scholarly journals Growth hormone treatment strategies in assisted reproduction for the poor responder patients

Author(s):  
Liailia Kh. Dzhemlikhanova ◽  
Ksenia V. Ob’edkova ◽  
Dariko A. Niauri ◽  
Igor Yu. Kogan ◽  
Maria A. Mazilina ◽  
...  

The goal of the study was to estimate the efficacy of growth hormone (GH) co-treatment to the antagonist protocol in IVF/ ICSI cycles in poor responders. A prospective observational study involved 75 patients. All patients underwent standard antagonist protocol with or without GH co-treatment. GH additional was given a daily subcutaneous injection of 1.33 mg (equivalent to 4 IU) of GH from day 1 of ovarian stimulation until the day of human chorionic gonadotropin (hCG). Concentrations of GH, insulin-like growth factor I (IGF-I) and IGF binding protein-3 (IGFBP-3) in serum and follicular fluid were analyzed. The GH co-treatment significantly lowered effective dose of gonadotropins, duration of stimulation, IGFBP-3 level in serum and follicular fluid day of oocytes retrieval. The number of oocytes recovered, metaphase II stage (MII) oocytes, 2 pronucleus (2 pn) zygote, good-quality transferred embryos were significantly higher in the GH+ group. Only patients GH+ group became pregnant. Positive correlation was found between IGF-I level in follicular fluid, dynamics of IGFBP-3 level changes during stimulation protocol and number of good-quality transferred embryos in the GH+ group. GH administration in IVF/ICSI cycles for poor responders raises ovarian sensitivity to the gonadotropin exogenous influence, this way, increasing number of high-quality embryos and the probability of pregnancy.

1995 ◽  
Vol 132 (6) ◽  
pp. 727-729 ◽  
Author(s):  
Jørn Müller ◽  
Jørgen Starup ◽  
J Sandahl Christiansen ◽  
Jens OL Jøgensen ◽  
Anders Juul ◽  
...  

Müller J, Starup J, Christiansen JS, Jørgensen JOL, Juul A, Skakkebaek NE, Growth hormone treatment during pregnancy in a growth hormone-deficient woman. Eur J Endocrinol 1995;132:727–9. ISSN 0804–4643 Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 2 5-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she became pregnant after donor insemination. The GH treatment was continued until variant GH production from the placenta was evident. Serum levels of GH, IGF-I and IGFBP-3 were measured monthly during pregnancy after 3 days off GH therapy. Abdominal ultrasound was performed five times. Hormonal levels were measured immediately after delivery and during the following days. Serum GH and IGF-I levels increased during the second half of pregnancy: serum IGFBP-3 remained constant throughout pregnancy at a normal level. Serum levels of GH fell within 1 h after delivery, and levels of IGF-I and IGFBP-3 decreased into the range of GH-deficient women 4 days after. The fetal biparietal diameter increased normally, and birthweight was 3.564kg, length 52 cm. No adverse events were recorded. We conclude that the role of GH replacement during pregnancy of GH-deficient women should be investigated further. Jørn Müller, Department of Growth and Reproduction, GR 5064, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen ø, Denmark


1996 ◽  
Vol 134 (2) ◽  
pp. 190-196 ◽  
Author(s):  
Christina Bergh ◽  
Kjell Carlström ◽  
Ulrika Selleskog ◽  
Torbjörn Hillensjö

