Women with premutation (PM) of the FMR1 gene may suffer from reduced ovarian reserve or even premature ovarian insufficiency (POI). We studied hormonal and ultrasound ovarian reserve, fertility and fertility preservation outcomes in these patients.

Retrospective cohort study of 63 female FMR1 premutation carriers.

Sixty-three female patients bearing an FMR1 premutation were included. Median age was 30 years [26.5–35]. Median number of CGG triplets was 83 [77.2–92]. Before diagnosis of PM, 19 women (30%) had had in all 35 pregnancies, resulting in 20 births, including 7 affected children. After diagnosis of PM, 17 women (26.1%) had in all 23 pregnancies, at a median age of 34.5 years [32.2–36.0]: 2 after pre-implantation genetic diagnosis, 3 after oocyte donation, 18 spontaneously, and 5 ending in medical termination for fragile X syndrome. Thirty-three patients (52.4%) had POI diagnosis (median age, 30 years [27–34]) with median FSH level 84 IU/L [50.5–110] and median AMH level 0.08ng/mL [0.01–0.19]. After POI diagnosis, 8 women had in all 9 pregnancies: 3 following oocyte donation, and 6 spontaneous in 5 women (15.1%). Eight of the 9 pregnancies resulted in a live birth (including 2 affected children) and 1 in medical termination for trisomy 13. The median age of the 30 patients without POI was 31 years [25.2–35.0].

Thirteen women (20.6%) underwent fertility preservation, at a median age of 29 years [24–33]: FSH 7.7 IU/L [6.8–9.9], AMH 1.1ng/mL [0.95–2.1], antral follicle count 9.5 [7.7–14.7]. A median 15 oocytes [10–26] were cryopreserved in a median 2 cycles [1–3]. At the time of writing, no oocytes had yet been thawed for in-vitro fertilization.

This study shows the importance of early fertility preservation after diagnosis of FMR1 premutation in women, due to early deterioration of ovarian reserve. Genetic counseling is essential in these patients, as spontaneous pregnancies are not uncommon, even in cases of impaired ovarian reserve, and can lead to birth of affected children.