O hormônio antimulleriano e a reserva ovariana: uma revisão integrativa da literatura / The anti-mullerian hormone and the ovarian reserve: an integrative literature review

O hormônio antimulleriano é secretado pelas células da granulosa dos folículos que estão em desenvolvimento no ovário. Por meio da sua dosagem, é possível avaliar a reserva ovariana. A mulher tem seu número máximo de oócitos no perío- do fetal, mas, conforme o tempo passa, existe uma queda do número de células germinativas. Desse modo, para mulheres que têm o desejo de engravidar, a dosa- gem de hormônios e a avaliação da reserva ovariana podem ajudar no processo. O objetivo do estudo foi encontrar evidências na literatura que comprovem que o hormônio antimulleriano é o melhor marcador da reserva ovariana. Para isso, foi realizada uma revisão integrativa, classificada como qualitativa; a busca de da- dos foi realizada no PubMed, utilizando a seguinte palavra-chave: "hormônio anti- mulleriano (HAM)". Foram encontrados oito artigos que abordavam diretamente o tema, e há evidências que corroboram a hipótese de que o hormônio antimulleria- no é um bom marcador da reserva ovariana, sendo necessários mais estudos para determinar a sua superioridade.

The anti-mullerian hormone is secreted by the granulosa cells of follicles that are developing in the ovary. Though its dosage is possible to evaluate the ovarian re- serve. Women have their maximum number of oocytes in the fetal period, but there is a decrease in the number of germinative cells as time goes by. Thus, women that desire to get pregnant can have hormones dosed and the ovarian reserve evalua- ted to help them with this process. The objective of this study was to find evidence in the literature that proves that the anti-mullerian hormone is the best marker of ovarian reserve. For this purpose, an integrative review was conducted, using the key word: "anti-mullerian hormone (AMH)". Eight articles were found on the subject and there is evidence that proves the hypothesis of the anti-mullerian hormone as a good marker, however more studies are needed to determine its superiority.

Attach great importance to the significance of serum anti-müllerian hormone and androgen in the evaluation of polycystic ovary syndrome / 中华预防医学杂志

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.

Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome.@*METHODS@#Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 μg/L, group B with serum (10-20) μg/L, and group C with serum ≥20 μg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed.@*RESULTS@#(1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) μg/L, 2.455 (1.370, 4.403) μg/L, 2.360 (1.430, 4.780) μg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05).@*CONCLUSION@#Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

La hormona antimulleriana y el síndrome de ovario poliquístico / Antimullerian hormone and polycystic ovary syndrome

Introducción: El diagnóstico del síndrome de ovario poliquístico, por su gran diversidad fenotípica ha sido y es objeto de debate. Es en este contexto que en los últimos años se ha propuesto la medición de la hormona antimulleriana como un indicador más eficaz en la evaluación de la disfunción folicular. Objetivo: Compilar información sobre la hormona antimulleriana y su utilidad diagnóstica en el síndrome de ovario poliquístico. Métodos: Revisión bibliográfica de 57 artículos obtenidos de las bases de datos Google Académico, Medline y Pubmed. Conclusiones: La concentración intrafolicular de hormona antimulleriana es inversamente proporcional al tamaño del folículo ovárico y sus niveles séricos son proporcionales a la reserva de folículos en estadio preantral o antral pequeño. En mujeres con síndrome de ovario poliquístico se ha observado incremento de hormona antimulleriana que se cree juega un papel en la patogenia de las alteraciones de la foliculogénesis y la disfunción ovárica. Por ello, la determinación de hormona antimulleriana se ha empleado con fines diagnósticos, como indicador de reserva folicular o como predictor de la respuesta a los tratamientos. Sin embargo, las dificultades técnicas para la medición y la variabilidad poblacional e interindividual, han llevado a que su utilidad práctica para el diagnóstico del síndrome de ovario poliquístico no haya podido establecerse consistentemente(AU)

