Over the past decades the use of assisted reproduction technology (ART) gradually increased worldwide. Pregnancies conceived by in vitro fertilisation (IVF) or intracytoplasmatic sperm injection (ICSI) have a higher risk for hypertensive complications, which in turn are a risk factor for peripartum cardiomyopathy (PPCM). PPCM is a devastating cardiomyopathy with acute or subacute heart failure and reduced ejection fraction in previously healthy women. Here we investigate the incidence and outcome of patients with reported reduced fertility (subfertility) with and without ART procedures in PPCM patients.
Methods and Results
Data were collected in n=108 PPCM patients in our outpatient clinic or by phone interview. Plasma levels of markers associated with infertility and preeclampsia were measured at diagnosis of PPCM (n=30), and in healthy postpartum matched controls (n=24), using Multiplex Immunoassays.
No history of subfertility was present in 70% (PPCM-f; n=76), whereas 30% (n=32) of the patients reported subfertility. Out of the subfertile PPCM patients 56% (n=18) received IVF/ICSI (PPCM-I), 34% (n=11) hormonal treatment and 9% (n=3) conceived naturally. The share of live births conceived by IVF/ICSI in the total number of live births of all interviewed PPCM patients was 12.1%, while it is 2.2% in the German total population (Federal Statistical Office of Germany, IVF registry).
Twin pregnancy (12/32 vs. 12/76; p=0.0213) and C-section rate (27/32 vs. 41/66; p=0.0347) were higher in subfertile PPCM patients, otherwise both groups had comparable clinical histories at diagnosis. In PPCM-I age (37±4 vs. 34±4; p=0.0160), twin pregnancy and C-section rate were significantly higher and gravidity as well as parity were significantly lower compared to PPCM-f. At PPCM diagnosis, plasma markers associated with impaired fertility and/or preeclampsia, i.e. PAI-1, VEGFA, IL-8, Endoglin were altered overall in subfertile PPCM patients compared to PPCM-f. At 12 months follow-up, LVEF was significantly higher in all subfertile PPCM patients (55±7% vs. 50±9%; p=0.0371) and also in the subgroup of PPCM-I (56±6% vs. 50±9%; p=0.0396) compared to PPCM-f.
In the present PPCM collective one third of the patients had documented subfertility and the application of ART was high with more live births conceived by IVF/ICSI compared to the total population in Germany. The recovery rate of PPCM with reported subfertility is better compared to PPCM-f, which could be due to better clinical monitoring leading to earlier diagnosis and treatment. This holds also true for PPCM-I suggesting that IVF/ICSI may be a risk factor for PPCM but are not associated with adverse outcome in PPCM patients. The observed alterations in plasma markers may point to a specific pathophysiology in PPCM with subfertility. To examine whether ART procedures or subfertile conditions per se are risk factors for PPCM, more studies in this context are necessary.