Indicators of an ovarian reserve in women of early reproductive age with PCOS depending on the phenotype

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Elgina Svetlana ◽  
Artymuk Natalia ◽  
Beglova Anzhelika
Keyword(s):  
Ovarian Reserve ◽  
Clinical Laboratory ◽  
Polycystic Ovary ◽  
Reproductive Potential ◽  
Average Diameter ◽  
Reproductive Age ◽  
Control Group ◽  
Volume Number ◽  
High Level ◽  
Ultrasound Parameters

Abstract Background The objective was to study ovarian reserve values in women of early reproductive age with polycystic ovary syndrome (PCOS) according to their phenotype. Materials and methods Two hundred women of early reproductive age with PCOS and without PCOS were studied by clinical, laboratory (hormonal), ultrasound and statistical methods. Results The anti-Müllerian hormone (AMH) index in women with PCOS with the main (A) and non-androgenic (D) phenotypes corresponded to a high level, with anovulatory (B), ovulatory (C) corresponding to a normal level. AMH in women with the main (A) phenotype differed and was higher compared with women with anovulatory (B) and ovulatory (C) phenotypes and had no differences to women with the non-androgenic (D) phenotype. No differences in the AMH level between anovulatory (B) and ovulatory (C) phenotypes have been established. Ultrasound parameters of the ovaries (volume, number of antral follicles in the section, average diameter of the follicles) of women with PCOS of the main (A), ovulatory (C) and non-androgenic (D) phenotypes were statistically significantly larger than healthy ones. With anovulatory (B) phenotype these figures did not differ from the control group. When comparing phenotypes by ultrasound parameters of the ovaries the main (A), ovulatory (C) and non-androgenic (D) phenotypes did not have any differences among themselves. Anovulatory phenotype (B) had lower ultrasound indices. Conclusion The study of indicators of ovarian reserve in women of early reproductive age with PCOS is a promising direction that will allow to more accurately determine the reproductive potential of each particular woman and influence the choice of treatment tactics.

Features of the ovarian reserve of women of reproductive age suffering from autoimmune diseases

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. 27-30
Author(s):  
Elena N. Andreeva ◽  
Olga R. Grigoryan ◽  
Yulia S. Absatarova ◽  
Irina S. Yarovaya ◽  
Robert K. Mikheev
Keyword(s):  
Type 1 Diabetes ◽  
Thyroid Gland ◽  
Autoimmune Diseases ◽  
Ovarian Reserve ◽  
Reproductive Potential ◽  
Reproductive Age ◽  
Control Group ◽  
Antithyroid Antibodies ◽  
Healthy Women

The reproductive potential of a woman depends on indicators of the ovarian reserve, such as the anti-Muller hormone (AMH) and the number of antral follicles (NAF). Autoimmune diseases have a significant effect on fertility and contribute to the development of premature ovarian failure. Aim.To evaluate the parameters of the ovarian reserve in patients with type 1 diabetes mellitus, carriers of antibodies to the thyroid gland in a state of euthyroidism and compare them with similar parameters in healthy women. Materials and methods.In the first block of the study, the level of AMH, follicle-stimulating hormone, luteinizing hormone, NAF was studied among 224 women with diabetes and 230 healthy women in the control group. In block II, the level of the above hormonal indices was studied in 35 carriers of antithyroid antibodies in the state of euthyroidism and 35 healthy women. Results.In patients with type 1 diabetes, the level of AMH, NAF was statistically significantly lower when compared with the control group. Among carriers of antithyroid antibodies and healthy women, no difference in AMH and NAF was found. Conclusion.The autoimmune processes accompanying diabetes are more influenced by the ovarian reserve indices than autoimmune aggression to the tissues of the thyroid gland.

scholarly journals The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shizhuo Wang ◽  
Jiahui Gu
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Reserve ◽  
Premenopausal Women ◽  
Laparoscopic Hysterectomy ◽  
Ovarian Tumors ◽  
Reproductive Age ◽  
Control Group ◽  
Significant Difference ◽  
Bilateral Salpingectomy ◽  
The Impact

