Manejo del Síndrome de Hiperestimulación Ovárica / Management of Ovarian Hyperstimulation Syndrome

INTRODUCCIÓN: El síndrome de hiperestimulación ovárica es una respuesta exagerada del ovario a los tratamientos hormonales para estimular la formación de óvulos. OBJETIVO: Describir el caso clínico de una mujer con síndrome de hiperestimulación ovárica; revisar el abordaje, manejo, tratamiento y cómo prevenirlo. CASO CLÍNICO: Paciente femenina de 37 años, multigesta, en tratamiento con metformina por Síndrome de ovario poliquístico , que presenta infertilidad secundaria a factor tubárico, que desarrolló un cuadro moderado de síndrome de hiperestimulación ovárica como consecuencia de la aplicación de las técnicas de fertilización in vitro (Folitropina alfa humana recombinante (GONAL-F®) y Cetrolerelix (CETROTIDE®); al cuarto día del procedimiento de aspiración folicular presenta dolor pélvico intenso, disuria, deposiciones diarreicas, ecografía abdominal y vaginal evidencia líquido libre en cavidad alrededor de 1000cc, además de ovarios tanto derecho e izquierdo con volumen de 102 mL y 189 mL respectivamente. Paciente es ingresada para realizar tratamiento hidratación parenteral, Enoxaparina 40mg subcutánea, Cabergolina 0.5mg vía oral, alta a las 72 horas. DISCUSIÓN: Las claves para la prevención del síndrome de hiperestimulación ovárica son la experiencia con la terapia de inducción de la ovulación y el reconocimiento de los factores de riesgo para el síndrome de hiperestimulación ovárica. Los regímenes de inducción de la ovulación deberían ser altamente individualizados, monitorizados cuidadosamente y usando dosis y duración mínimas del tratamiento con gonadotropinas para conseguir la meta terapéutica. CONCLUSIONES: El síndrome de hiperestimulación ovárica constituye la complicación más temida durante el uso de inductores de la ovulación; el conocimiento de factores de riesgo, puede prevenir o evitar que llegue a ser de un caso severo, lo cual puede causar mayor morbilidad o hasta mortalidad. La vitrificación se convierte en la técnica que permite prevenir el síndrome de hiperestimulación ovárica, junto con esta técnica hay 2 alternativas: la inducción con análogo de la hormona liberadora de gonadotropina o el uso de agonistas dopaminérgicos.

INTRODUCTION: Ovarian hyperstimulation syndrome is an exaggerated response of the ovary to hormonal treatments to stimulate egg formation. OBJECTIVE: To describe the clinical case of a woman with ovarian hyperstimulation syndrome; to review the approach, management, treatment and how to prevent it. CLINICAL CASE: 37-year-old female patient, multigestation, under treatment with metformin for polycystic ovary syndrome, presenting infertility secondary to tubal factor, who developed a moderate picture of ovarian hyperstimulation syndrome as a consequence of the application of in vitro fertilization techniques (recombinant human follitropin alfa (GONAL-F®) and Cetrolerelix (CETROTIDE®); On the fourth day of the follicular aspiration procedure she presents intense pelvic pain, dysuria, diarrheic stools, abdominal and vaginal ultrasound shows free fluid in the cavity of about 1000cc, in addition to right and left ovaries with a volume of 102 mL and 189 mL respectively. Patient was admitted for parenteral hydration treatment, Enoxaparin 40mg subcutaneous, Cabergoline 0.5mg orally, discharged after 72 hours. DISCUSSION: The keys to prevention of ovarian hyperstimulation syndrome are experience with ovulation induction therapy and recognition of risk factors for ovarian hyperstimulation syndrome. Ovulation induction regimens should be highly individualized, carefully monitored, and using minimal doses and duration of gonadotropin therapy to achieve the therapeutic goal. CONCLUSIONS: Ovarian hyperstimulation syndrome constitutes the most feared complication during the use of ovulation inducers; knowledge of risk factors, may prevent or avoid it from becoming a severe case, which may cause increased morbidity or even mortality. Vitrification becomes the technique that allows preventing ovarian hyperstimulation syndrome, along with this technique there are 2 alternatives: induction with gonadotropin-releasing hormone analog or the use of dopaminergic agonists.

