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AbstractObjectiveMethodsResultsConclusionsTo investigate the comprehensive effects of daily chronic asprosin administration on various pubertal and reproductive parameters in female rats. This study aims to elucidate the role of asprosin in regulating the onset of puberty and its influence on hormonal profiles and ovarian histology.Asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg daily for eight weeks. Hormonal assays and histological analyses were performed to evaluate the effects of asprosin on the onset of puberty and reproductive function.Daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays revealed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights.Role of adipokines in regulating puberty and reproductive function has increasingly gained recognition. This study aimed to provide the first comprehensive examination of the effects of daily chronic asprosin administration on pubertal and reproductive parameters in female rats. Utilising hormonal assays and histological analyses, asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg, daily, for eight weeks. Our findings revealed that daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays showed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. These results provide new insights into asprosin’s role in advancing the age of first oestrus and modulating hormonal profiles, thereby offering potential benefits to the female reproductive system. [ABSTRACT FROM AUTHOR]

We aimed to determine if a programme change to 12 hourly injections of FSH (150 IU per injection) for the first 2 days of stimulation in women with high ovarian reserve (AMH ≥ 30 pmol/L), followed by 24 hourly injections, would elicit increased earlier follicular recruitment, higher egg yields and blastocyst embryos for cryopreservation, leading to potential higher cumulative pregnancy rates, than conventional daily injections throughout. For safety reasons, the approach required mandatory cryopreservation of all blastocysts (mFET group; n = 74), after ovulation trigger with GnRH-agonist, in GnRH-antagonist controlled cycles. The 'Comparator group' (n = 91) comprised women with the same high AMH levels treated with the same base dose of FSH, with the aim of fresh blastocyst transfer and cryopreservation of supernumerary embryos, treated over the preceding 2 years. There was no difference in age, AMH, weight or BMI between the groups. The mFET group achieved higher egg (17.7 versus 11.7; p < 0.001) and embryo (10.9 versus 7.2; p < 0.001) yields and fewer cases with sub-optimal embryo yields (7% versus 22%; p = 0.018). The cumulative live birth rate was superior in the mFET group (73% versus 43%), as was the safety profile, and negligible rate of treatment plan modification. [ABSTRACT FROM AUTHOR]

Embryo quality and quantity are key factors that determine the success of IVF-ET. Yet it is still unclear if, for those patients with only one good-quality embryo in an IVF cycle, the inclusion of a poor-quality embryo increases the procedure's success rate. This is a common question for both clinicians and patients in determining their course of treatment. The purpose of this work was to answer this intriguing question in the context of prognosis of patients undergoing fresh cycles with only one good-quality and more than one poor-quality cleavage-stage embryos. To control for confounding effects, we only included patients at similar age, body mass index (BMI), level of basal follicle stimulating hormone (FSH) and endometrial thickness from January 2015 to June 2021. A propensity score-matched analysis was performed to extract the matched pairs. Then we evaluated pregnancy outcome, including the rate of clinical pregnancy, live birth, embryo implantation, early miscarriage, and ectopic pregnancy. We found that the clinical pregnancy rate (34.8 vs. 38.0%, p = 0.553), live birth rate (27.1 vs. 29.9%, p = 0.598), early miscarriage rate (18.1 vs. 9.5%, p = 0.171) and ectopic pregnancy rate (1.3 vs. 1.2%, p = 1.000) did not significantly differ between those two groups, notwithstanding significant difference of the implantation rate (34.8 vs. 21.3%, p <0.001). Our work indicates that, for prognosis patients at approximately 34 years old with only one good-quality embryo, having additional poor-quality embryos does not seem to help to improve ART success rates per intended embryo transfer. In conclusion, we found that simultaneous transfer of one good-quality and one poor-quality cleavage stage embryo does not improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The incidence of haematological malignancies is increasing in women of childbearing age. Survival rates accompany this increase, making it essential to assess the impact of treatments on their future quality of life, evaluate the impact of each treatment on ovarian reserve and define the fertility preservation techniques used by women with haematologic malignancies. A retrospective study was conducted after data collection from 61 women diagnosed with haematological malignancies and followed-up in a fertility preservation centre between January 2008 and June 2019. Cancer treatments caused a decrease in ovarian reserve, demonstrated by an increase in FSH levels and a decrease in AMH levels. When assessing which treatments have the greatest impact on AMH levels, we found that the BEACOPP regimen, and the agents vincristine, etoposide, procarbazine, prednisone and the haematopoietic stem cell transplantation were mainly responsible. Regarding pregnancy after oncological treatments, of the eleven women who became pregnant, ten did so spontaneously. This study reinforces the importance of referring patients to a fertility preservation consultation before starting oncological treatment, as most of them opt to preserve fertility. This work also helps to clarify the impact of each chemotherapeutic agent on the ovarian reserve. [ABSTRACT FROM AUTHOR]

Neurokinin B (NKB) belongs to the tachykinin family of proteins who's regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA. [ABSTRACT FROM AUTHOR]

This was a retrospective study that included 114 women younger than 40 years with induced primary ovarian insufficiency. Patients who presented vasomotor symptoms had a higher proportion (26 [63.41%] versus 58 [79.45%], OR 2.23, 95% CI 0.95–5.23, p =.065) to initiate hormone replacement therapy. Vasomotor symptoms were present in patients with ovarian cancer (OR 0.27, 95% CI 0.09–0.8, p =.18), haematologic cancer (OR 0.11, 95% CI 0.2–0.65, p =.014), radiotherapy (OR 2.62, 95% CI 1.04–6.54, p =.039) and chemotherapy with radiotherapy (OR 2.72, 95% CI 1.01–7.35, p =.049). Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy, and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms. What is already known on this subject? In young women with cancer, induced primary ovarian insufficiency can result as an ovarian surgery or as an adverse effect of chemotherapy or radiotherapy. Regardless of aetiology, patients are going to manifest early climacteric symptoms with an increased risk for cardiovascular disease, metabolic syndrome and osteoporosis. What do the results of this study add? Patients who presented vasomotor symptoms had initially a higher proportion of hormone replacement therapy. Patients that were treated exclusively with radiotherapy or with chemotherapy and concomitant radiotherapy have a significantly increased risk to manifest vasomotor symptoms. What are the implications of these findings for clinical practice and/or future research? Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms. [ABSTRACT FROM AUTHOR]

