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Study Question: Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome?Summary Answer: Eleven genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome.What Is Known Already: The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs.Study Design Size, Duration: The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile.Participants/materials, Setting, Methods: Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ERβ, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples.Main Results and the Role Of Chance: Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway.Limitations Reasons For Caution: Small sample size and retrospective design.Wider Implications Of the Findings: The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals.Study Funding/competing Interest(s): Supported by Merck Serono an affiliate of Merck KGaA, Darmstadt, Germany (research grant for the laboratory session; Merck KGaA reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors). The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

BACKGROUND: In 2004, a law regulating assisted reproduction techniques (ART) was passed in Italy. The new rules allow for the formation and transfer of a maximum of three embryos at one time, whereas embryo selection and embryo storage are prohibited. The aim of this study is to evaluate the impact of these restrictions on ICSI outcome in couples affected by severe male factor infertility. [ABSTRACT FROM PUBLISHER]

The objective of this study was to evaluate the Doppler flow variations which occur following the use of different protocols of ovarian stimulation in an IVF programme, and to investigate the thromboxane production by cultured endometrial cells and its influence on embryo implantation. A total of 60 patients underwent three different ovarian stimulation protocols: long gonadotrophin-releasing hormone agonist (GnRH-a), short GnRH-a and no GnRH-a. Transvaginal ultrasonography and colour Doppler analysis were performed before and during the treatment. On the day that the Doppler examination took place, luteinizing hormone, follicle stimulating hormone, plasma oestradiol and thromboxane concentrations were assayed. On the day of oocyte retrieval, endometrial cells were collected and cultured, and their thromboxane production evaluated. No significant differences in hormonal, ultrasonographic or Doppler parameters were observed between the three groups. Ten out of 56 patients who had a successful embryo transfer became pregnant. In the group of pregnant women the pulsatility index values of both uterine and spiral arteries was lower than in non-pregnant patients, and was associated with significantly lower thromboxane concentrations from cultured endometrial cells. It is concluded that thromboxane plays a role in embryo implantation, and that Doppler flow analysis of uterine and spiral arteries in infertile patients may be important in the management of ovarian stimulation. [ABSTRACT FROM AUTHOR]

A consistent body of and evidence suggests that insulin-like growth factor-I (IGF-I) and possibly growth hormone (GH) play a stimulatory role in the regulation of the ovarian follicular cycle. Administration of GH in protocols of induction of superovulation gave promising results. In the present study, 10 patients with a previously normal response to gonadotrophins were administered s.c. GH-releasing factor (GRF) combined with gonadotrophins for superovulation induction in an in-vitro fertilization/embryo transfer-gamete intra-Fallopian transfer (IVF/ET-GIFT) programme. Administration of GRF was followed by shortening of the stimulatory cycle and reduction of the total number of gonadotrophin ampoules utilized per patient relative to a previous stimulatory cycle with gonadotrophins alone. A significant increase of both follicular fluid IGF-I levels (compared to the previous cycle) and plasma GH levels immediately following GRF administration throughout the GRF cycle suggest that GRF supported the ovarian response to gonadotrophins through stimulation of the GH-IGF-I axis. A possible direct effect of GRF is discussed. Before employing GRF for superovulation In infertile patients, the pituitary GH response to provocative stimuli should be evaluated on an individual basis. [ABSTRACT FROM PUBLISHER]

A patient with hypothalamic amenorrhoea and a poor response in terms of pituitary growth hormone (GH) to acute administration of growth hormone-releasing factor has been treated with pulsatile gonadotrophin-releasing hormone (GnRH) combined with GH to induce ovulation. GH was administered daily untilsigns of ovulation were detected. The luteal phase was supported by pulsatile GnRH only. Combined treatment gave an improved follicular recruitment, higher plasma levels of 17β-oestradiol and an earlier ovulation, compared to the previous cycle with pulsatile GnRH only. The result was a twin pregnancy which ended with the birth of two healthy male babies. The role of GH inpotentiating the ovarian response to gonadotrophins, as well as the GH secretion abnormalities associated with dysfunctions of the hypothalamic-pituitary-gonadal axis, might provide a rationale for combined GH and pulsatile GnRHtreatment in such patients. [ABSTRACT FROM PUBLISHER]