O-285 Reproductive hormones at 7-10 years of age in children born after assisted reproductive technology

Abstract

Study question Do reproductive hormones and pubertal development differ at 7-10 years of age in children conceived after frozen embryo transfer, fresh embryo transfer or natural conception? Summary answer Pubertal development, reproductive hormones, and the prevalence of precocious puberty was not altered in the children conceived after ART. What is known already The global rise in the use of assisted reproductive technology (ART) reflects the declining fertility rates. Investigation of the long-term health of children born after ART is therefore important. A former registry-based study found a higher risk for early puberty in girls and late puberty in boys conceived after ART. Study design, size, duration The Health in Childhood following Assisted Reproductive Technology (HiCART) cohort included children conceived after ART with frozen embryo transfer (FET) n = 200, fresh embryo transfer (Fresh-ET) n = 203 and natural conception (NC) n = 203. The study was conducted from January 2019 to September 2021. Participants/materials, setting, methods Pubertal development and serum concentrations of reproductive hormones were evaluated in 606 singletons (292 boys) aged 7-10 years from the HiCART cohort. Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) were measured by immunoassays, and concentrations of estradiol (E2), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), androstenedione and 17-hydroxyprogesterone (17-OHP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Main results and the role of chance Among girls, clinical signs of puberty (Tanner ≥ B2) were found in 14% (16/107) in the FET-group, in 16% (15/98) in the fresh-ET-group and in 23% (23/98) in the NC-group, with no difference between the three groups (Chi-square p = 0.35). Clinical signs of puberty below the age of 8 (precocious puberty) years were found in 6/314 girls (median age 7.79 [range 7.46-7.87]), of whom three were in the FET-group and three in the NC-group. The concentration of LH was below 0.3 IU/L in all six girls, while four out of six girls had measurable estradiol. Among boys, clinical signs of puberty (testicular volume >3 ml) were absent in boys in the FET-group (0/86), while present in 2% (2/99) in the fresh-ET group and in 1% (1/101) in the NC-group. No significant difference was found in concentrations of hormones (LH, FSH, SHBG, E2, T, DHEAS, Androstenedione and 17-OHP) when comparing respectively girls and boys born after FET, Fresh-ET and NC, neither in the entire cohort nor after excluding pubertal children. Limitations, reasons for caution A slight risk of selection bias remains due to the lack of information on the cause of infertility. In addition, since the birth of the included children, today vitrification is the preferred freezing method in contrast to slow-freezing, which constitutes the most frequent method in our study. Wider implications of the findings Our data did not support previous findings, as pubertal development, reproductive hormones, and the prevalence of precocious puberty did not differ between the three conception groups. This is re-assuring on an individual and societal level as there is an increasing need for ART in many countries. Trial registration number Yes