Plasticizers containing phthalates have the potential to alter endocrine function in vertebrates. While non-phthalate plasticizers were previously considered to be environmentally friendly and safe, our research team discovered that bis-(2-ethylhexyl) adipate (DEHA) and acetyl tributyl citrate (ATBC) disrupt thyroid hormones in Japanese medaka (Oryzias latipes). We assessed reproductiveand estrogen-responsive gene expression patterns in Japanese medaka to determine whether the phthalate plasticizers bis-(2-ethylhexyl) phthalate (DEHP, positive control) and the non-phthalate plasticizers DEHA and ATBC disrupt endocrine signaling. The results showed that the levels of choriogenin H (chgH) and vitellogenin (vtg) genes increased after exposure to DEHP and ATBC, suggesting that these plasticizers may have estrogenic activity. Exposure to DEHP and DEHA resulted in the upregulation of kisspeptin (kiss), gonadotropin-releasing hormone (gnrh), and follicle-stimulating hormone beta (fshb) genes, suggesting that these plasticizers may interfere with reproductive function. To the best of our knowledge, this is the first study to demonstrate that the nonphthalate plasticizers DEHA and ATBC can disrupt reproduction-related hormonal activity in fish. [ABSTRACT FROM AUTHOR]

Substances such as tobacco and cannabis can negatively modulate seminal parameters and sex hormones and lead to fertility problems in males. The present study aimed to determine the effect of cigarettes, dipping tobacco, and cannabis on semen parameters and sex hormones in infertile males. A total of 160 infertile healthy participants (cigarette smokers n = 40, dipping tobacco users n = 40, cannabis users n = 40 and infertile controls n = 40) were included in the study. Fasting blood samples were collected from all the participants using the aseptic technique, and semen samples were collected by masturbation following sexual abstinence of 2–7 days. The levels of serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined using ELISA. The serum level of FSH was significantly higher in cannabis users relative to the control group (p = 0.043). A mild non-significant decrease in sperm count, serum LH and testosterone levels were observed in all drug users compared to controls. In conclusion, chronic use of tobacco and cannabis mildly modulates semen and hormonal parameters in infertile males. [ABSTRACT FROM AUTHOR]

Corifollitropin alpha has been demonstrated to be non-inferior to other gonadotropins in reproductive outcomes. However, its impact on follicular ovarian responsiveness has never been evaluated. Follicular Output Rate (FORT) is an option for objective assessment of the follicular responsiveness. A prospective study was conducted with 306 infertile patients undergoing in vitro fertilisation. Ovarian stimulation protocol was performed with a single dose of 100 μg (<60kg) or 150 μg (≥60kg) corifollitropin alpha in group 1 (n = 147), and 150-300 IU/day human menopausal gonadotropin in group 2 (n = 150). Comparing ovarian stimulation between corifollitropin alpha and human menopausal gonadotropin, no differences regarding FORT were found (40.0% for group 1 versus 40.83% for group 2; p = 0.930). Patients treated with corifollitropin alpha had a higher number of embryos when compared with human menopausal gonadotropin group (3.0 for group 1 versus 2.0 for group 2; p = 0.04). Other secondary outcomes preset were similar between groups. Therefore, corifollitropin alpha can be an excellent option to simplify in vitro fertilisation treatment due to the "patient-friendly" protocol. [ABSTRACT FROM AUTHOR]

Hypnotherapy is used in clinical settings to treat mental and physical health-related conditions. Hypnotic response can be measured through hypnotizability scales to help interventionists personalize treatment plans to suit the patients' individualized hypnotic abilities. Examples of these scales are the Elkins Hypnotizability Scale (EHS) and the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). According to the previous literature, these scales have good discriminating ability and internal consistency (α = 0.85) in collegiate samples, but the psychometric properties of the EHS for a targeted clinical population have not been determined yet. This study assessed said properties, and results showed adequate reliability of the EHS in a targeted clinical sample and strong convergent validity of the EHS to the SHSS:C. The authors conclude that the EHS is a strong and useful measure of hypnotizability that is pleasant, safe, brief, and sensible to individualities in hypnotic ability found in diverse clinical samples. [ABSTRACT FROM AUTHOR]

This case–control study aims to evaluate the oxidant-antioxidant balance in girls having central precocious puberty (CPP) and premature thelarche (PT). Thirty-four girls having CPP, 24 girls having PT, and 49 healthy growing girls between 7 and 9 years of age admitted to child health supervision were enrolled. Total antioxidant and oxidant capacity, myeloperoxidase, catalase, superoxide dismutase, total thiol, native thiol, and disulfide levels were analyzed in serum samples. Low total oxidant status (<12.0) was found to be highest in the CPP group, lowest in the control group, and the PT group was in between them. After controlling bone age and z score for body mass index, generalized linear models revealed lower oxidative stress index values in the CPP and the PT groups than the control group. Other studied parameters did not differ among groups. Precocious puberty in girls is associated with some changes in the oxidant-antioxidant status. [ABSTRACT FROM AUTHOR]

Our study aims to investigate the efficacy and clinical significance of the Zuogui pill (ZGP) on premature ovarian failure (POF) via the GDF-9/Smad2 pathway. Changes in clinical symptoms in the control group (treated with Femoston alone) and the treatment group (treated with ZGP combined with Femoston) were assessed before and after treatment. Sex hormone levels, serum inflammatory cytokine levels, and ultrasound parameters were measured before and after treatment. POF rat models were established using cyclophosphamide and the POF rats were treated with Femoston, or ZGP combined with Femoston. GDF-9 and Smad2 expression levels were determined by RT-qPCR. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), interleukin (IL)-6, and IL-21 levels, and the pulsatility index (PI) and resistance index (RI) values were decreased, while the estradiol (E2) and anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), mean ovarian diameter (MOD), and peak systolic velocity (PSV) values were increased in the treatment group compared to the control group. After treatment with ZGP combined with Femoston, GDF-9 and Smad2 expression in the ovarian tissues of POF rats increased. ZGP has a therapeutic effect on POF via modulation of the GDF-9/Smad2 pathway. [ABSTRACT FROM AUTHOR]