Mechanisms mediating the inhibitory effects of quercetin against phthalates-induced testicular oxidative damage in rats / 南方医科大学学报

OBJECTIVE@#To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats.@*METHODS@#Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting.@*RESULTS@#Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05).@*CONCLUSION@#Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.

C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.

An examination of predictive markers for successful sperm extraction procedures: a linear model and systematic review / 亚洲男科学杂志(英文版)

The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility, for example, follicle-stimulating hormone (FSH), testicular volume (TV), and testosterone (T), to better predict sperm retrieval rate (SRR). Twenty-nine studies were included, 9 with data on conventional testicular sperm extraction (cTESE) for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction (mTESE) for a total of 4760 patients. A weighted-means value of SRR, FSH, T, and TV was created, and a weighted linear regression was then used to describe associations among SRR, type of procedure, FSH, T, and TV. In this study, weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9% vs 40.1%. Multiple weighted linear regressions were created to describe associations among SRR, procedure type, FSH, T, and TV. The models showed that for every 1.19 mIU ml-1 increase in FSH, there would be a significant decrease in SRR by 1.0%. Seeking to create a more clinically relevant model, FSH values were then divided into normal, moderate elevation, and significant elevation categories (FSH <10 mIU ml-1, 10-19 mIU ml-1, and >20 mIU ml-1, respectively). For an index patient undergoing cTESE, the retrieval rates would be 57.1%, 44.3%, and 31.2% for values normal, moderately elevated, and significantly elevated, respectively. In conclusion, in a large meta-analysis, mTESE was shown to be more successful than cTESE for sperm retrievals. FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.

Incidence and genetic reproductive characteristics of AZFc microdeletion among patients with azoospermia or severe oligospermia / 中华医学遗传学杂志

OBJECTIVE@#To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment.@*METHODS@#A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate.@*RESULTS@#A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05).@*CONCLUSION@#The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.

Atypical pituitary hormone-target tissue axis / 医学前沿

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.

Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

LncRNA-m18as1 competitively binds with miR-18a-5p to regulate follicle-stimulating hormone secretion through the Smad2/3 pathway in rat primary pituitary cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.

Metformin improves polycystic ovary syndrome and activates female germline stem cells in mice / 生理学报

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.

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.

Endocrine aberrations of human nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic-pituitary-testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.

Follicle-stimulating hormone (FSH) levels prior to prostatectomy are not related to long-term oncologic or cardiovascular outcomes for men with prostate cancer / 亚洲男科学杂志(英文版)

Prior research suggests a link between circulating levels of follicle-stimulating hormone (FSH) and prostate cancer outcomes. FSH levels may also explain some of the observed differences in cardiovascular events among men treated with gonadotropin-releasing hormone (GnRH) antagonists compared to GnRH agonists. This study evaluates the association between preoperative FSH and long-term cardiovascular and oncologic outcomes in a cohort of men with long follow-up after radical prostatectomy. We performed a cohort study utilizing an institutional biobank with annotated clinical data. FSH levels were measured from cryopreserved plasma and compared with sex steroids previously measured from the same samples. Differences in oncologic outcomes between tertiles of FSH levels were compared using adjusted cox regression models. Major adverse cardiovascular events (MACE) were similarly assessed using hospital admission diagnostic codes. A total of 492 patients were included, with a median follow-up of 13.1 (interquartile range: 8.9-15.9) years. Dehydroepiandrosterone sulfate (DHEA-S) levels, but not other androgens, negatively correlated with FSH levels on linear regression analysis (P = 0.03). There was no association between FSH tertile and outcomes of biochemical recurrence, time to castrate-resistant prostate cancer, or time to metastasis. MACEs were identified in 50 patients (10.2%), with a mean time to first event of 8.8 years. No association with FSH tertile and occurrence of MACE was identified. Our results do not suggest that preoperative FSH levels are significantly associated with oncologic outcomes among prostate cancer patients treated with radical prostatectomy, nor do these levels appear to be predictors of long-term cardiovascular risk.

Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway / 中西医结合学报

OBJECTIVE@#Moxibustion, a common therapy in traditional Chinese medicine, has potential benefits for treating decreased ovarian reserve (DOR). The present study investigates the protective effect of moxibustion in a rat model of DOR and explores the possible mechanisms.@*METHODS@#Sixty-four female Sprague-Dawley rats were randomly divided into four groups: control, DOR, moxibustion (MOX), and hormone replacement therapy (HRT). The DOR rat model was established by intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGS), once daily for 14 days. MOX and HRT treatments were given from the day TGS administration was initiated. The ovarian reserve function was evaluated by monitoring the estrus cycle, morphological changes in ovaries, levels of serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), pregnancy rate and embryo numbers. Terminal-deoxynucleotidyl transferase-mediated nick-end-labeling staining was used to identify ovarian granulosa cell apoptosis, while the protein and mRNA expressions of Bax, B-cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in ovarian tissues were examined by immunohistochemistry, Western blot and quantitative reverse transcription-polymerase chain reaction.@*RESULTS@#Compared with the DOR group, MOX improved the disordered estrous cycle, promoted follicular growth, reduced the number of atresia follicles, increased the concentrations of serum E2 and AMH, and decreased serum FSH and LH concentrations. More importantly, the pregnancy rate and embryo numbers in DOR rats were both upregulated in the MOX treatment group, compared to the untreated DOR model. Further, we found that the MOX group had reduced apoptosis of ovarian granulosa cells, increased Bcl-2 expression and reduced expression of Bax. Furthermore, the PI3K/AKT signaling pathway was triggered by the moxibustion treatment.@*CONCLUSION@#Moxibustion improved ovarian function and suppressed apoptosis of ovarian granulosa cells in a rat model of DOR induced by TGS, and the mechanism may involve the PI3K/AKT signaling pathway.

Association of Overweight and Consistent Anovulation among Infertile Women with Regular Menstrual Cycle: A Case-control Study / Associação entre sobrepeso e anovulação consistente em mulheres inférteis com ciclo menstrual regular: Um estudo de caso-controle

Abstract Objective It has been suggested that excess body weight could represent a risk factor for infertility outcomes. The present study aimed to evaluate the association of overweight and anovulation among infertile women with regular menstrual cycles. Methods We conducted a retrospective case-control study with consistently anovulatory patients undergoing assisted reproduction treatment. The patients were stratified into normal weight (body mass index [BMI]: 18.5-24.9kg/m2) and overweight (BMI: 25.0- 29.9kg/m2).Those with polycystic ovary syndrome or obesity were excluded. The groups were matched for age, duration of infertility, prolactin, follicle stimulating hormone (FSH), thydroid stimulating hormone (TSH), luteinizing hormone (LH), and estradiol levels. Results Overweight was significantly associated with anovulation, when using the World Health Organization (WHO) criteria for anovulation: progesterone levels>5.65 ng/ml and ultrasonography evidence of follicle collapse (odds ratio [OR]: 2.69; 95% confidence interval [CI95%]: 1.04-6.98). Conclusion Body mass index above the normal range jeopardizes ovulation among non-obese infertile women with regular menstrual cycles.