Introduction: The diagnosis of polycystic ovary syndrome, due to its great phenotypic diversity, has been and is the subject of debate. It is in this context that in recent years the measurement of anti-Müllerian hormone has been proposed as a more effective indicator in the evaluation of follicular dysfunction. Objective: Compile information on the antimullerian hormone and its diagnostic utility in polycystic ovary syndrome. Methods: Bibliographic review of 57 articles obtained from the Google Scholar, Medline and Pubmed databases. Conclusions: The intrafollicular concentration of anti-Müllerian hormone is inversely proportional to the size of the ovarian follicle and its serum levels are proportional to the reserve of follicles in the preantral or small antral stage. An increase in anti-Müllerian hormone has been observed in women with polycystic ovary syndrome, which is believed to play a role in the pathogenesis of abnormal folliculogenesis and ovarian dysfunction. For this reason, the determination of anti-Müllerian hormone has been used for diagnostic purposes, as an indicator of follicular reserve or as a predictor of response to treatment. However, the technical difficulties for the measurement and the population and inter-individual variability have meant that its practical utility for the diagnosis of polycystic ovary syndrome has not been consistently established(AU)

Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with Diminished Ovarian Reserve: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD) in patients with diminished ovarian reserve (DOR).@*METHODS@#A total of 180 patients with DOR diagnosed from December 2013 to December 2014 were equally assigned into progynova and duphaston (E+D) group, Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization. Patients received E+D, Zuogui Pill or BYHD for 12 months, respectively. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, endometrial thickness, and the resistance indices (RIs) of ovarian arteries and uterine arteries were observed before and after treatment.@*RESULTS@#Nine women (4 from the E+D group, 3 from the Zuogui Pill group, and 2 from the BYHD group) withdrew from the study. After 6 months, Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH (all P<0.01). BYHD also resulted in E2 elevation (P<0.05), ovary enlargement (P<0.05), AFC increase (P<0.01), and RI of ovarian arteries decrease (P<0.05). After 12 months, further improvements were observed in the Zuogui Pill and BYHD groups (all P<0.01), but BYHD showed better outcomes, with lower FSH, larger ovaries and a thicker endometrium compared with the Zuogui Pill group (all P<0.01). However, E+D only significantly increased endometrial thickness (P<0.01) and no significant improvements were observed in the RI of uterine arteries in the three groups.@*CONCLUSIONS@#BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels, promoting ovulation, and repairing the thin endometrium. The combination of tonifying Shen (Kidney), benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients / 亚洲男科学杂志(英文版)

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

Decreased ovarian reserve and ovarian morphological alterations in female rat offspring exposed to a ketogenic maternal diet

SUMMARY OBJECTIVE: This study evaluates the effects of a ketogenic diet on morphology and follicle reserve. METHOD: Sixteen Sprague-Dawley rats were randomized into two groups: standard diet group (n=8) and ketogenic diet group (n=8). Rats were time mated. Dams were permitted to deliver spontaneously. The animals were monitored for the onset of puberty. All the rats were weighed and anesthetized, serum anti-Müllerian hormone level was measured, and the oviducts were removed. The morphological characteristics of follicles were determined and total ovarian volumes were calculated. RESULTS: The mean ovarian volume was statistically significantly lower in the ketogenic diet group compared to the standard diet group (14.41±0.99 mm3 versus 18.89±1.28 mm3) (p=0.000). The mean number of antral follicles was 13.63±1.80 in the standard diet group and 4.462±0.760 in the ketogenic diet group. The mean ovarian weight of the ketogenic diet group was significantly lower than that of the standard diet group (0.42±0.06 g versus 0.815±107 g). The mean anti-Müllerian hormone levels were significantly higher in the standard diet group compared to the ketogenic diet group (1.023±4.75 ng/mL versus 0.69±0.07 ng/mL) (p=0.000). The mean percentage of staining of Ki-67 was 35.28±4.75 in the standard diet group and 16.98±3.33 in the ketogenic diet group (p=0.000). CONCLUSION: Maternal ketogenic diet reduces ovarian follicular reserve in female offspring and has important implications for maintaining reproductive potential at a population level.

Comparison of age-related anti Müllerian hormone, inhibin-b levels and follicle reserve in rat ovarium / Comparación de la hormona anti-mülleriana relacionada con la edad, los niveles de inhibina-b y la reserva folicular en el ovario de rata

SUMMARY: Anti-Müllerian hormone (AMH) and Inhibin B (INHB) in the glycoprotein structure are members of the transforming growth factor β family and expressed by granulosa cells from puberty. AMH is a factor that increases the life span of small developing follicles. For this reason, it is widely used to determine the ovarian reserve and age. Inhibin-B secreted from granulosa cells plays a role in regulation of the Follicle Stimulating Factor (FSH) and determination of the follicle diameter. There are few studies on the effect of these two age-related hormones on ovarian histology in rats. In this study, AMH and INHB expression in ovarian tissues of female rats of different age groups, their relationship with ovarian structure and folliculogenesis were examined histologically and biochemically. Wistar Albino rats were used in the study and a total of 3 groups were formed. The ovaries of rats in the pre-oestrous period were collected, and follicle count was performed on tissue sections in batches. Expression of AMH in the follicles was identified immunohistochemically. In serum, AMH and INHB levels were assessed by ELISA method and their significance was evaluated statistically. Results from light microscopic examination determined that AMH was expressed from the granulosa cells of developing follicles. INHB expression during the prepubertal period and AMH had a protective effect on the ovarian reserve and the number of developing follicles, respectively.

