Early Pregnancy Loss - the role of Progesterone-Induced Blocking Factor (PIBF)

Nina Davidova, Lali Pkhaladze, Nana Kvashilava, Archil Khomasuridze

Abstract


Background and purpose: Pregnancy loss (PL) is one of the significant issues of reproductology. It seems to be a purely immunological phenomenon, which concerns especially the first weeks of gestation. Embrioprotective factors are activated from the first day of pregnancy. One is progesterone-produced blocking factor (PIBF), which maintains the pregnancy.

Aim: To assess the diagnostic value of PIBF in early pregnancy and compare it to Progesterone (PG) and beta-human chorionic gonadotropin (βhCG), and also to find the correlation between PIBF and PG, PIBF and βhCG.

Methods: 31 women, aged 18-35 (28.77±6.41), with one or more PL in anamnesis, were divided into three groups: Group I – patients with term delivery (n=11); Group II- patients, with miscarriage after delaying of menstruation (n=10); Group III – patients with miscarriage before delaying of menstruation (n=10). PIBF and progesterone levels were measured on the 7-8th day after ovulation. PG and βhCG were assessed on the 26th-27th of the menstrual cycle. All these factors were measured using the ELISA method. Data analysis was performed using SPSS software package version 26.0 for Windows.

Results: The mean PIBF level was not significantly different between groups II and III (10.3 ± 4.7 ng/ml and 10.1 ± 5.5 ng/ml) p>0.05. A statistically significant difference was found in the mean PG level between group II and group III (p<0.001). βhCG was significantly high in groups I and II compared to group III (79.97 ± 19.79 vs 46.90 ± 8.70 ng/ml), p<0.05.

PIBF level turned out to be more informative than the PG level in women with pregnancy loss. While PG and βhCG are more informative diagnostic of progressive pregnancy.

Conclusions: PIBF may be considered a possible prognostic marker of PL and even of Early Pregnancy Loss (EPL).

Keywords


Early pregnancy loss; Progesterone-induced blocking factor (PIBF); Miscarriage; Immunity of pregnancy; Progesterone (PG).

Full Text:

PDF

References


Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Medicine. 2013.

Laškarin G, Tokmadži VS, Štrbo N, Bogovi T, Szekeres-Bartho J, Randi L, et al. Progesterone induced blocking factor (PIBF) mediates progesterone induced suppression of decidual lymphocyte cytotoxicity. American Journal of Reproductive Immunology. 2002;

Cohen RA, Check JH, Dougherty MP. Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF). J Assist Reprod Genet. 2016;

Lachmann M, Gelbmann D, Kálmán E, Polgár B, Buschle M, Von Gabain A, et al. PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome. Int J Cancer. 2004;

De La Haba C, Palacio JR, Palkovics T, Szekeres-Barthó J, Morros A, Martínez P. Oxidative stress effect on progesterone-induced blocking factor (PIBF) binding to PIBF-receptor in lymphocytes. Biochim Biophys Acta Biomembr. 2014 Jan 1;1838(1 PARTB):148–57.

Check JH, Arwitz M, Gross J, Szekeres-Bartho J, Wu CH. Evidence that the expression of progesterone-induced blocking factor by maternal T-lymphocytes is positively correlated with conception. American Journal of Reproductive Immunology. 1997;38(1):6–8.

Szekeres-Bartho J, Polgar B. PIBF: The Double Edged Sword. Pregnancy and tumor. American Journal of Reproductive Immunology. 2010.

Szekeres-Bartho J, Kilar F, Falkay G, Csernus V, Török A, Pacsa AS. The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: I. Progesterone-treated lymphocytes release a substance inhibiting cytotoxicity and prostaglandin synthesis. American Journal of Reproductive Immunology and Microbiology. 1985;

Hudić I, Fatušić Z, Szekeres-bartho J, Balić D, Polgar B, Ljuca D, et al. Progesterone-induced blocking factor and cytokine profile in women with threatened pre-term delivery. American Journal of Reproductive Immunology. 2009;

Hudić I, Szekeres-Bartho J, Stray-Pedersen B, Fatušić Z, Polgar B, Ećim-Zlojutro V. Lower Urinary and Serum Progesterone-Induced Blocking Factor in Women with Preterm Birth. J Reprod Immunol. 2016;

Szekeres-Bartho J, Kilar F, Falkay G, Csernus V, Török A, Pacsa AS. The mechanism of the inhibitory effect of progesterone on lymphocyte cytotoxicity: I. Progesterone-treated lymphocytes release a substance inhibiting cytotoxicity and prostaglandin synthesis. American Journal of Reproductive Immunology and Microbiology. 1985;

Check JH, Szekeres-Bartho J, O’Shaughnessy A. Progesterone induced blocking factor seen in pregnancy lymphocytes soon after implantation. American Journal of Reproductive Immunology. 1996;

Check JH, Szekeres-Bartho J, Nazari P, Katz Y, Check ML. A corpus luteum is nota prerequisite for the expression of progesterone induced blocking factor by T-lymphocytes a week after implantation. J Assist Reprod Genet. 2001;18(11):603–7.

