OP0131 WHAT IS THE EFFECT OF METHOTREXATE ON SEMEN PARAMETERS OF MEN DIAGNOSED WITH IMMUNE-MEDIATED DISEASES? RESULTS OF A PROSPECTIVE COHORT STUDY (iFAME-MTX).

Abstract

BackgroundMethotrexate (MTX) is one of the most frequently prescribed medications for the treatment of several immune-mediated diseases (IMD). MTX has well-established safety and efficacy profiles. Nonetheless, the available scientific evidence to support the decision whether men with an active desire to become a father should be treated with MTX is dubious (1). This knowledge gap is characterized by a lack of prospective studies evaluating the semen parameters before and after exposure to MTX (2).ObjectivesOur objective is to compare the semen parameters (sperm concentration, volume and progressive motility) between men diagnosed with IMD (pre and post exposure to MTX) and healthy controls.MethodsThis is a prospective cohort study. Men diagnosed with an IMD (RA, SpA, psoriasis) who were older than 18 years and received a medical indication to start therapy with MTX were invited to participate (naïve cases). These men were instructed to produce 2 semen samples (a pre-exposure sample before initiating MTX therapy and a post-exposure sample 12 weeks after initiating MTX therapy). Healthy men who were over 18 years old were invited to participate as healthy controls. Furthermore, to evaluate the semen parameters of men chronically exposed to MTX, men diagnosed with an IMD who had been exposed to MTX (≥15 mg/week) for at least 1 year were also invited to participate (chronic cases). These men produced one semen sample (post-exposure). All participants were proven fertile (fathered a child or their partner reported a positive pregnancy test). Continuous variables were compared using a paired t-test or a one-way analysis of variance.ResultsIn total 18 naïve cases, 25 healthy controls and 5 chronic cases were included. Their demographic characteristics and the results of the conventional semen analysis are presented per group in Table 1. Compared to the semen parameters (sperm concentration, volume and progressive motility) from healthy controls, pre-exposure and post-exposure semen parameters from naïve cases were not statistically significant different (see Figure 1). The semen parameters of chronic cases were also not statistically significant different compared to pre-exposure samples from naïve cases and to healthy controls. Oligospermia (sperm concentration <15 10^6/mL) was identified in two samples from a naïve case (pre and post-exposure to MTX) and no cases of azoospermia were identified.Table 1.Demographic, clinical characteristics and semen parametersMTX naïveControlsMTX chronicp valuePre-exposurePost-exposureTotal, n18255Age, mean (95% CI)36.52 (33.65-39.39)34.56(32.75-36.36)36.80(31.95 – 41.64)MTX dose mg/week, mean (95% CI)-16.52(14.54 – 18.49)-18.00(14.59 – 21.40)Sperm concentration, mean × 10^6/ mL (95% CI)84.27(44.27-123.83)64.31(42.55 – 86.35)92.56(60.45 –124.66)44.60(25.11 – 64.08)p=0.358*p=0.280**Progressive motility*, % (95% CI)63.20(55.44-70.95)60.11(49.56-70.67)56.95(51.05-62.85)50.40(34.82 – 65.97)p=0.562*p=0.456**Semen volume, mean mL,(95% CI)2.93(2.09-3.76)2.90(2.08-3.71)3.12(2.51-3.73)2.50(1.55-3.44)p=0.608*p=0.593***Comparisons between pre and post exposure samples were tested using a paired t-test,**Comparisons between pre, post exposure and healthy controls were tested using a one way analysis of variance.ConclusionThis is the largest prospective study ever conducted to evaluate the impact of MTX on semen parameters in men diagnosed with IMDs. We demonstrated that exposure to MTX did not result in statistically significant different semen parameters. Based on semen parameters, our findings suggest that MTX therapy can be continued in men diagnosed with an IMD and a wish to become a father.