scholarly journals Comparison of the ongoing pregnancy rate of first frozen-thawed embryo transfer cycles in women undergoing IVF using progestin primed ovarian stimulation versus GnRH antagonist protocol

Authorea ◽  
2020 ◽  
Author(s):  
Hong Chen ◽  
zhi qin chen ◽  
Hung Yu Ernest Ng ◽  
Miaoxin Chen ◽  
Mei Zhao ◽  
...  
2021 ◽  
Author(s):  
Ya-su Lv ◽  
Yuan Li ◽  
Shan Liu

Abstract BackgroundUse of gonadotropin-releasing hormone (GnRH) antagonists during the late follicular phase can prevent premature luteinizing hormone (LH) surge. Many patients demonstrate an insufficient endogenous LH concentration during ovarian stimulation. Previous studies have demonstrated that ultra-low LH concentration influences pregnancy outcomes. However, affected patients cannot be distinguished prior to ovarian stimulation using baseline characteristics alone. With traditional fixed or flexible GnRH antagonist protocols, antagonist administration may further reduce LH activity. Previously, we proved that LH can be used as an indicator for the timing and dosage of antagonist. Patients with a persistently low LH concentration during ovarian stimulation may not require antagonists, whereas antagonist administration can affect reproductive outcomes. To further explore this hypothesis, we designed a randomized clinical trial to compare the LH-based flexible GnRH antagonist protocol with traditional flexible GnRH antagonist protocol in women with normal ovarian response. MethodsThis study was a multicenter, parallel, prospective, randomized, non-inferiority study. The primary efficacy endpoint was cumulative ongoing pregnancy rate per cycle. The study aimed to prove the non-inferiority of cumulative ongoing pregnancy rate per cycle with a LH-based flexible GnRH antagonist protocol versus traditional flexible GnRH antagonist protocol. Secondary endpoints were the high-quality embryo rate, clinical pregnancy rate, and cancellation rate. Differences in cost-effectiveness and adverse events were evaluated. The cumulative ongoing pregnancy rate per cycle in women with normal ovarian response was 70%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 14% (one-sided: α, 2.5%; β, 20%) and a total of 338 patients were needed. Anticipating a 10% dropout rate, the total number of patients required was 372.DiscussionThis is the first randomized controlled trial to compare the efficacy of a LH-based treatment regimen with a traditional flexible GnRH antagonist protocol during ovarian stimulation. We hypothesized no significant difference in cumulative ongoing pregnancy rate per cycle between the two protocols. Moreover, patients with insufficient endogenous LH during ovarian stimulation may benefit from LH-based GnRH antagonist protocols. The results will provide new information on when to introduce antagonists and the appropriate dosage of antagonist.Trial registration: ClinicalTrials.gov, ChiCTR1800018077. Registered on 29 August, 2018.


BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e047974
Author(s):  
Ya-su Lv ◽  
Yuan Li ◽  
Shan Liu

IntroductionMany patients demonstrate an insufficient endogenous luteinising hormone (LH) concentration during ovarian stimulation. With traditional fixed or flexible gonadotropin-releasing hormone (GnRH) antagonist protocols, antagonist administration may further reduce LH activity. Previously, we proved that LH can be used as an indicator for the timing and dosage of antagonist. Patients with a persistently low LH concentration during ovarian stimulation may not require antagonists, whereas antagonist administration can affect reproductive outcomes. To further explore this hypothesis, we designed a randomised clinical trial to compare the LH-based flexible GnRH antagonist protocol with traditional flexible GnRH antagonist protocol in women with normal ovarian response.Methods and analysisThis study was a multicentre, parallel, prospective, randomised, non-inferiority study. The primary efficacy endpoint was cumulative ongoing pregnancy rate per cycle. The study aimed to prove the non-inferiority of cumulative ongoing pregnancy rate per cycle with an LH-based flexible GnRH antagonist protocol versus traditional flexible GnRH antagonist protocol. Secondary endpoints were the high-quality embryo rate, clinical pregnancy rate and cancellation rate. Differences in cost-effectiveness and adverse events were evaluated. The cumulative ongoing pregnancy rate per cycle in women with normal ovarian response was 70%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 14% (one-sided: α, 2.5%; β, 20%) and a total of 338 patients were needed. Anticipating a 10% drop-out rate, the total number of patients required was 372.Ethics and disseminationThis trial has been approved by the Institutional Ethical Committee of Beijing Chao-Yang hospital. All participants in the trial will provide written informed consent. The study will be conducted according to the principles outlined in the Declaration of Helsinki and its amendments. Results of this study will be disseminated in peer-reviewed scientific journals.Trial registration numberChiCTR1800018077.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P K Sim ◽  
P Nadkarni

