Health outcomes in offspring born to survivors of childhood cancers following assisted reproductive technologies

Abstract

Purpose An increasing number of childhood cancer survivors are using assisted reproductive technologies (ART) to overcome treatment-related fertility impairment. We report perinatal and health outcomes of offspring born to survivors following ART. Methods The FeCt Multicenter Offspring Study surveyed the health of offspring of childhood cancer survivors. Health outcomes in offspring born to survivors following ART (n = 57, 4.6%) or after spontaneous conception (n = 1182) were assessed in the German cohort (n = 1239) using bivariate analysis. Findings were put into the context of the general German population by health outcome assessment in 1:1 matched-pair analysis (n = 2478). Results Nearly twice the survivors used ART compared with numbers reported for the German general population (4.6% vs. 2.6%). Successful pregnancies were achieved after a median of two cycles, mainly using non-cryopreserved oocytes/sperm. Multiple sibling births (p < 0.001, 28.1% vs. 3.0%) and low birth weight (p = 0.008; OR = 2.659, 95% CI = 1.258-5.621) occurred significantly more often in offspring born to survivors who utilized ART than spontaneously conceived children, whereas similar percentages were born preterm or too small for their gestational age. ART did not increase the prevalence of childhood cancer or congenital malformations in offspring born to survivors. Conclusion ART use by childhood cancer survivors was successful with both fresh and cryopreserved oocytes/sperm, and did not influence perinatal health or health outcomes when known confounders were taken into account. Implications for Cancer Survivors Oncofertility is an important component of patient care. Our study implicates that the utilization of ART by adult survivors of childhood cancer does not put offspring at additional risk for adverse perinatal or health outcomes.

The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors

“…Survivors of childhood cancer are at increased risk for fertility impairment, and thus, numbers of ART utilisation in this cohort have increased in recent years. In a previous study, ART was used by twice as many survivors as in the general population [ 30 ]. Our current analyses revealed that childhood cancer survivors also requested ART more often (4.5%) than their siblings (3.7%).…”

“…The underlying mechanisms, including epigenetic changes that may occur during preimplantation and the development of uterine reprogramming, are currently under debate [ 28 , 29 ]. Publications examining ART and health issues of childhood cancer survivor offspring are rare [ 30 ]. Our study compared: (i) the prevalence of ART utilisation in survivors and their siblings, (ii) perinatal outcomes, malformations, heart defects and cancer in ART-conceived survivor offspring with those conceived spontaneously and (iii) the outcomes of survivor offspring vs. sibling offspring.…”

Fertility preservation in the pediatric population—experience from a German Cryobank for ovarian tissue

“…There were more multiples born and a higher prevalence for low birth weight in the offspring of cancer survivors, whereas the prevalence for preterm birth or small for gestational age were comparable to spontaneously conceived offspring of cancer survivors. Neither childhood cancer nor congenital malformations were found to be increased in the offspring (1). Therefore, it is extraordinarily important that every patient of reproductive age and every child should have the possibility to be counseled in a specialized center by gynecologists, reproductive/ endocrine specialists, or urologists/andrologists before the gonadotoxic treatment starts as recommended by the current S2k guideline on fertility preservation for patients with malignant diseases (2).…”

Fertility Counseling in Survivors of Cancer in Childhood and Adolescence: Time for a Reappraisal?

“…These data are consistent with our findings. In contrast, a study on cancer survivors’ offspring conducted by a German group on 1239 women found that their health status was comparable with that of the general population [ 15 ].…”