Derks-Smeets Inge A P, de Die-Smulders Christine E M, Mackens Shari, van Golde Ron, Paulussen Aimee D, Dreesen Jos, Tournaye Herman, Verdyck Pieter, Tjan-Heijnen Vivianne C G, Meijer-Hoogeveen Madelon, De Greve Jacques, Geraedts Joep, De Rycke Martine, Bonduelle Maryse, Verpoest Willem M
Department of Clinical Genetics, Maastricht University Medical Centre +, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
Breast Cancer Res Treat. 2014 Jun;145(3):673-81. doi: 10.1007/s10549-014-2951-5. Epub 2014 Apr 19.
Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation. Only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC are evaluated in an observational cohort study on treatments carried out in two of Western-Europe's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. 70 Couples underwent PGD for BRCA1/2. 42/71 carriers (59.2 %) were female, six (14.3 %) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8 %) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9 % resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. PGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(PGD) in female carriers needs further evaluation.
植入前基因诊断（PGD）是一种生殖选择，适用于那些希望避免将遗传性乳腺癌和卵巢癌（HBOC）的易感性遗传给后代的BRCA1/2突变携带者。通过体外受精（IVF/ICSI）获得的胚胎会接受突变检测。只有BRCA阴性的胚胎才会被移植到子宫内。在一项观察性队列研究中，对2006年至2012年在西欧两个最大的PGD中心进行的治疗进行了评估，以确定PGD对HBOC的适用性和结果。男性携带者、无症状女性携带者和乳腺癌幸存者符合条件。如有可能，可对化疗前冷冻保存的胚胎进行PGD。必要时，基于单倍型分型开发通用的PGD-PCR检测方法，并结合突变检测。70对夫妇接受了BRCA1/2的PGD检测。42/71名携带者（59.2%）为女性，其中6名（14.3%）在PGD之前患有乳腺癌。总共进行了145个PGD周期。对720个胚胎进行了检测，其中294个（40.8%）被鉴定为BRCA阴性。在新鲜的IVF/PGD周期中，23.9%的周期获得了临床妊娠。三个周期涉及对化疗前冷冻保存的胚胎进行PGD；其中两名女性分娩了健康的婴儿。总体而言，有38名儿童存活出生。两名BRCA1携带者在PGD治疗后不久被诊断出患有乳腺癌，尽管在PGD之前筛查结果为阴性。事实证明，HBOC的PGD是合适的，对于无症状携带者和乳腺癌幸存者都能产生良好的妊娠率。由于治疗后不久出现了两例乳腺癌病例，女性携带者中IVF（PGD）对母体的安全性需要进一步评估。
