Serum Inhibin Research Articles

Evaluation of serum inhibin B and inhibin B/FSH ratio in the diagnosis of non-obstructive azoospermia and oligozoospermia.

Infertility affects approximately 15 % of couples globally, with 50 % cases of male factor infertility. Precise assessment of spermatogenesis is essential for evaluating male infertility. Recent studies suggest serum inhibin B as a promising biomarker for testicular function. This study aims to evaluate the diagnostic utility of serum inhibin B in predicting male infertility, particularly focusing on its relationship with sperm count. A cross-sectional study was conducted on 80 adult men (mean age 31.4±6.89 years) presenting with infertility at gynecology and urology outpatient departments. Semen analysis was performed following WHO (2010) guidelines, and serum inhibin B levels were quantified. The correlation between serum inhibin B levels and sperm parameters was assessed using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of serum inhibin B and the inhibin B/FSH ratio for non-obstructive azoospermia (NOA) and oligozoospermia. A significant positive correlation was observed between serum inhibin B and sperm count (r=0.94, p<0.001). ROC analysis demonstrated that the inhibin B/FSH ratio had the highest diagnostic accuracy for NOA and oligozoospermia (AUC=0.986), with sensitivity of 100 % and specificity of 91.67 %. Serum inhibin B alone also showed high diagnostic value (AUC=0.965 for NOA and 0.969 for oligozoospermia). Serum inhibin B is a reliable biomarker for assessing male infertility, particularly in evaluating spermatogenic function. The inhibin B/FSH ratio provides superior diagnostic accuracy for NOA and oligozoospermia, offering valuable clinical utility in male infertility diagnosis.

Markers of Fertility in Adolescents With Chronic Endocrinopathies at Transition From Paediatric to Adult Care

ABSTRACTObjectiveDuring the process of transition from paediatric to adult health care, counselling concerning fertility is an important issue and is based mainly on serum markers of gonadal function. Here, we analysed these markers in adolescents with various underlying endocrine diseases at the time of transition.MethodsAfter reaching near adult height and late puberty (girls: bone age [BA] ≥14 years, and boys: BA ≥16 years), we assessed stages of puberty according to Tanner and measured testes or ovarian volumes and serum markers of gonadal function (anti‐Mullerian hormone [AMH], inhibin B, 17β‐estradiol, testosterone).ResultsOne hundred and ten patients (56 females and 54 males) were included from May 2010 to March 2016 with multiple pituitary hormone deficiency (MPHD; n = 17), growth hormone deficiency (GHD; n = 35), Turner syndrome (TS; n = 27), short stature after being born small for gestational age (SGA; n = 20) and Klinefelter syndrome (KS; n = 11). Female and male adolescents exhibited mature secondary sexual characteristics. The levels of serum inhibin B and AMH were lower in TS and female MPHD than in GHD and SGA, each independently (p &lt; 0.05). The levels of serum AMH were higher whereas serum inhibin B were lower in male MPHD and KS (p &lt; 0.05). Ovary volumes were significantly smaller in patients with TS, and testicular volumes were smaller in patients with KS.ConclusionsAfter current established treatments with sex steroids, the development of secondary sexual characteristics was mature. However, impaired markers of fertility have been identified in patients with TS, KS and MPHD, reflecting gonadal dysgenesis in TS and KS, but gonadal immaturity in MPHD as gonadal gonadotropin stimulation is lacking throughout development. Consequently, in patients with MPHD, these markers cannot reliably predict individual fertility, which warrants consideration and incorporation in future treatment concepts.

Exceptional lymph node recurrence of an unusual ovarian tumor 16 years later: a case report

BackgroundSex cord-stromal tumors with annular tubules are a rare tumor accounting for less than 1% of all ovarian malignancies. However, they are characterized by very late recurrence, which can be as late as 30 years after diagnosis and treatment.Case presentationA 16-year-old female Caucasian patient was treated in our department for a stage IA ovarian sex cord-stromal tumors with annular tubules. She underwent a left salpingo-oophorectomy and ipsilateral pelvic node biopsy with no adjuvant treatment. She was seen for amenorrhea after being lost to follow up for 16 years. The diagnosis of recurrence was made by radiology and the elevation of serum inhibin B level. The patient underwent resection of the tumor, left segmental colectomy, and paraaortic lymphadenectomy because the mass was massively adherent to the left mesocolon. Histology confirmed the diagnosis with no metastatic lymph nodes. No adjuvant therapy was indicated. The patient was lost to follow-up again for 4 years and re-presented for amenorrhea. Serum inhibin B level was high. A second recurrence was suggested, and the patient underwent a laparoscopic surgery. We performed left pelvic and paraaortic lymphadenectomy, and 3 months after surgery the patient was pregnant.ConclusionSex cord-stromal tumors with annular tubules is a slow-growing ovarian tumor with a high potential for recurrence and metastasis. Surgery is the mainstay of treatment. Due to the rarity of these tumors, they are often unsuspected and thus incompletely staged before primary surgery; the diagnosis is made by histological examination. The prognosis of these patients is unknown, and they require long-term follow-up.

