LIF endometrial expression is impaired in women with unexplained infertility while LIF-R expression in all infertility sub-groups

Margioula‐Siarkou, Chrysoula; Prapas, Yannis; Petousis, Stamatios; Milias, Stefanos; Ravanos, Konstantinos; Dagklis, Themistoklis; Kalogiannidis, Ioannis; Mavromatidis, Georgios; Haitoglou, Costas; Πράπας, Νικόλαος; Rousso, David

doi:10.1016/j.cyto.2017.04.009

Cited by 24 publications

(15 citation statements)

References 28 publications

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“…Makled et al report a diagnosis of endometritis by hysteroscopy and endometrial biopsy in 15% of UI patients [25]. Anomalous endometrial cytokine (LIF, IL17, IL18, IL35), protein (PC6) and NK cell concentrations, which may negatively impact embryo implantation, have also been reported in UI women [[26], [27], [28], [29]].…”

Section: Discussionmentioning

confidence: 99%

Potential chances for natural fertility influence results of intrauterine inseminations

Moreau

Gatimel

Simon

et al. 2019

European Journal of Obstetrics & Gynecology and Reproductiv

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ObjectiveIntra-uterine insemination (IUI) is widely used for different indications. The aim of the present study was to evaluate the efficiency of intra-uterine insemination as a function of indication and origin of the inseminated spermatozoa.Study designThe retrospective study involved 827 first attempts of IUI in 827 couples between January 2011 and July 2017 in the Toulouse university hospital. Of these, 642 used fresh sperm from the husband, 40 frozen sperm from the husband and 145 frozen sperm from donors. The measured outcome parameter was live birth rate per attempt.ResultsWhen comparing couples lacking functional gametes (due to male or female causes), to couples who could potentially conceive spontaneously, i.e. subfertile, the latter were found to have a significantly lower live birth rate (18% vs 26%; P < 0.05). Even when adjusted for demographic parameters, which differed significantly between the 2 groups (female age, percentage of women suffering from primary infertility, BMI, number of inseminated motile spermatozoa and stimulation duration), this difference remained statistically significant (OR = 0.639 [0.425-0.961]; P = 0.0316).ConclusionWhen compared to couples lacking functional gametes, subfertile couples have poor IUI outcomes, suggesting a hidden cause of infertility, despite no apparent differences in ovarian reserve, tubal potency, results of ovarian stimulation and normal conventional sperm parameters. Further studies are required to better characterise and identify this subgroup of women with poor IUI outcomes.

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Section: Discussionmentioning

confidence: 99%

Potential chances for natural fertility influence results of intrauterine inseminations

Moreau

Gatimel

Simon

et al. 2019

European Journal of Obstetrics & Gynecology and Reproductiv

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“…Moreover, LIF knockout mice were infertile due to the implantation failure; however, LIF knockout embryos could develop in the uterus of wild-type mice ( 34 ). In addition, the frequency of relevant mutations of LIF was enhanced in infertility women, and LIF endometrial expression was impaired in UI women ( 20 , 21 , 35 ). We found that the endometrial LIF expression of UI patients was lower than that of control patients during the implantation window, suggesting the decreased pregnancy rate of UI patients might be due to the low receptivity of the endometrium.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies evaluated LIF expression in patients with UI, tubal factor, poor ovarian reserve, and endometriosis. They found LIF expression was significantly impaired in UI group compared with the control group, while no significant difference was observed in other infertility sub-groups ( 21 ). These studies demonstrated that the ECS and LIF are essential for the implantation and maintenance of the fetus.…”

Section: Introductionmentioning

confidence: 91%

The Roles of Anandamide, Fatty Acid Amide Hydrolase, and Leukemia Inhibitory Factor on the Endometrium during the Implantation Window

