High Follicle-stimulating Hormone Research Articles

Value of estrogen pretreatment in patients with diminished ovarian reserve and elevated FSH on a line antagonist regimen: a retrospective controlled study.

The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied. We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared. The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D3 quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05). The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.

A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.

The Influence of IGF-1, Progesterone, Androstenedione, Aromatase, and Estrogen in Successful and Unsuccessful IVF Treatments

Follicular steroidogenesis, involving proteins including insulin-like growth factor 1 (IGF-1), progesterone (P4), androstenedione, aromatase, and estrogen (E2), may influence the success of in vitro fertilization (IVF) treatments. This research aimed to 1) compare levels of these proteins in follicular fluid (FF) between subjects with successful (n=10) and unsuccessful (n=20) outcomes; 2) compare these proteins between FF and serum within each group; and 3) investigate correlations of these proteins with reproductive hormones. Classification into successful and unsuccessful groups was based on the detection of fetal heartbeat. Blood samples were collected to measure anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) at baseline as well as IGF-1, FSH, P4, androstenedione, aromatase, and E2 in FF and serum on the day of ovum pick-up (OPU). In unsuccessful pregnancies, FF and serum IGF-1 levels and FF aromatase levels were significantly higher, whereas FF and serum androstenedione levels were significantly lower when compared to successful pregnancies ( P&lt;0.05 all). There were no significant differences in FF E2 and P4 levels between groups; however, there was a non-significant trend towards decreased FF E2 levels in unsuccessful pregnancies. Levels of IGF-1, P4, androstenedione, and E2 were significantly higher in FF than in serum in both successful and unsuccessful groups ( P&lt;0.01 all). The FF/serum ratios for successful and unsuccessful subjects were 2.28 and 2.06 for IGF-1, 7,920.61 and 1,919.26 for P4, 5.49 and 4.00 for androstenedione, and 193.45 and 225.60 for E2, respectively. For correlation analyses, basal AMH showed significant positive correlations with serum androstenedione in all subjects and a significant negative correlation with FF E2 in unsuccessful subjects ( P&lt;0.05 all). Basal FSH levels were significantly negatively correlated with serum androstenedione levels in all subjects ( P&lt;0.05). On OPU day, FF androstenedione levels showed significant positive correlations with FF and serum E2 levels in unsuccessful subjects ( P&lt;0.05 all). Serum androstenedione levels were significantly positively correlated with FF E2 levels in successful subjects and with serum E2 levels in all and unsuccessful subjects ( P&lt;0.01 all). FF aromatase levels had significant positive correlations with serum FSH levels in all and unsuccessful subjects ( P&lt;0.01 all). FF E2 levels were significantly positively correlated with FF androstenedione levels in unsuccessful subjects and with serum androstenedione levels in successful subjects ( P&lt;0.01 all). In unsuccessful pregnancies, elevated aromatase levels, despite similar or insignificantly lower FF E2 levels, could likely result from high FSH levels, potentially indicating defective FF E2 production processes that may be due to inadequate substrate availability or decreased aromatase activity. Lower androstenedione levels in unsuccessful pregnancies suggest that there may be a defect in substrate production; however, we could not determine whether there is a defect in aromatase function in these subjects. Lower FF and serum androstenedione levels in unsuccessful pregnancies might be due to poor ovarian response, as indicated by lower basal AMH and higher FSH levels observed in these subjects in our previous study, findings further supported by a positive correlation between androstenedione and basal AMH, and a negative correlation with basal FSH. The elevated IGF-1 levels in the unsuccessful group might be attributable to high FSH levels. Higher levels of IGF-1, P4, androstenedione, and E2 in FF than in serum indicate that these hormones might be primarily secreted into FF before being released into circulation. In conclusion, unsuccessful pregnancies exhibited lower FF and serum androstenedione levels, but higher FF aromatase and IGF-1 levels in both FF and serum, indicating a decreased substrate availability for E2 production in subjects with poor ovarian response. IGF-1, P4, androstenedione, and E2 were likely synthesized primarily in FF rather than serum. This research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R016433005 and Grant to support Strategic Driving Project for pushing the World University Rankings by Subject, Fiscal Year 2021 ((IO) R016421007). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Predictive Validity of Multifactorial Injury Risk Models and Associated Clinical Measures in the U.S. Population.

