Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity.

Sperm production depends on proper Sertoli-germ cell interaction, and we hypothesized that receptor activator of nuclear factor κB ligand (RANKL) activity in Sertoli cells may influence spermatogenesis. Treatment with the RANKL inhibitor denosumab, normally used to treat osteoporosis, increased testicular weight, inhibin B, and germ cell proliferation in ex vivo testis cultures and in vivo in a humanized RANKL mouse. The effect on germ cell proliferation was positively associated with baseline serum concentrations of anti-müllerian hormone (AMH). In accordance, denosumab increased germ cell proliferation in ex vivo human testis cultures with low/moderate but not severe impairment of Sertoli cell function. In a placebo-controlled randomized clinical trial, denosumab had no effect on semen quality but increased sperm concentration in a subgroup of infertile men with serum AMH ≥38 pmol/L at baseline. In conclusion, high serum AMH may increase the probability of a beneficial response to denosumab treatment in infertile men, thus suggesting a possible venue for precision medicine in male infertility.

Prevalence of adrenal rest tumors and course of gonadal dysfunction in a clinical sample of men with congenital adrenal hyperplasia: a longitudinal analysis over 10 years.

BACKGROUND: Subfertility is prevalent in men with classic 21-hydroxylase deficiency (21OHD). We sought to characterize the long-term evolution of their gonadal function. METHODS: Retrospective longitudinal single-center study in 27 men (11 with testicular adrenal rest tissue [TART]), median observation period 12 years, testosterone (T), 11-oxygenated androgens, gonadotropins, and inhibin B measurement at each time point. RESULTS: T concentrations were below the normal range (n.s.) in 43.2% (no TART) and 54.6% (TART) per patient. After accounting for body mass index, sex hormone-binding globulin, and age, men with TART exhibited higher T (14.0 ± 0.80 nmol/L) than those without (11.9 ± 0.71 nmol/L). During the observation period, T levels rose in both groups but more in men with TART (from 10.1 ± 1.1 to 17.3 ± 1.9 nmol/L vs 10.3 ± 1.0 to 12.8 ± 1.9 nmol/L); this was accompanied by rising luteinizing hormone and diminishing hydrocortisone equivalent dosages (TART: from 38.1 ± 3.2 to 35.1 ± 1.8 mg/d; vs no TART: 28.8 ± 2.7 to 28.1 ± 1.6 mg/d) without correlation with any markers of adrenal androgen control. Inhibin B declined in men with large TART over time while TART status remained stable. CONCLUSION: T levels below the normal range are frequent in men with 21OHD, regardless of TART, but change little over time. Besides adrenal androgen control gonadal axis suppression from supraphysiological glucocorticoid dosages needs to be considered. While our results do not endorse regular screening for alterations in TART status among adults, Sertoli cell function should be monitored in men with large TART.

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

OBJECTIVE: During 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. METHODS: After 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, 17ß-estradiol, testosterone). RESULTS: One 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 < 0.05). The levels of serum AMH were higher whereas serum inhibin B were lower in male MPHD and KS (p < 0.05). Ovary volumes were significantly smaller in patients with TS, and testicular volumes were smaller in patients with KS. CONCLUSIONS: After 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.

Ovarian sclerosing stromal tumor mimicking malignancy: case series and literature review.

BACKGROUND: Sclerosing stromal tumors (SST) are rare ovarian neoplasms that often appear as solid unilateral tumors of the ovary with no specific clinical or radiological presentation. The definitive treatment is surgical removal. CASE PRESENTATION: Our article presents four cases of female patients with sclerosing stromal ovarian tumor with clinical characteristics mimicking malignant ovarian lesions. Interestingly, two of our cases had elevated levels of inhibin B. All patients were treated with surgery (oophorectomy) and had no disease recurrence. CONCLUSION: Tumors' macroscopic features are usually non-specific and often suggestive of possible malignancy, therefore diagnosis is always based on histopathological report.

Study on the value of Inhibin B in the diagnosis of nasopharyngeal carcinoma and its correlation with traditional Chinese medicine syndromes: An observational study.

To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage III + IV than that of patients with stage I + II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage III + IV than that of patients with stage I + II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage III + IV patients were lower than those in stage I + II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.

Effects of empagliflozin on reproductive system in men without diabetes.