The age-related reproductive disorders are the main concerns in old birds. It was suggested that a drop in egg production and reproductive performance, towards the end of their laying period was caused partly by a decrease in the baseline concentration of plasma LH. Urtica dioica (nettle) is a plant with natural aromatase inhibitors. Steroid hormone levels are regulated by inhibition of the aromatase enzyme. Few studies have examined the effect of nettle on the egg production in adult hens. The aim of this study was to investigate the effects of diet supplemented with nettle powder (NP) in aged quails. One hundred and forty-52-week-old Japanese quails were randomly assigned to four treatments consisting of seven replicates (n = 5; four females and one male) and fed with diets containing NP at 0% (control group), 0.5, 1.0, and 1.5% (treatment groups). At 62 week of age, our results indicated the NP improved egg production, feed conversion ratio, eggshell thickness and Haugh unit (p <.05). Notably, fertility and hatchability of fertile eggs were significantly increased, while total embryonic mortality decreased significantly by supplementing diet with nettle powder (p <.05). Higher luteinizing hormone, lower oestrogen, malondialdehyde and total cholesterol and triglyceride concentrations were associated with percent of the nettle powder in diet (p ≤.05). Elevated follicle-stimulating hormone/luteinizing hormone ratio ≥4 is associated with low egg production in control group and nettle supplementation can balance FSH/LH ratio to ≤2.7. It is concluded that nettle powder could be used as a worthwhile feed additive at the late laying period of aged quails. Nettle powder can be used as a food additive with aged quails at late laying period. Addition of 1 and 1.5% nettle powder improves egg production, FCR, egg shell thickness. Nettle enhances reproductive performances, such as fertility, hatchability, weight of ovary, and weight of follicles by balancing reproductive hormones at late laying period. [ABSTRACT FROM AUTHOR]

1. This study measured six reproduction traits in a Sichuan white goose population (209 individuals), including fertility, qualified egg rate, plasma concentrations of progesterone (P), follicle-stimulating hormone (FSH), prolactin (PRL) and oestrogen (E2). 2. Whole-genome resequencing data from the same goose population (209 individuals) were used in a genome-wide association study (GWAS) utilising a mixed linear model to investigate the genes and genetic markers associated with reproduction traits. The frequency of the selected SNPs and haplotypes were determined using the Matrix-Assisted Laser Desorption Ionisation Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) method. 3. In total, 42 SNPs significantly associated with these traits were identified. A haplotype block was constructed based on five SNPs that were significantly associated with qualified egg rate, with individuals having the haplotype CCTTAAGGAA having the lowest qualified egg rate. 4. In conclusion, these results provided potential markers for marker-assisted selection to improve goose reproductive performance and a basis for elucidating the genetics of goose reproduction. [ABSTRACT FROM AUTHOR]

To conduct an economic evaluation estimating the cost per live birth after controlled ovarian stimulation (COS) using Follitropin Alpha (Gonal-F), in the Greek National Health System setting. A secondary objective was to predict the live birth rateof the In Vitro Fertilization (IVF) procedure. A single arm, multi-center, prospective, non-interventional study was conducted on which economic, efficacy and safety data were collected by six of the largest IVF centers. The participants were 350 female patients. Three statistical methods were employed for the analysis of the study outcomes, namely (a) Generalized Linear Modeling for the estimation of the costs of IVF treatment, (b) multivariable logistic regression and (c) an Artificial Neural Network (ANN) model for live birth prediction. The mean total cost of IVF therapy per patient was estimated at €3728 (95% CI: €3679–€3780), while the total cost per live birth was €14,872 (95% CI: €12,441–€17,951). The live birth rate after 3 complete IVF cycles was estimated at 22.9%, while the percentage of those suffering from OHSS was limited at 0.57%. In logistic regression, the Ovarian Sensitivity Index (OSI) was a factor found to be positively associated with live birth (OR 7.39, 95% CI: 1.84–29.71). For the ANN, important predictors included number of gestational sacs and the duration of infertility. The present study constitutes the largest single-arm study based on real data in Greece to date. The cost of IVF treatment and the cost per live birth are not insignificant in this NHS setting. The live birth rate, cost per oocyte, and the cost per live birth are in line with literature. OSI was a main contributing factor to the accurate prediction of the live birth rate, while age and BMI were found to be negatively correlated. [ABSTRACT FROM AUTHOR]

Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the "circumstances of" nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-β-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the outcomes of in vitro maturation (IVM) cycles using gonadotropin releasing hormone agonist (GnRH-ag) triggering. A retrospective cohort of IVM cycles from January 2015 to December 2019 in a single university-affiliated centre was examined. Main outcome measures were: (i) IVM maturation rate; and (ii) IVM maturation result. Secondary outcome measures were: (i) metaphase II (MII) rate on the day of egg retrieval; (ii) final MII maturation rate; and (iii) pregnancy rates. A total of 98 IVM cycles were performed during the study period: 50 (51%) were triggered with GnRH-ag (17 received FSH priming and 33 did not) and 48 cycles (49%) were triggered by hCG (37 with FSH priming and 11 without). A significant (p = 0.01) difference was noticed in maturation rate on egg retrieval day, in favour of the GnRH-ag group, although not in the final maturation rate achieved. Pregnancy rates were comparable between treatment sub-groups. GnRH-ag triggering in IVM cycles is an optional triggering mode and can be considered an acceptable option, especially when fertility preservation is a concern. GnRH agonists resulted in higher maturation rate on day of oocyte retrieval, but no difference in the total maturation rate. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of chronological age on the in vitro fertilization (IVF) outcome in patients with diminished ovarian reserve (DOR). Four hundred and forty-nine women with DOR who underwent IVF cycles were enrolled in the study. There were only 296 patients who obtained available embryos. The patients with no available embryos had a significantly lower antral follicle count (AFC) and higher basal follicle-stimulating hormone (FSH) concentrations than those of women with available embryos, but chronological age in the two groups was comparable. However, patients aged >40 obtained a significantly lower ongoing pregnancy rate (OPR) than patients aged 35 − 40 or <35 (6.38% versus 26.15% versus 28.17%, respectively). Multivariate analysis also showed that chronological age was the only parameter associated with clinical results. It implied that patients with DOR still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. What is already known on this subject? Diminished ovarian reserve DOR is a disappointing issue in reproductive medicine. Ovarian reserve, which represents ovarian biological age, is closely related to chronological age. However, ovarian biological age does not always match chronological age. Some studies suggest that biological age is more important than chronological age in predicting the outcome of in vitro fertilization (IVF). However, these conclusions are controversial. What do the results of this study add? We found DOR patients with no available embryos had significantly lower antral follicle count (AFC) and higher follicle-stimulating hormone (FSH) concentrations than that of patients with available embryos, but chronological age in the two groups was comparable. However, for patients with available embryos, chronological age is the only parameter associated with clinical results. For women aged >40 with DOR, chronological age was significantly negatively associated with clinical results. What are the implications of these findings for clinical practice and/or further research? Patients with DOR can obtain available embryos and still have a reasonable chance of becoming pregnant, but their prognosis is greatly affected by chronological age. Therefore, patients with DOR should seek medical help for pregnancy as soon as possible. When DOR patients over the age of 40 plan IVF treatment, the cost-effectiveness of healthcare should be considered. [ABSTRACT FROM AUTHOR]

