Sirolimus may reduce fertility in male renal transplant recipients.
Assessment of sex hormones in organ transplant recipients suggests that sirolimus may impair testicular function. The aim of this study was to evaluate the frequency and severity of sirolimus-associated alterations in sperm parameters and their impact on fathered pregnancy rate. An observational study was carried out in male patients aged 20-40 years who received a kidney transplant during 1995-2005. Patients were sent a questionnaire by post, and sperm analysis was proposed. The fathered pregnancy rates according to the immunosuppressive regimen were estimated and compared using the Poisson model. Complete information was obtained from 95 out of 116 recipients. Patients treated with sirolimus throughout the post-transplant period had a significantly reduced total sperm count compared to patients who did not receive sirolimus (28.6 +/- 31.2 x 10(6) and 292.2 +/- 271.2 x 10(6), respectively; p = 0.006), and a decreased proportion of motile spermatozoa (22.2 +/- 12.3% and 41.0 +/- 14.5%, p = 0.01). Moreover, the fathered pregnancy rate (pregnancies/1000 patient years) was 5.9 (95% CI, 0.8-42.1) and 92.9 (95% CI, 66.4-130.0) in patients receiving sirolimus-based and sirolimus-free regimens, respectively (p = 0.007). Of six patients in whom sirolimus treatment was interrupted, only three showed a significant improvement in sperm parameters. Sirolimus is associated with impaired spermatogenesis and, as a corollary, may reduce male fertility.
Zuber
J
J
Department of Kidney Transplantation, Necker Hospital, Paris, France. julien.zuber@nck.aphp.fr
Anglicheau
D
D
Elie
C
C
Bererhi
L
L
Timsit
M-O
MO
Mamzer-Bruneel
M-F
MF
Ciroldi
M
M
Martinez
F
F
Snanoudj
R
R
Hiesse
C
C
Kreis
H
H
Eustache
F
F
Laborde
K
K
Thervet
E
E
Legendre
C
C
D000328:Adult; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007248:Infertility, Male / Q000139:chemically induced*; D016030:Kidney Transplantation; D008297:Male; D011247:Pregnancy; D018873:Pregnancy Rate; D020123:Sirolimus / Q000009:adverse effects*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects
D007166:Immunosuppressive Agents; D020123:Sirolimus