Antral Follicles Count and Anti-Müllerian Hormone Levels after Gonadotoxic Chemotherapy in Patients with Breast Cancer: Cohort Study / Contagem de folículos antrais e níveis de hormônio anti-Mülleriano após quimioterapia gonadotóxica em pacientes com câncer de mama: estudo de coorte

Abstract Aim To assess ovarian reserve (OVR) by means of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) measurement in eumenorrheic women with breast cancer, exposed to gonadotoxic chemotherapy. Method Fifty-two women (35.3 ± 3.8 years old) with breast cancer and undergoing cyclophosphamide-containing chemotherapy were enrolled. The assessment was performed before chemotherapy (T1) and after 2 (T2) and 6 months (T3). Results Six months after chemotherapy, the prevalence of regular cycles was 60%. Anti-Müllerian hormone decreased down to undetectable levels at T2 and T3 (T1: 2.53 [1.00–5.31]; T2 < 0.08; T3: < 0.08 [< 0.08–1.07] ng/mL), (p< 0.0001). Antral follicle count was 11 [8.0–13.5] follicles at T1 and lower at T2 (5.50 [3.75–8.0] and T3 (5.0 [2.5–7.0]) (p< 0.0001). In patients who remained with regular cycles during chemotherapy or resumed normal menses, FSH and estradiol levels remained unchanged. Conclusion Anti-Müllerian hormone and AFC are useful as markers of OVR decline in women exposed to chemotherapy. Follicle-stimulating hormone is only adequate in women who become amenorrheic.

Resumo Objetivo Avaliar a reserva ovariana (OVR) através da contagem de folículos antrais (AFC), dosagem sérica de hormônio folículo estimulante (FSH) e hormônio anti-Mülleriano (AMH) em mulheres com câncer de mama submetidas a quimioterapia gonadotóxica. Método Foram incluídas na pesquisa 52 mulheres (35,3 ± 3,8 anos) com câncer de mama, em tratamento com quimioterapia com ciclofosfamida. As dosagens e medidas foram realizadas antes do início da quimioterapia (T1) e após 2 (T2) e 6 meses (T3). Resultados Seis meses após quimioterapia, a prevalência de ciclos regulares foi de 60%. O AMH sérico diminuiu a níveis indetectáveis em T2 e T3 (T1: 2,53 [1,00–5,31] ]; T2 < 0,08; T3: < 0,08 [< 0,08–1,07] ng/mL) (p< 0,0001). A contagem de folículos antrais foi de 11 [8,0–13,5] folículos em T1, e ainda menor em T2 (5,50 [3,75–8,0] e T3 (5,0 [2,5–7,0]), (p< 0,0001). Em pacientes que mantiveram ciclos regulares durante a quimioterapia ou retomaram a menstruação normalmente, os níveis de FSH e estradiol permaneceram inalterados. Conclusão O AMH e a AFC são marcadores úteis do declínio da OVR em mulheres expostas à quimioterapia. O FSH só é adequado em mulheres que se tornam amenorreicas.

Follicle stimulating hormone and anti-mullerian hormone among fertile and infertile women in Ile-Ife, Nigeria: is there a difference?

Background: Reduced ovarian reserve predicts poor ovarian response and poor success rates in infertile women who undergo assisted reproductive technology [ART]. Ovarian reserve also decreases with age but the rate of decline varies from one woman to another. This study aims to detect differences in ovarian reserve as measured by basal serum follicle stimulating hormone [FSH] and anti-Mullerian hormone [AMH] between a matched cohort of fertile and infertile regularly menstruating women, 18-45 years of age

Materials and Methods: This case-control study involved 64 fertile and 64 subfertile women matched by age at recruitment. Peripheral blood samples were taken from the women recruited from the Gynecological and Outpatient Clinics of Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. Serum FSH and AMH were quantified using ELISA at the Metabolic Research Laboratory of LAUTECH Teaching Hospital, Ogbomoso, Nigeria

Results: A significant difference existed in the mean FSH of fertile [6.97 +/- 3.34] and infertile [13.34 +/- 5.24, P=0.013] women. We observed a significant difference in AMH between fertile [2.71 +/- 1.91] and infertile [1.60 +/- 2.51, P=0.029] women. There was a negative correlation between FSH and AMH in both fertile [r=-0.311, P=0.01] and infertile [r=-0.374, P=0.002] women