To demonstrate the change in serum kisspeptin levels during the reproductive period in healthy women and to investigate the relationship with other reproductive hormones. One hundred thirty-one healthy women with normal menstrual history were included and serum kisspeptin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), estradiol (E2), and anti-Müllerian hormone (AMH) levels were determined on cycle day 3. The data were analyzed in 5-year age groups. Serum kisspeptin levels of all women were found to be significantly and negatively correlated with age (r= −0.458). The kisspeptin levels were the highest in the group of women aged between 20 and 24 years compared to other age groups above 25 years (p <.01, p <.001, p <.0005, p <.0005). There was not any significant correlation between serum kisspeptin levels and AMH, FSH, LH, TSH, E2, and body-mass index (BMI), respectively. The Scatter and Violin plots showed that most of the women over 35 years of age had serum kisspeptin levels under the level of 500 pg/ml. The kisspeptin levels of women over 35 years of age clustered closely as opposed to the kisspeptin levels of those below the age of 35, which were scattered. The median serum kisspeptin levels were found to be high in women below the age of 35 (p <.0005). In healthy women, serum kisspeptin level is the highest in the group of women aged between 20 and 24 years and declines with age. It tends to be below the level of 500 pg/ml in women over the age of 35. [ABSTRACT FROM AUTHOR]

Endocrine and paracrine signals can be key regulators of ovarian physiology. The oocyte secretes growth factors which directly induce follicular development by a complex paracrine signalling process, and the transforming growth factorβ (TGF-β) superfamily has a pivotal role in this process. The bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes are relevant members of the TGF-β superfamily that encode proteins secreted by the oocytes into the ovarian follicles, where they contribute to creating an environment supporting follicle selection and growth. Their main functions include regulating cellular proliferation/differentiation, follicular survival/atresia, and oocyte maturation. Recent functional studies have validated genetic factors (Progesterone receptor membrane component 1 (PGRMC1)), Fragile X mental retardation 1 (FMR1, GDF9 and BMP15) as being causative of primary ovarian insufficiency (POI), BMP15/GDF9 gene variants were found to have a high incidence on the POI phenotype. This review considers the most recent research regarding the role of BMP15 and GDF9 in the genetic control of follicular development, paying special attention to the pathogenesis of POI. [ABSTRACT FROM AUTHOR]

To investigate if an immediate additional IVF-ET cycle bear an advantage to patients with poor ovarian response in comparison to a cycle performed at some delay. A cohort study including 632 patients who underwent a fresh IVF-ET cycle with high-dose (≥300 IU/d) FSH stimulation that yielded ≤4 oocytes and did not achieve a clinical pregnancy. All underwent a second stimulation and oocyte pick-up (OPU), either consecutively or separately within 180 days (nonconsecutive OPU). The oocyte yield, number of embryos available for transfer, pregnancy live birth rates of the second OPU were compared between patients who had consecutive and nonconsecutive cycles. Consecutive OPU was associated with more mature follicles in the second cycle compared to nonconsecutive OPU (p =.03) in addition to higher peak estradiol level (p <.0001), and more aspirated oocytes (p =.03) and available embryos (p =.023). There was no between-group difference in ongoing pregnancy and live birth rates. In a multivariate analysis of variance controlling for potential confounders, the difference in the number of aspirated oocytes and available embryos was associated significantly only with consecutive performance of the second cycle. Immediate sequential stimulation (without an intervening menstrual cycle) in poor responders is advantageous over delayed stimulation in terms of number of aspirated oocytes and available embryos. The administration of high-dose FSH in the first cycle may benefit follicular recruitment also in the subsequent cycle. Although the effect is modest, given that each additional oocyte aspirated contributes to the outcome, it might be of significance especially in younger patients. [ABSTRACT FROM AUTHOR]

To identify the specific region of eCG involved in FSH-like activity, the following mutant expression vectors were constructed targeting the amino acid residues 102–104 of the eCG β-subunit: single mutants, eCGβV102G/α, eCGβF103P/α, and eCGβR104K/α; double mutants, eCGβV102G;F103P/α, eCGβV102G;R104K/α, and eCGβF103P;R104K/α; triple mutant, eCGβV102G;F103P;R104K/α. The LH-like and FSH-like activities of eCG mutants were examined in CHO-K1 cells expressing rat LH/CG receptor and rat FSH receptor. The levels of eCGβV102G/α, eCGβR104K/α, and eCGβV102G;R104K/α in the culture supernatant were markedly lower than those of eCGβ/α-wt. The other mutants and rec-eCGβ/α-wt were efficiently secreted into the culture supernatant. The LH-like activities of eCGV104G/α, eCGβV102G;R104K/α, and eCGβF103P;R104K/α were approximately 61%, 52%, and 54%, respectively, of those of eCG-wt. The Rmax values of the mutants were 58.9%–78.8% those of eCG-wt with eCGβR104K/α exhibiting the lowest value. The FSH-like activities of single mutants were only 16%–20% of those of eCG-wt. Additionally, the FSH-like activity of double mutants was less than 10% of that of eCG-wt. In particular, the FSH-like activities of βV102G;R104K/α and βF103P;R104K/α were 2.5–2.9% of that of eCG-wt. These results suggest that the amino acid residues 102–104 of the eCG β-subunit are dispensable and that the residue 104 of the eCG β-subunit plays a pivotal role in signal transduction through the rat FSH receptor. Thus, these mutants may aid future studies on eCG interactions with mammalian FSH receptors in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The CaptureSelect™ FSH affinity matrix is a novel affinity chromatography resin, developed based on camel-derived VHH fragments, capable of capturing and purifying intact rhFSH with high efficacy and purity in a single step. Since some proteins bind very tightly to the CaptureSelect™ FSH affinity matrix, conventional methods for desorption are ineffectual, and purification efficiency is reduced. Therefore, the factors affecting the desorption of proteins have been investigated. Protein desorption was greatly improved by introducing pauses into the elution step, and using an elution buffer concentration between 2 and 3 M MgCl2 also increased protein desorption. However, in some cases, the concentration-dependent chaotropic properties of MgCl2 caused protein inactivation. After applying each 20 mL of the protein mixture, the flow rate was paused, which improved binding capacity. Eventually, an efficient purification method is developed, in which the formulation buffer dramatically enhances yield. The overall yield and purity were 68.8 and 97%, respectively. The purified rhFSH was identified and characterized by several physicochemical and biological methods, such as gel electrophoresis, western blotting, high-performance liquid chromatography, and mass spectrometry. Biological activity was determined by In Vitro Maturation, and finally, the quaternary structures and thermal stability were assayed. [ABSTRACT FROM AUTHOR]

