Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women

Al-Safi, Zain; Liu, Huayu; Carlson, Nichole E.; Chosich, Justin; Lesh, Jennifer; Robledo, Celeste; Bradford, Andrew P.; Gee, Nancy A.; Phang, Tzu L.; Santoro, Nanette; Kohrt, Wendy M.; Polotsky, Alex J.

doi:10.1210/jc.2015-1946

Cited by 23 publications

(33 citation statements)

References 45 publications

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“…Luteal estradiol (LE) priming is one of the other experimental modifications applied for POR to improve hypothalamic-pituitary-ovarian axis function [26]. Generally, LE priming is initiated on the 20th day of the previous cycle by daily administration of 4 mg of oral estradiol supplement or 0.1 mg of estradiol patch every other day, and is continued until day 2 of the following menstruation [27].…”

Section: Stimulation Modificationsmentioning

confidence: 99%

Ovarian stimulation modalities in poor responders

Özkan

2019

Turk J Med Sci

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In a group of IVF/ICSI cycles, despite the appropriate ovarian stimulation, the number of oocytes collected is below the expected value. This condition is defined as poor ovarian response (POR) to stimulation. POR brings the risk of cycle cancellation with an estimated rate of 20%. Infertility experts are trying to improve cycle outcomes of POR cases with multiple modifications. This review article will present the latest modifications on the management of POR. The studies performed for improving cycle outcome in POR cases were evaluated and their notable results were presented. The first intervention among infertility specialists is to make a standard definition for POR. The BOLOGNA criteria and the subsequent POSEIDON group definitions are the latest updates in POR management. GnRH antagonists, estradiol priming, double stimulation, letrozole administration, DHEA, and herbal therapy supplementations are the recent modifications done to improve oocyte retrieval and subsequent embryo transfer for POR cases. This review article presents the encouraging methods applied for POR cases to improve cycle outcome.

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Section: Stimulation Modificationsmentioning

confidence: 99%

Ovarian stimulation modalities in poor responders

Özkan

2019

Turk J Med Sci

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“…In this case mean FSH decreased in normal weight but increased in obese women. These results provide evidence that exogenous E2 priming might have a beneficial effect on HPG axis function by improving gonadotrope sensitivity and chronic, systemic inflammation in ovulatory, obese women [156].…”

Section: Pathophysiological Consequences: Effect Of Obesity-induced Imentioning

confidence: 62%

“…In addition, obese women had undoubtedly higher baseline pro-inflammatory cytokine levels such as IL-6 and IL-12. Following transdermal estrogen treatment mean LH and LH pulse amplitude increased in obese but decreased in normal weight participants [156]. Besides, estradiol treatment significantly decreased the levels of IL-1β, IL-12, and IL-8 in the serum obese subjects.…”

Section: Pathophysiological Consequences: Effect Of Obesity-induced Imentioning

confidence: 88%

“…Estradiol can be a potential link between these anomalies as it is an effective anti-inflammatory factor and exerts negative feedback on gonadotropin secretion. Clinical studies comparing regularly menstruating obese and normal weight women have found that mean serum LH and its amplitude was significantly lower in obese women, while its pulse frequency was not changed suggesting the importance of pituitary in the observed alterations [156]. In addition, obese women had undoubtedly higher baseline pro-inflammatory cytokine levels such as IL-6 and IL-12.…”

Section: Pathophysiological Consequences: Effect Of Obesity-induced Imentioning

confidence: 98%

“…Interestingly studies investigating the association between obesity and estradiol levels are inconsistent in their findings [153][154][155]. A recently published report suggested a possible mechanism for how estradiol affects obesity [156]. Obesity is characterized by a pro-inflammatory state and accompanied by fertility problems.…”

Section: Pathophysiological Consequences: Effect Of Obesity-induced Imentioning

confidence: 99%

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Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences

Barabás

Szabó-Meleg

Ábrahám

2020

IJMS

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Inflammation has a well-known suppressive effect on fertility. The function of gonadotropin-releasing hormone (GnRH) neurons, the central regulator of fertility is substantially altered during inflammation in females. In our review we discuss the latest results on how the function of GnRH neurons is modified by inflammation in females. We first address the various effects of inflammation on GnRH neurons and their functional consequences. Second, we survey the possible mechanisms underlying the inflammation-induced actions on GnRH neurons. The role of several factors will be discerned in transmitting inflammatory signals to the GnRH neurons: cytokines, kisspeptin, RFamide-related peptides, estradiol and the anti-inflammatory cholinergic pathway. Since aging and obesity are both characterized by reproductive decline our review also focuses on the mechanisms and pathophysiological consequences of the impact of inflammation on GnRH neurons in aging and obesity.

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Acute recapitulation of the hyperinsulinemia and hyperlipidemia characteristic of metabolic syndrome suppresses gonadotropins

Chosich

Bradford

Allshouse

et al. 2017

Obesity

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Objective To determine the effect of lipid/heparin versus saline infusion, with or without concurrent euglycemic hyperinsulinemia on serum FSH and LH. Obesity is associated with hyperlipidemia, insulin resistance, and relative hypogonadotropic hypogonadism. We hypothesized that acutely elevated fatty acids and insulin would impair gonadotropin secretion. Methods Regularly cycling women and men who were non-obese underwent a crossover 6-hour infusion study over 4 visits. Participants received infusions of: saline-control, lipid/heparin, insulin and lipid/heparin plus insulin. Serum FSH and LH were measured by immunoassay. Results In women (n=10), infusion of lipid plus insulin significantly reduced LH, from 4.6 (3.7-5.4) [mean (95% confidence interval)] to 3.3 (2.3-4.4); p=0.03 and FSH from 3.9 (3.2-4.6) to 3.1, (2.3-3.8) IU/L; p=0.03 compared to saline-control. Similarly, in men (n=10), LH, 3.3 (2.4-4.1) IU/L and FSH, 2.1 (1.4-2.8) IU/L were significantly reduced after the combined infusion, (2.2 (1.3-3.1) IU/L and 1.5 (0.8-2.1) IU/L; p=0.03, p=0.02, respectively). Neither lipid nor insulin alone significantly impacted gonadotropin levels compared to saline-control. Conclusions Hyperinsulinemia combined with elevated lipids acutely suppresses LH and FSH, providing a possible mechanism underlying the relative hypogonadotropic hypogonadism of obesity. Effects of insulin on the hypothalamic-pituitary-gonadal axis may be dependent on the concomitant metabolic environment.

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Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women

Abstract: E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.

Cited by 23 publications

References 45 publications

Ovarian stimulation modalities in poor responders

Ovarian stimulation modalities in poor responders

Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences

Acute recapitulation of the hyperinsulinemia and hyperlipidemia characteristic of metabolic syndrome suppresses gonadotropins

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