scholarly journals Luteinising hormone-based protocol versus traditional flexible gonadotropin-releasing hormone antagonist protocol in women with normal ovarian response: study protocol for a non-inferiority trial

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e047974
Author(s):  
Ya-su Lv ◽  
Yuan Li ◽  
Shan Liu
Keyword(s):  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Luteinising Hormone ◽  
Gnrh Antagonist ◽  
Ovarian Response ◽  
Gonadotropin Releasing Hormone ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

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.

scholarly journals A Luteinizing Hormone-based Protocol Versus Traditional Flexible Gonadotropin-Releasing Hormone Antagonist Protocol in Women with Normal Ovarian Response: Study Protocol for a non-Inferiority Trial

2021 ◽  
Author(s):  
Ya-su Lv ◽  
Yuan Li ◽  
Shan Liu
Keyword(s):  
Luteinizing Hormone ◽  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Gnrh Antagonist ◽  
Ovarian Response ◽  
Gonadotropin Releasing Hormone ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

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.

scholarly journals Luteal-phase protocol in poor ovarian response: a comparative study with an antagonist protocol

2017 ◽  
Vol 45 (6) ◽  
pp. 1731-1738 ◽  
Author(s):  
Yan Wu ◽  
Fu-Chun Zhao ◽  
Yong Sun ◽  
Pei-Shu Liu
Keyword(s):  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Gnrh Antagonist ◽  
Ovarian Response ◽  
Poor Ovarian Response ◽  
Stimulation Protocol ◽  
The Mean ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol ◽  
Luteal Phase Ovarian Stimulation

Objective This retrospective study compared the effect of the luteal phase ovarian stimulation protocol (LP group) with the gonadotrophin-releasing hormone (GnRH) antagonist protocol (AN group) in women with poor ovarian responses. Methods Ovarian stimulation was initiated with 225 IU of human gonadotrophin (hMG) daily. When the dominant follicle diameter exceeded 13 mm, 0.25 mg of a GnRH antagonist was used daily until human chorionic gonadotrophin (HCG) administration in the AN group. A GnRH antagonist was not used in the LP group. Ovulation was induced with HCG for all patients when at least one follicle reached a diameter of 16 mm or one dominant follicle reached 18 mm. The highest quality embryos were transferred or cryopreserved for later transfer. Results From January 2013 to December 2015, 274 women with poor ovarian response were included. A total of 108 patients underwent the luteal phase ovarian stimulation protocol while 166 patients underwent the GnRH antagonist protocol. hMG was used for more total days in the LP group was than in the AN group. Oestradiol levels on the day of HCG administration in the LP group were significantly lower than those in the AN group. The mean number of oocytes retrieved in the LP and AN groups was 3.5 ± 2.5 and 3.5 ± 2.9, respectively. The mean number of embryos of the highest quality was 1.7 ± 1.2 and 1.7 ± 1.5, respectively. The clinical pregnancy and implantation rates in the LP and AN groups were 26.2% (22/84) and 25% (29/116), and 15.5% (24/155) and 16.3% (35/215), respectively. Conclusions The luteal phase ovarian stimulation protocol can be applied in women with poor ovarian response and attain comparable clinical pregnancy and implantation rates to those of the GnRH antagonist protocol.

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