Recently published multicentre, randomized phase III studies suggested the therapeutic equivalence of biosimilar follitropin alpha medicaments compared to the reference product. The aim of this meta-analysis is to pool the results of the three phase III trials in order to provide an overall analysis about the clinical bioequivalence between biosimilars and the originator. The studies included in the analysis were pooled together in order to estimate the log odds ratio (OR) for binary outcomes and the weighted mean difference (WMD) for continuous outcomes along with the corresponding 95% confidence intervals (CI) by using a random effects model. The heterogeneity between the studies was evaluated with the Higgins and Chi-square tests. No differences were found in term of number of oocytes retrieved at ovum pick-up, the primary endpoint recommended by the European Medicines Agency. No statistical differences were also found for biochemical pregnancy rate, take home baby rate, total follitropin alpha dose, duration of stimulation, and OHSS risk. A significantly higher clinical pregnancy rate (p =.03) was observed in the originator group in comparison to the biosimilar follitropin alpha. Biosimilar follitropin alpha medicaments resulted comparable in comparison to the reference product with respect to the number of oocytes retrieved, that is the primary endpoint recommended by the European Medicines Agency.Further study is needed to evaluate the therapeutic bioequivalence between follitropin alpha biosimilar and the reference medication with respect to secondary endpoints. [ABSTRACT FROM AUTHOR]

Ovarian reserve (OR) decreases as women get older but there is considerable variation in the rate at which this occurs. Older women are at increased risk of complications during pregnancy. The aim of the study was to determine whether poor OR influences perinatal outcomes independent of age. All fresh IVF/ICSI cycles in which a single embryo was transferred between 1 January 2010 and 31 December 2016 were reviewed. An anti-Müllerian hormone (AMH) concentration of ≤5.4 pmol/l was considered poor and 5.41–24.99 pmol/l normal. Data were collected regarding cycle outcome, congenital anomalies, gestational age at delivery and birth weight. A total of 1520 women were included, of whom 1197 had normal OR and the remaining 323 had poor OR. Once pregnant, after adjusting for maternal age, women with poor OR (n = 109) were no more likely to experience a biochemical pregnancy or miscarriage (41.3% versus 41.6%, p = 0.809) than women with normal OR (n = 596). There were no significant differences in rates of congenital anomalies (1.8% versus 1.2%, p = 0.636), birth weight (3272 ± 630.7 g versus 3376.4 ± 576.3 g, p = 0.216) or gestational age at delivery (38.9 ± 2.3 weeks versus 39.1 ± 2.1 weeks, p = 0.517) between women with normal or poor OR. OR does not appear to affect pregnancy loss rates, incidence of congenital anomalies, birth weight, or gestational age at delivery after adjusting for maternal age. [ABSTRACT FROM AUTHOR]

Study the interchangeability of Roche Elecsys and Beckman Coulter Access anti-Müllerian Hormone (AMH) assays to select the gonadotropin starting dose in IVF cycles. Patients' AMH was measured using both Elecsys and Access automated assays. AMH values were then used to calculate the FSH starting dose. The main outcome is the percentage of women that would have been stratified to a different dose of gonadotropin due to differences in AMH values from the two tests. The Access assay systematically gives higher values compared with the Elecsys assay (slope = 0.88). For Follitropin Alfa, the difference in starting dose was > 15% in 2/113 patients, when Access AMH was used instead of Elecsys. For Follitropin Delta the difference in the starting dose was >15% in 21/113 patients when using Access AMH. When considering women with high ovarian reserve, only 4/51 would have received a Follitropin Delta dose that exceeded a 15% difference using Access AMH as a substitute for the Elecsys value. The use of the Roche Elecsys or Beckman Coulter Access leads to modest differences in AMH values, which seem to little affect the calibration of FSH dose used for ovarian stimulation. [ABSTRACT FROM AUTHOR]

Removal of ovarian tissue is a new option for fertility preservation for certain cancer patients in China. The aim was to investigate the impact of stepwise removed tissue on hormone levels and follicles in rats. Six to ten-week old rats were divided into six groups (% total ovarian tissue): 1 = control (100%), 2 (75%), 3 (50%), 4 (25%), 5 (12.5%), 6 (0%, bilateral ovariectomy). Blood test was carried out fortnightly to assess estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin B (INHB). Ovaries are obtained from surgical resections and from rats sacrificed after 12 weeks. During 12 weeks, groups 4, 5, and 6 had higher FSH and lower AMH and INHB values compared to control (p<.05), but in group 4 E2 and P was not significantly different from control (p>.05). All ovarian function parameters stopped in groups 5 and 6. Follicle morphology was not significantly different between baseline and 12 weeks after surgery in groups 1–5. For the first time, we demonstrated that even up to 75% of total ovarian tissue can be removed without impact on E2 and P production in rats, which, if confirmed in women, would mean that hazardous (or possibly contraindicated in cancer patients) hormone therapy is not required to avoid the negative consequences of hormone depletion. [ABSTRACT FROM AUTHOR]

Clarias gariepinus juveniles were exposed to environmentally relevant concentrations of 0 (control), 2.5, 25, 250 and 500 μg L−1 atrazine in a quality-controlled 28-day laboratory procedure. Findings revealed a significant decrease in the levels of follicle-stimulating hormone, luteinizing hormone and prolactin relative to control (p < 0.05). Atrazine reduced the levels of testosterone while increasing the concentration of progesterone. Histologically, the control and treatments presented three stages of oocyte maturation: the chromatin nucleolar oocyte stage, early perinucleolar oocyte stage and the vitellogenic oocyte stage. However, in the ovaries of the treatment group with the lowest treatment concentration (2.5 μg L−1), atretic oocytes with broken membranes invaded many of the dead ova and empty spaces. In other treatments (25, 250 and 500 μg L−1), interfollicular spaces, vacuolation in oocyte formation, and dissolution of oocyte walls were observed. Disruption of the yolk vesicle and clumping of the cytoplasm in maturing oocytes was observed only at the highest atrazine concentration (500 μg L−1). Gross alterations in ovarian histoarchitecture and reproductive hormone levels observed in this study showed interference with oogenesis which may result in reduced egg viability and fecundity in fish with ecological implications in water bodies exposed to atrazine even at reduced concentrations. [ABSTRACT FROM AUTHOR]

