Neutrophil:lymphocyte and estradiol:progesterone ratios as predictive markers for ovarian hyperstimulation syndrome (OHSS)
Emre Baser A , Demet Aydogan Kirmizi
A * , Runa Ozelci B , Oya Aldemir B , Berna Dilbaz B , Serdar Dilbaz B and Ozlem Moraloglu Tekin C
+ Author Affiliations
- Author Affiliations
A Department of Obstetrics and Gynecology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.
B Department of Obstetrics and Gynecology, Etlik Zubeyde Hanim Women’s Health Training and Research Hospital, Ankara, Turkey.
C Department of Obstetrics and Gynecology, Turkish Ministry of Health, Ankara City Hospital, University of Health Sciences, Ankara, Turkey.
Reproduction, Fertility and Development 34(3) 343-349 https://doi.org/10.1071/RD21182
Published online: 17 December 2021
© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing
Abstract
This study was based on the pathophysiology of the disease and aimed at predicting ovarian hyperstimulation syndrome (OHSS) by determining the importance of ratios obtained from the inflammatory process associated with oestradiol and progesterone in recent years. Out of 242 infertile women who underwent assisted reproductive therapy, 59 patients who developed OHSS were taken as the study group, while the remaining 122 normo-responder (NR) and 61 hyper-responder (HR) patients constituted the control group. The neutrophil to lymphocyte (NLR) and oestradiol/progesterone (EPR) ratios were found to be statistically significantly higher in the OHSS group (P < 0.001). A multivariate logistic regression analysis revealed that the NLR (OR = 2.410, P = 0.001) and EPR (OR = 1.701, P = 0.028) were independent predictors for the development of OHSS. In conclusion, in OHSS inadequate progesterone levels may inhibit suppression of the exaggerated inflammatory process caused by high E2 levels, and NLR and EPR can be used to predict the development of OHSS in patients undergoing controlled ovarian hyperstimulation during in vitro fertilisation cycles.
Keywords: assisted reproductive technologies, COH, high response, infertility, inflammation, neutrophil/lymphocyte ratio, oestrogen/progesterone ratio, OHSS.
References
Abo, T, and Kawamura, T (2002). Immunomodulation by the autonomic nervous system: therapeutic approach for cancer, collagen diseases, and inflammatory bowel diseases. Therapeutic Apheresis 6, 348–357.| Immunomodulation by the autonomic nervous system: therapeutic approach for cancer, collagen diseases, and inflammatory bowel diseases.Crossref | GoogleScholarGoogle Scholar | 12423529PubMed |
Aboulghar, M (2003). Prediction of ovarian hyperstimulation syndrome (OHSS). Estradiol level has an important role in the prediction of OHSS. Human Reproduction 18, 1140–1141.
| Prediction of ovarian hyperstimulation syndrome (OHSS). Estradiol level has an important role in the prediction of OHSS.Crossref | GoogleScholarGoogle Scholar | 12773437PubMed |
Abramov, Y, Schenker, JG, Lewin, A, Friedler, S, Nisman, B, and Barak, V (1996). Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome. Human Reproduction 11, 1381–1386.
| Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome.Crossref | GoogleScholarGoogle Scholar | 8671471PubMed |
Aksoy, AN, Toker, A, Celık, M, Aksoy, M, Halıcı, Z, and Aksoy, H (2014). The effect of progesterone on systemic inflammation and oxidative stress in the rat model of sepsis. Indian Journal of Pharmacology 46, 622–626.
| The effect of progesterone on systemic inflammation and oxidative stress in the rat model of sepsis.Crossref | GoogleScholarGoogle Scholar | 25538334PubMed |
Benlloch-Navarro, S, Trachsel-Moncho, L, Fernández-Carbonell, Á, Olivar, T, Soria, JM, Almansa, I, and Miranda, M (2019). Progesterone anti-inflammatory properties in hereditary retinal degeneration. Journal of Steroid Biochemistry and Molecular Biology 189, 291–301.