RESUMEN: La hormona antimülleriana (AMH) y la inhibina B (INHB) en la estructura de la glicoproteína son miembros de la familia del factor de crecimiento transformante β y se expresan en las células de la granulosa desde la pubertad. La AMH es un factor que aumenta la vida útil de los pequeños folículos en desarrollo. Por este motivo, se utiliza frecuentemente para determinar la reserva ovárica y la edad. La inhibina B secretada por las células de la granulosa tiene un rol en la regulación del factor estimulante de (FSH) y en la determinación del diámetro del folículo. Hay pocos estudios sobre el efecto de estas dos hormonas relacionadas con la edad en la histología ovárica en ratas. Se examinaron histológica y bioquímicamente la expresión de AMH e INHB en tejidos ováricos de ratas hembras de diferentes grupos de edad, su relación con la estructura ovárica y la foliculogénesis. Se utilizaron ratas Wistar Albino en el estudio y se formaron 3 grupos. En los ovarios de ratas en el período preestro se realizó el recuento de folículos en secciones de tejido. La expresión de AMH en los folículos se identificó inmunohistoquímicamente. En suero, los niveles de AMH e INHB se evaluaron mediante el método ELISA y su importancia se evaluó estadísticamente. Los resultados del examen con microscopio óptico determinaron que la AMH se expresaba a partir de las células de la granulosa de los folículos en desarrollo. La expresión de INHB durante el período prepuberal y AMH tuvo un efecto protector sobre la reserva ovárica y el número de folículos en desarrollo, respectivamente.

Insuficiencia ovárica primaria en adolescentes: revisión de la literatura a propósito de un caso clínico / Primary ovarian insufficiency in adolescents: review of the literature regarding a clinical case

El objetivo de este manuscrito es realizar una revisión y actualización de la literatura de la insuficiencia ovárica primaria (IOP) en población adolescente, a partir del diagnóstico, manejo y seguimiento de un caso clínico. La insuficiencia ovárica primaria se define como la menopausia en una mujer antes de los 40 años, acompañada de amenorrea, hipogonadismo hipergonadotrópico e infertilidad. Su prevalencia varía entre 1 a 2%, y en mujeres menores de 20 años su prevalencia es un caso de cada 10,000. Aunque se sabe que muchas afecciones pueden llevar a una IOP, la más común es la causa idiopática. La presentación clínica es diversa, y varios trastornos diferentes pueden también, llevar a esta condición. CASO CLÍNICO: Se presenta el caso de una adolescente de 17 años, previamente sana, con historia de amenorrea secundaria, no embarazada, con examen físico general y ginecológico normal. Se solicita estudio analítico complementario resultando con niveles de hormona folículo estimulante (FHS), estradiol (E2) y hormona antimülleriana (AMH) compatibles con una insuficiencia ovárica como la observada en la posmenopausia. Se inicia terapia hormonal (TH) clásica con estradiol y progesterona, siendo posteriormente reemplazada por anticoncepción hormonal combinada (AHC) oral, coincidente con el inicio de vida sexual, con respuesta favorable y sangrados regulares. La IOP tiene graves consecuencias para la salud incluyendo trastornos psicológicos como angustia, síntomas depresivos o depresión, infertilidad, osteoporosis, trastornos autoinmunes, cardiopatía isquémica, y un mayor riesgo de mortalidad. La enfermedad de Hashimoto es el trastorno autoinmune más frecuente asociado a la IOP. Su tratamiento y diagnóstico deben establecerse de forma precoz para evitar consecuencias a largo plazo. La terapia con estrógenos es la base del tratamiento para eliminar los síntomas de la deficiencia de estrógenos, además de evitar las consecuencias futuras del hipogonadismo no tratado. También el manejo debe incluir los siguientes dominios: fertilidad y anticoncepción, salud ósea, problemas cardiovasculares, función psicosexual, psicológica y neurológica, informando a los familiares y a la paciente sobre la dimensión real de la IOP y la necesidad de tratamiento multidisciplinario en muchos casos. CONCLUSIÓN: El caso presentado, pese a ser infrecuente, permite abordar de manera sistematizada el diagnostico de IOP y evaluar alternativas de manejo plausibles para evitar graves consecuencias en la salud, así como conocer respuesta clínica y de satisfacción de la adolescente.