Conclusion: The difference in ovarian reserve observed in this study suggests that reduced ovarian reserve in regularly menstruating women may be associated with early ovarian ageing or subfertility

Age as a predictor of embryo quality regardless of the quantitative ovarian response

Background: One determining factor of a successful in vitro fertilization [IVF] cycle is embryo quality. The aim of the present study was to evaluate associations of embryo quality and reserve markers like age, FSH and AMH

Materials and Methods: In this prospective study, 120 infertile women, aged 21-44 years, undergoing routine exploration during an unstimulated cycle preceding assisted reproductive technology [ART] at our center were studied prospectively, from February 2011 to December 2014. Descriptive parameters and patient characteristics were reported as mean [SD] or median [range] depending on the distribution. Student's t test was performed for continuous variables, Wilcoxon and Pearson's Test were used for not distributed variables and Fisher's Test was performed for categorical variables. P<0.05 was considered statistically significant

Results: Overall, at the time of investigation, patients had a mean age of 33.03 +/- 4.15 years old. On cycle day three, serum anti-Mullerian hormone [AMH] level was 3.50 +/- 1.54 ng/mL, serum follicle-stimulating hormone [FSH] level was 6.29 +/- 1.53 mUI/ mL, at baseline, women had 16.57 +/- 7.0 antral follicles. The mean of collected oocytes was 11.80 +/- 5.25, embryo I+II was 2.46 +/- 2.11. A greater number of embryos I+II was observed in young patients. By evaluating 120 patients, a significant relationship was observed between age and FSH [r=0.24, P=0.01], age with AMH [r=-0.22, P=0.02], age with collected oocytes [r=-0.23, P=0.03] and age with embryo I+II [r=-0.22, P=0.03]. A significant relationship was also observed between antral follicle count [AFC] and AMH [r=0.29, P=0.01], AFC and the number of transferred embryo [r=-0.18, P=0.03], AFC and total dose of the drugs [r=-0.23, P=0.03]. Significant relationship of FSH with total dose of drugs [r=0.19, P=0.02] was also observed. In addition, we determined significant relationships between AMH and the number of collected oocytes [r=0.38, P=0.01], AMH and the number of metaphase II oocytes [r= 0.35, P=0.01], AMH and the number of embryo [r=0.19, P=0.04] as well as AMH and total dose of the drugs [r=-0.25, P=0.01]

Conclusion: Commonly used clinical markers of ovarian reserve are reflection of the ovarian reserve, while the outcome measurements of ART and age are the best predictors of embryo quality

Tear osmolarity and tear function assessment in patients with polycystic ovary syndrome / Avaliação da osmolaridade lacrimal e da função lacrimal em pacientes com síndrome dos ovários policísticos

ABSTRACT Purpose: Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by chronic anovulation and hyperandrogenism. Hormonal changes can affect tear function. This study evaluates tear function and impact of hyperandrogenism on it in PCOS patients. Methods: Fifty patients with PCOS and thirty control volunteers were examined for tear break-up time, Schirmer-I and tear osmolarity. Also, serum levels of total testosterone, FSH, LH and AMH were determined in venous blood samples in the early follicular phase. PCOS patients were divided into two groups by plasma total testosterone level: Group A with normal (≤0.513 ng/ml;n=27), Group B with higher hormone level (>0.513 ng/ml;n=23). Healthy control group indicated as Group C (n=30). Results: LH, total testosterone levels were higher in the PCOS group than in the control group (p=0.012; p=0.025). Mean values of tear break-up time and Schirmer-I were different between groups and especially Group A and C were near to each other differing from B (p>0.05). Tear osmolarity results were higher in Group B, compared to A and C (p=0.049; p=0.033). No significant difference detected in tear osmolarity value means of Group A and C (p=0.107). AMH levels were higher in Group B, compared to A and C (p=0.002; p=0.001). AMH levels in Group A were higher than that of C (p=0.002). Positive correlation between levels of total testosterone and AMH was detected in all PCOS patients (n=50;Pearson's r=0.579; p<0.001). Conclusion: Tear function can be affected in PCOS patients with hyperandrogenism. Tear osmolarity is the most sensitive and objective assessment method for ocular surface changes in PCOS.

