A total of 309 children presented for in-person assessment of cardiometabolic outcomes (24% of the 1302 children enrolled in the DESCRT); of these, 19 children did not meet the age-related inclusion criteria or otherwise did not undergo baseline measurements, leaving 290 children (164 boys, 126 girls) for analyses (94% of those evaluated for Tanner stage).

Table 1 presents the distribution of descriptive characteristics of the study sample. The overall median age of children was 6 years (range, 4 to 18 years). In addition, the median ages of boys and girls separately were both 6 years (boys’ interquartile range, 5 to 10 years; girls’ interquartile range, 4 to 10 years; p = 0.83).

Children from the UA + NIFT group were significantly older at baseline assessment compared to children in the ART group with mean ages of 8.2 ± 3.5 years (n = 61) and 7.2 ± 3.5 years (n = 229), respectively (p = 0.02). We did not observe differences between the ART and UA + NIFT groups in terms of race or ethnicity (p = 0.37 and p = 0.80, respectively). We did not observe any differences between the two comparison groups in terms of current household income (p = 0.38) or mother’s highest education (p > 0.9) but information was only available for about two-thirds of participants for these variables.

The overall mean weight and height of the study population were 29 ± 14 kg and 128 ± 21 cm, respectively. UA + NIFT children had both higher mean height and mean weight compared to ART children (p = 0.04 and p = 0.02, respectively). We evaluated differences in age, height, and weight by method of conception for girls and boys (Fig. 1). We observed no differences in height and weight between girls and boys within categories of age (4–10 and 11–18 years); the only statistically significant difference was seen in girls aged 4 to 10 years, wherein the UA + NIFT group had a higher mean weight (p = 0.04).

Characteristics of children by method of conception, separately for boys and girls, DESCRT study, 2017–2022. Left, characteristics of girls; right, characteristics of boys. IVF, in vitro fertilization; NIFT, non-IVF fertility treatment. p-values are derived from the Kruskal–Wallis test

Children from the ART group tended to have smaller mean tricep skinfold thickness compared to the UA + NIFT group but the difference was not statistically significant (p = 0.13), which may be related to younger gestational age at delivery and/or older maternal age at delivery observed for this group (p = 0.04 and p < 0.001, respectively). We did not observe any differences between the two comparison groups in terms of antepartum complications during pregnancy or birthweight (Table 1).

Figure 2 illustrates the percentages of girls and boys in each Tanner stage distributed by method of conception. Five girls were missing a Tanner score for thelarche and four boys were missing a Tanner score for gonadarche. One hundred thirty-five (84.4%) boys were classified as being in stage 1 in terms of testicular development, and 95 (78.5%) girls received a breast Tanner score of 1. Of the children in the UA + NIFT group, 28 of 33 (84.8%) boys were classified as being in Tanner stage 1 for pubarche, while 21 of 28 (77.8%) girls were in Tanner stage 1 for pubarche. By comparison, in the ART group, we observed 108 of 131 (82.4%) boys and 79 of 98 (80.6%) girls in Tanner stage 1 for pubarche.

Percentages of boys and girls in Tanner stages 1–5, distributed by method of conception, DESCRT study, 2017–2022. a Pubarche stages in boys; b gonadarche stages in boys; c pubarche stages in girls; d thelarche stages in girls. IVF, in vitro fertilization; NIFT, non-IVF fertility treatment

In total, 62 (21.4%) children were from a multiple birth, including 39 (23.8%) boys and 23 (18.3%) girls; multiple birth data were unreported for eight (2.7%) children. Of these multiple birth children, 59 (95.2%) were conceived via fresh IVF or frozen IVF (37 boys and 22 girls), versus three (4.8%) children conceived without assistance or IUI (two boys and one girl (p < 0.001)). The overall median age of children, excluding those born in a multiple birth, was 6 years (range, 4 to 18 years). After excluding multiple birth children, we still observed no difference in birthweight between comparison groups, and additionally found no significant differences in gestational age at delivery (p = 0.75 and p > 0.9, respectively).

After adjustment for children’s age, height, and weight, boys from the ART group had a higher odds of being in a later Tanner stage compared to the reference group for both pubarche (OR = 2.33, 95% CI 0.44–12.21) and gonadarche (OR = 4.27, 95% CI 0.44–41.99), although the increase was not statistically significant (p = 0.32 and p = 0.21, respectively). In girls, the ART group had higher odds of being in both later pubarche (OR = 4.29, 95% CI 0.40–45.62) and thelarche (OR = 2.23, 95% CI 0.35–14.03) stages but these increases similarly did not reach statistical significance (p = 0.23 and p = 0.39, respectively).

When children belonging to a multiple birth were excluded from analyses, boys in the ART group had a higher odds of being in a later pubarche Tanner stage than boys in the UA + NIFT group (OR = 1.53, 95% CI 0.23–10.12), but a lower odds of being in a later stage for gonadarche (OR = 0.88, 95% CI 0.03–23.54), although neither of these differences achieved statistical significance (p = 0.66 and p > 0.90, respectively). Girls in the ART group had higher odds of being in later Tanner stages for both pubarche (OR = 2.67, 95% CI 0.19–38.04) and thelarche (OR = 4.55, 95% CI 0.45–46.20), but these increases were not statistically significant (p = 0.47 and p = 0.20, respectively).

Because only seven girls from the UA + NIFT group were classified as being of a Tanner stage of 2 or higher, we conducted a sub-analysis of children conceived only via ART by method of embryo transfer (comparing fresh vs. frozen IVF). Of the boys conceived via fresh embryo transfer, 13 (15.7%) received a Tanner score of 2 or greater for pubarche, while 13 (15.9%) were scored 2 or greater for gonadarche. Ten (20.8%) boys conceived via frozen embryo transfer were scored 2 or greater for pubarche and 9 (18.8%) for gonadarche. Regarding girls conceived via fresh embryo transfer, 13 (22.0%) and 13 (22.8%) were scored 2 or greater for pubarche and thelarche, respectively. Six (15.4%) girls conceived via frozen embryo transfer were scored 2 or greater for pubarche and 6 (16.2%) for thelarche. After adjusting for children’s age, height, and weight, boys conceived via frozen embryo transfer had a higher odds of being in a later Tanner stage for pubarche (OR = 2.06, 95% CI 0.26–16.57) but not gonadarche (OR = 1.03, 95% CI 0.09–12.29), compared to those conceived via fresh embryo transfer, though neither association was statistically significant (p = 0.49 and p > 0.90, respectively). Girls conceived via frozen embryo transfer had lower odds of being in a later Tanner stage for thelarche compared to girls conceived via fresh transfer (OR = 0.76, 95% CI 0.07–8.72), but the trend was not statistically significant (p = 0.82). An analysis could not be performed on pubarche Tanner scores in girls due to insufficient statistical power. The results of the logistic regression analyses are summarized in Table 2.

After excluding children belonging to a multiple birth, boys conceived via frozen transfer had a higher odds of being later in pubarche Tanner stage compared to the fresh transfer group (OR = 1.74, 95% CI 0.14–22.18) but the difference was not statistically significant (p = 0.67). Girls conceived via frozen embryo transfer had a higher odds of being in a later thelarche stage compared to girls conceived via fresh transfer (OR = 2.17, 95% CI 0.06–79.76), but the difference similarly failed to reach statistical significance (p = 0.67). Insufficient statistical power prevented the analyses of gonadarche Tanner stage in boys and pubarche Tanner stage in girls. The results of the logistic regression analyses excluding children born in a multiple birth are presented in Table 3.