Fertility treatments and pediatric neoplasms of the offspring: results of a population-based cohort with a median follow-up of 10 years.
Studies have questioned the long-term health effects of offspring conceived after fertility treatments.



We aimed to evaluate whether an association exists between mode of conception (in vitro fertilization, ovulation induction, or spontaneous pregnancy) and neoplasm risk (both benign and malignant tumors) among the offspring; we observed the offspring for up to 18 years.



A population-based cohort analysis was performed that compared the risk for neoplasms among children (up to the age of 18 years) based on mode of conception. Neoplasm diagnoses were based on hospital records of the same single tertiary center in the region. All singletons born during from 1991-2013 and discharged alive were included in the study. Offspring with congenital malformations were excluded from the analysis. Kaplan-Meier survival curves were constructed to compare cumulative neoplasms incidence; multivariable survival analyses were used to control for confounders that included gestational age, pregnancy complications, and maternal factors.



During the study period, 242,187 newborn infants met the inclusion criteria: 2603 (1.1%) were conceived after in vitro fertilization; 1721 (0.7%) were conceived after ovulation induction treatments, and 237,863 (98.3%) were conceived spontaneously. During the follow-up period (median, 10.55 years), 1498 neoplasms(0.6%) were diagnosed. Incidence density rate for neoplasms was higher among children conceived either after in vitro fertilization (1.5/1000 person years) or ovulation induction treatments (1.0/1000 person years), as compared with naturally conceived children (0.59/1000 person years; Kaplan-Meier log rank, P<.001). The association between in vitro fertilization and total pediatric neoplasms and the association between any fertility treatments and malignancies remained significant; we controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age (adjusted hazard ratio, 2.48; 95% confidence interval, 1.71-3.50; and adjusted hazard ratio, 1.96; 95% confidence interval, 1.14-3.36, for all neoplasms and all malignancies, respectively).



Children conceived after fertility treatments are at an increased risk for pediatric neoplasms.
Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: wainstoc@bgu.ac.il.
Tamar
T
Wainstock
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Asnat
A
Walfisch
Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Ilana
I
Shoham-Vardi
Ministry of Health, Jerusalem, Israel.
Idit
I
Segal
Department of Fertility and IVF unit, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Avi
A
Harlev
Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Ruslan
R
Sergienko
Department of Pediatrics, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Daniella
D
Landau
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Eyal
E
Sheiner
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007247:Infertility, Female / Q000628:therapy; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D010062:Ovulation Induction / Q000009:adverse effects*; D012307:Risk Factors; D013997:Time Factors
assisted reproduction technology; childhood cancer; fertility treatment; in vitro fertilization; ovulation induction