RESUMO Objetivo: A síndrome do ovário policístico (SOP) é uma doença endócrina caracterizada por anovulação crônica e hiperandrogenismo. As alterações hormonais podem afetar a função cardíaca. Este estudo avalia a função lacrimal e o impacto do hiperandrogenismo sobre ela em pacientes com SOP. Métodos: Cinquenta pacientes com SOP e trinta voluntárias de controle foram examinadas para tempo de ruptura lacrimal, Schirmer-I e osmolaridade lacrimal. Além disso, os níveis séricos de testosterona total, FSH, LH e HAM foram determinados em amostras de sangue venoso na fase folicular precoce.As pacientes com SOP foram divididas em dois grupos por nível de testosterona plasmática total: Grupo A com nível normal (≤0.513 ng/ml; n = 27), Grupo B com nível superior de hormônio (> 0,513 ng/ml; n = 23). Grupo de controle saudável indicado como Grupo C (n = 30). Resultados: Os níveis de LH e testosterona total foram maiores no grupo com SOP do que no grupo controle (p = 0,012; p = 0,025). Os valores médios de tempo de ruptura lacrimal e Schirmer-I foram diferentes entre os grupos, e especialmente os Grupos A e C estavam próximos um do outro, diferente do B (p > 0,05). Os resultados de osmolaridade lacrimal foram maiores no Grupo B, em comparação com A e C (p = 0,049; p = 0,033). Não houve diferença significativa detectada em valor médio de osmolaridade lacrimal nos Grupos A e C (p = 0,107). Os níveis de HAM foram maiores no Grupo B, em comparação com A e C (p = 0,002; p = 0,001). Os níveis de AMH no Grupo A foram superiores aos de C (p = 0,002). Uma correlação positiva entre os níveis de testosterona total e AMH foi detectada em todas as pacientes com SOP (n = 50; Pearson's r = 0,579; p < 0,001). Conclusão: a função lacrimal pode ser afetada em pacientes com SOP com hiperandrogenismo. A osmolaridade lacrimal é o método de avaliação mais sensível e objetivo para alterações da superfície ocular em SOP.

Hormônio anti-Mülleriano como preditor de reserva ovariana em pacientes lúpicas: uma revisão / Anti-Müllerian hormone levels as a predictor of ovarian reserve in systemic lupus erythematosus patients: a review

RESUMOO hormônio anti-Mülleriano (HAM) é secretado a partir das células da granulosa dos folículos ovarianos em crescimento e parece ser o melhor marcador endócrino capaz de estimar a reserva ovariana. O lúpus eritematoso sistêmico (LES) é uma doença autoimune que acomete predominantemente mulheres em idade reprodutiva e pode afetar negativamente sua fertilidade pela atividade da doença, bem como pelos tratamentos usados. Conhecer o real impacto do LES e de seu tratamento na fertilidade vem sendo o objetivo de estudos recentes, os quais têm usado o HAM para esse fim.

ABSTRACTThe anti-Müllerian hormone (AMH) is secreted from granulosa cells of growing ovarian follicles and appears to be the best endocrine marker capable of estimating ovarian reserve. Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age and may negatively affect their fertility due to disease activity and the treatments used. Recently, several studies assessed AMH levels to understand the real impact of SLE and its treatment on fertility.

What Number of Oocytes Is Appropriate for Defining Poor Ovarian Response?

PURPOSE: This study attempted to derive an objective and sophisticated definition of poor ovarian response (POR). MATERIALS AND METHODS: A total of 176 consecutive in vitro fertilization (IVF) cycles (137 patients) with conventional ovarian stimulation during 2009 to 2012 were studied by retrospective analysis. Optimal oocyte number (total or mature) was determined by statistics-based (distribution of oocyte number) and prognosis-based approaches (prediction for IVF outcome). Receiver operating characteristics curve analysis was used to show what number of oocytes could predict IVF pregnancy and whether clinical and laboratory variables could predict newly defined POR. RESULTS: The 25th percentile of the distribution corresponded to total oocytes 5 and mature oocyte >1. Considering the incidence of POR (34.1%), a reasonable definition of POR was decided as total oocytes < or =2 or mature oocyte < or =1. For the prediction of this new definition, the extreme cut-off value (by setting a false positive rate of 5%) of serum anti-Mullerian hormone (AMH) was < or =0.76 ng/mL, which was better than serum follicle stimulating hormone or age. A new simple definition of POR was derived as total oocytes < or =2 or mature oocyte < or =1 in a previous cycle or a serum AMH level of < or =0.76 ng/mL. When this simple criterion was re-applied to our data, the predictive performance was similar to the Bologna criteria. CONCLUSION: We here propose a new definition of POR, which is simple and supported by statistical and prognostic analyses.

