Peter R. Garner

Changes in protein C and protein S levels in normal pregnancy

OBJECTIVE The objective of the study was to determine the normal changes in the plasma concentrations of protein C and protein S that occur during each trimester of pregnancy. STUDY DESIGN The study was a prospective cross-sectional study of 91 normal pregnant women who had plasma concentrations of protein C and protein S measured during the first, second, and third trimesters. RESULTS There was no statistically significant change in antigenic or functional protein C levels during normal pregnancy. Total protein S levels also remained unchanged. Free protein S levels fell significantly from first to second trimesters (0.45 U/ml mean to 0.26 U/ml mean, p < 0.001), but no further fall occurred during the third trimester. CONCLUSIONS The second-trimester fall in free protein S levels is a physiologic pregnancy adaptation. Women with a thromboembolic event appearing for the first time during pregnancy should have investigations for protein S deficiency delayed until the postpartum period, to avoid misdiagnosis and treatment.

Changes in activated protein C resistance during normal pregnancy

OBJECTIVE The objective of this study was to determine the changes in activated protein C resistance that occur during normal pregnancy. STUDY DESIGN In this cross-sectional study activated protein C was measured in 128 women with normal pregnancies in the first, second, and third trimesters and in nonpregnant control subjects with 24 to 39 women in each group. In addition, factor V, factor VIII, free protein S, and functional protein C were measured and correlated with activated protein C levels. Polymerase chain reaction for factor V Leiden mutation was performed. RESULTS There was a significant fall in the activity of activated protein C in the second and third trimesters of pregnancy (p < 0.05). This was related to increased factor VIII and decreased free protein S levels (p = 0.002, R2 = 0.20). The prevalence of the factor V Leiden mutation was 7.3%. CONCLUSION Resistance to activated protein C is increased in the second and third trimesters of pregnancy. This is related to the alterations in other coagulation proteins, a phenomenon normally occurring during pregnancy.

Pregnancies after premature ovarian failure

&NA; Six women who conceived after a diagnosis of premature ovarian failure are discussed. Two pregnancies occurred while the women were receiving conjugated estrogen therapy, two while taking oral contraceptives, and two women conceived spontaneously. The possible role of exogenous estrogens in sensitizing the granulosa cells to the effect of follicle‐stimulating hormone and thereby inducing ovulation and conception in some women with premature ovarian failure is examined. (Obstet Gynecol 67:59S, 1986)

Natural cycle in vitro fertilization-embryo transfer at the University of Ottawa: an inefficient therapy for tubal infertility *

OBJECTIVE To describe our experience with natural cycle IVF making clinical and endocrine comparisons with our standard stimulated cycle IVF program. DESIGN We attempted 75 natural IVF-ET cycles with hCG given to preempt the LH surge and compared these with 450 attempts at standard superovulation IVF-ET done in our unit during the same time period. PATIENTS Natural cycle patients are normally ovulating women < age 38. Superovulation IVF-ET patients are all < 41 years old. Patients in both groups had partners with normal semen parameters and tubal factor infertility. MAIN OUTCOME MEASURES Cancellation rates, pregnancy rates per egg retrieval, per ET procedure, and luteal phase E2:P ratios of the treatment cycles are compared. RESULTS There were 35 of 75 (47%) natural cycle and 112 of 450 (25%) superovulation cycle cancellations. An egg was retrieved in only 24 of 40 (60%) natural cycles and 336 of 338 (99%) superovulation egg retrieval procedures. Pregnancy rates per ovum pick-up procedure were significantly higher: 65 of 338 (19%) in the superovulation versus 2 of 40 (5%) in the natural cycle groups. Pregnancy rates per ET were not significantly different between natural IVF-ET, 2 of 18 (11%) and superovulation IVF-ET, 65 of 298 (22%). The E2:P ratios 5 days after ET were similar in both groups at 18 +/- 4 after natural IVF-ET and 21 +/- 18 after superovulation IVF-ET. CONCLUSIONS [1] Cancellation rates for natural cycle IVF are very high. [2] Midluteal E2:P ratios are the same in both groups. [3] Pregnancy rates per egg retrieval are significantly lower for natural versus superovulation IVF-ET. [4] In our experience, natural cycle IVF-ET is an inefficient therapy for tubal infertility compared with superovulation IVF-ET.

Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population

To estimate the frequency of exposure to prescription Food and Drug Administration (FDA) category C, D, and X drugs in pregnant women, and to analyze the maternal characteristics associated with such an exposure.

