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ABSTRACT: Obesity is associated with vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) <50 nmol/l). We aimed to examine the effect of gender on vitamin D status in severe obesity.
Cross-sectional study of 2026 morbidly obese patients examined consecutively at a tertiary care centre between November 2005 and June 2010. Serum 25(OH)D concentration and use of vitamin D supplements were registered in all patients. Total vitamin D intake (μg/day) was assessed in a subgroup of 154 patients using a validated food frequency questionnaire.
The male (n=690) and female (n=1336) patients had a mean (s.d.) age of 45.0 (12.1) years and 42.2 (12.2) years (P<0.001), body mass index (BMI) of 44.6 (6.0) kg/m(2) and 44.3 (5.9) kg/m(2) (P=0.30) and waist circumference (WC) of 140 (13) cm and 127 (13) cm (P<0.001), respectively. Male patients had significantly lower mean 25(OH)D concentrations than female patients 50.0 (22.0) nmol/l versus 53.6 (22.4) nmol/l (P=0.001) and a higher rate of vitamin D deficiency (56% versus 47%; P<0.001). Obese men had significantly higher odds of vitamin D deficiency than women (odds ratio=1.41; 95% confidence interval: 1.17-1.70, P<0.001), also after adjustment for season, age, current smoking, intake of vitamin D supplements, BMI and WC (odds ratio=1.39; 95% confidence interval: 1.10-1.76).
Morbidly obese Norwegian men seeking weight loss treatment have significantly higher odds of vitamin D deficiency than women. Monitoring of 25(OH)D concentrations in obese patients should therefore take gender into account.
European journal of clinical nutrition 07/2011; 66(1):83-90. · 3.07 Impact Factor
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ABSTRACT: Surgical eradication of minimal and mild endometriosis has been shown to increase the birth rate both spontaneously and after intrauterine insemination. This study from a reproductive medicine unit at a referral university hospital examined whether surgical eradication of minimal and mild endometriosis prior to IVF improved the treatment outcome. Records of infertile patients with minimal and mild endometriosis (American Society for Reproductive Medicine stages I and II) with no prior IVF/intracytoplasmic sperm injection (ICSI) treatments were analysed. During the first treatment cycle, women who had undergone complete removal (n=399) of endometriotic lesions experienced, compared with women with diagnostic laparoscopy only (n=262), a significantly improved implantation rate (30.9% versus 23.9%, P=0.02), pregnancy rate (40.1% versus 29.4%, P=0.004) and live-birth rate per ovum retrieval (27.7% versus 20.6%, P=0.04). Surgical removal of minimal and mild endometriotic lesions also gave shorter time to first pregnancy and a higher cumulative pregnancy rate. The study shows that women with stages I and II endometriosis undergoing IVF/ICSI have significantly shorter time to pregnancy and higher live-birth rate if all visible endometriosis is completely eliminated at the time of diagnostic surgery. Surgical elimination of minimal and mild endometriosis has been shown to increase the birth rate both spontaneously and after intrauterine insemination. In this study from a reproductive medicine unit at a referral university hospital, we examined whether surgical elimination of minimal and mild endometriosis prior to IVF improved the outcome of this treatment as well. During the first IVF treatment cycle, women who had undergone complete surgical removal of endometriosis experienced, compared with women who still had their endometriosis, an improved rate of embryo implantation, pregnancy rate and live birth rate per ovum retrieval. Surgical removal of minimal and mild endometriotic lesions also gave shorter time to first pregnancy and a higher cumulative pregnancy rate. In summary, our study shows that women with minimal and mild endometriosis undergoing IVF have shorter time to pregnancy and higher live-birth rate if all visible endometriosis is completely eliminated before the start of treatment.
Reproductive biomedicine online 06/2011; 23(3):389-95. · 2.04 Impact Factor
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ABSTRACT: 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.
Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed.
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.
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.
Human Reproduction 10/2005; 20(9):2441-7. · 4.47 Impact Factor
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ABSTRACT: In this study we assessed how insulin resistance affects pregnancy rates in infertile women with the polycystic ovary syndrome (PCOS) treated with laparoscopic ovarian electrocautery. Sixty-four PCOS women were included in the study in a consecutive fashion. Following the CIGMA (continuous infusion of glucose with model assessment) test, 28 women were classified as insulin resistant and 36 women as non-insulin resistant. After the ovarian electrocautery patients were observed for 12-18 months. If pregnancy did not ensue, they were referred for one or more cycles of in vitro fertilization (IVF). Following ovarian electrocautery the non-insulin-resistant women more frequently achieved a regular menstrual cycle and ovulation than the insulin-resistant PCOS women. Consequently 18 (50%) of the non-insulin-resistant PCOS women achieved a pregnancy versus only five (18%) of women in the insulin-resistant PCOS group. Following treatment with both ovarian electrocautery and IVF, 27 (75%) of the non-insulin resistant PCOS women achieved a successful pregnancy, while 13 (46%) of the insulin-resistant PCOS group achieved this. In conclusion, insulin resistance may be an important marker of a poor outcome of treatment in PCOS infertility. Further studies are needed to evaluate the possible effect of treatment alternatives to alleviate the unfavorable influences of insulin resistance and hyperinsulinemia on ovulation induction in PCOS women.
