Teratogenic IgG From Sera of Women With Spontaneous Abortions Seem to Induce Anomalies and Yolk Sac Damage in Rat Embryos. A Possible Method to Detect Abortions of Immunologic Origin

PROBLEM: Spontaneous abortions due to immunological rejection of the embryo may be avoided by immunotherapy with paternal allogeneic leukocytes but there is no appropriate method to detect and differentiate this group of aborters from other groups. METHODS: In previous studies we have demonstrated that in about two-thirds of sera from women with spontaneous abortions the IgG antibodies are responsible (alone or in combination with other factors) for the embryotoxic effects of these sera on cultured rat embryos. We presently cultured 10.5-day-old rat embryos on highly teratogenic serum (“high risk” serum that induced anomalies in more than 50% of the embryos) from women with spontaneous abortions, where the IgG fraction was exchanged with IgG from control sera and vice-versa. We studied by Transmission Electron Microscopy (TEM) the extent of yolk sac damage in comparison to the rate of embryonic anomalies. RESULTS: In cases where IgG antibodies were teratogenic, embryos cultured in control sera with IgG from “high risk” sera exhibited ultrastructural yolk sac damage as well as embryonic anomalies, and the yolk sacs cultured in “high risk” sera with control IgG were normal. In cases in which the IgG exchange did not change the rate of anomalies, as IgG was not teratogenic, yolk sacs from embryos cultured in “high risk” sera remained damaged, while yolk sacs from embryos cultured in control sera after IgG exchange stayed normal. Although no significant difference in total IgG levels was found between the groups, a higher IgG1 level in sera from women with teratogenic IgG was observed in comparison to control women's sera. The obstetrical history of the women with two or more abortions who took part in our study showed that there were more cases of unknown etiology of the abortion in the women from the “high risk” group. CONCLUSIONS: The serum and the IgG fraction from women with habitual abortions can be tested in whole embryo culture to evaluate the embryonic and yolk sac damage. On this basis it may be possible to detect the women in whom the habitual abortions result from immunological rejection.     

In Vitro Suppression of Murine Blastocysts Growth by Sera From Women With Reproductive Disorders

ABSTRACT: Early mouse embryos at the two-cell stage were cultured in medium supplemented with sera from women with primary and secondary multiple spontaneous abortions and with long term unexplained infertility as compared to sera obtained from normal fertile women and pooled human male sera. On the basis of microscopic observation and uptake of ³H-thymidine we report a relationship between reproductive histories and the presence of a serum embryo inhibition factor in eight of ten sera samples from women with primary habitual abortions, six of ten sera from women with secondary habitual abortions, and ten of ten sera from women with unexplained infertility. This activity occurs independently of positive maternal antipaternal lymphocytotoxicity. Fractionation of serum samples by ammonium sulphate precipitation, resulted in removal of the embryo-inhibition factor with the IgG fraction in four of five primary habitual abortion cases and in two of five secondary habitual abortion patients, but not in the case of unexplained infertility. We propose that the appearance of such inhibition factor may be of relevance in the etiologies discussed in this paper and may possibly provide the basis for a new classification of idiopathic spontaneous habitual abortions, i.e. positive or negative for the embryo inhibition factor.     

The Effect of Sera Antisperm Antibodies in the Female Partner on In Vivo and In Vitro Pregnancy and Spontaneous Abortion Rates

PROBLEM: To determine the incidence of antisperm antibodies (ASA) in female sera from infertile couples or those suffering from recurrent abortions. Also to determine if the pregnancy and/or abortion rates are any higher in those positive versus those negative for ASA. METHOD: All registered patients had sera drawn and ASA measured by indirect immunobead test on initial study. Pregnancy and abortion rates were determined for patients undergoing in vivo or in vitro therapy. RESULTS: There was a low incidence of ASA in patients having in vivo or in vitro treatment. There was no decrease in pregnancy rates (PRs) or increase in spontaneous abortions (SAB) in those positive for ASA. CONCLUSION: Antisperm antibodies in female sera do not seem to be etiologic in causing infertility or SAB. Future studies might consider changing the antigen source from donor sperm to husband's sperm.     

Effects of Cyclic Increase in Gonadotropins on the In Vitro Development of Primordial Follicles to Antral Stage

The aim of this study was to evaluate the effects of FSH and LH on follicle development during a long-term culture of cryopreserved human ovarian tissue, using morphological and ultrastructural examinations. Thawed ovarian tissue slices from a 4-year-old child with Wilms tumor were cultured for 32 weeks in two different culture conditions, without (medium A) and with (medium B) a monthly peaked increase in FSH and LH. At week 32, in the medium B cultured tissue, a cluster of preantral follicles associated with two oocytes prematurely ovulated was observed, suggesting that the cyclic increase of gonadotropins promoted thawed follicles to grow up to the antral stage. However, the integrity and coordinated follicle development were not maintained. Indeed, ultrastructural analysis showed a well-preserved “naked” oocyte with concomitant features of immaturity and maturity, as if this culture condition had led to an asynchronous maturation of oocyte cytoplasmic components.