Extrapituitary Actions of GnRH Antagonists: Prospects for in vitro Fertilization Programs

Impicciatore, Gianna Gabriella; Tiboni, Gian Mario

doi:10.2174/138161212799040358

Cited by 7 publications

(6 citation statements)

References 76 publications

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“…Indeed, GnRH-ant (Cetrorelix) has 20 times greater affinity for GnRH receptors than natural GnRH and 2 times greater affinity than GnRH-a (Buserelin) 30. Therefore, despite the low chance of generating biological effects from endogenous GnRH interacting with GnRH receptors outside the pituitary, GnRH-ant is likely still able to directly affect embryo implantation through stronger binding to endometrial cells,31 which present GnRH receptors 32…”

Section: Discussionmentioning

confidence: 99%

<p>Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium</p>

Chen¹,

Feng²,

Li³

et al. 2019

DDDT

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Purpose: The two major ovarian-stimulation protocols for in vitro fertilization are gonadotropin-releasing hormone agonist (GnRH-a) protocol or GnRH antagonist (GnRH-ant) protocol; however, comparisons of their relative efficacy remain controversial. Additionally, conflicting data exist regarding their effects on endometrial receptivity. Thus, this study investigated how GnRH-a and GnRH-ant treatments alter the endometrium during the mid-secretory phase. Patients and methods: We compared proteomic profiles across human endometrium tissues of mid-secretory phase from normal control humans (n=5), patients treated with GnRH-a (n=5), and patients treated with GnRH-ant (n=5). Results: We identified 2088 proteins, with 362 that exhibited significantly different expression. Fuzzy c-means clustering (FCM) using the M Fuzz algorithm analysis showed that the same 87 proteins changed significantly in both the GnRH-a and GnRH-ant groups compared with those in the control. Moreover, Gene Ontology (GO) analysis showed that, of these 87, downregulated proteins were associated with energy metabolism and upregulated proteins were linked to cytoskeleton maintenance. Upregulated proteins involved in complement-mediated immunity were present in 151 proteins that exhibited significantly different expression in the GnRH-ant group only. Conclusion: We demonstrated that comparative proteomic analysis is useful for accessing endometrial receptivity, which seemed more strongly impaired by GnRH-ant than GnRH-a treatments. Our findings also revealed that energy metabolism and immunity response may be the key biological mechanisms underlying human endometrial receptivity.

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Section: Discussionmentioning

confidence: 99%

<p>Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium</p>

Chen¹,

Feng²,

Li³

et al. 2019

DDDT

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“…Another mechanism through which the GnRH antagonists can block oocyte maturation is the direct effect on the ovary through the GnRH receptors existing on granulosa cells (13,14,15) . In animal studies, it was determined that GnRH analogs were effective on the ovarian functions of in vitro granulosa luteal cells such as steroidogenesis, oocyte maturation, and follicle rupture (16) .…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness of GnRH antagonist implementation on hCG injection day

Özdemir

Ayas

Güven

et al. 2019

tjod

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Objective: To compare the outcomes of antagonist stimulation protocols and to compare the cost effectiveness. Materials and Methods: Between 2011 and December 2017, a total of 354 women who underwent intracytoplasmic sperm injection and controlled ovarian stimulation with antagonist protocols were enrolled in the study. The antagonist implementation on the day of human chorionic gonadotropin (hCG) was continued for 194 of women, whereas the antagonist was stopped 36 hours before in 160 women. The stimulation outcomes of patients and cost-effectiveness of the regimens were compared. Results: There was a significant difference between the groups in terms of number of cryopreserved embryos, mature/immature oocyte ratio, and embryo transfer cancellations (p<0.05). The median value for the mature/immature oocyte ratio was 1.1 (0.2-7.5) and 1 (0.5-15) (p=0.001), and the ET cancellation was 5.3% vs. 1% for group 1 and 2, respectively (p=0.037). There was no difference between the groups in terms of pregnancy rates (p=0.197). Conclusion: No difference was found in the clinical pregnancy rates between the two groups. For this reason, the cessation of antagonist implementation on the day of hCG seems more advantageous in terms of cost-effectiveness and fewer injections.

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“…The functional role of extrapituitary GnRH receptor has not yet fully clarified, but there is an increasing number of literatures to suggest they may serve roles in reproduction. GnRH receptor expressed in female reproductive tissues, such as the endometrium, can be blocked by GnRH antagonist, raising the possibility that GnRH antagonist can have consequences for successful IVF programs . This knowledge will surely assist investigators to develop specific therapeutics measures that will optimize embryo implantation for this popular used protocol.…”

Section: Discussionmentioning

confidence: 99%

Effects of GnRH antagonist on endometrial protein profiles in the window of implantation

et al. 2014

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GnRH antagonists can suppress luteinizing hormone and follicle-stimulating hormone (FSH), with less initial stimulatory effect and lower risk of ovarian hyperstimulation syndrome. The effects of GnRH antagonists on embryonic implantation remain controversial. To evaluate the effects of GnRH antagonists, endometrial tissues were biopsied from 12 women with intracytoplasmic sperm injection treatment, in which four subjects undergoing controlled ovulation stimulation with rFSH and GnRH antagonist, four subjects with a GnRH agonist long protocol, and four natural cycle controls. After iTRAQ quantification analysis, 24 proteins showed differential expression between natural cycle and agonist treatment group and 39 proteins between natural cycle and antagonist treatment group. A total of seven proteins demonstrated differential expression only in antagonist treatment group. Bioinformatic analysis implied these proteins can function in cell processes including angiogenesis, cell proliferation, apoptosis, cell migration, and immune response. Furthermore, GnRH antagonist suppressed the function of GNAS and ANPEP, which were important for endometrial functions. Immunohistochemical staining showed that ANPEP was mainly localized in the human endometrial stroma, while ACO2, CDC5L, and GNAS were mainly localized in the glands. This study could provide insights into the effect of GnRH antagonists on the endometrium, and help optimize the embryo implantation and improve the success rate for GnRH antagonist protocol.

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Extrapituitary Actions of GnRH Antagonists: Prospects for in vitro Fertilization Programs

Cited by 7 publications

References 76 publications

<p>Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium</p>

<p>Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium</p>

Cost-effectiveness of GnRH antagonist implementation on hCG injection day

Effects of GnRH antagonist on endometrial protein profiles in the window of implantation

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