L expression des gènes mitochondriaux dans les cellules du cumulus, reflet des processus de vieillissement ovarien ?

La diminution de la réserve ovarienne (DOR), qui représente près de 10 % des causes d infertilité, est définie par une altération qualitative et quantitative de la réserve ovarienne. La mitochondrie joue un rôle clé dans cette problématique du vieillissement ovarien, par l importance de la masse mitochondriale sur la qualité ovocytaire, et par son rôle dans l apoptose. Les cellules folliculeuses, en entretenant un système de signalisation bidirectionnelle avec l ovocyte, interviennent dans l acquisition de la compétence ovocytaire. Elles pourraient ainsi représenter des témoins non invasifs de cette qualité ovocytaire. Dans cette étude, nous avons comparé en fonction de la réserve ovarienne des patientes (NOR : normale, DOR : diminuée), la masse mitochondriale des cellules folliculeuses et l expression de certains gènes clés relatifs à la biogenèse et aux fonctions mitochondriales (stress oxydatif, apoptose). La masse mitochondriale dans les cellules folliculeuses a été évaluée entre 400 et 600 copies par cellules, sans différence significative entre le statut DOR ou NOR des patientes (p = 0.4), ni corrélation avec l ADN mitochondrial ovocytaire (p = 0.6). En revanche, il existe une augmentation de l expression de certains gènes mitochondriaux, comme la catalase chez les patientes DOR (p = 0.01). En conclusion, l étude de l expression génique mitochondriale, par le biais des cellules folliculeuses, nous semble prometteuse.Diminished ovarian reserve (DOR), estimated around 10 % among infertile women, is defined by a quantitative and qualitative alteration of the ovarian reserve. Mitochondria are key players in ovarian aging, through the mitochondrial mass on the oocyte quality, and its role in apoptosis. Follicular cells, which are involved in a bidirectional signaling system with the oocyte, suppport the acquisition of the oocyte ability. They could thus represent non invasive biomarkers of the oocyte quality. In this study, we have compared, according to the ovarian status NOR (Normal Ovarian Reserve) and DOR (Decreased Ovarian Reserve), the mitochondrial content in follicular cells and the expression of various genes related to the biogenesis and mitochondrial functions (oxidative stress, apoptosis). Mitochondrial content in follicular cells has been estimated between 400 and 600 copies per cell, neither significant difference between DOR and NOR (p = 0.4), nor correlation with oocyte s mitochondrial content (p = 0.6). However, an increase in the expression of some mitochondrial genes, like catalase, has been observed among DOR patients (p = 0.01). As a conclusion, the study of mitochondrial gene expression, via follicular cells, seems to be promising.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality

Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87; 95% CI [0.66–1.12]; p = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups (p = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, p = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality

Influence of Diminished Ovarian Reserve on Early Embryo Morphokinetics during In Vitro Fertilization: A Time-Lapse Study

There is great controversy as to whether women with Diminished Ovarian Reserve (DOR) exhibit only a quantitative decrease in ovarian reserve or also impaired oocyte and embryo quality. In this retrospective study, we aimed to evaluate the impact of DOR on embryo morphokinetic parameters with a time-lapse system. 1314 embryos were obtained from 256 couples undergoing IVF or ICSI cycles, with 242 embryos in the DOR group as classified by the Bologna and POSEIDON criteria and 1072 embryos derived from the Normal Ovarian Reserve (NOR) group. For each morphokinetic parameter (t2, t3, t4, t5, t8, tB, ECC2, cc2a, ECC3, s2, s3), a generalized linear mixed model was created to control for female age, BMI, smoking status, method of insemination and correlation between oocytes from a same cohort. No significant association was found between DOR and any of the morphokinetic parameters studied. In a secondary analysis, we evaluated the influence of maternal aging, comparing morphokinetic characteristics between two age groups (<37 and ≥37 years). In the univariate analysis, we found that embryos from older women displayed a slower embryo development (in particular for t3, t4, t5, tB, and ECC2), although without statistical significance in the multivariate analysis. In conclusion, our study did not reveal any substantial impact of ovarian aging on early morphokinetic parameters and suggested potential biases that may be a source of controversy in the literature

The cytokine profile of follicular fluid changes during ovarian ageing

International audienceObjective: Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing. Material and methods: Our cross-sectional study assesses the levels of 27 cytokines and growth factors in the FF of two groups of women undergoing in vitro fertilization. One group included 28 patients with ovarian ageing clinically characterized by a diminished ovarian reserve (DOR), and the other group included 29 patients with a normal ovarian reserve (NOR), serving as controls. Results: With univariate analysis, the cytokine profile was found to differ significantly between the two groups. After adjustment of the p-values, platelet-derived growth factor-BB (PDGF-BB) was the only cytokine with a significantly lower concentration in the DOR group (7.34 AE 16.11 pg/mL) than in the NOR group (24.39 AE 41.38 pg/mL) (p = 0.005), independently of chronological age. Conclusion: Thus, PDGF-BB would seem to be implicated in the physiopathology of DOR, potentially in relation to its role in folliculogenesis or in the protection against oxidative stress

Elevated Levels of Monocyte Chemotactic Protein-1 in the Follicular Fluid Reveals Different Populations among Women with Severe Endometriosis

International audienceTo determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis

Additional file 1: of ConFIRM trial - conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response to stimulation: a protocol for a multicentric, prospective randomized trial

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOCX 74 kb