anti-M Llerian Hormone Research Articles

The role of the anti-Müllerian hormone/anti-Müllerian hormone receptor type II signaling pathway in the eutopic and ectopic endometrium in patients with deep endometriosis: A cross-sectional study

Aim. To analyze the profile of anti-Mllerian hormone (AMH) and the expression level of the transmembrane AMH receptor type II (AMHRII) in the eutopic and ectopic endometrium of patients with deep infiltrative endometriosis (DIE).
 Materials and methods. A comparative analysis of AMHRII expression in epithelial and stromal cells of eutopic and ectopic endometrial samples and the level of serum AMH in patients of reproductive age with DIE (n=50) and tuboperitoneal infertility (n=9) was performed.
 Results. AMHRII expression in eutopic endometrial stromal cells of DIE patients was significantly higher compared to glandular cells in all study groups (p0.5). AMHRII expression was found to be significantly higher in glandular cells of the eutopic endometrium compared to the ectopic endometrium of pelvic peritoneal foci in DIE patients: 1.600.77 and 1.090.68 points, respectively (p=0.001).
 Conclusion. The inhibitory effect of AMH on cell proliferation and the proven expression of AMHRII by eutopic and ectopic endometrioid cells may indicate the role of AMH in the pathogenesis of endometriosis and endometriosis-associated infertility.

The hormonal status and the possibility of predicting outcomes in patients with different types of chronic disorders of consciousness

BACKGROUND: Chronic disorders of consciousness are rare clinical conditions that develop after coma and are accompanied by the restoration of wakefulness without the full restoration of consciousness 28 days or longer after brain damage. All women with chronic disorders of consciousness have menstrual irregularities such as oligomenorrhea or secondary amenorrhea. Clinical experience shows that recovery of the menstrual response in a number of patients with chronic disorders of consciousness precedes or is combined with recovery of clear consciousness. The results of a comprehensive examination of patients with different types of ovarian failure, depending on the type of chronic disorders of consciousness, have not been presented in the literature. Therefore, an analysis of the results of such an examination can become the basis for the selection of pathogenetically substantiated hormone-modulating therapy and the development of predictive models for assessing recovery of consciousness from chronic disorders of consciousness.
 AIM: The aim of this study was to assess the variants of ovarian failure in patients with different types of chronic disorders of consciousness and to develop prognostic models that evaluate the possibility of restoring consciousness.
 MATERIALS AND METHODS: This study enrolled 30 patients aged 18 to 44 years divided into three groups depending on the level of consciousness: vegetative state / unresponsive wakefulness syndrome (n = 12), minimally conscious state minus (n = 6), and minimally conscious state plus (n = 12). Here we examined lipid profile changes (total cholesterol, low-density lipoprotein, high-density lipoprotein) and levels of follicle-stimulating hormone, luteinizing hormone, prolactin, total testosterone, estradiol, free triiodothyronine, thyroxine, thyroid-stimulating hormone, adrenocorticotropic hormone, cortisol, and vitamin 25(OH)D in the blood, as well as levels of melatonin in the blood serum and 6-sulfatoxymelatonin in the urine. In addition, in the blood serum and cerebrospinal fluid, we evaluated levels of brain-derived neurotrophic factor, apoptosis antigen 1, Fas-ligand, glutamate, and S100 protein. We also performed ultrasound of the pelvic organs and mammary glands, magnetic resonance imaging of the chiasmal-sellar region, cervical screening, and genetic study (the prothrombin gene mutation and the Leiden factor).
 RESULTS: Hypogonadotropic and normogonadotropic ovarian failures were detected in 36.7% and 63.3% of patients, respectively. No differences in neurotrophin levels between the study groups were found. Three mathematical models were formulated for predicting the recovery of patients into a clear consciousness using the levels of thyroid-stimulating hormone, prolactin, follicle-stimulating hormone, anti-Mllerian hormone, total testosterone, and the age of patients.
 CONCLUSIONS: The presented prognostic models by determining hormone levels in the blood plasma allow for calculating the output of patients in clear consciousness. Further research and accumulation of data on patients with chronic disorders of consciousness are promising for the development of new effective approaches to the rehabilitation of this group of patients.

