Gender-Specific Alterations in Salivary Cortisol Levels in Pubertal Intracytoplasmic Sperm Injection Offspring

Abstract

Background: There is accumulating evidence that in vitro conception in humans may be associated with adverse health outcomes later in life. It has been proposed that suboptimal early life conditions may ‘program' key endocrine systems. A disturbance of the hypothalamic-pituitary-adrenal (HPA) axis leading to alterations in cortisol secretion in the offspring may be such a mechanism. To date, no data on cortisol levels in children conceived by intracytoplasmic sperm injection (ICSI) are available in the literature. Methods: In this cross-sectional study, salivary cortisol known as a key regulator of metabolism was measured and results were compared between 201 pubertal ICSI children and 196 spontaneously conceived (SC) counterparts. Results: ICSI females had lower mean salivary cortisol levels (9.0 µg/l; 95% CI 8.1-9.9) than SC females (10.6 µg/l; 95% CI 9.7-11.5; p = 0.01). This difference remained after adjusting for current characteristics, early life factors and maternal characteristics. In ICSI males, no difference in cortisol levels was found in comparison with the SC group. Conclusion: In our study, 14-year-old female but not male ICSI teenagers were found to have lower salivary cortisol concentrations in comparison with SC peers. However, before definite conclusions can be drawn, our results should be completed by longitudinal sampling.

Plasma Metabolomic Profiling Suggests Early Indications for Predisposition to Latent Insulin Resistance in Children Conceived by ICSI

“…Further studies are needed to investigate this observation. The decreased levels of cortisol in the ICSI compared to the NC group within the subset of girls analyzed using metabolomics is consistent with a recent publication reporting lower salivary cortisol levels in the ICSI-conceived girls [33]. Moreover, there is growing evidence of hypothalamo-pituitary-adrenal axis dysfunction and blunted cortisol response in children born preterm or small for gestational age [34]–[35].…”

Long‐term follow‐up of ICSI‐conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period

“…Glucocorticoids are important mediators of obesity and insulin resistance, and disruption of the hypothalamic–pituitary–adrenal axis has been proposed as a mechanism for unfavorable metabolic outcomes after in vitro conception (Belva et al ., ). Interestingly, lower salivary and serum cortisol levels have been reported in ICSI‐conceived girls compared to SC girls, although these results were based on single measurements (Belva et al ., ; Gkourogianni et al ., ). Mean salivary cortisol in the Belgium cohort was lower in ICSI‐conceived girls, which remained after adjusting for current characteristics, and early life and maternal factors (Belva et al ., ).…”

“…Interestingly, lower salivary and serum cortisol levels have been reported in ICSI‐conceived girls compared to SC girls, although these results were based on single measurements (Belva et al ., ; Gkourogianni et al ., ). Mean salivary cortisol in the Belgium cohort was lower in ICSI‐conceived girls, which remained after adjusting for current characteristics, and early life and maternal factors (Belva et al ., ). In a smaller cohort, an extensive review of plasma metabolomics also revealed lower cortisol levels in a subgroup of ICSI‐conceived girls aged 4 to 9 years compared to SC girls, alongside significant differences in 36 metabolites indicating early insulin resistance in the ICSI group (Gkourogianni et al ., ).…”

“…Another unexpected finding in this latter study was lower inflammatory markers in the ICSI group compared to SC controls including YKL‐40, which normally represents a marker of inflammation, obesity, and insulin resistance (Gkourogianni et al ., ). Collectively, these findings have been suggested to reflect an adaptive mechanism to counter the increased insulin resistance after ICSI conception, thereby maintaining metabolic homeostasis (Belva et al ., ; Gkourogianni et al ., ).…”

“…Interestingly, emerging data of fair quality demonstrates that ICSI‐conceived offspring may be at greater cardiometabolic risk, as indicated by increased adiposity (Belva et al ., ), insulin resistance (Gkourogianni et al ., ), differences in cortisol (Belva et al ., ; Gkourogianni et al ., ), and abnormal retinal vascularization (Wikstrand et al ., ). The possibility of heightened metabolic risk has also been suggested in other studies of IVF‐conceived offspring including another recent systematic review by Hart and Norman, with reports of higher blood pressure and triglycerides, vascular dysfunction, and glucose intolerance (Ceelen et al ., ; Sakka et al ., ; Hart & Norman, ).…”