Serum but not follicular fluid cytokine levels are increased in stimulated versus natural cycle IVF: a multiplexed assay study

Bersinger, Nick A.; Kollmann, Zahraa; Wolff, Michael von

doi:10.1016/j.jri.2014.06.003

Cited by 21 publications

(9 citation statements)

References 25 publications

(28 reference statements)

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“…In view of their biological properties (pleiotropism, synergy, antagonism, functional redundancy, and differential sensitivity) [ 58 – 60 ], cytokines should ideally be investigated in terms of their interrelationships as much as in terms of their absolute concentrations. Whilst a recent study by Bersinger et al [ 61 ] failed to demonstrate a difference in 13 FF cytokines between women undergoing NC and COH IVF, no specific attention was paid towards the complex interrelations within the cytokine networks. To date, there has been a paucity of studies focusing on minimal stimulation regimens and MNCs, and comparisons of isolated cytokine concentrations (e.g., vascular endothelial growth factor (VEGF) in COH and NC-IVF) have been inconsistent [ 62 , 63 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Exogenous Gonadotropin Stimulation on Circulatory and Follicular Fluid Cytokine Profiles

Baskind

Orsi

Sharma

2014

International Journal of Reproductive Medicine

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Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence.

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Section: Introductionmentioning

confidence: 99%

Impact of Exogenous Gonadotropin Stimulation on Circulatory and Follicular Fluid Cytokine Profiles

Baskind

Orsi

Sharma

2014

International Journal of Reproductive Medicine

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“…Our results indicated a nonstatistically significant difference in FF VEGF levels. This may be supported by studies reporting similar levels of FF VEGF when comparing COS and natural cycles 30,68 . Accounting for levels of pigment epithelium–derived factor (PEDF) and providing data on the PEDF‐to‐VEGF ratio could certainly provide further insight as PEDG appears to be more closely correlated with adequate folliculogenesis.…”

Section: Discussionmentioning

confidence: 88%

“…Another extensively examined growth factor is VEGF, which is actively secreted into FF by granulosa cells 29–32 . Increased levels of VEGF were observed in FF originating from in vitro fertilization (IVF) patients with low (or even no) response to controlled ovarian stimulation (COS) 33–36 .…”

Section: Introductionmentioning

confidence: 99%

Investigating apoptotic, inflammatory, and growth markers in poor responders undergoing natural in vitro fertilization cycles: a pilot study

Sfakianoudis¹,

Tsioulou

Maziotis

et al. 2020

Annals of the New York Academy of Sciences

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This study investigates follicular fluid (FF) from patients with poor and normal ovarian response undergoing natural assisted reproductive technology cycles. We report about (1) cell‐free DNA (cfDNA), which reflects apoptosis; (2) corticotropin‐releasing hormone (CRH); (3) interleukin (IL)‐15, which reflects inflammation; (4) granulocyte colony–stimulating factor (G‐CSF); (5) vascular endothelial growth factor (VEGF); and (6) insulin‐like growth factor I (IGF‐I), which reflects follicular growth. Forty‐four poor responders and 44 normal responders—according to the Bologna criteria—were recruited. FF samples were prepared for cfDNA quantification employing Q‐PCR and for CRH, IL‐15, G‐CSF, VEGF, and IGF‐I quantification employing ELISA. Statistically nonsignificant different levels of FF cfDNA, CRH, IL‐15, VEGF, and IGF‐I were observed. Interestingly, statistically significant higher G‐CSF levels were observed in normal responders (302.48 ± 474.36 versus 200.10 ± 426.79 pg/mL, P = 0.003). Lower cfDNA integrity was observed in cycles resulting in clinical pregnancy for both groups (normal: 0.07 ± 0.04 versus 0.25 ± 0.17 ng/μL, P < 0.001; poor: 0.10 ± 0.06 versus 0.26 ± 0.12 ng/μL, P < 0.001). The results predominantly showcase similarities between normal and poor responders pertaining to inflammatory, apoptotic, and growth factors. This may be attributed to the employment of natural cycles in order to exclude controlled ovarian stimulation as a factor—indicating its detrimental effect. As G‐CSF levels presented significantly higher in normal responders, its vital role in understanding a compromised ovarian response is highlighted.

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“…We have chosen these cytokines as previous studies have shown dysregulation of these factors in endometriosis in serum [6], peritoneal [9] and follicular fluid of conventional, gonadotropin-stimulated IVF [6,[16][17][18], suggesting these factors to be associated with endometriosis. The Bio-Plex® assay was performed according to the manufacturer's instructions and has previously been described [13]. As a consequence, follicular fluids were diluted 1:3 using the sample diluent provided with the kit.…”

Section: Multiplexed Cytokine Determinationsmentioning

confidence: 99%

“…However, the findings mentioned above were mostly obtained from cIVF in which the exogenous gonadotropins considerably affect the intrafollicular hormonal milieu [11] and immune system [13].…”

Section: Introductionmentioning

confidence: 99%

Intrafollicular inflammatory cytokines but not steroid hormone concentrations are increased in naturally matured follicles of women with proven endometriosis

Bersinger²,

Mueller³

et al. 2017

J Assist Reprod Genet

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Purpose The aim of this study was to assess whether the intrafollicular cytokine profile in naturally developed follicles is different in women with endometriosis, possibly explaining the lower reproductive outcome in endometriosis patients. Methods A matched case-control study was conducted at a university-based infertility and endometriosis centre. The study population included 17 patients with laparoscopically and histologically confirmed endometriosis (rAFS stages II-IV), each undergoing one natural cycle IVF (NC-IVF) treatment cycle between 2013 and 2015, and 17 age-matched NC-IVF women without diagnosed endometriosis (control group). Follicular fluid and serum was collected at the time of follicle aspiration. The concentrations of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-15, IL-18, TNF-α) and hormones (testosterone, estradiol, AMH) were determined in follicular fluid and serum by single or multiplexed immunoassay and compared between both groups. Results In the follicular fluid, IL-1β and IL-6 showed significantly (P < 0.001 and 0.01, respectively) higher median concentrations in the endometriosis group than in the control group and a tendency towards endometriosis severity (rAFS stage) dependence. The levels of the interleukins detectable in follicular fluid were significantly higher than those in the serum (P < 0.01). Follicular estradiol concentration was lower in severe endometriosis patients than in the control group (P = 0.036). Follicular fluid IL-1β and IL-6 levels were not correlated with estradiol in the same compartment in neither patient group. Conclusions In women with moderate and severe endometrioses, some intrafollicular inflammatory cytokines are upregulated and not correlated with intrafollicular hormone concentrations. This might be due to the inflammatory microenvironment in endometriosis women, affecting follicular function and thereby possibly contributing to the reproductive dysfunction in endometriosis.

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Serum but not follicular fluid cytokine levels are increased in stimulated versus natural cycle IVF: a multiplexed assay study

Cited by 21 publications

References 25 publications

Impact of Exogenous Gonadotropin Stimulation on Circulatory and Follicular Fluid Cytokine Profiles

Impact of Exogenous Gonadotropin Stimulation on Circulatory and Follicular Fluid Cytokine Profiles

Investigating apoptotic, inflammatory, and growth markers in poor responders undergoing natural in vitro fertilization cycles: a pilot study

Intrafollicular inflammatory cytokines but not steroid hormone concentrations are increased in naturally matured follicles of women with proven endometriosis

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