同一卵巢周期中的二次刺激：对行 PGT-A 的预后不良患者进行完全个体化治疗的一种选择。
Second stimulation in the same ovarian cycle: an option to fully-personalize the treatment in poor prognosis patients undergoing PGT-A.
机构信息
GeneraLife IVF, Clinica Valle Giulia, via G. De Notaris, 2b, 00197, Rome, Italy.
GeneraLife IVF, Livet, Turin, Italy.
出版信息
J Assist Reprod Genet. 2022 Mar;39(3):663-673. doi: 10.1007/s10815-022-02409-z. Epub 2022 Feb 7.
PURPOSE
Our primary objective was to assess whether immediately undergoing a second stimulation in the same ovarian cycle (DuoStim) for advanced-maternal-age and/or poor-ovarian-reserve (AMA/POR) patients obtaining ≤ 3 blastocysts for preimplantation-genetic-testing-for-aneuploidies (PGT-A) is more efficient than the conventional-approach.
METHODS
All AMA/POR patients obtaining ≤ 3 blastocysts after conventional-stimulation between 2017 and 2019 were proposed DuoStim, and 143 couples accepted (DuoStim-group) and were matched for the main confounders to 143 couples who did not accept (conventional-group). GnRH-antagonist protocol with recombinant-gonadotrophins and agonist trigger, intra-cytoplasmatic-sperm-injection (ICSI) with ejaculated sperm, PGT-A and vitrified-warmed euploid single-blastocyst-transfer(s) were performed. The primary outcome was the cumulative-live-birth-delivery-rate per intention-to-treat (CLBdR per ITT) within 1 year. If not delivering, the conventional-group had 1 year to undergo another conventional-stimulation. A cost-effectiveness analysis was also conducted.
RESULTS
The CLBdR was 10.5% in the conventional-group after the first attempt. Only 12 of the 128 non-pregnant patients returned (165 ± 95 days later; drop-out = 116/128,90.6%), and 3 delivered. Thus, the 1-year CLBdR was 12.6% (N = 18/143). In the DuoStim-group, the CLBdR was 24.5% (N = 35/143; p = 0.01), 2 women delivered twice and 13 patients have other euploid blastocysts after a LB (0 and 2 in the conventional-group). DuoStim resulted in an incremental-cost-effectiveness-ratio of 23,303€. DuoStim was costlier and more effective in 98.7% of the 1000 pseudo-replicates generated through bootstrapping, and the cost-effectiveness acceptability curves unveiled that DuoStim would be more cost-effective than the conventional-approach at a willingness-to-pay threshold of 23,100€.
CONCLUSIONS
During PGT-A treatments in AMA/POR women, DuoStim can be suggested in progress to rescue poor blastocyst yields after conventional-stimulation. It might indeed prevent drop-out or further aging between attempts.
目的
我们的主要目的是评估对于高龄和/或卵巢储备功能不良（高龄、POR）患者，在接受常规刺激后获得≤3 枚囊胚进行植入前遗传学检测-非整倍体（PGT-A）时，是否立即进行同一卵巢周期的第二次刺激（双刺激）比常规方案更有效。
方法
2017 年至 2019 年间，所有接受常规刺激后获得≤3 枚囊胚的高龄、POR 患者均被建议接受双刺激，并对 143 对夫妇（双刺激组）进行了匹配，以匹配主要混杂因素，与 143 对不接受双刺激的夫妇（常规组）进行了匹配。采用 GnRH 拮抗剂方案联合重组促性腺激素和激动剂扳机、卵胞浆内单精子注射（ICSI）联合射出精子、PGT-A 和冷冻解冻的整倍体单囊胚移植。主要结局是 1 年内意向治疗（ITT）的累积活产分娩率（CLBdR per ITT）。如果没有分娩，常规组有 1 年的时间进行另一次常规刺激。还进行了成本效益分析。
结果
常规组首次尝试后的 CLBdR 为 10.5%。仅有 128 名未怀孕患者中的 12 名（165±95 天后；脱落率=116/128，90.6%）返回，其中 3 名患者分娩。因此，1 年 CLBdR 为 12.6%（N=18/143）。在双刺激组中，CLBdR 为 24.5%（N=35/143；p=0.01），2 名女性分娩两次，13 名患者在活产后有其他整倍体囊胚（常规组中为 0 和 2）。双刺激的增量成本效益比为 23303 欧元。通过自举法生成的 1000 个伪重复中，98.7%的双刺激更昂贵但更有效，成本效益接受性曲线表明，在 23100 欧元的支付意愿阈值下，双刺激比常规方案更具成本效益。
结论
在高龄、POR 女性进行 PGT-A 治疗时，在常规刺激后，可以建议进行双刺激以提高囊胚产量。它确实可以防止在尝试之间出现脱落或进一步衰老。
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