What Number of Oocytes Is Appropriate for Defining Poor Ovarian Response?

PURPOSE: This study attempted to derive an objective and sophisticated definition of poor ovarian response (POR). MATERIALS AND METHODS: A total of 176 consecutive in vitro fertilization (IVF) cycles (137 patients) with conventional ovarian stimulation during 2009 to 2012 were studied by retrospective analysis. Optimal oocyte number (total or mature) was determined by statistics-based (distribution of oocyte number) and prognosis-based approaches (prediction for IVF outcome). Receiver operating characteristics curve analysis was used to show what number of oocytes could predict IVF pregnancy and whether clinical and laboratory variables could predict newly defined POR. RESULTS: The 25th percentile of the distribution corresponded to total oocytes 5 and mature oocyte >1. Considering the incidence of POR (34.1%), a reasonable definition of POR was decided as total oocytes < or =2 or mature oocyte < or =1. For the prediction of this new definition, the extreme cut-off value (by setting a false positive rate of 5%) of serum anti-Mullerian hormone (AMH) was < or =0.76 ng/mL, which was better than serum follicle stimulating hormone or age. A new simple definition of POR was derived as total oocytes < or =2 or mature oocyte < or =1 in a previous cycle or a serum AMH level of < or =0.76 ng/mL. When this simple criterion was re-applied to our data, the predictive performance was similar to the Bologna criteria. CONCLUSION: We here propose a new definition of POR, which is simple and supported by statistical and prognostic analyses.

Correlation between the Serum Luteinizing Hormone to Folliclestimulating Hormone Ratio and the Anti-Mullerian Hormone Levels in Normo-ovulatory Women

Serum anti-Mullerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.

Correlation between the Serum Luteinizing Hormone to Folliclestimulating Hormone Ratio and the Anti-Mullerian Hormone Levels in Normo-ovulatory Women

Serum anti-Mullerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.

Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model / 부인종양

OBJECTIVE: To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment. METHODS: Twenty-one adult female Sprague-Dawley rats were used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 microg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4degrees C for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30degrees C for hormone assays. RESULTS: All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Mullerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group. CONCLUSION: G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.

[Determination and comparison of estimated menopausal age based on serum anti-mullerian hormone in women with and without polycystic ovarian syndrome]

Menopause is defined as 12 months of constant amenorrhea in the absence of any pathology. Right now there is no definite test to predict menopause age and the ovarian reserve evaluations are mainly implemented on the basis of sonographic and hormonal measurements. The present study was conducted to determine and compare the menopausal age in women with polycystic ovarian syndrome [PCOS] and non PCOS women based on anti-mullerian hormone [AMH]. The present study is an epidemiologic case- control research in which from among 1019 women aged 20-40 years, 208 PCOS women and 811 normo-ovulatory controls were selected as the case and control groups respectively. Data collection was done through completing questionnaire, clinical examination and lab test measurements. After age and body mass index [BMI] matching, AMH levels in relation to age were displayed in an interactive graph and SPSS software version 21 was used for statistical analysis. Findings showed the mean age and BMI for case and control groups were 29.75 years - 27.1 [kg/m[2]] and 31.62 years - 26.1 [Kg/m[2]] respectively. Our results indicated significantly higher AMH levels in PCOS cases than in normal controls [P<0.0001]. The estimated menopausal age for PCOS and non PCOS women was 51 and 49 years respectively. To conclude PCOS patients reach menopause two years later than healthy women. If the length of reproductive period in these patients is higher than that the healthy women, it may be possible to use this period for increasing the fertility likelihood

Uso clínico do hormônio antimülleriano em ginecologia / Clinical use for anti-mullerian hormone in gynecology

