Growth Hormone Supplementation Research Articles

Long-term safety of growth hormone replacement therapy after childhood medulloblastoma and PNET: it is time to set aside old concerns.

To assess the long-term safety of administering growth hormone (GH) in patients with GH deficiency due to treatment for childhood medulloblastoma and primitive neuroectodermal tumor (PNET). Data were retrospectively retrieved on children receiving GH supplementation, assessing their disease-free and overall survival outcomes and risk of secondary malignancies using Kaplan-Meier and Cox models. Overall 65 children were consecutively collected from May 1981 to April 2013. All patients had undergone craniospinal irradiation (total dose 18-39Gy), and subsequently received GH for a median (interquartile range, IQR) of 81 (50.6-114.9) months. At a median (IQR) of 122.4 months (74.4-149.5) after the end of their adjuvant cancer treatment, two patients (3 %) experienced recurrent disease and 8 (12.3 %) developed secondary malignancies, all but one of them (an osteosarcoma) related to radiation exposure and occurring within the radiation fields. There was no apparent correlation between the administration of GH replacement therapy (or its duration) and primary tumor relapse or the onset of secondary malignancies [HR: 1.01 (95 % CI: 0.98, 1.03) for every additional 12 months of GH supplementation; p = 0.36). At univariate analysis, the large cell or anaplastic medulloblastoma subtype, metastases and myeloablative chemotherapy correlated with a higher risk of secondary malignancies (p < 0.1), but multivariate analysis failed to identify any factors independently associated with this risk. Our data supports once more the safety of long-term GH replacement therapy in children treated for medulloblastoma/PNET, previously reported in larger data sets. The neurooncology community now need to warrant large-scale meta-analyses or international prospective trials in order to consolidate our knowledge of factors other than GH, such as genetic predisposition, high-grade/metastatic disease, high-dose chemotherapy and era of treatment, in promoting the occurrence of secondary malignancies.

Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis.

Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06–4.28) and 2.96 (95% CI 1.17–7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16–5.04) and LBR (OR 2.18; 95% CI 1.01–4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome.

Hormone Therapy to Treat Cardiac Remodeling: Is There Any Evidence?

Cardiac remodeling can be defined as a set of molecular, cellular and interstitial cardiac variations, which manifest clinically as changes in heart size, mass, geometry and function in response to certain aggressions. That process has bad prognosis, because it is associated with ventricular dysfunction progression and malignant arrhythmias.1 Different therapeutic strategies have been assessed to prevent, or at least attenuate, cardiac remodeling.2,3 Some treatments, such as those using angiotensin-convert-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and aldosterone antagonists, have been well established. Other treatments, despite their pathophysiological potential, are still being studied.4 Of those, hormone therapy stands out, particularly with testosterone, thyroid hormone, and growth hormone (GH). Testosterone has received great attention in recent years. From the pathophysiological viewpoint, in the presence of ventricular dysfunction, testosterone can modulate the cardiac remodeling process, strengthen skeletal musculature, enhance exercise capacity and reduce inflammatory activity.5,6 It is worth noting that a significant number of patients with heart failure have reduced testosterone levels. In addition, low testosterone levels in patients with heart failure are an independent risk factor for hospital readmission within 90 days and for mortality.7 Thus, testosterone supplementation seems an attractive strategy to manage heart failure. In different clinical studies, testosterone supplementation improved the exercise capacity of patients with heart failure, regardless of their hormone levels. However, hormone treatment did not modify objective parameters of cardiac remodeling, such as left ventricular dimensions or ventricular function.8 Thus, the so far available evidence suggests that the beneficial effects of testosterone supplementation could derive from its preferential action on skeletal musculature rather than on cardiac remodeling. Regarding thyroid hormone, different actions have been described, such as inotropic, chronotropic and lusitropic effects.9,10 In addition, remodeling-related actions, such as antiapoptotic, antiinflammatory and antifibrotic properties, angiogenesis promotion, cardiac regeneration and induction of beneficial micro RNA profiles, have been reported. Thus, changes in thyroid function affect cardiac morphology and function, in addition to being risk factors for the appearance of heart failure.11,12 Of the changes in thyroid function associated with cardiac remodeling, low T3 syndrome stands out, characterized mainly by an increase in the conversion of T4 to reverse T3, an inactive form of the thyroid hormone. That syndrome can be present in approximately 30% of patients with advanced heart failure, being an independent predictor of cardiovascular mortality. In addition, experimental studies have shown that low cardiac T3 levels can occur in the presence of normal serum levels of thyroid hormones. It is worth noting that cardiac aggressions, such as myocardial infarction, arterial hypertension and diabetes, can reduce the cardiac tissue levels of T3.11-13 That has supported the use of thyroid hormones to prevent or attenuate cardiac remodeling. In different experimental models of aggression, the administration of thyroid hormones was accompanied by an improvement in the cardiac cellular, morphological and functional variables. However, in humans, the scarce information available results from small studies assessing only inconsistent hemodynamic and functional effects.11-14 Although GH has gained special attention in the past years because of its claimed effect of delaying aging process and potential increase in physical performance, it is considered a modulator of cardiac morphology and function.15 Both excess and deficiency of GH and its mediator (insulin-like growth factor I - IGF-1) are associated with cardiovascular disease. In different experimental models, GH administration was associated with a reduction in cardiac remodeling secondary to diverse stimuli.16-18 Approximately 30% of patients with heart failure have GH deficiency, and low IGF-1 levels were predictors of mortality.8 All those considerations support GH supplementation to patients with cardiac dysfunction. Although the first clinical studies have claimed beneficial effects of GH, two placebo-controlled studies have shown neutral results in patients with heart failure.19,20 Thus, the role played by GH in cardiac remodeling situations remains to be determined. Despite the solid pathophysiological evidence and consistent experimental results, so far there is no evidence of the clinical benefit of the routine administration of testosterone, thyroid hormone and GH to patients with cardiac remodeling.