Ovarian hyperstimulation syndrome in assisted reproductive technology programs in the ­Republic of Bashkortostan

Background. Ovarian hyperstimulation syndrome is a fatal complication of unknown etiology. In connection with the increase in the frequency of this complication, it is necessary to identify prognostically significant markers to discover the risk of its development.
 Aim. To analyze the frequency of ovarian hyperstimulation syndrome and search for the association of genes for differential growth factor 9, luteinizing hormone/horiogonadotropin receptor, and follicle-stimulating hormone receptor with different responses to ovulation stimulation.
 Material and methods. A retrospective single-center cohort study of the frequency and clinical parameters of early ovarian hyperstimulation syndrome was carried out in 147 patients, the average age was 36.5 [3338] years, who underwent an in vitro fertilization program in the period 20062021 in the Department of Assisted Reproductive Technologies of the Republican Medical Genetic Center in Ufa. The study of polymorphic loci of the genes for differential growth factor 9, luteinizing hormone/choriogonadotropin receptor, and follicle-stimulating hormone receptor was performed using TaqMan technology and real-time polymerase chain reaction. Deoxyribonucleic acid was isolated from peripheral blood samples. Statistical analysis was performed using the KruskalWallis criteria, median test, Pearson's 2 test, using the Statistica 12 software package.
 Results. 7577 procedures of assisted reproductive technologies were performed. 147 (2.3%) cases of ovarian hyperstimulation syndrome were registered, 53 (0.8%) cases of moderate and severe degree, 84 (1.3%) cases of mild degree. The *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene was associated with a poor ovarian response 15 (0.75); (2=4.00; p=0.02; odds ratio 3.4; 95% confidence interval 1.1310.27). The distribution of allele and genotype frequencies of the other studied genes did not differ statistically significantly in all the studied groups.
 Conclusion. The frequency of ovarian hyperstimulation syndrome in the Republic of Bashkortostan was 2.3%; the *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene, as well as the level of anti-Mllerian hormone, can serve as markers of a poor response and ovarian hyperstimulation to ovulation stimulation.

Expression of the anti-Müllerian hormone receptor (AMHR2) in the endometrium of patients with uterine anomalies

BACKGROUND: Uterine anomalies are a cause of female reproductive failure. Originally, malformations of the Mllerian ducts are believed to be the main reason for uterus abnormalities. There is an assumption that anti-Mllerian hormone (AMH) or AMH receptor (AMHR2) gene mutation may lead to alterations in the formation of the Mllerian ducts in female fetuses resulting in uterine anomalies.
 AIM: The aim of this study was to assess the AMHR2 expression in the endometrium of patients with uterine anomalies and a history of reproductive failure.
 MATERIALS AND METHODS: The present study included 112 women, of whom 92 patients were diagnosed with uterine anomalies (main groups): arcuate uterus (n = 30), septated uterus (n = 30), bicornuate uterus (n = 12), unicornuate uterus (n = 10), didelphys uterus (n = 10); and 20 patients had normal uterine anatomy (control group), with the secretory phase (n = 10) and the proliferative phase (n = 10) of menstrual cycle evaluated. Histological and immunohistochemical studies of the endometrium were carried out according to the standard technique with an assessment of AMHR2 marker expression in the biopsy samples.
 RESULTS: The AMHR2 area expression in the endometrial stroma was significantly lower in patients with septated uterus compared to those with arcuate uterus (р 0.001). The same tendency was noted when compared to other uterine anomalies and healthy controls. AMHR2 expression in the endometrial stroma of patients with arcuate uterus was significantly higher compared to unicornuate uterus (p 0.05).
 CONCLUSIONS: The data obtained suggest that morphofunctional characteristics of the endometrium in patients with uterine anomalies have no specific pathognomonic features. The decline in AMHR2 expression in the endometrial stroma seems to be related to chronic endometritis, as an inverse correlation exists between the AMHR2 area expression and chronic endometritis, compromising pregnancy occurrence.

The role of mutations in the PI3K/AKT/mTOR signal pathway in decreasing ovarian reserve in reproductive patients with deep infiltrative endometriosis