The objective of this manuscript is to review and update the literature on primary ovarian insufficiency (POI) in an adolescent population, based on the diagnosis, management and follow-up of a clinical case. Primary ovarian insufficiency is defined as menopause in a woman before the age of 40, accompanied by amenorrhea, hypergonadotropic hypogonadism, and infertility. Its prevalence varies between 1 to 2%, and in women under 20 years of age its prevalence is one case in every 10,000. Although it is known that many conditions can lead to POI, the most common is the idiopathic cause. The clinical presentation is diverse, and several different disorders can also lead to this condition. CLINICAL CASE: The case of a 17-year-old adolescent, previously healthy, with a history of secondary amenorrhea, not pregnant, with a normal general physical and gynecological examination is presented. A complementary analytical study is requested, resulting in levels of follicle stimulating hormone (FHS), estradiol (E2) and anti-müllerian hormone (AMH) compatible with ovarian insufficiency such as that observed in postmenopause. Classic hormonal therapy (HT) with estradiol and progesterone was started, later being replaced by combined hormonal contraception (CHC), coinciding with the beginning of sexual life, with a favorable response and regular bleeding. POI has serious health consequences including psychological disorders such as distress, depressive symptoms or depression, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and an increased risk of mortality. Hashimoto's disease is the most common autoimmune disorder associated with POI. Its treatment and diagnosis must be established early to avoid long-term consequences. Estrogen therapy is the mainstay of treatment to eliminate the symptoms of estrogen deficiency, in addition to avoiding the future consequences of untreated hypogonadism. Management should also include the following domains: fertility and contraception, bone health, cardiovascular problems, psychosexual, psychological and neurological function, informing family members and the patient about the real dimension of POI and the need for multidisciplinary treatment in many cases. CONCLUSION: The case, although infrequent, allows a systematic approach to the diagnosis of POI and evaluate plausible management alternatives to avoid serious health consequences, as well as to know the clinical response and satisfaction of the adolescent.

Hormona antimülleriana como marcador de respuesta ovárica en pacientes tratadas por fertilización in vitro / Anti-Müllerian hormone as a marker of ovarian response in patients treated with in vitro fertilization

Introducción: La infertilidad afecta al 15 por ciento de las parejas en edad fértil, de las que aproximadamente 4-8 por ciento requerirán técnicas de reproducción asistida de alta tecnología. Con la incorporación de la mujer a la vida laboral y la consiguiente postergación de la maternidad es posible el aumento de la infertilidad. La hormona antimülleriana en la mujer se produce por las células de la granulosa. Esta regula el reclutamiento de folículos, su crecimiento y previene el agotamiento folicular, por lo que constituye una importante herramienta en los protocolos de inducción de la ovulación. Objetivo: Evaluar los niveles de la hormona antimülleriana como marcador de respuesta ovárica en pacientes tratadas por fertilización in vitro. Método: Se realizó un estudio descriptivo, observacional y de corte transversal en la consulta protocolizada de Reproducción Asistida del Hospital Clínico Quirúrgico Hermanos Ameijeiras, en el periodo comprendido de abril 2017 hasta abril 2019. La muestra quedó conformada por 137 mujeres que participaron en esta consulta. Se empleó estadística descriptiva e inferencial. Resultados: La edad promedio de las pacientes fue de 33,1 ± 7,4 años. Predominó la concentración sérica normal de la hormona antimülleriana en mujeres entre 31-35 años (26,3 por ciento), nivel normal de FSH en (39,4 por ciento), recuento de folículos antrales normal (24,1 por ciento), buena calidad ovocitaria (39,4 por ciento), y buena calidad embrionaria (36,5 por ciento). Conclusiones: El nivel sérico de la hormona antimülleriana se asoció significativamente a la edad, la hormona folículo estimulante, el recuento de los folículos antrales, y la calidad ovocitaria y embrionaria(AU)

