Le Poulennec Tiphaine, Dubreuil Sophie, Grynberg Michael, Chabbert-Buffet Nathalie, Sermondade Nathalie, Fourati Salma, Siffroi Jean-Pierre, Héron Delphine, Bachelot Anne
Departement of Endocrinology and Reproductive Medicine, centre de référence des maladies endocriniennes rares de la croissance et du développement, centre de référence des pathologies gynécologiques rares, IE3M, hôpital Pitié-Salpêtrière, AP-HP, Paris, France; Sorbonne université médecine, Paris, France; Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
Departement of Endocrinology and Reproductive Medicine, centre de référence des maladies endocriniennes rares de la croissance et du développement, centre de référence des pathologies gynécologiques rares, IE3M, hôpital Pitié-Salpêtrière, AP-HP, Paris, France; Sorbonne université médecine, Paris, France; Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
Ann Endocrinol (Paris). 2024 Jul;85(4):269-275. doi: 10.1016/j.ando.2024.04.004. Epub 2024 May 1.
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.
携带脆性X智力低下基因1（FMR1）前突变（PM）的女性可能会出现卵巢储备功能下降，甚至卵巢早衰（POI）。我们研究了这些患者的激素水平、超声检查的卵巢储备功能、生育情况及生育力保存结局。
对63名携带FMR1基因前突变的女性进行回顾性队列研究。
纳入63名携带FMR1基因前突变的女性患者。中位年龄为30岁（26.5 - 35岁）。CGG三联体的中位数为83（77.2 - 92）。在诊断为PM之前，19名女性（30%）共怀孕35次，分娩20次，其中包括7名患病儿童。诊断为PM后，17名女性（26.1%）共怀孕23次，中位年龄为34.5岁（32.2 - 36.0岁）：2次为胚胎植入前遗传学诊断后怀孕，3次为卵母细胞捐赠后怀孕，18次为自然怀孕，5次因脆性X综合征而选择医学终止妊娠。33名患者（52.4%）被诊断为POI（中位年龄30岁（27 - 34岁））；促卵泡生成素（FSH）水平中位数为84 IU/L（50.5 - 110），抗缪勒管激素（AMH）水平中位数为0.08 ng/mL（0.01 - 0.19）。诊断为POI后，8名女性共怀孕9次：3次为卵母细胞捐赠后怀孕，5名女性中有6次为自然怀孕（15.1%）。9次怀孕中有8次分娩活婴（包括2名患病儿童），1次因13 - 三体而选择医学终止妊娠。30名未患POI的患者中位年龄为31岁（25.2 - 35.0岁）。13名女性（20.6%）进行了生育力保存，中位年龄为29岁（24 - 33岁）：FSH为7.7 IU/L（6.8 - 9.9），AMH为1.1 ng/mL（0.95 - 2.1），窦卵泡计数为9.5（7.7 - 14.7）。中位冷冻15枚卵母细胞（10 - 26枚），中位冷冻2个周期（1 - 3个周期）。在撰写本文时，尚未解冻任何卵母细胞用于体外受精。
本研究表明，由于卵巢储备功能早期恶化，FMR1基因前突变女性诊断后早期进行生育力保存很重要。遗传咨询对这些患者至关重要，因为即使卵巢储备功能受损，自然怀孕也并不罕见，且可能导致患病儿童出生。
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