scholarly journals Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to serum growth hormone levels (Study 3)

2020 ◽  
Vol 13 (3) ◽  
pp. 032-053
Author(s):  
John L Yovich ◽  
Syeda Zaidi ◽  
Minh DK Nguyen ◽  
Peter M Hinchliffe

Extending from our first two studies examining the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), this study examines its relevance to the testing of human growth hormone (hGH) levels on the same blood sample. These were taken in the morning during the early follicular phase of the woman’s menstrual cycle and included 408 women who were ART-naïve, undertaking the tests as part of an assessment cycle prior to any ART treatment. The growth hormone levels were also tested on a further 945 women classified as ART-interval cases. It was shown that the vast majority of hGH levels (73%) were very low at <1.0 ng/mL and 22% are extremely low <0.1 ng/mL, close to the detection level of the chemiluminescent immunoassay (0.03 ng/mL). Only 12% of hGH levels were recorded in the range ≥3.0 ng/mL, levels which exclude adult growth hormone deficiency (AGHD). Although IGF-1 levels are regarded as a screening test for AGHD, our studies showed no correlation between hGH levels and the entire range of IGF-1 levels, neither across IGFBP-3 levels, nor across IGF Ratios, albeit there was an apparent inverse trend for the latter. Across the entire age range, the hGH levels were not statistically different among neither the ART-naïve nor the ART-interval women. Furthermore, hGH levels were not different among the clinical parameters of stature or BMI; nor for ovarian reserve parameters AMH or AFC. It is concluded that serum hGH screening probably has very limited value as a screening test for potential AGHD.

2020 ◽  
Vol 13 (3) ◽  
pp. 064-078
Author(s):  
John L Yovich ◽  
Syeda Zaidi ◽  
Minh DK Nguyen ◽  
Peter M Hinchliffe

In this fourth study examining the relevance of measuring the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), we have examined the influence of recombinant growth hormone (rGH) prescribed as an adjuvant on the profile. Of 1633 ART-naïve women who completed an assessment cycle (AC) workup, and which included an IGF profile, 941 women proceeded to an in-vitro fertilization ± intracytoplasmic sperm injection (IVF±ICSI) treatment cycle during the period January 2011 to December 2019. Among those women, 90 were prescribed rGH because they were classified as likely poor-prognosis cases on the basis of advanced age or evidence of severely reduced ovarian reserve parameters. These women had their IVF±ICSI treatment within 3-months of their AC and consented to a second IGF profile measurement 4-6 weeks during their rGH treatment phase. Of the 90 women prescribed rGH adjuvant, 71 used the adjuvant and 19 deferred the treatment, but still completed the second IGF-profile. The data showed that rGH caused a significant elevation in IGF-1 (p<0.0001) as well as its main binding protein, IGFBP-3 (p<0.001), albeit to a lesser degree. Consequently, the IGF ratio, considered a more reliable marker of IGF-1 activity, was shown to be significantly reduced towards the normal range (p<0.0001). The data of clinical outcomes from these 90 women as well as the entire 941 women entering the IVF±ICSI treatment are presented for comparison, noting these data are not suitable for statistical evaluation as the groupings are disparate and unmatched. Further studies are intended to show the clinical relevance of increasing the IGF-1 levels in the analytical investigation of rGH as an adjuvant in ART.


2020 ◽  
Vol 10 (3) ◽  
pp. 122
Author(s):  
John L. Yovich ◽  
Syeda Zaidi ◽  
Minh D. K. Nguyen ◽  
Peter M. Hinchliffe

This study examines the IGF serum profile (IGF-1, IGFBP-3 and the IGF Ratio) from 1633 women who undertook an Assessment Cycle prior to any treatment by assisted reproduction. The idea is to progressively study the IGF profile with a view to identify those women who may be classified as having adult growth hormone deficiency (AGHD) and who may benefit from specific dynamic endocrinological testing to identify a potential benefit from growth hormone adjuvant treatment. This first study evaluates the IGF profile on clinical parameters, namely age, body mass index (BMI) and stature. The study shows a significant linear reduction in IGF-1 levels across the four age groups (<35 years, 35–39 years, 40–44 years and ≥45 years; p < 0.001). However, there was no variation in IGFBP-3 levels but the IGF Ratio showed a progressive linear elevation with advancing age (p < 0.001). With respect to both BMI and stature, none of the IGF profile parameters showed any variation. We conclude that further studies are warranted to examine the notion of underlying AGHD in the causation of the well-known feature of age-related poor prognosis in assisted reproduction.