Abstract Study question Between spontaneous ovulation (SPO) and induced ovulation (INO) comparing clinical pregnancy rate and ongoing pregnancy rate for frozen-thawed embryo transfer (FET) cycle, which is better? Summary answer Both spontaneous ovulation and induced ovulation protocols showed no significant difference in clinical pregnancy rates and ongoing pregnancy rates. What is known already Recent practice worldwide is moving towards elective freezing of all embryos and subsequent frozen-thawed transfer, both for a perceived higher pregnancy rate as well as the significant reduction of ovarian hyperstimulation. The timing of FET can be determined by either detecting the spontaneous Luteinizing Hormone surge (SPO group) or by the administration of hCG (INO group). There is still an ongoing debate to determine which is the best protocol for frozen-thawed embryo transfer in the non-hormone replacement therapy (non-HRT) cycle. Study design, size, duration This retrospective study included 500 FET cycles for patients who had regular menses between June 2017 and June 2020. The FET cycles were grouped by type as follows: SPO (n = 281) and INO (n = 219). The primary outcome was the clinical pregnancy rate and the secondary outcome was ongoing pregnancy rate. Ongoing pregnancy is defined as a viable intrauterine pregnancy at 12 weeks of gestation confirmed on an ultrasound scan. Participants/materials, setting, methods This study was conducted in a single IVF centre. Vitrification was used as the cryopreservation method. To standardize outcome measures, only patients having single blastocyst transfer and aged under 38 years old were included. The average age of the patient was 32.9. Gamete donation, embryo donation, pre-implantation testing and assisted hatching cycles were also excluded from the analysis. Categorical data were analysed using Chi-square test SPSS version 25. Main results and the role of chance Clinical pregnancy rate for SPO group was 54.8% (154/281) versus 52.9% (116/219) in INO group. Even though clinical pregnancy rate was higher in SPO group as compared to INO group, it did not reach significance level (ꭓ2 = 0.17, p = 0.68). As all patients had single blastocyst transferred, the implantation rate was the same as clinical pregnancy rate. Ongoing pregnancy rate was also found higher in SPO group as compared to INO group (135/281, 48.0% and 97/219, 44.3% respectively) but again failed to reach significance level (ꭓ2 = 0.70, p = 0.40). Limitations, reasons for caution The retrospective nature of the study and therefore, the analysis was not adjusted for confounding factors such as blastocyst grading, etiology of infertility, and ethnicity of patients. Wider implications of the findings: In natural cycle, both spontaneous ovulation and induced ovulation protocols had the same pregnancy outcomes for frozen-thawed embryo transfer. However, induced ovulation can facilitate in scheduling FET timing to avoid weekends and public holidays, if necessary. Trial registration number Not applicable


2020 ◽  
Author(s):  
Jingjuan Ji ◽  
Lihua Luo ◽  
Lingli Huang

Abstract Background: Cumulative live birth rate (CLBR) becomes a comprehensive and meaningful indictor of the success of IVF nowadays. Frozen-embryo transfer (FET) was associated with a higher rate of live birth and a lower risk of the ovarian hyperstimulation syndrome (OHSS) in polycystic ovary syndrome (PCOS) patients. Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol in which oral progestin been used to prevent premature luteinizing hormone (LH) surges during ovarian stimulation. The purpose of the current study is to investigate the CLBR of an in vitro fertilization (IVF) cycle in women with PCOS following PPOS protocol compared with gonadotropin releasing hormone (GnRH) antagonist protocol.Methods: It is a retrospective study. The first IVF cycle of 666 PCOS women were included. Ovarian stimulations were performed with PPOS or GnRH antagonist protocol. All patients included in the analysis had either delivered a baby or had used all their embryos of their first stimulated cycle. The patients were followed for 2–7 years until February 2020.Result(s): The CLBR were similar in the PPOS and GnRH antagonist group (64% vs 60.1%, P = 0.748). Logistic regression analyses showed treatment protocol (PPOS vs GnRH antagonist) did not show any significant correlation with the CLBR (adjusted OR: 0.898; 95% CI: 0.583-1.384, P=0.627). No statistically significant differences were found in the live birth rates per embryo transfer (41.3% vs. 38.4%) in the study group and controls.Conclusion(s): The results of this study showed that both the live birth rate per embryo transfer and the cumulative live birth rate were similar between PPOS and GnRH antagonist group. PPOS protocol is efficient in the controlled ovarian stimulation of patients with PCOS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shan Liu ◽  
Minghui Liu ◽  
Lingxiu Li ◽  
Huanhuan Li ◽  
Danni Qu ◽  
...  

ObjectiveTo verify if patients with deep ovarian suppression following gonadotropin releasing hormone (GnRH) agonist long protocol may benefit from a modified GnRH antagonist protocol based on luteinizing hormone (LH) levels.DesignRetrospective cohort study.SettingUniversity-based hospital.Patients110 patients exhibited ultra-low LH levels during ovarian stimulation using GnRH agonist long protocol.Intervention(s)As all the embryos in the first cycle were exhausted without being pregnant, these patients proposed to undergo a second cycle of ovarian stimulation. 74 of them were treated with a modified GnRH antagonist protocol based on LH levels. Other 36 patients were still stimulated following GnRH agonist long protocol.Main Outcome MeasureThe primary outcome was live birth rate (LBR). The second outcomes were biochemical pregnancy rate, clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and cancellation rate.ResultsReproductive outcomes were much better in the modified GnRH antagonist protocol. The OPR and LBR were much higher in the GnRH antagonist protocol group than in the GnRH agonist long protocol group [odds ratio (OR) 3.82, 95% confidence interval (CI) 1.47, 10.61, P=0.018; OR 4.33, 95% CI 1.38, 13.60, P=0.008; respectively]. Meanwhile, the cancellation rate was much lower in the GnRH antagonist protocol group (OR 0.13, 95% CI 0.02, 0.72; P=0.014). Mean LH level during stimulation did not have a predictive value on live birth. However, it was independently associated with the occurrence of ongoing pregnancy (OR 2.70, 95% CI 1.25, 5.85; P=0.01). The results of sensitivity analyses were consistent with the data mentioned above. The patients got completely different and excellent clinical outcomes in their second cycles stimulated with the modified GnRH antagonist protocol.ConclusionPatients with deep ovarian suppression following GnRH agonist long protocol may benefit from a modified GnRH antagonist protocol based on LH levels.


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