Seasonal distribution in conceptions achieved by artificial insemination by donor.

The distribution of conceptions after artificial insemination from a donor was studied in 259 conceptions at an artificial insemination clinic and found to be seasonal. Conception was not influenced by the number of donors or patients attending the clinic, the frequency of inseminations, or medical skill. Conception was more common from early winter until early spring (October to March) with a peak in November. As variables such as frequency of intercourse and ovulation were irrelevant in these women and highest sperm counts occur from February to March these results suggested a seasonal variation in the quality of the ovulated egg or endometrial receptivity. The waste of eggs after ovulation (or preimplantation conceptuses) at specific times of the year has implications in the treatment of infertility, particularly for in vitro fertilisation and gamete intrafallopian transfer.

Results of low-dose methotrexate treatment of persistent gestational trophoblastic disease in Sheffield 1980-1987.

Between January 1980 and October 1987, 115 evaluable patients were treated in Sheffield for persistent gestational trophoblastic disease (GTD) with a low dose methotrexate regimen (LD-MTX). Each course comprised MTX 50 mg given by i.m. injection for 4 doses on alternate days. Courses were repeated every 2 weeks and serum beta-hCG was used to monitor response. Overall, 80/115 (70%) of patients attained durable complete remissions (CR). Twenty-nine patients received the 'AVC' salvage combination of actinomycin-D 0.5 mg i.v. for 5 days, sequenced with cyclophosphamide 500 mg i.v. and vincristine 1 mg i.v., both given for 3 doses on alternate days. Sixteen (55%) patients attained a durable CR but 11 (38%) required further measures, 7 ultimately requiring hysterectomy. Two (7%) died during treatment. With 4 deaths overall (3 from metastatic GTD and 1 from infarction of the bowel), actuarial survival is 94% at over 7.5 years. A new Charing Cross prognostic scale weighted especially for hCG levels, number and sites of metastases, interval between pregnancy and start of treatment (score 0-6 each factor), was applied retrospectively to obtain a total score for each patient. Thus, 21/26 (81%) patients who scored greater than 8, required additional treatment after LD-MTX, compared with 18/89 (20%) of lower scoring patients (p less than 0.001). Because of the frequent morbidity associated with prolonged chemotherapy as well as the development of drug-resistant GTD, it is concluded that the 'high-risk' patients should receive more intensive combination chemotherapy at the outset.

Thyroid function in trophoblastic disease.

Human chorionic gonadotrophin (hCG) levels and thyroid function were monitored in 44 patients receiving chemotherapy for treatment of trophoblastic disease. We observed a strong correlation between hCG and thyroid stimulating hormone (TSH) concentrations measured by radioimmunoassay, and this appears to be due to cross-reactivity between hCG and the anti-TSH antibody used. The concentration of thyroid hormones was little affected by the raised levels of TSH or hCG, except when the concentration of the latter rose to high levels, usually above 100,000 i.u./l. The possible mechanisms of thyroid homeostasis in trophoblastic disease are considered.

Abnormal steroid excretion in gestational trophoblastic disease complicated by ovarian theca-lutein cysts.

Serum and urine steroids were examined in two subjects with trophoblastic disease accompanied by large ovarian theca-lutein cysts and compared with those from 10 patients with trophoblastic disease but without palpable cysts. In the patients without cysts normal values were obtained for serum oestradiol, progesterone, 17 alpha-hydroxyprogesterone and androstenedione, and for urinary total oestrogens, pregnanediol, pregnanetriol, and 17-oxosteroids. Nineteen urinary steroid metabolites, quantified by capillary gas-liquid chromatography, were either within reference limits or marginally raised. In several cases relatively minor increases in serum testosterone and cortisol and urinary free cortisol were observed. In contrast, the subjects with cysts showed pronounced excesses of androgen metabolites, 17 alpha-hydroxypregnenolone, pregnanediol, and pregnanetriol, and both exhibited a similar pattern of unusual additional metabolites. The profiles superficially resembled those seen in 21-hydroxylase deficiency adrenogenital syndrome, but there were important discrepancies reflecting known differences in ovarian and adrenal steroid metabolism. Chemotherapy led to decline of human chorionic gonadotrophin concentrations, regression of the cysts, and return to normal of the steroid profile. Excess steroids in the patients with cysts may have originated in the ovary rather than in the trophoblastic tissue.

A study of the effect of sodium/meglumine ioxaglate (Hexabrix) on thyroid function.

The effect of thyroid function was investigated in 22 patients undergoing arteriography with a new low osmolality contrast medium--sodium and meglumine ioxaglate (Hexabrix). Plasma thyroxine (T4), thyroxine resin uptake (TRU) and free thyroxine index (FTI) were measured before and at varying intervals up to 56 days after the arteriogram. Despite the large doses of Hexabrix used (up to 89.6 g of iodine), these tests of thyroid function did not reveal any significant change from pre-angiographic levels. It is concluded that Hexabrix as used for arteriography does not affect thyroid function.

Steroid excretion and metabolism by gonadal tissue from a subject with testicular feminization syndrome.

The initial clinical, pathological, and hormonal investigation of a patient with testicular feminization syndrome is described. Incubation of gonadal tissue with various radioactive substrates, together with the isolation and identification of the resulting metabolites, was demonstrated a high capacity to synthesize testosterone. Two biosynthetic pathways were demonstrated, originating from progesterone and pregnenolone. These are essentially similar to those of the normal adult testes. Low levels of activity were found in the phenolic fractions and no measurable production of oestrone, oestradiol, or oestriol was found.