Abstract Background Bilateral salpingectomy has been proposed to reduce the risk of ovarian cancer, but it is not clear whether the surgery affects ovarian reserve. This study compares the impact of laparoscopic hysterectomy for benign disease with or without prophylactic bilateral salpingectomy on ovarian reserve. Methods Records were reviewed for 373 premenopausal women who underwent laparoscopic hysterectomy with ovarian reserve for benign uterine diseases. The serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and three-dimensional antral follicle count (AFC) were assessed before surgery and 3 and 9 months postoperatively to evaluate ovarian reserve. Patients were divided into two groups according to whether they underwent prophylactic bilateral salpingectomy. The incidence of pelvic diseases was monitored until the ninth month after surgery. Results There was no significant difference between the two surgery groups in terms of baseline AMH, E2, FSH, LH, and AFC (all P > 0.05). There was no difference in potential bias factors, including patient age, operative time, and blood loss (all P > 0.05). There was also no significant difference between the two groups 3 months after surgery with respect to AMH (P = 0.763), E2 (P = 0.264), FSH (P = 0.478), LH (P = 0.07), and AFC (P = 0.061). Similarly, there were no differences between groups 9 months after surgery for AMH (P = 0.939), E2 (P = 0.137), FSH (P = 0.276), LH (P = 0.07) and AFC (P = 0.066). At 9 months after the operation, no patients had malignant ovarian tumors. The incidences of benign ovarian tumors in the salpingectomy group were 0 and 2.68 % at 3 and 9 months after surgery, respectively, and the corresponding values in the control group were 0 and 5.36 %. The incidences of pelvic inflammatory disease in the salpingectomy group were 10.72 and 8.04 % at 3 and 9 months after surgery, respectively, while corresponding values in the control group were 24.13 and 16.09 %. Conclusions Prophylactic bilateral salpingectomy did not damage the ovarian reserve of reproductive-age women who underwent laparoscopic hysterectomy. Prophylactic bilateral salpingectomy might be a good method to prevent the development of ovarian cancer. Larger clinical trials with longer follow-up times are needed to further evaluate the risks and benefits.

Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences

2021 ◽  
Author(s):  
Carrie Riestenberg ◽  
Anika Jagasia ◽  
Daniela Markovic ◽  
Richard P Buyalos ◽  
Ricardo Azziz
Keyword(s):  
United States ◽  
Polycystic Ovary Syndrome ◽  
Economic Burden ◽  
Polycystic Ovary ◽  
The United States ◽  
Reproductive Age ◽  
Cochrane Library ◽  
Control Group ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5-20% of women of reproductive age. A previous estimate noted that the economic burden of PCOS approximates $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, not considering the costs of pregnancy-related and long-term morbidities. Objective To estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS. Data Sources PubMed, EmBase and Cochrane Library. Study Selection Studies in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health (NIH), or Androgen Excess & PCOS (AE-PCOS) Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling were eligible for inclusion. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index (BMI) were included. Data Extraction Two investigators working independently extracted data on study characteristics and outcomes. Data Synthesis Data was pooled using random-effects meta-analysis. The I 2statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results The additional total healthcare-related economic burden due to pregnancy-related and long-term morbidities associated with PCOS in the United States is estimated to be $4.3 billion annually in 2020 USD. Conclusions Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.

scholarly journals Association analysis between the polymorphisms of HSD17B5 and HSD17B6 and risk of polycystic ovary syndrome in Chinese population

2015 ◽  
Vol 172 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Rong Ju ◽  
Wei Wu ◽  
Juan Fei ◽  
Yufeng Qin ◽  
Qiuqin Tang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Chinese Population ◽  
Chinese Women ◽  
Polycystic Ovary ◽  
Control Group ◽  
Model Assessment ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Significant Difference ◽  
High Level

ObjectiveTo assess whether single nucleotide polymorphisms of HSD17B5 (AKR1C3) (rs1937845 and rs12529) and HSD17B6 (rs898611) are associated with polycystic ovary syndrome (PCOS) in a Chinese population.DesignA case–control study was conducted to investigate the relation between HSD17B5 and HSD17B6 polymorphisms and PCOS.MethodsIn this study, 335 patients with PCOS and 354 controls were recruited. The genotypes of HSD17B5 (rs1937845 and rs12529) and HSD17B6 (rs898611) were detected by the TaqMan method.Results and conclusionsWe found that the genotypic frequencies of the rs1937845 polymorphism were different in subjects with PCOS compared with control, with the CT genotype being more commonly found in patients with PCOS than in controls (P=0.005). We observed a significantly 1.74-fold higher risk of CT genotype in the polymorphism rs1937845 in women with PCOS vs the control group (adjusted odds ratio (OR), 1.74; 95% CI=1.19–2.54; P=0.005). A similar, significant 1.47-fold higher risk (adjusted OR, 1.47; 95% CI=1.07–2.03; P=0.018) was demonstrated for T allele of polymorphism rs1937845 associated with PCOS. In patients with PCOS, the rs12529 (G>C) and rs1937845 (C>T) polymorphisms were strongly associated with the high level of testosterone. The TT carriers of polymorphism rs1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P=0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in genotype or allele distributions of the polymorphisms rs12529 of HSD17B5 and rs898611 of HSD17B6 between patients with PCOS and controls. Additionally, the two polymorphisms of HSD17B5 are associated with hyperandrogenemia in patients with PCOS. In conclusion, our findings showed a significant statistical association between HSD17B5 rs1937845 and PCOS risk in Chinese women. The CT genotype and T allele frequency are influenced significantly to a higher extent in patients with PCOS than controls. Further studies are needed to confirm the results and find out the exact molecular mechanism of the polymorphism on the risk of hyperandrogenemia and PCOS.

