Target antigen(s) in endometrial autoimmunity of endometriosis.

OBJECTIVE: To obtain the molecular weights (MW) of endometrial antigens eliciting immunoglobulin (Ig) G auto-antibodies in all endometriosis patients irrespective of their place of origin or race, and to verify their specificity and immunogenicity. STUDY DESIGN AND RESULTS: We tested the serum and peritoneal fluid (P.F.) of 76 endometriosis patients and 24 controls from 4 cities against endometrial and implant antigens by Western blot analysis. Endometrial and implant antigens with MW of 34, 46/48, 64, 84, 94 and 120 kDa bound with IgG in serum and PF of most patients, but not the controls. Antigen(s) with MW of 64 kDa was reactive against serum or P.F. IgG of patients from all cities. Specificity: Endometrial and implant extracts did not react with monoclonal antibodies to WBC subsets and 5 sera with nuclear antibodies. Also, the presence of nuclear and endometrial antibodies did not correlate in 20 other patients with endometriosis. Immunogenicity: We immunized rabbits with the native and eluted (MW 29 to 68 kDa and > or = 68 kDa) endometrial and implant proteins. The antiserum had specific IgG binding to the same glandular epithelial antigens as those bound by the patient's serum. CONCLUSIONS: Endometrial antigens with MW of 34, 46/48, 64, 94 and 120 kDa, especially 64 kDa appear to be specific, immunogenic and relevant to endometrial autoimmunity in all patients with endometriosis.

Premenstrual syndrome: an update for the clinician.

Premenstrual syndrome is a complex disorder in which a variety of symptoms can occur in the luteal phase of the menstrual cycle. The symptoms should occur each cycle only from the time near ovulation to soon after the onset of menses. There should be at least 1 week in follicular phase that is symptom-free. Symptoms should be severe enough to significantly interfere with the ability of the patient to function within her normal lifestyle. Diagnosis is based on clinical information from prospective charting of symptoms. Up to 50 per cent of patients who think they have PMS really suffer from another type of mental illness, usually a depressive disorder. Laboratory tests are not generally helpful in the diagnosis. Treatment is based on the type(s) of symptom(s). Available treatments are reviewed with documentation of results from double-blind placebo-controlled experimental designs. The etiology of PMS is not known. However, there are good empiric therapies available that can help most PMS patients.

Programmed follicular stimulation reduces cycle cost and stress with no compromise in cycle quality: use of a modified programmed protocol.

To reduce cycle cost and patient/staff stress in an ongoing in vitro fertilization (IVF) program, we have utilized a modified "programmed" (PP) follicle stimulation protocol with limited monitoring. We have compared our PP results with those using a conventional, individualized, and fully monitored protocol (OP) in order to show that PP does not compromise the quality of care. Hormonal presuppression made possible an arbitrary starting day for the cycle. In 80% of the cycles, oocyte retrieval (OR) was performed on the planned day or 1 day later. There was no statistically significant difference between the two regimens in oocyte/embryo numbers, quality or pregnancy rates. The cycle cost was significantly reduced. In addition, patient stress was lessened because of the reasonable predictability of cycle timing. We conclude that PP has significant financial and emotional advantages for the patient over OP but does not appear to diminish the chance for pregnancy in an IVF cycle. PP also allows program staff to manage time more effectively, thereby reducing staff stress.

Endometrial antigens involved in the autoimmunity of endometriosis.

Serum and peritoneal fluid from five fertile women without endometriosis and serum (n = 23) and peritoneal fluid (n = 12) from infertile women with endometriosis were tested for the presence of antibodies against endometrial tissue antigens by a Western blot analysis. Antigens with molecular weights (MW) of 19, 31, 38, and 42 kd reacted with antibodies in the serum and peritoneal fluid from both fertile and infertile women. Antibodies in 20 of 23 (87%) sera and all 12 (100%) peritoneal fluid samples from endometriosis patients reacted against endometrial antigens with molecular weights (MW) of 26 kd and/or 34 kd. Serum from 10 patients (43%) and peritoneal fluid from 6 patients (50%) also had antibodies to an endometrial antigen with MW of 21.5 kd. Reactivity to other endometrial antigens with MW 16, 24, 48, and 75 kd was also noted in patients with endometriosis. Antibodies in the serum and peritoneal fluid from fertile women failed to react against these antigens. It is concluded that the humoral and local endometrial autoimmunity detected in patients with endometriosis is primarily directed against antigens with MW of 26 and 34 kd.

Indications for drug therapy in premenstrual syndrome patients.

