Insulin resistance and free androgen index correlate with the outcome of controlled ovarian hyperstimulation in non-PCOS women undergoing IVF

Dickerson, Emily H; Cho, L.W.; Maguiness, S.D.; Killick, S.L.; Robinson, J. Elliott; Atkin, Stephen L.

doi:10.1093/humrep/dep393

Cited by 42 publications

(34 citation statements)

References 37 publications

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“…These results suggest for the first time that the down-regulation of aromatase in PCOS may be a result of the hyperandrogenic follicular environment. Consistent with previous studies (Dickerson et al 2010, de Resende et al 2010, Nejad et al 2011, Zhong et al 2012), the present study has shown that PCOS women have similar fertilization rates, good embryo quality rates and clinical pregnancy rates in ART as compared to non-PCOS women (Table 4). A possible reason for this might be that the pituitary suppression treatment necessary for ART have overcome the high LH level in PCOS (Table 3).…”

Section: Discussionsupporting

confidence: 92%

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Yang¹,

Ruan²,

Yang³

et al. 2015

Reproduction

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Women with polycystic ovary syndrome (PCOS) undergoing IVF-embryo transfer based-assisted reproductive technology (ART) treatment show variable ovarian responses to exogenous FSH administration. For better understanding and control of PCOS ovarian responses in ART, the present study was carried out to compare the follicular hormones and the expression of granulosa cell genes between PCOS and non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138 PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid collected from PCOS women showed high levels of testosterone. The expression of aromatase was found significantly reduced in luteinized granulosa cells from PCOS women. In cultured luteinized granulosa cells isolated from non-PCOS women, their exposure to testosterone at a level that was observed in PCOS follicles could decrease both mRNA and protein levels of aromatase in vitro. The inhibitory effect of testosterone was abolished by androgen receptor antagonist, flutamide. These results suggest that the hyperandrogenic follicular environment may be a key hazardous factor leading to the down-regulation of aromatase in PCOS.Reproduction (2015) 150 289-296

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Section: Discussionsupporting

confidence: 92%

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Yang¹,

Ruan²,

Yang³

et al. 2015

Reproduction

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“…17,18 Finally, we dichotomized HbA1c% using standardized cut points (< 6.5% as the referent versus ≥ 6.5%). Each of the outcome variables was assessed at baseline, 6 months, and 12 months post-intervention.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Sleep Debt on Excess Adiposity and Insulin Sensitivity in Patients with Early Type 2 Diabetes Mellitus

Arora

Chen

Cooper

et al. 2016

Journal of Clinical Sleep Medicine

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Study Objectives:We examined cross-sectional and prospective associations between sleep debt and adiposity measures, as well as homeostatic model assessment-insulin resistance (HOMA-IR) in early type 2 diabetes. Methods: Prospective data analysis from participants of a randomized controlled trial based on an intensive lifestyle intervention (usual care, diet, or diet and physical activity). Data were collected at baseline, 6 months, and 12 months post-intervention. The study was performed across five secondary care centers in the United Kingdom. Patients (n = 593) with a recent diagnosis of type 2 diabetes were recruited. Objective height and weight were ascertained for obesity status (body mass index [BMI]; ≥ 30 kg/m 2 ), waist circumference (cm) for central adiposity, and fasting blood samples drawn to examine insulin resistance (IR). Seven-day sleep diaries were used to calculate weekday sleep debt at baseline, calculated as average weekend sleep duration minus average weekday sleep duration. Results: At baseline, compared to those without weekday sleep debt, those with weekday sleep debt were 72% more likely to be obese (OR = 1.72 [95% CI:1.03-2.88]). At six months, weekday sleep debt was significantly associated with obesity and IR after adjustment, OR = 1.90 (95% CI:1.10-3.30), OR = 2.07 (95% CI:1.02-4.22), respectively. A further increase at 12 months was observed for sleep debt with obesity and IR: OR = 2.10 (95% CI:1.14-3.87), OR = 3.16 (95% CI:1.38-7.24), respectively. For every 30 minutes of weekday sleep debt, the risk of obesity and IR at 12 months increased by 18% and 41%, respectively. Conclusions: Sleep debt resulted in long-term metabolic disruption, which may promote the progression of type 2 diabetes in newly diagnosed patients. Sleep hygiene/education could be an important factor for future interventions to target early diabetes. Keywords: insulin resistance, type 2 diabetes mellitus, sleep debt, obesity, body mass index, waist circumference, central adiposity Citation: Arora T, Chen MZ, Cooper AR, Andrews RC, Taheri S. The impact of sleep debt on excess adiposity and insulin sensitivity in patients with early type 2 diabetes mellitus. J Clin Sleep Med 2016;12(5):673-680. I NTRO DUCTI O NThe International Diabetes Federation recently estimated that, globally, over 382 million individuals had diabetes in 2013 (an estimated 46.3% undiagnosed) and that this number is expected to rise to 592 million by 2035.1 The majority of affected individuals (over 90%) have type 2 diabetes, which is closely related to excess adiposity and its associated lifestyle factors such as poor diet and low physical activity. Sleep (duration and quality) may be another important factor associated with both obesity and type 2 diabetes, as suggested by both population and experimental studies.2-6 It has been hypothesized that social and work demands increasingly result in shorter sleep duration than required physiologically. 7 This sleep loss, accumulated into a sleep debt during weekdays, may be partially repaid by extra...

