The Evolution of Methotrexate as a Treatment for Ectopic Pregnancy and Gestational Trophoblastic Neoplasia: A Review

Methotrexate was developed in 1949 as a synthetic folic acid analogue to compete with folic acid and thus interfere with cell replication. While initially developed as a potential treatment for acute lymphoblastic leukaemia, a serendipitous observation led to methotrexate's use to effect the dramatic cure of a case of advanced choriocarcinoma. This prompted the exploration for the potential of methotrexate to treat other conditions involving disordered trophoblastic tissue. Methotrexate has subsequently revolutionized the treatment of two pregnancy-related conditions—gestational trophoblastic neoplasia and ectopic pregnancy. This article reviews the development of modern treatment protocols that use methotrexate to medically treat these two important gynaecological conditions

Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location

Ectopic pregnancy (EP) occurs in 1-2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a 'pregnancy of unknown location' (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL.Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.Serum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414-693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412-1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341-675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315-475 ng/mL) (p<0.003). There were no women with an ectopic pregnancy where serum MIC-1>1000 ng/mL.Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP

Molecular diagnostics and therapeutics for ectopic pregnancy

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Serum MIC-1 levels in women at first presentation with a PUL, categorised according to final pregnancy outcome.

<p>Serum MIC-1 levels &gt;1000 ng/mL exclude EP.</p

Participant categorisation and baseline characteristics according to final pregnancy outcome (median ± SEM).

<p>Participant categorisation and baseline characteristics according to final pregnancy outcome (median ± SEM).</p

Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of combination gefitinib and methotrexate to treat ectopic pregnancies (GEM II) : study protocol

Peer reviewedPublisher PD