Hormonal transition among middle-aged women with type 2 diabetes may exert an impact in the development of diabetic retinopathy (DR). In this cross-sectional study, we aimed to assess the levels of estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the presence of DR and their relationship with risk factors for DR among pre- and post-menopausal women with type 2 diabetes. Serum levels of estradiol, FSH, and LH were measured using the immunoassay technique. All statistical analysis was performed using SPSS software. From the 255 participants, diabetes duration-matched, 35 premenopausal, and 57 postmenopausal women were selected for analysis. The levels of estradiol, LH, and FSH were found to be similar in participants with and without DR among pre- and post-menopausal women with diabetes. Estradiol level was not found to be related with the risk factors of DR among women with type 2 diabetes. In conclusion, female sex hormone, estradiol is not related to the presence of DR. Further prospective studies are necessary to reveal the mechanistic role of this hormone in the development of DR. [ABSTRACT FROM AUTHOR]

This study aimed to examine the possible association between the oxidative stress parameters and clomiphene citrate resistance in polycystic ovary syndrome. The demographic data, hormone profiles and oxidant and antioxidant values of 50 clomiphene citrate-resistant polycystic ovary syndrome patients (Group 1), 32 clomiphene citrate-sensitive polycystic ovary syndrome patients (Group 2) and 87 non-polycystic ovary syndrome patients (Group 3) were compared. The average age, follicle-stimulating hormone, oestradiol, thyroid-stimulating hormone and prolactin values of the three groups were found to be homogeneous. Ferroxidase, catalase and myeloperoxidase levels were determined to be lower in the clomiphene citrate-resistant group compared to clomiphene citrate-sensitive and non-polycystic ovary syndrome groups (p <.001). As a result, Polycystic ovary syndrome patients with clomiphene resistance had lower antioxidant (catalase and ferroxidase) levels compared to those who were sensitive to clomiphene and who did not have polycystic ovary syndrome. The myeloperoxidase levels also demonstrated the same trend, which might be due to a compensation mechanism. What is already known on this subject? In the literature, there are many studies evaluating the association between PCOS and oxidative stress. No research related to antioxidants in clomiphene citrate-sensitive and clomiphene citrate-resistant PCOS patients was found in the relevant literature. What do the results of this study add? In this study, the antioxidants catalase and ferroxidase were found to be lower in PCOS women compared to non-PCOS; however, they were the lowest in clomiphene citrate-resistant PCOS women. Interestingly, myeloperoxidase, which is a part of oxidative stress, was also found to be higher in the non-PCOS group. What are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because it is the first to compare the relation between CC and oxidant and antioxidant markers. These markers will be a guide for PCOS management in patients with CC-R. [ABSTRACT FROM AUTHOR]

Introduction: Low testosterone and its symptoms is a condition affecting many males with severe repercussions on health. Testosterone affects metabolism, bones, joints, and ligaments, the cardiovascular system, liver, sexual functions, muscle mass, and the nervous system. Nowadays, due to recent research showing the benefits of testosterone replacement therapy, this treatment is gaining in popularity among aging men. However, testosterone replacement can increase the risk of infertility. Areas covered: Human chorionic gonadotropin (HCG) is used in the treatment of male infertility due to its luteinizing hormone (LH)-like action triggering testosterone and sperm production. Due to these positive effects on testosterone production, HCG has also been used to treat secondary hypogonadism. In this review, based on a literature review for the years 1977–2020 via Google Scholar, we summarize the current research on HCG as treatment for patients suffering from low testosterone and provide an overview of the pros and contras for HCG therapy as compared to testosterone replacement therapy for the treatment of secondary hypogonadism. Expert opinion: The testosterone and sperm production triggering effects of HCG without the side effects on fertility seen in testosterone replacement therapy make HCG therapy a prime candidate for patients suffering from secondary hypogonadism. [ABSTRACT FROM AUTHOR]

Objective: The aim of this article is to propose an algorithm that aids the clinician to choose the best therapeutic scheme of follicle-stimulating hormone (FSH) in the treatment of men with idiopathic infertility, based on testicular volume (TV) and serum total testosterone concentrations; highlighting the potential role of additional therapy with hCG in a sequential temporal scheme.Materials and Methods: We subdivided patients in four clinical groups: patients with normal TV and serum testosterone concentrations (A); patients with normal TV and reduced serum testosterone concentrations (B); patients with reduced TV and serum testosterone concentration (C); patient with low TV e normal serum testosterone concentrations (D). Then, we administered to each group a specific therapeutic scheme. Group A: treated with FSH alone for at least 3 months; group B: treated with hCG alone twice a week for 3 months and addition of FSH for poor responders (unmodified sperm parameters); group C: treated ab initio with FSH and hCG until the pregnancy was reached; group D: treated with FSH alone for 3 months and addition of hCG for moderate poor responders (increased TV but unmodified sperm parameters) or second cycle of FSH for 3 months for severe poor responders (unmodified TV and sperm parameters). After 6 months we evaluated the therapeutic response in term of sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate.Results: 40% of patients became normozoospermic after treatment, while 30% achieved spontaneous pregnancy. B was the group that best responded to treatment in terms of normalization of seminal parameters; while the highest spontaneous pregnancy rate was obtained from the D group. B group also obtained the highest sperm DNA fragmentation normalization rate.Conclusions: To date, no reliable predictors of response to treatment with FSH exist, but TV and serum testosterone concentrations can help the clinician to choose the best therapeutic scheme for men with idiopathic infertility. The groups treated with a sequential temporal scheme (B and D groups) showed better clinical results compared with two groups treated with conventional schemes (A and C groups). [ABSTRACT FROM AUTHOR]

This study was designed to investigate the protective effects of propolis and vitamin E against time-related metal (aluminum chloride)-induced toxicity on the male reproductive system in albino mice (n = 63). Animals were randomly divided into seven groups (n = 9 each). Group I (control) received 0.9% saline solution; group II was given 50 mg/kg of aluminum chloride (AlCl3); groups III and IV were administered vitamin E (150 mg/kg) and propolis (50 mg/kg), respectively; and groups V, VI and VII were administered AlCl3 + vitamin E, AlCl3 + propolis, and AlCl3 + vitamin E + propolis, respectively, for 45 days. Animals were sacrificed; blood and tissue samples were collected (thrice; fortnightly) for the estimation of hormones i.e., Follicle stimulating hormone (FSH), Luteinizing hormone (LH) and testosterone using Enzyme linked immunosorbent assay (ELISA). Testicular histology, testicular weight, sperm count and motility were estimated. Group II revealed a highly significant decrease in LH, FSH, testosterone, testis weight, sperm count and motility. Groups III–VII showed a significant increase in LH, FSH, testosterone, organ weight, sperm count and motility in the 3rd sampling, as compared to group II. Hence, it is concluded that vitamin E and propolis, acting individually as well as synergistically, mitigate metal-induced time-related toxicity on the reproductive system and testicular histology of male mice. [ABSTRACT FROM AUTHOR]

