Background

Peripartum Cardiomyopathy (PPCM) is a heart disease, characterized by heart failure in previously heart-healthy women. Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs, including in vitro fertilization (IVF) or intracytoplasmatic sperm injection (ICSI), are associated with a risk for cardiovascular complications. Here, we investigate the association of subfertility and ART procedures with PPCM.

Methods and Results

Data were obtained from the German PPCM registry. Fertility information was available in 111 PPCM patients, of whom 30% (33/111) reported subfertility (SF-PPCM). From SF-PPCM 55% (18/33) obtained IVF/ICSI, 33% (11/33) hormonal treatment and 12% (4/33) conceived naturally. Parity was lower (p<0.05) and twin pregnancy rate was higher (p<0.05) in SF-PPCM while NYHA classification, LVEF, and NT-proBNP levels were not different compared to PPCM patients with normal fertility (N-PPCM). The cardiac outcome, defined by LV-recovery rate, was comparable between SF-PPCM and N-PPCM patients. Compared to postpartum women in the German general population, PPCM patients were significantly older at pregnancy (p<0.01), the percentage of life-born infants conceived by IVF/ICSI was significantly higher (p<0.01), they had more multiple births (p<0.01), and C-section (p<0.01) and preeclampsia (p<0.01) were more frequent while smoking status and parity were comparable, and the prevalence of gestational diabetes was significantly (p<0.05) lower. Whole exome sequencing in 15 SF-PPCM patients revealed pathogenic or likely pathogenic gene variants in 53% (n=8) of the patients, associated with dilatative cardiomyopathy (DCM, mutations in Titin, n=3; Desmoplakin, n=1; Carnitine O-palmitoyltransferase 2, n=1) and/or in genes associated with DNA damage repair (DDR, Ataxia telangiectasia mutated, n=1; Excision repair cross-complementation group 5, n=1; Nibrin, n=1). 

Conclusion

Almost one third of the patients in the present PPCM cohort displayed documented subfertility, and the proportion of infants conceived by ART was 6-fold higher compared with the total population in Germany. Reasons for female subfertility, i.e. increased age, hormonal disorders and high prevalence of pathogenic gene variants are frequently present in PPCM patients and suggest a causal relationship between subfertility and PPCM. However, there is so far no evidence that the ART treatment per se increases the risk for PPCM. Nevertheless, women receiving fertility treatment should be closely monitored for signs of heart failure.