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for the treatment of type 2 diabetes, renal disease and chronic heart failure. The protein SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2), which is highly expressed in renal cortex, but also in the testes where glucose uptake may be essential for spermatogenesis and androgen synthesis. We postulated that in healthy males, SGLT2 inhibitor therapy may affect gonadal function. We examined the impact on gonadal and steroid hormones in a post-hoc analysis of a double-blind, randomized, placebo-controlled research including 26 healthy males who were given either placebo or empagliflozin 10 mg once daily for four weeks. After one month of empagliflozin, there were no discernible changes in androgen, pituitary gonadotropin hormones, or inhibin B. Regardless of BMI category, the administration of empagliflozin, a highly selective SGLT2 inhibitor, did not alter serum androgen levels in men without diabetes. While SGLT2 is present in the testes, its inhibition does not seem to affect testosterone production in Leydig cells nor inhibin B secretion by the Sertoli cells.

Basal and FSH-stimulated Inhibin B in Precocious Puberty.

OBJECTIVE: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP). METHODS: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test. RESULTS: Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11-1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. CONCLUSION: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size.

Association between aneuploidy screening analytes and adverse outcomes in twin gestations.

OBJECTIVES: To evaluate associations between serum analytes used for genetic screening and obstetric complications among twin pregnancies. METHODS: This cohort included twins delivered at a tertiary care hospital from 2009 to 2017. Abnormal levels of pregnancy associated plasma protein (PAPP-A), first and second trimester human chorionic gonadotropin (hCG), alpha fetoprotein (AFP), estriol, and inhibin, reported as multiples of the median (MoM), were defined as <5 %ile or >95 %ile for our cohort. Associations between abnormal analytes and preterm delivery, small for gestational age, and pregnancy-associated hypertension were calculated using Fisher's exact test. RESULTS: A total of 357 dichorionic/diamniotic and 123 monochorionic/diamniotic twins were included. Among dichorionic/diamniotic twins, elevated AFP (>3.70 MoM) was associated with increased preterm delivery <34 weeks (44.4 vs. 16.5 %, p=0.007), while elevated inhibin (>4.95 MoM) was associated with increased preterm delivery<37 weeks (94.1 vs. 58.8 %, p=0.004). For monochorionic/diamniotic twins, elevated inhibin (>6.34 MoM) was associated increased preterm delivery <34 weeks (66.7 vs. 24.8 %, p=0.04) and hypertension (66.7 vs. 21.4 %, p=0.03). CONCLUSIONS: Selected abnormal analyte levels were associated with increased rates of adverse outcomes in twin pregnancies, which differed by chorionicity. Our findings assist providers in interpreting abnormal analyte levels in twin pregnancies and may help to identify those at increased risk for adverse outcomes.

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

BACKGROUND: Sex 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 PRESENTATION: A 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. CONCLUSION: Sex 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.

Estimation of B-inhibin and anti mullerian hormone in functional azoospermia and their correlations with surgical sperm retrieval: A prospective case-control study.

OBJECTIVES: The current study estimated the levels of anti mullerian hormone (AMH) and inhibin-B and reproductive hormones in non obstructive azoospermic (NOA) cases and obstructive azoospermic (OA) cases as well as comparing between them as regards the sensitivity and specificity in determining the sperm retrieval hope in the NOA cases. Finally, we analyzed any potential correlation between all the hormones measured in the current study. METHODS: The current case control study was conducted at the andrology outpatient clinic from June (2021) to March (2022). The study recruited 135 participants divided equally into three groups NOA cases, OA cases and controls, respectively. RESULTS: The mean inhibin-B was significantly lower in the NOA cases compared to the OA cases and the controls. There was a positive moderate correlation between AMH and Inhibin-B. Also, there was a positive moderate correlation between inhibin-B and free testosterone (FT) and positive weak correlation between beta Inhibin and leutinizing hormone (LH). CONCLUSIONS: The current study asserts the observation that inhibin-B is also expressed by Leydig cells as it has demonstrated positive correlations with FT and LH.

Combined maternal risk factors and the Quadruple test to predict late-onset preeclampsia in pregnant Thai women.

BACKGROUND: This study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE). METHODS: All pregnant women that received the Quadruple test for Down syndrome at 15+ 0-20+ 6 weeks' gestation were recruited. Maternal serum α-fetoprotein, ß-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model's predictive ability. RESULTS: Fifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60). CONCLUSIONS: Our model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended.

