Background

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.

Methods

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 1.1 mg/day) was initiated before the fourth IVF procedure and unmasked central hypothyroidism; levothyroxine (75 mg/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.

Results

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. < 25 ng/mL], fT3 [3.7 vs. 2.5 pmol/L] and fT4 [1.45 vs. 0.84 ng/mL]. Concomitantly, there was dramatic improvement in oocyte quality (no abnormal morphologies) and embryo quality (grade A), allowing an embryo transfer with successful pregnancy.

Conclusions

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.

中文翻译：

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生长激素替代改善垂体功能减退患者的卵母细胞质量：卵泡液研究

背景

已知生长激素 (GH) 与卵巢卵泡发生和卵母细胞成熟有关。在没有生长激素缺乏 (GHD) 的卵巢反应差的患者中，辅助 GH 治疗可改善体外受精 (IVF) 的结果。仅在少数 GHD 患者中报道了通过 GH 替代改善 IVF 中的卵母细胞质量。我们报告了一个研究卵泡液的新病例。

方法

一名 29 岁的垂体功能减退患者被转诊至我们的不孕症中心。她正在接受激素替代治疗以治疗低促性腺激素性腺功能减退症和尿崩症，起初并未考虑替代 GH。 2011 年至 2014 年期间进行了四次 IVF 手术。在第四次 IVF 手术之前开始了生长激素替代疗法（生长激素 1.1毫克/天）和暴露的中枢性甲状腺功能减退症；引入了左甲状腺素（75 毫克/天）。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）用了10个月才达到治疗目标。在 GH 和甲状腺激素替代之前和之后测量血液和卵泡液中的 GH、IGF1 和甲状腺激素。还比较了卵母细胞和胚胎质量。

结果

前 3 次 IVF 程序是在没有更换 GH 的情况下进行的。62% 到 100% 的成熟卵母细胞出现一个或多个形态学异常：弥漫性细胞质颗粒、大的卵周间隙和碎片、第一极体碎裂、卵形或难以剥脱。胚胎质量中等至差（B至D级），胚胎移植后未怀孕。GH 替代后，卵泡液中的激素水平升高：GH [7.68 vs. 1.39 mIU/L]，IGF1 [ 109 vs. <  25  ng/mL]、fT3 [3.7 vs. 2.5  pmol/L] 和 fT4 [1.45 vs. 0.84 纳克/毫升]。同时，卵母细胞质量（无异常形态）和胚胎质量（A 级）显着改善，允许胚胎移植成功妊娠。

结论

这是第一份报告说明在垂体功能减退患者的体外受精过程中卵泡液中激素水平的变化以及 GH 替代对卵母细胞和胚胎质量的有益影响。这些结果表明，GH 替代有利于 GHD 患者的卵母细胞质量。