The toxicity of methotrexate in male fertility and paternal teratogenicity

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Abstract

There is a high prevalence of methotrexate (MTX) use in males of reproductive age. The scope of this paper reviews what is known regarding risks to fertility and partners' pregnancy outcomes with regard to MTX use in men. Areas covered: This paper reviews the evidence for current recommendations for MTX use and male fertility and aims to educate professionals regarding MTX use in reproducing males so that patients may be counseled appropriately. A literature search included peer-reviewed sources from PubMed searches and the literature referenced within. Expert opinion: There is a lack of evidence regarding effects of MTX on male fertility. The recommendation to stop MTX three months prior to conception is safe, but is not evidenced by an understanding of the impact of MTX on spermatogenesis or paternal-mediated teratogenicity but rather the timeframe of spermatogenesis. Given the unclear evidence, patients treated with MTX must be counseled on the likelihood of adverse effects of MTX and role of sperm cryopreservation. Future studies are needed to help elucidate the unclear evidence of MTX effects on male fertility and pregnancy outcomes.

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Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989).

Patrick Thonneau, Sophie Marchand, Anne Tallec … (1991)

To estimate the prevalence and main causes of infertility, a multicentre survey was conducted over 1 year (July 1988-June 1989) in three regions of France. All the 1686 couples in these regions, who consulted a practitioner for primary or secondary infertility during this period, were included in the investigation. The prevalence rate of infertility was found to be 14.1%, indicating that one woman out of seven in France will consult a doctor for an infertility problem during her reproductive life. The main causes of female infertility were ovulation disorders (32%) and tubal damage (26%), and of male infertility oligo-terato-asthenozoospermia (21%), asthenozoospermia (17%), teratozoospermia (10%) and azoospermia (9%). Infertility was also found to be caused by disorders in both the male and female partners together; thus in 39% of cases both the man and woman presented with disorders. The woman alone was responsible for infertility in one-third of cases and the man alone in one-fifth. Unexplained infertility was found in 8% of the couples surveyed.

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Testicular Biopsy Score Count – A Method for Registration of Spermatogenesis in Human Testes: Normal Values and Results in 335 Hypogonadal Males

Svend Johnsen (1970)

The paper describes a new and rapid method forregistration of spermatogenesis in human testes: the testicular biopsy score count. Each tubular section is given a score from 10 to 1 according to presence or absence of the main cell types arranged in the order of maturity. Presence of spermatozoa scores 10, 9 or 8; spermatids (and no further) 7 or 6; spermatocytes (and no further) 5 or 4; only spermatogonia 3, only Sertoli cells 2 and no cells 1. The theoretical background of the score count method is discussed and it is emphasized that tissue heterogeneity, being a main point in most conditions, is exposed and evaluated by the method. Normal values are given and results obtained in 335 cases including a great variety of forms of male hypogonadism are presented. Patognomonic score counts leading to immediate diagnosis at a glance are obtained in many instances. A high correlation between testicular biopsy score count and sperm count is found and it is concluded that by this method it has for the first time become possible in man to correlate endocrine conditions with the functional state of the testicular tissue.