Aim. To study the effect of deep infiltrative endometriosis on the state of the ovarian reserve in patients of reproductive age, as well as to evaluate the spectrum of mutations in the PIK3CA gene among patients with infiltrative form of external genital endometriosis.
 Materials and methods. The main group of the study included 50 patients of reproductive age with deep infiltrative endometriosis, in 18 of whom deep infiltrative endometriosis was combined with ovarian endometriomas. The comparison group included 25 patients of reproductive age who underwent laparoscopic metroplasty of an inconsistent uterine scar from a cesarean section. All patients underwent determination of the level of anti-Mllerian hormone, follicle-stimulating hormone and estradiol in the blood by enzyme immunoassay, as well as counting the number of antral follicles in the ovaries during transvaginal ultrasound examination. The search for activating mutations of the PIK3CA gene was carried out by sequencing a new generation of DNA in tissue samples of ovarian endometriomas in patients with a combination of infiltrative endometriosis and endometrioid ovarian cysts (n=18), as well as in biopsies of healthy ovarian tissue in all patients of the main group (n=50) and comparison groups (n=25).
 Results. When assessing the state of the ovarian reserve in the patients of the two groups, it was found that the anti-Mllerian hormone level in the patient with the infiltration form of external genital endometriosis was 2.62.2 ng/ml, while in the comparison group it was 3.63.5 ng/ml, however, the difference did not reach statistical significance, p0.05. The number of antral follicles according to transvaginal ultrasound was significantly lower in the main group (8.54.5) than in the comparison group (12.24.1), p=0.001. This difference was statistically significant both for patients with ovarian endometriomas (6.04.2, p0.001) and for patients without ovarian endometriomas (9.84.2, p=0.04). Our study did not reveal PIK3CA gene mutations in any of the ovarian endometrioma tissue samples from patients with a combination of infiltrative endometriosis and endometrioid ovarian cysts, as well as in none of the healthy ovarian tissue biopsies from patients of the main group and the comparison group using the new generation DNA sequencing method.
 Conclusion. The presence of deep infiltrative endometriosis is associated with a decrease in ovarian reserve in patients of reproductive age, regardless of the presence of endometrioid ovarian lesions. Population studies are needed to identify mutations of this gene in endometriosis, as well as to study mutations of other genes encoding proteins regulating the antiapoptotic signaling pathway PI3K/AKT/mTOR, to identify the mechanism of ovarian reserve depletion in infiltrative form of external genital endometriosis.

Main characteristics of IVF / ICSI protocols in patients with suboptimal response to controlled ovarian stimulation

Hypothesis/Aims of study: According to the number of oocytes retrieved in IVF/ICSI protocols, the ovarian response to controlled ovarian stimulation is divided into: poor (03 oocytes), suboptimal (49 oocytes), normal (1015 oocytes) and excessive (15 oocytes) response. However, the effectiveness of IVF / ICSI programs in women with a suboptimal response is poorly understood, since this cohort of patients is often fallen into the category of women with a normal response. The aim of this study was to determine the main characteristics of IVF / ICSI programs in patients with suboptimal response to be further compared to those in women with normal response to controlled ovarian stimulation.
 Study design, materials and methods: This retrospective study included 568 patients: 470 women with suboptimal response and 98 women with normal response to controlled ovarian stimulation. The comparative analysis comprised clinical and anamnestic data, as well as the main characteristics of assisted reproductive technology programs in the selected clinical groups.
 Results: It was found that patients with suboptimal response to controlled ovarian stimulation had significantly more frequent history of pelvic surgery (71.3 % vs. 55.1 %; p 0.01) and pelvic inflammatory diseases (70.9% vs. 60.2%; p 0.05). Parameters of ovarian reserve (serum anti-Mllerian hormone level and antral follicle count) in women with suboptimal response were significantly lower (p 0.001). In addition, the number of mature oocytes, 2PN zygotes, good quality embryos (p 0.001), as well as the clinical pregnancy rate in women with suboptimal response were found to be significantly lower than in patients with normal response to controlled ovarian stimulation (27.2% vs. 41.7%; p 0.01). It was noted that concomitant uterine fibroids enhanced the negative impact on the effectiveness of IVF / ICSI programs in women with suboptimal response to controlled ovarian stimulation (OR = 0.5; 95% CI: 0.30.9; p = 0.03). ROC analysis identified predictors of suboptimal response to controlled ovarian stimulation, such as serum anti-Mllerian hormone level (AUC = 0.80) with the cut-off value of 2.57 ng / ml (sensitivity 74%, specificity 75%) and antral follicle count (AUC = 0.90) with the cut-off value of 10 follicles (sensitivity 80%, specificity 94%).
 Conclusion: In women with suboptimal response to controlled ovarian stimulation, IVF / ICSI success rates are significantly reduced when compared to those in women with normal response. Concomitant uterine fibroids may further decrease the effectiveness of IVF / ICSI protocols in patients with suboptimal response. Predictors of suboptimal response include the serum anti-Mllerian hormone level and antral follicle count.

