Miura Kiyonori, Niikawa Norio
Departments of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto , Nagasaki, 852-8523, Japan.
J Hum Genet. 2005;50(1):1-6. doi: 10.1007/s10038-004-0216-6. Epub 2004 Dec 15.
Although monochorionic (MC) dizygotic twins (DZT) are extremely rare in natural pregnancy, six pairs of such twins have successively been reported in a recent short period. All six cases of MC DZT were the products of pregnancy by assisted reproductive technology (ART). In this overview, we summarize these six cases and discuss possible mechanisms of this twinning and clinical implications of confined blood cell chimerism (CBC). The placental MC membrane was diagnosed ultrasonographically in all cases and pathologically in four. The presence of CBC was confirmed in four cases by haplotyping at polymorphic marker loci in peripheral blood leukocytes, karyotyping of lymphocytes and skin fibroblasts, and/or ABO blood group typing. As CBC is attributable to placental vessel anastomosis between DZT, it may become a risk factor for twin-twin transfusion syndrome (TTTS), mortality, and for other complications in twins. MC DZT may produce psychological trauma, especially in a girl/woman when she grows up and is known to be chimeric for a male karyotype and vice versa, although genital organs are generally normal--unlike freemartin in cattle. In addition, CBC in twins may mislead physicians when genotyping for a disease-susceptibility test is performed in medical practice in the near future. Blood group chimera may also cause confusion if a blood transfusion is necessary. Therefore, sufficient informed consent prior to ART and genetic counseling before/after birth are absolutely necessary for improved quality of life. It is most likely that all six cases are the consequence of fusion between two outer cell masses from two zygotes. The ART used in the six MC DZT included in vitro fertilization-embryonic transfer (IVF-ET) into the uterus, FSH-induced superovulation followed by intrauterine insemination, and/or intracytoplasmic sperm injection (ICSI). The use of an ovulation-inducing agent and implantation of several fertilized eggs at close sites are probably the events common among these cases. Assisted hatching, simultaneous ET, the use of eggs that have developed to the blastcyst stage, and cell culture procedures that lead to changes of the nature of cell surface, all may increase the chance of a cell fusion. This "chance hypothesis" can simply explain why MC DZT are very rare in natural pregnancy. Large-scale research on the prevalence of ART-associated MC DZT and long-term follow-up of the twins are essential.
尽管单绒毛膜（MC）双卵双胎（DZT）在自然妊娠中极为罕见，但近期在短时间内相继报道了6对这样的双胞胎。所有6例MC DZT均为辅助生殖技术（ART）妊娠的产物。在本综述中，我们总结了这6例病例，并讨论了这种双胎妊娠的可能机制以及局限性血细胞嵌合体（CBC）的临床意义。所有病例均通过超声诊断胎盘MC膜，4例经病理诊断。4例通过外周血白细胞多态性标记位点的单倍型分析、淋巴细胞和皮肤成纤维细胞的核型分析和/或ABO血型分型，证实存在CBC。由于CBC归因于DZT之间的胎盘血管吻合，它可能成为双胎输血综合征（TTTS）、死亡率及双胎其他并发症的危险因素。MC DZT可能会造成心理创伤，尤其是当女孩/女性长大后，已知其具有男性核型嵌合体时，反之亦然，尽管生殖器官通常正常——这与牛的异性双胎不育不同。此外，在不久的将来，当在医疗实践中对疾病易感性检测进行基因分型时，双胞胎中的CBC可能会误导医生。如果需要输血，血型嵌合体也可能造成混淆。因此，ART前充分的知情同意以及出生前后的遗传咨询对于提高生活质量绝对必要。很可能所有6例都是两个受精卵的两个外层细胞团融合的结果。6例MC DZT所使用的ART包括子宫内体外受精 - 胚胎移植（IVF - ET）、FSH诱导的超排卵后子宫内授精和/或卵胞浆内单精子注射（ICSI）。使用促排卵剂以及在相近部位植入多个受精卵可能是这些病例中的共同事件。辅助孵化、同步胚胎移植、使用发育到囊胚期的卵子以及导致细胞表面性质改变的细胞培养程序，都可能增加细胞融合的机会。这种“机会假说”可以简单解释为什么MC DZT在自然妊娠中非常罕见。对ART相关MC DZT的患病率进行大规模研究以及对双胞胎进行长期随访至关重要。