Gestosis from a view of perinatal psychology

2017 ◽  
pp. 35-37
Author(s):  
S.I. Zhuk ◽  
◽  
O.D. Shchurevskaya ◽  
Keyword(s):  
Pregnant Women ◽  
Clinical Laboratory ◽  
Psychological Testing ◽  
Control Group ◽  
Psychological Component ◽  
The Subject ◽  
High Level ◽  
Perinatal Psychology ◽  
Pathological Subtypes

Preeclampsia is a clinical manifestation of the physiological and psychological maladaptation in the pregnant woman. The objective: to determine the characteristics of the psychoemotional status of pregnant women with pre-eclampsia based on the results of psychological testing using questionnaires using the Spielberger-Khanin technique and studying the psychological component of the gestational dominant (PCGD) Dobryakov [3]. Materials and methods. The subject of this study was the results of clinical-laboratory and psychological testing of 90 women in the III trimester of pregnancy. In 50 women, moderate and severe preeclampsia was diagnosed and they were included in the main group, and 40 women with a physiological pregnancy were included in the control group. Results. Pathological subtypes of the psychological component of the gestational dominant are revealed by the method of IV. Dobryakova and an increase in anxiety level by the Spielberger-Khanin technique. The high level of anxiety, the absence of a dominant pregnancy or the presence of its pathological subtypes in the case of gestosis is both a reflection of the maladaptation of the whole organism and the woman's unwillingness to transform her stereotypes of behavior in accordance with the needs of a new condition-pregnancy and forthcoming births, Have long-term consequences even from offspring [5]. The conclusion. The necessity of psychological counseling of pregnant women and correction of the revealed violations of the period of gestation is proved. Key words: pregnancy, delivery, preeclampsia, perinatal psychology, anxiety, gestational dominant.

scholarly journals Impact of Short-Term Isoflavone Intervention in Polycystic Ovary Syndrome (PCOS) Patients on Microbiota Composition and Metagenomics

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1622 ◽  
Author(s):  
Christoph Haudum ◽  
Lisa Lindheim ◽  
Angelo Ascani ◽  
Christian Trummer ◽  
Angela Horvath ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Biochemical Characterization ◽  
Polycystic Ovary ◽  
Alpha Diversity ◽  
Intestinal Bacteria ◽  
Reproductive Age ◽  
Control Group ◽  
Interventional Study ◽  
Ovary Syndrome ◽  
Receptor Modulator

Background: Polycystic ovary syndrome (PCOS) affects 5–20% of women of reproductive age worldwide and is associated with disorders of glucose metabolism. Hormone and metabolic signaling may be influenced by phytoestrogens, such as isoflavones. Their endocrine effects may modify symptom penetrance in PCOS. Equol is one of the most active isoflavone metabolites, produced by intestinal bacteria, and acts as a selective estrogen receptor modulator. Method: In this interventional study of clinical and biochemical characterization, urine isoflavone levels were measured in PCOS and control women before and three days after a defined isoflavone intervention via soy milk. In this interventional study, bacterial equol production was evaluated using the log(equol: daidzein ratio) and microbiome, metabolic, and predicted metagenome analyses were performed. Results: After isoflavone intervention, predicted stool metagenomic pathways, microbial alpha diversity, and glucose homeostasis in PCOS improved resembling the profile of the control group at baseline. In the whole cohort, larger equol production was associated with lower androgen as well as fertility markers. Conclusion: The dynamics in our metabolic, microbiome, and predicted metagenomic profiles underline the importance of external phytohormones on PCOS characteristics and a potential therapeutic approach or prebiotic in the future.

scholarly journals Extended High Frequency Audiometry in Polycystic Ovary Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Cuneyt Kucur ◽  
Suna Kabil Kucur ◽  
Ilay Gozukara ◽  
Ali Seven ◽  
Kadriye Beril Yuksel ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
High Frequency ◽  
Polycystic Ovary ◽  
Endothelial Damage ◽  
Reproductive Age ◽  
Control Group ◽  
Fasting Insulin ◽  
High Frequencies ◽  
High Frequency Audiometry ◽  
Significant Difference

