Increase In FSH Levels Research Articles

Features of reproductive function in infertile women with hyperthyroidism

Objective. The aim was to study the characteristics of reproductive function in women of fertile age with infertility and hyperfunction of the thyroid gland.
 Materials and methods. The object of the study was 148 women of fertile age. To compare the indicators obtained by special methods, the control group included the indicators of laboratory and instrumental examination of 30 non-pregnant women of reproductive age. Reproductive function was evaluated in 118 women with hyperthyroidism: 58 retrospectively (group I) and 60 prospectively (group II); the control group consisted of 30 healthy women of reproductive age. Hormonal studies were performed by radioimmune and enzyme immunoassay methods using the automatic analyzer "Cobb" ("Hoffmann La Roche", Switzerland), as well as DPS test systems the analyzer Immulite (USA). Ultrasound of the thyroid gland was performed by a linear sensor with a frequency of 7.5 MHz. The volume of the thyroid gland was calculated according to the Bruno formula.
 Results. For women of fertile age with hyperthyroidism, a decrease in ovarian reserve is characteristic that is manifested by a significant increase in FSH level (14.1 3.1 IU / L, p 0.05), and a decrease in inhibin B level (35.9 12,7 pg / ml, p 0.05). In 47.7 % of women of fertile age with hyperthyroidism, there is a decrease in ovarian volume and a significant reduction in the average number of antral follicles of normal size (4.34 1.56, p 0.05).
 Conclusions. Based on the results obtained, it can be assumed that in diffuse toxic goiter there are not only functional disorders (metabolism of hormones of the reproductive system), but also deep organic changes in the structure of the ovaries that leads to a rapid suppression of their functions. In cases of thyroid diseases, the clinical manifestation of these changes is premature and early menopause.

Diet enrichment and the reproductive season of captive Sunda Porcupine (Hystrix javanica F. Cuvier 1823)

This study aimed to extend our current knowledge of Sunda porcupine reproductive biology with emphasis on environmental enrichment and the reproductive season. Tomato and bean sprout feeding able to increase sperm quantity, sperm motility, and viability, as well as increase FSH and estrogen hormone levels. Four pairs of captive Sunda porcupine were used. Two pairs (fed with fresh tomato and bean sprout, enrichment group) and two pairs as control. The birth rate of enrichment group higher (with twin litter per year) than that in control (only one litter per year). It indicated that tomato and bean sprout feeding affect the birth rate in Sunda porcupine. The recent study showed that captive Sunda porcupine births occurred throughout the year, with no more than 1-2 litter per year and are have no interbirth-interval. The birth peak of captive Sunda porcupine occurs between April to August. Biparental activities during birth occurred. However, the female spent 50% of the time with the newborn. There was no courtship behaviour throughout the first two or three months of life of the cub.

Association of BMP15 and GDF9 variants to premature ovarian insufficiency.

To identify genetic variation associated to premature ovarian insufficiency (POI). A total of 74 women with POI (group POI), 45 women with increased FSH levels (group high FSH), and 88 controls (non-POI) were studied. Genotyping of BMP15:c.-9C>G (rs3810682), BMP15:c.328+905A>G (rs3897937), and BMP15:c.852C>T (rs17003221); and GDF9:c.134-694G>A (rs4705974), GDF9:c.-31-951G>A (rs11748063), GDF9:c.-152G>C (rs30177), and GDF9:g.1073C>T (rs803224) was performed by the TaqMan methodology. Chi-square and Fisher's exact tests were performed to evaluate the distribution of genotypes, alleles, odds ratio, and the Hardy-Weinberg equilibrium of each variation. Haplotype analysis was performed for each gene considering the case and control groups. Bonferroni's correction was applied to chi-square and Fisher's exact test data, and p values < 0.007 for genotypes and alleles and < 0.006 for haplotypes were considered significant. It was observed a statistically significant difference in genotype distribution of BMP15:c.852C>T between group POI and controls (p < 0.001). TT and TC genotypes were more frequently observed in group POI. Genotype distribution in case group POI, however, was not in the Hardy-Weinberg equilibrium, due to the increased number of heterozygotes in the sample. Concerning GDF9, no association was found among the studied genetic variants and POI or high FSH groups. It is concluded from the present study that the genotypes CT and TT from BMP15:c.852C>T variation may be risk factors for the development of POI.

