Table 2.

Influence of LIF in human infertility, miscarriage and assisted pregnancy Brief description of the study.

Normal fertile women, women with unexplained infertility and women who suffered recurrent miscarriages were studied. Researchers obtained uterine flushings from all the women for analysis. LIF in flushings obtained from women with unexplained infertility was significantly lower than normal fertile women. They concluded that decreased concentrations of LIF in women with unexplained infertility indicate how important the cytokine is to embryo implantation.	Laird et al., 1997
32 women with unexplained infertility and 17 fertile women were studied. Endometrial biopsy samples were obtained and studied using a sensitive enzyme-linked immunosorbent assay (ELISA). LIF secretion was 2.2 times higher during the secretory phase than proliferative phase in fertile women whereas infertile women did not have this elevation in cytokine production. They concluded that the deregulation of endometrial LIF secretion may be linked to unexplained infertility and repetitive failures of implantation.	Hambartsoumian, 1998
30 infertile women with multiple implantation failures (MIF) and a fertile control group were studied. Researchers obtained endometrial biopsies in the proliferative phase and measured expression of LIF using immunohistochemistry and western blotting. Lower expression of LIF was found in infertile women with MIF compared to fertile women. They determined that initial lower expression of LIF during the proliferative phase may be a cause of multiple failures of implantation.	Wu et al., 2013
Women diagnosed with infertility and a control group of fertile women were studied. Researchers took an endometrial biopsy post ovulation to examine LIF and LIF-R expression. No significant differences in LIF/LIF-R was found in the stromal cells but there was a significant reduction in LIF/LIF-R expression in infertile women in epithelial cells. They concluded that LIF and LIF-R are significantly under expressed in epithelial cells of infertile women.	Margioula-Siarkou et al., 2017
75 infertile women and 40 control women were studied. Levels of LIF and IL-11 were examined using qRT-PCR. Lower levels of LIF and IL-11 were linked to increased risk of having PCOS, tubal factor, and unexplained fertility, likely due to the critical role these genes play in embryo implantation.	Alzaidi et al., 2021
30 women with idiopathic recurrent pregnancy loss (RPL) and 30 fertile controls were studied. Endometrial biopsies were used to evaluate PROK1 and LIF expression. PROK1 and LIF expression was significantly increased in the endometriums of women with idiopathic RPL. They concluded that increased mRNA expression of PROK1 and LIF could contribute to risk of RPL.	Karaer et al., 2014
148 IVF patients received uterine flushing during egg retrieval to assess LIF levels. Uterine flushing did not appear to affect pregnancy rates. LIF was found in 46% of patients at time of sample collection but no indication of better pregnancy rates in patients that had LIF compared to those who did not.	Olivennes et al., 2003
Women who were undergoing assisted reproduction were studied. Researchers obtained endometrial biopsies from women with recurrent pregnancy loss and a control group of fertile women, 7 days after luteinizing hormone peaked and LIF expression was examined. There was no significant difference in LIF expression between the two study groups.	Xu et al., 2012
44 women with recurrent implantation failure (RIF), 63 women who had children via IVF and 65 fertile women with children and no history of miscarriage were studied. Women who had a polymorphism in ESR1 and LIF had increased chances of presenting with RIF. They concluded that ER1 and LIF polymorphisms can predict RIF.	Vagnini et al., 2019
Women from 4 different groups of diagnoses associated with LIF mutations and various causes of infertility were studied to determine the impact of mutation in the LIF gene on assisted pregnancy via in vitro fertilization (IVF). They concluded that women with LIF mutations, infertility and endometriosis have poorer outcomes with IVF than other groups.	Novotný et al., 2009
Nulligravid infertile women, a fertile control group and unrelated control group were screened for LIF gene mutations. 3 point-mutations were identified in the infertile group that reduced biological activity of the LIF protein. They concluded that a heterozygous LIF mutation could result in decreased availability of LIF in the uterus, leading to implantation failure and thus infertility.	Giess et al., 1999