Background: Popular movement-based injury risk screens were shown to lack predictive precision, leading to interest in multifactorial models. Furthermore, there is a lack of research regarding injury risk assessment for those currently or planning to be recreationally active. This study aims to provide injury risk insights by analyzing multifactorial injury risk models and associated clinical measures in the U.S. population. Methods: Data related to injury, inflammatory markers, physical functioning, body composition, physical activity, and other variables from 21,033 respondents were extracted from NHANES. Odds ratios for self-reported injury were calculated for single predictors and risk models. Case-control and principal component analyses (PCA) were conducted to elucidate confounders and identify risk factor clusters, respectively. Receiver operating characteristic analysis was used to test the precision of a risk factor cluster to identify pain points and functional difficulties. Results: Sociodemographic, individual, and lifestyle factors were strongly associated with higher odds of injury. Increases in fibrinogen and C-reactive protein were significantly associated with all risk groups. Membership to the high-risk group (age over 40, obesity, no muscle-strengthening activities, sedentary lifestyle, and low back pain) predicted at least one functional difficulty with 67.4% sensitivity and 87.2% specificity. In the injury group, bone turnover markers were higher, yet confounded by age, and there was a significantly higher prevalence of self-reported osteoporosis compared to the control. In males, low testosterone was associated with injury, and high estradiol was associated with pain and functional difficulties. In females, high follicle-stimulating hormone was associated with functional difficulties. PCA revealed four high-risk profiles, with markers and activities showing distinct loadings. Conclusions: A comprehensive approach to injury risk assessment should consider the nexus of aging, lifestyle, and chronic disease to enhance tailored injury prevention strategies, fostering safe and effective physical activity participation and reducing the burden of musculoskeletal disorders.

Human umbilical cord mesenchymal stem cells alleviate chemotherapy-induced premature ovarian insufficiency mouse model by suppressing ferritinophagy-mediated ferroptosis in granulosa cells

Primary ovarian insufficiency (POI) in younger women (under 40) manifests as irregular periods, high follicle-stimulating hormone (FSH), and low estradiol (E2), often triggered by chemotherapy. Though mesenchymal stem cell (MSC) therapy shows promise in treating POI, its exact mechanism remains unclear. This study reveals that human umbilical cord-derived MSCs (hUC-MSCs) can protect ovarian granulosa cells (GCs) from cyclophosphamide (CTX)-induced ferroptosis, a form of cell death driven by iron accumulation. CTX, commonly used to induce POI animal model, triggered ferroptosis in GCs, while hUC-MSCs treatment mitigated this effect, both in vivo and in vitro. Further investigations using ferroptosis and autophagy inhibitors suggest that hUC-MSCs act by suppressing ferroptosis in GCs. Interestingly, hUC-MSCs activate a protective antioxidant pathway in GCs via NRF2, a stress-response regulator. Overall, our findings suggest that hUC-MSCs improve ovarian function in CTX-induced POI by reducing ferroptosis in GCs. This study not only clarifies the mechanism behind the benefits of hUC-MSCs but also strengthens the case for their clinical use in treating POI. Additionally, it opens up a new avenue for protecting ovaries from chemotherapy-induced damage by regulating ferroptosis.

