Ovarian response in BRCA1 carriers: a case-control study

Study question: To assess ovarian response to conventional ovarian stimulation
(COS) as part of a pre-implantation genetic diagnostic (PGD) treatment in
BRCA1 mutation carriers.
Summary answer: BRCA1 mutation is not associated with a reduced response
to ovarian stimulation.
What is known already: Loss-of-function mutations in the tumour suppressor
genes BRCA1/2 are associated with an increased lifetime risk of developing
breast- and/or ovarian cancer. In more recent years it has been hypothesized that
germline mutations in BRCA-genes may be associated with in fertility-related
problems. This is because BRCA genes participate in repair and maintenance
of chromosome telomeres and the integrity of those is central in reproductive
wellbeing.
Study design, size, duration: A retrospective, case-control, non-randomised
and mono-centre study. In the study group and both control groups 39 first
treatment cycles were included (13:13:13). They were matched (1:1) for ovarian
stimulation protocol, starting dose of gonadotrophins, for age ±3 years and
pick-up date ±1 year. The study period covered 2006-2013.
Participants/materials, setting, methods: Academic PGD reference centre.
13 BRCA1 cases (group A) stimulated in an antagonistic scheme with starting
dose of 150 units of gonadotrophins, matched to two control groups, group B,
patients for PGD for monogenic disorders not associated with infertility, and
group C patients for ICSI and blastocyst transfer.
Main results and the role of chance: Statistical analysis was performed using
SPSS software (version 22.0). Numerical variables were compared using Mann-
Whitney U-test, continuous variables were analysed by Fisher's exact test.
Compared with the control groups, B1 and B2, BRCA patients do not produce
a significant lower amount of mature oocytes (A: 10.077 (SD:5.6); B: 11.62
(SD:5.1); C:9.308 (SD:5.9)) and no significant difference was found in the total
dose of gonadotrophins used in the three groups to achieve this result (A: 1431
(SD:257) U; B:1450 (SD:303) U; C:1315(SD:264) U). No difference in pregnancy
rate was found; the pregnancy rate in all groups was 23.1%. Overall there are
no significant differences in outcome parameters between the groups compared.
Limitations, reason for caution: Although this series is larger than those
previously reported, the numbers remain small and more extensive studies are
required. The retrospective character of the study reflects clinical practice, however
does not exclude selection bias.
Wider implications of the findings: Contrary to recent studies that have suggested
that BRCA1 mutations are associated with an earlier menopause and
occult primary ovarian insufficiency, our study did not confirm reduced ovarian
response. This implies that BRCA patients presenting for IVF and/or PGD can
use conventional stimulation schedules.
Study funding/competing interest(s): Funding by hospital/clinic(s), Universitair
Ziekenhuis Brussel.
Trial registration number: N/A.