The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors

Abstract

CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615–5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401–4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account.

Parenthood for childhood cancer survivors: unfounded fear of cancer development in offspring and related health behaviors

“…Nevertheless, after having survived cancer at a young age, it is not surprising that CCS anxiety and fear levels are higher, as they themselves were affected and often suffer long-term consequences of a life-threatening disease and its intensive treatment. However, this heightened fear does not stem from fact, as offspring of CCS are as healthy as other children (Sommerhäuser et al, 2021;Borgmann-Staudt et al, 2022). Rather, these results indicate that survivors harbor dysfunctional beliefs that their offspring have a higher risk of developing childhood cancer, which should be addressed during therapy.…”

“…Accordingly, an U.S. American CCS Study, which examined 4.699 offspring from 2.755 CCS regarding congenital anomalies, revealed no increased risk for malformations in offspring whose parents had received mutagenic therapies (Signorello et al, 2012). Overall, CCS´ offspring were found to be as healthy as their peers and did not exhibit an elevated risk of developing congenital anomalies compared to their counterparts, even after Assisted Reproductive Technology (ART; Sommerhäuser et al, 2021;Borgmann-Staudt et al, 2022). While Ripperger et al (2017) described a cancer predisposition syndrome, and familial immunodeficiency can increase the risk of childhood cancer in some cases (Armstrong et al, 2009), the influence of genetic variation in CCS is inconsistent in genome-wide association studies (Clemens et al, 2018).…”

Oocyte collection and outcome following oncologic treatment: a retrospective multicentre study

“…Fertility can be safeguarded via oocyte (unfertilised or fertilised) and/or ovarian tissue cryopreservation in adolescent and adult cancer patients. Where feasible, guidelines recommend the use of fertility preservation measures prior to cancer treatment [ 4 – 6 ]. These options, though, have limitations, which depend, among other factors, on cancer diagnose and treatment.…”

“…Current experimental approaches to overcome this barrier include in vitro maturation (IVM) of early stage oocytes or artificial ovaries [ 9 , 10 ]. Independent of whether or not fertility preservation measures were used prior to treatment, current guidelines recommend fertility surveillance and discussion of results and preservation options within the routine clinical follow-up after oncologic treatment [ 4 – 6 ]. Fertility monitoring following cancer treatment should include menstrual cycle information, which can be of value in detecting fertility irregularities, as well as hormone analyses, including anti-Mullerian hormone (AMH), a marker for ovarian reserve, and if indicated the antral follicle count (AFC) measured by ultrasound by a reproductive specialist.…”