Progesterone-induced Blocking Factor Concentrations Research Articles

Progesterone induced blocking factor (PIBF) taken in early pregnancy predicts the pregnancy outcome in women undergoing in vitro fertilization procedure

Earlier data suggest a relationship between PIBF concentrations and the outcome of pregnancy. The aim of the study was to compare serum and urine concentrations of PIBF in women with successful pregnancy after IVF with those of women without pregnancy after IVF procedure, and to evaluate the potential relation between PIBF and the outcome of pregnancy. Urine and serum were collected from 120 women, undergoing IVF. 87.5% of patients had primary infertility. 69.2% faced female causes of infertility: 10.8% tubal cause, 11.7% ovulation disorder, and 46.7% other causes of infertility. 30.8% of patients had male factor of infertility. Among non-pregnant women (42) mean concentrations of PIBF in urine and serum were significantly lower (15.8 ng/mL; 148.4 ng/mL) than in women with positive beta HCG value (78) (19.1 ng/mL; 225.9 ng/mL). In 49 patients pregnancy terminated with a term delivery, in 10 patients with pretem delivery, while in 19 patients the pregnancy terminated with a miscarriage. PIBF concentrations in urine (13.9 ± 2.8 ng/mL) and serum (124.6 ± 46.7 ng/mL) samples of women with miscarriage were significantly lower of those with preterm delivery (180.6 ± 54.4 ng/mL; 18.1 ± 4.4 ng/mL) and of those with term delivery (20.4 ± 8.5 ng/mL; 208.7 ± 114.3 ng/mL). Successful pregnancy after IVF procedure is predictable by measuring of urine and serum PIBF concentrations and could be important for predicting of early implantation and pregnancy outcome after IVF procedure and maybe to protect the risk pregnancy.

Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women

Progesterone-induced blocking factor (PIBF), which plays an important role in maintaining healthy pregnancies, has shown great promise as a prognostic biomarker for threatened miscarriage. To better characterise the physiological trends of progesterone and PIBF, we analysed serum progesterone and PIBF concentrations in healthy non-pregnant and pregnant women across trimesters. We saw increasing concentrations of progesterone and PIBF in pregnant women with advancing trimesters. The serum progesterone and PIBF percentiles across gestational age in healthy pregnancies can be used as a guide for the formulation of reference ranges. We also demonstrated a significant positive correlation between progesterone and PIBF levels. This study demonstrates increasing progesterone and PIBF concentrations in later trimesters and underscores the importance of progesterone and PIBF in healthy pregnancies. Characterisation of progesterone and PIBF across gestational age in healthy pregnant women may help to prognosticate pregnancy viability and support further research into the importance of progesterone and PIBF in the maintenance of healthy pregnancies.

Maternal serum progesterone-induced blocking factor (PIBF) in the prediction of preterm birth

The objective of this study was to analyze the maternal serum concentration of progesterone-induced blocking factor (PIBF) with regard to the prediction and the interval between sampling and the onset of preterm birth. A prospective study was conducted on a sample of 37 women with threatened pre-term birth and 41 healthy pregnant women between the 24th and 28th gestational weeks. Out of 37 patients with threatened preterm birth 11 delivered pre-term and three groups of patients were formed: the preterm delivery group, patients with threatened preterm delivery, and healthy pregnant women. In samples that were taken within 5 days before labor started (6/11, 54.5%), PIBF concentrations were significantly lower than in those obtained more than 5 days before labor (5/11, 45.5%; the mean interval between sampling and the onset of labor was 4.1±1.8 days). Multiple regression analysis of the individual contributions of each observed parameter for preterm delivery demonstrated the significant contribution of a lack of PIBF to preterm birth (p=0.002). Receiver operating characteristics (ROC) analysis was performed to evaluate the diagnostic accuracy of PIBF for the prediction of preterm birth of women with symptoms of pre-term delivery. The PIBF demonstrated an excellent diagnostic value in the prediction of preterm birth with an area under the ROC curve (AUC) of 0.956 (95% CI=0.884–0.989; p<0.0001). Our data suggest that pregnancy termination can be predicted by lower than normal pregnancy PIBF values within 5 days before labor and can contribute to the diagnosis of preterm birth.