| Progesterone anti-inflammatory properties in hereditary retinal degeneration.Crossref | GoogleScholarGoogle Scholar |
Binder, H, Dittrich, R, Einhaus, F, Krieg, J, Müller, A, Strauss, R, Beckmann, MW, and Cupisti, S (2007). Update on ovarian hyperstimulation syndrome: Part 1--Incidence and pathogenesis. International Journal of Fertility and Women’s Medicine 52, 11–26.
| 17987884PubMed |
Çakıroğlu, Y, Vural, F, and Vural, B (2016). The inflammatory markers in polycystic ovary syndrome: association with obesity and IVF outcomes. Journal of Endocrinological Investigation 39, 899–907.
| The inflammatory markers in polycystic ovary syndrome: association with obesity and IVF outcomes.Crossref | GoogleScholarGoogle Scholar | 26980590PubMed |
Calippe, B, Douin-Echinard, V, Laffargue, M, Laurell, H, Rana-Poussine, V, Pipy, B, Guéry, JC, Bayard, F, Arnal, JF, and Gourdy, P (2008). Chronic estradiol administration in vivo promotes the proinflammatory response of macrophages to TLR4 activation: involvement of the phosphatidylinositol 3-kinase pathway. Journal of Immunology 180, 7980–7988.
| Chronic estradiol administration in vivo promotes the proinflammatory response of macrophages to TLR4 activation: involvement of the phosphatidylinositol 3-kinase pathway.Crossref | GoogleScholarGoogle Scholar |
Celikbilek, M, Dogan, S, Ozbakır, O, Zararsiz, G, Kücük, H, Gürsoy, S, Yurci, A, Güven, K, and Yücesoy, M (2013). Neutrophil-lymphocyte ratio as a predictor of disease severity in ulcerative colitis. Journal of Clinical Laboratory Analysis 27, 72–76.
| Neutrophil-lymphocyte ratio as a predictor of disease severity in ulcerative colitis.Crossref | GoogleScholarGoogle Scholar | 23292894PubMed |
Chakrabarti, S, and Davidge, ST (2013). Estradiol modulates tumor necrosis factor-induced endothelial inflammation: role of tumor necrosis factor receptor 2. Journal of Vascular Research 50, 21–34.
| Estradiol modulates tumor necrosis factor-induced endothelial inflammation: role of tumor necrosis factor receptor 2.Crossref | GoogleScholarGoogle Scholar | 23095497PubMed |
Chistyakova, GN, Remizova, II, Gazieva, IA, and Сhermyaninova, OV (2014). Immunological and hemostasiological disorders in women with ovarian hyperstimulation syndrome. Gynecological Endocrinology 30, 39–42.
| Immunological and hemostasiological disorders in women with ovarian hyperstimulation syndrome.Crossref | GoogleScholarGoogle Scholar | 25200828PubMed |
Danninger, B, Brunner, M, Obruca, A, and Feichtinger, W (1996). Prediction of ovarian hyperstimulation syndrome of baseline ovarian volume prior to stimulation. Human Reproduction 11, 1597–1599.
| Prediction of ovarian hyperstimulation syndrome of baseline ovarian volume prior to stimulation.Crossref | GoogleScholarGoogle Scholar | 8921098PubMed |
Escobar-Morreale, HF, Luque-Ramirez, M, and Gonzalez, F (2011). Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertility and Sterility 95, 1048–1058. e1-2.
| Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis.Crossref | GoogleScholarGoogle Scholar | 21168133PubMed |
Fernandez, LA, Tarlatzis, BC, Rzasa, PJ, Caride, VJ, Laufer, N, Negro-Vilar, AF, DeCherney, AH, and Naftolin, F (1985). Renin-like activity in ovarian follicular fluid. Fertility and Sterility 44, 219–223.
| Renin-like activity in ovarian follicular fluid.Crossref | GoogleScholarGoogle Scholar | 2410302PubMed |
Golan, A, and Weissman, A (2009). Symposium: Update on prediction and management of OHSS. A modern classification of OHSS. Reproductive BioMedicine Online 19, 28–32.
