Assessment of follicular fluid leptin levels and insulin resistance as outcome predictors in women undergoing in vitro fertilization–intracytoplasmic sperm injection

Llaneza-Suárez, David; Llaneza, Plácido; González, Celestino; De-La-Fuente, Pedro; Garcia-Ochoa, Carlos; Garrido, Pablo; Castañón, Vanesa; Pérez‐López, Faustino R.

doi:10.1016/j.fertnstert.2014.09.012

Cited by 17 publications

(11 citation statements)

References 41 publications

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“…These cytokines did not correlate with age or AMH ( Figure 3 B,C). These results validate the efficacy of our cytokine antibody array approach because leptin was previously shown to increase follicular fluid with BMI [ 28 , 29 ]. Moreover, these results demonstrate that the cytokine signature that changes with age is independent of that related to BMI.…”

Section: Resultssupporting

confidence: 79%

Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid

Machlin

Barishansky

Kelsh

et al. 2021

IJMS

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The female reproductive system ages before any other organ system in the body. This phenomenon can have tangible clinical implications leading to infertility, miscarriages, birth defects and systemic deterioration due to estrogen loss. “Fibroinflammation” is a hallmark of aging tissues; there is an increase in inflammatory cytokines and fibrotic tissue in the aging ovarian stroma. We systematically evaluated immunomodulatory factors in human follicular fluid, which, like the stroma, is a critical ovarian microenvironment directly influencing the oocyte. Using a cytokine antibody array, we identified a unique fibroinflammatory cytokine signature in follicular fluid across an aging series of women (27.7–44.8 years). This signature (IL-3, IL-7, IL-15, TGFβ1, TGFβ3 and MIP-1) increased with chronologic age, was inversely correlated to anti-Müllerian hormone (AMH) levels, and was independent of body mass index (BMI). We focused on one specific protein, TGFβ3, for further validation. By investigating this cytokine in human cumulus cells and ovarian tissue, we found that the age-dependent increase in TGFβ3 expression was unique to the ovarian stroma but not other ovarian sub-compartments. This study broadens our understanding of inflammaging in the female reproductive system and provides a defined fibroinflammatory aging signature in follicular fluid and molecular targets in the ovary with potential clinical utility.

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Section: Resultssupporting

confidence: 79%

Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid

Machlin

Barishansky

Kelsh

et al. 2021

IJMS

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“…Some previous studies among women undergoing infertility treatment suggest an association between leptin concentrations, pregnancy rates, and live birth. One group examined follicular fluid leptin concentrations in women undergoing infertility treatment, finding that higher concentrations of follicular fluid leptin were associated with a lower likelihood of having a live birth after adjusting for waist circumference and insulin resistance [24]. This study did not adjust for BMI so it is unknown whether the association would remain after adjustment for an alternative marker of adiposity.…”

Section: Discussionmentioning

confidence: 99%

“…These studies tended to find higher concentrations of leptin, whether measured in serum or ovarian follicular fluid, and lower endometrial leptin expression among women with infertility [19–23]. Higher follicular fluid concentration of leptin was associated with lower likelihood of live birth among women undergoing in vitro fertilization [24], whereas another study found an association between higher nonfasting plasma leptin levels and improved likelihood of live birth in women with recurrent pregnancy loss [25].…”

mentioning

confidence: 99%

Preconception Leptin and Fecundability, Pregnancy, and Live Birth Among Women With a History of Pregnancy Loss

Plowden

Zarek

DeVilbiss

et al. 2019

Journal of the Endocrine Society

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Context With the increase of obesity, it is imperative to understand the neuroendocrine mechanisms, including the neuroendocrine hormone leptin, by which obese or overweight women are at increased risk for subfertility and infertility. Objective The objective was to examine associations between preconception serum leptin concentrations, fecundability, pregnancy, and live birth. Design Secondary analysis of a prospective cohort among women with prior pregnancy losses. Setting The study was conducted at four US medical centers (2006 to 2012). Intervention Not available. Materials and Methods Preconception serum leptin concentrations were measured at baseline, and women were followed for up to six menstrual cycles, and throughout pregnancy if they conceived. Discrete Cox proportional hazard regression models were used to assess fecundability odds ratios (FORs) and log-binomial regression to estimate risk ratios (RRs) for pregnancy and live birth. Models were adjusted for age, physical activity, treatment arm, and adiposity, either by measured waist-to-hip ratio or body mass index (BMI). Results High leptin concentrations were associated with decreased fecundability (FOR 0.72, 95% CI 0.58, 0.90), reduced risk of pregnancy (RR 0.87, 95% CI 0.78, 0.96) and live birth (RR 0.76, 95% CI 0.65, 0.89) comparing the upper to the lower tertile. However, adjustment for BMI in lieu of waist-to-hip ratio nullified observed associations. Conclusions In women with a history of pregnancy loss, relations between higher preconception leptin and fecundability were attenuated after adjustment for BMI, although not after adjustment for other markers of adiposity. Leptin may serve as a complementary marker of adiposity for assessment of obesity and reproductive outcomes.

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“…62 High leptin levels in follicular fluid were associated with abdominal obesity, IR, and a lower live birth rate after IVF-ICSI. 63 Leptin receptors are also present on immune cells. In the state of obesity-associated hyperleptinemia, on the basis of animal studies, leptin shifts the immune system toward a proinflammatory state.…”

Section: Leptinmentioning

confidence: 99%

The Emerging Role of Chronic Low-Grade Inflammation in the Pathophysiology of Polycystic Ovary Syndrome

et al. 2015

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Polycystic ovary syndrome (PCOS) has become increasingly common over recent years and is associated with reproductive features as well as cardiometabolic risk factors, including visceral obesity, dyslipidemia and impaired glucose homeostasis, and potentially cardiovascular disease. Emerging evidence suggests that these long-term metabolic effects are linked to a low-grade chronic inflammatory state with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle in the pathophysiology of PCOS. Dysregulation of the sympathetic nervous system may also act as an important component, potentially creating a tetrad in the pathophysiology of PCOS. The aim of this review is to examine the role of chronic inflammation and the sympathetic nervous system in the development of obesity and PCOS and review potential therapeutic options to alleviate low-grade inflammation in this setting.

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Assessment of follicular fluid leptin levels and insulin resistance as outcome predictors in women undergoing in vitro fertilization–intracytoplasmic sperm injection

Cited by 17 publications

References 41 publications

Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid

Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid

Preconception Leptin and Fecundability, Pregnancy, and Live Birth Among Women With a History of Pregnancy Loss

The Emerging Role of Chronic Low-Grade Inflammation in the Pathophysiology of Polycystic Ovary Syndrome

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