There is a meta-analysis study at 2009 from Kolinibianakis, et al from 6 trials.

This study
is intend to find relationship between GH addition to increase the probability of pregnancy in
poor responders undergoing ovarian stimulation with gonadotrophin releasing hormone (GnRH)
analogues and gonadotrophins for IVF. It is a meta-analysis evaluates with only six small trials
including 169 patients in. But there are several weakness in this study such as no significant
statistical heterogeneity in the definition of poor ovarian response and the protocol of GH
administration, and three studies not reported about the methods and study period. No pooling of
data was feasible for gonadotrophin requirement due to the fact that most studies reported
medians with corresponding interquartile ranges. However, it should be noted, that in the largest
study, a significantly lower requirement for gonadotrophins was observed in the GH group
(mean+SD: 3187+ 232 IUs of FSH) as compared with the control group (mean+SD: 4070+598
IUs of FSH) (P, 0.001).21
For the adverse event, slight oedema in two patients was reported in one study. Two studies
reported no adverse events, while in the remaining three studies no information was available
regarding the occurrence of adverse events associated with the use of GH
A observational study on the effect of the addition of recombinant GH to gonadotrophins on
assisted reproduction treatment outcome was performed between January 2002 and September
2007. The patients treated with 8 IU (1.33 mg) of recombinant human were compared
retrospectively to all patients with three or more failures during the same period of time but
stimulated only with recombinant FSH or HMG, without GH. And the patiens caracteristics:
With GH
Age
35.5 years 4.0
FSH dosage on day 3
6.7 2.0 IU/l
Total dose of gonadotrophins 2586 1237

Without GH
36.6 4.1
7.1 2.0 IU/l
2886 1300

(IU) used
The oestradiol concentration

1945 1132

(2215 1286

Result: The cleavage rates were equivalent, as were the mean numbers of transferred embryos,
while clinical pregnancy rate was significantly higher in the GH group (25.7% versus 18.7%, P <
0.01). Pregnancy evolution was comparable in the two groups, with 70.4% delivery per

pregnancy in the GH group, compared with 73.2% in the control group. Abortion and ectopic
pregnancy rates were 23.7% versus 25.4% and 1.8% versus 2.5%, respectively.22
A meta-analysis study to assess the effectiveness of adjuvant growth hormone in in-vitro
fertilisation protocols was made by James MN Duffy, et al. in 2010. Ten trials with a total of 440
subfertile couples were included in the meta-analysis with no consistency as to the dose or
timing of growth hormone administration.
Result: In women who are not considered poor responders undergoing in IVF there is no
evidence from randomised controlled trials to support the use of growth hormone. In women
who are considered poor responders the use of growth hormone has been shown to significantly
improve live birth and pregnancy rates. With OR = 3.28; 95% CI 1.74-6.20 at Poor responder as
defined by the study.23
A retrospective analysis of 20 cases of patients (mean age was 32.9 years old) who were
pregnant and had GH supplementation during IVF at the Singapore between 1993 and 2003.
They had 12 iu of GH every third day, starting on the day of gonadotropin stimulation, till the
administration of human chorionic gonadotropin (HCG). All these patients had previously failed
IVF due to poor stimulation, poor egg quality, poor fertilisation at intracytoplasmic sperm
injection (ICSI) or failed implantation, and they had documented GH deciency. This study is
tried to evaluate the GH status of the individual, and document its deciency, prior to
supplementation. From the study, they imply that GH supplementation may improve embryo
quality in selected patients. There is also an increase in the fertilisation rate at intracytoplasmic
sperm injection (ICSI).24
a sequential crossover study from 2002 to 2006 about growth hormone (GH) supplementation
assessed in poor-prognosis patients by John L Yovich, et al. GH was given 10 IU to 159 women
with an average age of 37.5 4.1 years.
A meta-analysis from 22 RCTs was made by Kyrou D, et al in 2009 assessing various
interventions proposed for improving the probability of regnancy in poor responders with five
eligible RCTs were identified evaluating GH addition in poor responders (n 128) stimulated.
Ovarian stimulation was performed in both groups (GH and placebo coadministration) using a
long follicular GnRH agonist protocol and hMG and/or human FSH, a short GnRH agonist

protocol and hMG/pure FSH (pFSH), a short GnRH agonist protocol and hMG, a long follicular
GnRH agonist protocol and hMG, and a long idluteal GnRH agonist protocol and hMG for IVF.
Regarding GH administration, frequency and dosage varied markedly among the eligible studies.
In those five trials, patients in the GH group received: 24 IU GH, 12 IU GH, 18 IU GH, on
alternate days, 0.1 IU of GH per kilogram of body weight, daily, and one RCT that compared two
different dosages (4or 12 IU/day) of GH versus placebo. Pooling the results of these studies
suggested that addition of GH significantly increased the probability of live birth in poor
responders (OR 5.22, CI 95% 1.0924.99 This result did not materially change when the data
from the 4 IU instead of the 12 IU group in the study were included in the analysis (OR 4.89, CI
95% 1.1920.05). The same was true when these two GH groups were combined as one group
(OR 4.18, CI 95% 1.0217.16).
However, it should be noted that no statistically significant differences were observed in
the duration of stimulation and the number of COCs retrieved in all the studies analyzed. The
total amount of gonadotropins required for ovarian stimulation was not significantly different in
four of the eligible studies, whereas in the study, significantly less ampoules of hMG were
required in patients who received GH compared with those who received placebo.25
A randomized prospective study was conducted between 2005 and june 2007 by Kucuk
T, et al. The study involved 61 patients who responded poorly to high dose gonadotropin
treatment in their first cycles in the same center. 31 couples wre allocated to Gh co-treatment
group (12 IU from day 21 of preciding cycle along with GnRHa until the day of HCG) and the
other 30 were allocated to only GnRHa long protocol group to serve as the control group.
Result: More pregnancies and more clonical pregnancies with fetal heart activity were achieved
in GH group (12 of 31), compared to the control group (6 of 30). Yet the difference did not reach
to statistical significance. A post-analysis showed that the sample size in this study must have
been 110 in each group to validate these result.26

21. Kolibianakis E.M, Venetis C.A, Diedrich K, Tarlatzis B.C, Griesinger G. Addition of
growth hormone to gonadotrophins in ovarian stimulation of poor responders treated

by in-vitro fertilization: a systematic review and meta-analysis. 26 June 2009. Human

Reproduction Update, Vol.15, No.6 pp. 613622.
22. A Hazout, et al. Effect of growth hormone on oocyte competence in patients with
multiple IVF failures. 20 March 2009. Reproductive BioMedicine Online Vol 18.(5):
664-670.
23. Duffy JMN, et al. Growth hormone for in vitro fertilization (Review). 2010. The
Cochrane Library, Issue 11.
24. Rajesh H, Yong Y Y, Zhu M, Chia D, Yu S L. Growth hormone deciency and
supplementation at in-vitro fertilization. 2007. Singapore Med J; 48 (6) : 514.
25. Kyrou D, et al. How to improve the probability of pregnancy in poor responders
undergoing in vitro fertilization: a systematic review and meta-analysis. 3 march
2009. Fertil Steril vol 91:74966.
26. Kucuk T, et al. Growth hormone co-treatment within a GnRH agonist long protocol in
patients with poor ovarian response: a prospective, randomized, clinical trial. 24 Jan
2008. J Assist Reprod Genet Vol 25: 123-127.