March 2022 · Volume 11 · Issue 3 Page 859 International Journal of Reproduction, Contraception, Obstetrics and Gynecology Kishore K et al. Int J Reprod Contracept Obstet Gynecol. 2022 Mar;11(3):859-863 www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789 Original Research Article Association of serum cytokines IL-6, TNF-α, PTX-3 and progesterone modulation in cases of recurrent pregnancy loss Kamal Kishore 1 , Sanjay Sharma 2 , Lavan Singh 3 , Manisha Agarwal 4 , Reema Bhatt 5 * INTRODUCTION Recurrent pregnancy loss (RPL) is a common clinical reproductive problem, described as the occurrence of 2 or 3 consecutive miscarriages prior to 20 th week of the gestation. 1 The causes of RPLs are diverse including immune, endocrine, parental and fetal genetic and epigenetic factors, metabolic malfunctions, infection factors, anatomic abnormalities and other unknown factors. Despite this, 50% of the patients who undergo a complete evaluation remain clueless as to the etiology. 2 Pregnancy is a state of immune suppression. Recently, the contribution of immunomodulatory factors (cytokines) to the etio-pathology of RPL have been recognised. 3 Immune response in RPL is mainly the imbalance of immune suppression and immune tolerance. Th1 cytokines exert pro-inflammatory effect (TNF-α, DOI: https://dx.doi.org/10.18203/2320-1770.ijrcog20220569 1 Department of Paedtric Surgery, 3 Department of Pathology, 5 Army Hospital Research and Referral, Delhi, India 2 Department of Obstetrics and Gynecology, AFMC Pune, Maharashtra, India 4 Department of Pathology, Command hospital Eastern Command, West Bengal, India Received: 14 January 2022 Revised: 09 February 2022 Accepted: 10 February 2022 *Correspondence: Dr. Reema Bhatt, E-mail: reemakamalbhatt@yahoo.co.in Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background: Cytokines are major immune regulators, which play a critical role in the pathophysiology of unexplained recurrent pregnancy loss. Th1 class of cytokines has been shown to exert deleterious effects on pregnancy causing early loss. Methods: The changeover in the levels of Th1 cytokines was studied in two major groups; Gp I (N=30) comprised of RPL subjects with two or more consecutive spontaneous miscarriages history and Gp II (N=30) comprised of normal pregnancy controls .The efficacy of oral micronized progesterone was assessed in regulation of cytokine levels ,with Gp Ia (N=15) treated with 200 mg oral micronized progesterone and Gp Ib (N=15) comprised of untreated RPL subjects and its role in improving pregnancy outcome was also determined. The present study determined the levels of cytokine TNF-α, IL-6 and PTX-3 in serum samples for all the subjects at three time points at the time of enrolment, with (GpIa) or without (Gp Ib) progesterone administration at 20 weeks or abortion if earlier and at the time of delivery. Results: The results indicated that the levels of Th1 cytokines (TNF-α [37.80 versus 78.09], IL-6 [16.93 versus 81.12] and PTX-3 [17.42 versus 73.53]) was found to be reduced at every time point in the treated cases with an RPL history as compared to untreated ones. Further, the cases treated with with oral micronized progesterone were found to have better pregnancy outcomes (p<0.005 significant number of live births). Conclusions: The levels of interlukins, TNF-α, IL-6, PTX-3 in cases of RPL may not have a major contributory role in predicting outcome, however exogenous progesterone decreases the Th1 pro inflammatory response and efficiently improves the pregnancy outcomes by modulation of cytokine levels. Keywords: Recurrent pregnancy loss, Th immunity, TNF-α, IL-6, PTX-3, Oral micronized progesterone