The Evolving Concept of Poor-Prognosis for Women Undertaking IVF and the Notion of Growth Hormone as an Adjuvant; A Single-Center Viewpoint.

IVF is currently regarded as a successful new technology with the number of IVF children currently well over 8 million worldwide. This has been achieved by an explosive plethora of facilities. However, from its earliest history, IVF has been beset by poor-prognosis on a treatment cycle basis, an aspect which has been a constant feature for the majority of treatments to this stage.

The Concept of Growth Hormone Deficiency Affecting Clinical Prognosis in IVF.

The current understanding of human growth hormone (hGH; here GH) action is that the molecule is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. It can be classified as a protein (comprising more than 50 amino acids) but true proteins have tertiary and quaternary chains creating a more complex structure, hence GH is usually classified as a polypeptide. GH is normally secreted at night during sleep and promotes skeletal, visceral and general body growth through the action of somatomedins or IGFs, notably IGF-1.

Growth hormone during in vitro fertilization in older women modulates the density of receptors in granulosa cells, with improved pregnancy outcomes.

Objective: To study the effect of aging and granulosa cell growth hormone receptor (GHR) expression, and the effect of growth hormone (GH) co-treatment during IVF on receptor expression.

Design: Laboratory study.

Setting: University.

Granulosa Cell Apoptosis in the Ovarian Follicle-A Changing View.

Recent studies challenge the previous view that apoptosis within the granulosa cells of the maturing ovarian follicle is a reflection of aging and consequently a marker for poor quality of the contained oocyte. On the contrary, apoptosis within the granulosa cells is an integral part of normal development and has limited predictive capability regarding oocyte quality or the ensuing pregnancy rate in fertilization programs. This review article covers our revised understanding of the process of apoptosis within the ovarian follicle, its three phenotypes, the major signaling pathways underlying apoptosis as well as the associated mitochondrial pathways.

Involvement of Bone Morphogenetic Proteins (BMP) in the Regulation of Ovarian Function.

Primordial germ cells migrate to the fetal gonads and proliferate during gestation to generate a fixed complement of primordial follicles, the so-called ovarian reserve. Primordial follicles comprise an oocyte arrested at the diplotene stage of meiosis, surrounded by a layer of pregranulosa cells. Activation of primordial follicles to grow beyond this arrested stage is of particular interest because, once activated, they are subjected to regulatory mechanisms involved in growth, selection, maturation, and ultimately, ovulation or atresia.

The effect of ovarian reserve and receptor signalling on granulosa cell apoptosis during human follicle development.

The poor oocyte quality in older women has previously been linked to the depletion of the ovarian reserve of primordial follicles and an increase in granulosal apoptosis. Granulosa cells were collected from 198 follicles and individually analysed by flow cytometry. In the young IVF patients, the level of apoptosis was inversely proportional to the expression of bone morphogenetic protein (BMPR1B) and follicle stimulating hormone (FSH) receptors.

Infertility and ovarian follicle reserve depletion are associated with dysregulation of the FSH and LH receptor density in human antral follicles.

The low take-home baby rate in older women in Australia (5.8%) undergoing IVF (5.8%) is linked to the depletion of the ovarian reserve of primordial follicles.

Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility.

Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry.

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep.

The aim of the present study was to determine the direct cause of the mutation-induced, increased ovulation rate in Booroola Merino (BB) sheep. Granulosa cells were removed from antral follicles before ovulation and post-ovulation from BB (n=5) and WT (n=12) Merino ewes. Direct immunofluorescence measurement of mature cell surface receptors using flow cytometry demonstrated a significant up-regulation of FSH receptor (FSHR), transforming growth factor beta type 1, bone morphogenetic protein receptor (BMPR1B), and LH receptor (LHR) in BB sheep.