The role of cholecalciferol in the pathogenesis of polycystic ovary syndrome

Objective to evaluate and compare clinical, anamnestic and laboratory data of patients with polycystic ovary syndrome (PCOS) and without syndrome, including the level of vitamin 25(OH) D3.
 Material and methods. In this work, 81 patients were examined, who, at the 1st stage of the study, were divided into two groups depending on the presence or absence of signs of PCOS. The main group included 51 patients with signs of PCOS. The control group included 30 healthy women without signs of PCOS, matched by sex and age with the main group. The main and control groups were compared by clinical and anamnestic data, including birth weight, by the presence of complications of pregnancy and childbirth in their mothers during their gestation, by the level of vitamin D. PCOS was verified on the basis of diagnostic criteria Rotterdam (2003) and International guidelines on PCOS (2018). Vitamin 25(OH)D3 was determined by mass spectrometry (ng/ml).
 At the 2nd stage of the study, the main group with PCOS was divided into 2 subgroups depending on the waist circumference (WT). Subsequently, the subgroups were compared with each other in the same parameters as at stage 1, as well as in the level of insulin, low-density lipoprotein (LDL), triglycerides (TG), anti-Mllerian hormone (AMH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). To reflect the statistical results, the parametric parameters of the Students t-test were applied for two independent samples with equal or different variance. For nominal data Pearsons Chi-test, when the means are not calculated and a test is carried out for the presence of a relationship between nominal variables.
 Results. There was no statistically significant difference in vitamin 25(OH)D3 levels in patients with and without PCOS. Statistically significant differences in vitamin 25(OH)D3 levels were found in women with PCOS, depending on the waist circumference (WT). In these subgroups, differences were also found in the level of insulin, LDL, TG.
 Conclusion. The values of the level of vitamin 25(OH)D3 do not differ in the groups of patients with PCOS and without PCOS, but significantly correlate with the metabolic profile of patients.

Suboptimal response to controlled ovarian stimulation in IVF / ICSI cycles

Hypothesis/Aims of study. Currently, the frequency of suboptimal response (4-9 retrieved oocytes) to controlled ovarian stimulation (COS) in woman is quite high; however, its efficacy is poorly studied. The aim of this study was to evaluate the main characteristics of IVF / ICSI programs in patients with a suboptimal response to COS.
 Study design, materials and methods. We performed a retrospective study of 412 IVF / ICSI cycles in women with a suboptimal response to COS, including a comparative analysis of clinical and embryological parameters, ovarian reserve and the efficacy of IVF / ICSI protocols.
 Results. Clinical pregnancy rate in ovarian stimulation cycles with a suboptimal response to COS was 27.9%. The efficacy of assisted reproductive technology (ART) programs in women with uterine fibroids was significantly lower than in patients without fibroids (19.1% vs. 30.5%, p = 0.03; OR = 0.54; 95% CI: 0.31-0.95). Clinical pregnancy rate in patients with male factor infertility was significantly higher than in women with anovulation (37.1% vs. 20.9%, р = 0.005; OR = 2.24; 95% CI: 1.27-3.94) or tubal factor infertility (37.1% vs. 24.8%, р = 0.02; OR = 1.79; 95% CI: 1.09-2.94). There were significant correlations between the number of retrieved oocytes with serum anti-Mllerian hormone (AMH) concentration (r = 0.32, p 0.001) and antral follicle count (AFC) (r = 0.38, p 0.001). In addition, the need for follicle-stimulating hormone (FSH) preparations during COS correlated significantly with ovarian reserve parameters (AMH and AFC) (r = 0.45 and 0.44, both p 0.001, respectively) and the age of patients (r = 0.47; p 0.001).
 Conclusion. The clinical pregnancy rate in women with a suboptimal response to COS was low. Concomitant uterine fibroids represented an additional factor of negative influence on IVF / ICSI outcomes in women with a suboptimal response to COS. The male factor of infertility in patients with a suboptimal response did not reduce the efficacy of ART programs. Ovarian reserve parameters in women with a suboptimal response correlated with the need for FSH preparations during COS and the number of retrieved oocytes.