Establishment of premature ovarian insufficiency kidney deficiency and blood stasis pattern mouse model with Tripterygium wilfordii polyglycoside for Bushen Culuan Decoction therapy

To establish a mouse model of premature ovarian insufficiency( POI) with kidney deficiency and blood stasis pattern by Tripterygium wilfordii polyglycoside( TWP) gavage,and to evaluate the ovarian function and fertility of the model,in order to find Bushen Culuan Decoction therapeutic mechanism. 60 SPF level Blab/c female mice with normal estrous cycle were randomly divided into 6 groups of 10 each: blank group 1( BG1),blank group 2( BG2),blank fertility group( BFG),model group( MG),model recovery group( MRG) and model fertility group( MFG). The mice in three model groups were treated by gastric gavage with TWP suspension 40 mg·kg-1 twice a day for 14 days,while the mice in three blank groups were treated by gastric gavage with same volume normal saline for 14 days. The mice in BG1 and MG were sacrificed and dissected on day 15. The mice in BG2,BFG,MRG and MFG were returned normal feeding from day 15 and were sacrificed and dissected on day 29. The mice in BFG and MFG were cohabited with male mice with a ratio of 2 ∶1( female ∶male) from day 15. The general situation and estrous cycles of all mice were observed every day. Serum sex hormone levels,ovarian index,uterine index,ovarian morphology,follicle count,ovarian VEGF and ES index were observed within the mice in BG1,BG2,MG and MRG. Pregnancy rate,litter size,survival number of newborn mice and male-female proportion were reported within the mice in BFG and MFG. In model establishing stage,the body weight of mice significantly decreased( P <0. 05) in MG and MFG. Compared with BG1,the mice in model group had irregular estrous cycle,decreased ovarian and uterine indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression and decreased ES expression( P <0. 05). Compared with blank group 2,the mice in model recovery group had irregular estrous cycle,increased FSH level,decreased ovarian indexes,less primordial and developing follicles,more atretic follicles,increased VEGF expression( P<0. 05). Compared with blank fertility group,the mice in model fertility group had smaller litter size and newborn mice survival count( P<0. 05). Gastric gavage with TWP 40 mg·kg-1 twice a day for 14 days is a feasible way to establish a POI kidney deficiency and blood stasis pattern mouse model. The mice ovarian functions didn't recovery on day 14 after stopping TWP intervening,which could suggest the effectiveness of subsequent therapeutic intervention.

The relationship of the psychological coping and adjustment strategies of infertile women with the success of assisted reproductive technology.

BackgroundThe success of assisted reproductive techniques plays a very important role in the quality of life of infertile couples and decreases the negative behavior states of infertility.ObjectiveThis study aimed at determining the relationship between psychological coping and adjustment strategies with the success of assisted reproductive technology (ART).Materials and MethodsThis correlational study was conducted on 204 women visiting Milad Infertility Center in Mashhad during 2015-2016. The research instruments included Fertility Adjustment Scale and Infertility Coping Strategies Scale. The positive result of two pregnancy tests within 48 hours was considered as the success of ART.ResultsThe mean and standard division score of adjustment in the group achieved treatment success (34.38.2) exceeded the group failed (33.68.8), the difference was not statistically significant (p= 0.381). Also, there was no significant difference between groups in the median and interquartile range of total coping strategies 81 (13) vs. 79.5 (12.25), (p= 0.369). Based on the logistic regression model for one increased transferred embryo, the chance of getting pregnant is 1.3 times, and for each unit increase in FSH level, the chance of ART success decreases 18%.Conclusion The results of this study showed that there is no relationship between psychological coping and adjustment strategies with ART success. However, the number of transferred fetus and tirthday FSH are introduced as factors that are related to the success of ART.