O hormônio antimülleriano (AMH) é uma glicoproteína produzida pelas células granulosas de folículos ovarianos primários, pré-antrais e pequenos folículos antrais e ultimamente sua aplicabilidade clínica tem sido demonstrada através de diversos estudos. A predição da resposta à estimulação ovariana para fertilização in vitro corresponde a sua mais frequente utilização na prática clínica, sendo rotineiramente realizada em muitos serviços para identificar subgrupos de mulheres suscetíveis a má resposta ou a Síndrome da Hiperestimulação Ovariana. Existem perspectivas de que o AMH possa ser aplicável na individualização do risco de injúria gonadal iatrogênica em mulheres portadoras de neoplasia que serão submetidas a quimioterapia. Também é provável que as dosagens de AMH sejam incluídas nos protocolos de investigação de amenorreias e oligomenorreias, uma vez que seus níveis encontram-se elevados em pacientes portadoras da Síndrome dos Ovários Policísticos, reduzidos em casos de falência ovariana prematura e normais em outras condições como a hiperprolactinemia e o hipogonadismo hipogonadotrófico. É possível que futuramente o AMH venha a ser utilizado na predição da idade de menopausa e do prognóstico reprodutivo da mulher, fornecendo bases sólidas ao aconselhamento conceptivo e contraceptivo.

Anti-mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of primary, pre-antral and small antral ovarian follicles and its clinical applicability has been recently demonstrated by several studies. Prediction of the response to ovarian stimulation for in vitro fertilization corresponds to the most frequent utilization of AMH in clinical practice, being routinely assessed in many services to identify subgroups of women susceptible to a poor response or to Ovarian Hyperstimulation Syndrome. There are great perspectives that AMH may be applicable to the individual determination of risk for iatrogenic gonadal injury in women with neoplasms who will be submitted to chemotherapy. It is also probable that AMH assessment will be included in protocols for the investigation of amenorrhea and oligomenorrhea, since AMH levels are increased in Polycystic Ovary Syndrome, reduced in premature ovarian failure and normal in other conditions such as hyperprolactinemia and hypogonadotropic hypogonadism. It is possible that AMH will be utilized in the future for the prediction of age at menopause and of reproductive prognosis, providing solid bases for pre-conceptive and contraceptive counseling.

El hábito de fumar se asocia a baja concentración plasmática de hormona antimülleriana en mujeres infértiles / Effects of smoking on plasma antimüllerian hormone concentrations among infertile women

Background: Smoking may hamperfemale fertility, probably modifying ovarian reserve. Antimüllerian hormone (AMH) is an accurate marker for ovarian reserve. Aim: To look for an association between smoking status and plasma AMH concentration. Patients and Methods: A cohort of 141 infertile women in a university setting in Santiago, Chile was studied. Demographic and smoking data, including the number of cigarettes smoked during the last week, were collected. A blood sample was obtained and kept frozen until determination of AMH by ELISA and follicle stimulating hormone (FSH) and estradiol at day three of the menstrual cycle, by radioimmunoanalysis. Results: Thirty two participants smoked (23%). There were no significant differences in age, parity, body mass index, causes of infertility and day three FSH and estradiol between smokers and nonsmokers. According to a regression analysis, there was a significant decrease in AMH concentration with age and active cigarette smoking. A drop in AMH of -0.189 ng/mL with a unitary change in age and a decrease of -2.29 ng/mL when everything else remains constant, except the smoking status, were established (p < 0.001 and r2 = 0.134). However, no dose response was observed when the number of cigarettes smoked during the last week were introduced in the model. Furthermore, no significant association ofplasma AMH with day three plasma FSH and estradiol concentrations was observed. Conclusions: Cigarette smoking is associated with decreased AMHplasma concentrations among infertile women. However there was no dose response relationship. The mechanisms underlying this association are unknown and further investigation is required.

