Table 1.
The randomized controlled studies on growth hormone cotreatment in poor ovarian responders.
| ART (Year) |
Inclusion Criteria | Main Exclusion Criteria | GH Usage /Stimulation Protocol |
Clinical Outcomes |
|---|---|---|---|---|
| IVF (2018) |
127 females (according to the Bologna consensus criteria [41]) |
BMI > 30 mg/m2, and women with other causes of infertility | Sustained-release of 20 mg of GH three times before and during COS/GnRH-Ant protocol | GH elevated the follicles number and the proportion of metaphase II oocytes; there was no significant differences in the percentages of clinical and ongoing pregnancy, or miscarriage [21]. |
| IVF (2019) |
184 females (according to the Bologna consensus criteria [41]) |
No description | Injection of GH at dosages of 4, 4, and 2 IU over three successive days, along with the ovulation induction/GnRH-a ultra-long protocol | GH elevated the ovarian response, the number of retrieved oocytes, the number of embryos available for transfer, clinical pregnancy rates, and ongoing pregnancy rates; there were no significant differences between groups regarding miscarriage rates [53]. |
| IVF/ ICSI (2019) |
130 females (≤1 IVF cycle, with ≤5 oocytes, rFSH dosage > 250 IU/d, basal FSH ≤ 15 IU, BMI < 33 kg/m2, and age < 41 years) |
Females with a history of malignant diseases or pituitary/hypothalamic diseases; current ovarian cysts (>3 cm) or chronic infectious diseases, PCOS, or AUB | Daily injection of 12 IU GH from day 1 of COS until the day of hCG/GnRH-Ant protocol | GH increased the number of retrieved oocytes and did not signficantly affect the LBRs or the number of transferred embryos [43]. |
| IVF/ ICSI (2019) |
105 females (according to the Bologna consensus criteria [41]) |
FSH > 20 IU/L, a history of infertility due to non-POR causes | Daily subcutaneous injection of 2.5mg of GH from the eighth day of the cycle until the injection of HCG /GnRH-Ant protocol |
GH significantly increased the number of retrieved oocytes, MII oocytes, fertilized oocytes, transferred embryos, and clinical PRs [54]. |
| IVF/ ICSI (2015) |
145 females (according to the Bologna consensus criteria [41]) |
FSH > 20 IU/L, women with other causes of infertility, and severe male factors | Daily injection of 2.5 mg of GH from day 6 of COS until the day of hCG/GnRH-a long protocol | GH increased the number of retrieved oocytes, MII oocytes, and the mean number of fertilized oocytes and elevated PRs without any significant differences between groups [38]. |
| IVF/ ICSI (2017) |
50 females (according to the Bologna consensus criteria [41]) |
FSH > 20 IU/L, BMI ≥ 35 kg/m2, and severe male factors | Daily injection of 4 IU of GH from day 1 of COS until the day of hCG/GnRH-Ant protocol | GH lowered the effective dose of Gn and the duration of stimulation while elevating the total number of oocytes, as well as the numbers of MII oocytes, 2PN zygotes, and good-quality transferred embryos and the probability of pregnancy [37]. |
| IVF/ ICSI (2018) |
240 females (according to the Bologna consensus criteria [41]) |
>45 years, FSH > 20 IU/L, tubal occlusion, and severe male factors | Daily injection of 7.5 IU of GH from day 21 of the previous cycle until the day of hCG/GnRH-a long protocol | GH improved the numbers of retrieved oocytes, MII oocytes, fertilized oocytes, transferred embryos, and cryopreserved embryos; there were no significant differences in the LBRs, whether fresh or cumulative [34]. |
| IVF/ ICSI (2016) |
141 females (according to the Bologna consensus criteria [41]) |
FSH > 20 IU/L, and women with other causes of infertility | Daily injection of 7.5 IU of GH from day 6 of COS until the day of hCG/GnRH-Ant protocol | GH lowered the effective dose of Gn and the duration of GnRH-Ant treatment while increasing the numbers of collected oocytes, MII oocytes, fertilized oocytes, and transferred embryos, and as well as the mean E2 levels on the day of hCG; there were no significant differences in clinical PRs per cycle or LBRs per cycle [17]. |
| IVF/ ICSI (2013) |
82 females (≥1 previous failed IVF-ET cycles with ≤3 retrieved oocytes and ≤3 subsequently obtained embryos using GnRH-a long protocol, and/or E2 levels ≤ 500 pg/mL on the day of hCG) | BMI ≥ 30 mg/m2, FSH > 15 IU/L, women with other causes of infertility, and azoospermia | Daily injection of 4 IU of GH from day 21 of the previous cycle until the day of hCG/GnRH-Ant protocol | GH increased the numbers of retrieved oocytes and obtained embryos; there were no significant differences between groups regarding implantation, or chemical and clinical PRs [27]. |
| IVF (2015) |
64 females (according to the Bologna consensus criteria [41]) | BMI ≥ 30kg/m2, women with other causes of infertility, altered karyotype in couples, and severe male factors | Daily injection of 0.5 IU of GH from day 1 of the agonist until the day of hCG/GnRH-a long protocol | GH increased the numbers of top-quality embryos and cryopreserved embryos[28]. |
| ICSI (2008) |
61 females who responded poorly to high doses of gonadotropin treatment during their first cycles in the same center | D3 FSH > 20 IU/L | Daily injection of 12 IU of GH from day 21 of the precious cycle until the day of hCG/GnRH-a long protocol | GH increased zygotes; although more pregnancies and more clinical pregnancies with fetal heart beat were achieved in the GH group (12/31), compared to the control group (6/30), the difference was not statistically significant [55]. |
D2-3, at day 2–3 of the menses; AUB, abnormal uterine bleeding; COS, control ovarian stimulation; MII oocytes, metaphase II stage oocytes; 2PN zygotes, two pronucleus zygotes; BMI, body mass index; GnRH-Ant, gonadotropin-releasing hormone antagonist; GnRH-a, gonadotropin-releasing hormone agonist; LBR, live birth rate; Gn, gonadotropin; PR, pregnancy rate; PCOS, polycystic ovary syndrome; hCG, human chorionic gonadotropin; PGT, preimplantation genetic testing.