Reproductive and Metabolic Health of Young Men Conceived Using ICSI

Background: Use of ICSI has escalated globally. Concerns include: 1) heritability of infertility, 2) effects of poor-quality spermatozoa on offspring health, 3) epigenetic effects of ICSI procedure. Aim: Compare reproductive and metabolic health of ICSI-conceived men to IVF-conceived and spontaneously conceived (SC) controls. Method: This study is part of a larger project investigating the health and development, reproductive and metabolic health, and epigenetic profiles of ICSI-conceived men (aged 18-25 years). Age-matched IVF-conceived controls were sourced from the Clinical review of the Health of 22–35-year-olds conceived with and without ART (CHART) study; SC controls were derived from the Western Australian Pregnancy Cohort (Raine) study. In subgroup analyses, ICSI-conceived men of fathers with spermatogenic failure (STF-ICSI) were compared with ICSI-conceived men whose fathers had an obstructive cause of infertility, and IVF- and SC controls. Semen parameters and serum reproductive hormones were compared between 120 ICSI-conceived men and 356 SC controls. Resting systolic and diastolic blood pressure (BP), height, weight, BMI, body surface area, and serum metabolic markers were compared between 121 ICSI-conceived men, and 74 IVF-conceived and 688 SC controls. Results: We found no compelling evidence of poorer reproductive health in ICSI-conceived men compared to age-matched SC controls, including a subgroup of STF-ICSI-conceived men. There was no correlation in any of the semen parameters between ICSI fathers and sons, including STF-ICSI father-son pairs. ICSI-conceived men compared with SC controls had higher resting diastolic BP and higher homeostasis model assessment for insulin resistance (HOMA-IR), but a similar proportion had insulin resistance. Metabolic parameters of ICSI-conceived men and IVF-conceived controls were comparable. Conclusion: This study is the largest to date and indicates comparable reproductive health of ICSI-conceived men, including men whose fathers had STF, to a similarly aged population-representative cohort of SC men. It shows few metabolic differences between ICSI-conceived men, and IVF-conceived and SC controls.