Gonadotropin-releasing hormone agonist combined with hormone replacement therapy does not improve the reproductive outcomes of frozen-thawed embryo transfer cycle in elderly patients: a retrospective study

Dong, Mei; Sun, Li; Huang, Li; Yi, Yong; Zhang, Xiqian; Ying, Tiejin; Song, Ge; Liu, Liling; Fu, Wei; Li, Fenghua

doi:10.1186/s12958-020-00626-8

Cited by 22 publications

(19 citation statements)

References 27 publications

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“…An interesting observation in our study is that the mean level of progesterone on the administration day in the HRT cycle was signi cantly higher than that in the GnRHa-HRT cycles (0.38±0.29 versus 0.53±0.47, P=0.001), which is consistent with the results in previous studies [12,14,22] . This might be due to a premature rise of LH levels in hormonal stimulation protocol without a GnRH agonist, which negatively alters the receptive window of the endometrium [16] .…”

Section: Discussionsupporting

confidence: 92%

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Gonadotropin-releasing Hormone Agonist Down Regulation Combined With Hormone Replacement Therapy Improves the Reproductive Outcome in the Frozen-thawed Embryo Transfer Cycle of Elderly Patients With Idiopathic Recurrent Implantation Failure

Peng

Yang

Zhang

et al. 2021

Preprint

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BackgroundTo determine whether Gonadotropin-releasing hormone (GnRH) agonist down regulation combined with hormone replacement treatment (HRT) can improve the reproductive outcomes in the frozen thawed embryo transfer (FET) cycle of elderly patients with idiopathic recurrent implantation failure (RIF). MethodsThis is a retrospective cohort study analyzing 594 elderly patients (aged 36~43 years old) undergoing third cleavage embryo or blastocyst transfer over nearly 5-year period (January 2015–November 2020) at Northwest Women’s and Children’s Hospital after IVF-ICSI cycles. Patients with known endometriosis or adenomyosis were excluded from the study.According to different endometrial preparation protocols, patients were divided into three groups: natural cycle group (NC, n=62), hormone replacement treatment cycle group (HRT, n=194) and GnRH agonist down regulation combined with HRT cycle group (GnRHa-HRT, n=290).Live birth rate was primary outcome while clinical pregnancy rate, miscarriage rate, on going pregnancy rate were secondary outcomes. ResultsLive birth rate in the GnRHa-HRT group (31.90%) was significantly higher than that in the HRT (21.65%) or NC (16.13%) groups (P<0.0001). Logistic regression model adjusting for the potential confounders showed that patients in the GnRHa-HRT group have significantly higher live birth rate compared with those in the HRT group (OR, 2.708; 95%CI,1.251-5.864, P=0.011). However, live birth rate was not significantly different between GnRHa-HRT and NC groups (OR, 1.509; 95% CI,0.657-3.463, P=0.332), which could be due to the small sample size in the NC group.ConclusionsGnRHa-HRT protocol improves live birth rate in FET cycles of elderly patients with RIF. We hypothesize that GnRHa-HRT protocol enhances implantation related factors and promotes optimal endometrium receptivity, leading to the improved live birth rate. These findings are also useful for further investigating the underlying mechanism of GnRHa-HRT protocol in improving the reproductive outcomes of elderly patients with RIF.Trial registration:The research protocol was approved by the hospital institutional ethics committee (2021002).

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Section: Discussionsupporting

confidence: 92%

“…Pretreatment with GnRHa before HRT in FET cycles is considered to be ineffective for the elderly patients, but it could be effective for the patients with RIF [12] . Recent studies also failed to demonstrate any signi cant effect of depot GnRHa-FET protocol in the live birth/ongoing pregnancy rate [6] .…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing Hormone Agonist Down Regulation Combined With Hormone Replacement Therapy Improves the Reproductive Outcome in the Frozen-thawed Embryo Transfer Cycle of Elderly Patients With Idiopathic Recurrent Implantation Failure