Does the addition of growth hormone to the in vitro fertilization/intracytoplasmic sperm injection antagonist protocol improve outcomes in poor responders? A randomized, controlled trial

To evaluate the effectiveness of the addition of growth hormone (GH) to the antagonist protocol in IVF/intracytoplasmic sperm injection cycles in poor responders. Parallel randomized, controlled, open-label trial. University hospital. A total of 141 patients (GH, n = 68; gonadotropins only, n = 73) were enrolled. Twenty-five patients had their cycles cancelled. Analysis was performed per cycle start as well as per ET. Patients received the antagonist protocol with or without GH supplementation. Mean number of cumulus complexes, metaphase II oocytes retrieved and fertilized, chemical and clinical pregnancy rates, early miscarriage rate, ongoing pregnancy and live birth rates. The addition of GH significantly lowered duration of hMG treatment, duration of GnRH antagonist treatment, and dose of gonadotropin. It significantly increased mean E2 levels on the day of hCG administration, number of collected oocytes (7.58 ± 1.40 vs. 4.90 ± 1.78 [mean ± SD]), number of metaphase II oocytes (4.53 ± 1.29 vs. 2.53 ± 1.18), number of fertilized oocytes (4.04 ± 0.96 vs. 2.42 ± 1.03), and number of transferred embryos (2.89 ± 0.45 vs. 2.03 ± 0.81). There was no significant difference in the clinical pregnancy rate per cycle (22.1% vs. 15.1%) or live birth rate per cycle (14.7% vs. 10.9%). Growth hormone as an adjuvant treatment in IVF/intracytoplasmic sperm injection cycles for poor responders should be cautiously used with the antagonist protocol, because there is still no identified impact on pregnancy outcomes. However, evaluation of the clinical pregnancy and live birth rates in our data was limited by low statistical power. ClinicalTrials.gov Identifier: NCT02195947.