Evidence is limited regarding the time intervals between human chorionic gonadotropin (hCG) administration and oocyte retrieval in controlled ovarian hyperstimulation cycles, and it is difficult to determine proper schedules to optimise outcomes for patients undergoing oocyte retrieval on the same day. We aimed to identify correlations between factors pertaining to treatment outcomes and time intervals to facilitate working schedules of ART centres. Our study included 2509 patients who underwent ICSI cycles. Based on different time intervals between hCG administration and oocyte retrieval, all cycles were divided into four groups: group 1 (34.00-35.99 hours), group 2 (36.00-36.99 hours), group 3 (37.00-37.99 hours) and group 4 (38.00-39.32 hours). Female age, basal FSH level, Gn starting stimulation dosage and total Gn dosage of group 1 were significantly higher than those of other groups. E2 level on hCG day and number of follicles aspirated were significantly higher in group 4 than in the other groups. Number of oocytes retrieved, oocyte retrieval rate, cleavage rate and number of usable embryos were positively correlated with the time interval, even after adjusting for female age, basal FSH level, E2 on hCG day and number of follicles aspirated. A fixed hCG administration time matching arranged oocyte retrieval is good enough for most patients to achieve maximal treatment outcomes. For patients with lower treatment expectations (expected no. of oocyte retrieval ≤3), moderately delayed oocyte retrieval would be more appropriate.Impact StatementWhat is already known on this subject? The time interval between hCG administration and OPU during COH is essential for ART treatment outcomes, but different intervals were reported in previous studies.What the results of this study add? Fixed hCG administration time matching arranged OPU is good enough for most patients to achieve maximal outcomes. For patients with lower treatment expectations (expected no. of oocyte retrieval ≤3), moderately delayed oocyte retrieval would be required.What the implications are of these findings for clinical practice and/or further research? We studied whether the oocytes and pregnancy outcomes changed along with extended time intervals, and there is no need to adhere to an exact interval for every patient. Therefore, it would help clinicians develop more reasonable time schedules for fertility centres and patients undergoing oocyte recovery on the same day. [ABSTRACT FROM AUTHOR]

While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to ovulation is disrupted in obese individuals. Follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) are two key regulators of follicle development, and the poorest reproductive outcomes have been recorded when these hormones are imbalanced. In order to understand how obesity impacts the reproductive axis, the present study induces reproductive dysfunction in female rats using a high-fat, high-sugar diet (HFHS). Results: In our study, several animals on the HFHS diet displayed abnormal estrous cycles. The HFHS diet also resulted in an increased prevalence of ovarian cysts and decreased formation of corpora lutea. Across all groups, the FSH/AMH ratio displayed a strong negative correlation with pre-antral, antral, and total follicle counts. Moreover, rats on the HFHS diet displayed larger adipocytes and produced higher levels of leptin than controls. When combined with average adipocyte size in multiple regression, the FSH/AMH ratio was strongly associated with cyst formation in the ovary. Conclusions: These findings provide strong evidence for the potential relevance of a combined FSH/AMH ratio as a marker of ovarian health and follicular status. Therefore, this ratio reflects a complex interaction between the reproductive and metabolic systems. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this systematic review and meta-analysis were to evaluate the effectiveness of soy isoflavones on serum levels of total testosterone (TT) and follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS).Methods: A meta-analysis was performed by searching for relevant randomised controlled trials (RCTs) in several databases. Of the four trials found, the eligibility criteria to evaluate the efficacy of soy isoflavones on serum levels of FSH were met by three trials and of TT by four trials. The Cochrane scale was used to evaluate the risk of bias. Fixed-effects and random-effects models were used to evaluate overall effect. The χ2 test (Cochran's Q test) and the I2 index were used to assess the heterogeneity of RCTs.Results: Our results showed that soy isoflavones significantly decreased TT (weighted mean difference [WMD] - 0.14; 95% confidence interval [CI] - 0.2, -0.02; p = 0.016; I2 = 89%, p < 0.001) but had no significant effect on FSH levels (WMD -0.25; 95% CI -0.54, 0.02; p = 0.06; I2 = 0%, p = 0.85).Conclusion: Although the results of this meta-analysis showed that soy isoflavones in women with PCOS decreased TT and had no significant effect on FSH, better and more valid studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Inhibin is a glycoprotein produced by granulosa cells and its main function is the negative feedback control of follicle stimulating hormone (FSH) which has an important role in folliculogenesis. Mutation in the INHα gene leading to decreased bioactive inhibin has been associated with primary ovarian insufficiency (POI). The aim of this study was to investigate the role of variations in the INHα gene in increasing the susceptibility to POI in Kashmiri women. INHα c.769G > A mutation was analysed in 100 POI cases and 100 controls using PCR-RFLP and agarose gel electrophoresis. The INHα c.769G > A mutation was found in 10% of POI cases with 8% having heterozygous mutation and 2% having a homozygous mutation. The frequency of mutation in healthy controls was zero. Statistically, a very significant association was found between INHα c.769G > A mutation and the occurrence of POI (p = 0.0015). Moreover, the mutation was also significantly associated with high levels of FSH in POI patients (p < 0.0001). Given the significant association of INHα c.769G > A mutation with the increased FSH levels and POI in Kashmiri population, we suggest this mutation can be used to identify POI variants for screening of women susceptible to POI before the disease onset and can further facilitate putative therapy for such patients. [ABSTRACT FROM AUTHOR]

Does corifollitropin alfa associated with hp-HMG protocol from the beginning of ovarian stimulation perform better than high dose rFSH alone for ovarian stimulation with GnRH antagonist in poor responders? This retrospective, monocentric, case-control pilot study was conducted in 65 poor responders (Bologna criteria) undergoing 2 consecutive IVF cycles. All patients underwent a first ovarian stimulation cycle with high dose rFSH (≥300 IU/day) alone in antagonist protocol, unfortunately leading to poor ovarian response and no pregnancy. The following cycle was performed with 150 μg of corifollitropin alfa associated with daily injections of hp-HMG from the beginning of the cycle. The primary outcome was the number of mature oocytes retrieved. The secondary outcomes were ovarian stimulation cancellation and embryo transfer rate per initiated cycle. The number of mature oocytes was not significantly different between the 2 groups. However, cycle cancellation rate was significantly lower and the proportion of cycles with embryo transfer was significantly higher with corifollitropin + hp-HMG protocol, leading to an encouraging clinical pregnancy rate of 24.1% per oocyte retrieval. This pilot study based on corifollitropin alfa associated with hp-HMG from the onset of stimulation appears to be promising for ovarian stimulation in poor responders. [ABSTRACT FROM AUTHOR]