Women with mild to moderate premenstrual syndrome (PMS) should have their symptoms controlled with conservative therapy, including diet, exercise, education and nutritional supplementation. Those patients with moderate to severe PMS whose condition cannot be controlled in this conservative fashion should undergo pharmacologic trials. Recent studies of progesterone supplementation showed no improvement when it was compared to placebo; the one exception was the use of oral micronized progesterone one therapy at a level of 300 mg/day, but the study remains to be repeated by other investigators. The most logical therapy at present is suppression of ovulation with a short-term trial of danazol, perhaps followed by long-term suppression with estrogen implants or depomedroxyprogesterone acetate. Surgical ovariectomy is warranted in a very small number of cases. Prostaglandin inhibitors are effective for the physical complaints that may be associated with PMS. Some antihypertensive agents, such as clonidine and verapamil, which are also antimania drugs, may have a place in the treatment of PMS.

An endometrial antibody assay in the clinical diagnosis and management of endometriosis.

Coded serum samples from 11 normal fertile men and 17 fertile women without endometriosis (control groups) and 41 women with endometriosis were tested blindly for the presence of endometrial antibodies by use of a passive hemagglutination assay. Endometrial antibodies were either absent or present in low baseline titers in the serum samples from the control group. In contrast, 17 of the 23 (74%) patients with untreated endometriosis had elevated titers of endometrial antibodies in their serum. Of the 18 patients treated with danazol, endometrial antibodies were absent in 7 women who showed a good response at repeat laparoscopy, whereas 4 of 5 women with a poor response had significantly positive titers of antibodies. Six patients treated with danazol did not have repeat laparoscopy, but were found to have endometrial antibody titers in the baseline control range. Endometrial antibody titers in women with a good response to danazol were significantly lower than those in women with untreated endometriosis or with a poor response to danazol (P = 0.003). No correlation was observed between the antibody titers and the stage of endometriosis. The results suggest that the assay for serum endometrial antibodies may prove to be a clinically useful, noninvasive aid in the diagnosis of endometriosis. Sequential determination of endometrial antibody titers may be helpful in assessing the efficacy of pharmacologic therapy for endometriosis and evaluating the cases of patients with possible recurrence of the disease.

Polycystic ovary syndrome.

Polycystic ovary syndrome comprises a group of chronic, progressive diseases of the female reproductive system. Clinical characteristics include disorders of ovulation and menstruation, hirsutism, infertility and obesity. Recommended treatment of the unacceptable manifestations includes the use of oral contraceptives or progestins. Fertility can often be achieved with clomiphene citrate and/or other agents. Rarely is surgical therapy indicated.

Primary polycystic ovary syndrome in a premenarchal girl. A case report.

A 12-year-old, premenarchal girl with hirsutism and virilization of nine months' duration was found to have highly elevated serum testosterone and a radiologic evaluation suggestive of bilaterally enlarged ovaries with a solid left ovarian mass. Serum gonadotropins were normal, with an LH:FSH ratio of 2:1. Exploratory laparotomy showed bilaterally enlarged polycystic ovaries, confirmed by wedge biopsies. No ovarian tumor was found. Oral contraceptives decreased the total serum testosterone to the normal female levels within three months. This was one of the youngest reported patients with primary polycystic ovary syndrome.

Pregnancy and reproductive function in a patient with non-mosaic Turner syndrome.

A patient with non-mosaic Turner syndrome and normal fertility had four documented pregnancies, two of which were carried to term. Although her fertility history can be considered normal, she did not have spontaneous sexual maturation or menarche, and bilateral streak gonads were identified on laparotomy for tubal ligation. A review of the literature on non-mosaic Turner syndrome and reproductive function indicates that there are several theories to account for the extreme variety of ovarian function in such patients, but not enough data are yet available to form a conclusion.

Potencies of oral contraceptives.

PIP: This letter is a response to the discussion by Edgren and Sturtevant (125:1029, 1976) on potencies of oral contraceptives (OCs). It is agreed that the results of studies in animal models on OC potencies may not necessarily reflect true potencies in human subjects, however, these animal models do allow the evaluation of the biological effects and interactions of the components of OCs. Data obtained in animal studies are acknowledged to be valuable aids in the study of human diseases. Likewise, mouse uterine response to contraceptive steroids is 1 criterion to be used in evaluating steroid potency. As previously reported, the importance of the mouse uterine response is that the contribution of the progestin component to the total estrogenic potency of the OC is demonstrated.^ieng

Autonomic innervation and plasma estradiol-17beta and progesterone levels in rats with subcutaneous ovarian autografts.

