Rodney P. Shearman

Autoimmune oophoritis: a clinicopathologic assessment of 12 cases.

Twelve cases of histologically confirmed autoimmune oophoritis are described. Eight presented with symptoms and laboratory evidence of premature ovarian failure (POF). Four were diagnosed unexpectedly after hysterectomy for endometrial pathology or for sequelae of cystic enlargement of the ovaries. Two of eight patients tested had serum anti-ovarian autoantibodies (Aab), while five of seven had anti-adrenal Aab. Two women had, or subsequently developed, Addisons disease, and two patients had Hashimotos disease at presentation. All women with this disease risk the development of adrenal failure and hypothyroidism. Microscopically, 11 cases showed a lymphoplasmacytic infiltrate that spared primordial follicles but involved, with progressive intensity, early and late preovulatory follicles and corpora lutea. Sparse perivascular and perineural inflammatory infiltrates were also present. The twelfth case appeared to be a unique case of granulomatous oophoritis, considered autoimmune because of the folliculotropic nature of the inflammatory process. Three cases showed evidence of follicular dysplasia.

Treatment of Recurrent Spontaneous Abortion by Immunization With Paternal Lymphocytes: Results of a Controlled Trial

PROBLEM: It remains unclear whether maternal immunization with paternal lymphocytes prior to conception improves the reproductive outcome in women with recurrent abortion in whom all secondary causes have been excluded.

Premature hypergonadotropic ovarian failure: clinicopathological study of 19 cases.

SummaryDuring the 5-year period 1977–1982, 57 patients below 35 years of age with secondary amenorrhea were assessed for hypergonadotropic (primary) ovarian failure. The histological findings within the ovaries as well as pertinent clinical and laboratory correlates are described. Nineteen had diagnostic ovarian biopsies performed. The importance of this technique is stressed. The ovaries of 14 patients showed absence of primordial follicles (true premature menopause); three others showed “resistant ovary syndrome” characterized by the presence of primordial follicles but little or no follicular development (including a case of galactosemia, in which the associated ovarian failure has been ascribed to follicular atresia). The remaining two revealed florid chronic perifollicular inflammatory reactions in the presence of both primordial and also developing follicles one lymphoplasmacytic and the other granulomatous. The former has been previously suggested as evidence of an autoimmune process, but the latter has not hitherto been reported.

FETAL PLASMA STEROIDS IN RELATION TO PARTURITION

Total plasma corticosteroid levels were measured by a competitive protein‐binding technique in matched umbilical arterial and venous samples obtained from 234 infants immediately following vaginal delivery. Both arterial and venous levels were related to the gestational age of the infant at delivery, rising to a peak at 37 to 38 weeks gestational age and thereafter declining. Corticosteroid levels were generally less in infants delivered following oxytocin‐induced (or augmented) labour than in those delivered following spontaneous labour. The mean umbilical arterial levels (±S.E.) of plasma corticosteroids at 38 to 40 weeks were 213.2 ± 16.3 ng./ml. for the spontaneous labour group and 171.9 ± 12.3 ng./ml. for the oxytocin‐induced and augmented group. The corresponding mean venous levels were 242.9 ± 14.8 ng./ml. and 227.4 ± 13.2 ng./ml. The mean plasma corticosteroid level in four fetuses spontaneously miscarried at 17 to 20 weeks was 65.0 ± 21.6 ng./ml. The results suggest that the human fetal adrenal may have an active role in fetal maturation and the initiation of labour.

Pharmacokinetics of ethynyloestradiol in women from different populations

The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.

Assessment of possible luteolytic effect of intra-ovarian injection of prostaglandin F2α in the human

A group of five patients awaiting laparoscopic tubal diathermy were followed by daily assay of luteinising hormone (LH) and progesterone. Between five and eight days after the LH peak, prostaglandin F-2ALPHA (PGF-2ALPHA) was injected into either the corpus luteum or the ovarian stroma. Doses of 100 mu-g into the corpus tuteum, 1000 mu-g into the adjacent stroma and 500 mu-g into an indeterminate ovarian structure had no effect on peripheral plasma progesterone levels or uterine bleeding. An injection of 500 mu-g or 1000 mu-g given unequivocally into the corpus luteum produced a rapid and profound fall in plasma progesterone levels, the nadir coinciding with the onset of uterine bleeding which commenced 24 hours after the injection and persisted for more than seven days. Injection of 100 mu-g in the same volume of saline had no such effect. Despite continued bleeding plasma progesterone levels returned to normal luteal levels for three days and then fell again.

A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol

Summary: : A randomized and double‐blind trial was carried out comparing intranasal nafarelin acetate (400 μg daily) and oral danazol (600 mg daily), given over 6 months, in the treatment of 49 patients with laparoscopically proven endometriosis. Both drugs produced a highly significant and similar reduction (of 60 to 70%) in objective American Fertility Society scoring, even in severe disease. No effect was seen on adhesions. Both drugs suppressed oestradiol levels to a similar extent, although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy. Nafarelin suppressed LH substantially and FSH, testosterone and prolactin to a small degree, whereas FSH and LH increased slightly during danazol. Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin, and in 6 of 14 in the danazol group. Side‐effects were reported at a similar rate with both drugs, but the pattern was different. Hot flushes were the predominant side effect with nafarelin, although oestradiol levels were not suppressed to the extent expected. Small amounts of spotting or light bleeding were experienced with both drugs, but these tended to decrease with time with nafarelin and increase with danazol.

Experimental amniotic fluid embolism: mechanism and treatment

Abstract Cardiorespiratory dynamics were studied in the experimental animal after the intravenous administration of filtered and unfiltered human amniotic fluid. Pulmonary hypertension, a severe fall in lung compliance, and arterial hypoxemia were observed. All these consequences of amniotic fluid embolism could be prevented or abolished by the administration of isoproterenol.

MATERNAL AND FETAL VENOUS PLASMA STEROIDS IN RELATION TO PARTURITION

This paper presents the results obtained from the study of Oestriol and pregnanediol in maternal peripheral venous plasma throughout normal pregnancy. Changes of oestriol pregnanediol and II‐hydroxysteroid levels throughout the day in late pregnancy were studied. The levels of these steroids found in maternal peripheral venous blood and umbilical venous blood in patients delivered normally and by elective Caesarean section have been compared.

Rate of metabolism of norethisterone in women from different populations.

The rate of metabolism of orally administered norethisterone was compared in fourteen centres by measuring plasma levels of the steroid by radioimmunoassay at varying times after oral administration of a 1 mg dose. The inter-centre differences were of the same order as the intra-centre differences. Variations in metabolism appeared not to be due to variations in body size.