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.

Anogenital distance in a cohort of 169 infant boys with uni- or bilateral cryptorchidism including 18 boys with vanishing testes.

Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)? Length of AGD seemed to differ in different groups of patients with cryptorchidism. AGD, which is used as an indicator of prenatal androgen action, tends to be shorter in boys with cryptorchidism compared to unaffected boys. Shorter AGDs have also been reported in boys with hypospadias, in men with poor semen quality, and in men with testicular cancer. A prospective descriptive cohort study was performed using data from consecutively selected boys with cryptorchidism (n = 169) operated in a single center over a period of 3 years (September 2019 to October 2022). AGD was measured in 169 infant boys, at 3 to 26 months of age, during anesthesia with a vernier caliper measuring the distance from the anus to the base of the scrotum (AGDAS) and from the anus to the anterior base of the penis (AGDAP) in two body positions according to the methods by 'The Infant Development and the Environment Study' (TIDES) and 'Cambridge Baby Growth Study', resulting in four mean values per patient (TIDES AGDAS/AP and Cambridge AGDAS/AP). Normal values for AGD by age were set by our hospital Department of Growth and Reproduction based on a large cohort of healthy infant boys (n = 1940). Testicular biopsies were performed at orchidopexy as a clinical routine. The germ cell number (G/T) and type Ad spermatogonia number (AdS/T) per cross-sectional tubule of at least 100 and 250 tubules, respectively were measured and related to normal samples. Blood samples were obtained by venipuncture for measuring serum LH, FSH, and inhibin B. They were analyzed in our hospital Department of Growth and Reproduction where the normal reference was also established. Correlations between the four mean AGD measurements for each boy were evaluated by Spearman rank correlation analyses. The AGD measurement of every boy was transferred to the multiple of the median (MoM) of the normal AGD for age and named MoM AGD. There were 104 boysoperated for unilateral, and 47 boys operated for bilateral, undescended testes, whereas 18 boys had vanished testis including one boy with bilateral vanished testes. Only 6% of cases with vanished testes had a MoM AGD higher than the normal median compared to 32% with undescended testes (P < 0.05). MoM AGD increased with the age at surgery for boys with vanished testis (Spearman r = 0.44), but not for boys with undescended testes (Spearman r = 0.14). Boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism (P < 0.005) and (P < 0.000001). Although being the largest published material of AGD measurements of infant boys with cryptorchidism, one limitation of this study covers the quite small number of patients in the different groups, which may decrease the statistical power. Another limitation involves the sparse normal reference material on G/T and AdS/T. Finally, there are currently no longitudinal studies evaluating AGD from birth to adulthood and evaluating childhood AGD in relation to fertility outcome. Our study is hypothesis generating and therefore the interpretation of the results should be regarded as exploratory rather than reaching definite conclusions. The study findings are in agreement with literature as the total included group of boys with cryptorchidism exhibited shorter than normal AGDs. However, new insights were demonstrated. Boys with vanished testis had shorter AGDs compared to unaffected boys and to boys with undescended testes. This finding challenges the current concept of AGD being determined in 'the masculinization programming window' in Week 8 to 14 of gestation. Furthermore, boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism, suggesting that the lack of fetal androgen in hypogonadotropic hypogonadism is not that significant. No external funding was used and no competing interests are declared. The trial was not registered in an ICMJE-recognized trial registry.

Protective effect of functional food containing Dendrobium officinale via mediation of the FSHR/PI3K/AKT signaling pathway on menopausal syndrome in rats