Predictive factors for clinical pregnancies of poor responders diagnosed according to the Bologna criteria in ovarian stimulation in vitro fertilization (IVF)

Objective To explore the predictive factors for clinical pregnancies of poor responders diagnosed according to the Bologna criteria in ovarian stimulation in vitro fertilization (IVF). Methods The present study included 392 poor responders diagnosed according to the Bologna criteria (392 first poor response cycles and 247 subsequent conventional stimulation cycles) in our IVF center. Binary Logistic regression analysis was used to study the association between possible predictive factors and clinical pregnancy of poor responders in ovarian stimulation IVF. Results The significant predictive factors for clinical pregnancies of poor responders in ovarian stimulation IVF were female age, number of embryos transferred and ovarian stimulation protocol. Female age had the best predictive value for clinical pregnancy of poor ovarian responders. Conclusion Poor responders should be encouraged to attempt further ovarian stimulation IVF treatment as soon as possible because the pregnancy rate decreases with advancing female age. Growth hormone supplementation, intracytoplasmic sperm injection (ICSI) procedure or assisted hatching seem not be able to prominently improve the pregnancy outcomes of poor responders diagnosed according to the Bologna criteria in ovarian stimulation IVF.

Strategies for Controlled Ovarian Stimulation in the Setting of Ovarian Aging

In the context of assisted reproduction, the term ovarian aging is often used to refer to declining potential of ovaries to produce oocytes in adequate number or quality in response to controlled ovarian stimulation (COS). Different aspects of COS have been modified with the intention to increase the number and quality of oocytes obtained for in vitro fertilization. In the setting of ovarian aging, suppression of the luteinizing hormone (LH) surge with gonadotropin-releasing hormone (GnRH) antagonist or short GnRH agonist protocol and stimulation with a daily gonadotropin dosage of ≤ 300 IU/day seem to be appropriate first choices, and there is a strong need for well-designed randomized controlled trials investigating effects of addition of LH activity, estradiol priming, transdermal testosterone administration, and growth hormone supplementation. Given the lack of high-quality evidence showing effectiveness of one approach over another, other factors such as duration of stimulation, total gonadotropin consumption and cost of medication, patient friendliness, and possible side effect profiles must be considered in tailoring the COS protocol according to each individual's needs and desires.

Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.

Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy. In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation. CKD-related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that. Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease.

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.

Prognostic factors of craniopharyngioma with special reference to autocrine/paracrine signaling: underestimated implication of growth hormone receptor

Craniopharyngioma is a slow-growing tumor classified as benign, but tight adhesion and significant local infiltration to the vital structures are common. In spite of improvement of modern microsurgery techniques and precise anatomical understanding not few cases of this tumor recur, and long-term tumor control and maintenance of quality of life are sometimes difficult. However, very little is known about the effects of the molecular characters of craniopharyngioma on the prognosis. Ninety eight cases of craniopharyngioma surgically treated at the Department of Neurosurgery, Tohoku University Hospital and Kohnan Hospital from April 1996 to May 2014, 45 males and 53 females aged from 2 to 80 years (mean, 40.84 years) were retrospectively reviewed, and postoperative outcomes and the possible involvement of the autocrine/paracrine mechanism were investigated. The patients were followed up at intervals of 6 months to assess tumor recurrence, and clinical outcomes were correlated with the findings of immunohistochemical examinations used growth hormone receptor (GHR) and downstream hormones. The follow-up period ranged from 3 to 209 months. Hormone expression was examined in 88 patients, of which 46 specimens (52.3 %) showed high expression of GHR. The GHR high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p = 0.007). Simultaneous high expression of growth hormone (GH) and GHR was found in 33 specimens (37.5 %), and the high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p = 0.011). No other hormones showed statistically significant differences in outcomes. High expression of GHR is associated with shorter duration of postoperative stable disease in patients with craniopharyngioma. If the surgical specimens were craniopharyngiomas with high GHR expression, GH supplementation would be introduced quite prudently.

Low-dose growth hormone supplementation increases clinical pregnancy rate in poor responders undergoing in vitro fertilisation

Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p < 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p < 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR) mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex’s action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

Early diagnosis of slipped capital femoral epiphysis on magnetic resonance imaging: A case report with review of literature

