Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China.
Front Endocrinol (Lausanne). 2023 Mar 6;14:1117706. doi: 10.3389/fendo.2023.1117706. eCollection 2023.
Growth hormone (GH) supplementation has been shown to improve oocyte quality and live birth, but few studies have examined whether GH can reduce embryonic aneuploidy. Chromosomal abnormalities in preimplantation embryos have been regarded as the principal cause of implantation failure and miscarriage, and an increased percentage of aneuploid embryos has been observed in patient cohorts with unexplained recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and advanced maternal age.
This prospective cohort study was conducted on women whose previous PGT-A cycle ended up with no transferrable blastocysts, or the aneuploidy rate was above 50% and no live birth was acquired. The participants were divided into GH co-treatment and comparison groups according to whether GH was administered in the subsequent PGT-A cycle. In addition, within the GH co-treatment group, the previous failed cycle constituted the self-control group.
208 women were recruited in the study (GH co-treatment group: 96 women, comparison group: 112 women). Compared to the self-control and comparison groups, the rate of euploid blastocysts was significantly higher in the GH co-treatment group (GH vs self-control: 32.00% vs 9.14%, odds ratio [OR]: 4.765, 95% confidence interval [CI]: 2.420-9.385, P < 0.01; GH vs comparison: 32.00% vs. 21.05%, OR: 1.930, 95% CI: 1.106-3.366, P = 0.021), and their frozen embryo transfers resulted in more pregnancies and live births. In the subgroup analysis, for the <35 and 35-40 years groups, the euploidy rate in the GH co-treatment group was significantly higher than those in the self-control and comparison groups, but in the >40 years group, there was no difference in euploidy rate.
Our study presents preliminary evidence that GH supplementation may ameliorate blastocyst aneuploidy and improve pregnancy outcomes in women who have previously experienced pregnancy failures along with high aneuploidy rates, particularly in those younger than 40 years. Therefore, the use of GH in such women should be considered. However, considering the limited sample size and mixed indications for PGT-A, further scientific research on the underlying mechanism as well as clinical trials with larger sample sizes are needed to confirm the effects and optimal protocols.
生长激素(GH)补充已被证明可以改善卵母细胞质量和活产,但很少有研究检查 GH 是否可以降低胚胎非整倍体率。胚胎植入前染色体异常被认为是着床失败和流产的主要原因,在不明原因复发性妊娠丢失(RPL)、反复着床失败(RIF)和高龄产妇的患者队列中,观察到非整倍体胚胎的比例增加。
这项前瞻性队列研究针对的是那些在前一个 PGT-A 周期中没有可移植的囊胚,或者非整倍体率高于 50%且没有获得活产的女性。根据是否在随后的 PGT-A 周期中给予 GH,参与者被分为 GH 联合治疗组和对照组。此外,在 GH 联合治疗组中,前一个失败的周期构成了自身对照。
本研究共纳入 208 名女性(GH 联合治疗组:96 名女性,对照组:112 名女性)。与自身对照和对照组相比,GH 联合治疗组的整倍体囊胚率明显更高(GH 与自身对照:32.00% vs 9.14%,优势比[OR]:4.765,95%置信区间[CI]:2.420-9.385,P < 0.01;GH 与对照组:32.00% vs. 21.05%,OR:1.930,95% CI:1.106-3.366,P = 0.021),并且她们的冷冻胚胎移植导致更多的妊娠和活产。在亚组分析中,对于<35 岁和 35-40 岁组,GH 联合治疗组的整倍体率明显高于自身对照和对照组,但在>40 岁组,整倍体率没有差异。
我们的研究初步表明,GH 补充可能改善高龄和高非整倍体率反复妊娠失败患者的囊胚非整倍体率,并改善妊娠结局。因此,对于这些女性,应考虑使用 GH。然而,考虑到样本量有限且 PGT-A 的适应证混杂,需要进一步进行基础机制的科学研究和更大样本量的临床试验来证实其效果和最佳方案。