Introduction: Infertility affects to 15 percent of the couples in childbearing age, and approximately 4-8 percent of them will need high-tech assisted reproduction techniques. With the participation of women in work life and the subsequent delay of maternity, it is possible the increase of infertility. Anti-Müllerian in women is produced by granular cells. These cells control the recruitment of follicles, their growth and prevent follicles exhaustion; therefore, it represents an important tool in the protocols of ovulation induction. Objective: Assess the levels of anti-Müllerian hormone as a marker in the ovarian response in patients treated with in vitro fertilization. Methods: It was conducted a descriptive, observational and cross-sectional study in the consultation of Assisted Reproduction in "Hermanos Ameijeiras" Surgical Clinical Hospital, in the period April, 2017 - April, 2019. The sample was formed by 137 women who attended to this consultation. It was used descriptive and inferential statistics. Results: Average age of the patients was 33,1 ± 7,4 years old. There was predominance of normal serum concentration of anti-Müllerian hormone in women among 31-35 years old (26,3 percent), FSH normal level in (39,4 percent), normal recount of antral follicles (24,1 percent), good oocyte quality (39,4 percent), and good embryonic quality (36,5 percent). Conclusions: The serum level of the anti-Müllerian hormone was significantly associated to age, the follicle-stimulating hormone, the recount of antral follicles, and the oocyte and embryonic quality(AU)

Age-specific serum anti-Mullerian hormone reference values for infertile Filipino women in a tertiary in vitro fertilization center in the Philippines / Philippine Journal of Obstetrics and Gynecology

Background@#Anti-Mullerian hormone (AMH) levels have been used as an invaluable tool in reproductive medicine for over a decade, especially in predicting ovarian reserve and follicular response during in vitro fertilization (IVF) cycles. Age-specific reference values of AMH levels have been derived from mostly Western and few Asian population groups but none from the Philippines. In this study, we attempted to determine the first age-specific AMH reference values from infertile Filipino women to be able to provide local infertility centers a guide in treating Filipinos and those with similar racial and lifestyle characteristics. @*Materials and Methods@#This was a retrospective cross-sectional study that was conducted at the Center for Advanced Reproductive Medicine and Infertility at St. Luke's Medical Center Global City. Age, serum AMH levels, body mass index (BMI), and cause of infertility of Filipino women who underwent IVF from August 2015 to March 2020 were taken. AMH was assayed using the automated Access AMH Immunoassay (Beckman Coulter). @*Results@#A total of 1463 women who underwent IVF and with valid AMH results were initially found but only 1233 were included in the study. Mean age was 36.67 + 4.35 years and mean BMI was 24.43 + 4.14 kg/m2. There was minimal effect of BMI on AMH levels and increasing age (R2 = 0.0068), but there were significant differences of mean AMH levels among the general causes of infertility. The mean and median AMH values decreased with advancing age (R2 = 0.1391) although the mean values were consistently higher than the median values. The mean level of the AMH was 2.32 ± 1.90 ng/mL with a 0.16 ng/ml (confidence interval: 0.14–0.19 ng/ml) level decrease per year of increase in age. By age category, the following were the derived AMH values (ng/ml) at the 25th to 75th percentiles: 25–29 = 1.52–4.92; 30–34 = 1.60–4.10; 35–39 = 0.95–3.13; 40–44 = 0.44–1.99; 45 = 0.47–1.08. The mean AMH in this study appears to be similar to several but lower than most other reported AMH nomograms from other population groups. @*Conclusion@#The first age-specific AMH reference values for infertile Filipino women are presented and may serve as a useful diagnostic marker in local infertility centers, especially those treating Filipino patients or others with similar characteristics.

Evaluación de la reserva ovárica: pasado, presente y futuro / Ovarian Reserve: Past, Present and Future / Avaliação da reserva ovariana: passado, presente e futuro