Menopausal symptoms are age-related disorders related to the deficiency of estrogen that can be influenced by emotional and dietary habits. Guocaoyin superior-national-functional food (GSNF), a traditional Chinese medicine primarily containing Dendrobium officinale, offers notable benefits for mitigating metabolic disorders caused by unhealthy diet. Currently, there is limited research on the impact of GSNF on menopausal syndrome, and its underlying pharmacological mechanisms remain poorly understood. The aim of this study was to evaluate the ameliorative effect of GSNF on menopausal syndrome and to investigate its effect on endocrine metabolic disorders induced by ovarian failure. The findings demonstrate that GSNF raised levels of serum estradiol (E2), anti-mullerian hormone (AMH), and inhibin B (INHB), reduced levels of serum gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone (FSH), and ameliorated ovarian pathological damage in rats experiencing menopausal syndrome. It was discovered that GSNF enhanced ovarian FSHR and ERα protein expression, stimulated follicular development by activating the PI3K/AKT pathway, and hindered ovarian follicular apoptosis while improving ovarian function through the regulation of apoptosis-related proteins Bcl-2, BAX, and Caspase-3 expression. Furthermore, GSNF augmented the expression of hippocampal FSHR protein and upregulated the expression of hippocampal PI3K and AKT proteins. Additionally, it reduced serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, facilitated the release of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE), and boosted hippocampal tissue neuron count, thereby ameliorating depression-like symptoms during menopause. Moreover, GSNF supplementation improved glucose-lipid metabolism disorders and mitigated hepatic steatosis in model rats. Overall, our research revealed a new function for GSNF in mitigating the adverse impact of negative emotion and unhealthy dietary habits on menopausal symptoms. These findings indicate that GSNF may be a viable option for treating menopausal syndrome.

Effects of Varicocele Repair on Testicular Endocrine Function: A Systematic Review and Meta-Analysis.

The objective of this manuscript is to assess the effect of varicocele repair (VR) in patients with clinical varicoceles on serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin B serum levels. The study was performed in compliance with the Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE) guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study design) model. The values of each outcome measured after VR were compared to the before parameters and, when available, to the values on patients with unrepaired varicocele, and to those of healthy controls with no varicocele. For total testosterone, the values were sub-analyzed based on the mean total testosterone levels before VR (<300 ng/dL or >300 ng/dL), the fertility status, the time of follow-up and the technique used for VR. From a total of 460 abstracts retrieved, 48 articles were included in our meta-analysis. Serum total testosterone levels were significantly higher after VR compared to both pre-treatment levels (mean difference [MD] 82.45 ng/dL, 95% confidence interval [CI]: 64.14-100.76; p<0.00001) and to the levels of patients with unrepaired varicocele (MD 91.64 ng/dL, 95% CI: 62.30-120.99; p<0.00001). They did not differ from the levels of healthy controls with no varicocele (MD -22.01 ng/dL, 95% CI: -68.59-24.58; p=0.35). The increase resulted to be independent from the mean total testosterone levels before VR, fertility status, time of follow-up and type of VR. After VR, a trend toward lower serum LH levels was found compared to before values (MD -0.37 IU/L, 95% CI: -0.74-0.01; p=0.06). When compared to the levels of patients with unrepaired VR, LH levels after VR were significantly lower (MD -0.96 IU/L, 95% CI: -1.56 to -0.35; p=0.002). LH levels were not significantly higher than healthy men without varicocele (MD 0.84 IU/L, 95% CI: -0.68-2.36; p=0.28). Patients with VR had significantly lower FSH levels compared to their pre-treatment values (MD -1.43 IU/L, 95% CI: -1.82 to -1.04; p<0.00001), and also to those of patients with non-repaired varicocele (MD -2.35 IU/L, 95% CI: -4.06 to -0.65; p=0.007). When compared to healthy controls with no varicocele, FSH levels were significantly higher (MD 2.71 IU/L, 95% CI: 1.12-4.31; p=0.0009). Lastly, after VR no significant change in inhibin B serum levels was seen compared to pre-treatment levels (MD 11.76 pg/mL, 95% CI: -3.83-27.35; p=0.14). The present meta-analysis is the largest to date to assess the impact of VR on Leydig cell and Sertoli cell function using a before-after analysis for uncontrolled studies, and using data from patients with unrepaired varicoceles or healthy patients without varicocele as controls. VR was found to increase and restore to normality serum levels of total testosterone and LH. This evidence could be of value in considering the treatment of varicocele in patients with low testosterone or those who show a progressive decline in testosterone levels.

Mediation of association between semen microcystin exposure and semen quality by sex hormones in Chinese men

Numerous studies have shown microcystins (MCs) inducing male reproductive toxicity, but the underlying mechanisms in humans are unclear. Therefore, this study aimed to evaluate the mediating role of serum sex hormones in the association between MC exposure and semen quality. In this study, we measured the levels of semen MCs and serum sex hormones in Chinese men [sample 1 (n = 649); sample 2 (n = 924)]. The results showed that there was a non-significant dose-dependent relationship between semen MCs and semen volume reduction (p for trend = 0.079) in sample 1, and semen MCs were significantly negatively associated with total motility, progressive motility, curvilinear velocity, mean angular displacement and acrosome integrity (p < 0.05) in sample 2. We also found that semen MCs were significantly positively associated with serum follicle stimulating hormone (FSH) (β = 0.151; 95% CI: 0.065, 0.236), but negatively associated with serum inhibin B (INHB) (β = −0.605; 95% CI: −0.944, −0.265), and these linear associations were confirmed in restricted cubic spline (RCS) models (all pnon-linearity > 0.1). Furthermore, mediation analysis revealed that serum INHB mediated 19.86% of the adverse effect of MC exposure on acrosome integrity. In conclusion, this study reveals the mediating roles of serum sex hormones in the relationship between MC exposure and decreased semen quality in men.

