mercaptopurine and Infertility--Male

Topics: Adaptation, Psychological; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Female; Humans; Immunosuppressive Agents; Infertility, Female; Infertility, Male; Inflammatory Bowel Diseases; Male; Mercaptopurine; Mesalamine; Pregnancy; Pregnancy Complications; Reproductive Behavior; Stress, Psychological; Sulfasalazine

Cytotoxic drugs, which are widely used as immunosuppressive and antiinflammatory agents in patients with neoplastic conditions, and cancer chemotherapy preparations, are of long-range concern due to the problem of cumulative organ toxicity which is not manifested until damage is extensive. These considerations have arisen because of their widespread use in recent years. Those involved in hepatic toxicity are the antimetabolites methotrexate and 6-mercaptopurine. Bisulfin, bleomycin, and methotrexate have been linked to pulmonary toxicity. Daunomycin and adriamycin, used as anticarcinogens, are examined for their cardiac toxicity. Cyclophosphamide and streptozotocin affect the urinary tract. These drugs have specific toxic effects on fertility in both males, through its disruption of the testicular function, and in females, for ovarian disruptions. Antifolics, 6-mercaptopurine, azathioprine, and alkylating agents, used for therapy in pregnant women, particularly in the first 4 months, are linked to the appearance of fetal abnormalities. The process of carcinogenesis is examined for clues to possible chemotherapy-related 2nd tumors, which appear during the course of treatment.

Topics: Alkylating Agents; Antineoplastic Agents; Azathioprine; Bleomycin; Busulfan; Carcinogens; Chemical and Drug Induced Liver Injury; Daunorubicin; Doxorubicin; Female; Fetus; Folic Acid Antagonists; Follow-Up Studies; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infertility, Female; Infertility, Male; Liver; Lung Diseases; Male; Mercaptopurine; Methotrexate; Myocarditis; Neoplasms; Ovary; Pregnancy; Procarbazine; Streptozocin; Testis; Urologic Diseases

Azathioprine and 6-mercaptopurine interact in purine metabolism and DNA synthesis, thus their potential mutagenic effects have been of concern in the management of inflammatory bowel disease (IBD), especially in patients of childbearing age. Although several clinical studies have indicated their safety in both reproduction and pregnancy, in a recent large epidemiological study concerns were raised about their adverse effects in pregnant patients with IBD, and experimental or basic data on this subject are limited. The aim of this study was to investigate sperm production, sperm quality, and reproductive outcome following prolonged 6-MP administration to male mice.. Highly inbred Balb/c adult male mice were used. 6-MP at doses of 2, 5, and 8 mg/kg (n = 9 for each group) was given daily for 51 days and the treatment group was compared with controls. After 45 days of treatment, the mice were mated with females. Following 13 days of pregnancy, the products of conception were evaluated and live fetuses were examined for gross malformations. Sperm production and morphology were examined after 51 days of 6-MP administration.. Treatment with 6-MP at all doses did not affect sperm morphology and sperm production in the testicular tubules, as compared with controls (70% normal sperm). However, pregnancy rates were inversely related to escalating doses of 6-MP: 55%, 41%, 28%, and 16% for control, 2, 5, and 8 mg/kg groups, respectively. Resorption rates (abortions) were 21% in the control group as compared with 45-50% in all the treatment groups, but the incidence of major congenital malformations was not increased.. Long-term 6-MP treatment in male mice did not impair sperm production and sperm morphology. However, a significantly high rate of embryonic resorption indicated occult sperm damage. Thus, normal sperm analysis does not necessarily imply that sperm damage at genetic level did not occur. It is difficult to extrapolate from these results to the clinical use of 6-MP/azathioprine in IBD patients; however, further basic genetic testing for DNA damage and clinical follow-up are warranted.

Topics: Animals; Embryo Loss; Female; Fetal Diseases; Immunosuppressive Agents; Infertility, Male; Male; Mercaptopurine; Mice; Pregnancy; Pregnancy Outcome; Reproduction; Spermatogenesis; Spermatozoa

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Azathioprine; Colitis, Ulcerative; Crohn Disease; Female; Fetal Diseases; Humans; Infertility, Female; Infertility, Male; Male; Mercaptopurine; Metronidazole; Pregnancy; Pregnancy Complications; Risk; Sulfasalazine

Dominant-lethal assays in male mice were made with the following cytostatics: Cyclophosphamide, TS-160, Edikron, Penberol, Cytembena, Mercaptopurine, Butocin, and Damvar. The cytostatics were administered mostly for 14-day periods, with the exception of Butocin (7 days) and high doses of Cyclophosphamide and TS-160 (single administrations). From the first day of administration on, the males were mated with intact females mostly at eight one-week intervals, and the quality of pregnancy was checked. Antifertility effects were found with TS 160, Penberol (at high dosage), and Mercaptopurine. Effects on permiogenesis with genetic risk were found with Cyclophosphamide, TS-160, Mercaptopurine, and less marked ones also with Cytembena. The effects were mostly manifested by increases in the numbers of early fetal resorptions, and less frequently by preimplantation loss of ova. No genetic risk was revealed by the assay in the cytostatics Edikron, Penberol, Butocin, and Damvar.

Topics: Acrylates; Alkylating Agents; Animals; Antimetabolites, Antineoplastic; Cyclophosphamide; Drug Evaluation, Preclinical; Female; Fetal Resorption; Infertility, Male; Male; Mercaptopurine; Mice; Mutagens; Nitrogen Mustard Compounds; Pregnancy; Spermatogenesis

Topics: Administration, Oral; Adolescent; Antineoplastic Agents; Cyclophosphamide; Drug Synergism; Follow-Up Studies; Humans; Infertility, Male; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Paternity; Prednisone; Remission, Spontaneous; Spermatozoa; Time Factors