Urinary steroid profile in early pregnancy after in vitro fertilization.

OBJECTIVE: The aim of the study was to compare the levels of urinary steroid metabolites of patients with successful in vitro fertilization and patients who failed to achieve pregnancy. DESIGN: Comparison of urinary steroid profiles prior to oocyte pick-up and three weeks after embryo transfer. SETTING: University hospital. SAMPLE: Eleven women in the same age range with pregnancy after in vitro fertilization and eleven women who failed to achieve pregnancy. METHODS: The standard "long" protocol was used for ovarian stimulation and intracytoplasmic sperm injection for assisted in vitro fertilization. The steroid metabolites in urine samples collected for 24 h were determined by gas chromatography-mass spectrometry. MAIN OUTCOME MEASURES: Steroid metabolite levels in urine samples determined in the early pregnancy period. RESULTS: The levels of androsterone, etiocholanolone, pregnanediol, tetrahydro-11-dehydrocorticosterone and tetrahydro-corticosterone were significantly higher (p < 0.05) in the urine of women with successful pregnancy three weeks after the embryo transfer, while the levels of tetrahydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol and α-cortolone became higher in the group of patients with unsuccessful pregnancy. CONCLUSIONS: The production of androgens, progesterone and corticoid steroid metabolites is altered in the early pregnancy period after in vitro fertilization.

Akt/protein B and estradiol receptor alpha expressions in postmenopausal endometrium.

OBJECTIVE: Estrogen receptor interacts in several types of cells with phosphatidyl-inositol 3-kinase/Akt pathway regulating cell survival and apoptosis. No data are available of the Akt/PKB signaling and its role in the endometrial homeostasis of the postmenopausal uterus. The aim of the present investigation was to study the Akt/protein kinase B signaling in tissue samples retrieved from postmenopausal endometrium of the human uterus with parallel observation of the changes of the expression and phosphorylation of ERalpha. STUDY DESIGN: Sixty disease-free postmenopausal women were enrolled in the study. Endometrial tissue samples were obtained from diagnostic curettage or direct from the uterus after hysterectomy done for benign uterine lesions other than endometrial disease. For comparison, the studied parameters were also analyzed in endometrial samples of women with regular menstrual cycles (n=16). In each individual tissue sample the expression and phosphorylation of ERalpha, Akt, and cyclin D1 was analyzed by Western blotting. RESULTS: The level of Akt protein did not show significant change, however, the activation of Akt proteins and the expression of ERalpha increased parallel with serum estrogen (E2) levels, suggesting the role of E2 in Akt activation and ERalpha expression. The level of pERalpha(Ser167) changed parallel with pAkt(Ser473) levels. Significant correlation was found between the changes of pERalpha and ERalpha (r=0.650399, p<0.005), and in that of pERalpha and pAkt (r=0.639643, p<0.007), respectively. The expression of cyclin D1 was increased in samples with elevated pAkt levels. CONCLUSION: The results are indicating that the postmenopausal endometrium responds to E2 by both genomic and nongenomic mechanism. The interaction between ERalpha and Akt plays crucial role in the regulation of proliferative activity in postmenopausal endometrium.

Possible role of natural killer and natural killer T-like cells in implantation failure after IVF.

During implantation, maternal immunoactivation and tolerance are not only limited to the decidua but are also observed in the periphery, predominantly affecting the innate immune system. Since unexplained female infertility, as well as recurrent spontaneous abortion and implantation failure, are thought to be associated with pathological maternal immunotolerance mechanisms, this study focused on immune profile analysis of IVF candidates. Previous studies on peripheral natural killer (NK) cell characteristics of IVF patients have been limited to the comparison of blood samples taken prior to the IVF procedure. This study performed a follow-up study and compared patient's data obtained on the day of oocyte collection with the data 1 week after embryo transfer. The aim was to investigate phenotypic (subpopulations, CD69, T-cell immunoglobulin mucin 3 and NK-activating receptor expression) and functional (perforin and CD107a expression) changes in the peripheral NK and NK T (NKT)-like cell populations. During this short period of time around the IVF procedure, women with failed IVF reflected unfavourable Th1-oriented changes of NK and NKT-like cells. In comparison the follow-up data for women with successful conception remained principally constant. The observed peripheral changes during early pregnancy in the same individual may also have importance in successful embryo implantation.

Low-dose aspirin therapy to prevent ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the effect of low-dose aspirin therapy on ovarian hyperstimulation syndrome (OHSS) in an unselected group of patients undergoing in vitro fertilization (IVF). DESIGN: Randomized clinical trial. SETTING: Division of Reproductive Medicine at the Department of Obstetrics and Gynecology, University of Pécs, Faculty of Medicine, Pécs, Hungary. PATIENT(S): Patients who underwent IVF between 2000 and 2006. INTERVENTION(S): Initiation of 3154 IVF cycles, for which gonadotropin-releasing hormone agonist was used in 2425 cycles; 1503 cycles randomly selected for low-dose aspirin treatment starting from the first day of controlled ovarian hyperstimulation compared with no treatment in the remaining 922 cycles. MAIN OUTCOME MEASURE(S): The incidence of severe or critical OHSS and the rate of clinical pregnancy. RESULT(S): During this time period, 45 cases of severe OHSS were detected. Only two of the OHSS patients had received aspirin previously. CONCLUSION(S): Based on our preliminary results, introduction of low-dose aspirin therapy during ovulation induction for the prevention of OHSS in high-risk patients should be considered.

Involvement of FKHR (FOXO1) transcription factor in human uterus leiomyoma growth.

OBJECTIVE: To study the expression of FOXO1 and pSer256-FOXO1 parallel to Akt and pSer473-Akt in leiomyoma compared with adjacent myometrium from human uteri. DESIGN: Prospective study. SETTING: University departments. PATIENT(S): Thirty-eight cyclic and 20 menopausal women who underwent hysterectomy for benign indications. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Western blot analyses were used for evaluation in leiomyoma and adjacent myometrium of Akt and pSer473-Akt, 14-3-3 gamma proteins and expression and subcellular distribution of FOXO1 and pSer256-FOXO1 during the menstrual cycle and at menopause. RESULT(S): The present study demonstrates the expression of FOXO1 and pSer256-FOXO1 at the tissue level in the human uterus leiomyoma and adjacent myometrium. The level of phosphorylated FOXO1 in leiomyoma was higher than in matched myometrium. The pSer256-FOXO1 in leiomyoma during menstrual phases was located mostly in the nuclear fraction comparison to that of the myometrium. The reason for this difference is presumably the simultaneously detected lower level of 14-3-3 protein. CONCLUSION(S): Abundant level of the phosphorylated FOXO1, its impaired nucleocytoplasmic shuttling, and the lowered expression of 14-3-3 protein in leiomyoma induces a shift in the cellular machinery toward a prosurvival execution program and thus presents a potential therapeutic target for treatment of leiomyoma.