hCG Triggering in ART: An Evolutionary Concept

Klement, Anat Hershko; Shulman, Adrian

doi:10.3390/ijms18051075

Cited by 16 publications

(12 citation statements)

References 40 publications

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“…To examine the relationship between VEGF and Ang-Tie signaling pathways, we silenced Tie1 and quantified the VEGF level in SVOG cells cultured in the absence or presence of hCG. We found that VEGF and Tie1 levels were higher in treated SVOG cells than in the corresponding controls, consistent with previous studies that showed increased VEGF mRNA and protein levels in identically treated granulosa cells 11 , 15 . These findings prompted us to use the cell line for subsequent in vitro experiments that aimed to elucidate the roles of VEGF and Tie1.…”

Section: Discussionsupporting

confidence: 92%

“…Other studies have confirmed that an elevated serum VEGF level following hCG administration can trigger the development of OHSS in women undergoing in vitro fertilization (IVF) 12 , 13 , indicating that the serum VEGF level can predict the risk of OHSS and that the odds of developing OHSS may be reduced by inactivating VEGF receptors and inhibiting the VEGF signaling pathway 14 . At the cellular level, hCG has been reported to trigger OHSS by upregulating VEGF expression in luteinized granulosa cells 15 . Other studies have demonstrated VEGF expression in peripheral blood mononuclear cells from women with OHSS 16 , suggesting a role for circulating immune cells in the pathophysiology of OHSS, as well as in granulosa cells, where the VEGF level has been shown to significantly increase in response to hCG.…”

Section: Introductionmentioning

confidence: 99%

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Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

et al. 2022

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The expression of tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 (Tie1), a transmembrane protein expressed almost exclusively by endothelial cells, has been reported in granulosa cells. However, its significance in ovarian hyperstimulation syndrome (OHSS), which can occur after the injection of gonadotropins in infertile women undergoing controlled ovarian stimulation, is unknown. Here, we report significantly increased Tie1 and vascular endothelial growth factor (VEGF) expression in cultured granulosa cells from OHSS patients, as well as ovaries from rats with experimentally established OHSS, compared to controls, with the levels of both proteins also increasing in granulosa and SVOG cells (a nontumorigenic human granulosa-lutein cell line) treated with an acute dose of human chorionic gonadotropin (hCG). Tie1 silencing abolished the hCG-induced VEGF level in SVOG cells and attenuated the progression of OHSS in rats, as determined by histological analysis. Further studies in SVOG cells revealed that the hCG-induced upregulation of Tie1 expression involved the phosphoinositide 3-kinase/protein kinase B signaling pathway. We also report that early growth response protein 1 (EGR1), whose expression was also upregulated by hCG, bound directly to the Tie1 promoter and activated its transcription. Taken together, our results indicate that Tie1 may be a therapeutic target in cases of moderate-to-severe OHSS. Further studies are needed to address its clinical relevance.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

et al. 2022

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“…Both hCG and LH are complex heterodimeric glycoproteins with high cystine content. hCG has structural similarity to LH, sharing the same α subunit and 85% of the amino acid structure of the β subunit ( 81 ). This property affords hCG the ability to stimulate the LH receptor ( 4 ) and to induce luteinization of granulosa cells and the resumption of meiosis ( 82 ).…”

Section: Current Modes To Induce Final Oocyte Maturationmentioning

confidence: 99%

Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment

2018

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Infertility affects one in six of the population and increasingly couples require treatment with assisted reproductive techniques. In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotropin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication “ovarian hyperstimulation syndrome” (OHSS), which can cause considerable morbidity and, rarely, even mortality in otherwise healthy women. The use of GnRH agonists (GnRHas) has been pioneered during the last two decades to provide a safer option to induce final oocyte maturation. More recently, the neuropeptide kisspeptin, a hypothalamic regulator of GnRH release, has been investigated as a novel inductor of oocyte maturation. The hormonal stimulus used to induce oocyte maturation has a major impact on the success (retrieval of oocytes and chance of implantation) and safety (risk of OHSS) of IVF treatment. This review aims to appraise experimental and clinical data of hormonal approaches used to induce final oocyte maturation by hCG, GnRHa, both GnRHa and hCG administered in combination, recombinant LH, or kisspeptin. We also examine evidence for the timing of administration of the inductor of final oocyte maturation in relationship to parameters of follicular growth and the subsequent interval to oocyte retrieval. In summary, we review data on the efficacy and safety of the major hormonal approaches used to induce final oocyte maturation in clinical practice, as well as some novel approaches that may offer fresh alternatives in future.

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“…Recombinant and urine‐purified hCG is widely used in ovulation induction protocols to promote follicular rupture in low‐complexity infertility treatment or trigger oocyte maturation in IVF cycles. Some protocols suggest the use of hCG to support the luteal phase and improve IRs 50 …”

Section: Discussionmentioning

confidence: 99%

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review

Cavalcante

Sarno

et al. 2020

American J Rep Immunol

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Studies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: “recurrent implantation failure,” “intrauterine infusion,” “Platelet‐Rich Plasma (PRP),” “Peripheral Blood Mononuclear Cells (PBMC),” “Granulocyte Colony‐Stimulating Factor (G‐CSF),” and “Human Chorionic Gonadotropin (hCG).” The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G‐CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies.

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hCG Triggering in ART: An Evolutionary Concept

Cited by 16 publications

References 40 publications

Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review

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