Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

BACKGROUND: The effect of in vitro fertilisation (IVF) on breast cancer risk for BRCA1/2 mutation carriers is rarely examined. As carriers may increasingly undergo IVF as part of preimplantation genetic diagnosis (PGD), we examined the impact of ovarian stimulation for IVF on breast cancer risk in BRCA1/2 mutation carriers. METHODS: The study population consisted of 1550 BRCA1 and 964 BRCA2 mutation carriers, derived from the nationwide HEBON study and the nationwide PGD registry. Questionnaires, clinical records and linkages with the Netherlands Cancer Registry were used to collect data on IVF exposure, risk-reducing surgeries and cancer diagnosis, respectively. Time-dependent Cox regression analyses were conducted, stratified for birth cohort and adjusted for subfertility. RESULTS: Of the 2514 BRCA1/2 mutation carriers, 3% (n = 76) were exposed to ovarian stimulation for IVF. In total, 938 BRCA1/2 mutation carriers (37.3%) were diagnosed with breast cancer. IVF exposure was not associated with risk of breast cancer (HR: 0.79, 95% CI: 0.46-1.36). Similar results were found for the subgroups of subfertile women (n = 232; HR: 0.73, 95% CI: 0.39-1.37) and BRCA1 mutation carriers (HR: 1.12, 95% CI: 0.60-2.09). In addition, age at and recency of first IVF treatment were not associated with breast cancer risk. CONCLUSION: No evidence was found for an association between ovarian stimulation for IVF and breast cancer risk in BRCA1/2 mutation carriers

Prenatal Diagnosis and Preimplantation Genetic Testing for Inherited Cardiac Diseases

Inherited cardiac diseases (cardiomyopathies and channelopathies) are associated with an increased risk of sudden cardiac death (SCD). A common hallmark is the variable disease expression and incomplete penetrance. Therefore the phenotype varies widely between and within families. Carriers of a severe genetic disease have several reproductive options to fulfill their child wish due to progress in molecular genomics and assisted reproductive technology (Prenatal Diagnosis or Preimplantation Genetic Testing (PGT)). In this chapter, we describe the different reproductive techniques and evaluate the number of prenatal diagnoses and referrals for PGT for inherited cardiac diseases in literature and in the Netherlands in the past years. Although inherited cardiac diseases can exhibit a severe phenotype or a severe family history of sudden cardiac death, the number of patients with inherited cardiac diseases opting for and continuing with PND and PGT is small