Serum gonadal hormones levels and hypogonadism in ART naïve newly diagnosed HIV infected adult males in Mwanza, Tanzania

BackgroundHuman immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania.MethodsThis was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15.ResultsThe median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259–534] versus 517 [396–605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1–6.5] versus 2.6 [1.8–4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism.ConclusionSerum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies

BackgroundExposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. ObjectiveTo investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. MethodsIn 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. ResultsThe LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): −2.8 (−4.2;-0.4); MEHP: −1.4 (−3.4,0.2)] and higher FSH [∑DINP: 11.8 (−0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [−4.28 (−8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: −12.22 (−21.09;-1.18); oxo-MEHP: −12.73 (−22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. ConclusionWe observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

Mechanism Research of DHEA Treatment Improving Diminished Ovarian Reserve by Attenuating the AMPK-SIRT1 Signaling and Mitophagy.

This study aims to investigate the effect and mechanism of dehydroepiandrosterone (DHEA) on diminished ovarian reserve (DOR) by modulating the AMPK-SIRT1 signaling and mitophagy in rats. Three-month-old female Sprague-Dawley (SD) rats were randomized and injected intraperitoneally with sesame oil as the control or deoxyvinylcyclohexene (VCD) to induce DOR. The VCD-injected rats were randomized and injected subcutaneously with vehicle as the model group or with DHEA for 21days as the DHEA group. After being identified in proestrus, rat blood sampleswere collected to prepare serum samples, and their ovarian tissues were dissected. Compared with the controls, significantly lower serum estradiol (E2), anti-Müllerian hormone (AMH), and inhibin B (IHNB) and higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected in the model group (DOR rats). The model group of rats displayed an increase in follicular atresia and a decrease in ovarian volume and the number of growing follicles and corpus luteum, accompanied by increased frequency of oocyte apoptosis and reduced levels of mitochondrial function. Furthermore, significantly higher levels of the AMPK-SIRT1 signaling and mitophagy were observed in the ovaries of rats in the model group. In contrast, treatment with DHEA significantly ameliorated the hormone disorder and morphological changes in the ovaries, reduced the frequency of apoptotic oocytes, and improved mitochondrial function in the ovaries of DOR rats. Mechanistically, DHEA treatment significantly attenuated the AMPK-SIRT1 signaling and mitophagy in the ovaries of DOR rats. DHEA treatment reduced the severity of DOR and enhanced ovarian reserve function by attenuating the AMPK-SIRT1 signaling and mitophagy in the ovaries of rats.

Pharmacological Protection of Ovaries During Program Drug Chemotherapy in Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Patients

Aim. To assess the efficacy of ovarian protection and options for fertility preservation with the use of gonadotropin-releasing hormone agonists (a-GnRH) in patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphomas (NHLs) during program drug chemotherapy.&#x0D; Materials &amp; Methods. The study enrolled 247 female patients (187 with cHL and 60 with NHLs) undergoing program drug chemotherapy from 2019 to 2023. The patients were aged 13–42 years (median 24 years). Prior to chemotherapy and after it was completed, the serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol levels were measured. Besides, antral follicle count was estimated by pelvic ultrasound. To provide ovarian protection during chemotherapy, a-GnRH was administered to 67 (27 %) out of 247 patients. Ovarian reserve was assessed based on ultrasound and AMH, FSH, and estradiol levels in 2–3 months after completing the program of drug chemotherapy or after spontaneous menstrual recovery.&#x0D; Results. Menstrual cycle recovered in 194 (78.5 %) out of 247 patients, regardless of lymphoid malignancy variant. Among them, there were 79.7 % (n = 149) of cHL patients and 75 % (n = 45) of NHL patients. Accordingly, ovarian function was lost in 20.3 % (n = 38) of cHL patients and 25 % (n = 15) of NHL patients. Predictors of ovarian function recovery appeared to be age ≤ 28 years and AMH level &gt; 2.45 ng/mL. Pharmacological protection of ovaries did not impact the probability of menstrual cycle recovery. Regardless of immunomorphological variant of lymphoid malignancy, a regular menstrual cycle was completely restored in 48 (71.6 %) out of 67 a-GnRH recipients and in 146 (81.1 %) out of 180 patients without a-GnRH treatment.&#x0D; Conclusion. Most of cHL and NHL patients of early reproductive age (≤ 30 years) have a fair chance of menstrual cycle recovery after completing the program drug chemotherapy similar to BEACOPP, EACODD(PP)-14, R-CHOP, R-Da-EPOCH and other regimens. Ovarian reserve cannot be preserved by means of a-GnRH administration during chemotherapy. High baseline FSH and low baseline AMH levels indirectly indicate evidence of impaired ovarian reserve. Patients belonging to this category are those who, if intensive combined cytostatic therapy regimens are planned, should undergo prior oocyte/embryo retrieval with subsequent cryopreservation due to the risk of premature loss of ovarian function.