Resumo Objetivo O excesso de peso corporal tem sido associado como fator de risco para infertilidade. Este estudo teve como objetivo avaliar a associação de sobrepeso e anovulação entre mulheres inférteis com ciclos menstruais regulares. Métodos Realizamos um estudo retrospectivo de caso-controle com mulheres com anovulação consistente em tratamento por reprodução assistida. As pacientes foram estratificadas entre aquelas com peso normal (índice de massa corporal [IMC]: 18,5- 24,9 Kg/m2) e as com sobrepeso (IMC: 25,0-29,9 Kg/m2). As pacientes com síndrome do ovário policístico ou obesidade foram excluídas. Os grupos foram pareados por idade, duração da infertilidade, níveis de prolactina, hormônio folículo-estimulante (FSH), hormônio tiroestimulante (TSH), hormônio luteinizante (LH) e estradiol. Resultados O excesso de peso associou-se significativamente à anovulaçãoquando usados os critérios de anovulação da Organização Mundial de Saúde (OMS): níveis de progesterona>5,65 ng/ml e evidência ultrassonográfica de colapso folicular (razão de chances [RC]: 2,69; IC95%: 1,04-6,98). Conclusão O IMC acima da faixa normal compromete a ovulação em mulheres inférteis não obesas com ciclos menstruais regulares.

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen / Melhorando a taxa de implantação no 2° ciclo de ICSI através do estímulo ovariano com FSH e LH no regime com antagonista do GnRH

Abstract Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

Resumo Objetivo: Investigar se há algum efeito da suplementação com hormônio luteinizante (LH, na sigla em inglês) no regime com antagonista do hormônio liberador de gonadotropina (GnRH, na sigla em inglês) sobre os resultados dos ciclos consecutivos de injeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês). Métodos Para o presente estudo retrospectivo de caso-controle, foram avaliados 228 ciclos de microinjeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês) realizados em 114 pacientes entre 2015 e 2018 em um centro privado de fertilização in vitro (FIV) afiliado a uma universidade. O estímulo ovariano controlado (EOC) foi feito com hormônio folículo- estimulante recombinante (rFSH, na sigla em inglês) (Gonal-f, Serono, Genebra, Suíça) no primeiro ciclo de ICSI (grupo rFSH), e com rFSH e rLH (Pergoveris, Merck Serono S.p.A, Bari, Itália) no segundo ciclo (grupo rFSH + rLH). Os desfechos dos ciclos de ICSI foram comparados entre os grupos. Resultados Níveis mais elevados de estradiol, de recuperação oocitária, taxa de embriões de alta qualidade no 3° dia e taxa de implantação, e menor taxa de aborto foram observados no grupo rFSH + rLH. Em pacientes < 35 anos, a taxa de implantação foi maior no grupo rFSH + rLH em comparação com o grupo rFSH. Em pacientes com ≥ 35 anos, maiores níveis de estradiol, recuperação oocitária, a taxa de embriões de alta qualidade no 3° dia e a taxa de implantação foram observados no grupo rFSH + rLH. Em pacientes com baixa resposta ao EOC (≤ 4 oócitos recuperados), a recuperação oocitária, a taxa de oócitos maduros, a taxa de velocidade normal de clivagem, a taxa de implantação e a taxa de aborto foram melhoradas no grupo rFSH + rLH. Em pacientes com resposta normal ao EOC (≥ 5 oócitos recuperados), níveis mais elevados de estradiol, recuperação oocitária e taxa de implantação foram observados no grupo rFSH + rLH. Conclusão A estimulação ovariana com suplementação de LH resultou em taxas de implantação mais altas, independentemente da idade materna e da resposta ao EOC, em comparação com os ciclos anteriores estimulados apenas com rFSH. Melhorias também foram observadas nos resultados da ICSI e na taxa de aborto quando as pacientes foram estratificadas por idade e número de oócitos recuperados.

Morphology and Biochemistry of Ovulation Morfologia e bioquímica da ovulação

Abstract The process of ovulation involves multiple and iterrelated genetic, biochemical, and morphological events: cessation of the proliferation of granulosa cells, resumption of oocyte meiosis, expansion of cumulus cell-oocyte complexes, digestion of the follicle wall, and extrusion of the metaphase-II oocyte. The present narrative review examines these interrelated steps in detail. The combined or isolated roles of the folliclestimulating hormone (FSH) and luteinizing hormone (LH) are highlighted. Genes indiced by the FSH genes are relevant in the cumulus expansion, and LH-induced genes are critical for the resumption ofmeiosis and digestion of the follicle wall. A nonhuman model for follicle-wall digestion and oocyte release was provided.

