John R. Marshall

Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy: I. Normal pregnancy☆

n To describe normal relationships between the various plasma unconjugated estrogens and progesterone during the second half of human pregnancy, the plasma concentrations of progesterone, 17-hydroxyprogesterone (17-OHP), and unconjugated estrone (E1), estradiol (E2), and estriol (E3) were measured in 126-310 normal women. Progesterone and unconjugated E1, E2, and E3 increased gradually throughout later pregnancy; 17-OHP increased only after the thirty-third week. At term the mean value of progesterone was 9 times higher than that 17-OHP. Throughout pregnancy the mean value of E2 was higher than that of E1 or E3. During the second half of pregnancy the ratios of progesterone to estradiol and estriol and of estradiol to estriol remained unchanged, indicating no preferential increase of plasma concentration of maternal or fetal hormones.n

Biologic and morphologic development of donated human ova recovered by nonsurgical uterine lavage

Using uterine lavage performed 5 days after the luteinizing hormone peak, we collected 25 uterine ova from five fertile donors who had had a single, periovular artificial insemination. After examination, all recovered ova were transferred to recipient uteri and resulted in three intrauterine and one tubal pregnancy. Morphologic development ranged from degenerating single-cell ova to mature blastocysts. Ages of the ova at recovery ranged from 93.5 to 130.0 hours postovulation. Mean age of the five blastocysts, 109.1 hours, was not significantly different from the mean age of the 20 less mature ova, 108.1 hours. Neither the mean interval from insemination to recovery for blastocysts nor the mean interval from insemination to ovulation for blastocysts was significantly different from the mean intervals of the other ova. The five blastocysts resulted in intrauterine pregnancies in three recipients. There were no intrauterine pregnancies from the other 20 transfers (p less than 0.004). A transferred 12-cell ovum with degenerating blastomeres was associated with tubal pregnancy in the recipient. The large variability in the state of intrauterine ova observed in the relatively fixed postovulatory interval of this study appears to be due to differences in viability and maturation, not differences in ovum age. Maturational state of the ova at the time of transfer appears to be a significant determinant of the likelihood of ensuring pregnancy.

Pituitary tumors and pregnancy

This paper contains a review of the natural history of pituitary tumors in nonpregnant and pregnant patients. Data were drawn from previously published reports and from responses to a questionnaire and were analyzed by life-table techniques. Follow-up of 62 nonpregnant patients with untreated pituitary tumors with and without visual field changes revealed a median time to treatment of 15 1/2 years and similar, relatively constant hazard functions. In 91 pregnancies occurring in 73 women with previously untreated pituitary tumors, ovulation had occurred spontaneously in 9 per cent, headache occurred in 23 per cent, and visual disturbances in 25 per cent with 61 per cent remaining asymptomatic. In those patients who developed symptoms, median time to headache was 10 weeks and to visual disturbance, 14 weeks. The hazard functions were relatively constant and similar. The relative risk of developing symptoms is independent of whether or not the first or second pregnancy occurred in the presence of the pituitary tumor. Of the pregnant patients with previously untreated pituitary tumors, 30 per cent required surgery or radiation therapy. Median time to treatment was 19 weeks. None of the 69 pregnant women without pituitary therapy had permanent sequelae. Only four patients who underwent surgery or received radiation treatment developed permanent symptoms and none was serious. In 78 pregnancies occurring in 73 women with previously treated pituitary tumors, headache occurred in 4 per cent and visual disturbances in 5 per cent. Only one patient required therapy. Treatment during pregnancy results in significantly increased prematurity rates but unchanged abortion and perinatal mortality rates. Small pituitary tumors do not constitute a contraindication to either induction of ovulation or pregnancy.

Meconium passage: a new classification for risk assessment during labor.

The significance of MSAL as a sign of fetal distress is controversial. To better assess this condition, we present a classification of MSAL based on the timing and quantity of meconium passed and divided into early light, early heavy, and late passage of MSAL. By means of this classification with a problem-oriented risk assessment system, 2,933 pregnancies were prospectively evaluated during labor. The incidence of meconium passage was 22 per cent, of which early light constituted 53.6 per cent, early heavy 25.2 per cent, and late passage 21.2 per cent. Early heavy MSAL is associated with increased fetal and neonatal morbidity and death, and with a number of antecedent obstetric problems. Late passage of MSAL encountered no perinatal losses, but is associated with increased neonatal morbidity occurring late in labor. Early light MSAL, constituting over half of all our meconium group of patients, is not associated with any increased intrapartum or neonatal morbidity or death. This classification of MSAL is an effective tool for risk assessment during labor.

The medical treatment of unruptured ectopic pregnancy with methotrexate and citrovorum rescue: preliminary experience *

Seven women with unruptured tubal pregnancies diagnosed on laparoscopy were treated with methotrexate and citrovorum rescue. Criteria for inclusion in the study were that the level of human chorionic gonadotropin (hCG) be plateaued or rising, that the ectopic pregnancy not exceed 3 X 3 cm, that the tubal serosa be intact, and that there be no active bleeding. The women were followed with serial measurements of hCG, complete blood counts, and liver function tests. All women responded to a single course of therapy. The median time to resolution (from the first day of treatment to when the hCG was undetectable) was 31 days (range, 5 to 50 days). Follow-up hysterosalpingograms were available for five women. Four women demonstrated tubal patency, and one showed a unilateral occlusion on the side of the ectopic. One woman was found to have an intrauterine pregnancy prior to the scheduled time of hysterosalpingogram.

