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We can truly sympathise with your predicament. We're glad that the Methotrexate is working well. However, if you want to start having a family it can affect pregnancy so needs serious consideration. A man wishing to have children whilst they are taking Methotrexate is a well-recognised issue. However, currently there are few studies focusing on this aspect and available data is limited because the number of men taking part in these few studies is relatively small.
What is methotrexate and how does it work?
Methotrexate is a medicine used in the treatment of a number of autoimmune conditions including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, cancer and irritable bowel syndrome. It stops the action of an enzyme called dihydrofolate reductase. This enzyme is essential in making DNA and other natural processes in the body. It depletes folic acid from the body so it is usual to have a folic acid supplement on a weekly or twice weekly basis if you are taking Methotrexate.
How does it affect fertility and the unborn child?
It depletes folic acid in the body so it is known to have harmful effects on unborn children. It does not appear to have effects on testicular function but it is known to affect sperm count probably because of its effect on the folate levels in the body. The folate levels can reduce the production of DNA.
Methotrexate is thought to be harmful when a woman takes it during pregnancy but there have been mixed results when the effects of Methotrexate have been studied in humans.
Supporting (evidence based) studies
One study reported in a dermatology journal in 1980 Methotrexate was used in the treatment of psoriasis showed that the structure and the making of sperms were impaired but there was no effect on the levels of testosterone.(2)
Testosterone is a male hormone which amongst other functions is needed for the production of sperms.
Whilst another study showed that there was no effect on the sperm or the baby.(1)
The Motherisk Programme conducted at the University of Toronto in 2003 conducted by French and Koren reported that there have been ‘no reports of pregnancy outcomes among men exposed to methotrexate before conception’ (3)
In 2009 a team who were involved in the treatment of a man being treated with Methotrexate for Crohn’s disease reported that a 41year old man who was taking Methotrexate and Infliximab had a healthy baby who weight 2.8kg(4)
In 2011 the Journal of Rheumatology reported a study that looked at the risk of major malformation in the case of fathers taking Methotrexate at the time of conception. The dose of Methotrexate ranged from 7.5mg-30mg taken once a week. Out of the 42pregnancies involving 40men who took part 36 resulted in live births, 3spontaneous abortions and 3 voluntary abortions. There were no congenital malformations observed at birth.
In 2014 a team led by Weber-Shendorfer followed 113 fathers whose partners had conceived whilst they were taking low dose Methotrexate and compared the results to 412 fathers whose partners had also conceived but were not taking Methotrexate. They found very little difference in the two groups leading them to conclude that the risk of harmful effects on the babies born to fathers taking methotrexate was no greater than those who did not take methotrexate at the time of conception. They suggested that there is no need to postpone family planning if the father is taking low-dose Methotrexate.(5)
In 2015 the British Society of Rheumatology produced a full guideline on the effects of drugs in pregnancy and lactation in a PDF format.
The guideline reported that there were four groups, three case series and a case report that looked at 263 pregnancies where fathers were taking low dose methotrexate. The journal stated that ‘Overall, the quality of these studies was low with information lacking from several studies primarily looking at safety of other medications. A large study however, published after our final search date of 113 pregnancies after paternal exposure to low dose MTX did not identify an increased risk of adverse fetal outcomes compared with 412 non-exposed pregnancies’
1.Feagins LA, Kane SV. Sexual and reproductive issues for men with inflammatory bowel disease. Am J Gastroenterol 2009; 104: 768–73.
2. Sussman A, Leonard JM. Psoriasis, methotrexate, and oligospermia. Arch Dermatol 1980; 116: 215–7.
3. French AE, Koren G. Effect of methotrexate on male fertility. Can Fam Physician 2003; 49: 577–8.
4. Lamboglia F, D'Inca R, Oliva L, Bertomoro P, Sturniolo GC. Patient with Severe Crohn's Disease Became a Father While on Methotrexate and Infliximab Therapy. Inflamm Bowel Dis 2009; 15: 648–9
5. Weber-Schoendorfer C, Hoeltzenbein M, Wacker E, Meister R, Schaefer C. No evidence for an increased risk of adverse pregnancy outcome after paternal low-dose methotrexate: an observational cohort study. Rheumatology 2014; 53: 757–63.
The data available is limited and consists of less than 250 pregnancies where the father was taking low dose Methotrexate. These data did not identify any increased risk of congenital malformation, growth restriction, spontaneous abortion or preterm delivery and other harmful effects to the baby.
The reports suggest that any harmful effects can be related to the dose.
Most medical guidelines suggest that due to a lack of enough evidence of safety that it would be a good idea to wait 6months after stopping Methotrexate.
We suggest that both of you discuss this matter thoroughly with your husband’s GP and rheumatologist. They may decide that your husband continues taking low dose Methotrexate and continue to try for a baby. If you become pregnant whilst your husband is taking Methotrexate then you will need more frequent detailed scans and monitoring will be required.
You will find more information in the web links below.
RCOG - Methotrexate effects on fetus
Medicines in pregnancy - Paternal use of methotrexate
Medicines in pregnancy - Methotrexate
Rheumatology - Guidelines
We hope this helps.
Answered by the Health at Hand nurses
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