Low Serum Inhibin B/Follicle-Stimulating Hormones and Anti-Müllerian Hormone/Follicle-Stimulating Hormones Ratios as Markers of Decreased Germ Cells in Infants with Bilateral Cryptorchidism.

PURPOSE: In cryptorchidism, germ cell development failure presents from infancy and may be reflected by altered hormonal levels produced by Sertoli cells. Our object was to assess for associations between serum hormone levels and testicular histopathology in cryptorchidism with an infertility risk according to the pretreatment undescended testicular positions. MATERIALS AND METHODS: Prepubertal cryptorchid boys aged 7-91 (median 20) months who underwent orchidopexy between 2014 and 2019 were included (122 unilateral [median 19 months {range 7-91}], 23 bilateral [24 months {11-81}]). We evaluated the pretreatment testicular position and size; serum hormone levels; and the mean number of germ cells per tubule transverse section (G/T). We also performed a subgroup analysis of boys aged ≤24 months at orchidopexy. RESULTS: Serum inhibin B levels and G/T were significantly lower in bilateral than in unilateral cryptorchid boys (median 96 [range 46-197] pg/ml vs 125 [21-354] pg/ml, p=0.026; 0.20 [0-2.59] vs 0.65 [0-4.55], p <0.001, respectively). Inhibin B/follicle-stimulating hormones (FSH) and anti-Müllerian hormone (AMH)/FSH ratios were positively correlated with G/T in bilateral cryptorchid boys aged ≤24 months (12, p=0.008 and p=0.019, respectively). Low inhibin B/FSH and AMH/FSH ratios and high FSH were predictors of impaired G/T as per receiver operating characteristic curves (p=0.019, p=0.004 and p=0.004, respectively), whereas in unilateral cryptorchid boys aged ≤24 months, serum hormone levels and G/T did not differ with the pretreatment testicular positions. CONCLUSIONS: In bilateral cryptorchid boys aged ≤24 months at orchidopexy, low inhibin B/FSH and AMH/FSH ratios may reflect impaired G/T and future infertility risk.

The utility of serum inhibin B, anti-Müllerian hormone and insulin growth factor-1 in predicting a positive response to GnRH analogs for diagnosing central precocious puberty in girls.

OBJECTIVES: The use of inhibin B (INHB), anti-Müllerian hormone (AMH) and insulin-like growth factor-1 (IGF-1) in differentiating central precocious puberty (CPP) from non-CPP was evaluated. METHODS: In total, 115 Chinese girls were recruited (CPP: 44, non-CPP: 71). The diagnostic performance of INHB, AMH and IGF-1 in differentiating CPP from non-CPP was analyzed using receiver operating characteristic (ROC) curves. RESULTS: INHB levels were higher in the CPP group than in the non-CPP group (55.56 ± 22.42 vs. 32.97 ± 15.59 pg/mL; p<0.001). AMH levels were similar in the CPP and non-CPP groups (6.63 ± 3.74 vs. 5.70 ± 3.15 pg/mL; p=0.158), and IGF-1 levels were much higher in the CPP group than in the non-CPP group (290.75 ± 79.78 vs. 200.10 ± 54.01 pg/mL; p<0.001). The area under the ROC curve (AUC) was greatest for INHB (0.819, standard error (SE) 0.041), followed by IGF-1 (0.809, SE 0.047) and AMH (0.567, SE 0.057). Among the ROC curves including combinations of these parameters, the AUC for INHB + IGF-1 was 0.849 and that for INHB + AMH was 0.768. CONCLUSIONS: Serum INHB and IGF-1 measurements could predict positive responses to gonadotropin-releasing hormone (GnRH) analog stimulation in girls with precocious puberty.

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening.

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to -112.8%] and -23.3% [95%CI -41.9% to -4.7%]. Passing-Bablok indicated significant systematic (-2.78 [95%CI -3.57 to -2.04]) and proportional bias (1.30 [95%CI 1.15 to -1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65-0.78]) between inhibin-A assays. The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and -0.0001 [SD = 0.2078], and -0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81-83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Clinical application value of Inhibin B alone or in combination with other hormone indicators in subfertile men with different spermatogenesis status: A study of 324 Chinese men.