Multi-omics study identifies that PICK1 deficiency causes male infertility by inhibiting vesicle trafficking in Sertoli cells

BackgroundInfertility affects approximately 10–15% of reproductive-age men worldwide, and genetic causes play a role in one-third of cases. As a Bin-Amphiphysin-Rvs (BAR) domain protein, protein interacting with C-kinase 1 (PICK1) deficiency could lead to impairment of acrosome maturation. However, its effects on auxiliary germ cells such as Sertoli cells are unknown.PurposeThe present work was aimed to use multi-omics analysis to research the effects of PICK1 deficiency on Sertoli cells and to identify effective biomarkers to distinguish fertile males from infertile males caused by PICK1 deficiency.MethodsWhole-exome sequencing (WES) was performed on 20 infertility patients with oligozoospermia to identify pathogenic PICK1 mutations. Multi-omics analysis of a PICK1 knockout (KO) mouse model was utilized to identify pathogenic mechanism. Animal and cell function experiments of Sertoli cell-specific PICK1 KO mouse were performed to verify the functional impairment of Sertoli cells.ResultsTwo loss-of-function deletion mutations c.358delA and c.364delA in PICK1 resulting in transcription loss of BAR functional domain were identified in infertility patients with a specific decrease in serum inhibin B, indicating functional impairment of Sertoli cells. Multi-omics analysis of PICK1 KO mouse illustrated that targeted genes of differentially expressed microRNAs and mRNAs are significantly enriched in the negative regulatory role in the vesicle trafficking pathway, while metabolomics analysis showed that the metabolism of amino acids, lipids, cofactors, vitamins, and endocrine factors changed. The phenotype of PICK1 KO mouse showed a reduction in testis volume, a decreased number of mature spermatozoa and impaired secretory function of Sertoli cells. In vitro experiments confirmed that the expression of growth factors secreted by Sertoli cells in PICK1 conditional KO mouse such as Bone morphogenetic protein 4 (BMP4) and Fibroblast growth factor 2 (FGF2) were decreased.ConclusionsOur study attributed male infertility caused by PICK1 deficiency to impaired vesicle-related secretory function of Sertoli cells and identified a variety of significant candidate biomarkers for male infertility induced by PICK1 deficiency.

Dose inhibin B or anti-Müllerian hormone relate to precocious puberty in girls? result of a systematic review and meta-analysis

BackgroundsExisting studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent.ObjectiveThe aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls.MethodsPubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model.ResultsA total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH.ConclusionScientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.

Association of serum inhibin a with pre-eclampsia: An observational cohort study with propensity score matching.

To assess whether serum inhibin A at 14-20 weeks of gestation is associated with the occurrence of pre-eclampsia. A retrospective cohort study using propensity score matching was conducted on 11 682 singleton pregnant women with established deliveries at the Obstetrics and Gynecology Hospital of Fudan University between January 2017 and July 2019. We investigated serum inhibin A levels at 14-20 weeks of gestation and calculated the relative risk between inhibin A and pre-eclampsia by multifactorial logistic regression analysis. Smoothed, fitted curves were used to observe the effect of inhibin A in relation to the occurrence of pre-eclampsia. The risk of pre-eclampsia occurrence increased with elevated serum inhibin A. After full adjustment for confounders, the risk ratio for pre-eclampsia in the group of pregnant women with high inhibin A was 2.92 (95% confidence interval [CI] 2.08-4.11) compared with those with normal inhibin A. The results of sensitivity analysis suggested a consistent effect of inhibin A on the risk of pre-eclampsia in different populations. Elevated serum inhibin A at 14-20 weeks of gestation is associated with pre-eclampsia and may provide an early warning signal for pregnancy outcomes associated with pre-eclampsia.

Testicular function after non-cytotoxic and immunotherapy drug treatment.