Homologous artificial insemination for oligoasthenospermia: a randomized controlled study comparing intracervical and intrauterine techniques

Homologous artificial insemination (AIH) is used to treat infertility caused by oligoasthenospermia, despite the lack of controlled studies confirming its benefit. This prospective randomized controlled trial was undertaken to determine whether intracervical (IC-AIH) or intrauterine (IU-AIH) homologous artificial insemination improves pregnancy rates in couples with infertility attributable to oligoasthenospermia alone. Twenty couples were randomized to receive IC-AIH or IU-AIH. Sixty-three insemination cycles were completed. During the same study period, 35 cycles with timed vaginal intercourse alone were assessed. Four pregnancies occurred, all following timed vaginal intercourse. No pregnancies resulted from IC-AIH or IU-AIH. This suggests that neither IC-AIH nor IU-AIH is of benefit when oligoasthenospermia is the cause of infertility. Pregnancies previously attributed to AIH may also have been conceived as a result of vaginal intercourse. This confounding effect on the results of AIH should always be considered.

Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population

Objective:To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population.Study Design:Historical cohort study.Result:A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy.Conclusion:About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.

Congenital adrenal hyperplasia in pregnancy

The congenital adrenal hyperplasias (CAH) are a group of inherited enzymatic defects of adrenal steroid biosynthesis. Deficiencies of each enzyme required in the steroid biosynthesis pathway are known, and these deficiencies are all inherited as autosomal recessive disorders. During pregnancy, maternal and fetal problems are confined to women who have 21-hydroxylase deficiency (P450c21 deficiency), 11-hydroxylase deficiency (P450c11 deficiency), and 3 beta-hydroxysteroid dehydrogenase deficiency (3 beta HSD deficiency), because other adrenal enzyme deficiencies are not compatible with fertility. The interposition of the placenta on the hypothalamic-pituitary-adrenal axis and other endocrine changes during pregnancy impact considerably on the clinical evaluation of the congenital adrenal hyperplasias. Successful management of CAH in pregnancy requires a firm knowledge of normal adrenal anatomic and endocrine changes that occur during gestation. Women with severe forms of CAH have decreased fertility rates because of oligo-ovulation, and successful conception requires a combination of good therapeutic compliance, careful endocrine monitoring, and often ovulation induction. From a fetal and neonatal standpoint, accurate prenatal diagnosis of 21-hydroxylase deficiency and 11-hydroxylase deficiency is now possible, which allows for prenatal treatment in an attempt to minimize clinical problems in the neonates. Prevention of masculinization of affected female fetuses by corticosteroid suppression has been attempted in both 21-hydroxylase deficiency and 11beta-hydroxylase deficiency CAH, with variable degrees of success. This review provides an overview of the congenital adrenal hyperplasias and their management during pregnancy.

Elevated serum dehydroepiandrosterone sulfate levels in patients with insulin resistance, hirsutism, and acanthosis nigricans

The association of insulin resistance, hyperandrogenism, and acanthosis nigricans is well established. The ovary is thought to be the site of the excess androgen production. The purpose of this study was to assess the adrenal contribution to the hyperandrogenic state in these women. Twenty-three patients presenting with the combination of hyperinsulinemia, elevated testosterone (T) levels, and acanthosis nigricans were investigated for the source of the increased androgen production. Twelve patients had elevated serum dehydroepiandrosterone sulfate (DS) levels (high DS group) suggestive of increased adrenal androgen production. Eleven patients had normal DS levels (normal DS group). Both normal DS and high DS groups had similar basal serum insulin levels and similar insulin response curves after a 3-hour, 75-gm, oral glucose tolerance test. No correlation was found between serum T or DS levels and either basal serum insulin levels or the area under the insulin response curve. These data suggest that DS levels are frequently elevated in patients with hirsutism, acanthosis, and hyperinsulinemia. Furthermore, the lack of association between serum DS and serum insulin levels suggests that insulin does not directly affect adrenal androgen production, or vice versa.

Thrombosis in Pregnancy: A Review

Abstract Venous thrombo-embolism (VTE) is the leading cause of maternal mortality. Thrombotic events are increased during pregnancy due to physiological changes in coagulation, venous stasis and pelvic vein injury. Symptoms of VTE can often be confused with normal pregnancy states. A high index of suspicion is essential to prevent serious morbidity and mortality following misdiagnosis. This article will outline the epidemiology, pathophysiology, investigations and treatment of VTE during pregnancy.