Stimulation with recombinant FSH acutely and significantly increases inhibin B and estradiol in women after GnRH antagonist treatment: a model to study FSH regulation of ovarian function

Obesity is associated with decreased pituitary output of LH and FSH, inadequate folliculogenesis, and reduced ovarian steroid and peptide hormone production. It remains unclear whether the underlying pathophysiology is related to abnormal hypothalamic-pituitary dynamics, abnormal ovarian environment, or both. The persistent deficit in FSH secretion, despite the lack of restraint and normal pituitary FSH reserve, remains unexplained. FSH pulsatility is challenging to evaluate, given its long half-life and low signal-to-noise ratio, and current analytic methods fail to adequately characterize the hormone secretion dynamics of FSH and its feedback. We hypothesized that both Inhibin B and Estradiol (E2) levels will be acutely increased following exogenous, pulsatile recombinant (r) FSH administration, after a GnRH antagonist blockade. This will establish a model to study ovarian, FSH-stimulated E2 and inhibin secretion, independent of the pituitary, to determine mechanisms underlying the FSH/ovarian dysregulation in obesity. A pilot, cohort study of 9 normal-weight, cycling women at the University of Colorado School of Medicine. Participants (mean age 26.3 ± 4.9 years; BMI 22.2 ± 1.3 kg/m2) underwent frequent blood sampling (q10 min) during a 26-hour overnight study visit. Following an initial baseline10-hour collection to assess unstimulated LH and FSH secretion, Cetrotide (EMD Serono) was administered subcutaneously twice: 3 mg at hour 10 and 0.25mg at hour 16. Frequent blood sampling resumed (hours 16-26) and rFSH (Gonal-F; 30 IU) was given intravenously every hour. LH, FSH and E2 were measured by immunoassays (Centaur XP, Siemens). Functional sensitivity is 0.1 mIU/mL and the intra- and inter-assay coefficients of variation were 3.8 and 4.1%, respectively. Inhibin B was analyzed by ELISA (Beckman Coulter). Functional sensitivity is 10 pg/mL and the intra- and inter-assay coefficients of variation were 1.8 and 4.9%, respectively. Statistical significance was determined by paired t test. Normal LH & FSH pulsatility was confirmed for the 10-hour baseline frequent sampling period for all subjects. Administration of Cetrotide reliably suppressed endogenous LH and FSH secretion. Repeated boluses of rFSH mimicked endogenous FSH pulses and significantly increased FSH levels over the course of the infusion (p<0.001). Starting from 6 hours post rFSH administration (after 180 IU) we observed a significant increase in both inhibin B (60%) and E2 (80%) production (p=0.01 and p<0.01 respectively). We herein report that exogenous FSH, administered in a pulsatile fashion after GnRH blockade, induced significant, acute increases in both E2 and Inhibin B, in normal weight women. This experimental paradigm can be used to investigate FSH feedback mechanisms in obesity or other environmental insults impacting ovarian function.

Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?

Few studies of patients with a 45,X/46,XY mosaicism have considered those with normal male phenotype. The purpose of this study was to evaluate the clinical outcome of 45,X/46,XY boys born with normal or minor abnormalities of external genitalia, notably in terms of growth and pubertal development. Retrospective longitudinal study of 40 patients followed between 1982 and 2017 in France. Twenty patients had a prenatal diagnosis, whereas 20 patients had a postnatal diagnosis, mainly for short stature. Most patients had stunted growth, with abnormal growth spurt during puberty and a mean adult height of 158 ± 7.6 cm, i.e. -2.3 DS with correction for target height. Seventy percent of patients presented Turner-like syndrome features including cardiac (6/23 patients investigated) and renal malformations (3/19 patients investigated). Twenty-two patients had minor abnormalities of external genitalia. One patient developed a testicular embryonic carcinoma, suggesting evidence of partial gonadal dysgenesis. Moreover, puberty occurred spontaneously in 93% of patients but 71% (n = 5) of those evaluated at the end of puberty presented signs of declined Sertoli cell function (low inhibin B levels and increased FSH levels). This study emphasizes the need to identify and follow-up 45,X/46,XY patients born with normal male phenotype until adulthood, as they present similar prognosis than those born with severe genital anomalies. Currently, most patients are diagnosed in adulthood with azoospermia, consistent with our observations of decreased testicular function at the end of puberty. Early management of these patients may lead to fertility preservation strategies.

