Research Article Journal of Gynecological Oncology Published: 11 Nov, 2019 The Impact of Endometrial Hyperplasia without Atypia on In Vitro Fertilization Outcome Levakov SA1, Blinova EV2,3, Lukianova IS1, Kudriavtzev MJ1, Tumutolova OM3, Blinov DS4* and Makarkina VN5 1Department of Obstetrics and Gynecology, Sechenov University, Russia 2Department of Clinical Anatomy, Sechenov University, Russia 3Department of Obstetrics and Gynecology, National Research Mordovia State University, Russia 4Laboratory of Molecular Pharmacology, All-Union Research Center for Biological Active Compounds Safety, Russia 5Department of Fundamental Medicine, Lomonosov Moscow State University, Russia Abstract Context: A role of endometrial hyperplasia in efficacy of assisted reproductive technology remains unclear as do involvement of local antioxidant defense system and vitamin D serum level. Aim: To determine whether endometrial hyperplasia without atypia impacts in vitro fertilization outcome as well as highlight a role of local antioxidant defense system and 25-hydroxicalciferol serum level as possible markers for ART efficacy in infertile women with endometrial hyperplasia. Setting and design: Two-stage observational non-interventional study with 2000 clinical cases analyzed during retrospective stage and 250 participants on prospective stage. Materials and methods: Pregnancy rate was assessed to determine an influence of endometrial hyperplasia without atypia on in vitro fertilization outcome. Local antioxidant defense level was registered by superoxide-dismutase activity detection and total antioxidant capacity measurement OPEN ACCESS in endometrial tissue prior to embryo transplantation. 25-hydroxicalciferole serum concentration *Correspondence: was determined by quantitative enzyme-linked immunosorbent assay method. Blinov DS, Laboratory of Molecular Statistical analysis used: We applied “Chi-square” criterion to comparatively assess in vitro Pharmacology, All-Union Scientific fertilization outcome. The normality of the variance distribution was determined using one-way Centre for Biological Active Compounds Analysis of Variance (ANOVA), while Newman-Keuls criterion was used to intergroup assessment. Safety, 23 Kirova Street, Staraja Kupavna, Moscow Region, 142450, Results: Pregnancy rate among women with endometrial hyperplasia without atypia undergone Russia, Tel: +7-9271971422; Fax: +7- in vitro fertilization was lower than in control group largely due to results obtained in subgroup of women older than 40. Negative outcome associates with depletion of antioxidant system potency in 4957029586; hyperplastic endometrium and decrease of vitamin D serum level. E-mail: [email protected] Received Date: 16 Oct 2019 Conclusion: Superoxide-dismutase activity in endometrial tissue and local total antioxidant Accepted Date: 05 Nov 2019 capacity along with vitamin D serum level may be considered as potential biomarkers of fertilization Published Date: 11 Nov 2019 outcome in endometrial hyperplasia without atypia. Citation: Keywords: In vitro fertilization outcome; Endometrial hyperplasia without atypia; Superoxide- Levakov SA, Blinova EV, Lukianova IS, dismutase; Total antioxidant capacity; 25-hydroxicalciferol Kudriavtzev MJ, Tumutolova OM, Blinov DS, et al. The Impact of Endometrial Key Messages Hyperplasia without Atypia on In Vitro Endometrial hyperplasia without atypia worsens in vitro fertilization outcome in women with Fertilization Outcome. J Gynecol Oncol. tubal infertility. Negative outcome associates with depletion of antioxidant system potency in 2019; 2(3): 1019. hyperplastic endometrium and decrease of 25-hydroxicalciferole serum level. Copyright © 2019 Levakov SA. This is Introduction an open access article distributed under the Creative Commons Attribution At present, hyperplastic processes in endometrium are considered as a precancerous endometrial License, which permits unrestricted condition with a different degree of malignancy probability [1,2]. The primary etiological factor in use, distribution, and reproduction in the formation of the pathological process is suggested to be long-lasting hyperoestrogenism, which any medium, provided the original work develops against the background of relatively low concentrations of endogenous progesterone. is properly cited. Although the peak of Endometrial Hyperplasia (EH) incidence occurs in women between the ages of Remedy Publications LLC. 1 2019 | Volume 2 | Issue 3 | Article 1019 Levakov SA, et al., Journal of Gynecological Oncology 50 and 60, nevertheless, the disease incidence in younger age groups pregnancy rate) confirmed by ultrasound examination four weeks is significant [3]. Current opinions consider following risk factors after ET. The prospective stage of the