Resumo O processo de ovulação envolve modificações genéticas, bioquímicas e morfológicas múltiplas e interrelacionadas: suspensão da proliferação das células da granulosa, reinício da meiose do oócito, expansão das células do complexo cumulus-oócito, digestão da parede folicular, e extrusão do oócito. Esta revisão narrativa examina em detalhes cada um desses eventos e os principais genes e proteínas envolvidos. Mais importante, a ação combinada ou isolada do hormônio folículo-estimulante (HFE) e do hormônio luteinizante (HL) é destacada. Detalha-se o papel do HFE na expansão do cumulus e do HL na digestão da parede folicular, permitindo a extrusão do oócito na superfície ovariana. Proveu-se um modelo não humano para explicar a digestão da parede folicular.

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.

Buchholzia coriacea (wonderful kola) seeds induce male reproductive toxicity by suppressing the pituitary-gonadal axis in Wistar rats

The methanolic extract of Buchholzia coriacea seeds (MEBC) has been reported to induce male reproductive toxicity by decreasing sperm parameters and fertility index. To elucidate the possible mechanism(s), the effects of graded doses of MEBC on sex hormones and sperm profile were investigated in this study. The MEBC (e.g., 50, 200, 400, and 600 mg/kg) was administered daily (p.o.) to male Wistar rats for 6 weeks, while a concurrent control group received distilled water (vehicle). Then, the animals were sacrificed under sodium pentobarbital anaesthesia. Weights of organs were recorded, and the sperm profile was determined microscopically. Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were assayed from the obtained serum using the ELISA technique. Sperm motility was significantly reduced by MEBC (i.e., 50 and 200 mg/kg), and sperm count reduced in all treated groups in a dose-dependent manner compared with that of the control. Serum testosterone, LH, and FSH decreased in treated rats. A histopathological examination of testes showed a considerable depletion and necrosis of the epithelium of seminiferous tubules. The result suggests that Buchholzia coriacea seeds induce male reproductive toxicity by suppressing the pituitary-gonadal axis.

Advantages of integrated Chinese and western medicine in diagnosis and treatment of anovulatory infertility due to kidney deficiency and blood stasis / 中国中药杂志

Under the guidance of the theory of "kidney governing reproduction", this study demonstrated the mechanism of six types of ovulatory infertility caused by kidney deficiency and blood stasis, including anovulatory bleeding, polycystic ovary syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, luteal phase deficiency, and primary ovarian insufficiency. A series of studies have confirmed that integrated Chinese and western medicine can increase the responsiveness of the ovaries to gonadotropins and improve ovarian function by regulating the effects of estradiol(E_2), prolactin(PRL), and reducing follicle-stimulating hormone(FSH), luteinizing hormone(LH), progestin(P), and testosterone(T). It can also improve ovulation rate and pregnancy success rate by promoting follicle development, discharging, and synchronizing endometrial growth. This study illustrated the diagnosis and treatment of ovulatory infertility caused by kidney deficiency and blood stasis with integrated traditional Chinese and Western medicine in the "disease-syndrome-symptom" research mode, and highlighted the traditional Chinese medicine(TCM) idea of differentiating diseases based on syndromes and unique advantages of the combination of disease differentiation and syndrome differentiation, and interpreted TCM principle of "treating different diseases with the same method".

Acupuncture-moxibustion treatment by stages based on the theory of "transformation of / 中国针灸

OBJECTIVE@#To compare the efficacy between acupuncture-moxibustion treatment by stages and femoston for premature ovarian insufficiency (POI).@*METHODS@#A total of 66 patients with POI were randomly divided into an observation group (33 cases, 3 cases dropped off) and a control group (33 cases, 2 cases dropped off). The patients in the observation group, based on the theory of "transformation of @*RESULTS@#Compared before treatment, the serum levels of FSH and LH were decreased (@*CONCLUSION@#Acupuncture- moxibustion treatment by stages based on the theory of "transformation of