| Symposium: Update on prediction and management of OHSS. A modern classification of OHSS.Crossref | GoogleScholarGoogle Scholar | 19573287PubMed |
Hendriks, DJ, Klinkert, ER, Bancsi, LFJMM, Looman, CWN, Habbema, JDF, te Velde, ER, and Broekmans, FJ (2004). Use of stimulated serum estradiol measurements for the prediction of hyperresponse to ovarian stimulation in in vitro fertilization (IVF). Journal of Assisted Reproduction and Genetics 21, 65–72.
| Use of stimulated serum estradiol measurements for the prediction of hyperresponse to ovarian stimulation in in vitro fertilization (IVF).Crossref | GoogleScholarGoogle Scholar | 15202733PubMed |
Hoffman, M, Blum, A, Baruch, R, Kaplan, E, and Benjamin, M (2004). Leukocytes and coronary heart disease. Atherosclerosis 172, 1–6.
| Leukocytes and coronary heart disease.Crossref | GoogleScholarGoogle Scholar | 14709350PubMed |
Imtiaz, F, Shafique, K, Mirza, SS, Ayoob, Z, Vart, P, and Rao, S (2012). Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. International Archives of Medicine 5, 2.
| Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population.Crossref | GoogleScholarGoogle Scholar | 22281066PubMed |
Jiang, C, Wang, J, Li, X, Liu, C, Chen, N, and Hao, Y (2009). Progesterone exerts neuroprotective effects by inhibiting inflammatory response after stroke. Inflammation Research 58, 619–624.
| Progesterone exerts neuroprotective effects by inhibiting inflammatory response after stroke.Crossref | GoogleScholarGoogle Scholar | 19333725PubMed |
Kahnberg, A, Enskog, A, Brännström, M, Lundin, K, and Bergh, C (2009). Prediction of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Acta Obstetricia et Gynecologica Scandinavica 88, 1373–1381.
| Prediction of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization.Crossref | GoogleScholarGoogle Scholar | 19878052PubMed |
Kan, Ö, Gemici, A, Alkilic, A, Cetindag, EN, Cakir, C, Dur, R, and Altay, M (2019). The effect of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on predicting rupture risk in tubal ectopic pregnancies. Gynecologic and Obstetric Investigation 84, 378–382.
| The effect of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on predicting rupture risk in tubal ectopic pregnancies.Crossref | GoogleScholarGoogle Scholar | 30654361PubMed |
Kelly, RW, King, AE, and Critchley, HO (2001). Cytokine control in human endometrium. Reproduction 121, 3–19.
| Cytokine control in human endometrium.Crossref | GoogleScholarGoogle Scholar | 11226025PubMed |
Lee, A, Whyte, MK, and Haslett, C (1993). Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. Journal of Leukocyte Biology 54, 283–288.
| Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators.Crossref | GoogleScholarGoogle Scholar | 8409750PubMed |
Lee, D, Han, SJ, Kim, SK, and Jee, BC (2018). A retrospective analysis of the follicle-stimulating hormone starting dose in expected normal responders undergoing their first in vitro fertilization cycle: proposed dose versus empiric dose. Clinical and Experimental Reproductive Medicine 45, 183–188.
| A retrospective analysis of the follicle-stimulating hormone starting dose in expected normal responders undergoing their first in vitro fertilization cycle: proposed dose versus empiric dose.Crossref | GoogleScholarGoogle Scholar | 30538949PubMed |
Marquardt, RM, Kim, TH, Shin, JH, and Jeong, JW (2019). Progesterone and estrogen signaling in the endometrium: what goes wrong in endometriosis? International Journal of Molecular Sciences 20, 3822.
| Progesterone and estrogen signaling in the endometrium: what goes wrong in endometriosis?Crossref | GoogleScholarGoogle Scholar |
Mathur, RS, Jenkins, JM, and Bansal, AS (1997). The possible role of the immune system in the aetiopathogenesis of ovarian hyperstimulation syndrome. Human Reproduction 12, 2629–2634.