Ovaries were removed from female rats and immediately autografted into a subcutaneous pouch in the flank in order to quantitate the relationship of graft re-innervation, steroid secretion and vaginal smear pattern. Animals were killed at thre time periods: three days after grafting, on the first day a cornified vaginal smear appeared and at the first metestrus. In addition, control animals were killed at metestrus. Plasma samples were obtained from all rats and analyzed for estradiol-17beta and progesterone concentration by radioimmunoassay. At the first day of vaginal cornification after grafting, plasma estradiol-17beta (45.8+/-4.0 pg/ml) was elevated in comparison to controls at metestrus (24.0+/-2.6 pg/ml), but plasma progesterone (21.5+/-4.0 ng/ml) was not different (30.6+/-1.7 ng/ml). Subsequently, at the first metestrus following grafting, plasma estradiol-17beta (23.0+/-3.5 pg/ml) was comparable to control values. In contrast, progesterone was decreased (17.5+/-1.9 ng/ml). A definite correlation was detected between the vaginal smear and plasma levels of steroid hormones in the castrated female rat with subcutaneous ovarian autographs Histochemical techniques were used to study the adrenergic and cholinergic innervations of grafts three days after grafting, at the first day of vaginal cornification, and at the first metestrus. No correlation was shown between density of adrenergic or cholinergic innervation and plasma levels of estradiol-17beta and progesterone or onset of a cycling vaginal smear.

Fine structure of the corpus luteum of the autografted ovary in the rat.

The rat ovary has been transplanted successfully to subcutaneous tissue areas by several investigators. Light microscopy has revealed that corpora lutea in ovarian autografts are formed by luteinization of intact follicles and contain entrapped ova. In the present study, corpora lutea from autografted ovaries in castrate rats were obtained at metestrus and examined electron microscopically to determine whether their cellular morphology correlated with the normal progesterone levels in these animals. Cellular features usually accepted as regressive were apparent. The findings suggest either structural luteolysis is occurring before functional luteolysis or that the adrenal has increased steroidogenic activity in the castrate with ovarian autografts to account for the normal progesterone levels.

Estrogen potencies of three new low-dose oral contraceptives.

The estrogen potencies of three new oral contraceptive formulations--Brevicon, Modicon, and Lo/Ovral--were determined. Brevicon and Modicon were found to have estrogen potency equal to mestranol 50 mug and equal to or greater than Norinyl 1 + 50 and Ortho-Novuum 1 + 50. Lo/Ovral, which is identical to Ovral in the type and ratio of progestin but 40 per cent lower in drug content, could be estimated to have an estrogen potency of 0.73 relative to mestranol 50 mug and therefore, by inference, to Brevicon and Modicon.

The effect of frozen ovarian autografts on compensatory ovulation and steroid production in unilaterally ovariectomized rats.

In the present study rats were unilaterally ovariectomized (ULO) and the surgically removed ovary was frozen for 13 days. After allowing the remaining ovary to compensate with respect to number of ova shed, the frozen graft was thawed and transplanted subcutaneously to determine the effect on ovulation number, cycle length, uterine weight, ovarian weight and plasma levels of estradiol-17beta (E2) and progesterone. Rats ULO at 45 days of age, which received an autograft 13 days later, had a decrease in the number of eggs shed as compared to control ULO rats (6.4 +/- 0.8 vs. 11.1 +/- 0.9 eggs, respectively) and a decrease in plasma E2 (14.5 +/- 1.7 VS. 21.0 +/- 1.5 PG/ML, respectively). No differences were observed in progesterone concentration, uterine weight, ovarian weight or cycle length. In contrast, rats ULO at 31 days of age, which received an autograft 13 days later, showed no differences in comparison to control ULO rats. Castrates which received ovarian autografts developed cycling vaginal smears and had increased E2 (31.9 +/- 4.3 pg/ml) and decreased progesterone (18.3 +/- 1.9 ng/ml) levels. Since ULO animals with autografts shed fewer ova, the present study demonstrates that the amount of ovarian tissue influences ovulation number either by utilization of gonadotropins or by an, as yet, undefined mechanism.

Estrogen potency of oral contraceptive pills.

The estrogen potencies of 9 oral contraceptive pills, Enovid-E, Enovid-5, Ovulen, Demulen, Norinyl+80, Norinyl+50, Ovral, Norlestrin 1 mg. and Norlestrin 2.5 mg., were determined by bioassay. Relative estrogen potency was determined by analysis of variance. Enovid-5, the most estrogenic compound, had a potency of 4.88 compared to ethinyl estradiol, 50 mcg. equal 1.00; Ovral, the least estrogenic compound, had a potency of 0.81, a sixfold difference. Estrogen potencies at a fractional dose of 0.00155 correlate with reports of the incidence of minor side effects and thromboembolic disease. The effect of progestins on estrogen potency was purely additive (norgestrel and norethynodrel), purely antagonistic, or additive at low concentrations and antagonistic at high concentrations (norethindrone, norethindrone acetate, and ethynodiol diacetate). These results suggest that pills with a greater margin of safety might be developed by utilizing greater ratios of progestin to estrogen. In addition, differences in relative estrogen potency of oral contraceptive pills may be used as a basis for better clinical selection.