Molecular signature of immunological mechanism behind impaired endometrial receptivity in polycystic ovarian syndrome

Amjadi, Fatemehsadat; Zandieh, Zahra; Mehdizadeh, Mehdi; Ajdary, Marziyeh; Aghamajidi, Azin; Raoufi, Ehsan; Aflatoonian, Reza

doi:10.20945/2359-3997000000476

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…In women suffering PCOS, endometrial receptivity has been postulated to be affected via several mechanisms: (1) sustained androgenic exposure due to the abberant hormonal milieu [69,70], (2) metabolic alterations that regulate decidualization [71], (3) compromised PR functions led to total failure of the uterus in supporting embryo implantation [72], and (4) altered intrauterine microenvironment via deregulation of local inflammatory mediators [73,74]. In clinical practice, PCOS is related to a higher risk of miscarriage and adverse pregnancy outcomes [75], though its effect on IVF and FET cycles remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen–Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

Ho,

Tomai

et al. 2024

Biomedicines

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This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen–thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.

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Section: Discussionmentioning

confidence: 99%

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen–Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

Ho,

Tomai

et al. 2024

Biomedicines

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“…Any dysregulation in MMPs is associated with scarring and fibrosis in inflammation and wound healing. A study investigating the transcriptome profile of endometrium in PCOS showed significantly lower expression of MMP7 in PCOS compared to healthy controls [ 69 ]. The inflammatory environment inherent to PCOS could potentially cause loss of the association of MMP7 with 25(OH)D 3 in these non-obese PCOS subjects.…”

Section: Discussionmentioning

confidence: 99%

A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D

Nandakumar,

Das,

Sathyapalan

et al. 2024

IJMS

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Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D3 and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS (n = 29) and controls (n = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D3 (25(OH)D3) and the active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D3 and 1,25(OH)2D3 levels did not differ between groups. Nine CVRPs were higher in PCOS (p < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D3 correlated with five CVRPs in PCOS and one in controls (p < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D3, suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.

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The role of the oviduct environment in embryo survival

Juengel,

Reader,

Maclean

et al. 2024

Reprod. Fertil. Dev.

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Context Declining fertility is an issue in multiple mammalian species. As the site of fertilisation and early embryo development, the oviduct plays a critical role in embryo survival, yet there is a paucity of information on how the oviduct regulates this process. Aims We hypothesised that differences in steroid hormone signalling and/or immune function would be observed in a model of poor embryo survival, the peripubertal ewe. Methods We examined expression of steroid hormones in systemic circulation, oviductal expression of oestrogen receptor α and genes important in steroid hormone signalling, and immune function in pregnant and cyclic peripubertal and adult ewes on day 3 after oestrus. Key results Concentrations of progesterone, but not oestradiol, were decreased in the peripubertal ewe compared to the adult ewe. Oestrogen receptor α protein expression was increased in the peripubertal ewe, but pathway analysis of gene expression revealed downregulation of the oestrogen signalling pathway compared to the adult ewe. Differential expression of several genes involved in immune function between the peripubertal and adult ewe was consistent with an unfavourable oviductal environment in the peripubertal ewe lamb. Oestradiol concentration was positively correlated with the expression of multiple genes involved in the regulation of immune function. Conclusions Differences in the immune environment of the oviduct, potentially linked to differential modulation by steroid hormones, may partially underly the poor fertilisation and early embryo survival observed in the peripubertal ewe. Implications A unfavourable oviductal environment may play an important role in limiting reproductive success.

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Molecular signature of immunological mechanism behind impaired endometrial receptivity in polycystic ovarian syndrome

Cited by 3 publications

References 44 publications

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen–Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen–Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D

The role of the oviduct environment in embryo survival

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