This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P < 0.005) was identified in this study. Concentrations of progesterone below 50 nmol/l and above 99 nmol/l were associated with decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P < 0.001 and P = 0.002 for clinical pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates.

The role of growth hormone (GH) in human fertility is widely debated with some studies demonstrating improvements in oocyte yield, enhanced embryo quality, and in some cases increased live births with concomitant decreases in miscarriage rates. However, the basic biological mechanisms leading to these clinical differences are not well-understood. GH and the closely-related insulin-like growth factor (IGF) promote body growth and development via action on key metabolic organs including the liver, skeletal muscle, and bone. In addition, their expression and that of their complementary receptors have also been detected in various reproductive tissues including the oocyte, granulosa, and testicular cells. Therefore, the GH/IGF axis may directly regulate female and male gamete development, their quality, and ultimately competence for implantation. The ability of GH and IGF to modulate key signal transduction pathways such as the MAP kinase/ERK, Jak/STAT, and the PI3K/Akt pathway along with the subsequent effects on cell division and steroidogenesis indicates that these growth factors are centrally located to alter cell fate during proliferation and survival. In this review, we will explore the function of GH and IGF in regulating normal ovarian and testicular physiology, while also investigating the effects on cell signal transduction pathways with subsequent changes in cell proliferation and steroidogenesis. The aim is to clarify the role of GH in human fertility from a molecular and biochemical point of 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 in vitro 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.

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