Objective. Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting 5–10% of women in reproductive age. Insulin resistance, dyslipidemia, glucose intolerance, hypertension, and obesity are metabolic disorders accompanying the syndrome. PCOS is a chronic proinflammatory state and the disease is associated with endothelial dysfunction. In diseases with endothelial damage, hearing in high frequencies are mostly effected in early stages. We evaluated extended high frequency hearing loss in PCOS patients.Material Methods. Forty women diagnosed as PCOS and 25 healthy controls were included in this study. Age and BMI of PCOS and control groups were comparable. Each subject was tested with low (250–2000 Hz), high (4000–8000 Hz), and extended high frequency audiometry (8000–20000). Hormonal and biochemical values including LH, LH/FSH, testosterone, fasting glucose, fasting insulin, HOMA-I, and CRP were calculated.Results. PCOS patients showed high levels of LH, LH/FSH, testosterone, fasting insulin, glucose, HOMA-I, and CRP levels. The hearing thresholds of the groups were similar at frequencies of 250, 500, 1000, 2000, and 4000 Hz; statistically significant difference was observed in 8000–14000 Hz in PCOS group compared to control group.Conclusion. PCOS patients have hearing impairment especially in extended high frequencies. Further studies are needed to help elucidate the mechanism behind hearing impairment in association with PCOS.

scholarly journals FEATURES OF ENDOMETRIUM STRUCTURE IN ALCOHOL-ABUSING HIV-INFECTED INDIVIDUALS

2021 ◽  
Vol 8 (1) ◽  
pp. 52-58
Author(s):  
M. Lytvynenko
Keyword(s):  
Wall Thickness ◽  
Reproductive System ◽  
Morphological Changes ◽  
Average Diameter ◽  
Relative Volume ◽  
Reproductive Age ◽  
Maximum Diameter ◽  
Control Group ◽  
Minimum Diameter ◽  
Secretory Type

Background. Patients with comorbid pathology occupy leading positions in the practice of a doctor of any specialty especially in patients with HIV. Reproductive system is known to be the gateway for viruses. This fact could explain the severity of changes developing in the female reproductive system infected with HIV, in particular in the endometrium. The purpose of this study was to assess morphological changes in the endometrium caused by the combined effects of HIV infection and chronic alcoholism. Materials and methods: The study included sectional material taken from 60 women of reproductive age (20-40 years). They were all divided into two groups. The first group (30 people) consisted of HIV-positive individuals who, according to a survey of relatives and according to an autopsy (the main symptom is the presence of alcoholic cirrhosis of the liver), alcohol abuse was confirmed. The following parameters were determined: the average diameter of the endometrial glands (proliferative type), the minimum diameter of the endometrial glands (proliferative type), the maximum diameter of the endometrial glands (proliferative type), wall thickness (proliferative type), the relative volume of the epithelium (proliferative type), the average diameter of the glands (secretory type), the minimum diameter of the glands (secretory type), the maximum diameter of the glands (secretory type), the relative volume of the epithelium (secretory type), the thickness of the epithelium. Results. the average diameter of the endometrial glands (proliferative type) decreased from 51.71 ± 2.90 x 10-6 m in the comparison group to 39.42 ± 2.35 x 10-6 m in the HIV-infected group, which was 23.77%. The minimum diameter of the endometrial glands (proliferative type) reduced from 32.47 ± 1.83 x10-6 m to 27.13 ± 1.73x10-6 m (16.45%), the maximum diameter from 72.14 ± 2.21 x10-6 m to 63.84 ± 3.29 x10-6 m (11.5%). the relative volume of the epithelium (proliferative type) decreased by 5.41% (from 54.43 ± 1.79% in the study group to 49.02 ± 2.65% in the control group). The thickness of the uterine wall was also significantly reduced from 15.18 ± 1.60 x10-6 m to 14.52 ± 1.19 x10-6 m, which was 4.35%. The maximum volume of glands (secretory type) changed from 127.98 ± 2.10 x10-6 m to 97.18 ± 3.12 x10-6 m (24%). Changes by 3.6% were also observed when examining the wall thickness (from 13.02 ± 1.36 x10-6 m to 12.55 ± 1.68 x10-6 m). Conclusion. The study evaluated features of endometrial restructuring in alcohol-abusing HIV-infected women.

scholarly journals Risk Factors Associated with Impaired Ovarian Reserve in Young Women of Reproductive Age with Crohn’s Disease