| The possible role of the immune system in the aetiopathogenesis of ovarian hyperstimulation syndrome.Crossref | GoogleScholarGoogle Scholar | 9455826PubMed |
Nakamura, I, Shibata, M, Gonda, K, Yazawa, T, Shimura, T, Anazawa, T, Suzuki, S, Sakurai, K, Koyama, Y, Ohto, H, Tomita, R, Gotoh, M, and Takenoshita, S (2013). Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression involving MDSCs and systemic inflammation in patients with cancer of the digestive system. Oncology Letters 5, 1682–1686.
| Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression involving MDSCs and systemic inflammation in patients with cancer of the digestive system.Crossref | GoogleScholarGoogle Scholar | 23761834PubMed |
Orvieto, R, Ben-Rafael, Z, Abir, R, Bar-Hava, I, Fisch, B, and Molad, Y (1999). Controlled ovarian hyperstimulation: a state of neutrophil activation. American Journal of Reproductive Immunology 42, 288–291.
| Controlled ovarian hyperstimulation: a state of neutrophil activation.Crossref | GoogleScholarGoogle Scholar | 10584983PubMed |
Papanikolaou, EG, Pozzobon, C, Kolibianakis, EM, Camus, M, Tournaye, H, Fatemi, HM, Van Steirteghem, A, and Devroey, P (2006). Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertility and Sterility 85, 112–120.
| Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.Crossref | GoogleScholarGoogle Scholar | 16412740PubMed |
Papanikolaou, EG, Humaidan, P, Polyzos, NP, and Tarlatzis, B (2010). Identification of the high-risk patient for ovarian hyperstimulation syndrome. Seminars in Reproductive Medicine 28, 458–462.
| Identification of the high-risk patient for ovarian hyperstimulation syndrome.Crossref | GoogleScholarGoogle Scholar | 21082503PubMed |
Pietrowski, D, Szabo, L, Sator, M, Just, A, and Egarter, C (2012). Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A. Human Reproduction 27, 196–199.
| Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A.Crossref | GoogleScholarGoogle Scholar | 22016416PubMed |
Practice Committee of the American Society for Reproductive Medicine (2016). Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertility and Sterility 106, 1634–1647.
| Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline.Crossref | GoogleScholarGoogle Scholar | 27678032PubMed |
Soave, I, and Marci, R (2014). Ovarian stimulation in patients in risk of OHSS. Minerva Ginecologica 66, 165–178.
| 24848075PubMed |
Stein, DG (2011). Is progesterone a worthy candidate as a novel therapy for traumatic brain injury? Dialogues in Clinical Neuroscience 13, 352–359.
| Is progesterone a worthy candidate as a novel therapy for traumatic brain injury?Crossref | GoogleScholarGoogle Scholar | 22033509PubMed |
Stein, DG, Wright, DW, and Kellermann, AL (2008). Does progesterone have neuroprotective properties? Annals of Emergency Medicine 51, 164–172.
| Does progesterone have neuroprotective properties?Crossref | GoogleScholarGoogle Scholar | 17588708PubMed |
Sunkara, SK, La Marca, A, Seed, PT, and Khalaf, Y (2015). Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes. Human Reproduction 30, 1473–1480.
| Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes.Crossref | GoogleScholarGoogle Scholar | 25883033PubMed |
Takano, T, Azuma, N, Satoh, M, Toda, A, Hashida, Y, Satoh, R, and Hohdatsu, T (2009). Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions. Archives of Virology 154, 775–781.
| Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions.Crossref | GoogleScholarGoogle Scholar | 19343474PubMed |
Venetis, CA, Kolibianakis, EM, Bosdou, JK, Lainas, GT, Sfontouris, IA, Tarlatzis, BC, and Lainas, TG (2015). Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles. Human Reproduction 30, 684–691.
| Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles.Crossref | GoogleScholarGoogle Scholar | 25586787PubMed |
Verit, FF, Cetin, O, Yildirim, O, Keskin, S, Yucel, O, and Yalcinkaya, S (2014). Neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio as an early predictor of moderate/severe ovarian hyperstimulation syndrome. Journal of Obstetrics and Gynaecology 34, 639–643.
| Neutrophil to lymphocyte ratio is superior to platelet to lymphocyte ratio as an early predictor of moderate/severe ovarian hyperstimulation syndrome.Crossref | GoogleScholarGoogle Scholar | 24911966PubMed |
