High estradiol levels during a long agonist IVF protocol are associated with decreased food intake, higher leptin concentrations, and lower levels of high-sensitivity C-reactive protein.

PURPOSE: To study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol. METHODS: Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test. RESULTS: During the stimulation protocol, leptin concentrations elevated (P < 0.001), and energy intake decreased (P = 0.03), while estradiol levels increased (P < 0.001). GLP-1 levels unchanged (P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased. CONCLUSION: No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.

The effect of different estradiol levels on carotid artery distensibility during a long agonist IVF protocol.

BACKGROUND: This study was made to figure out, does low and high estradiol levels during in vitro fertilization (IVF) cycles have a different effect on carotid artery distensibility (Cdis), carotid artery diameter (Cdia), blood pressure and metabolic factors? Can the stimulation protocol be considered safe to women's vasculature? METHODS: We studied 28 women having a long agonist protocol IVF-treatment in Kuopio University Hospital during the years 2011-2016. Patients were examined at three time points: in the beginning of their own period (low estradiol), during the gonadotrophin releasing hormone (GnRH) analogue downregulation (low estradiol) and during the follicle stimulating hormone (FSH) stimulation (high estradiol). Women served as their own controls and their menstrual phase (2- to 5-day period after the beginning of menstruation with low estrogen) was used as the reference. Cdis and Cdia were assessed using ultrasound. Blood pressure, weight, estradiol levels and lipids were monitored. RESULTS: Cdis, Cdia, systolic and diastolic blood pressures peaked during the GnRH-analogue treatment with the lowest estradiol levels. Cdis, Cdia and systolic blood pressures declined by 11% (P = 0.002), 3,8% (P < 0.001) and 2,5% (P = 0.026) during the FSH-stimulation when the estradiol levels were high. Cdis correlated significantly (P < 0.05) with systolic blood pressure, diastolic blood pressure and triglycerides in high estrogenic environment and with diastolic blood pressure (P < 0.05) when estrogen profiles were low. CONCLUSIONS: Carotid artery stiffens during the high estradiol levels compared to low levels and this was not explained by the higher diameter of the carotid artery, hyperlipidemia or blood pressure profiles. All the changes in Cdis and Cdia are variations of normal, and if there is no history of cardiovascular problems, it can be considered, that the stimulation protocol is not hazardous to vasculature.

Socioeconomic status affects the prevalence, but not the perinatal outcomes, of in vitro fertilization pregnancies.

STUDY QUESTION: Does maternal socioeconomic status (SES) confound or modify the association between IVF and perinatal outcome among singleton births? SUMMARY ANSWER: There were substantial socioeconomic differences in the frequency of IVF pregnancies, but maternal SES was not associated with the outcome of IVF pregnancies. WHAT IS KNOWN ALREADY: The use of IVF is associated with SES. Additionally, women with lower SES tend to have an increased risk of adverse perinatal outcomes such as preterm birth and small for gestational age birth. STUDY DESIGN, SIZE, DURATION: We conducted a population-based cohort study using the Finnish Medical Birth Register (2006-2010). PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed the total population of singleton births in Finland (n = 291 004) and then compared the unadjusted and adjusted incidences of adverse perinatal outcomes for singleton births after IVF (n = 5647) and non-IVF pregnancies (n = 285 357) in relation to SES. MAIN RESULTS AND THE ROLE OF CHANCE: SES did not confound or modify the association between IVF and perinatal outcomes after adjustments for age, parity, smoking, gestational diabetes, maternal diabetes and pre-eclampsia. However, the prevalence of IVF pregnancies increased with SES; on average 1.9% of singleton infants were born after IVF pregnancies, while the corresponding percentages were 3.2 and 1.2% for the highest and lowest SES strata, respectively. IVF was statistically significantly associated with 1.27-, 1.49-, 1.63-, 1.47-, 1.35-, 1.40-, 4.97- and 1.14-fold higher incidences of admission to a neonatal unit, stillbirth, preterm birth, low birthweight, low Apgar scores (<7 at 5 min), Cesarean section, placenta previa and major congenital anomaly, respectively. Irrespective of the SES group, women who became pregnant through IVF were older and more often nulliparous and non-smokers compared with women with non-IVF pregnancies. LIMITATIONS, REASONS FOR CAUTION: The occupation of 22% of the women was unknown and that of a further 25% did not match any of the criteria for our SES strata. Additionally, infertility is a problem for couples but the definition of SES in this study was based only on the mother's occupation at the time of birth. WIDER IMPLICATIONS OF THE FINDINGS: The prevalence of IVF-conceived pregnancies was highest among the highest SES group, but SES did not confound the perinatal outcomes of IVF pregnancies after adjusting for background factors. However, the magnitude of risks associated with the IVF technique itself may be more significant than previously thought. STUDY FUNDING/COMPETING INTEREST(S): None of the authors received any funding specifically for this study, and we have no competing interests.