Bergh C, Carlström K, Selleskog U, Hillensjö T. Effect of growth hormone on follicular fluid androgen levels in patients treated with gonadotropins before in vitro fertilization. Eur J Endocrinol 1996;134:190–6. ISSN 0804–4643 Forty normally ovulating women aged 25–38 years from one private and two university in vitro fertilization (IVF) centres were used in this randomized, double-blind, parallel, placebo-controlled study to explore the effect of recombinant human growth hormone (GH) on follicular fluid (FF) levels of steroid hormones, particularly androgens. All the women had tubal factor infertility and were classified as poor responders with at least two previously performed and failed IVF treatments in which less than five oocytes had been retrieved following ovarian hyperstimulation. Growth hormone (GH 0.1 IU/kg body wt per day) or placebo was given as pretreatment during down-regulation with gonadotropin-releasing hormone agonist and during stimulation with human menopausal gonadotropin (hMG) according to the randomized protocol. Follicular fluid concentrations of steroids were measured and changes related to the levels of insulin-like growth factor I (IGF-I) and IGF binding proteins 1 and 3 and to the mode of GH administration. Pretreatment with GH, i.e. administration of GH before hMG stimulation only, caused significantly elevated follicular fluid concentrations of estrone, testosterone and dehydroepiandrosterone (DHEA) and higher values for markers of aromatase activity (ratios between estrone and androstenedione and between estradiol-17β and androstenedione) than in the placebo group, as well as in the two groups receiving GH during hMG stimulation. The highest values for markers of steroid sulfatase activity (ratios between DHA and DHEA sulfate and between unconjugated and conjugated estrone) were found in the patients pretreated with GH. Positive correlations were found between follicular fluid IGF-I and IGF binding protein 3 on the one hand and androgens on the other. This study showed that the administration of adjuvant GH to women who were poor responders to gonadotropins alters the endocrine/paracrine ovarian response to gonadotropins. Torbjörn Hillensjö, Department of Obstetrics and Gynecology, Huddinge University Hospital, S-141 86 Huddinge, Sweden


1991 ◽  
Vol 275 (2) ◽  
pp. 441-446 ◽  
Author(s):  
C D Scott ◽  
R C Baxter

Insulin-like growth factors (IGFs) circulate predominantly in a growth-hormone-dependent ternary complex of 125-150 kDa. This study investigates the production of the alpha-subunit of this complex, an acid-labile glycoprotein without intrinsic IGF-binding activity, which binds to the IGF-binding protein IGFBP-3 in the presence of IGFs. Medium conditioned by primary cultures of rat hepatocytes produced alpha-subunit with similar complex-forming activity to purified rat serum alpha-subunit. Bovine growth hormone stimulated hepatocyte production of both IGF-I and alpha-subunit. IGF-I tracer bound to pure rat IGFBP-3 was converted from approx. 60 kDa to 150 kDa by serum alpha-subunit, whole rat serum or rat hepatocyte culture medium; this converting activity was destroyed by transient acidification. In contrast, IGF-I bound to hepatocyte-medium IGF-binding proteins could not be converted into a high-molecular-mass from by purified rat serum alpha-subunit. Rat serum and hepatocyte-medium alpha-subunit appeared identical by electrophoretic analysis, since reaction of either with cross-linked IGF-I.IGFBP-3 tracer resulted in bands of molecular mass 130 kDa and 160 kDa, probably representing intact and partially deglycosylated complexes. However, IGF-binding proteins in rat serum and hepatocyte medium were different, in that affinity labelling of medium binding proteins, depleted of endogenous IGFs, showed no evidence of the 50-60 kDa cluster of bands characteristic of rat serum IGFBP-3. We conclude that rat hepatocytes in primary culture produce alpha-subunit similar to that in rat serum; however, alpha-subunit is unable to form ternary complexes with hepatocyte IGF-binding proteins, since cultured hepatocytes do not secrete IGFBP-3.


1998 ◽  
pp. 633-639 ◽  
Author(s):  
T Sugimoto ◽  
D Nakaoka ◽  
M Nasu ◽  
M Kanzawa ◽  
T Sugishita ◽  
...  