2020 ◽  
Vol 18 (2) ◽  
pp. 200-209 ◽  
Author(s):  
Yue Zhao ◽  
Baili Chen ◽  
Yao He ◽  
Shenghong Zhang ◽  
Yun Qiu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Crohn’S Disease ◽  
Young Women ◽  
Ovarian Reserve ◽  
Disease State ◽  
Reproductive Age ◽  
Control Group ◽  
Women Of Reproductive Age ◽  
Factors Associated ◽  
Active Disease

Background/Aims: Crohn’s disease (CD) primarily affects young female adults of reproductive age. Few studies have been conducted on this population’s ovarian reserve status. The aim of study was to investigate potential risk factors associated with low ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) in women of reproductive age with CD.Methods: This was a case-control study. Cases included 87 patients with established CD, and healthy controls were matched by age, height and weight in a 1:1 ratio. Serum AMH levels were measured by enzyme-linked immunosorbent assay.Results: The average serum AMH level was significantly lower in CD patients than in control group (2.47±2.08 ng/mL vs. 3.87±1.96 ng/mL, respectively, <i>P</i><0.001). Serum AMH levels were comparable between CD patients and control group under 25 years of age (4.41±1.52 ng/mL vs. 3.49±2.10 ng/mL, <i>P</i>=0.06), however, serum AMH levels were significantly lower in CD patients over 25 years of age compared to control group (<i>P</i><0.05). Multivariable analysis showed that an age greater than 25 (odds ratio [OR], 10.03; 95% confidence interval [CI], 1.90–52.93, <i>P</i>=0.007), active disease state (OR, 27.99; 95% CI, 6.13–127.95, <i>P</i><0.001) and thalidomide use (OR, 15.66; 95% CI, 2.22–110.65, <i>P</i>=0.006) were independent risk factors associated with low ovarian reserve (serum AMH levels <2 ng/mL) in CD patients. Conclusions: Ovarian reserve is impaired in young women of reproductive age with CD. Age over 25 and an active disease state were both independently associated with low ovarian reserve. Thalidomide use could result in impaired ovarian reserve.

Features of the functional state of the pituitary-ovarian systems in women with polycystic ovary syndrome at different periods of reproductive age

2020 ◽  
Vol 75 (6) ◽  
pp. 653-660
Author(s):  
O. V. Krusko ◽  
L. F. Sholokhov ◽  
L. V. Belenkaya ◽  
M. A. Rashidova ◽  
I. N. Danusevich ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Follicle Stimulating Hormone ◽  
Reproductive Age ◽  
Sex Steroid ◽  
Control Group ◽  
Ovary Syndrome ◽  
Steroid Binding ◽  
Stimulating Hormone

Background. PCOS is one of the most common endocrinological pathologies in women of reproductive age, manifested by a wide range of clinical manifestations. There are many unresolved issues related to the pathogenesis, diagnosis and treatment of this pathological condition in different periods of reproductive age. Aim the objective of the study was to identify the features of the functioning of the pituitary-ovarian system in women with PCOS at different periods of reproductive age. Methods. Study was performed in 20172019 at the FSPSI SCFHHRP, and involved women aged 1845 years. The study groups included women (a group of women with PCOS and a control group) in the follicular phase from 1 to 12 days of the menstrual cycle. As a result of the survey, a group of 44 women with PCOS and a group of 56 healthy women were formed. PCOS was diagnosed according to ESHRE/ASRM criteria (Rotterdam, 2003). Next, subgroups of women in early reproductive age from 35 to 45 years were formed: a group of women with PCOS (n = 29) and a control group (n = 22). And groups of women in late reproductive age from 35 to 45 years were formed: a group of women with PCOS (n = 15) and a control group (n = 34). Conducted: questionnaire survey, general and gynecological examination, ultrasound examination of the pelvic organs, laboratory tests, statistical data analysis. Results. In women with polycystic ovary syndrome of early reproductive age (1835 years), we detected an increase in the level of testosterone by 2 times, DHEA-S by 1.3 times, 17-OH-progesterone by 2 times, sex steroid-binding globulin by 1.4 times, in comparison with control group. The ratio of luteinizing hormone to follicle-stimulating hormone increased by 52%. In women with polycystic ovary syndrome of late reproductive age (3545 years), we detected an increase in the level of testosterone by 1.5 times, 17-OH-progesterone by 1.9 times, luteinizing hormone by 1.4 times, sex steroid-binding globulin by 1.6 times, in comparison with control group, without any significant differences in DHEA-S. At the same time, the ratio of luteinizing hormone to follicle-stimulating hormone increased by 60%. Conclusion. The hormonal profile of women with PCOS of early and late reproductive period is characterized by series of age-related changes in the pituitary-ovarian system, which should be taken into account in preventive and therapeutic measures.

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