Lipid profile in women of reproductive age with various polycystic ovary syndrome phenotypes

Hypothesis/Aims of study. Dyslipidemia is a common metabolic disorder and is an atherogenic factor in the development of cardiovascular disease in women with polycystic ovary syndrome. Currently, four phenotypes of polycystic ovary syndrome are distinguished, associated in varying degrees of severity with dyslipidemia, insulin resistance, impaired glucose tolerance, and diabetes mellitus on one hand and chronic inflammation and oxidative stress on the other. Hyperandrogenic phenotypes (A, B, C) in polycystic ovary syndrome are associated with the development of adverse metabolic disorders and associated complications. The aim of this study was to evaluate the lipid profile in the serum of women of reproductive age with various polycystic ovary syndrome phenotypes.
 Study design, materials and methods. The study included 86 women of reproductive age from 22 to 37 years old (average age was 26.6 4.3 years), who, in accordance with polycystic ovary syndrome phenotypes (A, B, C, D), were divided into four groups. We studied the levels of anti-Mllerian hormone, follicle-stimulating and luteinizing hormones, prolactin, estradiol, and androgens from days 2 to 5 of the menstrual cycle. The levels of progesterone in the blood serum were determined by the enzyme immunoassay on days 20 to 23 of the menstrual cycle for three consecutive cycles. We also used echographic methods for diagnosing polycystic ovaries. All women underwent a biochemical blood test with an assessment of the lipid profile parameters (total cholesterol, triglycerides, high-density lipoproteins (HDL), and low-density lipoproteins, LDL). Besides, an oral glucose tolerance test was assessed with the study of plasma glucose and insulin levels on an empty stomach and two hours after ingestion of 75 g of glucose, the HOMA-IR index being used to assess insulin resistance.
 Results. Phenotype A was found in 40 (46.5%) women with polycystic ovary syndrome, phenotype B in 22 (25.6%), phenotype C in 10 (11.6%), and phenotype D (non-androgenic) in 14 (16.3%) patients with PCOS. Of those 42 (48.8%) individuals had changes in carbohydrate metabolism (impaired glucose tolerance), of whom 39 (92.8%) women had androgenic polycystic ovary syndrome phenotypes (A, B, C). Both non-androgenic phenotype D and impaired glucose tolerance were found in 7.2% of cases. In women with hyperandrogenic polycystic ovary syndrome phenotypes, both the fasting and stimulated insulin levels were increased significantly comparing to the non-androgenic anovulatory phenotype (p 0.05). The HOMA-IR index in women with phenotypes A, B and C was significantly (p 0.05) higher than in patients with non-androgenic phenotype D. When evaluating the lipid profile parameters, no significant differences in cholesterol level and atherogenic coefficient in women with various polycystic ovary syndrome phenotypes were found. The levels of triglycerides and LDL were significantly (p 0.05) higher in women with androgenic phenotype B compared to those in patients with non-androgenic phenotype D and they correlated significantly (p 0.05) with the serum levels of androgens and sex hormone-binding globulin (SHBG). Patients with androgenic polycystic ovary syndrome phenotypes (A and B) had significantly (p 0.05) decreased HDL levels that correlated negatively (r = 0.29; p 0.05) with the levels of free testosterone and SHBG, when compared to the same parameters in women with non-androgenic phenotype D. In women with androgenic polycystic ovary syndrome phenotypes (A, B, C), a significant correlation (r = 0.27; p 0.05) between the levels of stimulated insulin and SHBG were found, and a direct relation (r = 0.32; p 0.05) between those parameters and increased levels of triglycerides and LDL was also revealed.
 Conclusion. In women with hyperandrogenic and anovulatory polycystic ovary syndrome phenotypes A and B, atherogenic dyslipidemia and impaired carbohydrate metabolism were significantly more pronounced, when compared with patients with non-androgenic phenotype D. A differential and personalized approach to the examination of patients with various polycystic ovary syndrome phenotypes is an important step in the prevention of the risks of developing cardiovascular diseases in women of reproductive age.

Anti-Mullerian hormone and its predictive value for assessing oocyte quality

The article systematizes information on the diagnostic capabilities of modern clinical and laboratory markers of ovarian reserve. The diagnostic capabilities of anti-Mllerian hormone (AMH) as a marker of ovarian reserve are discussed, which make it possible to adjust the dose of hormonal drugs and predict the response of the ovary to stimulation in programs of assisted reproductive technologies. This paper discusses for the first time the role of AMH in assessing the quality of oocytes and subsequent embryos. Despite insufficient literature data, further study of AMH, as well as full-scale research in this direction, seems to be extremely promising.

Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk.

Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs. A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile). Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001). In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.

