Growth hormone co-treatment on controlled ovarian stimulation in normal ovarian response women can improve embryo quality

Application of Growth Hormone in in vitro Fertilization

“…When it is used in patients with repeat implantation failure which is defined as failure of pregnancy despite implantation of a high-quality embryo at least three times or of over 10 embryos on repeat implantation failure (1, 63, 80–82), the mechanism of this action is, as stated before, related to GH stimulating proliferation and differentiation of granulosa cells, increasing production of estradiol in both early and late follicular development for animal and human ovaries, enhancing effect of FSH on the development of ovarian follicles and improving endometrial thickness (82, 98–100). A recent randomized controlled clinical trial performed in China of GH co-treatment on controlled ovarian stimulation in normal ovarian response women showed significantly ( P < 0.05) higher two pronuclei rate (33.92 vs. 30.92%) and higher quality embryo rate (63.4 vs. 59.33%) besides significantly increased number of embryos available (3.79 ± 2.74 vs. 2.90 ± 2.12, P < 0.001) and higher endometrial thickness on hCG day (11.96 ± 2.24 vs. 11.62 ± 2.81, P = 0.036) in 781 patients receiving GH of 1IU/4IU administered daily since day two of the previous cycle or day two in accordance with controlled ovarian stimulation until hCG trigger in comparison with the control group without GH adjuvant therapy (79). Among a total of seven systematic reviews and meta analyses found online (pubmed) up to 2019 investigating the effect of GH adjuvant therapy on poor responders undergoing IVF (9–11, 65, 67, 68, 101), only two meta analyses demonstrated no improvement in the liver birth rate (65) or the clinical pregnancy rate (OR 0.051, 95% CI −0.033 to 0.134, P = 0.197) (67).…”

“…As stated before, GH adjuvant therapy was clinically widely used in poor ovarian responders (7, 8, 10, 11, 14, 16, 19, 60–63, 67–76), poor quality of embryos (16, 17, 67, 70, 74, 77), improper endometrial reaction (5, 12, 56, 78, 79) and repeated implantation failure (1, 63, 80–82). When it is used in patients with repeat implantation failure which is defined as failure of pregnancy despite implantation of a high-quality embryo at least three times or of over 10 embryos on repeat implantation failure (1, 63, 80–82), the mechanism of this action is, as stated before, related to GH stimulating proliferation and differentiation of granulosa cells, increasing production of estradiol in both early and late follicular development for animal and human ovaries, enhancing effect of FSH on the development of ovarian follicles and improving endometrial thickness (82, 98–100).…”

“…However, some randomized controlled trials discouraged the use of GH in IVF because no definitive benefits have been demonstrated in increasing the live birth rate for poor responders (18, 19), but careful evaluation of these trials showed severe drawbacks as stated before. Up to now, GH has been widely applied in the reproduction area but primarily for poor ovarian responders (7, 8, 10, 11, 14, 16, 19, 60–63, 67–76), poor quality of embryos (16, 17, 67, 70, 74, 77), improper endometrial reaction (5, 12, 56, 78, 79) and repeated failure of embryo transfer (1, 63, 80–82).…”

The Role of Growth Hormone on Ovarian Functioning and Ovarian Angiogenesis

“…This study, carried out in 380 POR, showed that the administration of the hormone significantly improved the rate of utilization of oocytes and embryo quality increasing the live birth rates, even in older patients who had previously experienced unsuccessful results from classical techniques (85). Moreover, another recent study demonstrated that co-treatment with GH in patients with normal ovarian response significantly increased pregnancy rate (86). Therefore, from these and other studies, it seems to be clear that GH plays a key role in ovarian fertility and Assisted Reproductive Techniques.…”

Growth Hormone and Endometrial Receptivity

“…Moreover, local insulin growth factor 1 (IGF-1) production (known downstream mediator of GH) has been shown to be controlled by gonadotropins and estradiol as well (10). Evidence emerging from clinical practice suggests that GH administration during ovarian stimulation may improve oocyte quality [higher number of oocytes collected, higher fertilization rate, and higher number of embryos reaching the transfer stage (11–15)], increase pregnancy rate (16–24), implantation rate (16, 20–23, 25, 26), and live birth rate (12, 16, 19, 20, 23, 25, 27). The accumulating beneficial effects of GH on assisted reproduction outcomes do not exclude the possibility that this effect is due, at least in part, to an action of GH on endometrial receptivity.…”