Impact on testicular function of a single ablative activity of 3.7 GBq radioactive iodine for differentiated thyroid carcinoma

What are the consequences of radioactive iodine (RAI) therapy for testicular function? A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities. Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function. A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment. Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test. Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01). Among the 40 patients included in the study, only 24 had all the parameters available at all visits. Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed. This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work. NCT01150318.

Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model.

Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles.

Histological alterations in Leydig cells and macrophages in azoospermic men.

The study aimed to compare the histological features of Leydig cells and macrophages in the testicular interstitium of obstructive versus nonobstructive azoospermia. Thirty-nine azoospermic men undergoing testicular sperm extraction during intracytoplasmic sperm injection were allocated into obstructive azoospermia group (GI) and nonobstructive azoospermia group (GII) which was subdivided into Sertoli cell-only syndrome (GIIA), germ cell arrest (GIIB) and hypospermatogenesis (GIIC) subgroups. Serum LH, FSH and testosterone levels were measured. Ultrastructural changes and the mean number of CD68-positive cells were estimated in the different groups. In GIIA, Leydig cells' processes came in contact with macrophages and showed smooth endoplasmic reticulum dilatation. In GIIB, Leydig cells showed apoptotic changes. Macrophages were commonly encountered in their vicinity demonstrating large number of lysosomes. In GIIC, Leydig cells showed euchromatic nuclei. Macrophages showed expulsion of their lysosomal contents in the interstitium surrounded by apoptotic bodies. The mean count of total CD68-positive macrophages was higher in cases of obstructive azoospermia with nonsignificant differences compared to nonobstructive azoospermia groups. Significant increase in FSH level was detected in GIIA compared to GI. It is concluded that structural interactions might take place between Leydig cells and macrophages in the interstitial tissue of azoospermic men.

Can Elevated Levels of Basal Follicle Stimulating Hormone Predict a Decrease in Fertility in Young Women Undergoing ART Cycles?

Background: The determination of ovarian reserve is often measured in normal cycling women through day 3 basal FSH. This determination will help to choose patients who are eligible for starting assisted reproductive technique (ART) cycles. Female age and basal FSH level are independently associated with IVF outcome. Objective:This study aims’ at evaluating the impact of basal FSH level associated with female age on IVF outcome. Methods: A retrospective study that included 367 patients undergoing ICSI cycles. Basal FSH levels were measured using the same immunoenzymatic method for all patients. The age of women was checked before they were undergoing pituitary desensitization. Patients were divided into 4 groups according to their age and basal FSH levels. Then its correlation with IVF outcome was evaluated. Results:The increase of FSH levels was associated significantly with reduced oocytes retrieved, and embryos obtained in young women. Nevertheless, there was no significant difference in terms of fertilization or pregnancy rate. Cancellation rates were significantly higher among patients with high day 3 FSH levels compared to patients having normal FSH levels in all age groups. Loss rates were affected by FSH levels among patients < 38 years old. However, they were significantly higher in older patients having elevated day 3 FSH levels. Younger women with high FSH levels produced less but better quality embryos resulting in acceptable pregnancy rate. Conclusion: Female age is the most important prognostic factor. The basal FSH should be used to identify women who are purveyors of poor response to ART and should not be used to exclude them from fertility treatment.

Leptin receptor null mice with reexpression of LepR in GnRHR expressing cells display elevated FSH levels but remain in a prepubertal state.