Diagnosis of congenital sexual maldevelopment in boys with bilateral inguinal cryptorchidism during minipuberty

Cryptorchidism is associated with the risk of infertility and can be a symptom of congenital sexual maldevelopment. To assess the functional status of the pituitary gland and sexual glands in boys aged 16 months with bilateral inguinal cryptorchidism and to reveal the congenital sexual maldevelopment during minipuberty. Twenty-one boys aged 16 months (the minipuberty period) with isolated bilateral inguinal cryptorchidism and 40 healthy boys aged 23 months (the control group) were examined. The gonadal status was assessed and serum levels of sex hormones were measured. Molecular genetic testing was performed if there were indications for it. The results of hormone analysis were used to divide the patients into three groups: group 1 patients with normal serum levels of gonadotropin and sex hormones; group 2 patients with elevated gonadotropin level and low levels of anti-Mllerian hormone (AMH) and inhibin B, and group 3 patients with zero gonadotropin and testosterone levels and low levels of AMH and inhibin B. Group 1 patients had no functional disturbances in the pituitarygonadal system. Failure of Sertoli cells associated with a high risk of infertility was detected in group 2 patients. Group 3 patients were diagnosed with hypogonadotropic hypogonadism verified by molecular genetic tests. Hormonal testing of patients with bilateral inguinal cryptorchidism during minipuberty makes it possible to early detect the congenital sexual maldevelopment.

An alternative method of surgical treatment of ovarian endometriomas from the standpoint of preservation of the ovarian reserve

Hypothesis/aims of study. Ovarian endometriomas are a great danger to the female reproductive function. In addition to the negative impact of the disease itself on ovarian reserve, the reproductive capabilities of women are influenced by surgery on the ovaries and subsequent hormonal therapy. Ovarian reserve after cystectomy of the endometriomas suffers more than after removal of other benign ovarian tumors. The solution of the problem can be obtained using sclerotherapy during laparoscopy. The aim of this study was to assess the impact of sclerosing endometriomas during laparoscopy on the ovarian reserve.&#x0D; Study design, materials and methods. The study involved 36 patients aged 2535 years. Inclusion criteria were genital endometriosis, endometrioma of one of the ovaries with a volume of 15100 cm3, and pregnancy planning. Exclusion criteria were uterine fibroids, endometrial hyperplasia, polycystic ovary syndrome, and the previous operations on the ovaries and uterine tubes. The main group consisted of 18 patients who underwent sclerotherapy of an endometrioma during laparoscopy with a 70% ethanol solution. The comparison group comprised 18 patients who underwent cystovariectomy with bipolar coagulation of the tumor lining. Within 4 months after surgery, gonadotropin-releasing hormone agonists were administered. An ultrasound examination of the pelvic organs and determination of anti-Mllerian hormone (AMH) level were performed before surgery, after surgery, and after hormonal treatment.&#x0D; Results. In both study groups, AMH level decreased immediately after surgery: in the main group, it reduced by 1.4 times, in the comparison group by 2.4 times. After termination of therapy with gonadotropin-releasing hormone agonists and recovery of the menstrual cycle, AMH level increased slightly (it was 2.9 0.40 ng/ml in the main group, and 1.8 0.24 ng/ml in the comparison group). Within 12 months after surgery, pregnancy occurred in 44.4% of patients in the main group and in 33.3% of patients in the comparison group. Over 16 months of follow-up, not a single case of recurrence of the disease was subsequently detected.&#x0D; Conclusion. Sclerotherapy of endometriomas during laparoscopy is supposed to be an effective and promising technique aimed at preserving the ovarian reserve in this category of patients.

The Non-linear Association Between Serum Level of Anti-M�llerian Hormone and in vitro Fertilisation Outcome

Aim of the study was to analyse the relationship between Anti-M�llerian Hormone (AMH) serum level and in vitro fertilisation (IVF) with and without intra-cytoplasmic sperm injection (ICSI) outcome. We performed a retrospective study which included 1073 patients (mean age 34.68�4.28 years, mean body mass index 22.7�15.65 kg/m2) who performed IVF or IVF/ICSI between January 2013 and December 2016.We found that AMH serum level was age-independent positively related with oocytes (beta=0.329, p[0.0001) and zygotes number (beta=0.248, p[0.0001) and negatively correlated with fertilization rate (beta=-0.108, p=0.001). In multivariate regression, after adjustment for confounders, only oocytes number, but not AMH serum level, was associated with zygotes number (beta=0.814, p[0.0001) and fertilisation rate (beta=- 0.133, p=0.001). Patients with AMH in the range 1.1-5 ng/mL had significantly higher biochemical (65.3% versus 56.6%, p=0.009) and clinical pregnancy rates (57.7% versus 49.2%, p=0.014) in comparison with patients with AMH below 1.1 ng/mL and higher clinical pregnancy rates in comparison with patients with AMH above 7 ng/mL (57.7% versus 44%, p=0.011). Logistic regression analysis showed that AMH was positively associated with biochemical (OR 1.19, p=0.003) and clinical pregnancy (OR 1.16, p=0.009) independently of age and number of good embryos transferred in patients with AMH below 5 ng/mL. In turn, when only patients with normal ovarian reserve were analysed (AMH above 1.1 ng/mL), we found an age-independent negative association between AMH and clinical pregnancy (OR 0.93, p=0.014). AMH serum level is associated with both quantitative response (oocytes number) and qualitative parameters (pregnancy rate) during IVF/ICSI. We also found a bimodal relationship between AMH and pregnancy rates, which were positively associated in patients with AMH below 5 ng/mL, although higher AMH values seem to have a negative impact on pregnancy chances.

