生殖医療の総合的取り組みからみたヒト生殖のロスの研究(第56回学術講演会講演要旨)

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The precise diagnosis on the causes of recurrent pregnancy loss and its effective treatment for maintenance of gestation have been getting more important in reproductive medicine, further in recent Japanese population dynamics with low birth rate. Balanced chromosome rearrangements have been found at an increased frequency in couples with recurrent pregnancy loss compared with the general population. Chromosomal analysis of peripheral blood cells was performed on both partners of 1,639 couples. Among these, 63 chromosomal anomalies of 1,635 male partners (3.9%), 96 out of 1,639 female partners (5.9%) were found. The major anomalies were robert-sonian or reciprocal translocations. The most minor variants included pericentric inversion of chromosome 9. Both major and minor anomalies indicated approximately 80-90% spontaneous abortion rate. Upon our basic reproductive studies and through routine examinations based on the results of these investigations for recurrent reproductive wastages, antiphospholipid antibodies to anionic phospholipids such as cardiolipin (aCL) and phosphatidylserine (aPS) and zwitterionic phosphatidylethanolamine (aPE) were analyzed with enzyme-linked immunosorbent assays system developed in our laboratory. In recurrent pregnancy loss of the first trimester, IgG and IgM of aPE were significantly higher as compared to those of other phospholipid antibodies. Among recurrent pregnancy loss in the second and third trimester, again IgM of aPE and IgG of aCL were significantly higher. In another multicenter study including 15 institutes and hospitals conducted between 2000 and 2002 on antiphospholipid antibodies, similar positive rate of IgG and IgM of aPE were detected among females partners with a history of recurrent pregnancy loss. Co-agulation facto XQ, prekallikrein and high molecular weight kininogen are known as plasma contact protein in the intrinsic pathway of blood coagulation. Deficiencies of these proteins are not associated with clinical bleeding despite marked prolongation of in vitro surface-activated coagulation time, suggesting that these proteins possess anticoagulant and profibrinolytic activities. By making exact diagnosis on antiphospholipid antibody syndrome through our analysis of these antiphospholipid antibodies and factor XE, recurrent pregnancy loss due to this syndrome has been effectively treated with oral low dose aspirin and/or heparin injection, reducing abortion rate and maintening pregnancy to full-term deliveries. Antiphospholipid syndrome is not only pathologic to pregnancy but playing role to induce severe ischemic attach on vital organs including cerebral and cardio-vascular system. Therefore life-time management is essential for both the patient and her gynecologist. The beneficial effect of immunotherapy using husbands lymphocytes was revealed after deleting other pathologic factors to induce recurrent pregnancy loss. Congenital uterine anomaly with a consequent suboptimal uterine environment may have an influence on ovum implantation and early fetal development and thus may be a candidate in the etiology of reproductive wastage. Out of 2,061 hysterosalipingographies on the female partners with a history of recurrent pregnancy loss, 278 congenital uterine anomalies (13.5%) were detected. In these anomalies, approximately 60% were arcuate uterus and 30% were partial septate uterus, however incidences of spontaneous abortion were equally higher (more than 90%) as compared to normal pregnancy without anomaly. Histological findings using CD 34 positive staining as a maker of blood capillary distribution revealed that vascular system, especially arterial system, was significantly poor in the septum and uterine fundus muscle layer of congenital uterine anomaly as compared to those of normal uterus. This lack of blood capillary system then may reduce cytokines secretion and may disturb essential endocrine and metabolic function of the uterine endometrium. Following these basic fingings, and ideal metroplastic surgery has been introduced for the patients with congenital uterine anomaly. Before this metroplasty, 173 patients with the anomaly experienced 427 pregnancy losses out of 458 pregnancies, indicating 93.2% of abortion rate. However post operative abortion rate was significantly reduced to 12.5%. This post-operative prognosis of pregnancy is also significant when compared to the prognosis of the randomized unoperated control group with the anomaly. The results of the present investigation clearly indicate that there may be a selective mechanism in human reproduction which eliminates unfits conceptions, however that the number of pregnancy wastages can be minimized by comprehensive routine examination of each case and administration of appropriate therapy for each etiologic factor.
社団法人日本産科婦人科学会の論文
2004-08-01

生殖医療の総合的取り組みからみたヒト生殖のロスの研究(第56回学術講演会講演要旨)

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