Female patients with systemic lupus erythematosus (SLE)-associated antiphospholipid syndrome (APS) have a lower ovarian reserve than either primary APS or SLE patients

Abstract Objectives To evaluate the ovarian reserve (OR) in women with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), especially SLE-associated APS, and to determine the association between OR and clinical and laboratory parameters. Methods We compared the antral follicle count (AFC), anticardiolipin antibody, and anti-Müllerian hormone (AMH), inhibin B (INHB), antiphospholipid (aPL) antibody, follicle-stimulating hormone (FSH), progesterone (P), testosterone (T), and estradiol (E2) among patients with primary APS (PAPS), SLE-APS, and SLE who were treated at Jinhua Central Hospital between 2017 and 2020. We conducted correlations and logistic regression analyses to identify the risk factors of OR failure in women with APS. Results Serum AMH were positively correlated with AFC and INHB in APS patients, and low AMH was independent risk factor for OR decline in APS patients. The ROC curve showed a high accuracy for AMH in the prediction of OR failure. Compared to healthy subjects (HS), patients with PAPS, SLE-APS, and SLE exhibited lower serum AMH, AFC, INHB, and E2 levels and higher FSH and levels (p&lt;0.05). Of all the patients, those with SLE-APS manifested the lowest serum AMH, AFC, INHB, and E2 levels and the highest FSH levels (p&lt;0.05). Conclusions APS and SLE patients showed lower indications of OR, including AFC and AMH, compared to HS. SLE-APS patients also appeared to have a lower OR than either SLE or PAPS patients.

The Importance of Discordant Follicle Stimulating Hormone and Inhibin B Levels in Primary Infertile Men: Findings from a Cross-Sectional Study.

We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Data from 1,230 consecutive men presenting for primary couple's infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34-41 years] vs. 36.0 years [31-40 years]); had smaller testicular volume (TV) (12 mL [10-15 mL] vs. 15 mL [12-20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9-11.0 million/mL] vs. 13.8 million/mL [3.1-36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%-25.3%] vs. 20.0% [7.0%-36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Low libido despite high normal testosterone levels in a male with an FSH-secreting pituitary macroadenoma.

Functioning gonadotroph adenomas with clinical manifestations are extremely rare and the majority of these are FSH-secreting macroadenomas. Clinical symptoms are due to excess gonadotrophins and sex hormones, and these may be present for a long time before the diagnosis of pituitary adenoma is made. We present the case of a 37-year-old Caucasian male with clinical manifestations of an FSH-secreting pituitary macroadenoma. He had sexual dysfunction for a year followed by bilateral testicular pain and enlargement which was initially treated as suspected recurrent epididymitis, but his symptoms did not resolve. He presented a year later with headaches and bilateral superior temporal visual field defects. Brain imaging confirmed a pituitary macroadenoma with optic chiasm compression. Pituitary profile demonstrated an unusually high FSH with high normal LH and normal testosterone level. The patient successfully underwent transsphenoidal hypophysectomy and histology confirmed gonadotroph differentiation and immunoreactivity predominantly with FSH. Gonadotrophin levels and testosterone dropped significantly after surgery, and he was started on testosterone replacement. MR imaging, 2 years post surgery, showed no recurrence of pituitary adenoma. In conclusion, testicular enlargement and hypogonadal symptoms associated with low testosterone levels are recognised features in FSH-secreting pituitary adenomas. Our patient had hypogonadal symptoms but consistently high normal testosterone levels prior to surgery. The reason for low libido despite high testosterone is unclear. Our case highlights the need to suspect such rare underlying pituitary pathology when dealing with unusual combinations of hypogonadal symptoms, testicular enlargement with low or normal testosterone levels. Functioning pituitary adenomas that secrete excess follicle-stimulating hormone (FSH) are very rare and often present with symptoms related to pituitary mass effect. Testicular enlargement alongside sexual dysfunction are commonly reported symptoms amongst male patients. Pituitary profile results demonstrate a raised FSH level with either a low, normal, or even high testosterone level which may not always correlate to clinical symptoms. Pituitary pathology should be considered in males presenting with unusual combinations of testicular enlargement and hypogonadal symptoms even with normal testosterone levels.

