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Biomedical subjects

R Storeng

Publications and source records attributed to R Storeng.

At least 19 recordsLinked to original sources

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression.

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.

Adult↗

Cycle characteristics of day 3 embryo transfers with 4-cell embryos only.

PURPOSE: Patient and cycle characteristics of day 3 transfers with developmentally lagging 4-cell embryos only were analyzed and related to the outcome of a live birth. METHODS: Day 3 transfers with either 4-cell embryos only (study group; n = 138) or 8-cell embryos only (control group; n = 282) were compared retrospectively. RESULTS: The total dose of FSH per treatment was higher, while the number of oocytes, zygotes, and transferred embryos was lower in the study group cycles compared to controls. The implantation, pregnancy, and live birth rates were dramatically lower in the study group compared to the control group. In the study group, the few cycles resulting in a live birth were characterized by a normal ovarian response to stimulation, similar to that of control group cycles with- or without a live birth. CONCLUSIONS: In cycles characterized by intensive ovarian stimulation, but poor response, the chance for a live birth is extremely low after day 3 transfer of 4-cell embryos.

Adult↗

The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial.

Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS). We examined whether metformin, given prior to and during ovarian stimulation for in vitro fertilization (IVF), altered follicle stimulating hormone (FSH) requirement and increased the number of collected oocytes in these women. Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment, the order of treatments being randomized using a table of random numbers. Metformin treatment (1500 mg/day) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH. Nine women completed both cycles, the results of eight women being excluded because of pregnancy after the first cycle (n = 4) or because the protocol of the study was not followed (n = 4). Mean total FSH dose was 2301 IU (range 1500-6563 IU) in metformin cycles and 2174 IU (range 1200-3900 IU) in parallel control cycles, while the mean number of collected oocytes was 8.6 (range 2-28) and 4.6 (range 1-16), respectively. Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10%, and of 0.61 that at least 10% more oocytes are collected after metformin co-treatment. Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH.

Adult↗

Effects of follicular fluid and steroid hormones on chemotaxis and motility of human spermatozoa in vitro.

The 'Transwell system' was used to test the response of human spermatozoa to human follicular fluid, progesterone, estradiol and mifepristone. Motility parameters were assessed with computer-assisted sperm analysis. Follicular fluid and progesterone induced significant accumulation of spermatozoa. Changes compatible with an increased progressive and hyperactivation-like motility were obtained with follicular fluid but not with progesterone. Mifepristone eliminated the progesterone-induced accumulation of spermatozoa but had no significant effect on the accumulation of spermatozoa in wells containing human follicular fluid. Furthermore, mifepristone abolished the motility changes effected by follicular fluid. Estradiol had no effect on accumulation or motility of spermatozoa. Human follicular fluid exerted a strong effect on sperm chemoattraction and motility in vitro, while progesterone influenced sperm chemoattraction only.

Chemotaxis↗

Natural cycle IVF in unexplained, endometriosis-associated and tubal factor infertility.

BACKGROUND: To elucidate possible differences between unexplained and minimal peritoneal endometriosis-associated infertility, we studied their outcome in natural cycle IVF (NIVF). METHODS: A prospective cohort study was carried out on unexplained (33 couples), minimal peritoneal endometriosis-associated (30 couples) and tubal factor (24 couples) infertility in 223 NIVF cycles, using human chorionic gonadotrophin (HCG) for ovulation induction. RESULTS: During the first NIVF attempt, follicular and luteal phase oestradiol, FSH, LH and progesterone concentrations, as well as endometrial thickness and follicular diameter were similar among the three groups. Periovulatory follicular growth monitored from day of HCG administration to oocyte aspiration was significantly lowered in unexplained infertility compared with minimal endometriosis-associated and tubal factor infertility. The fertilization rate, clinical pregnancy rate per initiated cycle, per successful oocyte retrieval and per embryo transfer, in minimal endometriosis (80.0, 10.4, 16.0 and 23.5% respectively) were similar to that in tubal factor infertility patients (68.6, 5.8, 11.4 and 16.0%) but significantly higher (P < 0.05) than that of the unexplained infertility group (62.2, 2.6, 5.4 and 8.7%). CONCLUSIONS: The significant reduction in follicular periovulatory growth, fertilization and pregnancy rates in unexplained infertility compared with minimal peritoneal endometriosis patients may be explained by sub-optimal follicular development with possibly reduced oocyte quality, intrinsic embryo quality factors or by impaired implantation. From a clinical point of view, NIVF is less suited to unexplained infertility treatment, but might represent an interesting treatment option for minimal peritoneal endometriosis-associated infertility.

