IVF Unit, Department of Obstetrics and Gynecology, Shaare-Zedek Medical Center, Hebrew University Medical School, Jerusalem, Israel.
Hum Reprod. 2010 Oct;25(10):2629-36. doi: 10.1093/humrep/deq203. Epub 2010 Aug 16.
PGD for fragile X syndrome (FRAX) is inefficient, probably owing to fewer oocytes, poor embryo quality and difficulties in genetic analysis. We investigated IVF-PGD in FRAX mutation carriers compared with controls, looking at the effects of oocyte and embryo number/quality on live birth outcome.
We performed IVF-PGD in 27 patients with the FRAX mutation and 33 controls with other genetic diseases. Genetic testing was by multiplex PCR.
Seventy-nine and 108 IVF-PGD cycles were started in FRAX mutation carriers and controls, respectively. Twenty-two patients had a premutation (CGG repeat number 60-200) and five had a full mutation (300-2000 CGG repeats). FRAX patients required higher doses of gonadotrophins (6788 ± 2379 versus 4360 ± 2330, P< 0.001) but had lower peak serum estradiol levels (8166 ± 5880 versus 10 211 ± 4673, P = 0.03) and fewer oocytes retrieved (9.8 ± 6 versus 14 ± 8, P = 0.01). The cancellation rate (unsatisfactory ovarian response) was higher in the FRAX group than in the control group (13 versus 1%, P < 0.001). When embryos were transferred, ongoing pregnancy/live birth rates per transfer were similar (29 versus 36%, P = 0.54).
Ovarian dysfunction in FRAX carriers is more prevalent and profound than previously appreciated, with a high cancelation rate and reduced efficiency of PGD. The main determinant for successful PGD for FRAX is ovarian dysfunction. When embryo transfer is possible, the results are comparable to PGD for other monogenic diseases.
脆性 X 综合征（FRAX）的 PGD 效率低下，可能是由于卵母细胞数量较少、胚胎质量差和遗传分析困难。我们研究了 FRAX 突变携带者与对照组的 IVF-PGD，观察卵母细胞和胚胎数量/质量对活产结局的影响。
我们对 27 名 FRAX 突变携带者和 33 名患有其他遗传疾病的对照组患者进行了 IVF-PGD。遗传检测采用多重 PCR 法。
FRAX 突变携带者和对照组分别启动了 79 和 108 个 IVF-PGD 周期。22 名患者携带前突变（CGG 重复数 60-200），5 名患者携带全突变（300-2000 CGG 重复）。FRAX 患者需要更高剂量的促性腺激素（6788±2379 与 4360±2330，P<0.001），但血清雌二醇峰值较低（8166±5880 与 10211±4673，P=0.03），获得的卵母细胞较少（9.8±6 与 14±8，P=0.01）。FRAX 组的取消率（卵巢反应不佳）高于对照组（13%与 1%，P<0.001）。当进行胚胎移植时，每个移植的活产/妊娠率相似（29%与 36%，P=0.54）。
FRAX 携带者的卵巢功能障碍比以前认识到的更为普遍和严重，取消率高，PGD 效率降低。FRAX PGD 成功的主要决定因素是卵巢功能障碍。当胚胎移植可行时，结果与其他单基因疾病的 PGD 相当。