Sperm retrieval rate and patient factors in azoospermia factor c microdeletion azoospermia: a systematic review.

To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live-birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle-stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live-born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work.

Elevated circulating follicle stimulating hormone level is associated with dyslipidemia in male type 2 diabetes mellitus patients: A cross-sectional study.

Type 2 diabetes mellitus (T2DM) commonly combines with dyslipidemia, and both are known as the risk factors of cardiovascular events and aggravate the arteriosclerosis progression. In this study, we investigated the relationship between follicle-stimulating hormone (FSH) and lipid profiles in male T2DM patients. We collected clinical data of male T2DM patients in the Chinese Han population hospitalised from January 2018 to June 2020. A total of 963 patients with a mean age of 58.89±12.25years old were enroled in this study. The results showed that the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL)-C levels were decreased gradually from the highest quartile groups (Q4) to Q1 group relevant to luteinising hormone and FSH, and no significant difference was observed in high-density lipoprotein-C levels among Q4-Q1 groups. Sub-groups analysis showed that, with the increased FSH level, TC, TG, and LDL-C levels were increased in the elder group (40-59years old) than those in the younger group (20-39years old). Spearman's analysis revealed a positive correlation between FSH and the levels of TC, TG, and LDL-C (r=0.354, r=0.336, r=0.312, p<0.001, respectively). The effect of FSH is independent of the changes in total testosterone level. Multivariate analysis found that increased FSH levels (≥9.26mIU/mL) and decreased total testosterone levels (<13.30nmol/L) were positively correlated with high TC, TG, and LDL-Cemia (OR=4.014, 1.565, 1.602, 1.660, 2.127, 1.322, respectively, p<0.05). Our data suggest that high serum FSH level in male T2DM patients could be a potential independent risk factor correlated with the elevated TC, TG, and LDL-C.

Clinical outcome of different embryo transfer strategies after late rescue ICSI procedure: a 10-year total fertilisation failure cohort study

BackgroundLate rescue intracytoplasmic sperm injection (r-ICSI) has not been widely accepted as an alternative solution for unexpected total fertilisation failure (TFF) after in vitro fertilisation (IVF), due to the time-dependent in vitro deterioration of oocyte quality and endometrial growth not being synchronised with embryo development. This study aimed to evaluate the safety profile and effectiveness of freeze-all blastocyst transfer in combination with late r-ICSI.MethodsThis was a retrospective cohort study carried out at the Reproductive Centre of Peking University Third Hospital, Beijing, China. All participants received treatment between 2009 and 2019. 2,270 patients in the aggregate encountered unexpected TFF during 149,054 cycles of IVF and adopted a late r-ICSI procedure. Among these patients, 263 women did not have cleavage-stage embryos available for evaluation. The remaining patients were grouped according to different embryo transfer (ET) strategies (926 women in Group 1 underwent fresh ET, 365 women in Group 2 underwent freeze-all ET, 716 women in Group 3 experienced blastulation failure). Patients received different ET strategies after r-ICSI, with the main outcome measures included live birth rate (LBR), cumulative live birth rate (cLBR), and conservative cLBR.ResultsTFF occurred in 7.4% of all IVF cycles. Group 1 tended to be older at oocyte retrieval, with more infertile years, higher follicle-stimulating hormone (FSH) levels, higher gonadotropin consumption, and fewer oocytes retrieved. Group 2 exhibited considerably better LBRs following the first ET cycle (37.53% vs. 4.64%) and cLBRs (52.60% vs. 8.21%). After adjustment for covariates using binary logistic regression analyses, Group 2 still showed better obstetric performance in LBRs [OR:11.77, 95% CI (8.42–16.45)], cLBRs (OR:11.29, 95% CI (7.84–16.27)], and conservative cLBRs (OR:2.55, 95% CI (1.83–3.55)]. Additionally, the two groups showed similar miscarriage rates, whilst no new-borns with malformations or congenital diseases were reported.ConclusionsFreeze-all blastocyst stage ET serves as an optimal strategy to support late r-ICSI. However, for women with limited oocytes available for r-ICSI use, weighing the benefits against the costs of the procedure might be prudent before implementing in vitro blastulation.