Preoperative Serum Anti-Mullerian Hormone Level in Women with Ovarian Endometrioma and Mature Cystic Teratoma

PURPOSE: To investigate whether preoperative serum anti-mullerian hormone (AMH) levels are lower in women with ovarian endometrioma and in women with mature cystic teratoma of the ovaries. MATERIALS AND METHODS: In a tertiary university hospital, a retrospective case-control study was performed. Serum AMH levels between an advanced (stage III and IV) endometrioma group (n=102) and an age- and body mass index (BMI)-matched control group were compared. Serum AMH levels between an ovarian mature cystic teratoma group (n=48) and age- and BMI-matched controls were also compared. RESULTS: Absolute serum AMH and multiples of the median for AMH (AMH-MoM) relevant to Korean standards were lower in the endometrioma group than controls, but this was not statistically significant (mean+/-SEM, 2.9+/-0.3 ng/mL vs. 3.3+/-0.3 ng/mL, p=0.28 and 1.3+/-0.1 vs. 1.6+/-0.1, p=0.29, respectively). Specifically, the stage IV endometriosis group (n=51) exhibited significantly lower serum AMH and AMH-MoM (2.1+/-0.3 vs. 3.1+/-0.4 ng/mL, p=0.02 and 1.1+/-0.1 vs. 1.7+/-0.2, p=0.03, respectively). Serum AMH and AMH-MoM levels were similar between stage III endometriosis and controls (3.7+/-0.5 vs. 3.4+/-0.5 ng/mL and 1.6+/-0.2 vs. 1.5+/-0.2, respectively), as well as between the mature cystic teratoma group and controls (4.0+/-0.5 ng/mL vs. 4.0+/-0.5 ng/mL and 1.6+/-0.2 vs. 1.6+/-0.3, respectively). Interestingly, AMH-MoM level was negatively correlated with endometriosis score with statistical significance (r2=0.13, p<0.01). CONCLUSION: In women with advanced ovarian endometrioma, preoperative serum AMH values tended to be lower than those for age and BMI-matched controls. Notably, stage IV endometrioma appeared to be closely associated with decreased ovarian reserve, even before operation. Clinicians should keep this information in mind before undertaking surgery of ovarian endometrioma.

Serum anti-mullerian hormone [AMH] in prediction of oocyte quality and in vitro fertilization [IVF] outcome

Growing evidence indicates that serum Anti-mullerian hormone [AMH] levels could be of great importance for understanding the relationship with oocyte quality for IVF. The aim of the present study was to investigate the role of serum level of AMH in differentiation of infertile female patients with good quality oocytes, who are good responder and ready to enter the IVF cycles. This study included 25 infertile females classified into two groups: [15] females with Tubal obstruction and 10 females with polycystic ovary syndrome [PCOS]. Also, nineteen fertile females were served as controls. Investigation included serum measurements of AMH, Inhibin B, FSH, LH, E2, Prolactin and TSH on day 3 of previous menstrual cycle, serum measurement of progesterone [P4] on day 21 of previous menstrual cycle [before starting ovulation induction]. Also AMH, Inhibin B and E2 were measured on day of hCG administration [after long ovulation protocol]. The mean [ +/- SD] value of serum AMH was significantly decreased in female patients after ovarian stimulation protocol compared to that before ovarian stimulation,[P< 0.01]. Also, the mean [ +/- SD] value of serum AMH of female patients with good quality oocyte was significantly higher than that of those with bad quality oocyte, [P<0.01]. This study revealed that measurement of serum AMH is good marker in prediction of good responder infertile females for IVF technique after ovarian stimulation protocol

Hormônio anti-Mülleriano sérico para predição da resposta ovariana em ciclos de reprodução assistida / Serum anti-Müllerian hormone to predict ovarian response in assisted reproduction cycles

