TNF-alpha in the testis is produced by round spermatids, pachytene spermatocytes, and testicular macrophages. The type 1 TNF receptor has been found on Sertoli and Leydig cells and numerous studies suggest a paracrine mode of action for TNF-alpha in the normal testis. TNF promotes cell survival during spermatogenesis.
There is still some uncertainty if prolonged TNF inhibition is associated with infertility in men. Furthermore, although most studies show TNFi in men are not associated with poor pregnancy outcomes or congenital abnormalities, more data would be helpful.
On Saturday morning at EULAR 2016, researchers from Romania presented data on 13 men who fathered 14 children while on prolonged TNFi (more than 12m) for AS (ETN 9, ADA 3, INF 1). These were compared to age-matched controls.
All the newborns of TNFi exposed men were born healthy, delivered at term, had normal weight and no congenital defects. There were no adverse pregnancy-related maternal outcomes including pre-eclampsia, miscarriage, stillbirth, or pre-term birth.
Interestingly, there was a difference between time from decision for reproduction to conception between the TNFi exposed group (14.3m) and the control group (7.7m).
With regards to the safety of TNFi exposure in men considering reproduction, the data is consistent with the available literature. This gives us more evidence to reassure patients that it is safe for them to try starting a family while on therapy.
The part of this data that is controversial is the implication that prolonged TNFi exposure could contribute to infertility in men. Unfortunately, they did not collect data on frequency of intercourse and other fertility-related variables which could also explain these differences. Scientifically, there is some basis to TNFi and infertility. I suppose in couples who are having difficulty with fertility, we could consider holding TNFi until conception.
As with most of our diseases and clinical questions, more data is needed but this is a good start.
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.View Full Bio