Peng

Yang

Zhang

et al. 2021

Preprint

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“…There is insufficient evidence that the use of a depot GnRH agonist combined with an HRT cycle is better or worse than the NC or HRT protocol for reproductive outcomes in FET cycles, especially for patients with RIF. Pretreatment with a GnRH agonist before HRT in FET cycles is considered ineffective for patients of advanced reproductive age, but this does not include patients with RIF [ 16 ]. A recent study also failed to demonstrate any significant effect of a depot GnRH agonist–HRT protocol on the live birth/ongoing pregnancy rate for patients with RIF [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure

Peng

Yang

Zhang

et al. 2022

Reprod Biol Endocrinol

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Background To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF). Methods This retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates. Results The live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist–HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381–0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181–0.796; P = 0.010). Conclusions The GnRH agonist–HRT protocol improves the live birth rate in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF. Trial registration This research protocol was approved by the hospital institutional ethics committee (No. 2021002).

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“…Only three studies considered live birth rate as outcome, and our results were consistent with our previous study focus on elderly patients and another retrospective study. In those two studies, the use of GnRH agonist in arti cial endometrium cycles to increase live birth rates cannot be established 21,22 . Another prospective randomized trial we mentioned above has concluded that the supplement of GnRH agonist associated with higher live birth rates 9 .…”

Section: Discussionmentioning

confidence: 99%

Endometrial Preparation for Frozen–Thawed Embryo Transfer With or Without Pretreatment With Gonadotropin-Releasing Hormone Agonist in Regular Menstrual Cycles: Results of a Retrospective Cohort Study

Wei

Liu

Dong

et al. 2021

Preprint

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ObjectsTo compare the treatment outcomes of FET in hormonal replacement treatment (HRT) protocol with and without long-acting gonadotropin-releasing hormone agonist (GnRHa) pretreatment in patients with regular menstrual cycles. MethodsA total of 5049 patients from three centers were recruited in this retrospective study. The study population was divided into two groups. In HRT with GnRHa group, endometrial preparation with supplement estrogen 6mg daily initiated following down-regulation of long-acting GnRH agonist. In HRT group, the same dose of estrogen administration only for two weeks. Live birth rates were the primary outcomes measured in both groups. ResultsThere were no differences in implantation rate, β-HCG positive rate, clinical pregnancy rate, and early miscarriage rate between the two groups. The ongoing pregnancy rate and the live birth rate were higher in HRT group compared to the agonist group (47.3% vs 42.7% and 44.7% vs 39.8%, respectively). However, the co-treatment with GnRH agonist in HRT protocol was not associated with clinical pregnancy rate (OR 0.94; 95% CI 0.78 to 1.12) and live birth rate (OR 0.82; 95% CI 0.71 to 1.02) after logistic regression analysis. In the first FET cycle, patients in HRT group achieved higher clinical pregnancy rate and live birth rate. In addition, there was no differences in clinical pregnancy rate and live birth rate between the two groups in standard patients.ConclusionsThe HRT protocol for FET seems to be as effective as the HRT protocol involving preliminary pituitary suppression with GnRH agonist in regular menstrual cycles.

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Gonadotropin-releasing hormone agonist combined with hormone replacement therapy does not improve the reproductive outcomes of frozen-thawed embryo transfer cycle in elderly patients: a retrospective study

Cited by 22 publications

References 27 publications

Gonadotropin-releasing Hormone Agonist Down Regulation Combined With Hormone Replacement Therapy Improves the Reproductive Outcome in the Frozen-thawed Embryo Transfer Cycle of Elderly Patients With Idiopathic Recurrent Implantation Failure

Gonadotropin-releasing Hormone Agonist Down Regulation Combined With Hormone Replacement Therapy Improves the Reproductive Outcome in the Frozen-thawed Embryo Transfer Cycle of Elderly Patients With Idiopathic Recurrent Implantation Failure

Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure

Endometrial Preparation for Frozen–Thawed Embryo Transfer With or Without Pretreatment With Gonadotropin-Releasing Hormone Agonist in Regular Menstrual Cycles: Results of a Retrospective Cohort Study

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