Effects of androgens on aromatase activity and 11C-vorozole binding in granulosa cells in vitro.

Background: Locally produced androgens and estrogens are important in the hormonal regulation of follicular development. The present study aimed to further elucidate the mechanism through which androgens exert their ambivalent effects on aromatization.

Methods: Non-cultured human granulosa-luteal cells (GC) were treated with different concentrations of androstenedione (A4), testosterone (T), 5alpha-androstane-3,17-dione (5alpha-A) and dihydrotestosterone (DHT).

Does pronuclear morphology and/or early cleavage rate predict embryo implantation potential?

A total of 340 patients referred for in-vitro fertilization was included in a retrospective, comparative study in which zygotes were studied regarding alignment and polarization of nucleolar precursor bodies (NPB) and also early cleavage in relation to implantation and pregnancy rates for the 680 transferred embryos. At assessment of the pronucleus 18-19 h after sperm injection, NPB were checked for alignment/polarization. Twenty-six hours after sperm insemination the zygotes were assessed for early cleavage.

Reducing the time of co-incubation of gametes in human in-vitro fertilization has no beneficial effects.

Reports concerning the benefit of reducing the co-incubation time of gametes in connection with IVF have been conflicting. The present randomized study was undertaken to determine whether a reduced co-incubation time would improve the embryo development and consequently the pregnancy and implantation rates. Oocytes from 87 patients were collected and half the oocytes from each patient (n = 488, group A) were randomized to 2 h incubation and the other half (n = 504, group B) to overnight incubation.

Cytologic screening and human papilloma virus test in women undergoing artificial fertilization.

Background: Infertile women in Sweden are offered in vitro fertilization (IVF) within the frame of the social security system. The present investigation was undertaken to evaluate the prevalence of genital human papilloma virus (HPV) infection in relation to the results of cytologic screening and to the infertility in these women.

Material And Methods: Two hundred and fourteen women, mean age 32 years (range 20-40), admitted to the Center for Reproduction at Uppsala University Hospital for investigation of infertility and IVF were studied.

Follicles are found in the ovaries of adolescent girls with Turner's syndrome.

Infertility caused by ovarian failure is a characteristic feature in Turner's syndrome. Spontaneous pregnancies are seen in 2-5% of these women, and up to 30% have at least some pubertal development, indicating the presence of follicles in their ovaries in adolescence. It has not been clear at which age the follicles disappear.

Embryo transfer after 2 or 5 days of IVF culture: a retrospective comparison.

Background: To determine whether prolongation of embryo culture in vitro from day 2 to day 5 after ovum pick-up (OPU) and fertilization can improve the results of in vitro fertilization (IVF), and the morphology of the spare embryos on day 2 can predict the developmental capacity during prolonged culture. We also wanted to consider this as a strategy to avoid twin pregnancies if it could be possible to transfer only one blastocyst at a time in the future.

Methods: A retrospective analysis with embryo transfer timed according to the weekday of OPU.

In vitro evaluation of aromatase enzyme in granulosa cells using a [11C]vorozole binding assay.

An in vitro method for measuring aromatase cytochrome P450 enzyme (P450AROM) in human granulosa cells (GC) has been developed, based on binding of the 11C-labeled aromatase inhibitor vorozole. GC were obtained following superstimulation during in vitro fertilisation. The method revealed a binding affinity (Kd) of 0.

A high degree of aneuploidy in frozen-thawed human preimplantation embryos.

We have studied the chromosomal content in 68 normally fertilised freeze-thawed human embryos of good morphology from 34 patients with an average maternal age of 32,6 years. Forty embryos showed post-thaw cellular division and twenty-eight post-thaw cleavage arrest. After spreading of the embryos on microscope slides, analysis of chromosomes X, Y, 15, 16, 17 and 18 was performed using two rounds of fluorescent in situ hybridisation (FISH).

Comparison of buserelin and nafarelin in IVF cycles and in subsequent frozen-thawed embryo transfer cycles.

Objective: To compare two gonadotropin-releasing hormone agonists for down-regulation prior to superovulation in in vitro fertilization/embryo transfer treatment.

Methods: Infertility patients (n=181) were randomized to receive buserelin (1200 microg/day, n=90) or nafarelin (800 microg/day, n=91) intranasally starting in the luteal phase. Serum levels of LH, estradiol and progesterone were measured during the treatment.

Evidence of interplay between plasma endothelin-1 and 17 beta-estradiol in regulation of uterine blood flow and endometrial growth in infertile women.

Objective: To determine the effects of gonadotropin-induced ovarian stimulation on the plasma levels of endothelin-1 as well as on uterine blood flow and endometrial thickness.

Design: Controlled cross-over clinical study.

Setting: Academic research environment.

Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles.

Objective: To verify whether uterine artery impedance, measured as pulsatility index and resistance index is related to the outcome of in IVF-ET cycles.

Design: Prospective study of infertile women participating in an IVF-ET program.

Setting: University Hospital.

High bone density in hyperandrogenic women: effect of gonadotropin-releasing hormone agonist alone or in conjunction with estrogen-progestin replacement.

We studied 20 hirsute patients with high levels of serum testosterone (T), calculated free T, androstenedione, and dehydroepiandrosterone sulfate and 19 age-matched nonhirsute normoandrogenic control women. The bone mineral density (BMD) in the lumbar spine, femoral neck, and trochanter major region in hirsute patients was higher than that in the controls. BMD in the lumbar spine and proximal femur correlated positively with the body mass index and with serum T and free T in hyperandrogenic women and the whole study group, but not with serum androstenedione or dehydroepiandrosterone sulfate levels.

