Reproductive Medicine and Biology Department, Cytogenetics and CECOS of Picardy, Amiens University Hospital, Picardy, France; Peritox UMR_I 01, CURS, Jules Verne University of Picardy, Amiens, France.
Endocrine and Bone Biology Department, Amiens University Hospital, Picardy, France.
Ann Endocrinol (Paris). 2021 Dec;82(6):590-596. doi: 10.1016/j.ando.2021.05.003. Epub 2021 Jun 27.
Growth hormone (GH) is known to be involved in ovarian folliculogenesis and oocyte maturation. In patients with poor ovarian response without growth hormone deficiency (GHD), adjuvant GH treatment improves in-vitro fertilization (IVF) results. Improvement of oocyte quality in IVF by GH replacement was reported in only a few patients with GHD. We report on a new case with study of follicular fluid.
A 29-year-old patient with hypopituitarism was referred to our infertility center. She was undergoing hormonal replacement for hypogonadotropic hypogonadism and diabetes insipidus, and did not consider at first GH replacement. Four IVF procedures were performed between 2011 and 2014. Growth hormone replacement (somatotropin 1.1mg/day) was initiated before the fourth IVF procedure and unmasked central hypothyroidism; levothyroxine (75mg/day) was introduced. It took 10 months to reach the treatment objectives for insulin-like growth factor 1 (IGF1), free triiodothyronine (fT3) and free thyroxine (fT4). GH, IGF1 and thyroid hormones were measured in the blood and follicular fluid before and after GH and thyroid hormone replacement. Oocyte and embryo quality were also compared.
The first 3 IVF procedures were performed without GH replacement. 62% to 100% of mature oocytes presented one or more morphologic abnormalities: diffuse cytoplasmic granularity, large perivitelline space with fragments, fragmentation of the first polar body, ovoid shape, or difficult denudation. Embryo quality was moderate to poor (grade B to D), and no pregnancy was obtained after embryo transfer. After GH replacement, hormones levels increased in follicular fluid: GH [7.68 vs. 1.39 mIU/L], IGF1 [109 vs. <25ng/mL], fT3 [3.7 vs. 2.5pmol/L] and fT4 [1.45 vs. 0.84ng/mL]. Concomitantly, there was dramatic improvement in oocyte quality (no abnormal morphologies) and embryo quality (grade A), allowing an embryo transfer with successful pregnancy.
This is the first report illustrating changes in hormonal levels in follicular fluid and the beneficial effect of GH replacement on oocyte and embryo quality during an IVF procedure in a patient with hypopituitarism. These results suggest that GH replacement is beneficial for oocyte quality in patients with GHD.
生长激素(GH)已知参与卵巢卵泡发生和卵母细胞成熟。在没有生长激素缺乏(GHD)的卵巢反应不良的患者中,辅助 GH 治疗可改善体外受精(IVF)结果。GH 替代治疗仅在少数 GHD 患者中报告改善了 IVF 中的卵母细胞质量。我们报告了一例新病例,并对卵泡液进行了研究。
一名 29 岁的垂体功能减退症患者被转介到我们的不孕不育中心。她正在接受促性腺激素低下性性腺功能减退症和尿崩症的激素替代治疗,最初并不考虑 GH 替代治疗。2011 年至 2014 年期间进行了 4 次 IVF 程序。在第四次 IVF 程序之前开始进行 GH 替代治疗(生长激素 1.1mg/天),并揭示了中枢性甲状腺功能减退症;开始使用左甲状腺素(75mg/天)。达到胰岛素样生长因子 1(IGF1)、游离三碘甲状腺原氨酸(fT3)和游离甲状腺素(fT4)的治疗目标花费了 10 个月。在 GH 和甲状腺激素替代治疗前后,分别在血液和卵泡液中测量 GH、IGF1 和甲状腺激素。还比较了卵母细胞和胚胎的质量。
前 3 次 IVF 程序均未进行 GH 替代治疗。62%至 100%的成熟卵母细胞存在一种或多种形态异常:弥漫性细胞质颗粒状、较大的卵周隙伴碎片、第一极体碎片化、卵母细胞呈椭圆形或难以去透明带。胚胎质量为中度至差(B 级至 D 级),胚胎移植后未获得妊娠。GH 替代治疗后,卵泡液中的激素水平升高:GH[7.68 与 1.39 mIU/L]、IGF1[109 与 <25ng/mL]、fT3[3.7 与 2.5pmol/L]和 fT4[1.45 与 0.84ng/mL]。同时,卵母细胞质量(无异常形态)和胚胎质量(A级)显著改善,允许胚胎移植并成功妊娠。
这是首例报告,说明了垂体功能减退症患者在 IVF 过程中卵泡液中激素水平的变化以及 GH 替代治疗对卵母细胞和胚胎质量的有益影响。这些结果表明,GH 替代治疗对 GHD 患者的卵母细胞质量有益。