study involved 150 women of for the development of the disease: long-term an ovarial syndrome reproductive age with tubal infertility and EH without atypia, which with normal level of gonadatropins, increased levels of endo-and was established according to the results of hysteroscopy with guided exogenous oestrogen, and obesity [4]. According to the modern biopsy (RCOG/BSGE Joint Guideline, 2016) during preparation for classification revised in 2014, the disease is divided into EH without IVF ET at Obstetrics and Gynecology University Clinic of Sechenov atypia and EH with atypia [5]. The main diagnostic method is targeted University from October 2017 till August 2018. biopsy of the endometrium with morphological verification of the Inclusion criteria were as follows: age of patients from 18 to 45 years diagnosis, since other diagnostic methods do not allow excluding the old, voluntary informed consent to participate in the study, infertility presence of a malignant process and possess a number of limitations of tubal origin, EH without atypia (for the main group) diagnosed in such characteristics as sensitivity and specificity [6]. for the first time and verified by targeted biopsy and subsequent Up to now, there is no strict evidence of the negative effect of morphological examination of endometrial tissue specimens, no EH without atypia on the Assisted Reproduction Technologies (ART) more than 2 unsuccessful IVF attempts. Exclusion criteria for the outcome. Scientific publications emerged in recent years contain study were the presence of acute and chronic inflammatory diseases very ambiguous information on this issue, the studies described of the uterus during the last 12 months, endometriosis of any location, in them have been made on a small sample and, moreover, usually the presence of acute or chronic infectious diseases (including viral included women with endometrial malignancies [7,8]. In one of the hepatitis and HIV infection) during the last 3 months, chronic studies conducted by Gaducci et al. [9] the authors have shown that somatic diseases (arterial hypertension, kidney and liver disease). In the completion of hormonal therapy, accompanied by clinical and control group we enrolled 100 infertile women without hyperplastic laboratory effects, has led to the successful implementation of fertile changes in endometrium who met inclusion criteria in the absence of function, both naturally and with the use of In Vitro Fertilization and exclusion criteria, and voluntarily agreed to participate in the study. Embryo Transfer (IVF ET) protocols [9]. Ethics Involvement of oxidative stress reactions and free radical The Study Protocol (No. 1275) was reviewed and approved by generation has been shown for EH development in fertile women and Sechenov University Ethics Committee (No. of review 128, date of IVF ET outcome in infertile females [10,11]. Cinar et al. [10] have Review meeting April 12, 2017). Expressed informed consent was demonstrated high predictive potency of catalase, malondialdehyde received from each of the study participant. All medical procedures, and xanthine oxidase in EH development. Nishihara et al. [12] services and manipulations were free of charge for the women due to have reported depletion of total antioxidant capacity and different Russian Government financial support of ART programmers in the deviation of glutathione level in infertile women in dependence country. on gynecological cause of infertility. Vitamin D both serum and follicular fluid levels attract particular attention of scientists since its IVF protocol role in reproduction has been demonstrated [13,14]. Thus, it has been We induced ovulation with gonadatropins-releasing hormone shown that vitamin D and its biologically active metabolites regulated antagonists (Diphereline®, Beaufor Ipsen Pharma, France) according sex steroid hormones secretion both in follicular and placental tissue, to the standard method. Oocyte fertilization was carried out by IVF. influenced gonadatropins’ expression [15,16]. However, studies on On the 5th cultivation day selective transfer of 1 blastocyst of 4 to 5 effectiveness of ART methods in women of reproductive age with EH quality class was performed. without atypia, identification of molecular and biochemical markers Methods of local oxidative stress measurement and predictors of IVF ET success have not been carried out yet, which We assessed oxidative stress activity in visually intact and determines the undoubted relevance and timeliness of this work. hyperplastic endometrial specimens by Superoxide-Dismutase The main aim of the study is to determine whether EH without (SOD) activity detection and Total Antioxidant Capacity (TAC) atypia impacts IVF ET outcome as well as highlight a role