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.

Reduced in-vitro fertilization of human oocytes from patients with raised basal luteinizing hormone levels during the follicular phase 58, 203-212. Vandenberg, J . L. & Y e n , S. S. (1973) Effect of antioestrogenic action of clomiphene during the menstrual cycle: evidence for a change in the feedback sensitivity. J Clipl Endocrind Mercrh 37, 356-365. Whittingham, D . (1971) Culture of mouse ova. J Reprod Fertil 14, [Suppl.] 7-21,

In a sequential crossover study of IVF conducted from 2002 to 2006, growth hormone (GH) supplementation was assessed in poor-prognosis patients, categorized on the basis of past failure to conceive (mean 3.05 cycles) due to low response to high-dose stimulation (<3 metaphase II oocytes) or poor-quality embryos. Pregnancy rates in both fresh and frozen transfer cycles and the total productivity rates (fresh and frozen pregnancies per egg collection) were compared. In all, 159 patients had 488 treatment cycles: 221 with GH and 241 without GH. These cycles were also compared with 1572 uncategorized cycles from the same period. GH co-treatment significantly improved the clinical pregnancy rate per fresh transfer (P<0.001) as well as per frozen-thawed embryo derived from GH cycles (P<0.05) creating a highly significant productivity rate (P<0.001). The effect was significant across all age groups, especially in younger patients, and was independent of stimulation modality or number of transfers. GH cycles resulted in significantly more babies delivered per transfer than non-GH cycles (20% versus 7%; P<0.001) although less than the uncategorized cycles (53%). The data uniquely show that the effect of GH is directed at oocyte and subsequent embryo quality.

Declining female fecundity at later age and the increasing tendency for women to delay childbirth have lead to a drastic rise in the number of women seeking assisted reproductive technology. Many women fail to respond adequately to standard ovarian stimulation regimens, raising a significant therapeutic challenge. Recently, we have demonstrated that the administration of GH, as an adjunct to ovarian stimulation, has improved the clinical outcomes by enhancing the oocyte quality. However, the mechanism(s) by which GH facilitated this improvement is yet to be understood. This study aimed to determine these potential mechanism(s) through the use of immunofluorescent localisation of GH receptors (GHRs) on the human oocyte and unbiased computer-based quantification to assess and compare oocyte quality between women of varying ages, with or without GH treatment. This study demonstrates for the first time, the presence of GHRs on the human oocyte. The oocytes retrieved from older women showed significant decrease in the expression of GHRs and amount of functional mitochondria when compared with those from younger patients. More interestingly, when older patients were treated with GH, a significant increase in functional mitochondria was observed in their oocytes. We conclude that GH exerts a direct mode of action, enabling the improvement of oocyte quality observed in our previous study, via the upregulation of its own receptors and enhancement of mitochondrial activity. This result, together with recent observations, provides scientific evidence in support of the use of GH supplementation for the clinical management of poor ovarian response.

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PIVET Medical Centre has developed an empirical algorithm for the dose of FSH administration based upon day-2 FSH, antral follicle count, anti-Müllerian hormone, body mass index, age and smoking parameters in an attempt to reduce the incidence of ovarian hyperstimulation syndrome particularly in at-risk women with elevated antral follicle count and anti-Müllerian hormone. The algorithm utilized the incremental dosage capabilities of the recombinant FSH pens to fine-tune the daily concentration of FSH. Application of the algorithm aimed to minimize any form of excessive follicle recruitment that necessitated increased clinical awareness. The measure used to assess the impact of the algorithm was the number of women who, after oocyte retrieval, were considered to be potentially at risk of any degree of OHSS and were allocated to increased monitoring. Compared with the previous 20-month period, introduction of the algorithm significantly reduced both the incidence of referral for increased monitoring, treatment for OHSS and the incidence of freeze-all cycles (all P < 0.05). This was particularly focused on those considered to be at risk without reducing the fresh cycle pregnancy rate.