Adult↗

The impact of ovarian stimulation on implantation and fetal development in mice.

The objective of this study was to evaluate, using an embryo donation model, whether impaired oocyte/embryo developmental competence and/or changes in uterine milieu are responsible for the previously observed adverse effects of superovulation with gonadotrophins on implantation and fetal development in mice. Embryos from superovulated and non-stimulated females were transferred to separate uterine horns within the same superovulated or non-stimulated pseudopregnant recipient mice. Embryo development was impaired as a significantly higher proportion of normal embryos from control donors (61%) were blastocysts on transfer day compared with superovulated donors (41%; P = 0.001). The implantation rate in control recipients was significantly reduced after transfer of embryos from superovulated donors (12%) compared with control donors (25%; P = 0.001). Uterine receptivity was impaired in superovulated recipients. The implantation rate of control embryos was significantly higher in control (25%) than in superovulated recipients (7%; P = 0.001). Transfer of embryos recovered from superovulated donors resulted in significantly higher post-implantation fetal mortality in superovulated recipients (69%) than in control recipients (36%; P = 0.01), and the mean weight of live fetuses was significantly lower for fetuses obtained from superovulated recipients (0.51 g) compared with that of fetuses obtained from control recipients (0.72 g; P = 0.006). Hence, ovarian stimulation appears to impair oocyte/embryo quality as well as uterine milieu.

Animals↗

The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome.

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.

Androstenedione↗

Simplification of continuous infusion of glucose with model assessment in the evaluation of insulin resistance in women with PCOS.

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The mean concentrations of glucose and insulin at 50, 55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis, and an insulin resistance index (IR1) was obtained. Using insulin and glucose values at 60 min only, a new insulin resistance index (IR2) was obtained using the same mathematical method. In addition, fasting insulin, fasting C-peptide, fasting glucose, fasting insulin:glucose ratio and fasting C-peptide:glucose ratio were also used to assess insulin resistance. There were significant correlations between IR1 and IR2, fasting glucose, fasting insulin, fasting insulin:glucose ratio, fasting C-peptide:glucose ratio. IR2 had the highest correlation with IR1 (r = 0.97, p < 0.001) and provided the best combination of sensitivity (82.9%), specificity (93.9%), positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion, the simplified CIGMA test, using insulin and glucose concentration at 60 min of glucose infusion only, is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.

Adult↗

Leptin and leptin binding activity in the preovulatory follicle of polycystic ovary syndrome patients.

To investigate the clinical importance of leptin's intraovarian effects, we studied the concentration of leptin and leptin binding activity in the plasma and in the follicular fluid of PCOS patients (n=20; median BMI: 27.1 kg/m2, range 19.7-36.3) undergoing controlled ovarian stimulation with long-term GnRH agonist, recombinant FSH, and in vitro fertilization. Follicular fluid and blood samples were collected during follicle aspiration for IVF. Total leptin concentration was measured by radioimmunoassay, and specific leptin binding activity was accessed by a gel filtration column assay. Follicular fluid and plasma leptin levels were similar (median 1135 pmol/l vs. 1409 pmol/l; p=0.81). Follicular fluid to plasma leptin ratio was independently associated with cumulative FSH dose (r=0.63; p=0.006) and insulin resistance index (r=-0.45; p=0.04). Specific leptin binding activity was higher in the plasma than in the follicular fluid [median 7.94% vs. 3.49%; p<0.001]. When multivariate analysis was used to predict FSH consumption, only follicular fluid leptin levels were significantly associated with cumulative FSH dose (r=0.46; p=0.04). We infer that at least in part by increased intrafollicular leptin levels, obesity directly affects ovarian function in PCOS, and may induce a relative resistance to gonadotropin stimulation. This intraovarian effect of leptin can be even more profound because of low leptin binding activity in the preovulatory follicle of obese patients.

Adult↗

Human chorionic gonadotropin levels in successful implantations after assisted reproduction techniques.

To assess successful implantation and early post-implantation embryonic development in assisted reproduction techniques, serum human chorionic gonadotropin (hCG) levels in early gestation in pregnancies with a singleton live birth as the outcome were evaluated. The study was performed as a prospective cohort study of patients undergoing in vitro fertilization (IVF) or artificial insemination by husband (AIH) following ovarian stimulation. Serum hCG levels on days 14, 16, 20 and 27 following ovulation induction with hCG were examined. Serum hCG values were significantly lower in early gestation in IVF compared with AIH, but no difference in hCG doubling times was observed. No difference in serum hCG values between IVF treatment with or without gonadotropin-releasing hormone agonist (GnRHa) was observed. Significantly lower hCG values but no difference in doubling times in early gestation in IVF compared with AIH may be explained by late but successful implantation in IVF. The mechanism for this assumed late implantation is not clear. Altered endometrial receptivity or factors of embryonic origin might explain the observed variation in hCG values and the assumed late implantation.

