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Reduced Serum Testosterone Levels in Infant Boys Conceived by Intracytoplasmic Sperm Injection

University Department of Growth and Reproduction (C.M.K., K.M.M., N.E.S., A.J.), and The Fertility Clinic (A.N.A., A.L.), Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Anders Juul, M.D., D.M.Sc., Ph.D., University Department of Growth and Reproduction GR, Rigshospitalet section 5064, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail: ajuul{at}rh.hosp.dk.

Context: Concern has been raised for the health of the offspring conceived by assisted reproduction technologies. Basal reproductive hormones around 3 months of age reflect the pituitary-testicular axis, which is transiently active at this age.

Objectives: We tested the hypothesis that transmission of impaired testicular function from father to son could be detected at 3 months of age in boys conceived by intracytoplasmic sperm injection (ICSI), which is predominantly used in the management of male infertility.

Design: We conducted a longitudinal prospective cohort study, including 125 boys conceived by ICSI, 124 boys conceived by in vitro fertilization (IVF), and 933 naturally conceived (NC) boys.

Intervention: Anthropometrical measurements were performed at birth and at 3 months of age; 58, 67, and 64% of ICSI, IVF, and NC boys, respectively, had a blood sample taken at 3 months.

Main Outcome Measures: We measured serum levels of LH, FSH, SHBG, inhibin B, testosterone, as well as penile length.

Results: Serum testosterone levels were significantly lower in boys conceived by ICSI (2.4 nmol/liter; 0.2–4.9 nmol/liter) (median; 2.5th–97.5th percentiles) compared with NC boys (3.3 nmol/liter; 0.6–7.6 nmol/liter; P < 0.001), and the LH to testosterone ratio was increased (0.8; 0.2–7.9 vs. 0.5; 0.2–2.3, respectively; P = 0.001). Boys conceived by IVF because of female infertility factors had a normal serum testosterone and LH to testosterone ratio compared with controls. Adjusted analyses for confounders did not alter the results.

Conclusions: Our results point toward a subtle impairment of Leydig cell function in boys conceived by ICSI, possibly inherited from their fathers. The clinical significance of our findings is uncertain. However, our findings should raise concern because ICSI is increasingly used to overcome male infertility.

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