et al. 2017

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Background/aimsWe investigated the role of the endocannabinoid system (ECS) in the endometrium of unexplained infertility (UI) patients, and effect of anandamide (AEA) on leukemia inhibitory factor (LIF).MethodsPatients were divided into UI and control groups. Endometrium samples were collected at the midluteal phase. Levels of cannabinoid type 1 (CB1), fatty acid amide hydrolase (FAAH), and LIF were examined. LIF productions were measured after AEA, CB1 antagonist AM251, and CB2 antagonist AM630 stimulation.ResultsRates of available embryo, successful implantation and pregnancy, and the endometrial thickness of UI group were significantly lower than control, suggesting uterine receptivity was decreased in UI group. FAAH and LIF levels were significantly decreased, whereas endometrial CB1 was slightly increased in UI group. LIF production was promoted by low amount of AEA administration (1–10 μM), while the promotion was reduced by higher concentration of AEA (50 μM). LIF levels were decreased by AM251 or AM630, compared with AEA alone. Expressions of FAAH and LIF were closely associated with uterus receptivity and implantation rate of UI patients. Different concentrations of AEA could stimulate dynamic changes in LIF production.ConclusionOur data indicated the important role of the ECS in human fertility, which may promote new strategies for successful implantation and treatments for reproductive diseases.

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“…[18][19][20] a simultaneous expression of adequate quantity of LIFR is also needed for successful implantation, representing the central role of LIF-LIFR interaction in the establishment of infertility. 21 In women's samples, LIF assessment identified that the expression of LIF classically happened at some stages in the window of implantation in receptive endometrium. 22 The expression of LIF and its receptor LIFR in the endometrium of controls during luteal phase (days 6 to 9) has a positive correlation with pinopods expression, whereas the contradictory was detected in women with UEX-IF.…”

Section: Principal Findingsmentioning

confidence: 99%

Association of novel stop‐gained leukaemia inhibitory factor receptor gene (rs121912501) variant, leukaemia inhibitory factor and ovarian steroids with unexplained infertility among Pakistani women

et al. 2021

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Aims and Objectives: Embryo implantation is a complex process that requires sequential steps at the interface of embryo interaction with decidual endometrium. Many women after experiencing multiple attempts of assisted reproductive techniques fail to get implantation because of instability of leukaemia inhibitory factor and leukaemia inhibitory factor receptor-signal transducer and activator of transcription factor 3 (LIF-LIFR STAT3) signalling cascade. Therefore, this study explores the association of ovarian steroids, LIF and LIFR stop-gained variant using the tetra primer amplification refractory mutation system-polymerase chain reaction (TARMS-PCR) with unexplained infertility (UEX-IF) among Pakistani women. Materials and Methods:This is a case-control study, a total of 81 unexplained infertile women and 162 fertile controls (with age and BMI matched) were inducted.Serum estradiol, progesterone and LIF were determined using enzyme-linked immunosorbent assay (ELISA). T-ARMS-PCR was designed using Primer 1 software.Genomic DNA was extracted from peripheral blood and amplified using T-ARMS-PCR followed by sequencing for validation and comprehensive concordance.Results: This study established differences in LIF levels (χ 2 = 9.857, P < .05) between patients and controls as well as explored the decreased LIF significantly raised the risk of UEX-IF (OR = 2.316; 95% CI = 1.214, 4.416). Progesterone (P) was significantly associated with UEX-IF between fertile and infertile counterparts (χ 2 = 20.347, P < .05). It was also observed that increased Progesterone reduced the risk of UEX-IF (OR = 0.306; 95% CI = 0.166, 0.567). A rapid and inexpensive method for genotyping novel LIFR gene polymorphism through T-ARMS-PCR was successfully developed.LIFR gene SNP (rs121912501) had significant association (χ 2 = 200.681, P < .05) with UEX-IF. LIFR rs121912501 "TT" genotype (OR = 5.417; 95% CI = 1.868, 15.709) and "CT" genotype (OR = 3.104, 95% CI = 1.586,6.076) were at increased risk of infertility. Conclusion: UEX-IF can be caused by LIFR gene variation irrespective of increased P. It may open the doors for the discovery of new management plans for infertile women.

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LIF endometrial expression is impaired in women with unexplained infertility while LIF-R expression in all infertility sub-groups

Cited by 24 publications

References 28 publications

Potential chances for natural fertility influence results of intrauterine inseminations

Potential chances for natural fertility influence results of intrauterine inseminations

The Roles of Anandamide, Fatty Acid Amide Hydrolase, and Leukemia Inhibitory Factor on the Endometrium during the Implantation Window

Association of novel stop‐gained leukaemia inhibitory factor receptor gene (rs121912501) variant, leukaemia inhibitory factor and ovarian steroids with unexplained infertility among Pakistani women

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