Intrauterine administration of human chorionic gonadotropin improves the live birth rates of patients with repeated implantation failure in frozen-thawed blastocyst transfer cycles by increasing the percentage of peripheral regulatory T cells

Liu, Xuemei; Ma, Ding; Wang, Wenjuan; Qu, Qinglan; Zhang, Ning; Wang, Xinrong; Fang, Jianye; Ma, Zhi; Hao, Cuifang

doi:10.1007/s00404-019-05047-6

Cited by 32 publications

(21 citation statements)

References 27 publications

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“…Interestingly, our recent, unpublished results show that pregnant women have a higher number of Tregs in the peripheral blood, likely secondary to the hCG‐mediated upregulation of Tregs in pregnancy. This is in agreement with a recently published report in IVF patients, which demonstrated increased peripheral Tregs after intrauterine infusion of hCG at the time of FET 73 Also, women who had higher numbers of Tregs in the endometrium from a pre‐pregnancy endometrial biopsy had a higher chance of pregnancy, suggesting that Tregs may be able to be used to predict pregnancy. Our findings are in agreement to previous reports on the impact of hCG on Tregs.…”

Section: Hcg Impact On Tregssupporting

confidence: 92%

“…To evaluate other routes of hCG administration, several studies have looked at the impact of hCG as an intrauterine infusion in an effort to influence the endometrium prior to embryo transfer. While many studies have found an overall positive influence on pregnancy rates in certain patient populations, the data have been mixed 67‐73 . Collectively, there are many reports to suggest that hCG may be a valuable adjuvant endometrial preparation agent; however, large‐scale trials are lacking.…”

Section: Hcg As a Potential Adjuvant Therapymentioning

confidence: 99%

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Novel predictive and therapeutic options for better pregnancy outcome in frozen embryo transfer cycles

Huber

Sauerbrun‐Cutler

Krueger

et al. 2020

American J Rep Immunol

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Since 1978, in the first decades of in vitro fertilization (IVF), the use of ovarian hyperstimulation allowed for the development and transfer of multiple embryos. As IVF technology improved, the number of multiple pregnancies increased, which led to gradual reduction in the number of embryos that were transferred. Embryo freezing (vitrification) was recommended to allow subsequent transfer if the fresh cycle was unsuccessful. However, experimentation has continued to improve pregnancy outcomes. We discuss here the significance of frozen embryo transfer cycle and the impact of uterine and peripheral immunity dominated by NK cells and regulatory T cells and human chorionic gonadotropin on pregnancy outcome in this innovative mode of IVF therapy.

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Section: Hcg Impact On Tregssupporting

confidence: 92%

Section: Hcg As a Potential Adjuvant Therapymentioning

confidence: 99%

Novel predictive and therapeutic options for better pregnancy outcome in frozen embryo transfer cycles

Huber

Sauerbrun‐Cutler

Krueger

et al. 2020

American J Rep Immunol

View full text Add to dashboard Cite

show abstract

“…The decision to include also the pregnancy hormone hCG as a supplement was based on the results obtained by intrauterine application of hCG prior to embryo transfer in clinical settings (Bielfeld et al 2019). Liu et al (2019) showed an improvement in implantation rate, pregnancy rate and live birth rate with intrauterine administration of hCG 3 days prior to cryo transfer. For the in vivo studies, 100-1000 IU hCG were used (Craciunas et al 2016;Mansour et al 2011;Strug et al 2016).…”

Section: Effect Of Steroid Hormones and Hcg On Polarized Endometrial mentioning

confidence: 99%

Steroid hormones and human choriogonadotropin influence the distribution of alpha6-integrin and desmoplakin 1 in gland-like endometrial epithelial spheroids