Follicle Stimulating Hormone (FSH) as a Predictor of Decreased Oocyte Yield in Patients with Normal Anti-Müllerian Hormone (AMH) and Antral Follicle Count (AFC).

The purpose of the current study was to determine the utility of early follicular phase follicle-stimulating hormone (FSH) testing in patients undergoing in vitro fertilization (IVF). This was a retrospective review of patients from 2012 to 2015 at Mayo Clinic in Rochester, Minnesota, USA. Included subjects had a normal anti-Müllerian hormone (AMH) of 1 to 9 ng/ml and antral follicle count (AFC) of 10 to 29. Patients were stratified by FSH level when associated estradiol was less than 50 ng/ml. In total, 225 patients were categorized into three groups: high FSH (FSH ≥10 IU/L; n= 36), normal FSH (>5 IU/L and <10 IU/L; n=170), and low FSH (FSH ≤5 IU/L; n= 19). ANOVA and multiple logistic regression were used for statistical comparisons and for evaluation of the relationships between variables; significance level was set at <0.05. There were no significant differences in demographics, IVF cycle type, or peak estradiol level between the groups. Patients with a high basal FSH level had a similar clinical pregnancy rate and live birth rate compared to controls and patients with low FSH. High FSH level was associated with decreased follicular development (17 versus 22; p<0.01), oocyte yield (15 versus 18; p=0.02), and embryo yield (8 versus 10; p=0.04) despite higher total doses of gonadotropins. Patients with normal AMH and AFC levels could be further stratified into lower responders and starting doses of medications can be adjusted based on high basal FSH levels. Therefore, it is suggested to counsel patients on pregnancy outcomes which seem to be quite similar regardless of the FSH level.

Osteoporosis and bone metabolism in patients with Klinefelter syndrome.

Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6-15% of osteoporosis and of 25-48% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced insulin-like factor 3 and 25-OH vitamin D levels, and high follicle-stimulating hormone and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although dual-energy x-ray absorptiometry is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score, high-resolution peripheral quantitative computed tomography and vertebral morphometry seem promising tools to better estimate the fracture risk of patients with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.

Effectiveness of combined seeds (pumpkin, sunflower, sesame, flaxseed): As adjacent therapy to treat polycystic ovary syndrome in females.

