Reduced serum testosterone levels in infant boys conceived by intracytoplasmic sperm injection.

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.

Impaired kidney growth in low-birth-weight children: distinct effects of maturity and weight for gestational age.

BACKGROUND: Low birth weight is an important risk factor for hypertension and unfavorable prognoses of a number of renal diseases. It is also associated with reduced kidney size and nephron number. A differentiation between the effects of low birth weight versus being born premature or small for gestational age has, however, not been addressed. METHODS: The influence of weight for gestational age (percentage deviation from expected mean), gestational age, birth weight, and early diet on kidney growth was studied in 178 children born pre- or postmature and/or small or large for gestational age, comparing them to 717 mature children, birth weight appropriate for gestational age. Kidney size was determined by bilateral ultrasonography measuring length, width and depth, using the equation of an ellipsoid for volume calculation. The examinations were performed at 0, 3, and 18 months of age together with measurements of body weight, height, and skinfold thickness. RESULTS: Weight for gestational age had a significant, positive effect on combined kidney volume at all three ages (0 months, P < 0.001; 3 months, P < 0.001; and 18 months, P < 0.001). A slight catch-up growth in kidney size was seen in the most growth-retarded infants (<10th percentile) between 0 and 18 months of age (mean Deltaz score(0-18 mo)=+0.22 SD) (P= 0.037). Premature children had smaller kidneys compared to mature at all ages (0 months, P= 0.001; 3 months, P= 0.007; and 18 months, P= 0.042), without any significant catch-up with age. Relative kidney volume was inversely correlated with weight for gestational age at birth (P= 0.007) but positively at 18 months (P= 0.008). Relative kidney growth 0 to 18 months was positively correlated to weight for gestational age (P= 0.013). Low birth weight was associated with impaired relative kidney growth in response to formula feeding. CONCLUSION: Being small for gestational age is associated with small kidneys at birth and impaired kidney growth in early childhood. The present data suggest that intrauterine growth has a regulatory influence on nephron formation and renal function in humans reaching beyond the neonatal period.