The effects of novel non-cytotoxic and immunotherapy drugs for cancer treatment on human testicular function have not been studied systematically. The present study aimed to characterize effects of non-cytotoxic and immunotherapy drugs in patients with cancers who had not been previously treated with gonadotoxic chemo- or radiotherapy. This study involved 34 men, not previously treated with gonadotoxic regimens, in a mixed longitudinal (Cohort 1: 19 men about to start and approximately 1year on non-cytotoxic and immunotherapy treatment) and cross-sectional (Cohort 2: 15 men already on non-cytotoxic and immunotherapy treatment) study using data modeling to estimate within-person time-course changes in testicular exocrine and endocrine functions. Cohort 1 provided 45 paired semen and blood samples (34 prior to and nine during treatment) and Cohort 2 provided 45 sets of samples (15 pre-treatment, 30 on treatment), including six men in Cohort 2 who had pre-treatment spermatozoa cryostorage prior to the study. Men on non-cytotoxic and immunotherapy treatment had undergone a median of 33.5months long-term treatment. Spermatozoa output and concentration were reduced by about 50%, with corresponding increases in serum follicle-stimulating hormone and decreases in serum inhibin B. Serum testosterone, luteinizing hormone, and sex hormone-binding globulin were unaffected by non-cytotoxic and immunotherapy treatment. Within limits of the present study of sample size and duration of on-non-cytotoxic and immunotherapy treatment, non-cytotoxic and immunotherapy drugs have a modest effects on testicular exocrine function (sperm production) or its hormonal correlates (follicle-stimulating hormone, inhibin B), with minimal impact on testicular endocrine (testosterone, luteinizing hormone) function.

SERUM ACTIVIN A &amp; INHIBIN A: POSSIBLE BIOCHEMICAL MARKERS OF PREECLAMPSIA &amp; PREGNANCY INDUCED HYPERTENSION

Objective: The objective of this study was to compare the levels of Serum Activin A and Inhibin A in Pregnancy induced hypertension, Preeclampsia &amp; Normal Pregnancy Material and Methods: An analytical, cross-sectional study conducted at Chemical Pathology Laboratory Collaborating with Gynae/Obstetric Department of Pakistan Railway Teaching Hospital, Rawalpindi over the period of one year (18 Sep 2019 to 18 March 2020). The study started after the approval of Ethical Review Committee, Riphah International University Islamabad. The sample size was calculated using WHO sample size calculator. Taking Prevalence of PIH and PE is 8%.3 Non probability convenient sampling technique was used. An overall 100 pregnant women with gestation of 20 – 25 weeks, were included. Patients of UTI, Carcinomas, Diabetes Mellitus and other chronic disorders were not included. The subjects were divided into three groups. Group I PIH: This group included 30 pregnant women of PIH; 20 - 25 weeks of gestation, BP: ≥140/90 mmHg on two separate occasions without proteinuria. Group II PE: This group included 20 pregnant women of preeclampsia; 20 - 25 weeks of gestation, BP: ≥140/90 mmHg on two separate occasions with proteinuria (&gt;0.3 g protein/24 hours Urine). Group III Control Group: This group included 50 pregnant women with gestational age of 20 – 25 weeks without any complication as healthy controls. Results: It was determined that Serum Activin A and Serum Inhibin A levels were significantly increased in PIH and PE groups as compared to healthy group. Mean of Serum Activin A in PIH, PE and Control group was (251.53+200.23 pg/ml), (466.95 + 237.40 pg/ml) and (43.35 + 85.22 pg/ml) respectively. Similarly Mean and Standard Deviation of Serum Inhibin A levels in PIH, PE and Control group was (194.78 + 173.00 pg/ml), (349.20 + 190.30 pg/ml) and (17.27 + 44.33 pg/ml) respectively. One-way ANOVA and post-hoc Tukey analysis was conducted to compare the mean of Serum Activin A and Serum Inhibin A levels among three different groups i.e Group 1(PIH and PE), Group 2(PIH and Control) and Group 3 (PE and Control). p-value&lt; 0.05 was considered as statistically significant. Conclusion: It can be concluded that Serum Activin A and Serum Inhibin A can be used as biochemical markers of PIH and PE. Estimation of Serum Activin A and Inhibin A at an early stage can detect PIH and PE early and further prevents their complications such as Eclampsia and HELLP syndrome. Keywords: Pregnancy induced hypertension (PIH), Pre-eclampsia (PE), HELLP syndrome (H – Hemolysis, EL- Elevated Liver Enzymes, LP – Low platelets count), Serum activin A, Serum inhibin A.

Effects of Varicocele Surgical Repair on Serum Hormone and Inhibin B Levels for Patients With Varicocele: A Systematic Review and Meta-Analysis.

Varicocele surgical repair can improve the function of the testis for patients with varicocele. We carried out a systematic review and meta-analysis to assess the effects of varicocele surgical repair on serum hormones and inhibin B levels in patients with varicocele. A literature search was performed in August 2022, and no language or geographic region restrictions were applied. The search included the following databases: PubMed, Embase, and Medline. A literature review was performed to identify all published clinical trials assessing serum hormone and inhibin B levels before and after varicocele surgical repair. The reference lists of retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Eight articles were selected from 162 articles, including 452 patients. The combined analysis showed that after surgical treatment, mean serum testosterone, inhibin B, and sperm concentration levels increased compared with preoperative levels (p < .05). After surgical treatment, mean serum follicle-stimulating hormon (FSH), and Luteinizing hormone (LH) levels decreased compared with preoperative levels (p < .05). This meta-analysis demonstrates that varicocele surgical repair can improve testicular function, increase serum testosterone, and inhibin B levels and decrease serum FSH and LH levels in patients with varicocele. This might be related to the improvement of infertility. A large-scale multicenter randomized controlled study is needed for further confirmation.

Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism.

Delayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development. This was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced (complete, cHH), or had commenced but not completed puberty (partial, pHH), by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed. 78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients (height p=0.004, weight p=0.021). 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. p=0.023). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay. Key clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment. .

Association of Serum Inhibin B and Primary Male Reproductive Hormone with Semen Quality in Normal and Infertile Men

Association of Serum Inhibin B and Primary Male Reproductive Hormone with Semen Quality in Normal and Infertile Men

The relationship between ultrasonographically measured testicular volumes and cord blood inhibin B concentrations in healthy term male neonates

Serum inhibin B (INHB) concentrations are associated with testicular volumes (TV) in all periods of childhood. The aim of the study was to investigate the relationship between TV measured by ultrasonography (US) and cord blood inhibin B and total testosterone (TT) concentrations, stratified by mode of delivery. In total 90 male infants were included. Testes of healthy, term newborns were evaluated by US on the third day after delivery. TV were calculated using two formulae: The ellipsoid formula [length (mm) × width (mm2) × π/6] and Lambert formula [length (mm) x width (mm) x height (mm) x 0.71]. Cord blood was taken for the determination of total testosterone (TT) and INHB. TT and INHB concentrations were evaluated according to TV percentiles (<10th, 10th-90th, >90th). There was a strong positive correlation between mean TV calculated with both formulae by percentile group (r = 0.777, r = 0.804, r = 0.846; p < 0.001). Cord blood INHB, but not TT were significantly lower in newborns with TV < 10th percentile compared to those with TV between 10 and 90th percentile and > 90th percentile (p < 0.05). There was a positive correlation between left and right TV calculated by either formula, and cord blood INHB (r = 0.212, 0.313, 0.320, 0.246,p < 0.05), not TT. There was no significant difference between hormones and TV when grouped by mode of delivery (p > 0.05). The Lambert and ellipsoid formulas are equally reliable in calculating neonatal testicular by ultrasound. INHB concentration is high in cord blood and positively correlated with neonatal TV. Cord blood INHB concentration may be an indicator for early detection of testicular structure and function disorders in neonates.

Androgen and inhibin B levels during ovarian stimulation before and after 8 weeks of low-dose hCG priming in women with low ovarian reserve.

Does 8 weeks of daily low-dose hCG administration affect androgen or inhibin B levels in serum and/or follicular fluid (FF) during the subsequent IVF/ICSI cycle in women with low ovarian reserve? Androgen levels in serum and FF, and inhibin B levels in serum, decreased following 8 weeks of hCG administration. Recently, we showed that 8 weeks of low-dose hCG priming, in between two IVF/ICSI treatments in women with poor ovarian responder (anti-Müllerian hormone (AMH) <6.29 pmol/l), resulted in more follicles of 2-5 mm and less of 6-10-mm diameter at the start of stimulation and more retrieved oocytes at oocyte retrieval. The duration of stimulation and total FSH consumption was increased in the IVF/ICSI cycle after priming. Hypothetically, hCG priming stimulates intraovarian androgen synthesis causing upregulation of FSH receptors (FSHR) on granulosa cells. It was therefore unexpected that antral follicles were smaller and the stimulation time longer after hCG priming. This might indicate a different mechanism of action than previously suggested. Blood samples were drawn on stimulation day 1, stimulation days 5-6, trigger day, day of oocyte retrieval, and oocyte retrieval + 5 days in the IVF/ICSI cycles before and after hCG priming (the control and study cycles, respectively). FF was collected from the first aspirated follicle on both sides during oocyte retrieval in both cycles. The study was conducted as a prospective, paired, non-blinded, single-center study conducted between January 2021 and July 2021 at a tertiary care center. The 20 participants underwent two identical IVF/ICSI treatments: a control cycle including elective freezing of all blastocysts and a study cycle with fresh blastocyst transfer. The control and study cycles were separated by 8 weeks (two menstrual cycles) of hCG priming by daily injections of 260 IU recombinant hCG. Women aged 18-40 years with cycle lengths of 23-35 days and AMH <6.29 pmol/l were included. Control and study IVF/ICSI cycles were performed in a fixed GnRH-antagonist protocol. Inhibin B was lower on stimulation day 1 after hCG priming (P = 0.05). Dehydroepiandrosterone sulfate (DHEAS) was significantly lower on stimulation day 1 (P = 0.03), and DHEAS and androstenedione were significantly lower on stimulation days 5-6 after priming (P = 0.02 and P = 0.02) The testosterone level in FF was significantly lower in the study cycle (P = 0.008), while the concentrations of inhibin B and androstenedione in the FF did not differ between the study and control cycles. A lower serum inhibin B in the study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the study cycle. This contradicts the theory that hCG priming increases the intraovarian androgen level, which in turn causes more FSHR on developing (antral up to preovulatory) follicles. However, based on this study, we cannot rule out that an increased intra-follicular androgen level was present at initiation of the ovarian stimulation, without elevating the androgen level in serum and that an increased androgen level may have rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. We retrieved significantly more oocytes in the Study cycle, and the production of estradiol per follicle ≥10-mm diameter on trigger day was comparable in the study and control cycles, suggesting that the rescued follicles were competent in terms of producing oocytes and steroid hormones. The sample size was small, and the study was not randomized. Our study design did not allow for the measurement and comparison of androgen levels or FSHR expression in small antral follicles before and immediately after the hCG-priming period. The results make us question the mechanism of action behind hCG priming prior to IVF. It is important to design a study with the puncture of small antral follicles before and immediately after priming to investigate the proposed hypothesis. Improved cycle outcomes, i.e. more retrieved oocytes, must be confirmed in a larger, preferably randomized study. This study was funded by an unrestricted grant from Gedeon Richter awarded to the institution. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co and payment for participation in an advisory board for Preglem. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S, and equipment and travel support has been given to the institution by Gedeon Richter Nordics AB. The remaining authors have no conflicts of interest to declare. ClinicalTrials.gov Identifier: NCT04643925.

