Emery A. Wilson

Studies on the surgical induction of endometriosis in the rat.

As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial or uterine tissue to the peritoneum. Rats (n = 46) were randomly assigned to one of four surgical techniques: (1) four uterine squares sutured to the peritoneal cavity; (2) uterine luminal lavages instilled into the peritoneal cavity; (3) endometrial scrapings flushed into the peritoneal cavity; and (4) sham-operated controls. Rats were examined at various days after surgery for the presence of endometrial implants. The autotransplantation of uterine squares to the peritoneal cavity was the only treatment that yielded healthy endometriotic implants. These implants grew into ellipsoidal cystic structures that were composed of both endometrial glands and stroma and were found to contain prostaglandin F (202 ng/mg) at concentrations similar to those measured in uterine tissue (205 ng/mg). To examine the effect of surgically induced endometriosis upon fecundity, rats (n = 40) were autotransplanted with uterine squares or were sham operated and mated. The presence of ectopic endometrial tissue reduced the number of pups at term by 48% and the number of day 14 embryos by 28% (P less than 0.05). Peritoneal adhesions were greater in rats with induced endometriosis than in sham-operated controls (P less than 0.05); however, in rats with induced endometriosis, no differences were noted in the severity of adhesions between pregnant and nonpregnant rats. Endometriotic implants underwent complete regression in the day 14 pregnant rat but had doubled in size in the nonpregnant rat. At term, the endometriotic implants were larger than in the day 14 pregnant rat (P less than 0.05) and similar to their original size. The successful growth and development of surgically transplanted endometrial tissue in the rat offers a research model that can be used to study those aspects of endometriosis that cannot be adequately investigated in women.

Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F

The severity of the symptoms of endometriosis has not always correlated well with the anatomic severity of the disease. This lack of correlation may be due to variations in the metabolic activity of the endometriotic implants present at different stages of the disease. Because prostaglandin F (PGF) has been implicated as a hormonal mediator of the clinical symptoms of endometriosis, PGF synthesis and content was measured in implants from 14 patients with mild, moderate, severe, or extensive disease. To assess whether PGF production was related to the status of implants, the authors classified implants, based on gross and histologic criteria, as petechial or reddish; intermediate or brown; or powder-burn or black. PGF production of implants from patients with mild or moderate disease was greater than that of implants from patients with severe or extensive disease (P less than 0.05), and PGF content was similar for all stages of endometriosis. Petechial implants produced twice the amount of PGF than intermediate implants (P less than 0.05), which in turn produced more PGF than powder-burn implants (P less than 0.05). Powder-burn implants did not have the in vitro capacity to produce PGF, and the amount of PGF contained in implants of all classes was similar. Therefore, endometriotic implant PGF production and possibly other biochemical activities are dependent on the physical status of the implant. The classification of implants by morphologic appearance may afford additional assistance in determining the prognosis of the disease and in the examination of the subtle effects of the disease on symptoms.

How does mild endometriosis cause infertility

30-40% of patients with endometriosis are infertile, and 6-15% of infertile women have endometriosis. Although the cause of the infertility observed in patients with mild endometriosis has not been established, several hypotheses have been proposed. Recent investigations have shown a link between endometriosis, altered prostaglandin (PG) secretion and metabolism, and infertility. Increased levels of PG metabolites have been found in the peritoneal fluid (PF) washings from patients with endometriosis; increased PF volume has also been noted. The increased PG concentration may alter ovarian function and tubal motility. Other studies have found endometriosis to coexist with anovulation. When both problems are treated, pregnancy rates improve. Many women with endometriosis may have a luteal phase defect. An autoimmune response to endometriosis has been considered as a cause of infertility as well. This response could produce rejection of the early implanted embryo or interfere with sperm transport. Endometriosis has also been regarded as a cause for some spontaneous abortion, but there may be a mediating mechanism, e.g., immune response or luteal phase defect. It is not known whether the various phenomena associated with endometriosis have a genetic basis or represent a secondary effect of endometriosis. A multivariate hypothesis, in which any or all of the factors noted in previous studies may be responsible for endometriosis-associated infertility and to varying degrees in different patients, is proposed. There may be genes that interfere with PG metabolism or lead to deficient immune status. If the multivariate causation theory is confirmed, patient evaluation may require performance of several diagnostic tests to determine the presence or absence of each factor and the extent to which that factor affects fertility. This approach will permit appropriate individualization of therapy.

