No abstract

The purpose of this study was to quantify the various sources of estrone (E1) and 17 beta-estradiol (E2) production in normal men and in women with testicular feminization. The mean production rate of E1 in four young adult men was 58 micrograms/24 h, while that of E2 was 44 micrograms/24 h. In these men, E1 production could be accounted for totally by extraglandular formation through 1) aromatization of plasma androstenedione, 2) conversion of E2 which was formed from the aromatization of plasma testosterone, and 3) conversion of secreted E2. In these men, only 12 micrograms or less of E2 production could not be accounted for by extraglandular formation from plasma C19 precursors, and is presumed to have arisen by testicular secretion. In six women with testicular feminization, the mean production rate of E1 was 99 micrograms/24 h, while that of E2 was 77 micrograms/24 h. THe amount of E2 production that arose by glandular secretion could be computed in four of these women and was considerably greater than that found in the young adult men. In these women with testicular feminization, an average of 44 micrograms/24 h E2 could not be accounted for by extraglandular formation and is presumed to have arisen by testicular secretion. The mean plasma production rate of testosterone in the normal men was 5.7 mg/24 h, while that in the women with testicular feminization was 8.3 mg/24 h. However, the range of plasma production rates of testosterone in the women with testicular feminization was large (1.3--17.0 mg/24 h).

The overall increase in live births demonstrated by this study indicates that the effort and expense to culture embryos in a low-O(2) environment is justified. The study was registered at clinicaltrials.gov. NCT00708487.

Fetal wastage syndrome is characterized by recurrent spontaneous abortion. Many syndromes are associated with recurrent fetal loss, including anatomical anomalies, endocrine/hormonal abnormalities, and coagulation defects, with coagulation defects accounting for ∼30% of cases. Most procoagulant factor defects are due to inadequate fibrin-mediated implantation of the fertilized ovum into the decidua. However, blood protein/ platelet defects leading to hypercoagulability and thrombosis are associated with thrombosis of placental vessels, precluding viability of the implanted ovum or later fetus. During the past 2 years, we have seen 46 patients with fetal wastage syndrome due to thrombosis-associated hemostasis defects. In this group, there have been three patients with sticky platelet syndrome, one patient with dysfibrinogenemia, four patients with congenital protein S deficiency, 35 patients with anticardiolipin antibodies, and one patient with a lupus anticoagulant. Patients were started on one low-dose aspirin (ASA), 81 mg per day preconception, at time of diagnosis, and low-dose s.c. porcine heparin at 5,000 units every 12 h was added immediately postconception. The combination of low-dose ASA plus low-dose s.c. porcine heparin was used throughout pregnancy. All patients achieving pregnancy have had uneventful, normal deliveries. It appears that blood protein/platelet defects leading to thrombosis and associated with recurrent fetal loss can be successfully managed with the use of preconception low-dose ASA, followed by immediate postconception addition of fixed low-dose porcine heparin, both used throughout pregnancy. Using this regimen, our success rate has been 100%. Ideal heparin doses, which might be much lower than our empirically chosen and currently used doses, remain to be defined in this particular indication. Key Words: Fetal wastage syndrome—Heparin—Aspirin.