OBJETIVOS: Comparar as concentrações séricas do hormônio anti- Mülleriano (AMH) no sétimo dia de estimulação ovariana em pacientes boas e más respondedoras. MÉTODOS: Foram incluídas 19 mulheres com idade ≥35 anos, ciclos menstruais regulares e que foram submetidas à estimulação ovariana para reprodução assistida. Foram excluídas mulheres portadoras de endometriose ou síndrome dos ovários policísticos ou aquelas submetidas previamente à cirurgia ovariana. Foram coletadas amostras de sangue periférico no dia basal e no sétimo dia de estimulação para dosagens de AMH, hormônio folículo estimulante (FSH) e estradiol. Os níveis de AMH foram avaliados pelo método de enzimoimunoensaio (ELISA) e os níveis de FSH e estradiol foram avaliados por imunoquimioluminescência. Ao final do ciclo, as pacientes foram classificadas como normo (obtenção de quatro ou mais oócitos durante a captação) ou más respondedoras (obtenção de menos de quatro oócitos ou cancelamento do ciclo por má resposta) e analisadas comparativamente em relação aos níveis hormonais, duração da estimulação ovariana, número de folículos recrutados, embriões produzidos e transferidos através do teste t. A associação entre os níveis de AMH e os parâmetros acima também foi avaliada pelo teste de correlação de Spearman. RESULTADOS: Não houve diferença significativa entre os grupos para os níveis de AMH, FSH e estradiol no dia basal e no sétimo dia de estimulação ovariana, sendo observada correlação significativa entre os níveis de AMH do sétimo dia e a quantidade total de FSH exógeno utilizada (p=0,02). CONCLUSÕES: Os níveis de AMH obtidos no sétimo dia do ciclo de estimulação ovariana não parecem predizer o padrão de resposta ovariana, não sendo recomendadas as suas dosagens para esta finalidade.

PURPOSE: To compare serum anti-Mullerian hormone (AMH) levels on the seventh day of ovarian stimulation between normal and poor responders. METHODS: Nineteen women aged ≥35, presenting with regular menses, submitted to ovarian stimulation for assisted reproduction were included. Women with endometriosis, polycystic ovarian syndrome or those who were previously submitted to ovarian surgery were excluded. On the basal and seventh day of ovarian stimulation, a peripheral blood sample was drawn for the determination of AMH, FSH and estradiol levels. AMH levels were assessed by ELISA and FSH, and estradiol by immunochemiluminescence. At the end of the stimulation cycle patients were classified as normal responders (if four or more oocytes were obtained during oocyte retrieval) or poor responders (if less than four oocytes were obtained during oocyte retrieval or if the cycle was cancelled due to failure of ovulation induction) and comparatively analyzed by the t-test for hormonal levels, length of ovarian stimulation, number of follicles retrieved, and number of produced and transferred embryos. The association between AMH and these parameters was also analyzed by the Spearman correlation test. RESULTS: There was no significant difference between groups for basal or the seventh day as to AMH, FSH and estradiol levels. There was a significant correlation between seventh day AMH levels and the total amount of exogenous FSH used (p=0.02). CONCLUSIONS: AMH levels on the seventh day of the ovarian stimulation cycle do not seem to predict the pattern of ovarian response and their determination is not recommended for this purpose.

Analysis of anti-Müllerian hormone (AMH) and its receptor (AMHR2) genes in patients with persistent Müllerian duct syndrome / Pesquisa de mutações nos genes do hormônio antiMülleriano (AMH) e do seu receptor (AMHR2) em pacientes com síndrome de persistência dos ductos Müllerianos

OBJECTIVE: To screen for mutations in AMH and AMHR2 genes in patients with persistent Müllerian duct syndrome (PMDS). PATIENTS AND METHOD: Genomic DNA of eight patients with PMDS was obtained from peripheral blood leukocytes. Directed sequencing of the coding regions and the exon-intron boundaries of AMH and AMHR2 were performed. RESULTS: The AMH mutations p.Arg95*, p.Arg123Trp, c.556-2A>G, and p.Arg502Leu were identified in five patients; and p.Gly323Ser and p.Arg407* in AMHR2 of two individuals. In silico analyses of the novel c.556-2A>G, p.Arg502Leu and p.Arg407* mutations predicted that they were harmful and were possible causes of the disease. CONCLUSION: A likely molecular etiology was found in the eight evaluated patients with PMDS. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p.Arg502Leu in AMH; and p.Gly323Ser in AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8.

OBJETIVO: Analisar os genes AMH e AMHR2 em indivíduos com síndrome de persistência dos ductos de Müller (SPDM). PACIENTES E MÉTODO: Amostras de DNA genômico de oito pacientes com SPDM foram obtidas de leucócitos de sangue periférico. Sequenciamento direto da região codificadora e das áreas intrônicas próximas aos éxons dos genes AMH e AMHR foi realizado. RESULTADOS: As mutações p.Arg95*, p.Arg123Trp, c.556-2A>G e p.Arg502Leu no gene AMH foram identificadas em cinco pacientes e as mutações p.Gly323Ser e p.Arg407* no gene AMHR2, em dois indivíduos. As análises in silico das mutações c.556-2A>G, p.Arg502Leu e p.Arg407*, não descritas anteriormente na literatura, previram que elas são deletérias e possivelmente a causa da doença. CONCLUSÃO: Uma provável etiologia molecular foi encontrada nos oito pacientes portadores de SPDM avaliados. No gene do AMH foram identificadas quatro mutações e no AMHR2, duas mutações. Três das seis mutações encontradas são mutações novas, c.556-2A>G e p.Arg502Leu no gene AMH; e p.Gly323Ser no AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8.