Endothelial function and concentrations of high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha during a long agonist IVF protocol.

We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.

Cumulative baby take-home rate among women with PCOS treated by IVF.

OBJECTIVE: This study was designed to evaluate cumulative live birth rates after an in vitro fertilisation (IVF) programme in polycystic ovary syndrome (PCOS) women. SUBJECTS AND METHODS: IVF outcomes of 66 women with PCOS diagnosed via Rotterdam criteria, who failed to conceive after ovulation induction, were compared with 106 women with tubal factor infertility. One hundred and twenty-five cycles were analysed in the PCOS group and 225 cycles in the control group (1-4 cycles per woman). Results of frozen-thawed cycles, occurrence of ovarian hyperstimulation syndrome (OHSS) and drop-outs were also included. RESULTS: Despite a lower pregnancy rate among women with PCOS versus controls, the cumulative baby take-home rate did not differ between the groups (48.5% and 44.3%). The first cycle was the most successful cycle for living birth rate in PCOS group. One-third of PCOS women, who did not continue after unsuccessful treatment, had more miscarriage but not more OHSS compared to those who continued. CONCLUSIONS: Although the baby take-home rate was similar among women with PCOS, and controls, the outcomes of consecutive cycles were not equal. Cumulative data give more realistic information than pooled cycles.

Fracture risk and bone density of peri- and early postmenopausal women with uterine leiomyomas.

OBJECTIVES: Fracture risk and bone mineral density (BMD) among peri- and early postmenopausal women with leiomyomas requiring hysterectomy was evaluated. METHODS: We counted fractures among women with or without leiomyomas using data from the Kuopio Osteoporosis Study. The study population consisted of 6086 women aged 47-56 years with never-use of hormone replacement therapy (HRT) responding to the baseline and 5-year follow-up inquiries. Part of the sample (n=1271) underwent bone densitometry. RESULTS: Hysterectomy was carried out in 927 women, and 59% reported that this was attributable to leiomyomas. The hazard ratio (HR) was 0.68 (95% CI 0.49-0.94) for any and 0.73 (95% CI 0.43-1.26) for distal forearm fracture among women with leiomyomas compared to those without any. Among women postmenopausal at baseline, the corresponding HRs were 0.62 (95% CI 0.44-0.87) and 0.54 (95% CI 0.31-0.96); after adjusting for age, time since menopause weight, height and previous fracture 0.69 (95% CI 0.49-0.97) and 0.63 (95% CI 0.35-1.11). The baseline BMDs were 1.15 g/cm2 among hysterectomized leiomyoma and 1.12 g/cm2 (ns) among non-hysterectomized women at lumbar (L2-L4), and 0.94 and 0.93 g/cm2 (ns) at femoral sites. The follow-up lumbar BMDs were 1.13 and 1.09 g/cm2 (p<0.001) and the corresponding femoral values were 0.90 and 0.89 g/cm2 (ns), respectively. Among postmenopausal women, the corresponding baseline lumbar BMDs were 1.15 and 1.08 g/cm2 (p<0.001), femoral 0.93 and 0.90 g/cm2 (p=0.003); the follow-up lumbar BMDs 1.13 g/cm2 versus 1.07 g/cm2 (p<0.001); femoral BMDs 0.89 versus 0.87 (ns). CONCLUSIONS: Peri- and early postmenopausal women with a history of leiomyomas seem to have better BMD and less fractures compared with those without leiomyomas. This may be mediated through higher estrogen levels leading to higher BMD and the growth of leiomyomas.

Does hormone-replacement therapy prevent fractures in early postmenopausal women?

The purpose of this population-based prospective cohort study was to examine the effect of hormone-replacement therapy (HRT) on the risk of fractures. The study population consisted of 7217 postmenopausal women aged 47-56 years (mean, 53.3 years) at baseline from data taken from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) in Finland. We compared fracture incidences between HRT users and nonusers. A total of 679 (9.4%) women recorded validated fractures during the 5-year follow-up. Of these, 268 (39%) women had a distal forearm fracture. Two thousand six hundred seventy women (37%) had used HRT >6 months during the follow-up--one-half of them continuously. The relative risk, estimated as hazard ratio with Cox regression, was 0.69 (95% CI, 0.58-0.82) for any fracture and 0.49 (0.36-0.66) for distal forearm fracture among HRT users as compared with never-users. After adjusting for age, body mass index (BMI), number of chronic health disorders, fracture history, and time since menopause (independent risk factors) the corresponding risks were 0.67 (0.55-0.81) and 0.53 (0.37-0.74), respectively. The respective adjusted risks for continuous HRT users were 0.62 (0.48-0.79) and 0.41 (0.26-0.67). The adjusted risk of other than distal forearm fracture was 0.74 (0.55-0.98). The results suggest that HRT has a beneficial effect on prevention of fractures in general and on that of distal forearm fracture in particular in early postmenopausal women.