Slipped capital femoral epiphysis (SCFE) is a common hip condition occurring in adolescents, with a prevalence of 10 cases per 100,000 children. It usually affects younger age group from 10 to 17 years. The condition is usually found to be coexistent with various other conditions such as obesity, growth surges, and endocrine disorders such as hypothyroidism, growth hormone supplementation, hypogonadism, and pan-hypopituitarism. Patients present with limping and a poorly localized pain in the hip, groin, thigh, or knee. Diagnosis of the condition is often delayed due to its nonassociation with trauma and hence increases the chances of developing various complications such as avascular necrosis, chondrolysis and deformity. Majority of researches of SCFE are from Europe and North America, while studies in Asian populations are rare. Delay in diagnosis of SCFE is usually due to patients presenting with knee pain. Imaging can thus aid in early diagnosis and appropriate treatment of the disease, which in turn reduces incidence of deformity and disability in the affected children. Bilateral hip radiography - anteroposterior and frog's-leg lateral views and magnetic resonance imaging (MRI) are the radiological techniques that help in early diagnosis. MRI detects early physeal changes of both preslip and SCFE even when radiographs and computed tomography are normal. MRI should be routinely used to diagnose early SCFE in preslip stage to avoid further complications.

Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: The role of zinc-α2-glycoprotein

Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-α2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5-year GH replacement therapy were compared with age-, gender- and BMI-matched healthy controls. Euglycemic hyperinsulinemic clamp was used to assess whole-body and adipose tissue-specific insulin sensitivity. Glucose tolerance was determined by oGTT, visceral and subcutaneous abdominal adiposity by MRI, adipocyte size morphometrically after collagenase digestion, lipid accumulation and release was studied in differentiated human primary adipocytes in association with GH treatment and zinc-α2-glycoprotein gene silencing. Five-year GH replacement therapy improved glucose tolerance, adipose tissue insulin sensitivity and reduced adipocyte size without affecting adiposity and whole-body insulin sensitivity. Adipose tissue zinc-α2-glycoprotein expression was positively associated with whole-body and adipose tissue insulin sensitivity and negatively with adipocyte size. GH treatment to adipocytes in vitro increased zinc-α2-glycoprotein expression (>50%) and was paralleled by enhanced lipolysis and decreased triglyceride accumulation (>35%). Moreover, GH treatment improved antilipolytic action of insulin in cultured adipocytes. Most importantly, silencing zinc-α2-glycoprotein eliminated all of the GH effects on adipocyte lipid metabolism. Effects of 5-year GH supplementation therapy on adipose tissue lipid metabolism and insulin sensitivity are associated with zinc-α2-glycoprotein. Presence of this adipokine is required for the GH action on adipocyte lipid metabolism in vitro.

Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown.

Effects of Growth Hormone Supplementation in Patients Undergoing IVF/ICSI-ET with Poor Ovarian Response to Gonadotropin

Objective To analyze the effects of growth hormone (GH) supplementation during IVF/ICSI-ET in Chinese patients who had prior IVF cycle with poor response to gonadotropin (Gn). Methods Ovulation was stimulated in 389 consecutive patients who all had poor ovarian response, among them, 102 patients (GH cycle) received 4 IU GH and the other 287 patients (non-GH cycle) underwent IVF without GH. Fisher's exact test, Chi square test and Student's t-test were used to analyze IVF/ICSI-ET outcomes. Results After GH treatment, 102 patients had significantly more large- and medium-sized follicles, oocytes retrieved, 2 pronucleus oocytes, metaphase II stage (MII) oocytes, and high-quality embryos than in previous cycles without GH. However, the number of embryos transferred, clinical pregnancy rate, transfer rate and biochemical pregnancy rate were not significantly different. Furthermore, the 102 patients given GH had significantly lower luteinizing hormone levels and biochemical pregnancy rates; thicker endometrium and more Gn administration days; and more large- and medium-sized follicles and MII oocytes than 287 other patients undergoing IVF/ICSI-ET without GH. However, these groups did not differ significantly in clinical pregnancies, high-quality embryos, MII oocytes, and embryo implantation rates. Conclusion GH may improve some IVF/ICSI-ET outcomes for women with poor ovarian response.

Growth Hormone Supplementation in the Luteal Phase Prior to Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and increase the production of estradiol in animal and human ovaries1-3. Fertility specialists have therefore explored the potential for GH supplementation to improve outcomes in women undergoing in vitro fertilization (IVF), with the greatest interest in women with diminished ovarian reserve, for whom successful fertilization remains a therapeutic challenge4.

Sanjad-sakati syndrome and its association with superior mesenteric artery syndrome.