BACKGROUND: In this study, we investigated the clinical value of serum Inhibin B alone or in combination with other hormone indicators in subfertile men. METHODS: This is a multicenter study involving 324 men from different cities in China. Testicular volume, routine semen analysis, serum Inhibin B, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and prolactin were measured. Testicular tissue samples were also analyzed in 78 of 129 patients with azoospermia to distinguish impaired spermatogenesis from obstructive azoospermia. RESULTS: The concentration of Inhibin B, FSH, and AMH is related to spermatogenesis. For men with impaired spermatogenesis, including mild-to-moderate oligozoospermia (IMO) and severe oligozoospermia (ISO), serum levels of Inhibin B and FSH are highly correlated with sperm counting. However, in patients with idiopathic moderate oligozoospermia or severe oligozoospermia, there was no significant correlation between Inhibin B (or FSH) and sperm concentration. The upper cutoff value of Inhibin B to diagnose ISO is 58.25 pg/ml with a predictive accuracy of 80.65%. To distinguish between nonobstructive azoospermia (NOA) and obstructive azoospermia (OA), the area under the curve (AUC) for AMH + Inhibin B + FSH is very similar to Inhibin B (0.943 vs. 0.941). The cutoff level of Inhibin B to diagnose nonobstructive azoospermia is 45.9 pg/ml with a positive and negative prediction accuracy of 97.70% and 85.71%, respectively. CONCLUSION: In summary, Inhibin B is a promising biomarker alone or in combination with other hormone indicators for the diagnosis of testicular spermatogenesis status, helping clinical doctors to distinguish NOA from OA.

Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.

OBJECTIVES: Maternal serum inhibin-A, pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine artery pulsatility index (UtA PI) were analysed to study their ability to predict pre-eclampsia (PE). STUDY DESIGN: Serial serum samples for the nested case-control study were collected prospectively at 12-14, 18-20 and 26-28 weeks of gestation from 11 women who later developed early-onset PE (EO PE, diagnosis < 34 + 0 weeks of gestation), 34 women who developed late-onset PE (LO PE, diagnosis ≥ 34 + 0 weeks) and 89 controls. MAIN OUTCOME MEASURES: Gestational age -adjusted multiples of the median (MoM) values were calculated for biomarker concentrations. Multivariate regression analyses were performed to combine first trimester biomarkers, previously reported results on PlGF, maternal risk factors and UtA PI. Area under curve (AUC) values and 95% confidence intervals (CIs) for the prediction of PE and its subtypes were calculated. RESULTS: A high first trimester inhibin-A predicted PE (AUC 0.618, 95%CI, 0.513-0.724), whereas PAPP-A and PlGF predicted only EO PE (0.701, 0.562-0.840 and 0.798, 0.686-0.909, respectively). At 26-28 weeks PAPP-A2 and inhibin-A predicted all PE subtypes. In the multivariate setting inhibin-A combined with maternal pre-pregnancy body mass index, prior PE and mean UtA PI predicted PE (0.811,0.726-0.896) and LO PE (0.824, 0.733-0.914). CONCLUSIONS: At first trimester inhibin-A show potential ability to predict not only EO PE but also LO PE whereas PlGF and PAPP-A predict only EO PE. At late second trimester inhibin-A and PAPP-A2 might be useful for short-term prediction of PE.

Can Inhibin B Reflect Ovarian Reserve of Healthy Reproductive Age Women Effectively?

Objective: The reference range and potential value of inhibin B are still unclear and controversial. This study aimed to define the variation trend of inhibin B in healthy women with age and explore its value in the reflection of ovarian reserve. Methods: A total of 2524 healthy reproductive age women from eight medical institutes nationwide were recruited. The variation tendency of inhibin B with age was primarily established in the first group of 948 women and validated in another 605. We evaluated the relationship between inhibin B and classic ovarian reserve and function markers. The potency of inhibin B in predicting AFC <5-7 was also estimated and compared with FSH. Results: The nomogram showed that serum levels of inhibin B rapidly decreased after the age of 40. Inhibin B was positively correlated with AMH (R = 0.57, P < 0.001), AFC (R = 0.34, P < 0.001) and testosterone (R = 0.10, P = 0.002), and negatively correlated with FSH (R = -0.41, P < 0.001) and LH (R = -0.20, P < 0.001) and FSH/LH (R=-0.18, P < 0.001), while no correlation was found with PRL. Unexpectedly, Inhibin B (AUC = 0.74, P < 0.001 for the establishment population; AUC = 0.78, P < 0.001 for the validation population) had a slightly higher value than FSH (AUC = 0.71, P < 0.001 for the establishment population; AUC = 0.72, P < 0.001 for the validation population) in diagnosing AFC <5-7. Conclusions: For healthy reproductive age women, the decline of inhibin B can reflect decreased ovarian reserve effectively, having a good consistency with AMH and AFC. More importantly, inhibin B had an advantage in predicting AFC <5-7 compared with FSH, which suggested the potential of inhibin B in predicting ovarian response. These results will be helpful to the clinical application of inhibin B in the evaluation of female ovarian reserve and the assessment of their reproductive capacity. Trial registration: http://clinicaltrials.gov; NCT02294500.