Background and objective: Growth hormone deficiency (GHD) is one of the most important endocrine and treatable causes of short stature. Reports regarding the sensitivity and specificity of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-3) are not consistent. The aim of our study was to analyze the relevance of IGF-1 and IGFBP-3 concentrations as a screening test for diagnosis of GHD. Design: We retrospectively studied 40 patients whom were evaluated for short stature at the Endocrinology Department of King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia between January 2015 to December 2018. For IGF-1 and IGFBP-3 concentrations, laboratory reference ranges were based on age and sex. For all eligible patients, IGF-1 and IGFBP-3 concentrations were determined and an insulin tolerance test (ITT) was performed. Patients with a peak GH of ≤5.0 ng/ml were considered to be GHD. Results: We retrospectively included 40 patients evaluated for SS for analysis. Mean age was 14.7 ±1.7 years. There were 38 males (80.9%) and 9 females (19.1%) and mean IGF-1 concentration was 146.4 ±69.4 ng/dl. The observed male to female ratio was 4.2:1. Results from the ITT indicated that 27 (57.4%) had GHD. Age was not statistically significant different between GHD (14.7 ±1.8 years) and non-GHD (14.8 ±1.6 years), p=0.9. Moreover, there was non statistical significant more males (59%) than females (50%) in the GHD patients, P=0.7. In addition, there were not statistically significantly different between GHD and non-GHD patients in mean IGF-1 concentration (156.0 ±71.1 ng/dl vs. 140.8 ±68.1 ng/dl, p=0.5) and IGFBP-3 concentration (3752.9 ±1295.9mcg/L vs. 3816.8 ±867.0mcg/L, p=0.9). The mean peak for GH concentration was significantly lower in patients with GHD than without GHD (2.2 ±1.3 ng/ml vs. 9.9 ±5.6 ng/ml, p<0.0001). Peak GH concentration was not significantly positively correlated with IGF-1 concentration (r=0.181, P=0.3) and IGFBP-3 concentration (r=0.103, P=0.5). With a threshold of IGF-1 concentration, sensitivity was 48% (95% confidence interval (95%CI); 26%, 70%), specificity was 37% (95%CI; 16%, 62%) and the negative predictive value for the diagnosis of GHD was 39% (95% CI; 24%, 57%). With a threshold of IGF-1+IGFBP-3 concentration, the sensitivity was 19% (95% CI; 5%, 42%) and the specificity was 89% (95%CI; 67%, 99%). A positive predictive value of 67% (95% CI; 29%, 91%) but a negative predictive value of 50% (95%CI; 44%, 56%). 17 of the patients with IGF-1+IGFBP-3 concentration above the threshold (N = 34) were normal and 17 had GH deficiency. These 17 GHD patients had IGF-1+IGFBP-3 concentration below the reference range for age and sex that did not differ significantly from those of their GH-sufficient counterparts (66.7% vs 50% , P=0.7) respectively. If IGF1+IGFBP-3 concentration was used as a screening test (with a concentration threshold below the reference range for age and sex) and ITT as a confirmatory test, 34 (85%) out of 40 ITT would not have been performed, leading to the misdiagnosis of 17 GH-deficient adults. Thus, in our study population, such a procedure would misdiagnose 17 out of 21 GHD patients (81%) and yield a sensitivity of 19%. Conclusion: Our study demonstrated the good negative predictive value of IGF-1+IGFBP-3 concentration for the diagnosis of GHD, making it possible to minimize the use of the “reference test” method ITT. This observation remains to be validated by population-based studies.


1978 ◽  
Vol 25 (5) ◽  
pp. 437-442 ◽  
Author(s):  
YOSHIAKI OKADA ◽  
KAZUO WATANABE ◽  
TORU TAKEUCHI ◽  
TOSHIO ONISHI ◽  
KIYOJI TANAKA ◽  
...  

GYNECOLOGY ◽  
2019 ◽  
Vol 21 (4) ◽  
pp. 6-8
Author(s):  
Andrey Y Romanov ◽  
Anastasiya G Syrkasheva ◽  
Nataliya V Dolgushina ◽  
Elena A Kalinina

The paper analyzes the literature data on the use of the growth hormone (GH) in ovarian stimulation in assisted reproductive technologies (ART). Routine use of GH in ovarian stimulation in patients with a normal GH level does not increase pregnancy and childbirth rates in ART. Also, no benefits of using GH have been identified for patients with polycystic ovary syndrome, despite the increase in insulin and IGF-1 blood levels. The main research focus is to study the use of GH in patients with poor ovarian response. According to the meta-analysis conducted by X.-L. Li et al. (2017), GH in ovarian stimulation of poor ovarian responders increases the number of received oocytes, mature oocytes number, reduces the embryo transfer cancellation rate and does not affect the fertilization rate. The pregnancy and live birth rates are significantly higher in the group of GH use - by 1.65 (95% CI 1.23-2.22) and 1.73 (95% CI 1.25-2.40) times, respectively. Thus, it is advisable to use GH in ovarian stimulation in poor ovarian responders, since it allows to increases live birth rate in ART. However, further studies should determine the optimal GH dose and assesse it`s safety in ART programs.


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