The formation and release of eggs during ovulation are impacted by high amounts of androgens. Seed cycling is powerful in the treatment of polycystic ovary syndrome (PCOS). For efficacy studies, 90 women with PCOS, between 15 and 40 years were selected from the department of gynecology, Tertiary care unit. Women with PCOS were divided into three groups (T0, T1, T2) (20 women/group). Among these three groups, the first was the control group (T0). The second group was the experimental group (T1). In T1, 20 women with PCOS were treated with a portion control diet and METFORMIN 500 mg tab/day for 90 days. The third group was also an experimental group (T2). In this group, 20 women with PCOS were also treated with another treatment plan for 90 days, in which portion control diet and seed cycling were included. During the 12-week efficacy trial, the highest follicle stimulating hormone (FSH) levels were found in the control group T0 (8.18 ± 0.13 mIU/mL). In T2, FSH falls from 6.545 ± 0.16 mIU/mL to 3.51 ± 0.13 mIU/mL throughout a 12-week period. Overall, a portion-controlled diet and seed cycling reduced FSH levels by 1.2% to 2.5%. LH value was 10.118 ± 0.1874 IU/L in the control group (T0), which climbed 12.82 ± 0.15 IU/L, but decreased from 10.62 ± 0.26 IU/L to 9.79 ± 0.17 U/L and 11.015 ± 0.24 IU/L 6.217 ± 0.167 IU/L in the other groups (T1, T2). It was determined that the LH levels were reduced by 1.5%-2% in T2. Conclusively, the seed cycling approach is effective and has significant results in women with PCOS. Seed cycling improves hormonal disturbance in women which promotes a healthy life.

Biochemical identification of prepubertal boys with Klinefelter syndrome by combined reproductive hormone profiling using machine learning.

Klinefelter syndrome (KS) is the most common sex chromosome disorder and genetic cause of infertility in males. A highly variable phenotype contributes to the fact that a large proportion of cases are never diagnosed. Typical hallmarks in adults include small testes and azoospermia which may prompt biochemical evaluation that typically shows extremely high FSH and low/undetectable inhibin B serum concentrations. However, in prepubertal KS individual biochemical parameters are largely overlapping those of prepubertal controls. We aimed to characterize clinical profiles of prepubertal boys with KS in relation to controls, and to develop a novel biochemical classification model to identify KS before puberty. Retrospective, longitudinal data from 15 prepubertal boys with KS and data from 1475 controls were used to calculate age- and sex-adjusted standard deviation scores (SDS) for height and serum concentrations of reproductive hormones and used to infer a decision tree classification model for KS. Individual reproductive hormones were low but within reference ranges and did not discriminate KS from controls. Clinical and biochemical profiles including age- and sex-adjusted SDS from multiple reference curves provided input data to train a 'random forest' machine learning (ML) model for detection of KS. Applied to unseen data, the ML model achieved a classification accuracy of 78% (95% CI, 61% - 94%). Supervised ML applied to clinically relevant variables enabled computational classification of control and KS profiles. The application of age- and sex-adjusted SDS provided robust predictions irrespective of age. Specialized ML models applied to combined reproductive hormone concentrations may be useful diagnostic tools to improve the identification of prepubertal boys with KS.

Association of Endogenous Hormones and Bone Mineral Density in Postmenopausal Women.

The aim of this study was to examine the association between endogenous hormones and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study of 798 postmenopausal women aged 47-85 years. Data were collected on age, age at menopause, years since menopause, smoking status, body mass index, adiposity, BMD, physical activity, and Vitamin D supplementation. Measured hormonal parameters were: follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, ∆4-androstenedione, cortisol, insulin-like growth factor-1, 25-hydroxyvitamin D, and parathormone (PTH) levels. BMD was measured at the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. A directed acyclic graph was used to select potential confounding variables. Multivariable analysis showed significant associations between cortisol and femoral neck BMD (β: -0.02, 95% confidence interval [CI]: -0.03--0.00), and PTH with femoral neck BMD (β: -0.01, 95% CI: -0.02--0.01) and total hip BMD (β: -0.01, 95% CI: -0.01--0.00). Hormonal factors more likely associated with a higher risk of low BMD (osteopenia or osteoporosis) were FSH (odds ratio [OR]: 1.02, 95% CI: 1.01-1.03) and PTH (OR: 1.02, 95% CI: 1.01-1.04). Higher cortisol and PTH levels were inversely associated with BMD. Postmenopausal women with higher FSH or PTH levels were likely to have low BMD.