Schwangerschaftsrate und Schwangerschaftsoutcome bei BRCA1/2-Mutationsträgerinnen

Abstract

Die retrospektive Studie untersuchte den Einfluss pathogener Varianten (pV) in gBRCA1/2 auf Fertilität, Nutzung reproduktionsmedizinischer Leistungen und Schwangerschaftskomplikationen bei Frauen. Insgesamt wurden 229 Ratsuchende des Zentrums Familiärer Brust- und Eierstockkrebs der Charité (2016–2020) analysiert, darunter 166 Frauen mit pV in gBRCA1/2 und 63 Frauen ohne pathogene Variante.

Frauen mit gBRCA1/2 zeigten mit 38% einen höheren Anteil an Kinderlosigkeit im Vergleich zu Frauen ohne pV (30,2%). Sie nutzten zudem häufiger reproduktionsmedizinische Leistungen (6,6% vs. 1,6%) und berichteten häufiger über einen unerfüllten Kinderwunsch von über 12 Monaten (11,4% vs. 4,8%). Das Durchschnittsalter bei der Geburt des ersten Kindes war bei Frauen mit pV um 1,2 Jahre höher.

Im Hinblick auf Schwangerschaftskomplikationen und Frühgeburtlichkeit ergaben sich nach Adjustierung keine statistisch signifikanten Unterschiede zwischen den Gruppen.

Die Ergebnisse zeigen, dass Frauen mit gBRCA1/2 möglicherweise häufiger reproduktionsmedizinische Unterstützung benötigen und stärker von Fertilitätsproblemen betroffen sind. Weitere groß angelegte Studien sind nötig, um die Zusammenhänge zu bestätigen und Unterschiede zwischen gBRCA1- und gBRCA2-Trägerinnen zu beleuchten. Diese Erkenntnisse könnten die Beratung und Betreuung betroffener Frauen verbessern.

The aim of this retrospective study was to examine whether women with a pathogenic variant (pv) in gBRCA1/2 were more frequently childless compared to women without evidence of a pv in gBRCA1/2 against the background of the lower follicular reserve and thus potentially reduced fertility, whether more reproductive medical services were uti-lized and whether the rate of pregnancy complications was increased.

Patients and Methods The study examined 229 women seeking advice from Charité's Familial Breast and Ovarian Cancer Center (FBREK), 166 (72%) of whom were found to have a pathogenic germline variant in BRCA1/2 between 2016 and 2020. Data from 63 (28%) women without a pathogenic germline variant in BRCA1/2 were ana-lyzed as a comparison cohort. All subjects were between 18 and 85 years old at the time of data collection. A digital questionnaire was developed to retrospectively record preg-nancy rates, pregnancy complications and pregnancy outcomes.

Results The proportion of nulliparous women was 38% (N=63) for pV in gBRCA1/2 carriers and 30.2% (N=19) for women without pathogenic germline alterations (p=0.1). 6.6% (N=11) of those seeking advice with a pv-detection used reproductive medical services, com-pared to 1.6% (N=1) of those seeking advice without pathogenic germline alterations. 11.4% (N=19) of women with a pathogenic germline variant in BRCA1/2 reported an un-fulfilled desire to have children for longer than 12 months compared to 4.8% (N=3) of women without a pathogenic germline variant in BRCA1/2 (p=0.1). The average age of the woman at the birth of the first child differed by 1.2 years (p=0.2) compared to women without pathogenic germline alteration (gBRCA1/2: 28.5 Jahre : wtBRCA: 27.3 Jahre ). The influence of the presence of one of the pathogenic germline variants in BRCA1/2 on the rate of pregnancy complications (p=0.09; 95% CI: 0.2-1.2) and premature birth (p=0.94; 95% CI: 0.3-3.2) was not statistically significant after adjustment using logistic regression.

Conclusion

The present study provides evidence that pregnancy complications and preterm birth were not more frequent in women with a pv in gBRCA1/2 compared to women with wtBRCA. However, women with a pathogenic germline variant in BRCA1/2 were more likely to require reproductive medical support, were more likely to be childless and more likely to complain of an unfulfilled desire to have children over 12 months. These findings should be further investigated in larger cohort studies against the back-ground of the controversial fertility differences described in the literature and the lower AMH level in women with pathogenic germline variants in BRCA1/2. Differences between the two pathogenic variants (gBRCA1 and gBRCA2) have also been described and should be addressed in subsequent studies. The results may further the understanding of the impact of these pV in gBRCA1/2 on pregnancy and be helpful in specific counseling of carriers.