Changes of Progesterone-Induced Blocking Factor in Patients After Kidney Transplantation

The prediction of graft rejection can play an important part in graft survival. Analysis of immune reactions has shown that graft rejection shares mechanisms with recurrent abortions during pregnancy. Progesterone-induced blocking factor (PIBF), a mediator of progesterone that blocks natural killer cell activity in peripheral blood, produces antiabortive effects. The aim of this study was to examine the PIBF concentration in the urine of transplanted recipients. The study included 116 white adults (70 men and 46 women) of median age 49.3 years, who had undergone kidney transplantations. The median duration after transplantation was 3.46 years. The average period between renal disease and our measurement was 12.3 years, and the median interval between graft rejection and our study was 1.75 years. Urine samples were used to measure PIBF concentrations by an enzyme-linked immunsorbent assay. PIBF urinary concentrations decreased significantly in patients who experienced ≥1 rejection episode (31.8 ± 2.2 ng/mL) compared with those without any episode (22.7 ± 1.2 ng/ml; P < .01). Moreover, the urinary PIBF level was significantly lower among patients who had increased creatinine and urea nitrogen levels in blood samples ( P < .05 and P < .01, respectively). Decreased PIBF values in kidney transplant patients followed previous rejection episodes. A close negative correlation was observed between urinary PIBF concentrations and blood levels of creatinine and urea nitrogen. These findings suggested that PIBF detection may predict graft rejection in transplant recipients.

Dydrogesterone supplementation in women with threatened preterm delivery—the impact on cytokine profile, hormone profile, and progesterone-induced blocking factor

Progesterone is indispensable in creating a suitable endometrial environment for implantation, and also for the maintenance of pregnancy. Successful pregnancy depends on an appropriate maternal immune response to the fetus. A protein called progesterone-induced blocking factor (PIBF) acts by inducing Th2-dominant cytokine production to mediate the immunological effects of progesterone. The aim of this prospective study was to compare serum concentrations of progesterone (P), estradiol (E2), anti-inflammatory (IL-10) and pro-inflammatory (IL-6, TNFα, IFNγ) cytokines, and serum PIBF concentrations in women with threatened preterm delivery who were given progesterone supplementation (study group) with those of women with threatened preterm delivery who were not given progesterone supplementation (control group). After dydrogesterone treatment of patients in the study group, serum PIBF as well as progesterone concentrations significantly increased. Women in this group had significantly higher serum levels of IL-10 than controls. The length of gestation was significantly higher in the group of women who were given progesterone supplementation. Our data suggest that dydrogesterone treatment of women at risk of preterm delivery results in increased PIBF production and IL-10 concentrations, and lower concentrations of IFNγ.

ORIGINAL ARTICLE: Progesterone‐Induced Blocking Factor and Cytokine Profile in Women with Threatened Pre‐Term Delivery

Problem The objective of this study was to compare serum concentrations of progesterone‐induced blocking factor (PIBF), anti‐inflammatory (IL‐10), and pro‐inflammatory (IL‐6, TNFα, and IFNγ) cytokines of women with threatened pre‐term delivery, with those of women with normal pregnancy and to evaluate the impact of PIBF on the outcome of pregnancy.Method of study A prospective study was conducted on a sample of 30 women with threatened pre‐term delivery (study group) and 20 healthy pregnant women (control group) between the 24th and 37th gestational weeks. Serum PIBF, anti‐inflammatory (IL‐10), and pro‐inflammatory (IL‐6, TNFα, and IFNγ) cytokine concentrations were measured by enzyme‐linked immunosorbent assay (ELISA).Results Thirteen of 30 patients (43.3%) with symptoms of threatened pre‐term delivery, and one of 20 patients (5%) in the control group delivered before the 37th week of gestation. Mean PIBF concentrations in serum samples of patients with threatened pre‐term delivery were significantly lower than in those of healthy pregnant women (171.12 ± 162.06 ng/mL versus 272.85 ± 114.87 ng/mL; P &lt; 0.05). Women with symptoms of threatened pre‐term delivery had significantly lower serum levels of IL‐10, and higher levels of IL‐6 as well as IFNγ compared with healthy controls.Conclusion Our results indicate that measuring PIBF and cytokine concentrations in serum during pregnancy is feasible and may be important for understanding immunological causes of pre‐term delivery.

