粒细胞集落刺激因子预处理可改善卵巢储备功能不良患者的胚胎质量和妊娠率：一项随机对照试验。

Granulocyte colony-stimulating factor priming improves embryos and pregnancy rate in patients with poor ovarian reserve: a randomized controlled trial.

机构信息

Women's Clinic Jinno, 3-11-7 Kokuryou-Chou, Choufu City, Tokyo, 182-0022, Japan.

Ikebukuro Metropolitan Clinic, Toshima-Ku, Tokyo, 171-0021, Japan.

出版信息

Reprod Biol Endocrinol. 2023 Mar 21;21(1):29. doi: 10.1186/s12958-023-01082-w.

DOI:10.1186/s12958-023-01082-w

PMID:36944952

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10029156/

Abstract

BACKGROUND

Granulocyte colony-stimulating factor (G-CSF) administration increased ovarian preantral follicles and anti-Müllerian hormone (AMH) in animal models with diminished ovarian reserve. We investigated whether G-CSF priming before treatment with assisted reproductive technology (ART) improved embryo development and pregnancy rate while increasing serum AMH in patients with poor ovarian reserve.

METHODS

In this prospective randomized open-label controlled trial, 100 patients 20 to 42 years old with AMH below 2 ng/mL were randomized to priming or control groups (50 patients each). None had over 1 ART failure, day-3 follicle-stimulating hormone (FSH) above 30 IU/L, uterine anomalies, or a partner with azoospermia. All patients initially underwent conventional infertility treatment for 2 consecutive cycles in which the priming group but not controls received a subcutaneous G-CSF priming injection during the early luteal phase. Each group then underwent 1 cycle of in vitro fertilization/intracytoplasmic sperm injection and fresh embryo transfer (IVF/ICSI-fresh ET), followed by cryopreserved ET if needed until live birth or embryo depletion. AMH was measured before and after priming.

RESULTS

Fertilization rate, embryonic development, and implantation rate by fresh ET were significantly improved by priming. Clinical and ongoing pregnancy rates by IVF/ICSI-fresh ET were significantly higher with priming (30% and 26% in 47 ART patients; 3 delivered with conventional treatment) than in controls (12% and 10% in 49 ART patients; 1 dropped out). With priming, significantly more patients achieved cryopreservation of redundant blastocysts. The cumulative live birth rate was 32% in 50 patients with priming, significantly higher than 14% in 49 controls (relative risk, 2.8; 95% confidence interval, 1.04-7.7). Infants derived from priming had no congenital anomalies, while infant weights, birth weeks, and Apgar scores were similar between groups. Among 4 variables (age, day-3 FSH, AMH, and priming), logistic regression significantly associated age and priming with cumulative live birth. Priming significantly increased serum AMH. No adverse effects of priming were observed.

CONCLUSION

G-CSF priming improved embryonic development and pregnancy rate during ART treatment and increased AMH in patients with poor ovarian reserve. Enhanced preantral follicle growth likely was responsible.

TRIAL REGISTRATION

UMIN registration in Japan (UMIN000013956) on May 14, 2014. https://www.umin.ac.jp/ctr/index.htm .

摘要

背景

粒细胞集落刺激因子（G-CSF）可增加动物模型中卵巢储备功能降低患者的原始卵泡和抗苗勒管激素（AMH）。我们研究了在卵巢储备功能不良的患者中，在接受辅助生殖技术（ART）治疗前进行 G-CSF 预处理是否可以改善胚胎发育和妊娠率，同时提高血清 AMH。

方法

这是一项前瞻性随机开放标签对照试验，共纳入 100 名年龄在 20 至 42 岁之间、AMH 低于 2ng/ml 的患者，随机分为预处理组和对照组（每组 50 例）。所有患者均无 1 次以上的 ART 失败、第 3 天卵泡刺激素（FSH）大于 30IU/L、子宫畸形或伴侣无精子症。所有患者最初均接受 2 个连续周期的常规不孕治疗，其中预处理组在早黄体期接受皮下 G-CSF 预处理注射，而对照组则未接受。然后，每组均进行 1 个周期的体外受精/胞浆内单精子注射和新鲜胚胎移植（IVF/ICSI-新鲜 ET），如果需要，随后进行冷冻胚胎移植，直到活产或胚胎耗尽。在预处理前后测量 AMH。

结果

预处理可显著提高受精率、胚胎发育和新鲜 ET 的胚胎着床率。IVF/ICSI-新鲜 ET 的临床妊娠率和持续妊娠率均显著高于预处理组（47 例 ART 患者中的 30%和 26%；3 例接受常规治疗），高于对照组（49 例 ART 患者中的 12%和 10%；1 例退出）。预处理组有更多的患者获得多余的囊胚冷冻。预处理组 50 例患者的累积活产率为 32%，明显高于对照组 49 例患者的 14%（相对风险，2.8；95%置信区间，1.04-7.7）。预处理组婴儿无先天畸形，而两组婴儿体重、出生周数和阿普加评分相似。在 4 个变量（年龄、第 3 天 FSH、AMH 和预处理）中，逻辑回归显著与累积活产相关的是年龄和预处理。预处理显著增加了血清 AMH。未观察到预处理的不良反应。