Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders

Abstract

In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 μg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (<40 years old) and 12% in older women (≥40 years old), p = 0.68. Similarly, in patients treated with the long agonist protocol younger women had an OPR of 26.7% versus 12.5% in older women, p = 0.23. Among patients treated with the short flare-up, live births rate were 15% and 4.3% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.32. Similarly, in patients treated with the long agonist protocol, live births rate were 25% and 12.9% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.41. None of the patients reported any serious adverse event related to treatment. According to our results, CFA followed by hpHMG in a short flare-up or long GnRH agonist protocol appears to be a feasible option for poor ovarian responders. Large phase III trials are mandatory prior to introduction in clinical practice.

Chinese abstract

在两个前瞻性非控制的可行性试验中，检测对卵巢低反应妇女应用绒促卵泡素a (CFA)后应用高纯人绝经期促性腺激素（hpHMG），比较短期flare- up促性腺激素释放激素(GnRH)激动剂方案和GnRHa长方案的效果。总体，45名患者应用短期flare- up方案，47名患者应用GnRHa长方案。所有患者应用单剂量150 μg CFA，7天后应用300IU hpHMG，10000 IUhCG触发排卵，CSI和3天胚胎移植。持续妊娠率（OPRs），GnRHa短期方案的15.6%和长方案的17%间没有差异(p=0.85)。在应用短期flare-up方案的患者中，OPRs在年轻患者(<40岁)为20%，高龄患者(≥40岁)为12%，p=0.68。同样的在应用GnRHa长方案的患者中，年轻妇女OPR为26.7%，高龄妇女为12.5%, p= 0.23。在应用短期flare-up方案的患者中，年轻患者(<40岁)活产率为15%，高龄患者(≥40岁)活产率为4.3%，p=0.32。同样的，在GnRHa长方案的患者中，年轻患者(<40岁)活产率为25%，高龄患者(≥40岁)活产率为12.9%，p=0.41。没有患者报告有与治疗相关的不良事件。根据结果，在的短期flare- up方案或者GnRHa长方案中应用CFA后序贯hpHMG对卵巢低反应患者是可行性的选择。在引入临床实践前还必须有大型III期试验。

• Bologna criteria
• corifollitropin alfa
• GnRH agonist
• hpHMG
• poor ovarian responders

Acknowledgements

The authors would like to thank the study nurses of the coordinating center in UZ Brussel: Elsie Nulens, Patricia Ackermans, Ellen Van Moer, Nicky Dooms and Saskia Van Ginderdeuren, for their invaluable help for the set up and conduction of the current studies and for providing information to study participants. The authors would also like to thank Walter Meul for his invaluable help for the handling and extraction of patients' data.

Declaration of interest

N. P. P. has received honoraria for giving lectures and consultation fees from MSD and Ferring Pharmaceuticals unrelated to the study, C. B. has received honoraria for giving lectures and consultation fees from MSD and Ferring Pharmaceuticals unrelated to the study, P. H. has received honoraria for giving lectures and consultation fees from MSD, Merck Serono and Nordic Infucare unrelated to the current study. The authors report no conflicts of interests.

Appendix Figure A1. Flowchart of patients' selection.