Resumen: La necesidad de investigar la reserva ovárica para apoyar la consejería acerca del éxito o fracaso de los tratamientos de reproducción asistida, principalmente en pacientes con riesgo de falla reproductiva, ha generado la descripción y el uso de pruebas histológicas, basales, dinámicas y ultrasonográficas. La presente revisión tiene como objetivo describir y analizar las diferentes pruebas de evaluación de la reserva ovárica, sus limitaciones y ventajas, y ampliar la información referente a las que, por sus características y resultados, son más utilizadas en la actualidad. Para cumplirlo se realizó búsqueda en bases de datos, incluyendo investigaciones originales, revisiones sistemáticas, metaanálisis, reportes de casos y consensos de expertos, en inglés y español, desde 1980. En cuanto a los resultados, puede decirse que pruebas como la biopsia ovárica, medición de Inhibina B, test de estímulo con FSH o con GnRH, y con citrato de clomifeno, han caído en desuso; la medición de la FSH, si bien todavía utilizada, claramente tiene menor capacidad predictiva que el Conteo de Folículos Antrales (CFA) y la Hormona Antimülleriana (HAM). Se concluye que el CFA y la medición de ham son las pruebas más recomendadas, con mejor capacidad predictiva y que, no obstante algunas limitaciones, permiten un acercamiento a la estimación de la respuesta al estímulo ovulatorio. Se plantean opciones para el futuro que permitirán, a mediano plazo, resolver los interrogantes sobre la "verdadera" reserva ovárica.

Abstract: The need to investigate the ovarian reserve to support counseling about the success or failure of assisted reproduction systems has generated the description and use of histological, basal, dynamic, and ultrasound text. The purpose of this review is to describe and analyze the different tests for evaluating ovarian reserve, their limitations and advantages, and to expand the information regarding those that, due to their characteristics and results, are most widely used today. To achieve this, databases searches were carried out, including for original research, systematic reviews, meta-nalyses, case reports and expert consensus, in English and Spanish, since 1980. Regarding the results, it can be said that tests such as ovarian biopsy, measurement of Inhibin B, FSH or GnRH stimulation test, and with clomiphene citrate, have fallen into disuse. FSH measurement, although still used, clearly has a lower predictive capacity than the Antral Follicle Count (AFC) and the Antimullerian Hormone (AMH). It is concluded that the AFC and the AMH measurement are the most recommended tests, with better predictive capacity and that, despite some limitations, they allow closer estimation of the response to ovulatory stimulus. Options for the future that will allow solving the questions in the medium term about the "true" ovarian reserve are proposed.

Resumo: A necessidade de pesquisar sobre a reserva ovariana para apoiar o aconselhamento acerca do sucesso ou do fracasso dos tratamentos de reprodução assistida, principalmente em pacientes com risco de falha reprodutiva, vem gerando a descrição e o uso de exames histológicos, basais, dinâmicos e ultrassonográficos. Esta revisão tem o objetivo de descrever e analisar os diferentes exames de avaliação da reserva ovariana, suas limitações e vantagens, e ampliar a informação referente aos que, por suas características e resultados, são mais utilizados na atualidade. Para isso, foi realizada busca em base de dados, que incluiu pesquisas originais, revisões sistemáticas, meta-aná-lise, relatos de caso e consenso de especialistas, em inglês e em espanhol, desde 1980. Quanto aos resultados, pode-se dizer que os exames como biópsia ovariana, a medição de Inibina B, exame de estímulo com FSH ou com GnRH, e com citrato de clomifeno estão em desuso; a medição da FSH, embora ainda utilizada, claramente tem menor capacidade preditiva que a contagem de folículos antrais (CFA) e o hormônio antimulleriano (HAM). Conclui-se que o CFA e a medição do HAM são os exames mais recomendados, com melhor capacidade preditiva e que, apesar de algumas limitações, permitem uma aproximação da estimativa da resposta ao estímulo da ovulação. São apresentadas opções para o futuro que possibilitarão, em médio prazo, resolver as questões sobre a "verdadeira" reserva ovariana.

Intelectin-1 and Endocrinological Parameters in Women with Polycystic Ovary Syndrome: Effect of Insulin Resistance / 이화의대지

OBJECTIVES: We aimed to evaluate the effect of insulin resistance (IR) on serum Intelectin-1 and endocrinological hormones levels in obese and non-obese women with and without polycystic ovary syndrome (PCOS) in Basrah, Iraq.METHODS: From 124 women volunteers, 60 patients with primary and 64 patients with secondary, while 56 normal ovulatory women were taken as controls. Their fasting insulin hormone, intelectin-1, anti-Mullerian hormone, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), estradiol (E2) and testosterones (T) were determined by ELISA methods. BMI, glucose and quantitative insulin sensitivity check index as well as IR was determined by the homeostasis model assessment.RESULTS: A significant changes (P<0.05) were seen in the level of homeostasis model assessment-IR, E2 and T. Levels of anti-Mullerian hormone, LH, LH/FSH ratio and prolactin were significantly (P<0.01) increased and level of intelectin-1 and E2/T ratio were significantly (P<0.01) decreased, while quantitative insulin sensitivity check index level was not significantly different (P>0.05) between the patients (1°PCOS and 2°PCOS) and control groups. On the other hand, our data reported that FSH level was significantly (P<0.05) lower in obese and higher in non-obese patients with PCOS as compared to control group.CONCLUSION: Levels of intelectin-1 and endocrinological hormones have significantly associated with body mass index, IR and physical activity in patients and normal groups and the strategies that can modulate levels of these parameters would improve metabolic disarrangements in women with PCOS.