Adult↗

Impaired insulin action on granulosa-lutein cells in women with polycystic ovary syndrome and insulin resistance.

We studied the in vitro response to insulin of granulosa-lutein cells derived from patients with polycystic ovary syndrome (PCOS) and clinically defined insulin resistance. Insulin sensitivity was assessed by continuous infusion of glucose with model assessment test (CIGMA). Insulin resistant (PCOS-IR; n = 8), noninsulin resistant (PCOS-NIR; n = 9) patients with PCOS, and women with tubal factor infertility (TF; n = 8) underwent controlled ovarian stimulation with long-term gonadotropin-releasing hormone (GnRH) agonist, recombinant follicle stimulating hormone (FSH), and in vitro fertilization. Primary cultures of granulosa-lutein cells were incubated with insulin (10, 100, 500 ng/ml) and/or luteinizing hormone (LH) (10, 100 ng/ml) in the presence of low density lipoprotein (100 micrograms/ml). The progesterone and lactate accumulation were measured in the culture medium. LH potently stimulated the progesterone secretion in all groups. Insulin alone had no effect on progesterone release in any of the groups, but stimulated lactate formation in the PCOS-NIR and TF groups. Insulin augmented the effect of LH on progesterone secretion selectively in the PCOS-NIR group. The expression of the insulin receptor was determined by Western blotting in separate cultures of granulosa-lutein cells, and showed receptor down-regulation in the PCOS-IR patients. We infer that the in vitro effect of insulin on progesterone and lactate release by granulosa-lutein cells is impaired in insulin resistant PCOS patients.

Androstenedione↗

Obesity is a risk factor for early pregnancy loss after IVF or ICSI.

BACKGROUND: Experience with polycystic ovary syndrome shows that insulin resistance is related to early pregnancy loss. This association was examined by comparing pregnancy outcome in obese and lean women. METHODS: A cohort of 383 patients conceiving after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) was studied. Ovarian stimulation was achieved by GnRHa and FSH or hMG (n=362), by FSH or hMG alone (n=16), or by clomiphene citrate and FSH or hMG (n=5). Luteal phase was supported with progesterone. Pregnancies were defined by >10 IU/l plasma beta-hCG on day 14. Ultrasound scan on week 6 and week 12 confirmed fetal viability. RESULTS: Lean group (body mass index [BMI]<25 kg/m2; n=304) and obese group (BMI > or =25 kg/m2; n=79) were established. Obese patients had fewer oocytes collected (median: 8 vs 10 p=0.03), they had higher abortion rate during the first 6 weeks (22% vs 12%; p=0.03) and lower live-birth rate (63% vs 75%; p=0.04). The relative risk of abortion before week 6 was 1.77 (95% CI: 1.05 to 2.97). Multivariate logistic regression analysis revealed that obesity and low oocyte count were independently associated with spontaneous abortion. In the obese group, low oocyte number was associated with a more profound increase in the risk of abortion than among lean patients. The effect of age, history of past pregnancies, or infertility diagnosis on the probability of miscarriage were not significant. CONCLUSIONS: Obesity is an independent risk factor for early pregnancy loss. This risk is, in part, related to the lower number of collected oocytes in obese women.

Abortion, Spontaneous↗

Clinical outcome of day 2 versus day 3 embryo transfer using serum-free culture media: a prospective randomized study.

PURPOSE: The objective was to evaluate whether extending the embryo culture period from 2 to 3 days would yield a more optimal selection of viable embryos, thereby increasing the implantation and live birth rates. METHODS: Patients undergoing in vitro fertilization with at least one oocyte fertilized were prospectively randomized to 2 or 3 days of embryo culture in serum-free media. On the basis of their morphology and cleavage rate, a maximum of three embryos was selected for transfer. RESULTS: Embryos transferred on day 2 or day 3 were similar morphologically, however, a higher proportion of retarded embryos was observed on day 3. The implantation rate was 15.8 and 14.3% for day 2 and day 3 transfers, respectively. The increase in live birth rate from 18.5 to 22.6%, possibly suggesting a better embryo selection on day 3, was not statistically significant. CONCLUSIONS: Extending the embryo culture period from 2 to 3 days had no effect on implantation and live birth rates.