Effect of dydrogesterone on the hormonal profile and concentration of progesterone-induced blocking factor in pregnant women with threatened abortion

Problem: The therapeutic value of progestogens in threatened abortion is still under debate. In the presence of sufficient progesterone levels during pregnancy, lymphocytes synthesize a mediator [progesterone-induced blocking factor (PIBF)] that is anti-abortive in mice. The aim of this study was to evaluate the effect of dydrogesterone on pregnancy outcome of threatened aborters.&#x0D; Method of study: Twenty-seven threatened aborters were treated for 10 days with dydrogesterone (30-40 mg/day). Sixteen healthy pregnant controls received no treatment. Serum progesterone and estradiol concentrations as well as urine PIBF concentrations were measured by enzyme-linked immunosorbent assay (ELISA).&#x0D; Results: Pregnancy outcomes in dydrogesterone-treated threatened aborters did not statistically differ from those in healthy controls. Serum progesterone concentrations in control patients, but not those in threatened aborters increased as pregnancy progressed. Following dydrogesterone treatment, initially low PIBF concentrations of threatened aborters significantly increased (P = 0,001) to reach the PIBF level found in healthy controls.

The Impact of Dydrogesterone Supplementation on Hormonal Profile and Progesterone‐induced Blocking Factor Concentrations in Women with Threatened Abortion

The therapeutic value of progestogens in threatened abortion is still under debate. In the presence of sufficient progesterone levels during pregnancy, lymphocytes synthesize a mediator [progesterone-induced blocking factor (PIBF)] that is anti-abortive in mice. The aim of this study was to evaluate the effect of dydrogesterone on pregnancy outcome of threatened aborters. Twenty-seven threatened aborters were treated for 10 days with dydrogesterone (30-40 mg/day). Sixteen healthy pregnant controls received no treatment. Serum progesterone and estradiol concentrations as well as urine PIBF concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Pregnancy outcomes in dydrogesterone-treated threatened aborters did not statistically differ from those in healthy controls. Serum progesterone concentrations in control patients, but not those in threatened aborters increased as pregnancy progressed. Following dydrogesterone treatment, initially low PIBF concentrations of threatened aborters significantly increased (P = 0.001) to reach the PIBF level found in healthy controls. These data suggest that by inducing PIBF production, dydrogesterone might improve pregnancy success rates in threatened aborters.

Urinary progesterone-induced blocking factor concentration is related to pregnancy outcome.

Peripheral lymphocytes from healthy pregnant women secrete a mediator protein named the progesterone-induced blocking factor (PIBF) that exerts an immunomodulatory function and contributes to the maintenance of pregnancy in mice. The gene coding for PIBF mRNA has been cloned and sequenced, and now the recombinant human protein is available. The aim of this study was to develop an ELISA test for determining PIBF concentrations in biological samples of pregnant women. We determined urinary PIBF concentrations of 86 healthy nonpregnant individuals and from almost 500 pregnant women by ELISA. During normal pregnancy, the concentration of PIBF continuously increased until the 37th gestational week and was followed by a sharp decrease after the 41st week of gestation. In pathological pregnancies, urinary PIBF levels failed to increase. The onset of labor was predictable on the basis of this test, whether it was term or preterm delivery. In urine of patients with preeclampsia, PIBF concentrations were significantly lower than in normal pregnancy and showed a correlation with the number of symptoms presented. These data, in line with previous in vivo findings, suggest that PIBF production is a characteristic feature of normal pregnancy, and determination of PIBF concentration in urine might be of use for the diagnosis of threatened premature pregnancy termination.