Buck

Kohlen

Sternberg

et al. 2021

Histochem Cell Biol

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In human glandular endometrial epithelial cells, desmosomal and adherens junction proteins have been shown to extend from a subapically restricted lateral position to the entire lateral membrane during the implantation window of the menstrual cycle. Similarly, a menstrual cycle stage-dependent redistribution of the extracellular matrix adhesion protein α6-integrin has been reported. These changes are believed to be important for endometrial receptiveness and successful embryo implantation. To prove the hypothesis that steroid hormones and human choriogonadotropin can induce the redistribution of these adhesion molecules, we used the human endometrial cell line Ishikawa in a 3D culture system. Gland-like spheroids were grown in reconstituted basement membrane (Matrigel™). The lumen-bearing spheroids were treated for 2 or 4 days with ovarian steroids or human choriogonadotropin and then assessed by immunofluorescence microscopy. In addition, human endometrial biopsies were obtained from patients, who were in therapy for assisted reproductive technology, and were examined in parallel. Lateral redistribution of the desmosomal plaque protein desmoplakin 1 was observed in the spheroids treated either with progesterone, medroxyprogesterone acetate or human choriogonadotropin. Furthermore, the extracellular matrix adhesion protein α6-integrin showed an increased lateral membrane localization upon gestagen stimulation in the 3D culture system. The results of this study demonstrate that the 3D endometrial Ishikawa cell culture might be suited as an experimental model system to prove the effect of hormonal changes like those occurring during the window of implantation.

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“…Intrauterine hCG injection. Two observational studies investigated the effect of intrauterine hCG injection in women with RIF 28,151 . Primary outcomes Chances of clinical pregnancy (fixed effects model, OR 1.81; 95% CI 1.23-2.65; p = 0.002; I 2 = 0%) 28,151 and live birth (OR 1.78; 95% CI 1.02-3.09; p = 0.04) 151 resulted significantly increased in treated women (Fig.…”

Section: References Therapy/intervention Reason For Exclusionmentioning

confidence: 99%

Efficacy of therapies and interventions for repeated embryo implantation failure: a systematic review and meta-analysis

Busnelli

Somigliana

Cirillo

et al. 2021

Sci Rep

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The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle outcome. Twenty-two RCTs and nineteen observational studies were included. Pooling of results showed a beneficial effect of intrauterine PBMC infusion on both CPR (RR 2.18; 95% CI 1.58–3.00; p < 0.00001; OR 2.03; 95% CI 1.22–3.36; p = 0.006) and LBR (RR 2.41; 95% CI 1.40–4.16; p = 0.002; OR 3.73; 95% CI 1.13–12.29; p = 0.03), of subcutaneous G-CSF administration on CPR (RR 2.29; 95% CI 1.58–3.31; p < 0.0001) and of intrauterine PRP infusion on CPR (RR 2.45; 95% CI 1.55–3.86; p = 0.0001). Observational studies also demonstrated a positive effect of IVIG and intrauterine hCG infusion on both CPR and LBR and of atosiban on CPR. Studies investigating intrauterine G-CSF infusion, LMWH, intravenous intralipid, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome. The quality of the evidence that emerged from RCTs focused on intrauterine PBMC infusion and subcutaneous G-CSF administration was moderate. For all other therapies/interventions it varied from low to very low. In conclusion, intrauterine PBMC infusion and subcutaneous G-CSF administration are the most promising therapeutic options for RIF. However, further well conducted RCTs are necessary before their introduction into clinical practice.

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Intrauterine administration of human chorionic gonadotropin improves the live birth rates of patients with repeated implantation failure in frozen-thawed blastocyst transfer cycles by increasing the percentage of peripheral regulatory T cells

Cited by 32 publications

References 27 publications

Novel predictive and therapeutic options for better pregnancy outcome in frozen embryo transfer cycles

Novel predictive and therapeutic options for better pregnancy outcome in frozen embryo transfer cycles

Steroid hormones and human choriogonadotropin influence the distribution of alpha6-integrin and desmoplakin 1 in gland-like endometrial epithelial spheroids

Efficacy of therapies and interventions for repeated embryo implantation failure: a systematic review and meta-analysis

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