Birth Rate↗

[Intracytoplasmic sperm injection].

The first results of intracytoplasmic sperm injection (ICSI) in Norway are presented. Acceptable fertilization rates were obtained for all indications; severe male infertility, as well as moderately reduced sperm quality where in vitro fertilization (IVF) and embryo transfer had previously failed. Furthermore, in cases where IVF had failed despite normal sperm quality, fertilization rates of 50-60% were achieved. The overall pregnancy rate was 24.9% per embryo transfer, and the live pregnancy rate per started cycle was 13.4%. As expected, the results improved with experience. The results were greatly influenced by the age of the female. In the age group 34 years or less, the total pregnancy rate per cycle was 32.4%, with a miscarriage rate of 24.2%. In the age group 35 years or more, (42% of the study group), the total pregnancy rate per embryo transfer was 15.2%, with a miscarriage rate of 75%. The corresponding implantation rates were 17.4% and 7.9% respectively. 23 children have been born so far, none with major malformations or chromosome abnormality symptoms.

Adult↗

Treatment with gonadotropins impaired implantation and fetal development in mice.

PURPOSE: The effect of gonadotropins on implantation and fetal development in mice was investigated by superovulation with pregnant mare serum gonadotropin and human chorionic gonadotropin. In a previous study fetal growth was found to be highly retarded. RESULTS: Assessment of implantation in vivo revealed that late implantation did occur. Gestational length was highly extended, the mean number of live fetuses per pregnant mouse was lower and their mean weight significantly reduced. In vitro experiments revealed no significant difference in the rate of blastocyst adhesion and trophoblast outgrowth development. Immunohistochemical staining, however, showed that blastocysts from superovulated mice had smaller trophoblastic outgrowths than control embryos. Staging embryonic development at the time of flushing, however, revealed retarded embryo development in vivo in hormone-treated mice. After correlation with embryonic stage at the beginning of the culture, there was no difference in the size of trophoblastic outgrowths. CONCLUSION: Treatment with gonadotropins impaired implantation and embryonic/fetal development. Changes in maternal milieu, rather than in embryo quality, may be responsible for the adverse effects observed.

Animals↗

Adverse effects of gonadotrophin treatment on pre- and postimplantation development in mice.

The effect of gonadotrophins on pre- and postimplantation development in mice was investigated by superovulating C57BL/6J/Bom females with pregnant mares' serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) or by inducing ovulation with hCG. In both hormone treated groups, the proportion of abnormal preimplantation embryos increased compared with naturally ovulating animals. Postimplantation mortality increased and the mean number of live fetuses per pregnant mouse decreased in superovulated and hCG-treated mice compared with controls. Embryonic growth was highly retarded. Mean weight of live fetuses in superovulated and hCG-treated mice was reduced and skeletal examination revealed developmental retardation. In conclusion, superovulation as well as induction of ovulation adversely affected embryonic and fetal development.

Animals↗

Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas.

The major polycyclic aromatic hydrocarbon inducible-cytochrome P4501A1 gene (CYP1A1) is presumed to be important in pulmonary carcinogenesis and toxicology because its product, the cytochrome P4501A1-dependent (CYP1A1-dependent) monooxygenase, transforms selected xenobiotics (including polycyclic aromatic hydrocarbon procarcinogens in cigarette smoke) to potent carcinogenic metabolites. CYP1A1 messenger RNA (mRNA) expression has not, however, been previously demonstrated in human pulmonary tissue. This report defines CYP1A1 gene expression in normal lung tissue and primary pulmonary carcinoma tissue obtained at thoracotomy from 56 patients with lung cancer. When Northern blot hybridization analyses were performed, 17 of 19 (89%) and zero of five (0%) samples of normal lung tissue from active cigarette smokers and nonsmokers, respectively, expressed the normal 2.8-kilobase CYP1A1 mRNA. In addition, a time-dependent decrease in expression of the CYP1A1 gene was noted in normal lung tissue from individuals who were former smokers, with a decrease in expression occurring as early as 2 weeks following cessation of cigarette smoking. Expression became undetectable in all patients who had stopped smoking more than 6 weeks prior to study. When CYP1A1 gene expression was evaluated in lung cancers, mRNA levels were detectable in one of four (25%) tumors from nonsmokers; two of 24 (8%) tumors from former smokers; and seven of 15 (47%) tumors from cigarette smokers. In addition, an approximately 10-kilobase CYP1A1 RNA species, which was not detectable in normal lung tissue, was observed in five of ten (50%) of the lung cancers that expressed the CYP1A1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome P-450 CYP1A1↗