The present study was performed to investigate the age-dependent changes in body composition and the possible role of growth hormone (GH), insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) in these changes in postmenopausal Japanese women. A total of 161 Japanese women aged 45-88 years (mean 62) were enrolled in the cross-sectional study. Body composition (bone mineral content (BMC), lean body mass (LBM) and fat) was measured by dual-energy X-ray absorptiometry, and the percentage of BMC, LBM and fat was calculated by dividing each absolute value of body composition by total body mass. Urinary GH concentration divided by creatinine in nocturnal urine samples collected just after waking was used as an index of endogenous GH secretion. Serum levels of IGF-I and IGFBP-3 were measured by RIA. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 declined with age. BMC, %BMC and LBM also declined with age, while fat mass and %fat did not obviously change with age. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 correlated positively with BMC, even if age was taken into account. On the other hand, urinary GH correlated negatively with fat and %fat. In contrast, serum levels of IGF-I and IGFBP-3 correlated positively with fat and %fat. LBM did not correlate with either urinary GH or serum IGFBP-3 levels but exhibited a weakly positive correlation with serum IGF-I level. The present study suggests that the GH-IGF-I-IGFBP-3 axis positively regulates bone mass, and that GH and IGF-I-IGFBP-3 inversely regulate fat mass, i.e. GH negatively and IGF-I-IGFBP-3 positively regulates it.


1994 ◽  
Vol 131 (2) ◽  
pp. 150-155 ◽  
Author(s):  
M Kassem ◽  
K Brixen ◽  
W Blum ◽  
L Mosekilde ◽  
EF Eriksen

Kassem M, Brixen K, Blum W, Mosekilde L, Eriksen EF. No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis. Eur J Endocrinol 1994;131:150–5. ISSN 0804–4643 To test the hypothesis that a dysfunctional growth hormone (GH)–insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg−1·day−1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean ± sem): IGF-I, 16.5 ± 1.3 versus 16.0 ± 1.3 nmol/l (NS); IGF-II, 79.9 ± 3.6 versus 72.5 ± 4.1 nmol/l (NS); and IGFBP-3, 125.7 ± 6.5 versus 130.3 ± 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 ± 26% versus 369 ± 22%, IGF-II, 125 ± 4% versus 119 ± 5%, IGFBP-3, 141 ± 5% versus 147 ± 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH–IGF axis in women with spinal osteoporosis. Kim Brixen, University Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage-Hansens gade 2, DK-8000 Aarhus C, Denmark


1995 ◽  
Vol 7 (3) ◽  
pp. 345
Author(s):  
C Beanland ◽  
C Browne ◽  
R Young ◽  
J Owens ◽  
P Walton ◽  
...  

Insulin-like growth factors mediate many of the effects of growth hormone and are important in the regulation of growth, especially in the fetus where growth is less dependent on circulating growth hormone. In the ovine fetus, insulin-like growth factor-I (IGF-I) is bound mainly to the low molecular weight insulin-like growth factor-binding proteins (IGFBP), IGFBP-1 and IGFBP-2, with little binding to IGFBP-3 until near term at 147 days gestation. To determine if there was any difference in plasma IGF-I and IGFBP-3 concentrations in growth-retarded fetal sheep with altered renal status, concentrations were measured by specific radioimmunoassay from bilaterally nephrectomized fetal sheep between Days 113 and 135 gestation. Plasma IGFBP-3 concentrations were significantly (P < 0.001) increased in bilaterally nephrectomized fetuses (4.19 +/- 0.19 micrograms mL-1, n = 7) compared with control fetuses (2.33 +/- 0.10 micrograms mL-1, n = 7). There was no change in plasma IGFBP-3 concentration with gestational age in either experimental group. Maternal plasma IGFBP-3 concentrations did not differ between the bilateral nephrectomy group (3.11 +/- 0.09 micrograms mL-1, n = 7) and the control group (3.25 +/- 0.11 micrograms mL-1, n = 7) and showed no change within groups over the experimental period. Total plasma IGF-I concentrations in bilaterally nephrectomized fetuses and ewes were similar to those in control fetuses and ewes. The results indicate that the profile of IGF binding in fetal plasma is altered in the anephric fetal sheep. In nephrectomized fetal sheep, increased IGFBP-3 concentrations, and therefore increased IGF-binding capacity in fetal plasma, may have contributed to a decrease in free IGF in plasma and decreased IGF-I bioactivity. This would provide a possible mechanism for the growth retardation reported in bilaterally nephrectomized fetal sheep.


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