Endometrial cell apoptosis impairment associated with hormonal imbalance as a key factor in the development of endometriosis

The review describes the effect of certain hormones and their imbalance on apoptosis of retrogradely refluxed endometrial cells in the abdominal cavity and the effects of estrogen, progesterone, anti-Mullerian hormone, and gonadotropin-releasing hormone on the internal and external apoptotic pathways of various cell populations in endometriotic foci. The nuclear estrogen receptor β (ER-β) is shown to inhibit TNF receptors that trigger the external apoptotic pathway, but the effects of estrogens do not play a key role in the pathogenesis of endometriosis. The role of progesterone and changes in the receptor status towards prevalence of PR-A with a decreased response of endometrial tissue to progesterone and inhibition of apoptosis are described. We discuss the role of the anti-Müllerian hormone and gonadotropin-releasing hormone II (GnRH II) as activators of apoptosis in normal endometrial tissue and in endometriosis. Investigation of endocrine effects on apoptosis of parenchymal and stromal cells of endometriotic foci may provide a theoretical basis for searching for new therapeutic targets in this hormone-dependent pathology.

Effects of electroacupuncture at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency

To explore the effects of electroacupuncture (EA) at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency (POI). A total of 48 SD female rats with regular estrus were divided into a blank group (n=8), a model group (n=10), an EA group (n=10), a binding group (n=10) and a tamoxifen (TAM) group (n=10). The rats in the model group, EA group, binding group and TAM group were all treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 15 consecutive days to establish the model of POI; the rats in the blank group were treated with normal diet. After the model was established successfully, the rats in the EA group were treated with EA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) with continuous wave (1 to 3 Hz, 0.1 to 1 mA) for 20 minutes, once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the TAM group were treated with subcutaneous injection of tamoxifen (1mg/kg), once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the binding group were bound by a small sack as the EA group. The rats in the blank group and the model group were treated with normal diet. After four weeks, the sexual gland weight and index were tested in each group; the ELISA method was applied to test the level of anti-mllerian hormone (AMH) and inhibin B; the morphology of ovary was observed; the number of primordial follicles, primary follicle, antral follicle and atretic follicle was counted; the expression of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) were measured. (1) Compared with the blank group, the ovary weight, ovary index, uterus weight and uterus index were significantly decreased after treatment in the model group, EA group, binding group and TAM group (all P<0.01); but the differences between the model group and the EA group, binding group, TAM group were not significant (all P>0.05). (2) Compared with the blank group, the levels of serum AMH, inhibin B and E2 were significantly reduced; the levels of FSH and LH were significantly increased in the model group; EA group, binding group and TAM group (all P<0.01). Compared with the model group, the levels of serum AMH, inhibin B and E2 were significantly increased, the level of FSH and LH were significantly reduced in the EA group and TAM group (all P<0.01). (3) Compared with the blank group, in the model group, EA group, binding group and TAM group the ovary was dark red and pale, surrounded by particle or not; the morphology was small and atrophic; the primordial follicles was reduced even vanished; the structure of primary follicle was damaged and loosely arranged; the mature follicle was few; the atretic follicle and interstitial gland were increased. (4) Compared with the blank group, the expressions of IGF-1 mRNA and IGF-1R mRNA were increased in the model group (all P<0.01); compared with the blank group, the expression of IGF-1 mRNA was increased in the binding group (P<0.05), but that of IGF-1R mRNA was not significantly different (P>0.05); compared with the model group, the expression of IGF-1 mRNA was not significantly different in the EA group, binding group and TAM group (all P>0.05), but that of IGF-1R mRNA was reduced (P<0.05, P<0.01). EA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) has improvement effect on ovarian function in rats with VCD-induced POI, which is likely to be related to regulating the IGF-1R mRNA expression to improve the IGF-1/ IGF-1R axis.

