Gunnar Rannevik

The success rate of in vitro fertilization of human oocytes in relation to the concentrations of different hormones in follicular fluid and peripheral plasma

Seventeen infertile patients were stimulated with clomiphene citrate and human chorionic gonadotrophin (hCG). During laparotomy or laparoscopy, follicles were aspirated. At least one fertilizable oocyte was obtained from 13 patients, who had normal preovulatory plasma 17 beta-estradiol (mean 2.2 nmol/l) in contrast to the 4 patients with infertilizable oocytes (mean 0.4 nmol/l). A close association was found between the success rate of fertilization and the increment of plasma progesterone from the day before to the day after the operation. If the concentrations of 17 beta-estradiol and progesterone in follicular fluid were below an arbitrary limit (17 beta-estradiol less than 500 nmol/l in association with progesterone less than 2,000 nmol/l), no oocytes could be fertilized. Apparently aspiration of oocytes and follicular fluid did not disturb ovarian steroid production during the luteal phase. The results suggest that plasma 17 beta-estradiol and progesterone determinations may serve as useful predictors for oocyte fertilizability in an in vitro system, following clomiphene-hCG stimulation and multiple oocyte recovery.

A prospective long-term study in women from pre-menopause to post-menopause: changing profiles of gonadotrophins, oestrogens and androgens

To permit a more detailed hormonal characterization of the peri-menopause, 30 healthy women were examined at regular intervals over a 7-yr period, starting about 3 yr before the menopause. Even though most of the subjects periodically experienced climacteric symptoms, no hormonal supplementation was given. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and oestrone that were recorded essentially confirmed previous data obtained in cross-sectional studies. Within the 6-mth period around the menopause the serum levels of testosterone and androstenedione showed small but significant decreases of 18 and 16%, respectively. These decreases continued over the following years and amounted to about 30% after 3 yr. In contrast, neither the mean level of dehydroepiandrosterone (DHA) nor the DHA/DHA sulphate (DHAS) ratio changed significantly at the menopause, but DHA and DHAS concentrations declined slowly by about 20% over the 7-yr observation period. The mean level of DHAS showed an isolated increase during the last few months before the menopause. A similar, although not significant, increase was also seen in DHA and testosterone levels. After the first post-menopausal year a significant positive correlation was found between the levels of oestrone and androstenedione. This longitudinal study of individual women appeared to lend itself well to the investigation of even subtle hormonal fluctuations during the gradual transition to an established post-menopausal pattern.

Outcome of Pregnancy After Clomiphene Therapy

Abstract. Of 159 pregnancies conceived after clomiphene therapy, 141 ended in childbirth, including seven sets of twins. There was a probable increase in the number of infants born with major malformations. These were exclusively to women who had not previously borne a normal infant. The incidence of malformed infants compares well with that published after gonadotropin therapy. The possibly higher incidence of malformations seen after drug‐induced ovulation would therefore seem to be due to the underlying subfertility state and thus not a direct drug effect.

CLINICAL TRIAL OF A NEW ORAL CONTRACEPTIVE PILL CONTAINING THE NATURAL OESTROGEN 17β‐OESTRADIOL

The natural oestrogen, 17β‐oestradiol, has been shown not to depress fibrinolysis and apparently has less influence on liver function and lipid metabolism than ethinyl oestradiol, the synthetic oestrogen in conventional‘combined’oral contraceptive tablets. A triple‐blind study was therefore made of 215 women during 2051 treatment cycles with oral contraceptives containing either (i) 4 mg of micronized 17‐oestradiol and 3 mg norethisterone (Netagen 403), (ii) 4 mg 17‐oestradiol plus 2 mg of oestriol and 3 mg norethisterone (Netagen 423) or (iii) 50 μg ethinyl oestradiol and 3 mg norethisterone (Netasyn). There were no pregnancies or thrombotic incidents. The numbers discontinuing treatment were about the same in the three groups, the main reasons being intermenstrual spotting in those on Netagen 423, amenorrhoea and weight gain in those on Netagen 403 and nausea and weight gain in those on Netasyn. The natural oestrogen showed promise as a new and safe component of the‘combined’pill.