The effect of cryopreservation in prevention of ovarian hyperstimulation syndrome.

Objective: To evaluate the effect of elective cryopreservation of all embryos in the prevention of severe ovarian hyperstimulation syndrome in women at increased risk, following superovulation for in vitro fertilisation.

Design: Three hundred and ninety women undergoing superovulation for in vitro fertilisation between September 1991 and December 1992.

Setting: University Infertility Clinic, Helsinki, Finland.

Estrogen replacement does not potentiate gonadotropin-releasing hormone agonist-induced androgen suppression in treatment of hirsutism.

The therapies presently available for treating ovarian hirsutism are not uniformly effective, and therefore, much has been expected from GnRH agonists. These inhibit the secretion of gonadotropins and thereby suppress ovarian function, but at the same time cause hypoestrogenic side-effects. We, therefore, administered goserelin, a long-acting GnRH agonist, for treatment of 20 hirsute women (18 with polycystic ovaries) for 9 months; half of them were randomized to receive cyclic estradiol and medroxyprogesterone replacement from the fourth month onward.

In vitro and in vivo binding of toremifene and its metabolites in rat uterus.

The in vitro binding affinities of toremifene (TOR), 4-hydroxy toremifene (4-OH-TOR) and several other metabolites for the rat uterine cytosolic estrogen receptor were compared with those of tamoxifen (TAM) and 4-hydroxy tamoxifen (4-OH-TAM). Only small differences were observed and the binding affinities of both 4-hydroxy metabolites were similar to that of estradiol (E2). Uterine uptake and subcellular distribution of [3H]TOR and [3H]TAM were then compared at 1, 8 and 72 h after administration to castrated rats.

The bio/immuno ratio of serum luteinizing hormone increases after orchiectomy in prostatic cancer patients and is associated with decreased molecular weight and appearance of isohormones with alkaline pI values.

Serum concentrations of bioactive (B) and immunoreactive (I) luteinizing hormone (LH) were determined in six patients with prostatic cancer before castration and at frequent intervals after the operation up to 6 mo. B-LH increased in 6 mo from 11 +/- 1 to 90 +/- 9 (mean +/- SEM, n = 6) IU/liter (p less than 0.01), and I-LH from 9 +/- 1 to 37 +/- 5 IU/liter (p less than 0.

Pancreatic and catalytic phospholipase A2 in relation to pregnancy, labor and fetal outcome.

The serum pancreatic and catalytic phospholipase A2 level (PLA2) in human pregnancy is normal, and the increase of pancreatic enzyme before delivery is small. In patients with pruritus associated with obstetric hepatosis maternal serum had a slightly lower pancreatic PLA2 level if the cholic acid level was higher. Umbilical cord blood has twice as much pancreatic PLA2 as maternal blood.

Influence of pregnancy and lactation on serum and breast fluid estrogen levels: implications for breast cancer risk.

We investigated estrogen (estrone and estradiol) levels in serum and in nipple aspirates of breast fluid in relation to reproductive and menopausal characteristics in 104 normal women. In general, breast fluid and serum estrogen levels were not correlated and breast fluid estrogen levels were approximately 5 to 45 times higher than serum levels. Serum estrogen levels were lower in post-menopausal than in pre-menopausal women.

Changing concepts of active androgens in blood.

We have provided a brief historical review of developments in our understanding of the endocrine mechanisms underlying the expression of androgen action in women. An alternative to the free hormone concept is considered which proposes that, at least in some target cells, androgens bound to SHBG are the biologically relevant molecules. In nearly every instance, the changes in blood levels of SHBG that have been observed are consistent with this idea.

Maternal aspirin administration inhibits pulmonary arachidonic acid metabolism in fetal rabbits.

Pregnant rabbits were treated with aspirin (100 mg/kg/day) for ten consecutive days during the last third of the pregnancy. The ability of isolated perfused fetal rabbit lungs to metabolize arachidonic acid (AA) was studied on the 31st day of the pregnancy. After the infusion of 14C-AA (100 nmol) into the pulmonary circulation about 10% of the radioactivity was found in the nonrecirculating perfusion effluent and about 80% was incorporated into the lung lipids.

The metabolism of arachidonic acid in hamster lung microsomes is not completely inhibited by aspirin and indomethacin.

Aspirin (100 microM or 1 mM) or indomethacin (10 microM or 100 microM) was incubated with a microsomal preparation of hamster lungs in the presence of NADPH for 10 min. Then 14C-arachidonic acid (20 microM) was added and the incubation was continued for an additional 20 min. The metabolites were extracted with ethyl acetate first at pH 7.

The metabolism of prostaglandin E2 in perinatal rabbit lungs.

The inactivation of prostaglandin E2 (PGE2) was studied in isolated perfused lungs of fetal and neonatal rabbits. 200 nmol of 14C-PGE2 was infused into the pulmonary circulation and the metabolites of PGE2 were analysed from the nonrecirculating perfusion effluent. The amount of the main metabolite, 13,14-dihydro-15-keto-PGE2, increased significantly between the 28th and 30th day of fetal life, remained relatively constant at the time of birth and increased again between 1st and 7th postnatal day.

The metabolism of arachidonic acid in isolated perfused fetal and neonatal rabbit lungs.

The developmental pattern of fetal and neonatal rabbit lungs to metabolize arachidonic acid (AA) to different cyclo-oxygenase products was studied in isolated rabbit lungs, which were perfused with Krebs bicarbonate buffer. 14C-AA (66 nmol) was injected into the pulmonary circulation and the nonrecirculating perfusion effluent was collected for four minutes. About ten per cent of the injected radioactivity was found in the 0-4 min perfusion effluent.