MTX and Paternal

Exposure
Fertility and Offspring
NABIEL MIR UQ MBBS MSIV

 jdnjdd

No studies were found that evaluated the effect of

methotrexate for men on miscarriages/birth defects OR
male fertility

Zenas Z. N. Yiu, Richard B. Warren, Ulrich

Mrowietz & Christopher E. M. Griffiths (2015)
Safety of conventional systemic therapies for
psoriasis on reproductive potential and
outcomes, Journal of Dermatological Treatment,
26:4, 329-334,
Impact of systemic
psoriasis therapies on

Male Fertility and Mutagenicity

MTX found in rat testicular fluid 18-50x lower in
Seminiferous Tubules vs plasma no studies in
human
@ non-cancer doses: Mixed evidence on
impairment of semen quality (Higher cancer
doses for osteosarcoma testicular injury BUT
COFOUNDED by concomitant chemo)
Underlying mechanism may include
interference with maturation of spermatids

Psoriasis, methotrexate, and

oligospermia. Arch Dermatol 1980,
116:215-217.
26 yo M Fertility Evaluation. Normal Puberty with no
libido or potency issues. One child in 1968 with former
wife + intermittent treatment with MTX for severe
Psoriasis over past 8 y.
At the time patient got a total of 880 mg of MTX (seen in
August but last dose on July 20 th)
Normally got 5mg of MTX ever 12 houts for 3 doses at 1
week intervals.
PE: Severe deforming arthritis with Psoriasis. Testes 4x2.5
cm bilaterally with normal consistency
Labs: Normal WBC, ALP, SGOT, BUN. Multiple Seminal
fluid specimens post 3 day abstinence=Sperm [c],
Morphology and stained

Underlying mechanism may include

interference with maturation of spermatids

Beghin, D., M.-P. Cournot, C. Vauzelle, and E.

Elefant. "Paternal Exposure to Methotrexate
and Pregnancy Outcomes." The Journal of
Rheumatology 38.4 (2011): 628-32.

1997-2009: 42 pregnancies conceived by 40

fathers treated with with a mean age of 38M
and 31F
54.8% mainly for rheumatic diseases (n = 18)],
9 for psoriasis (21.4%), 8 for a malignant
disease (19.0%
Median dose was 15mg/week (7.5-30mg) with
higher doses not only for cancer.
76.2% had MTX as their ONLY medication
others had DMARDs, Vitamin A and MT inh
39/42 conceptions occurred while on MTX

Nevertheless, because of the mutagenic potential of MTX and the

lack of information on its presence in seminal fluid, it seems wise,
if possible, to stop paternal MTX 3 months before conception and
to use condoms during sexual intercourse with a pregnant
woman.

No excess risks in offspring with paternal

preconception exposure to disease-modifying
antirheumatic drugs. Wallenius M1, Lie E, Daltveit AK,
Salvesen K, Skomsvoll JF, Kalstad S, Lexberg S,
Mikkelsen K, Kvien TK, stensen M. Arthritis
Rheumatol. 2015 Jan;67(1):296-301.

Examine pregnancy outcomes in the partners of

male patients with inflammatory joint disease
who were or were not exposed to DMARDS
before conception vs reference subjects from
the general population.
Nt = 1796 of which 2777 births noted 110/2777
had a father exposed to DMARD within 12 weeks
before conception.
MTX n=49, others like SSA and TNFi
39% of 110 were SpA, 23% PsA, 16% RA, 16%
Unspec and 5% JIA reference population had
similar distribution
Mean maternal age at delivery was (27.3-36.7)

RR of Malformation 1.22 (0.45,3.31) P=0.69 vs non-exposed RR 0.7 (0.26,1.86), P

1 MTX exposed birth
with VSDexposure to DMARDs within 12 weeks of
The data indicate that paternal
conception does not increase the risk of severe congenital malformations

Wallenius, Marianne, Elisabeth Lie, Anne K. Daltveit, Kjell .

Salvesen, Johan F. Skomsvoll, Synve Kalstad, se S. Lexberg,
Knut Mikkelsen, Tore K. Kvien, and Monika stensen. "Brief
Report: No Excess Risks in Offspring With Paternal Preconception
Exposure to Disease-Modifying Antirheumatic Drugs." Arthritis &
Rheumatology 67.1 (2014): 296-301. Web.

1995-2012: Fathers to be with LD MTX(<30mg/week) for

rheumatic/infl diseases AT Conception
113 pregnancies,
19 of which had paternal MTX exposure limited to
Preconception
94 lasted UNTIL conception or longer
50% had RA>Psoriasis/PsA
Median dose was 15mg/week (0.6-30)
Median exposure after LMP in post-conception was 10
w (2-41w)
Objectives were to evaluate the risk of
Spontaneous abortion (SAB)
Major birth defects
Elective termination of pregnancy (ETOP)
Prematurity and reduced birth weight

PREGNANCY OUTCOMES

Amniocentesis was performed in 12/113 (10.6%) pregnancies

in the MTX cohort, and except for one trisomy 16, no
chromosomal aberrations were diagnosed.

BIRTH DEFECTS

Description of birth defects

MTX
cohort birth defects were
The
observed
not at all indicative of MTX
embryopathy.

CONCLUSION

Nor the use of condoms during pregnancy seems to be

necessary in the case of paternal low dose MTX therapy

References

Visser, K. "Multinational Evidence-based Recommendations for the Use

of Methotrexate in Rheumatic Disorders with a Focus on Rheumatoid
Arthritis: Integrating Systematic Literature Research and Expert
Opinion of a Broad International Panel of Rheumatologists in the 3E
Initiative." Annals of the Rheumatic Diseases 68.7 (2008): 1086-093.
Zenas Z. N. Yiu, Richard B. Warren, Ulrich Mrowietz & Christopher E. M.
Griffiths (2015) Safety of conventional systemic therapies for psoriasis
on reproductive potential and outcomes, Journal of Dermatological
Treatment, 26:4, 329-334
Beghin, D., M.-P. Cournot, C. Vauzelle, and E. Elefant. "Paternal
Exposure to Methotrexate and Pregnancy Outcomes." The Journal of
Rheumatology 38.4 (2011): 628-32.
Wallenius, Marianne, Elisabeth Lie, Anne K. Daltveit, Kjell . Salvesen,
Johan F. Skomsvoll, Synve Kalstad, se S. Lexberg, Knut Mikkelsen,
Tore K. Kvien, and Monika stensen. "Brief Report: No Excess Risks in
Offspring With Paternal Preconception Exposure to Disease-Modifying
Antirheumatic Drugs." Arthritis & Rheumatology 67.1 (2014): 296-301.
Web.
Weber-Schoendorfer, C., M. Hoeltzenbein, E. Wacker, R. Meister, and C.
Schaefer. "No Evidence for an Increased Risk of Adverse Pregnancy