inhibitor, can suppose oestradiol level. Combination of letrozole with
 misprostol has shown to improve the complete abortion rate in miscarriage. As a result,
 addition of letrozole may cause a higher success rate in the medical treatment of ectopic
 pregnancy.

 As the evidence of combination of MTX and letrozole in tubal ectopic pregnancies is not
 available, the objective of the present study is to evaluate efficacy of combination of MTX
 and letrozole in women with tubal ectopic pregnancies
Tubal ectopic pregnancies occur in around 1-2% of all pregnancies. Traditionally, surgery
 with salpingectomy was the mainstay of treatment; however, it comes with anaesthetic and
 operatives risks in addition to an increased cost for operative procedures. In recent years,
 systemic methotrexate (MTX), a dihydrofolate reductase inhibitor, has been a widely used
 alternative for management for unruptured tubal ectopic pregnancies. The success rate of
 systemic MTX at a doses of 50mg/m2 body surface area is around 70% which ranges from 65 to
 95%, depending greatly on the level of human chorionic gonadotrophin (hCG), the size of
 adnexal mass and presence of fetal heart pulsation.

 Use of systemic MTX as the first-line management has been proposed for women with unruptured
 ectopic pregnancy where the adnexal mass is smaller than 35mm, serum hCG level is less than
 5000 IU/l and fetal heartbeat is absent.

 Letrozole is a third generation non-steroidal reversible aromatase inhibitor. It can suppress
 oestradiol level up to 95% to 99% after administration according to pharmacodynamics and
 pharmacokinetics studies. Oestrogen is important in the support of early pregnancy, other
 than progesterone with well-known pivotal effect on the maintenance of early pregnancy.

 Animal studies showed the combination of mifepristone and letrozole worked synergistically
 and induced almost 100% termination of pregnancies in rats. Letrozole induced 50% miscarriage
 rate in pregnant baboons. Letrozole combined with vaginal misoprostol regimen was associated
 with a higher complete abortion rate than misoprostol alone in pregnancies up to 63 days.

 The use of letrozole in ectopic pregnancy has never been explored. It is hypothesized that
 letrozole can suppress serum oestradiol level, which in turn, may cause failure of pregnancy
 in ectopic pregnancy. The aim of this study is to investigate the clinical effectiveness of
 letrozole in the medical treatment of ectopic pregnancy.
Inclusion Criteria:

 -  Tubal ectopic pregnancy suggested by presence of a heterogenous adnexal mass with
 suboptimal rise of hCG i.e. <= 63% rise over 48 hours

 -  hCG level <= 5000 IU/l

 -  Absence of fetal heart pulsation

 -  Mean diameter of adnexal mass <= 3.5cm

 -  Haemodynamically stable

 -  No significant abdominal pain

 Exclusion Criteria:

 -  Presence of significant amount of free fluid in pelvis

 -  Allergic to MTX

 -  Deranged liver function test (AST/ ALT or GGT >= 2 upper limit of normal)

 -  Deranged renal function test (eGFR <= 45ml/min)

 -  Heterotopic pregnancies