Sanjad-Sakati syndrome (SSS) is an autosomal recessive disorder found exclusively in people of Arabian origin. It was first reported in the Kingdom of Saudi Arabia in 1988 and confirmed by a definitive report in 1991. The syndrome comprises of congenital hypoparathyroidism, seizures, severe growth and developmental retardation, low IQ, and atypical facial features. Supportive treatment in the form of vitamin D and growth hormone supplementation is often offered to patients suffering from SSS. This case study focuses on the steps taken to help a patient who was found to have very unusual symptoms and was later found to have superior mesenteric artery syndrome.

Panhypopituitarism due to craniopharyngioma with bilateral slipped capital femoral epiphysis

Craniopharyngiomas are rare primary intracranial tumors. Despite their benign histological appearance, they are often associated with an unfavorable prognosis. The typical manifestations upon diagnosis are headache, visual impairment, polyuria/polydypsia, growth retardation, disturbance of pubertal development, and significant weight gain. The treatment options include radical surgery or radiotherapy, or a combination of these modalities. Slipped capital femoral epiphysis (SCFE) is the most common adolescent hip disorder. SCFE occurs when the capital femoral epiphysis displaces posteriorly on the femoral neck at the level of the physis. The etiology of SCFE is thought to be multifactorial and may include obesity, growth surges, and less common endocrine disorders. The related endocrine disorders include hypothyroidism, growth hormone supplementation, hypogonadism, and panhypopituitarism. Reported herein is a case of panhypopituitarism caused by craniopharyngioma combined with SCFE.

Growth hormone, gender and face shape in prader–willi syndrome

Prader-Willi syndrome is a neurodevelopmental disorder resulting from the absence of expression of paternally expressed gene(s) in a highly imprinted region of chromosome 15q11-13. The physical phenotype includes evidence of growth retardation due to relative growth hormone deficiency, small hands and feet, a failure of normal secondary sexual development, and a facial appearance including narrow bifrontal diameter, almond-shaped palpebral fissures, narrow nasal root, and thin upper vermilion with downturned corners of the mouth. Anecdotally, the face of individuals with PWS receiving hGH treatment is said to "normalize." We used dense surface modelling and shape signature techniques to analyze 3D photogrammetric images of the faces of 72 affected and 388 unaffected individuals. We confirmed that adults with Prader-Willi syndrome who had never received human growth supplementation displayed known characteristic facial features. Facial growth was significantly reduced in these adults, especially in males. We demonstrated that following human growth hormone (hGH) supplementation, vertical facial growth of affected individuals falls within the normal range. However, lateral and periorbital face shape and nose shape differences in affected children who have received hGH therapy remain sufficiently strong to be significantly discriminating in comparisons with age-sex matched, unaffected individuals. Finally, we produced evidence that age at initiation and length of treatment with hGH do not appear to play a role in normalization or in consistent alteration of the face shape of affected individuals. This is the first study to provide objective shape analysis of craniofacial effects of hGH therapy in Prader-Willi syndrome.

Effects of growth hormone on the ontogenetic allometry of craniofacial bones.

Organism size is controlled by interactions between genetic and environmental factors mediated by hormones with systemic and local effects. As changes in size are usually not isometric, a considerable diversity in shape can be generated through modifications in the patterns of ontogenetic allometry. In this study we evaluated the role of timing and dose of growth hormone (GH) release on growth and correlated shape changes in craniofacial bones. Using a longitudinal study design, we analyzed GH deficient mice treated with GH supplementation commencing pre- and post-puberty. We obtained 3D in vivo micro-CT images of the skull between 21 and 60 days of age and used geometric morphometrics to analyze size and shape changes among control and GH deficient treated and non-treated mice. The variable levels of circulating GH altered the size and shape of the adult skull, and influenced the cranial base, vault, and face differently. While cranial base synchondroses and facial sutures were susceptible to either the direct or indirect effect of GH supplementation, its effect was negligible on the vault. Such different responses support the role of intrinsic growth trajectories of skeletal components in controlling the modifications induced by systemic factors. Contrary to the expected, the timing of GH treatment did not have an effect on catch-up growth. GH levels also altered the ontogenetic trajectories by inducing changes in their location and extension in the shape space, indicating that differences arose before 21 days and were further accentuated by a truncation of the ontogenetic trajectories in GHD groups.