Release of sICAM-1 in Oocytes and In Vitro Fertilized Human Embryos

Background: During the last years, several studies have reported the significant relationship between the production of soluble HLA-G molecules (sHLA-G) by 48–72 hours early embryos and an increased implantation rate in IVF protocols. As consequence, the detection of HLA-G modulation was suggested as a marker to identify the best embryos to be transferred. On the opposite, no suitable markers are available for the oocyte selection. Methodology/Principal Findings: The major finding of the present paper is that the release of ICAM-1 might be predictive of oocyte maturation. The results obtained are confirmed using three independent methodologies, such as ELISA, Bio-Plex assay and Western blotting. The sICAM-1 release is very high in immature oocytes, decrease in mature oocytes and become even lower in in vitro fertilized embryos. No significant differences were observed in the levels of sICAM-1 release between immature oocytes with different morphological characteristics. On the contrary, when the mature oocytes were subdivided accordingly to morphological criteria, the mean sICAM-I levels in grade 1 oocytes were significantly decreased when compared to grade 2 and 3 oocytes. Conclusions/Significance: The reduction of the number of fertilized oocytes and transferred embryos represents the main target of assisted reproductive medicine. We propose sICAM-1 as a biochemical marker for oocyte maturation and grading

New perspectives for the treatment of pulmonary hypertension

Pulmonary hypertension (PH) is a debilitating disease with a poor prognosis. Therapeutic options remain limited despite the introduction of prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase 5 inhibitors within the last 15 years; these interventions address predominantly the endothelial and vascular dysfunctionS associated with the condition, but simply delay progression of the disease rather than offer a cure. In an attempt to improve efficacy, emerging approaches have focused on targeting the pro-proliferative phenotype that underpins the pulmonary vascular remodelling in the lung and contributes to the impaired circulation and right heart failure. Many novel targets have been investigated and validated in animal models of PH, including modulation of guanylate cyclases, phosphodiesterases, tyrosine kinases, Rho kinase, bone morphogenetic proteins signalling, 5-HT, peroxisome proliferator activator receptors and ion channels. In addition, there is hope that combinations of such treatments, harnessing and optimizing vasodilator and anti-proliferative properties, will provide a further, possibly synergistic, increase in efficacy; therapies directed at the right heart may also offer an additional benefit. This overview highlights current therapeutic options, promising new therapies, and provides the rationale for a combination approach to treat the disease

LH-Receptor Gene Expression in Human Granulosa and Cumulus Cells from Antral and Preovulatory Follicles

CONTEXT: Human granulosa cells (GC) acquire LH receptor (LHR) expression during the follicular phase of the menstrual cycle. Currently, the precise follicular stage is unknown, and specific roles of LH in the follicular development are not fully understood. OBJECTIVE: Our objective was to measure LHR gene expression on GC and cumulus cells (CC) from normal human follicles with diameters form 3–20 mm. DESIGN, SETTING, AND PATIENTS: At a university hospital, GC, CC, and the corresponding follicular fluid (FF) were collected from patients undergoing fertility preservation by having one ovary frozen and patients undergoing infertility treatment. INTERVENTIONS: Cells and fluids were isolated from surgically excised ovaries or from aspirated preovulatory follicles. MAIN OUTCOME MEASURES: We evaluated gene expression of LHR, FSHR, androgen receptor (AR), aromatase (CYP19a1), and AMHR2 normalized to the GAPDH expression and associated with FF levels of anti-Mullerian hormone, inhibin-B, and steroids. RESULTS: LHR expression was maximal in GC from preovulatory follicles before ovulation induction. A majority of 150 antral follicles (3–10 mm in diameter) showed LHR expression at approximately 10% of the maximum, and LHR expression showed significant associations with FSHR, AR, CYP19a1, and AMHR2 and with FF estradiol and progesterone. Levels of FSHR continued to decline in GC as the follicular diameter increased. CONCLUSIONS: The LHR gene is expressed in GC of human antral follicles throughout the follicular phase and is significantly associated with expression of the CYP19a1 gene and with the corresponding FF concentrations of estradiol and progesterone. LH appears to affect human follicular development during most the follicular phase in normal women

Clomiphene citrate versus high doses of gonadotropins for <it>in vitro</it> fertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial

Abstract Background The aim of the present randomised controlled non-inferiority trial is to test whether in women with compromised ovarian reserve requiring in vitro fertilisation, a protocol of ovarian stimulation using exclusively clomiphene citrate performs similarly to a regimen with high doses of gonadotropins. Methods Women with day 3 serum FSH > 12 IU/ml on at least two occasions or previous poor response to hyper-stimulation were recruited at four Italian infertility units. Selected women were allocated to clomiphene citrate 150 mg/day from day 3 to day 7 of the cycle (n=145) or to a short protocol with GnRH agonist 0.1 mg and recombinant FSH 450 IU daily (n=146). They were randomised by means of a computer-generated list into two groups. The study was not blinded. The main outcome of the study was the delivery rate per started cycle. Results The study was interrupted after the scheduled two years of recruitment before reaching the sample size. 148 women were allocated to clomiphene citrate and 156 to the short protocol with high doses of gonadotropins; 124 and 125 participants were analysed in the groups, respectively. Women allocated to high doses of gonadotropins retrieved more oocytes and had a higher probability to perform embryo-transfer. However, the chances of success were similar. The delivery rate per started cycle in women receiving clomiphene citrate and high-dose gonadotropins was 3% (n=5) and 5% (n=7), respectively (p=0.77). The mean estimated cost per delivery in the two groups was 81,294 and 113,107 Euros, respectively. No side-effects or adverse events were observed. Conclusions In women with compromised ovarian reserve selected for in vitro fertilisation, ovarian stimulation with clomiphene citrate or high-dose gonadotropins led to similar chances of pregnancy but the former is less expensive. Trial registration Trial registered on http://www.clinicaltrials.gov (NCT01389713)</p