Isolated Follicle-Stimulating Hormone Deficiency in Man

Two men with serum levels of follicle-stimulating hormone (FSH) persistently below 3 mIU/ml and normal levels of luteinizing hormone (LH), thyroid-stimulating hormone (TSH), growth hormone, prolactin, cortisol, and testosterone are reported. The intravenous administration of thyrotropin-releasing factor led to a normal increase in TSH and prolactin levels. Gonadotropin-releasing factor stimulation resulted in a net increase of 2 mIU/ml and 25 mIU/ml for FSH and LH, respectively. The administration of clomiphene resulted in a normal FSH increase in both patients, an LH increase in one, and a serum testosterone increase in the other. These results suggest a possible defect for FSH production at a level above the pituitary. Semen analyses revealed abnormalities in motility and morphology. A testicular biopsy from one patient revealed delayed maturation of spermatogenesis. It is recommended that serum FSH determinations be included in studies of male infertility patients.

Serum progesterone and estradiol-17β levels in premature and term labor

A total of 30 to 50 per cent of premature labors occur without identifiable predisposing conditions. To evaluate the hormonal status of these pregnancies, serum progesterone (P) and estradiol (E2) were measured by radioimmunoassay singly in 60 premature labor patients and serially in 19 normal pregnancies. Premature labor patients as a group have significantly lower P and E2 levels than controls. Pregnancies complcated by idiopathic premature labor (IPL) (p less than 0.01), premature labor secondary to abruptio-marginal separation (A-MS) (p less than 0.05), and premature rupture of membranes (PROM) (p less than 0.05) have significantly lower P levels than controls. Patients with IPL and A-MS have significantly lower P levels (p less than 0.01) than PROM patients. No significant change in P or E2 occurs immediately prior to normal term labor. Conclusions are that (1) premature labor patients have significantly lower Pand E2 levels than controls, (2) the degree of P depression varies according to the type of premature labor and (3) IPL is characterized by premature labor with no identifiable predisposing factors.

Antimicrobial therapy of postpartum endomyometritis: II. Prospective, randomized trial of mezlocillin versus ampicillin

Seventy patients with postpartum endomyometritis were treated with either intravenous mezlocillin (16 gm/day) or ampicillin (8 gm/day) in a prospective, randomized, double-blind comparison. Endocervical dilatation was routinely performed. Clindamycin (2 gm/day) was added if patients failed to improve within 48 hours of beginning therapy. Pretreatment clinical and microbiologic profiles were comparable in the two groups. Bacteremia was documented in 21 patients (30%). Anaerobic cocci and Bacteroides spp. (non-B. fragilis) comprised 19 of 29 (65%) blood isolates. Thirty of 33 mezlocillin-treated patients (91%) and 30 of 37 ampicillin-treated patients (81%) responded to initial therapy (P greater than 0.4). Resolution was noted after the addition of clindamycin in all ten nonresponders; two of these patients also required surgical wound debridement. Objective parameters of clinical response were not significantly different in the two treatment groups. Side effects of mezlocillin therapy were minimal. We conclude that mezlocillin and ampicillin are equally effective and safe for therapy of postpartum endomyometritis. That mezlocillin was not superior to ampicillin, despite expanded activity against B. fragilis and members of Enterobacteriaceae, suggests that these pathogens are less important than was previously considered in postpartum endomyometritis.

Clinical and microbiologic risk evaluation for post—cesarean section endometritis by multivariate discriminant analysis: Role of intraoperative mycoplasma, aerobes, and anaerobes

The clinical and microbiologic risk factors for postpartum endometritis were studied prospectively in 77 patients undergoing cesarean section without antibiotic prophylaxis at Harbor-University of California at Los Angeles Medical Center. Intraoperative cultures were obtained from the amniotic fluid, lower uterine segment, and abdominal wound for isolation of genital mycoplasmas, aerobes, and anaerobes. Postsection endometritis developed in 21 (27%) patients and was significantly associated with presence of either high-virulence bacteria (predominantly, coliforms, streptococci, anaerobic cocci, and bacteroides) (35% to 60% versus 10% to 24%; p less than 0.05) or Ureaplasma urealyticum (15% to 42% versus 0% to 10%; p less than 0.05) at any site compared with afebrile women. Multivariate analysis identified primary cesarean section, younger maternal age, presence of ruptured membranes, and presence of Ureaplasma as significant risk factors independent of other confounding variables (p less than 0.01). It is suggested that genital mycoplasmas could play a primary role in some cases of postsection endometritis or that they are cofactors or markers for the presence of other high-virulence aerobic and anaerobic bacteria.

Plasma estradiol, estriol, and progesterone in human pregnancy

Abstract The plasma concentrations of unconjugated estradiol (E 2 ), estriol (E 3 ), and progesterone (P) were measured by radioligand and radioimmunoassay in 8 patients with severe and 4 patients with mild Rh-isoimmunization disease. An abnormal ratio of either E 2 /E 3 or P/E 3 was found to precede each of 5 perinatal deaths attributed to hemolytic disease. Normal ratios of both E 2 /E 3 and P/E 3 were found in 6 of 12 patients and were associated with good fetal prognosis. A normal ratio of only one of either E 2 /E 3 or P/E 3 was associated with 2 and 1, respectively, of the 5 perinatal deaths attributed to the hemolytic disease. Determining both E 2 /E 3 and P/E 3 ratios is necessary for predicting fetal well-being in patients with Rh-isoimmunization disease. The method may be helpful in the follow-up of patients who undergo intrauterine fetal transfusion and may provide a more thorough assessment of fetoplacental function.