Novel homozygous mutation in a colombian patient with persistent müllerian duct syndrome: expanded phenotype

ABSTRACT The anti-Müllerian hormone triggers the regression of uterus and fallopian tubes in male embryos; if there are problems in the synthesis or action of this protein, Müllerian structures persist in an otherwise phenotypic male. The most frequent clinical presentation of Persistent Mullerian Duct syndrome is cryptorchidism and inguinal hernia. The few cases reported in adults are incidental findings or inguinal hernias. However, we present an adult male with history of bilateral cryptorchidism with unsuccessful orchidopexy, who presents with a large abdominal mass with the finding of a seminomatous tumor and persistence of Müllerian structures, in whom the variant c.916delC (p.Leu306Cysfs*29) in the AMHR2 gene not previously reported was documented.

Insuficiencia ovárica prematura / Premature ovarian insufficiency

RESUMEN La insuficiencia ovárica prematura es la pérdida de la función ovárica antes de los 40 años de edad. Se caracteriza por hipogonadismo hipergonadotrófico y amenorrea u oligomenorrea. Su etiología es multifactorial, pudiendo deberse a causas iatrogénicas, genéticas, metabólicas, autoinmunes y ambientales; siendo de origen idiopático en el 90 % de los casos. Su incidencia es de 1 cada 100 mujeres menores de 40 años y 1 cada 1000 mujeres menores de 30 años. En la actualidad no existe un único marcador que se pueda utilizar para calcular la reserva ovárica; sin embargo, en los últimos años la hormona antimülleriana ha demostrado presentar algunas ventajas respecto a los biomarcadores clásicamente utilizados. Además, diversos estudios indican que existe una correlación positiva entre los niveles de esta hormona y el recuento de folículos antrales, que es, por el momento, el método más confiable para evaluar reserva ovárica debido a las actuales dificultades técnicas para la determinación de hormona antimülleriana.

ABSTRACT Premature ovarian insufficiency, the loss of ovarian function before the age of 40 years, is characterized by hipergonadotrofic hipogonadism and amenorrhea or oligomenorrhea. The etiology is multifactorial, and can be due to genetic, metabolic, autoimmune, environmental or iatrogenic causes, being idiopathic 90% of cases. Currently there is not a single marker that can be used for estimate ovarian reserve in this patients; however, in recent years antimüllerian hormone has proved to have some advantages over other classical biomarkers. Moreover, several studies indicate a positive correlation between antimüllerian hormone concentration and antral follicle count, considered nowadays the most reliable method for ovarian reserve estimation.

Síndrome de Mayer-Rokitansky- Küster-Hauser asociado con malformación anorectal / Mayer-Rokitansky-Küster-Hauser syndrome associated with anorectal malformation

La agenesia vaginal es una entidad poco frecuente que puede presentarse en forma aislada o acompañada de otras anomalías congénitas. El desconocimiento de esta asociación puede retardar su diagnóstico, causar complicaciones indeseadas y comprometer el resultado del tratamiento. Se describen tres casos clínicos con agenesia vaginal y malformación anorrectal, cuyos diagnósticos no fueron realizados en el momento del nacimiento. Aunque la coexistencia de anomalías vaginales y anorectales sean poco frecuentes, los médicos responsables de su tratamiento deben ser conscientes de su existencia y practicar examen perineal cuidadoso.

Vaginal agenesis is a rare condition. It may exist in isolation or be associated with other congenital anomalies. A lack of awareness on this association may delay diagnosis, cause undesirable complications and compromise treatment outcomes. We describe three cases of vaginal agenesis associated with anorectal malformation which were not diagnosed at birth. Although the coexistence of vaginal and anorectal anomalies is uncommon, treating physicians should be aware of them and perform a detailed perineal examination.

Poorly-Controlled Type 1 Diabetes Mellitus Impairs LH-LHCGR Signaling in the Ovaries and Decreases Female Fertility in Mice

PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.