Ethnic-specific reference range affects the efficacy of quadruple test as a universal screening for Down syndrome in a developing country.

OBJECTIVE: To evaluate the efficacy of the quadruple test for potential use as a Thai national policy for Down syndrome (DS) screening and establish an accurate equation for risk estimation of Down syndrome based on gestational age, weight and the ethnic-specific reference range of our population. METHODS: A prospective study was conducted on singleton pregnancies at 14 to 21 weeks of gestation to evaluate the efficacy of quadruple DS screening using the automatically calculated Western European descent factor (WF) in our population and the impact of screening using a specific Thai ethnic factor as well as to establish an equation for the risk estimation of DS based on gestational age, weight and a local Thai ethnic factor to correct for the impact of ethnic factor on the screening efficacy. RESULTS: Of a total of 5,515 women, 12 cases of DS and 8 cases of other aneuploidies were found. The detection rate, false positive rate and specificity were 75.0%, 9.1% and 90.9%, respectively, by automatic calculation with the widely used WF; the screening efficacy was lower when used in Asian populations than in other studies. The best-fitted regression equation of serum quadruple screening of AFP, free ß-hCG, uE3 and inhibin A was established by adjustment for gestational age (GA) in days, maternal weight and our Thai-specific ethnic reference range which was created for this study. Calculations with our Thai-specific ethnic model gave a better detection rate of 83.3%, a false positive rate of 9.6% and specificity of 90.4%. CONCLUSION: The serum quadruple test had a lower detection rate than expected when the risk estimation was based on the WF reference range. The serum quadruple test using WF had significantly different levels when corrected with our ethnic-specific factor. Using our local ethnic specific model could increase the detection rate of DS screening in Thailand with a minimal increase in false positive rates. Our findings indicate that DS screening should be adjusted with an appropriate individual ethnic factor when used for national screening.

Hormonal markers as noninvasive predictors of sperm retrieval in non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA.

Interactions between serum FSH, inhibin B and antral follicle count in the decline of serum AMH during the menstrual cycle in late reproductive age.

Objective: To investigate the hormonal interrelationships during the menstrual cycle in women of late reproductive age with suppressed serum AMH and antral follicle count (AFC). Methods: Serum hormones (AMH, FSH, LH, estradiol, progesterone, inhibin A, inhibin B), AFC (2-10 mm) and AMH/AFC ratio (an estimate of AMH/follicle) were assessed every 2-3 days across the menstrual cycle in 26 healthy ovulatory women aged 18-50 years. Results: An 11-fold fall in AMH/AFC was observed in women aged ≥45 years compared to those 18-45 years (P < .001). Although women ≥45 years exhibited normal menstrual cycle patterns of serum estradiol, progesterone, LH and inhibin A, FSH was elevated (P < .001) and inhibin B suppressed (P < .001) compared to the younger group. Overall FSH was inversely correlated (r = .55, P < .05) and AMH directly correlated (r = .88, P < .01) with AFC; however, these relationships were curvilinear and more pronounced when AFC was low. Inhibin B was directly linearly correlated (r = .70, P < .01) with AFC across both high and low AMH/follicle groups. Conclusions: It is hypothesized that the marked fall in AMH/follicle in late reproductive age is attributed to the change in the hormonal interplay between the pituitary and ovary. The fall in AFC leads to a decrease in inhibin B and a concomitant increase in FSH by a recognized feedback mechanism. It is postulated the elevated FSH suppresses AMH either directly or indirectly through oocyte-specific growth factors leading to a marked fall in AMH/follicle. We propose that pituitary-ovarian and intra-ovarian regulatory systems underpin the accelerated fall in AMH/follicle during the transition to menopause.