Gynecological Endocrinology 11/2004; 19(4):182-9. · 1.58 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Journal of Assisted Reproduction and Genetics 10/2003; 20(9):352-7. · 1.84 Impact Factor
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ABSTRACT: 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.
Gynecological Endocrinology 07/2003; 17(3):207-14. · 1.58 Impact Factor
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ABSTRACT: In order to study androgen secretion during controlled ovarian hyperstimulation for in-vitro fertilization-embryo transfer, an open randomized study comparing the response to recombinant or urinary follicle-stimulating hormone (FSH) in down-regulated cycles was performed. During FSH administration significant increases in testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) levels were observed. During the same period a slight decrease in luteinizing hormone (LH) levels was seen. At all times during the stimulation period a significant correlation between estradiol and testosterone or androstenedione levels was observed. We conclude that FSH, through granulosa derived paracrine factors, initiates thecal androgen synthesis and secretion.
Gynecological Endocrinology 01/2002; 15(6):407-12. · 1.58 Impact Factor
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ABSTRACT: To elucidate possible differences between unexplained and minimal peritoneal endometriosis-associated infertility, we studied their outcome in natural cycle IVF (NIVF).
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.
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%).
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.
Human Reproduction 12/2001; 16(12):2587-92. · 4.47 Impact Factor
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ABSTRACT: 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.
Gynecological Endocrinology 09/2001; 15(4):286-92. · 1.58 Impact Factor
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ABSTRACT: 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.
Gynecological Endocrinology 07/2001; 15(3):192-7. · 1.58 Impact Factor
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ABSTRACT: 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.
Human Reproduction 07/2001; 16(6):1086-91. · 4.47 Impact Factor
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ABSTRACT: 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.
Scandinavian Journal of Clinical and Laboratory Investigation 01/2001; 60(8):649-55. · 1.38 Impact Factor
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ABSTRACT: 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.
Gynecological Endocrinology 11/2000; 14(5):327-36. · 1.58 Impact Factor
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ABSTRACT: 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.
Gynecological Endocrinology 09/2000; 14(4):258-63. · 1.58 Impact Factor
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ABSTRACT: To determine whether there was any difference in the outcome of in vitro fertilization when retrieval of oocytes was done 34 hr (group A) or 38 hr (group B) after hCG injection.
A total of 170 patients with tubal failure were randomized into either group A (83 patients) or group B (87 patients). They underwent in vitro fertilization according to described protocols and were compared with regard to the frequency of spontaneous ovulation, number of oocytes retrieved, oocyte cumulus complex quality, embryo quality, and implantation and pregnancy rates.
There was no significant difference for any of the parameters tested for in group A and group B.
HCG can be administered at any time within the time interval of 34 to 38 hr before retrieval of oocytes without affecting the results of in vitro fertilization.
Journal of Assisted Reproduction and Genetics 08/2000; 17(6):319-22. · 1.84 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Acta Obstetricia Et Gynecologica Scandinavica 02/2000; 79(1):43-8. · 1.77 Impact Factor
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Human Reproduction 01/2000; 15(1):227-8. · 4.47 Impact Factor
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ABSTRACT: 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.
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.
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.
Extending the embryo culture period from 2 to 3 days had no effect on implantation and live birth rates.
Journal of Assisted Reproduction and Genetics 12/1999; 16(10):529-34. · 1.84 Impact Factor
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ABSTRACT: There is increased risk of early pregnancy loss after assisted reproduction. In this study the use of serum human chorionic gonadotrophin (HCG) concentrations on day 12 after in-vitro fertilization (IVF) and embryo transfer was evaluated to predict pregnancy outcome. A total of 417 IVF pregnancies were included. Early pregnancy loss was defined as biochemical pregnancies, ectopic pregnancies and first trimester abortions. Vital pregnancies were defined as delivered singletons, multiple pregnancies and second trimester abortions. On the post embryo transfer day 12, the mean HCG concentration of the vital pregnancy group was significantly higher than in early pregnancy loss outcomes (P < 0.00001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value of HCG giving maximal sensitivity and specificity in order to discriminate early pregnancy losses from vital pregnancies. A patient with a HCG value higher than the calculated cut-off value (55 IU/l) had a 90% chance of having a vital pregnancy after IVF and embryo transfer. It can be concluded that a discriminatory HCG value on day 12 after IVF and embryo transfer cycles may be useful in predicting pregnancy outcome and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population.
Human Reproduction 06/1999; 14(6):1642-6. · 4.47 Impact Factor
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ABSTRACT: There have been numerous inconclusive studies examining the differences between unexplained and peritoneal endometriosis-associated infertility. Hence, the choice of artificial reproductive technique may be difficult. This prospective study compares outcome in couples with unexplained infertility and with minimal or mild endometriosis-associated infertility, undergoing treatment with ovarian stimulation combined with artificial insemination by husband. No differences were found between the unexplained infertile and the endometriosis group as to patient characteristics, response to ovarian stimulation and semen qualities. There was a significantly higher total pregnancy rate, with more multiple gestations, in the unexplained infertile compared with the endometriosis group. The difference in outcome could reflect differences in pathogenesis and aetiology for the two groups.
Human Reproduction 10/1998; 13(9):2602-5. · 4.47 Impact Factor