Anti-Müllerian hormone as a new marker of the ovarian reserve function preservation by goserelin during (neo)adjuvant chemotherapy for young breast cancer patients / 北京大学学报(医学版)

OBJECTIVE@#To observe the dynamic change of anti-Müllerian hormone (AMH) in 1 year after chemotherapy which is the best biochemical marker of ovarian reserve in reproductive medicine setting and to evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa)goserelin to prevent ovarian reserve function during (neo)adjuvant chemotherapy for young breast cancer patients.@*METHODS@#Between December 2015 and June 2017, 101 breast cancer patients of age ≤ 45 years with stages I to III had been enrolled. The patients were assigned without interference to receive either (neo) adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH and menstrual status were evaluated before, during and 0.5 year, 1 year after chemotherapy. Primary end point was the incidence of low AMH value (<0.4 μg/L) at the end of 1 year. Secondary end point was the incidence of amenorrhea (the absence of menses in the preceding 12 months after assignment).@*RESULTS@#In the study, 51 patients chose to join the chemotherapy group, while the other 50 patients selected goserelin to preserve their ovarian reserve function. More unmarried or childless, hormone receptors negative,receiving breast conservation therapy patients with earlier stage selected goserelin before chemotherapy. The incidence of low AMH value was significantly higher in chemotherapy group than in goserelin group (74.5% vs. 38.0%, P<0.001) in 1 year after chemotherapy. The incidence of amenorrhea was consistent with AMH (56.9% vs. 24.0%, P=0.001). And more patients' menstruation (78.9% vs. 54.5%) and AMH value (71.0% vs. 53.8%) recovered in goserelin group within 6 months after chemotherapy. In subgroup analysis, AMH and menstruation seemingly recovered more in goserelin group independent of age, chemotherapy regimen and use of tamoxifen. Especially, AMH value of 36.4% (8/22) patients in chemotherapy group and 18.4% (7/38) patients in goserelin group still maintained low level (<0.4 μg /L) although their menstruation had recovered 1 year after chemotherapy. In addition, 41 patients (20 patients in chemotherapy group, 21 patients in goserelin group) could be evaluated for the dynamic change of AMH and menstrual status during chemotherapy. The mean level of AMH in chemotherapy group declined rapidly to very low level before the 3rd cycle, while 70% of the patients kept presence of menstruation. At the same time, the mean level of AMH in goserelin group was still above 0.4 μg /L, but all of the patients had menopause.@*CONCLUSION@#Our study has offered evidence that Goserelin with chemotherapy could protect against ovarian reserve failure for young breast cancer patients, now that more patients' AMH value recovered earlier who had selected co-treatment. AMH may be a more precise marker than menstrual status to clinically evaluate ovarian reserve function pre-, during and post- chemotherapy.

Interpretation of androgen and anti-Mullerian hormone profiles in a Hispanic cohort of 5- to 8-year-old girls with premature adrenarche

PURPOSE: Premature adrenarche (PA) often leads to polycystic ovary syndrome (PCOS). Higher anti-mullerian hormone (AMH) levels are reported in PCOS. We studied the androgen profile and AMH profiles in Hispanic girls with PA (aged 5–8 years) and age and body mass index (BMI) matched controls. METHODS: Retrospective review of electronic medical records of girls who met the inclusion criteria for premature adrenarche were done. RESULTS: PA girls (n=76) were matched to control girls (n=12) for age (mean±standard deviation) (6.7±1 years vs. 6.2±1.3 years) and BMI (20±10 kg/m2 vs. 17.8±2.7 kg/m2). Dehydroepiandrostenedione sulfate (63.3±51.3 μg/dL vs. 29.8±17.3 μg/dL, P < 0.001) and testosterone levels (11.4±4.8 ng/dL vs. 8.2±2.9 ng/dL, P=0.001) were significantly higher in the PA group than controls. AMH values ( < 14 years: reference range, 0.49–3.15 ng/mL) were 3.2±2.2 ng/mL vs. 4.6± 3.2 ng/mL respectively in the PA and control groups and were not different (P=0.4). AMH did not show a correlation with bone age (P=0.1), and testosterone (P=0.9) in the PA group. 17-hydroxyprogesterone levels (17-OHP ng/dL) were 39.5±30.5 ng/dL vs. 36.8±19.8 ng/dL in PA versus control girls. The concentration of 17-OHP was not statistically different between the control and PA groups. CONCLUSIONS: Higher AMH was not observed in PA girls and no correlation with BA and androgen levels was observed.