Understanding the etiology of recurrent pregnancy loss (RPL) has been increasing in importance in reproductive medicine, especially in societies with low birth rates. Since the cause of human miscarriage is often complicated and multifactorial, effective treatment for the successful maintenance of pregnancy requires the comprehensive clinical management of recurrent wastages. Immunology for the maintenance of pregnancy is a very attractive field; however, the role of immunology during human gestation cannot be confirmed in couples with a history of recurrent pregnancy loss unless other clinical causes of miscarriage are especially ruled out.
Balanced chromosomal rearrangements have been found at an increased frequency in couples with recurrent pregnancy loss compared with the general population. The major anomalies are Robertosonian or reciprocal translocations, while most minor variants include pericentric inversion of chromosome 9. Both major and minor anomalies result in a spontaneous abortion rate of approximately 80-90%. Though the incidences of these chromosomal abnormalities vary in reported studies, a survey indicated an incidence of 9.8% (3.9% in male partners and 5.9% in female partners) among 1,639 couples with a history of recurrent pregnancy loss.
Congenital uterine anomaly resulting in a suboptimal uterine environment may influence ovum implantation and early fetal development and may be a candidate in the etiology of reproductive wastage.
A review on the relation between congenital uterine anomalies and the spontaneous abortion rate concluded that a precise diagnosis of uterine cavity deformity, especially arcuate uterus, is a key issue for determining the clinical prognosis during human gestation. After establishing diagnostic criteria for uterine cavity anomaly, 278 congenital uterine anomalies were detected in a series of 2,061 hysterosalpingographies (13.5%) performed in women with a history of recurrent pregnancy loss. Among these abnormalities, the incidences of spontaneous abortion were equally high among patients with arcuate uterus and those with partial septate uterus. A few studies on abortion mechanism in patients with congenital uterine anomalies have been reported. Histological findings using CD34- positive staining indicate the lack of a blood capillary system in both the uterine septum and the fundus muscle layer. The results of metroplastic surgery on congenital uterine anomaly are also controversial. Based on our fundamental findings of the maldistribution of uterine capillaries, we performed ideal metroplastic surgery in 173 women and significantly reduced the spontaneous abortion rate from a pre-operative values of 93.2% to a post-operative value of 12.5%.
Anti-cardiolipin antibody was first described by Huge et al. as a pathogenic auto-antibody capable of causing recurrent pregnancy loss. Since then several other candidates for zwitterionic antiphospholipid antibodies to anionic phospholipids that are capable of inducing miscarriage such as phosphatidylethanolamine (aPE) and phosphatidylserine (aPS). In a multicenter study on antiphospholipid antibodies conducted at 15 insitutes and hospitals between 2000 and 2002, significant levels of IgG and IgM for aPE were detected among women with a history of recurrent pregnancy loss. By establishing an enzyme-linked immunosorbent assay system, we determined that the IgG and IgM levels for aPE were significantly higher than those for other phospholipids antibodies during the first trimester recurrent spontaneous abortions. Coagulation factor XII, prekallikrein and the high molecular weight molecule kininogen have been reported as plasma contact proteins in the intrinsic pathway of the blood coagulation system. Deficiencies of these proteins are not associated with clinical obstetrical intrauterine bleeding, suggesting that these proteins possess anticoagulant and profibrinolytic activities.
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