Risk of cancer in children and young adults conceived by assisted reproductive technology

Abstract

STUDY QUESTION Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers’ questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE The median follow-up was 21 years (interquartile range (IQR): 17–25) and was shorter in ART-conceived children (20 years, IQR: 17–23) compared with naturally conceived children (24 years, IQR: 20–30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72–1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90–1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73–2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81–2.85; 1.80, 95% CI: 0.65–4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81–7.37) and melanoma (HR = 1.86, 95% CI: 0.66–5.27) were non-significantly increased for ART-conceived compared with naturally conceived children. LIMITATIONS, REASONS FOR CAUTION Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare. WIDER IMPLICATIONS OF THE FINDINGS Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important...

Observational retrospective study of UK national success, risks and costs for 319,105 IVF/ICSI and 30,669 IUI treatment cycles

“…The added risks have been reported for singleton IVF babies and singletons after fetal reduction having pre-term weights, and large sized babies from frozen embryo procedures. Late onset diseases relating to increased risk of some cancers are being reported 25 26. In vitro embryo cultures and exposures may affect later life developments along with any (epi) genetic modifications provide added risks27 or lead to higher imprinting disorders such as Beckwith-Wiedemann syndrome28–30 30 compared with naturally conceived children.…”

Cancer Risk in Children and Young Adults (Offspring) Born after Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

“…In our selection, the risk estimation was reported as OR for 15 studies [18,29,33,35,[38][39][40][41]52], RR for six studies [19,31,32,36,46,51], SIR for four studies [27,30,43,50], and HR for seven studies [17,44,[47][48][49]53,54]. [27,32,38,40,41], twenty-two studies reported tumors occurring in children aged <15 years [16,18,19,28,[30][31][32][34][35][36][38][39][40][41][42][43]45,[50][51]…”

“…The quality scores varied in the range from five to nine (median: seven; median for cohort studies: eight; median for case control studies: six). High-quality studies (i.e., those studies that had a score greater than or equal to seven) included 17 cohort studies [16,17,19,27,[30][31][32]37,43,44,[46][47][48][49][50][51]53] and seven case-control studies [18,[33][34][35]38,42,45].…”

“…In particular, we excluded the studies by Bradbury et al [63], by Källén et al [64], by Lerner-Geva et al [65], by Lidegaard et al [66], and by Pinborg et al [67], which were included in the meta-analysis by Wang et al [62]. By contrast, we included the studies by Brinton et al [51], by Hargreave et al [44], by Marees et al [36], by Munzer et al [35], by Wennerholm et al [53], by Spaan et al [47], and by Spector et al [46]. Therefore, the different search strategies and inclusion criteria yielded to dissimilar results.…”

Long-term health of children conceived after assisted reproductive technology

“…While no overall significant increase in cancer was observed, there was an increase of hepatic cancer and embryonal tumours among ART children in two sub-analyses. A recent study from the Netherlands, including 24,268 ART children and 13,761 children from spontaneous conceptions, but also including a control group of 9,660 children from subfertile couples, did not observe any increase in risk of cancer among the ART children (32). The study period was between 1980 and 2001, and the children were followed for a mean of 21 years.…”