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“…Recruitment details and methods have been described previously. 1 In short, 49 women with male factor infertility, without PCOS were recruited preceding an IVF cycle. All women had a regular menstrual cycle and none had polycystic ovaries on ultrasound.…”

Section: Methodsmentioning

confidence: 99%

“…1 The treatment cycle was abandoned if the total follicle count was below 5, above 25 or if other signs/symptoms of ovarian hyperstimulation were observed. Abandoned cycles were not excluded from analysis.…”

Section: Methodsmentioning

confidence: 99%

“…We have shown that the free androgen index (FAI) calculated using total testosterone measured by immunoassay was positively correlated with the ovarian response to hyperstimulation in women without PCOS undergoing in vitro fertilization (IVF); however, there was no correlation of testosterone levels with oocyte fertilization rates. 1 Others in a retrospective study have reported that androstenedione and testosterone measured by immunoassay had a positive and negative impact on IVF parameters, respectively. 2 There is a considerable cross-reactivity of total testosterone with other androgens in women especially androstenedione and dehydroepiandrosterone sulfate.…”

Section: Introductionmentioning

confidence: 99%

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Androstenedione and testosterone levels correlate with in vitro fertilization rates in insulin-resistant women

Sathyapalan

Dickerson²,

Maguiness³

et al. 2017

BMJ Open Diab Res Care

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BackgroundThe free androgen index (FAI) calculated using total testosterone measured by immunoassay does not correlate with oocyte fertilization rates; however, there is considerable cross-reactivity for testosterone with other androgens by immunoassay that is not found using isotope dilution liquid chromatography–tandem mass spectrometry (LC/MS/MS).AimsThis study was done to determine relationship between total testosterone and androstenedione measured by LC/MS/MS and fertilization rates.Study design49 infertile women without polycystic ovary syndrome were recruited preceding an in vitro fertilization (IVF) cycle. Serum testosterone and androstenedione were measured by LC/MS/MS and correlated with IVF parameters non-insulin resistant compared with insulin resistant (homeostatic model assessment >2.5) women.ResultsFor non-insulin resistant women, total testosterone FAI and androstenedione did not correlate with oocyte fertilization rates. In insulin-resistant women, there was a negative correlation between both testosterone and FAI and fertilization rates (r=−0.62, p<0.03) and r=−0.73, p=0.02, respectively). There was a positive correlation between androstenedione and fertilization rates (r=0.87, p<0.01).ConclusionFor insulin-resistant women, increases in testosterone and FAI were associated with reduced fertilization rates and androstenedione was associated with increased fertilization rates when measured by LC/MS/MS that should be considered to be the measurement method of choice.

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Insulin resistance and free androgen index correlate with the outcome of controlled ovarian hyperstimulation in non-PCOS women undergoing IVF

Abstract: Our results suggest a positive correlation of HOMA-IR levels above a threshold level of 2.5 and a continuous positive correlation of free androgen (FAI) to total ovarian follicle count following COH in the non-PCOS patient.

Cited by 42 publications

References 37 publications

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

The Impact of Sleep Debt on Excess Adiposity and Insulin Sensitivity in Patients with Early Type 2 Diabetes Mellitus

Androstenedione and testosterone levels correlate with in vitro fertilization rates in insulin-resistant women

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