Studies on the decreased gonadotropin response after administration of LH/FSH-releasing hormone during pregnancy and the puerperium

The responsiveness of the pituitary to luteinizing hormone releasing hormone (LRH) during pregnancy and the puerperium was studied in 15 women 18-32 years of age (3 puerperal, 6 pregnant, and 6 eumenorrheic). 25 mcg LRH dissolved in 1 ml sterile water was administered iv to all the subjects. Blood samples were obtained 10 minutes prior to, immediately prior to, and 10-120 minutes following injection. LH and follicle stimulating hormone (FSH) were determined by double antibody radioimmunoassay. No significant (p more than .05) FSH response was observed 8-10 days postdelivery. However, 2 weeks postpartum the mean FSH response was significant (p less than .01) but not that of LH (p more than .05). 4 weeks postpartum revealed a significant LH (p less than .05) and FSH (p less than .01) response. The response of pregnant women to LRH was insignificant (p more than .05). The LH response in eumenorrheic women was significant (p less than .01) as was that of FSH (p less than .01). It is concluded that, like pregnant women, puerperal women are less responsive to LRH than are aumenorrheic women.

Plasma Protein Pattern in Recurrent Cholestasis of Pregnancy

The plasma concentrations of 17 major plasma proteins were determined specifically in a series of women with recurrent cholestasis of pregnancy and in a control series of normal pregnant women. The plasma protein pattern found in recurrent cholestasis of pregnancy showed mostly mild changes typical of hepatocellular damage and biliary obstruction, but cold insoluble globulin increased markedly and showed a close correlation with the serum y-glutamyl transpeptidase activity and a weak correlation with the alkaline phosphatase activity. These findings might indicate a common cause of the increase of the protein and the enzymes. Only minor and inconclusive protein changes were seen in the infants of mothers with recurrent cholestasis of pregnancy.

Free Testosterone and Testosterone/SHBG Index in Hirsute Women: A Comparison of Diagnostic Accuracy

Serum levels of sex hormone binding globulin (SHBG), total testosterone (T), free testosterone (fT), 4-androstene-3,17-dione (A-4) and dehydroepiandrosterone sulfate (DHAS) were determined in 30 patients with the polycystic ovary syndrome. Subnormal levels of SHBG were found in 60% of the patients. Elevated levels of T were found in 53%, of fT in 53%, of the T/SHBG ratio in 90%, of A-4 in 75% and of DHAS in 36% of the patients. The better diagnostic accuracy of the T/SHBG ratio compared to fT may be explained by the regulatory effect of SHBG binding upon the albumin-bound fraction of T, which may be another biologically active T fraction. It is concluded that the assay of fT does not offer any further diagnostic advance compared to conventional determinations of T. Assays of fT do not provide any information about the origin of the elevated levels of biologically active androgen.

Decreasing serum levels of sex hormone-binding globulin around the menopause and temporary relation to changing levels of ovarian steroids, as demonstrated in a longitudinal study

Abstract Blood samples collected longitudinally in 17 women over a period of 3 years, starting 1½ years before the menopause, were assessed for sex hormone-binding globulin (SHBG), 17β-estradiol (E 2 ), progesterone, and total testosterone. A slight (7.2%) decrease in mean SHBG from 4.25 ± 1.67 (standard deviation) mg/l to 3.95 ± 1.61 mg/1 was observed within the 6-month period encompassing the menopause. More specifically, the decrease appeared to commence at the menopause and to become clearly significant ( P = 0.01) some 2 to 6 months later. During the subsequent year, a further decrease to 3.64 ± 1.42 mg/l was observed, amounting to a total decrease in mean SHBG by 14.4% ( P 2 exhibited a marked decrease ( P P = 0.013) only with those of E 2 . It is concluded that decreasing E 2 levels appear to play a significant role in the downward modulation of SHBG levels commencing at the menopause.

Peripheral and Ovarian Venous Concentrations of Gonadal Steroids and CEA in Women with Ovarian Tumors

Abstract. In an effort to improve our knowledge of certain marker substances in human ovarian neoplastic diseases (both benign and malignant) 12 patients with ovarian tumors were studied. Ten of these were postmenopausal.

Effect of oral contraceptives on the liver in women with recurrent cholestasis (hepatosis) during previous pregnancies.

The hepatic effects of various sex steroids on 61 women who had had intrahepatic cholestasis of pregnancy and 19 control patients have been studied. Chlormadinone acetate and lynestrenol produced little or no increase of the serum enzyme activity. With the mestranol and a combined preparation of mestranol and chlormadinone acetate an increase of the serum enzyme activity was found, which, however, soon returned towards normal. No increase in the concentration of the serum bilirubin was found in any of the patients. The supposed risk of jaundice during the use of hormone contraceptives by such patients has been exaggerated.