Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Clin Endocrinol (Oxf). 2018 Jan;88(1):77-87. doi: 10.1111/cen.13481. Epub 2017 Oct 16.
OBJECTIVES: To investigate the effects of low-dose human chorionic gonadotropin (hCG) combined with human menopausal gonadotropin (HMG) protocol on cycle characteristics and outcomes of infertile women with hypogonadotropic hypogonadism (HH) undergoing ovarian stimulation for in vitro fertilization (IVF). DESIGN: A retrospective cohort study. SETTING: Tertiary-care academic medical centre. PATIENT(S): Forty-six infertile patients with HH and seventy-one infertile patients with tubal factor (TF) infertility undergoing IVF. INTERVENTION(S): In the study group, all 46 HH patients were given low-dose hCG (50-300IU/d) in combination with HMG daily from cycle day 3. Meanwhile, a control group consisting of 71 patients with tubal factor infertility was set up, where the infertile women were given triptorelin 3.75 mg on cycle day 3 for desensitization and started stimulation with HMG only 5 weeks later. Transvaginal ultrasound and serum sex steroids were used for monitoring the development of follicles. Ovulation was triggered by hCG 5000IU when dominant follicles matured. Viable embryos were transferred on the third day after ovum pickup or cryopreserved for later transfer. MAIN OUTCOME MEASURE(S): The primary outcome measure was the clinical pregnancy rate. Secondary outcomes included hCG day P4, ratio of E2/follicle count, number of oocytes retrieved, number of viable embryos, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate. RESULT(S): With lower basal FSH, LH and E2, HH patients showed longer HMG stimulation duration (13 (10-22) d vs 12 (8-18) d, P < .001) and higher HMG dose (2960 ± 560 IU vs 2663 ± 538 IU, P = .005). Whilst the antral follicle count (AFC), number of follicles with diameters greater than 10mm on trigger day and oocytes retrieved were less in the HH group, the number of follicles with diameters greater than 14 mm and viable embryos were comparable. The ratio of E2/follicle count (>10 mm) and E2/follicle count (>14 mm) were distinctively higher in the HH group (1056 ± 281 vs 830 ± 245, P < .001; 1545 ± 570 vs 1312 ± 594pmol/L, P = .037; respectively). The clinical pregnancy rate, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate per woman were comparable between the two groups. Comparison among the subgroups with different hCG dosage showed that HMG duration shortened with the increase of daily hCG dose (14.84 ± 2.88 vs 13.96 ± 2.63 vs 12.96 ± 1.30 days, P = .037). No significant differences were detected in outcomes between fresh embryo transfer (ET) group and frozen-thawed embryo transfer (FET) group. CONCLUSION(S): Low-dose hCG combined with HMG is a feasible protocol for HH women undergoing ovarian stimulation in IVF, providing favourable cycle characteristics and pregnancy rates. Low-dose hCG reduces HMG duration, whilst the hCG dose and embryo quality are not positively correlated. The outcomes of FET are comparable to ET, which provides a greater chance of success from IVF in the low responders with HH.
目的:探讨小剂量人绒毛膜促性腺激素(hCG)联合人绝经期促性腺激素(HMG)方案对低促性腺激素性性腺功能减退症(HH)行体外受精(IVF)卵巢刺激的患者的周期特征和结局的影响。
设计:回顾性队列研究。
地点:三级保健学术医疗中心。
患者:46 例 HH 不孕患者和 71 例输卵管因素(TF)不孕患者接受 IVF。
干预措施:在研究组中,所有 46 例 HH 患者从周期第 3 天开始每天给予小剂量 hCG(50-300IU/d)联合 HMG。同时,设立了一个由 71 例输卵管因素不孕患者组成的对照组,这些患者在周期第 3 天接受三磷酸瑞林 3.75mg 脱敏,5 周后才开始用 HMG 进行刺激。经阴道超声和血清性激素用于监测卵泡的发育情况。当优势卵泡成熟时,用 hCG 5000IU 触发排卵。取卵后第 3 天移植有活力的胚胎,或冷冻保存以备以后移植。
主要观察指标:主要观察指标是临床妊娠率。次要观察指标包括 hCG 日 P4、E2/卵泡计数比、获卵数、有活力胚胎数、着床率、持续妊娠率和累积妊娠率。
结果:HH 患者的基础 FSH、LH 和 E2 水平较低,HMG 刺激时间更长(13(10-22)d vs 12(8-18)d,P<.001),HMG 剂量更高(2960±560IU vs 2663±538IU,P=0.005)。虽然 HH 组的窦卵泡计数(AFC)、触发日大于 10mm 的卵泡数和获卵数较少,但大于 14mm 的卵泡数和有活力的胚胎数相当。E2/卵泡计数(>10mm)和 E2/卵泡计数(>14mm)的比值在 HH 组中明显更高(1056±281 vs 830±245,P<.001;1545±570 vs 1312±594pmol/L,P=0.037)。两组的临床妊娠率、着床率、持续妊娠率和累积妊娠率相当。不同 hCG 剂量亚组之间的比较显示,随着每日 hCG 剂量的增加,HMG 持续时间缩短(14.84±2.88 vs 13.96±2.63 vs 12.96±1.30d,P=0.037)。新鲜胚胎移植(ET)组和冷冻胚胎移植(FET)组之间的结局无显著差异。
结论:低剂量 hCG 联合 HMG 是 HH 患者行 IVF 卵巢刺激的一种可行方案,可提供良好的周期特征和妊娠率。低剂量 hCG 缩短了 HMG 的持续时间,而 hCG 剂量和胚胎质量之间没有正相关。FET 的结局与 ET 相当,为低反应性 HH 患者从 IVF 中获得更高的成功率提供了更大的机会。
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