Ovarian reserve in patients who have undergone endometriosis surgery

Background/Aim. Endometriosis is a gynaecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. The aim of this paper was to determine the effect of laparoscopic cystotomy and cystectomy on ovarian function, as well as to compare these two methods in terms of qualitative and quantitative damage to the ovaries, achieved pregnancies and recurrence. Methods. The prospective study, conducted in ?Narodni Front? Obstetrics and Gynaecology Clinic in Belgrade at the Endoscopic Infertility Treatment Ward, included a total of 150 patients. The study group was represented by 100 patients who underwent a surgical treatment of endometrial ovarian cysts. The patients in the study group were divided into 2 subgroups: Subgroup I consisted of 50 patients who underwent a laparoscopic cystotomy (incision of the cyst and thermal coagulation) and subgroup II which included 50 women who underwent a laparoscopic cystectomy. The control group consised of patients who underwent a surgery due to tubal factor infertility. The following parameters of the ovarian function were tested: the ovarian volume, the antral follicle count, the presence of the preovulatory follicle on the operated ovary, the serum levels of anti- M?llerian hormone (AMH), follicle-stimulating hormone (FSH), ovarian tumor marker (Ca 125), inhibin B, as well as the rate of achieved pregnancies one year after the surgery. Results. The ovarian volume and the antral follicle count as well as the FSH values were significantly higher in the control group in comparison with the patients in the study group. There were no significant differences in the ovarian volume, the antral follicle count, the AMH values and inhibin B values in the study group between the patients with cystectomy and those with the incision and coagulation of the cyst. Conclusion. Both surgical techniques diminished the ovarian reserve: cystectomy was more aggressive method in terms of the damage inflicted on the ovarian tissue, and incision with coagulation carried a higher risk of recurrence.

Seminal plasma anti-M�llerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE)

To assess seminal plasma anti-Müllerian hormone (AMH) level relationships in fertile and infertile males. Eighty-four male cases were studied and divided into four groups: fertile normozoospermia (n = 16), oligoasthenoteratozoospermia (n = 15), obstructive azoospermia (OA) (n = 13) and non-obstructive azoospermia (NOA) (n = 40). Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction (TESE) in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE (n = 19) and successful TESE (n = 21). Seminal plasma AMH was estimated by enzyme linked immunosorbent assay (ELISA) and serum follicular stimulating hormone (FSH) was estimated in NOA cases only by radioimmunoassay (RIA). Mean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance (41.5 +/- 10.9 pmol/L vs. 30.5 +/- 10.3 pmol/L, P < 0.05). Seminal AMH was not detected in any OA patients. Seminal AMH was correlated positively with testicular volume (r = 0.329, P = 0.005), sperm count (r = 0.483, P = 0.007), sperm motility percent (r = 0.419, P = 0.021) and negatively with sperm abnormal forms percent (r = -0.413, P = 0.023). Nonsignificant correlation was evident with age (r = -0.155, P = 0.414) and plasma FSH (r = -0.014, P = 0.943). In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE (57.5%) and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE (58.2%). Seminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases.

Molecular analysis of the anti-Müllerian hormone, the anti-Müllerian hormone receptor, and galactose-1-phosphate uridyl transferase genes in patients with the Mayer-Rokitansky-Küster-Hauser syndrome.

Müllerian agenesis, also named the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) or vaginal aplasia, is the second most common cause of primary amenorrhea. It is characterized by the congenital absence of the Müllerian structures including the Fallopian tubes, the uterus, and the internal portion of the vagina in an otherwise normally feminized 46,XX subject. Most cases are sporadic in inheritance, but the occurrence of some patients with chromosomal translocations or even familial aggregates suggest a genetic basis for the disease, although the etiology of the disease is still unknown. It has been suggested that activating mutations in the anti-Müllerian hormone (AMH) or in its receptor (AMHRII) are potential sources for the defect. In this study we describe the molecular analysis of both the AMH and AMHR genes in a group of 15 patients with Müllerian agenesis. After sequencing all exons and exon/intron junctions of both genes, we were not able to detect any deleterious mutation. Five new polymorphisms, 2 of them in the AMHRII gene and 3 of them in the AMH gene, were identified. No significant differences between patients and controls were observed in the frequency of a given polymorphism. This work reinforces the view that molecular defects in the AMH or AMHR are unlikely sources for the MRKHS syndrome.