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Diabetes & Obesity International Journal Research Article 5 min read

The Pro-Inflammatory and Anti-Inflammatory Cytokines as Key Tool for Infertility Linked PCOS Diagnosis and Treatment Efficacy

Rafik Ragheb*
* Corresponding author
ISSN: 2574-7770  10.23880/doij-16000197  Received: April 10, 2019  Published: April 13, 2019
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Keywords
Anti-Inflammatory Pro-Inflammatory Infertility Infertility
Abstract

Polycystic Ovary Syndrome (PCOS) and PCOS related ovarian dysfunction are the main causes of anovulatory infertility.

Editorial

Polycystic Ovary Syndrome (PCOS) and PCOS related ovarian dysfunction are the main causes of anovulatory infertility. POCS is estimated to have prevalence as it represents 20%-33% in the general population [1]. There is variation in the prevalence of PCOS as reported 15-20% in other publications based on the diagnostic criteria followed [2]. The pathophysiology of this syndrome is still not completely understood as it has not being addressed clearly. The result of initial autopsies of placenta from women with PCOS has shown macroscopic and microscopic alteration in comparison to healthy control group.

At the molecular level, it has been extremely difficult to pin down the genes responsible for PCOS. Data from Genome wised Association Studies (GWAS) results showed, The DENND1A (Differentially Expressed in Normal and Neoplastic Development isoform A1) gene was identified as a potential risk marker. McAllister’s group showed that DENND1A.V2 protein is more expressed in PCOS theca cells compared to normal theca cells that subsequently resulting in increased androgen biosynthesis. It has been proven that the DENND1A variant 2 is potentially one of the mechanisms involved with the intrinsic abnormality in ovarian theca cells steroidogenesis in PCOS [3].

Among the current challenges, it has been reported that infertility affects 40% of women with PCOS [4]. PCOS is reported as the most common cause of anovulatory infertility. It is estimated that 90%–95% of anovulatory women presenting to infertility clinics have PCOS. PCOS women show a normal number of primordial follicles and The Pro-Inflammatory and Anti-Inflammatory Cytokines as Key Tool for Infertility Linked PCOS Diagnosis and Treatment Efficacy primary and secondary follicles are increased significantly. Because of the derangements in factors involved during normal follicular development, its growth gets impacted. The follicular growth becomes arrested as the follicles reach a diameter ranging between 4 to 8 mm. As a result, the dominant follicle does not develop and the ovulation does not ensue [5]. Further, spontaneous abortion incidences occur more frequently in PCOS ranging from 42%-73% [6, 7].

In addition, PCOS women who are manifested with obesity, hyperandrogenism and insulin resistance are less likely to respond to the common treatment protocols. This is to suggest that extra factors could be prominent causes for the pathophysiology of the disease. Given the multifaceted pathogenesis of PCOS, the disease is considered as a heterogeneous disease characterized by chronic oligoanovulation as manifested by clinical and biochemical dysregulation [8, 9, 10].

A growing body of evidences have demonstrated that PCOS is a low grade pro-inflammatory state. Furthermore, a strong body of literature has shown that the Pro- inflammatory cytokines were found to be elevated in PCOS women [11, 12, 13]. Cytokines are directly involved in maintaining the delicate balance of hypothalamo-pituitary overian axis and the maintenance of normal menstrual cycles [14]. This is to highlight the importance of performing the cytokine panel test as a screening and monitoring tool during the course of treatment.

The Pro-inflammatory cytokine, interleukin (IL)-1 activates the hypothalamus-pituitary-adrenal (HPA) axis Diabetes Obes Int J

[15]. HPA axis controls adrenal steroidogenesis and metabolic factors including insulin and obesity related signals [16]. Also, IL-6, TNFα and MCP-1 were found to have a high statistical significance in PCOS women [1, 17].

