Hugues J N, Cédrin-Durnerin I, Howles C M, Amram M, Angelini A, Balen A, Barbereau D, Birkhauser M, Boujenah A, De Leo V, De Placido G, Dessole S, Favrin S, Ferrazi E, Gay C, Germond M, Hedon B, Hocke C, Jolly C, Lamarca-Roth E, Lanzone A, Marchand F, Marcolin G, Mascaretti G, Moreau L, Massobrio M, Nappi C, Pardi G, Pennehouat G, Porcu E, Seibert M, Selvaggi L, Thiers D, Venturini P
Reproductive Medicine Unit, Jean Verdier Hospital, University Paris XIII, Paris, France.
Hum Reprod. 2006 Nov;21(11):2817-22. doi: 10.1093/humrep/del265. Epub 2006 Jul 27.
In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol.
Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration.
Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy.
The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.
对于慢性无排卵的女性,促卵泡生成素(FSH)起始剂量的选择以及后续剂量调整方式对于控制过度刺激风险至关重要。这项前瞻性随机研究的目的是评估在根据慢性低剂量(CLD;14天内每天75 IU FSH,每次递增37.5 IU)逐步递增方案治疗WHO II型无排卵的女性中,当主导卵泡直径达到10 - 13 mm时应用递减FSH剂量方案的疗效和安全性。
209名不孕女性根据CLD逐步递增方案接受重组人FSH(r - hFSH)(果纳芬)诱导排卵治疗。当主导卵泡直径达到10 - 13 mm时,158名参与者通过计算机生成的列表随机分组,分别接受达到卵泡发育阈值所需的相同FSH剂量(CLD方案)或该FSH剂量的一半[序贯(SQ)方案]。仅当直径≥16 mm的卵泡不超过3个和/或血清雌二醇(E₂)值<1200 pg/ml时才给予人绒毛膜促性腺激素(HCG)。主要结局指标是HCG给药时直径≥16 mm的卵泡数量。
随机分组时两组的临床特征和卵巢参数相似。CLD和SQ方案在卵泡总数以及中等大小或成熟卵泡(≥16 mm)方面实现了相似的卵泡生长(分别为1.5±0.9和1.4±0.7)。此外,HCG给药时两组的血清E₂水平相当(CLD和SQ方案分别为441±360和425±480 pg/ml)。单卵泡发育率以及排卵和怀孕患者的百分比相同。
结果表明,CLD逐步递增方案用于FSH给药对于促进WHO II型无排卵女性的单卵泡排卵是有效且安全的。本研究证实,在逐步递增方案中,在增加剂量前将相同的FSH起始剂量维持14天对于充分控制过度反应风险至关重要。对于WHO II型无排卵的女性,应推荐严格应用CLD方案。