Rafiee M, Rezaei A, Alipour R, Sereshki N, Motamedi N, Naseri M. Progesterone-induced blocking factor (PIBF) influences the expression of membrane progesterone receptors (mPRs) on peripheral CD4+ T lymphocyte cells in normal fertile females. Hormones. 2021;

Madendag Y, Sahin E, Madendag IC, Sahin ME, Acmaz G, Karaman H. High immune expression of progesterone-induced blocking factor in epithelial ovarian cancer. Technol Cancer Res Treat. 2018;

Polgár B, Nagy E, Mikó E, Varga P, Szekeres-Barthó J. Urinary Progesterone-Induced Blocking Factor Concentration Is Related to Pregnancy Outcome1. Biol Reprod. 2004 Nov 1;71(5):1699–705.

Kalinka J, Szekeres-Bartho J. The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion. American Journal of Reproductive Immunology. 2005;

Beta J, Szekeres-Bartho J, Skyfta E, Akolekar R, Nicolaides KH. Maternal serum progesterone-induced blocking factor at 11-13 weeks’ gestation in spontaneous early preterm delivery. Fetal Diagn Ther. 2011;

Miko E, Halasz M, Jericevic-Mulac B, Wicherek L, Arck P, Arató G, et al. Progesterone-induced blocking factor (PIBF) and trophoblast invasiveness. J Reprod Immunol. 2011 Jun 1;90(1):50–7.

Lim MK, Ku CW, Tan TC, Lee YHJ, Allen JC, Tan NS. Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women. Sci Rep. 2020 Dec 1;10(1):1–9.

Hudic I, Szekeres-Bartho J, Vrtacnik EB, Klun IV, Brkic S, Frangez HB, et al. Progesterone induced blocking factor (PIBF) taken in early pregnancy predicts the pregnancy outcome in women undergoing in vitro fertilization procedure. J Reprod Immunol. 2020;

1 in 6 people globally affected by infertility: WHO [Internet]. [cited 2023 Aug 3]. Available from: https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-infertility

Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLoS Med. 2012 Dec 18;9(12):e1001356.

Chaubey L, B. Singh , T, Kaithwas K, Doharey N, Chowdary Peddappolla S. Risk factors associated with primary and secondary infertility in eastern part of north India: A pilot study. The Journal of Community Health Management. 2020 Dec 28;5(4):188–91.

Borumandnia N, Alavi Majd H, Khadembashi N, Alaii H. Worldwide trend analysis of primary and secondary infertility rates over past decades: A cross-sectional study. International Journal of Reproductive BioMedicine (IJRM). 2022 Feb 18;37–46.

Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Medicine. 2013.

Buckett W, Sierra S. The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019 Oct;39(4):633–40.

Hudić I, Fatušić Z, Szekeres-bartho J, Balić D, Polgar B, Ljuca D, et al. Progesterone-induced blocking factor and cytokine profile in women with threatened pre-term delivery. American Journal of Reproductive Immunology. 2009;

Check JH, Arwitz M, Gross J, Szekeres-Bartho J, Wu CH. Evidence that the expression of progesterone-induced blocking factor by maternal T-lymphocytes is positively correlated with conception. American Journal of Reproductive Immunology. 1997;38(1):6–8.

Lim MK, Ku CW, Tan TC, Lee YHJ, Allen JC, Tan NS. Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women. Sci Rep [Internet]. 2020 Dec 1 [cited 2021 Apr 25];10(1):1–9. Available from: https://www.nature.com/articles/s41598-020-59452-y

Hudic I, Szekeres-Bartho J, Vrtacnik EB, Klun IV, Brkic S, Frangez HB, et al. Progesterone induced blocking factor (PIBF) taken in early pregnancy predicts the pregnancy outcome in women undergoing in vitro fertilization procedure. J Reprod Immunol. 2020;


Refbacks

  • There are currently no refbacks.




 

Become a REVIEWER 

 

ISSN: 2346-8491 (online)