Gonadotrophin stimulation for in vitro fertilization significantly alters the hormone milieu in follicular fluid: a comparative study between natural cycle IVF and conventional IVF

Wolff, Michael von; Kollmann, Zahraa; Flück, Christa E.; Stute, Petra; Marti, Ulrich; Weiss, Benedicte; Bersinger, Nick A.

doi:10.1093/humrep/deu044

Cited by 78 publications

(54 citation statements)

References 23 publications

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“…As the follicular function is strongly affected by high-dosage gonadotropin stimulation [11], we aimed to analyse the effect of endometriosis on naturally matured follicles in natural cycle IVF (NC-IVF).…”

Section: Discussionmentioning

confidence: 99%

“…We had previously characterised the intrafollicular milieu in naturally matured follicles [11]. Based on these findings and the study from Wunder et al, who found decreased follicular fluid estradiol concentrations in endometriosis patients undergoing cIVF [16], and studies suggesting AMH to be a marker of oocyte quality [32,33,34], we chose testosterone, E 2 and AMH to characterise the endocrine milieu.…”

Section: Discussionmentioning

confidence: 99%

“…A dysregulated intrafollicular hormone milieu [11] as well as an abnormal intrafollicular cytokine profile might therefore be a cause of reduced fertility in endometriosis patients. This suggestion is in line with studies from oocyte donation programmes.…”

Section: Introductionmentioning

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%

“…Natural cycle IVF (NC-IVF) seems to be an adequate model for a physiological follicle because the follicles undergo the maturation process without any stimulation apart from a single HCG administration to induce ovulation and therefore closely represent natural follicles [11]. Therefore, we have used the model of NC-IVF in a selected group of women with histologically proven endometriosis and carefully selected matched controls to analyse the concentrations of several inflammatory cytokines and hormones present in the follicular fluid and serum at the time of follicular aspiration.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%