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      Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study

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          Abstract

          Background

          The implantation process after embryo transfer depends on the embryo quality and endometrial receptivity. It is estimated that fifty to seventy-five per cent of pregnancies are lost due to a failure of implantation. There is evidence that there is an early secretion of human chorionic gonadotrophin before embryo implantation, and this secretion has been linked to an important function in angiogenesis and the inflammatory response that promotes the implantation process. Our objective was to determine the effects of intrauterine injection of human chorionic gonadotropin (hCG) before the embryo transfer in an in vitro fertilisation cycle.

          Methods

          A prospective randomised study was conducted in Reproductive Medicine Centre PROCREA in Mexico City. Infertile patients who had a medical indication for in vitro fertilisation were studied. Two groups were included (n 210); the intervention group received an intrauterine injection of 500 IU of hCG before the embryo transfer (n 101). The control group (n 109) did not receive hCG. Comparisons were performed using a chi-square test.

          Results

          The clinical pregnancy rate (CPR) was our principal outcome. The implantation rate was a secondary outcome. The implantation rate was significantly higher in the hCG group compared to the control group (52.4% vs 35.7%, p 0.014). The clinical pregnancy rate was also significantly higher (50.4 vs 33.0%, p 0.010). No adverse effects were observed.

          Conclusions

          The intrauterine injection of hCG before embryo transfer showed a significant increase in the clinical pregnancy rate. More clinical trials are needed to reproduce these results on this promising intervention. The live birth rate must be included in subsequent studies.

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          Most cited references9

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          Is human chorionic gonadotropin directly involved in the regulation of human implantation?

          The regulation of human implantation is not fully understood. hCG as one of the earliest embryonal signals may be a major regulator in the parakrine embryo-endometrial communication. The expression of full-length hCG/LH-receptor mRNA could be demonstrated in human endometrium throughout the follicular and secretory phase of the menstrual cycle. In contrast, in early pregnancy decidua only truncated variants could be detected. To investigate direct effects of hCG on the human endometrium, an intrauterine microdialysis device was developed to measure parakrine mediators within the uterine cavity in vivo. Using this system, hCG was applied in the secretory phase and the endometrial response was evaluated. The administration of hCG (500 IU/ml) provoked a significant inhibition of intrauterine IGFBP-1 and M-CSF, while LIF, VEGF and MMP-9 were significantly stimulated. Taken together there appear to be multiple direct effects of hCG on the endometrium that precede the classical endocrine role of the hormone.
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            Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study.

            To investigate the value of intrauterine injection of human chorionic gonadotropin (hCG) before embryo transfer (ET). Prospective randomized study. The Egyptian IVF-ET Center. Infertility patients younger than 40 years undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). The study group (n = 167) received either 100 IU of hCG (n = 83), or 200 IU of hCG (n = 84) via intrauterine administration before ET. The control group (n = 93) underwent ET without hCG. After the interim analysis, the modified study group (n = 107) received intrauterine injection of 500 IU of hCG, and the control group (n = 105) underwent ET without hCG. Clinical pregnancy rate (PR) and implantation rate (IR). The IR and PR were statistically significantly higher in the 500 hCG group (41.6% and 75%, respectively) as compared with the control group (29.5% and 60%, respectively). The IR and PR were 26.6% and 54% in the 100 hCG group, 28.3% and 57% in the 200 IU hCG group, and 29.4% and 60% in the control group, respectively, with no statistically significant difference. Intrauterine injection of 500 IU of hCG before ET statistically significantly improved the implantation and pregnancy rates in IVF/ICSI. CLINICAL TRIALS.GOV NUMBER: NCT 01030393. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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              Hyperglycosylated human chorionic gonadotropin stimulates angiogenesis through TGF-β receptor activation.

              Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous cytotrophoblasts and by choriocarcinoma, was evaluated for its angiogenic role. hCG-H was purified by HPLC from choriocarcinoma supernatant, and the glycosylation pattern was determined by 2D gel analysis. Angiogenesis models used were aortic ring assay with wild-type and LHCGR-knockout mice, endothelial and mural cell proliferation, and migration assays. The TGF-β signaling pathway was studied by coimmunoprecipitation, competitive binding, TGF-β reporter gene assays, and Smad immunoblotting. hCG-H displayed a potent angiogenic effect [3.2-fold increase of number of vessel intersections in wild-type aortic rings (11.406 to 36.964)]. hCG-H-induced angiostimulation was independent of the classic hCG signaling pathway since it persisted in LHCGR-knockout mice [4.73-fold increase of number of vessel intersections (10.826 to 51.288)]. Using TGF-β signaling inhibitors, Tβ-RII was identified as the hCG-H receptor responsible for its angiogenic switch. hCG-H exposure enhanced phosphorylation of Smad 2 in endothelial and mural cells and genomic activation of Smad-responsive elements. Interaction between hCG-H and Tβ-RII was demonstrated by coimmunoprecipitation and binding competition with (125)I-TGF-β. This new paracrine interaction between trophoblast and endothelial cells through the hCG-H and the TGF-β receptor complex plays a key role in angiogenesis associated with placental development and tumorigenesis.
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                Author and article information

                Journal
                Reprod Biol Endocrinol
                Reprod. Biol. Endocrinol
                Reproductive Biology and Endocrinology : RB&E
                BioMed Central
                1477-7827
                2014
                29 January 2014
                : 12
                : 9
                Affiliations
                [1 ]Procrea, Reproductive Centre, 1st floor 670 Ejercito Nacional Avenue, Polanco Reforma, 11550 Mexico City, Mexico
                Article
                1477-7827-12-9
                10.1186/1477-7827-12-9
                3911962
                24476536
                1e4c5512-9e34-452c-9352-3614b0835652
                Copyright © 2014 Santibañez et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 5 July 2013
                : 16 January 2014
                Categories
                Research

                Human biology
                pregnancy rate,icsi,implantation rate,ivf,intrauterine hcg
                Human biology
                pregnancy rate, icsi, implantation rate, ivf, intrauterine hcg

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