Relationship between fertilization results after intracytoplasmic sperm injection, and intrafollicular steroid, pituitary hormone and cytokine concentrations.
ABSTRACT Previous studies relating hormone and cytokine concentrations in follicular fluid to oocyte fertilizability were flawed by the uncertainty about the actual oocyte maturity status at the time of recovery and by the possible contribution of the male factor to failures of conventional in-vitro fertilization. This is the first study in which oocyte maturity was assessed immediately after recovery and only mature oocytes were selected for treatment by intracytoplasmic sperm injection. Fertilization outcomes were related to follicular fluid concentrations of 17beta-oestradiol, progesterone, follicle stimulating hormone, luteinizing hormone (LH), growth hormone (GH), prolactin (PRL), interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha). Those oocytes that subsequently showed normal fertilization were harvested from follicles with higher concentrations of progesterone, GH, PRL, IL-1 and TNF alpha as compared with those of oocytes that failed to fertilize. Among the normally fertilized oocytes, low GH concentrations were associated with the failure of cleavage and with poor morphology of cleaving embryos, whereas rapidly cleaving embryos developed from oocytes recovered from follicles with high concentrations of LH and IL-1. These data suggest important roles for GH, IL-1 and TNF alpha, and of residual LH after pituitary suppression, as positive regulators of the final phase of oocyte intrafollicular development.
Article: The effect of treatment with growth hormone on fertility outcome in eugonadal women with growth hormone deficiency: report of four cases and review of the literature.[show abstract] [hide abstract]
ABSTRACT: To highlight the clinical role of standard GH replacement treatment on fertility and pregnancy outcomes in four infertile eugonadal women with GH deficiency (GHD). Case report. Department of endocrinology and infertility clinic, tertiary-care university hospital. Four normogonadotrophic, normoprolactinemic patients with long-standing infertility, affected by GHD. In two patients (aged 30 and 34 years) GHD was diagnosed after a brain injury. The third patient (age 30 years) had a primary empty sella, documented by magnetic resonance imaging of the pituitary. The last patient (age 28 years) underwent transsphenoidal surgery for Ratke's cyst. The LH and FSH responses to GnRH were normal in all four patients. Two of the four patients also had secondary hypoadrenalism and hypothyroidism. Patients received recombinant human GH replacement therapy (0.9-1.8 mg/week) for 6-12 months until pregnancy was first indicated by biochemical markers (beta-hCG) and later confirmed by transvaginal sonography. The GH therapy was discontinued after confirmation of pregnancy. Pregnancy. All patients remained off treatment throughout pregnancy; they had uneventful pregnancies and term deliveries. The babies were healthy and normal in terms of length and weight. Our case studies confirm the important clinical role of the GH-insulin-like growth factor I system in oocyte fertilization and the beginning of pregnancy in a selected population of eugonadotrophic infertile women.Fertility and sterility 12/2008; 91(3):930.e7-11. · 3.97 Impact Factor
Article: Biological versus chronological ovarian age: implications for assisted reproductive technology.[show abstract] [hide abstract]
ABSTRACT: Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART) treatment. Literature searches supplemented with the authors' knowledge. Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment outcomes for women with biologically older ovaries. Exogenous GH may improve oocyte development and counteract the age-related decline of oocyte quality. The effects of GH may be mediated by insulin-like growth factor-I, which works synergistically with follicle-stimulating hormone on granulosa and theca cells. Patients with biologically older ovaries may benefit from a tailored approach based on individual patient characteristics. Among the most promising adjuvant therapies for improving ART outcomes in women of advanced reproductive age are the administration of exogenous LH or GH.Reproductive Biology and Endocrinology 09/2009; 7:101. · 2.05 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1β, IL-6, IL-18, IFN-γ, IFN-α, TNF-α, IL-12, and IL-23;, and anti-inflammatory: G-CSF), chemokines (MIP-1α, MIP-1β, MCP-1, RANTES, and IL-8), and other biomarkers (sAPO-1/Fas, CD44(v6)) in 153 women undergoing in vitro fertilization (IVF). Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1α and CD44(v6) were found to correlate with polycystic ovary syndrome, IL-23, INF-γ, and TNF-α with endometriosis, higher CD44(v6) but lower IL-β and INF-α correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6) characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1β were associated with successful IVF-induced pregnancy.Clinical and Developmental Immunology 01/2012; 2012:606459. · 1.84 Impact Factor