The focus of this short editorial review is to address the importance for measuring the two sets of cytokines, the Pro-inflammatory and Anti-inflammatory. The cytokine array/ panel measurements can be performed by using a very small blood sample as a screening diagnostic tool. The cytokine panel testing will be a key and diagnostic tool monitoring during the protocol used for PCOS treatment with the support of the hormonal testing conducted routinely.

References

  1. Shafiq H Hussein Al-Musawy, Ihsan E Al-Saimary, Maysoon Sheril Flaili (2018) Level of Cytokines in Polycystic Ovary Syndrome. The Medical Journal of Babylon 15(2): 124-128.
  2. Palomba S, Russo T, Falbo A, Di Cello A, Tolino A, et al. (2013) Macroscopic and microscopic findings of the placenta in women with polycystic ovary syndrome. Human Reproduction 28(10): 2838-2847.
  3. Rosenfield RL, Ehrmann DA (2016) The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism. Endocr Rev 37(5): 467-520.
  4. Teede H, Deeks A, Moran L (2010) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 8: 41.
  5. Brassard M, AinMelk Y, Baillargeon JP (2008) Basic infertility including polycystic ovary syndrome. Med Clin North Am 92(5): 1163-1192.
  6. Glueck C, Phillips H, Cameron D, Sieve-Smith L, Wang P (2001) Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril 75(1): 46-52.
  7. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts K, Nestler JE (2002) Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 87(2): 524-529.
  8. Fauser BC, Diedrich K, Devroey P Evian Annual Reproduction Workshop Group 2007 (2008) Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod 14(1): 1-14.
  9. Imani B, Eijkemans MJ, de Jong FH, Payne NN, Bouchard P, et al. (2000) Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 85(2): 676-682.
  10. Kurabayashi T, Suzuki M, Fujita K, Murakawa H, Hasegawa I, et al. (2006) Prognostic factors for ovulatory response with clomiphene citrate in polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 126(2): 201-205.
  11. Duleba AJ, Dokras A (2012) Is PCOS an inflammatory process? Fertil Steril 97(1): 7-12.
  12. González F (2012) Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77(4): 300-305.
  13. Repaci A, Gambineri A, Pasquali R (2011) The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 335(1): 30-41.
  14. Tabibzadeh S (1994) Cytokines and the hypothalamic-pituitary-ovarian-endometrial axis. Hum Reprod 9(5): 947-967.
  15. Turnbull AV, Rivier CL (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79(1): 1-71.
  16. Lansdown A, Rees DA (2012) The sympathetic ner vous system in polycystic ovary syndrome: a novel therapeutic target? Clin Endocrinol (Oxf) 77(6): 791- 801.
  17. Daan NM, Koster MP, de Wilde MA, Dalmeijer GW, Evelein AM, et al. (2016) Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study PLoS One 11(11): e0165033. Rafik Ragheb. The Pro-Inflammatory and Anti-Inflammatory Cytokines as Key Tool for Infertility Linked PCOS Diagnosis and Treatment Efficacy. Diabetes Obes Int J 2019, 4(2): 000197.
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@article{rafik2019,
  title   = {The Pro-Inflammatory and Anti-Inflammatory Cytokines as Key Tool for Infertility Linked PCOS Diagnosis and Treatment Efficacy},
  author  = {Rafik Ragheb},
  journal = {Diabetes & Obesity International Journal},
  year    = {2019},
  volume  = {4},
  number  = {2},
  doi     = {10.23880/doij-16000197}
}
Rafik Ragheb (2019). The Pro-Inflammatory and Anti-Inflammatory Cytokines as Key Tool for Infertility Linked PCOS Diagnosis and Treatment Efficacy. Diabetes & Obesity International Journal, 4(2). https://doi.org/10.23880/doij-16000197
TY  - JOUR
TI  - The Pro-Inflammatory and Anti-Inflammatory Cytokines as Key Tool for Infertility Linked PCOS Diagnosis and Treatment Efficacy
AU  - Rafik Ragheb
JO  - Diabetes & Obesity International Journal
PY  - 2019
VL  - 4
IS  - 2
DO  - 10.23880/doij-16000197
ER  -