Carol S. Sloan

Chronic low-level lead toxicity in the rat: I. Maternal toxicity and perinatal effects☆☆☆

Abstract The first in a series of studies on the chronic exposure of rats to lead (Pb) is reported here. Weanling females were provided semipurified diets containing no detectable Pb, and drinking water containing 0, 0.5, 5, 25, 50, or 250 ppm Pb (as Pb-acetate). Rats were exposed to Pb-acetate for 6–7 weeks, then mated and exposed continuously throughout gestation and lactation. No statistically significant change in food or water consumption was noted in any exposure group. Females in the 50- and 250-ppm groups exhibited significant growth retardation within 1 to 3 weeks after exposure began. In addition, vaginal opening was significantly delayed in the 50- and 250-ppm groups, and to a lesser extent in the 25-ppm group. The level of Pb exposure used here did not affect the ability to conceive, to carry a normal litter to term, or to deliver the young. The percentage of malformed fetuses, resorptions, and postpartum pup deaths to weaning were unaffected by Pb exposure. Body lengths of female offspring in the 250-ppm exposure group were significantly shorter than those of controls, and there was a tendency for all young in this group to be smaller. The estimated dose of Pb consumed (mg/kg) indicated that groups were exposed to different amounts of Pb, and tissue (blood, brain, and bone) Pb concentrations indicated dose-related patterns. Urinary aminolevulinic acid concentrations were significantly dose related and were significantly correlated with blood Pb concentrations. Maternal toxicity occurred in groups exposed to 25 ppm Pb or higher and was associated with a minimum blood Pb concentration of 20 μg/dl.

Factors affecting pregnancy rates in a donor insemination program using frozen semen

The results of therapy of 226 women receiving frozen and fresh donor semen are reported. Overall, 45.6% of patients conceived with a monthly fecundability of 0.102. The effect of a variety of factors on fertility rates was analyzed in life-table analysis of 1000 cycles. Optimal pregnancy rates were obtained in couples with azoospermia (0.17) or no female infertility factors (0.2). Patients with ovulatory dysfunction treated with clomiphene also had optimal pregnancy rates (0.17 per cycle). Endometriosis reduced fecundability significantly (0.04 per cycle). There was no significant difference in pregnancy rates per cycle between fresh (0.12) and frozen (0.09) semen. Acceptable pregnancy rates were obtained with frozen semen therapy and in patients with treated ovulatory dysfunction.

Positive correlation between body weight, length of human menopausal gonadotropin stimulation, and oocyte fertilization rate *

One hundred four normally cycling women were treated with fixed low-dose human menopausal gonadotropin (hMG) (2 ampules/day) in preparation for oocyte aspiration for in vitro fertilization. The response rate was related to age, weight, and the ratios weight/height2 and weight/height. The required dose of hMG was related to total body weight, but not to age or either of the weight/height ratios. In patients who required fewer than 5 days of hMG (rapid responders), a significantly higher number (P less than 0.02) of oocytes were harvested, compared with slow responders. However, a smaller percentage of the oocytes from rapid responders fertilized (P less than 0.003) and resulted in a reduced rate of embryo transfer. The difference in pregnancy rates was not statistically significant. The results of the study suggest that patients undergoing in vitro fertilization who weigh less than 55 kg may benefit from treatment with a lower dose of hMG to prolong the stimulation cycle.

Genetic screening of donors for artificial insemination

A routine has been established for genetic screening of donors in an artificial insemination and frozen sperm bank program. This report is a summary and analysis of the information obtained on the first 168 donor applicants and 89 recipients who were genetically screened. The specific forms for screening, family information obtained, characteristics of the donor and recipient groups, and guidelines for acceptance or rejection of donors are discussed. The donor and recipient often failed to perceive that the disorders in the family were genetic. The simple question of whether or not there were genetic or hereditary problems in the family was ineffective, even when the donor or recipient had formal medical training.

Application of interspecies in vitro fertilization in the initial assessment of the infertile couple

Methods to evaluate male reproductive potential are limited. Conventional semen analysis does not necessarily reflect sperm functionality. In this study we investigated the correlation of the interspecies penetration test with clinical evaluation of 106 infertile couples. In vitro penetration results in 92 of 106 men correlated well with clinical diagnosis. In 28 couples with a male infertility factor, the mean penetration rate was 18%, whereas in 78 infertile couples with no known male factor, the rate was 50%. The mean for all patients tested was 40%. This was well below a mean of 73% for a donor population. The major discrepancy between the interspecies penetration test and clinical findings occurred in a group of nine patients with 0% penetration who had been judged normal by history and semen analysis. In general, the interspecies penetration test correlates well with male clinical evaluation but does the complementary information in certain cases. At present, its greatest utility seems to be in evaluation of unexplained infertility, in unexplained failure of female therapy, or in selection of patients for donor insemination.

Normalization of Testosterone Levels Using a Low Estrogen-containing Oral Contraceptive in Women with Polycystic Ovary Syndrome

Oral contraceptives reduce the elevated androgen levels in polycystic ovary disease. However, treatment with oral contraceptives is associated with undesirable side effects because of their high estrogen content. This study was undertaken to examine the effects of low estrogen-containing oral contraceptive (Loestrin:norethindrone acetate 1.5 mg and ethinyl estradiol 30 μg) on 25 women with polycystic ovary disease of ovarian origin. Loestrin treatment normalized the elevated luteinizing hormone and total and unbound testosterone levels and increased testosterone binding globulin levels. In a time–course study, unbound testosterone declined within a week of initiating treatment and by 12 to 16 weeks was completely normal. Reduction in hair growth and improvement in complexion were noted by about 12 to 16 weeks. Side effects of treatment were minimal.