Suppression of human chorionic gonadotropin by progestational steroids

The dynamics of the secretion of human chorionic gonadotropin (hCG) were studied by culturing explants of normal term placentas for as long as 144 hours. A significant accumulation of immunoreactive hCG (beta-subunit) was first detected at 48 to 72 hours, and a sixfold increase in hCG was observed in control culture medium at 144 hours. Compared to control cultures, progesterone (P < 0.001) in physiologic tissue levels of 5 to 20 micrograms/ml, pregnenolone (P < 0.001), 20 micrograms/ml, and 20 alpha-dihydroprogesterone (P < 0.001), 20 micrograms/ml, suppressed the secretion of hCG throughout the study period. Progesterone decreased the secretion of hCG in a dose-response manner (r = -0.8S87, P < 0.1). No suppression of hCG was observed in the presence of cortisol, testosterone, dihydrotestosterone, 17 beta-estradiol, or estriol. The secretion of human chorionic somatomammotropin was unchanged in the presence of progesterone. The augmented hCG response in the presence of dibutyl cAMP (P < 0.001) was significantly, but not completely, suppressed by progesterone 20 micrograms/ml culture medium (P < 0.01). Under these conditions progestational steroids or their immediate metabolites suppress the secretion of hCG, and they may be responsible for the decline in the levels of hCG during pregnancy.

Tuberculosis complicated by pregnancy

Abstract Ten cases of tuberculosis during pregnancy are presented and discussed. The literature is reviewed and recommendations for therapy are presented.

Prolactin hyperstimulation in response to thyrotropin-releasing hormone in patients with endometriosis

In order to clarify the role of hyperprolactinemia as a possible cause of infertility in patients with endometriosis, baseline serum prolactin (PRL) concentrations and the PRL response to thyrotropin-releasing hormone (TRH) stimulation were measured in 14 infertile women with endometriosis and in 13 normal, fertile women. Baseline PRL concentrations were 2-fold greater in the endometriosis group than in normal subjects, but the mean values did not differ significantly. Following TRH administration, a significant increase in peak PRL concentrations was observed in patients with endometriosis (211.5 +/- 34.9 ng/ml) when compared with corresponding values in control subjects (117.1 +/- 14.9 ng/ml, P less than 0.05). This hypersecretory state was selective for PRL because no significant differences between the baseline and TRH-stimulated thyroid-stimulating hormone (TSH) concentrations or total serum thyroxine concentrations were observed. In summary, some infertile women with endometriosis exhibit a greater capacity for PRL secretion than normal women. These results suggest that relative hyperprolactinemia may be responsible for the infertility associated with endometriosis, and that PRL suppression may be indicated in these patients.

Coital activity and premature delivery.

The coital activities of 111 patients who delivered after spontaneous premature labor were compared to a matched group of patients who subsequently delivered at term. The percentage of patients who were sexually active, the mean coital frequency, and the incidence of orgasm with coital activity were not significantly different between the two groups. Coital activity in the group delivering prematurely was significantly greater (p less than 0.05) than that in the group delivering at term only when no apparent reason for premature labor (18 or 111 cases) was evident. This relationship was especially true after the thirty-second week of gestation. Normal coital activity does not result in premature delivery and should not be discouraged during pregnancy in the absence of complications.

Ultrastructure and steroid-binding studies in leiomyomatosis peritonealis disseminata

Leiomyomatosis peritonealis disseminata (LPD) is characterized by the development of numerous leiomyomata throughout the peritoneal cavity which appear grossly malignant but histologically benign. The etiology of this disorder has been controversial. The tenth reported case of LPD is presented with ultrastructural evidence that these tumors arise from smooth muscle cells. The cytoplasmic estrogen and progesterone bindings by these tumors were ninefold and twofold greater than receptor concentrations in normal myometrium from the same patient. In addition to the steroid binding data, the strong association of this disorder with pregnancy or, as in this case, oral contraceptives suggests that the stimulus for neoplastic initiation and growth is hormonally related.

Effect of estradiol and progesterone on human chorionic gonadotropin secretion in vitro

Many of the substances known to control the secretion of pituitary gonadotropins also modulate the secretion of human chorionic gonadotropin (hCG) by the placenta. In order to study the effect of estrogens and progestins on hCG secretion, term placental explants were cultured in culture media for 144 hours. During the culture period, hCG secretion increased after 48 hours, and a fortyfold increase was observed after 144 hours (p less than 0.001). Compared to concentrations of hCG in control cultures, secretion of hCG was markedly suppressed in the presence of progesterone 2.25 X 10(-5)M (p less than 0.001), a concentration similar to that found in term placental tissue (1.7 +/- 0.2 micrograms/gm of tissue). Suppression of hCG by progesterone occurred in a dose-response manner (r = -0.9100, p less than 0.01). Estradiol, an important steroid modulator of pituitary gonadotropins, did not significantly suppress the secretion of hCG, except in pharmacologic concentrations (10(-4)M), and physiologic concentrations of estradiol had no effect on the suppression of hCG by progesterone. These results suggest that the mechanism by which progesterone suppresses the secretion of hCG differs from the manner in which steroids modulate the secretion of pituitary gonadotropins.

Successful pregnancies from men with retrograde ejaculation with the use of washed sperm and gamete intrafallopian tube transfer (GIFT)

Viable sperm were collected from men suffering from retrograde ejaculation by the technique of rapid washing of semen/urine in a buffered collection solution. The utilization of washed semen/urine from two men with retrograde ejaculation in the GIFT procedure lead to successful conceptions and the birth of two healthy female babies. Thus, the technique of rapid washing of sperm from retrograde ejaculating men coupled with GIFT represents a viable alternative for the attainment of pregnancy.