New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker / Novas perspectivas no diagnóstico do hipogonadismo pediátrico masculino: a importância do AMH como marcador de células de Sertoli

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHβ mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.

As células de Sertoli são a população de células mais ativa nos testículos durante a primeira e segunda infância. Neste período, o hipogonadismo só pode ser evidenciado sem o uso de testes estimulatórios se a função das células de Sertoli for avaliada. O AMH é um marcador útil do número e da atividade das células de Sertoli no período pré-puberal. A concentração sérica de AMH é alta da metade da vida fetal até a metade da puberdade. A produção de AMH pelos testículos aumenta em resposta ao FSH e é potencialmente inibida por androgênios. O AMH sérico não é detectável em pacientes anorquídicos. No hipogonadismo central ou primário afetando a gônada inteira, ou estabelecido na vida fetal ou infância, a concentração de AMH sérica é baixa. Por outro lado, quando o hipogonadismo afeta apenas as células de Leydig (por exemplo, nas mutações, LHβ, defeitos do receptor de LH/CG ou das enzimas esteroidogênicas), a concentração de AMH sérico é normal ou alta. Em meninos púberes com hipogonadismo central, a concentração de AMH é baixa para o estágio na escala de Tanner (refletindo a falta de estímulo pelo FSH), mas alta para a idade (indicando a falta do efeito inibidor da testosterona). O tratamento com FSH provoca um aumento do AMH sérico, enquanto a administração de hCG aumenta os níveis de testosterona, que fazem a downregulation do AMH. Em conclusão, a concentração sérica de AMH é útil na avaliação da função gonadal, excluindo a necessidade de testes estimulatórios, e direciona o diagnóstico etiológico do hipogonadismo pediátrico masculino. Além disso, o AMH sérico é um marcador excelente da ação do FSH e dos androgênios nos testículos.

Anti-mullerian hormone as a predictive factor in assisted reproductive technique of polycystic ovary syndrome patients

This study aimed to assess the relationship between the serum levels of anti-mullerian hormone [AMH] and other hormonal markers and results of assisted reproductive techniques [ART] in polycystic ovary syndrome [PCOS] patients. This cohort study was conducted on 60 PCOS patients who were candidates for assisted reproductive techniques. In all patients the serum levels of AMH, follicle stimulating hormone [FSH] and luteinizing hormone [LH], estradiol [E2], free testosterone [fT], testosterone [T] and inhibin B were measured in the 3rd day of menstrual cycle. The relationship between serum level of measured hormonal markers with retrieved oocytes, mature oocytes, the number of transferred fetus and pregnancy rate were assessed. The cut-off value for the serum level of AMH and retrieved oocytes were determined. There was a significant direct correlation between the serum mullerian inhibiting substance [MIS] level with number of total picked up oocytes [r=0.412], mature oocytes [r=0.472] and embryo transfer [r=0.291]. There was a linear and significant correlation between inhibin B and fertilization [r=0.283] Cut-off point for AMH level according to presence or absence of pregnancy was 4.8 ng/ml and it was not statistically significant [P=0.655]. Area under curve [AUC] was 0.543. Cut-off point for MIS according to picked up oocytes was 2.7 ng/ml with area under the curve [ROC curve] of 0.724 [CI=0.591-0.831] [P=0.002]. Patients with PCOS who had AMH more than 2.7 ng/ml, the number of retrieved oocytes [6 or more] was higher than MIS/AMH<2.7 ng/ml [P=0.002]. As a marker of ovarian responsiveness to controlled ovarian hyperstimulation [COH] and despite a small sample size of our study, it is revealed that pretreatment MIS/AMH is highly associated with the number of mature oocytes retrieved during COH in PCOS women