Leptin signals energy sufficiency to the reproductive hypothalamic-pituitary-gonadal (HPG) axis. Studies using genetic models have demonstrated that hypothalamic neurons are major players mediating these effects. Leptin receptor (LepR) is also expressed in the pituitary gland and in the gonads, but the physiological effects of leptin in these sites are still unclear. Female mice with selective deletion of LepR in a subset of gonadotropes show normal pubertal development but impaired fertility. Conditional deletion approaches, however, often result in redundancy or developmental adaptations, which may compromise the assessment of leptin's action in gonadotropes for pubertal maturation. To circumvent these issues, we adopted a complementary genetic approach and assessed if selective reexpression of LepR only in gonadotropes is sufficient to enable puberty and improve fertility of LepR null female mice. We initially assessed the colocalization of gonadotropin-releasing hormone receptor (GnRHR) and LepR in the HPG axis using GnRHR-IRES-Cre (GRIC) and LepR-Cre reporter (tdTomato or enhanced green fluorescent protein) mice. We found that GRIC and leptin-induced phosphorylation of STAT3 are expressed in distinct hypothalamic neurons. Whereas LepR-Cre was observed in theca cells, GRIC expression was rarely found in the ovarian parenchyma. In contrast, a subpopulation of gonadotropes expressed the LepR-Cre reporter gene (tdTomato). We then crossed the GRIC mice with the LepR null reactivable (LepR(loxTB)) mice. These mice showed an increase in FSH levels, but they remained in a prepubertal state. Together with previous findings, our data indicate that leptin-selective action in gonadotropes serves a role in adult reproductive physiology but is not sufficient to allow pubertal maturation in mice.

Getting Older Women Pregnant: Contemporary Thoughts.

For women of advanced age with abnormally increased FSH levels, standardized hormonal stimulation often represents a cost-intensive procedure with a low success rate. It is well established now that with mild ovarian stimulation, there is a greater percentage of good-quality eggs (although a smaller number) than with higher-dose conventional stimulation. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotropins used and the mean number of oocytes retrieved. The proportion of high-quality and euploid embryos seems to be higher compared with conventional stimulation protocols, and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. The low number of embryos available for transfer poses a great challenge in the management of older women going in for IVF. A potential management of these older women is to create a sufficient pool of embryos by accumulating vitrified good-grade embryos over several minimal stimulation and natural cycles. At the end of the accumulation process, these embryos can be subjected to a preimplantation genetic screening using next-generation sequencing and then the pool would have only chromosomal normal embryos with maximal chances of implantation. This would potentially make the chances of success for older women similar to normal responders. This management, however, is unthinkable without an outstanding vitrification program. The option of accumulating embryos has become a promising reality with the advent of vitrification technologies.

Are FSHR polymorphisms risk factors to premature ovarian insufficiency?

Premature ovarian insufficiency (POI) is an ovarian dysfunction characterized by increased FSH levels and amenorrhea before 40 years old. In recent years, the search for genetic causes of POI intensified and studies have been published relating the presence of mutations and polymorphisms in genes associated with development, recruitment and oocyte atresia. The aim of this study was to evaluate the presence of FSHR polymorphisms in our population and contribute with the elucidation of POI etiology. To achieve it, we have studied 100 patients with POI (G1), 60 patients with border line levels of FSH (G2) and 123 controls with regular menopause onset. Cytogenetic analysis of patients’ samples and genotyping of Asn680Ser and Ala307Thr polymorphisms were performed in cases and controls. Cytogenetic analysis showed that 92% of G1 patients had normal karyotype, 4% presented polymorphic variants, 3% presented mosaic karyotype involving X chromosome. In G2, 91.6% had normal karyotype results, 3.2% displayed polymorphic variants, and 3.3% presented a mosaic karyotype involving X chromosome. Statistical comparison showed that the polymorphic allele of Ala307Thr polymorphism is more frequent in patients than in controls (G1: p < 0.001 and G2: p = 0.0259). This association has not been previously reported. We concluded that Ala307Thr polymorphism in FSHR can be potentially associated to POI development and can be considered as a screening marker in patients with ovarian failure signals.

Oocyte Quality in Patients with Increased FSH Levels.

The present study consists of quality comparison among oocytes retrieved from women under 37 years old showing increased levels of FSH (prone to premature ovarian insufficiency) and women at the same age with normal hormone levels. Oocyte quality was accessed according to Lucinda L. Veeck parameters (1986) and the statistical analyses were carried out using Chisquared, SPSS for Windows 13.0 (SPSS, Inc., Chicago, IL). All pvalues were twotailed, and 95% confidence intervals (CIs) were calculated. A P value <0.05 was considered statistically significant. Eight morphologic changes variables were considered in the study and two of them showed statistically significant differences between cases and controls: granular cytoplasm (P=0.002) and presence of vacuoles (P=0.025), both more frequent among the study group patients. As a conclusion, patients with increased FSH levels presented oocytes with worst quality variables than controls. This can be an indicative of ovarian aging and can impact negatively on oocyte development into viable embryos.