P-682 Androgen and Inhibin B levels during ovarian stimulation before and after eight weeks of low dose hCG priming in women with low ovarian reserve

Abstract Study question Does eight weeks of low dose human chorionic gonadotropin (hCG)-priming affect androgen or Inhibin B levels in serum and follicular fluid during IVF/ICSI treatment? Summary answer Inhibin B was reduced on stimulation day 1 in the IVF/ICSI cycle following hCG-priming. Androgen levels in serum and follicular fluid was not increased. What is known already In our recently published pilot study, eight weeks of low-dose hCG-priming was used to stimulate the intraovarian androgen synthesis in women with AMH &amp;lt;6.29 pmol/L. Priming resulted in more retrieved oocytes and more follicles sized 2-5 mm and less sized 6-10 mm at the start of stimulation. Stimulation time and FSH consumption was increased after priming. HCG priming potentially stimulate the intraovarian androgen synthesis causing upregulation of FSH receptors on granulosa cells, and therefore it was unexpected that the antral follicles were smaller and stimulation time longer following priming. This might indicate a different mechanism of action than previously thought. Study design, size, duration A prospective, paired, non-blinded, single-center study including 20 women conducted between January 2021 and July 2021 at a tertiary referral hospital. Participants underwent two identical IVF treatments: a Control cycle including elective freezing of all blastocysts and a Study cycle with fresh blastocyst transfer. The Control and Study cycles were separated by eight weeks (two menstrual cycles) of hCG-priming by daily injections of 260 IE hCG (details in our previously published paper). Participants/materials, setting, methods Women aged 18-40 years with cycle lengths of 23-35 days and AMH &amp;lt;6.29 pmol/L. Control and Study IVF cycles were performed in a fixed GnRH-antagonist protocol. Blood samples were taken on stimulation day 1, stimulation day 5-6, trigger day, day of oocyte pick up (OPU), and trigger day + 7 days in the Control and Study cycles. Follicular fluid was collected from the first aspirated follicle on both sides during OPU in both cycles. Main results and the role of chance Inhibin B serum levels were significantly lower on stimulation day 1 after hCG-priming, but no other significant differences in serum Inhibin B or androgen levels were seen. The concentrations of Inhibin B and androstenedione in the follicular fluid from the Study and Control cycle did not vary but testosterone was significantly lower in the Study cycle. A lower Inhibin B in the Study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the Study cycle. This contradicts the theory that androgen priming causes more FSH receptors on developing (antral up to preovulatory) follicles. Instead, we hypothesize that androgen priming rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. The mechanism of action was likely an increase in androgen levels and FSH receptor expression within these small follicles, however, not enough to elevate androgen levels in serum. We retrieved significantly more oocytes in the Study cycle and the production of estradiol per follicle ≥10 mm on trigger day was comparable in the Study and Control cycle, suggesting that the rescued follicles were competent in producing oocytes and steroid hormones. Limitations, reasons for caution The sample size was small, and androgen and Inhibin B levels were not the primary outcome. We have not demonstrated a higher androgen level or FSH receptor expression in small antral follicles following hCG-priming. Wider implications of the findings The results make us question the mechanism of action behind hCG-priming prior to IVF. It is important to design a study with retrieval of small antral follicles immediately after priming to investigate the proposed hypothesis and to confirm improved cycle outcomes i.e., more retrieved oocytes in a larger study population. Trial registration number NCT04643925

