Papanikolaou Evangelos G, Yarali Hakan, Timotheou Evi, Grynberg Michael, Zafeiratis Odysseas, Tournaye Herman, Najdecki Robert
Centre of Reproduction and Genetics, Assisting Nature, Thessaloniki, Greece.
3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Front Endocrinol (Lausanne). 2018 Mar 1;9:25. doi: 10.3389/fendo.2018.00025. eCollection 2018.
A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in fertilization (IVF) is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017.
The efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients. In the first part, five healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day 10. End points were first to inhibit the LH surge later in the follicular phase and, second, to retrieve mature oocytes for IVF. In the second part, five infertile women received the same bolus injection of degarelix administered during the luteal phase at day 24. Different gonadotropin starting days (day 2 through day 8) were tested in order to observe possible differences in ovarian stimulation. In these infertile patients, fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity.
In the first part of the study, all donors were effectively downregulated with a single luteal dose of 0.5 ml of degarelix for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved after 36 h from all patients and all produced 2-7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy) had blastocysts transferred and pregnancy occurred in three out of five women.
A single dose of the long-acting antagonist degarelix during the luteal phase appears to be effective in downregulating hypophysis during ovarian stimulation. This represents a possible new protocol for IVF, which should be further elucidated in RCTs.
促性腺激素释放激素（GnRH）拮抗剂方案在体外受精（IVF）中的一个缺点是其在周期规划方面的灵活性有限。本概念验证研究探讨了单剂量长效GnRH拮抗剂IVF方案的疗效。试验注册号为NCT03240159，于2017年3月8日进行回顾性注册。
首先在健康供体中探讨单剂量长效拮抗剂地加瑞克的疗效，随后在不孕患者中进行研究。在第一部分，五名健康卵母细胞供体采用这种新方案进行卵巢刺激：在黄体晚期，即第24天，皮下注射一剂地加瑞克以控制卵泡期的促黄体生成素（LH）峰。随后从第7天至第10天开始用促性腺激素进行卵巢刺激。终点指标一是在卵泡期后期抑制LH峰，二是获取成熟卵母细胞用于IVF。在第二部分，五名不孕女性在黄体期第24天接受相同剂量的地加瑞克注射。测试了不同的促性腺激素起始日（第2天至第8天），以观察卵巢刺激中可能存在的差异。在这些不孕患者中，进行了新鲜胚胎移植，以评估该方案对妊娠结局的妊娠疗效，并探讨其对子宫内膜容受性的任何可能负面影响。
在研究的第一部分，所有供体在黄体期单剂量注射0.5毫升地加瑞克后均有效下调，直至最终触发卵母细胞成熟日，长达22天。所有患者在36小时后均获取到成熟卵母细胞，且均产生了2至7个囊胚。在第二部分，所有五名不孕患者的LH均得到充分下调，完成了卵巢刺激且未出现任何LH峰。所有患者（除一名采用全冷冻策略的患者外）均进行了囊胚移植，五名女性中有三名怀孕。
黄体期单剂量长效拮抗剂地加瑞克似乎在卵巢刺激期间有效下调垂体功能。这代表了一种可能的IVF新方案，应在随机对照试验中进一步阐明。
