Patient is a 31 year old woman with positive family history of thrombophilia –paternal grandfather with stroke, paternal uncle with myocardial infarction. She has had no significant illness. There is no personal history of thrombotic and autoimmune diseases.
Medical diagnosis and summary of pregnancies:
1) Full term pregnancy with a Cesarean section delivery due to a decrease in amniotic liquid and rupture of membranes at the 38th week. No complications during pregnancy;
2) Miscarriage due to suspected fetal growth delay - Miscarriage around the 17th week, with no cardiac activity revealed by ultrasound; no previous threat of miscarriage. Histological examination suggested a cystic lymphangioma in the left lateral-cervical region. Normal karyotype.
3) Miscarriage treated with ASA - Miscarriage around the 12th week, with no cardiac activity revealed by ultrasound, no previous threat of miscarriage. Histological examination showed decidual tissue infiltrated with lymphocyte elements and chorionic villi. Normal karyotype, female fetus.
The patient underwent hysteroscopy to remove intrauterine adhesions.
4) Miscarriage around the 8th week, with no cardiac activity revealed by ultrasound. During the first few weeks of pregnancy, appearance of high fever due to presumed streptococcal pharyngitis, treated with amplital and tachipirina. Normal Beta HCG levels; normal thyroid hormones values. The medical treatment consisted of folic acid and ASA, 75 mg/day, starting at least two months before conception; Seleparina, 4,000 UI/day, starting at conception; and with Benexol. Normal karyotype, female fetus.
Medical diagnosis and tests were done at the Poliabortivity Center, ROME, and at the Polyclinic TOR, Vergata. The results were compared with the previous ones and showed a re-positivation of the ANA (1/180). A cross-match was also performed and gave negative results; the serologic HLA Class I and Class II typing showed the following:
PHENOTYPE AB (serologic): A2, A2, B8, B62(15)
PHENOTYPE DR (serologic): DR3, DR4, DR52, DR53, DQ2, DQ8(3)
The patient’s husband underwent the same HLA typing testing with the following results:
PHENOTYPE AB (serologic) A2, A26(10), B51(5), B35
PHENOTYPE DR(serologic):DR402, DR11, DR53, DR52, DQ7(3), DQ8(3)
In T-lymphocyte test, a reduction of the total number of T-cell subpopulations, with phenotype CD4+ and CD4+/CD8+ ratio, are found to be within normal range.
5) Miscarriage around the 9th week, with no cardiac activity revealed by the ultrasound. The prophylaxis was: Prefolic, 1 tablet/day; Aspirinetta, 1 tablet/day; Seleparina, 6000 UI/day; Deltacortene 1 and 1/2 tablet of 5 mg/day (total 7.5 mg); Benexol, 1 tablet/day; Ferrograd, 1 tablet/day; the patient started also Prontogest, 1 vial/day.
The histological analysis showed the following: Multiple grey-brownish fragments measuring 4cmx3cm when aggregated. Microscopic analysis shows that the material is composed of residues with blood extravasation and necrosis, chorionic villi of various size, with irregular profile, and some with a cistern-like formation and minor hyperplasia of the throphoblast. The endometrium appears glandular, ARIAS-STELLA type, with nucleated erythrocyte and embryonic residues. Similar histological patterns can be observed also during partial mole. HCG monitoring is recommended. Normal karyotype, female fetus.
In the course of several medical consultations up to date, it has been confirmed to the patient that nothing of significance has emerged to justify 4 miscarriages: Anti-thyroid antibodies, ANA and anti-phospholipids were tested positive but not with high values; mutation in the MTHFR of heterozygotes is fairly common; there isn’t a particularly clear thrombophilia (though the last two pregnancies were similarly interrupted). Finally, there doesn’t seem to be any incompatibility in the couple since the cross-match result is negative and also in view of the first pregnancy which was carried to full term without any problems.