Shortened Estrous Cycle Length, Increased FSH Levels, FSH Variance, Oocyte Spindle Aberrations, and Early Declining Fertility in Aging Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice: Concomitant Characteristics of Human Midlife Female Reproductive Aging

Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

DNA methylation in spermatozoa as a prospective marker in andrology

Recent studies have shown associations of aberrant DNA methylation in spermatozoa with idiopathic infertility. The analysis of DNA methylation of specific genes could therefore serve as a valuable diagnostic marker in clinical andrology. For this purpose, rapid and reliable detection methods, reference values and the temporal stability of spermatozoal DNA methylation need to be established and demonstrated. In this prospective study, swim-up purified semen samples from 212 consecutive patients (single samples), 31 normozoospermic volunteers (single samples) and 10 normozoospermic volunteers (four samples at days 1, 3, 42 and 45 plus a fifth sample after 180-951days) were collected. Spermatozoal DNA was isolated, bisulphite converted and DNA methylation was analysed by pyrosequencing. DNA methylation of the maternally imprinted gene MEST was measured in samples of 212 patients and 31 normozoospermic volunteers and the temporal stability of eight different genes and two repetitive elements was examined in consecutive samples of 10 normozoospermic volunteers. MEST DNA methylation was significantly associated with oligozoospermia, decreased bi-testicular volume and increased FSH levels. A reference range for spermatozoal MEST DNA methylation (0-15%) was established using the 95th percentile of DNA methylation in normozoospermic volunteers. Using this reference range, around 23% of our patient cohort displayed an aberrant MEST DNA methylation. This epigenetic aberration was found to be significantly associated with bi-testicular volume, sperm concentration and total sperm count. DNA methylation in normozoospermic volunteers was stable over a time period of up to 951days in contrast to classical semen parameters. Our data show that MEST DNA methylation fulfils the prerequisites to be used as routine parameter and support its use during andrological workup if a prognostic value can be shown in future.

Uterine artery embolization – clinical problems

The aim of the study was to present clinical issues concerning uterine artery embolization (UAE) in women with uterine fibromas. In order to ensure high clinical efficiency of UAE and prevent subsequent complications, it is necessary to carefully select patients eligible for the procedure. Patients with intramural fibromas, who do not plan to conceive, are the best candidates for the procedure. Fibroma necrosis, with following infection, and premature ovarian failure remain to be the most common complications after UAE. UAE may cause amenorrhea and increase FSH levels, what is typical for menopause. Thus, it may be responsible for problems with conception as well as optimal development of a pregnancy. It may also cause premature, iatrogenic menopause. This complication significantly more frequently occurs in women over the age of 45 as compared to younger patients. UAE is considered as an alternative therapeutic procedure, available to women who do not desire the surgery or wish to preserve the uterus. Patients subject to this procedure should be informed about the possible side effects.

Ovarian function in Duarte galactosemia

To determine if girls with Duarte variant galactosemia (DG) have an increased risk of developing premature ovarian insufficiency based on prepubertal anti-Müllerian hormone (AMH) levels. Cross-sectional study. University research laboratory. Study volunteers included 57 girls with DG, 89 girls with classic galactosemia (GG), and 64 control girls between the ages of <1 month and 10.5 years. Blood sampling. We determined AMH and FSH levels in study volunteers with and without Duarte variant or GG. FSH levels were significantly higher and AMH levels significantly lower in girls with GG than in age-stratified control girls, but there was no significant difference between FSH and AMH levels in girls with DG and control girls. Although >80% of girls with GG in this study demonstrated low to undetectable AMH levels consistent with diminished ovarian reserve, 100% of girls with DG in our study demonstrated no apparent decrease in AMH levels or increase in FSH levels, suggesting that these girls are not at increased risk for premature ovarian insufficiency.

Thinking outside the square: considering gender in Klinefelter syndrome and 47, XXY

Thinking outside the square: considering gender in Klinefelter syndrome and 47, XXY