O-135 Application of AMH determination in preoperative evaluation of micro-TESE in NOA patients

Abstract Study question To investigate the value of anti-Müllerian hormone(AMH) determination for estimating the sperm retrieval rate(SRR) of microdissection testicular sperm extraction(micro-TESE) in non-obstructive azoospermia(NOA) patients. Summary answer NOA with low AMH would have more opportunity to present heterogeneous seminiferous tubules when micro-TESE was performed and had higher SRR, especially in idiopathic cases. What is known already For infertile patients with NOA, micro-TESE is considered to have higher SRR than traditional surgery methods. However, serum inhibin B, follicle-stimulating hormone (FSH) and various clinical parameters are not reliable predictors for the presence of focal spermatogenesis and SRR. In male, AMH is a glycoprotein secreted by Sertoli cells and facilitate the regression of Müllerian structures in the developing foetus. It is still controversial that whether AMH level has value to predict the SRR of micro-TESE. Study design, size, duration This was a retrospective case-control study. From September 2014 to May 2022, 502 NOA patients treated with micro-TESE were divided into different groups according to their surgery outcome and seminiferous tubules appearance. Age, testis volume, serum AMH, FSH and testosterone level were compared between the different groups. The differences of SRR and AMH level in NOA patients with different etiologies were also compared. Participants/materials, setting, methods Micro-TESE was performed at x10 to x20 magnification. An attempt was made to identify seminiferous tubules that were larger and more opaque than others. The procedure was terminated when sperm were retrieved. If all tubules were seen to have an identical appearance, at least three samples (upper, middle, and lower) were extracted. Venous blood samples were drawn from each patient (7–10 AM) after an overnight fast. FSH and AMH were measured by electrochemiluminescence immunoassay. Main results and the role of chance Testicular sperms were successfully retrieved in 270 cases (SRR=53.8%). There were no statistical differences in age, testicular volume, FSH and testosterone levels between the patients who succeeded and failed to obtain sperm (all P&amp;gt;0. 05). The patients who obtained sperms had lower serum AMH level than those without sperm [0.81(0.16, 3.26)μg/L vs.1.37(0.21, 4.84)μg/L, P&amp;lt;0.05]. Patients with orchitis or AZFc deletion, cryptorchidism, KS, idiopathic azoospermia would have different AMH level [0.15(0.01, 0.41)μg/L, 5.71(3.57, 8.26)μg/L, 2.29(1.36, 3.81)μg/L, 0.15(0.05, 0.39)μg/L, 2.46(0.75, 5.49)μg/L, P&amp;lt;0.05]. Idiopathic azoospermia patients who obtained sperms had higher age but lower testosterone and AMH level than those without sperm [(35.2±8.9) years vs. (32.5±5.5) years, P&amp;lt;0.05, (3.1±1.4)μg/L vs. (3.7±2.1)μg/L, P&amp;lt;0.05; 1.63(0.35, 3.84)μg/L vs.3.00(1.20, 6.68)μg/L, P&amp;lt;0.05], there were no statistical differences in testicular volume and FSH level between the two groups (P&amp;gt;0.05). Receiver operating characteristic (ROC) curve showed that cut-off of serum AMH for successful sperm retrieval of idiopathic azoospermia patients was determined to be 2.96, with a sensitivity of 0.710 and specificity of 0.523, area under the curve (AUC) was 0.649. In the cases presenting heterogeneous seminiferous tubules during micro-TESE had lower AMH level and higher SRR than those presenting homogeneous seminiferous tubules [0.55(0.12, 2.05)μg/L vs.2.99(0.76, 6.11)μg/L, 75.9%(236/311)vs. 17.8%(34/191), all P&amp;lt;0.05]. Limitations, reasons for caution Pathology analysis should be involved in the following study. Randomized controlled trial comparing micro-TESE and traditional TESE would demonstrate that whether idiopathic azoospermia patients with higher serum AMH level would have less benefit by microsurgery than patients with lower AMH level. Wider implications of the findings Recently, in our pathologic research, NOA patients with extremely lower serum AMH level were observed to have more opportunity to present severe hyalinization in their seminiferous tubules. Tubules with severe hyalinization have less Sertoli cells and seem very thin. Therefore, tubules with spermatogenesis would be easy to identify during micro-TESE. Trial registration number not applicable