Hum Reprod. 2014 Jul;29(7):1500-7. doi: 10.1093/humrep/deu105. Epub 2014 May 9.
Does the initiation of corifollitropin alfa administration on cycle day 4 instead of cycle day 2 result in a reduced total rFSH consumption in a GnRH antagonist protocol?
Initiation of corifollitropin alfa on cycle day 4 compared with day 2 results in significantly reduced total rFSH consumption at the end of the follicular phase.
In vitro fertilization treatment is associated with significant physical, psychological and emotional stress in infertile patients. This notion has fuelled the search for simplified treatment approaches that may reduce the treatment burden. The introduction of corifollitropin alfa has provided a more patient-friendly treatment protocol because it obviates the need for daily hormonal injections. In addition, postponing the initiation of hormonal stimulation should also reduce the total gonadotrophin consumption and the number of injections needed.
STUDY DESIGN, SIZE, DURATION: A prospective randomized controlled pilot study was conducted in a university centre in Belgium. Between December 2011 and March 2013, 59 patients were randomized in the study and 52 of these patients received the allocated intervention.
PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients were randomly assigned to the control group (CD2), with initiation of corifollitropin alfa on cycle day 2, or to the study group (CD4) with initiation of stimulation on day 4. The GnRH antagonist was administered from cycle day 7 onwards in both treatment arms. The main outcome measure was the total rFSH consumption at the end of the follicular phase after corifollitropin alfa treatment.
The total dose of rFSH at the end of the follicular phase was significantly reduced in the CD4 group compared with the CD2 group (324 (276) IU in the CD2 group versus 173 (255) IU in the CD4 group, P = 0.015, mean difference -151, 95% confidence interval (CI) -301 to -1). A significant reduction of total duration of rFSH stimulation in the CD4 group was also observed (8.6 (1.4) days in CD2 group versus 7.8 (1.2) days in the CD4 group, P = 0.008, mean difference -0.8, 95% CI -1.6 to -0.1). The number of cumulus-oocyte-complexes was comparable in both treatment groups (12.8 (7.3) in CD2 group versus 14.7 (8.8) in the CD4 group, P = 0.461, mean difference 1.8, 95% CI -2.7 to 6.4). Ongoing pregnancy rates of 48% in the CD2 group and 41% in the CD4 group were achieved (P = 0.60, relative risk (RR) 0.85, 95% CI 0.46-1.56). Final oocyte maturation was triggered with GnRH agonist instead of hCG in two patients in the CD2 group and in eight patients in the CD4 group, because of an increased risk of ovarian hyperstimulation syndrome (P = 0.078, RR 3.7 (95% CI 0.88-15.8).
LIMITATIONS, REASONS FOR CAUTION: Before general implementation can be advised, this trial should be validated in a much larger randomized trial. WIDER IMPLICATIONS OF THE FINDINGS If the approach of starting ovarian stimulation on Day 4 of the cycle could be implemented in a large population of infertile patients, it would result in a significant reduction of gonadotrophin consumption.
STUDY FUNDING/COMPETING INTEREST(S): No external finance was involved in this study. C.B and N.P.P. have received fees from MSD. Otherwise the authors declare no conflict of interest regarding this study.
The trial was registered at clinicaltrials.gov (NCT01633580).
在 GnRH 拮抗剂方案中，相较于第 2 天，第 4 天开始给予促卵泡素是否会导致总 rFSH 消耗减少？
与第 2 天相比，第 4 天开始给予 Corifollitropin Alfa 治疗可显著降低卵泡期结束时的总 rFSH 消耗。
体外受精治疗会给不孕患者带来明显的身体、心理和情感压力。这一观点促使人们寻找更简化的治疗方法，以减轻治疗负担。Corifollitropin Alfa 的引入提供了一种更适合患者的治疗方案，因为它避免了每天进行激素注射的需要。此外，推迟激素刺激的开始也应该减少总促性腺激素的消耗和所需的注射次数。
研究设计、规模、持续时间：这是一项在比利时一所大学中心进行的前瞻性随机对照试验研究。2011 年 12 月至 2013 年 3 月期间，59 名患者被随机分配到该研究中，其中 52 名患者接受了分配的干预措施。
参与者/材料、设置、方法：所有患者随机分为对照组（CD2），在第 2 天开始给予 Corifollitropin Alfa 治疗，或在第 4 天开始给予刺激的研究组（CD4）。在两个治疗组中，从第 7 天开始给予 GnRH 拮抗剂。主要观察指标是 Corifollitropin Alfa 治疗结束时卵泡期的总 rFSH 消耗。
与 CD2 组相比，CD4 组的 rFSH 总剂量在卵泡期结束时显著降低（CD2 组为 324（276）IU，CD4 组为 173（255）IU，P=0.015，平均差异-151，95%置信区间（CI）-301 至-1）。在 CD4 组中，rFSH 刺激的总持续时间也显著缩短（CD2 组为 8.6（1.4）天，CD4 组为 7.8（1.2）天，P=0.008，平均差异-0.8，95%CI-1.6 至-0.1）。两组的卵丘-卵母细胞复合物数量相当（CD2 组为 12.8（7.3），CD4 组为 14.7（8.8），P=0.461，平均差异 1.8，95%CI-2.7 至 6.4）。CD2 组和 CD4 组的持续妊娠率分别为 48%和 41%（P=0.60，相对风险（RR）0.85，95%CI 0.46-1.56）。由于卵巢过度刺激综合征的风险增加，有两名患者在 CD2 组和八名患者在 CD4 组中改用 GnRH 激动剂而不是 hCG 触发最终卵母细胞成熟（P=0.078，RR 3.7（95%CI 0.88-15.8）。
局限性、谨慎的原因：在更大规模的随机试验验证之前，不建议普遍采用该试验。
如果在大量不孕患者中采用第 4 天开始卵巢刺激的方法，将显著减少促性腺激素的消耗。
研究资金/利益冲突：本研究没有涉及外部资金。C.B 和 N.P.P. 从 MSD 获得了费用。否则，作者们对这项研究没有任何利益冲突的声明。
该试验在 clinicaltrials.gov 上注册（NCT01633580）。
