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Reduced serum testosterone levels in infant boys conceived by intracytoplasmic sperm injection
Claudia Mau Kai1, Katharina M Main, Anders Nyboe Andersen
1University Department of Growth and Reproduction, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Insights
Boys conceived via intracytoplasmic sperm injection (ICSI) show subtle Leydig cell dysfunction. This may indicate a potential inherited impairment from fathers with male infertility, raising concerns due to ICSI
Area of Science:
- Reproductive Endocrinology
- Pediatric Endocrinology
- Assisted Reproductive Technologies
Background:
- Assisted reproductive technologies (ART) raise concerns regarding offspring health.
- Early reproductive hormone levels in infants reflect transient pituitary-testicular axis activity.
Purpose of the Study:
- To investigate potential transmission of impaired testicular function from father to son.
- To assess Leydig cell function in 3-month-old boys conceived via intracytoplasmic sperm injection (ICSI).
Main Methods:
- Longitudinal prospective cohort study comparing ICSI, in vitro fertilization (IVF), and naturally conceived (NC) boys.
- Measurement of serum reproductive hormones (LH, FSH, SHBG, inhibin B, testosterone) and penile length at 3 months of age.
- Analysis included 125 ICSI boys, 124 IVF boys, and 933 NC boys.
Main Results:
- Boys conceived by ICSI exhibited significantly lower serum testosterone levels compared to NC boys.
- The luteinizing hormone (LH) to testosterone ratio was elevated in ICSI-conceived boys.
- No significant differences in testosterone or LH/testosterone ratio were observed in IVF-conceived boys (due to female infertility) compared to controls.
Conclusions:
- Findings suggest subtle Leydig cell dysfunction in boys conceived by ICSI, potentially inherited from fathers.
- The increasing use of ICSI for male infertility warrants attention to these findings.
- Clinical significance requires further investigation, but raises concern for ART-related outcomes.
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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