The study was to compare the efficacy, safety, and tolerability of low dose versus ultra-low dose hormone therapy (HT) in the management of perimenopause symptoms and quality of life. Retrospective analysis of perimenopause patients prescribed for 25 weeks HT in the outpatient clinic of menopause. A total of 132 perimenopause women were included in two treatment regimens: one with low dose HT (LD-HT) and one with ultra-low dose HT (ULD-HT). Changes in serum levels of follicle-stimulating hormone, estradiol as well as transvaginal ultrasound (TVUS), the 36-item Short Form Health Survey (SF-36), the Kupperman Index (KI), and adverse effects were assessed at baseline, 4, 13, and 25 weeks. By the end of 25 weeks of treatment, each score of SF-36 domains for both LD-HT and ULD-HT groups were increased, the KI decreased, and the endometrial thickness increased in both groups and there was no statistical difference between two groups. Both groups have negligible differences in incidence of adverse effects. Low dose and ultra-low dose HT both can serve in improving symptoms of perimenopause, thereby offering a better quality of life with decreased incidence of side effects. Ultra-low dose treatment may have a better advantage on safety and tolerance. [ABSTRACT FROM AUTHOR]

Kallmann syndrome (KS) is a rare inherited disorder, which has significantly genotypic and phenotypic heterogeneity. KS is clinically characterized by the combination of hypogonadotropic hypogonadism and hypo/anosmia. At present, there is no relevant report that intron mutation in SEMA7A gene helps induce KS. A 17-year-old Chinese female (46, XX) came to our department due to primary amenorrhea, who actually had hyposmia since her childhood. Hypogonadotropic hypogonadism was then detected. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were remarkably low. And estradiol level was extremely low. The laboratory test results were consistent with KS. A heterozygous point mutation of intron 13 in SEMA7A (NM_003612.3:c.1640-3C > A) was identified. The patient received the treatment of pulsatile gonadotropin-releasing hormone (GnRH) pump, which could imitate physiological ovarian stimulation, thus resulting in mature follicle and a peak of LH. The patient was injected subcutaneously every 90 min with a dose of 10 µg per pulse, which had bona efficacy. She acquired menarche at about 43 days after the treatment. We firstly report a case of KS caused by a novel mutation site in the intron of SEMA7A gene. We mainly provide insight into the clinical manifestations, genetic diagnosis and treatment of KS. [ABSTRACT FROM AUTHOR]

Aim: Sex differences have long been reported in schizophrenia leading to the hypothesis that sex hormones may be implicated in the pathophysiology of the disorder. We assessed gonadal hormones during the fasted state in drug-naïve patients with psychosis. Method: Fasting serum concentrations of follicular-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, free-testosterone, Sex Hormone Binding Globulin (SHBG) and oestradiol (E2) were compared between a group of 55 newly diagnosed, drug-naïve, first-episode men with psychosis and a group of 55 healthy controls, matched for age, smoking status and BMI. Testosterone, free-testosterone and SHBG were compared between a group of 32 drug-naïve, first-episode females with psychosis and a group of 32 healthy controls matched for age, smoking status and BMI. Results: Testosterone and free-testosterone levels were significantly lower in the patients' group and SHBG levels significantly higher in the patients' group compared to those in healthy controls. The two female groups had similar values in the hormones which were measured. Conclusion: Our findings provide evidence of lower testosterone and free-testosterone levels and increased SHBG levels in drug-naïve, first-episode males with psychosis. Reduced testosterone and free-testosterone levels in drug-naive, first-episode males with psychosis. Increased SHBG levels in drug-naive first-episode males with psychosis. No difference in FSH, LH and E2 levels between drug-naive first episode males with psychosis and controls. No difference in testosterone, free-testosterone and SHBG levels between drug-naive, first-episode women with psychosis and controls. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of chronic growth hormone deficiency (GHD) and its association with other hormonal deficiencies was determined in middle-aged patients post-stroke with and without consideration of body mass index (BMI). Methods: Clinical records were reviewed to determine pituitary function at least 3 months post-stroke. Patients with a history of endocrine anomalies were excluded. GHD was determined by utilizing standard peak GH cutoffs following the glucagon stimulation test. A secondary analysis was conducted with stricter BMI-adjusted cutoffs. The accuracy of IGF-1 in predicting GHD was also examined. Results: GHD was diagnosed in 54% of patients (≥5.0 μg/L), with 32% falling into the severe (≤3 μg/L) category. Patients with GHD had lower levels of FSH, T3, LH, and SHBG. Analyzes of BMI-adjusted GH levels, revealed that 14% of patients were GHD. These patients had higher prolactin. IGF-1 values were not predictive of GHD. Latency to be admitted to post-acute rehabilitation was greater in patients with GHD. Conclusions: Evidence suggests patients with stroke may be at risk for developing GHD. GHD was associated with decreased levels of other hormones. Co-morbidities for stroke and neuroendocrine dysfunction overlap and may have implications for recovery following stroke. [ABSTRACT FROM AUTHOR]

Testosterone deficiency in males is associated with serious comorbidities such as cardiovascular disease, diabetes type two, and also an increased risk of premature death. The pathogenetic mechanism behind this association, however, has not yet been clarified and is potentially bidirectional. The aim of this clinical trial was to gain insight into the short-term effect of changes in testosterone on blood analytes in healthy young men. Thirty healthy young male volunteers were recruited and monitored in our designed human model. Blood sampling was performed prior to and 3 weeks after pharmacological castration with a gonadotropin-releasing hormone antagonist. Subsequently, testosterone replacement with 1000 mg testosterone undecanoate was given and additional blood samples were collected 2 weeks later. The alterations in the levels of 37 routine biomarkers were statistically analysed. Eight biomarkers changed significantly in a similar manner as testosterone between the time points (e.g. prostate specific antigen, creatinine and magnesium), whereas seven other markers changed in the inverse manner as testosterone, including sexual hormone-binding globulin, urea, aspartate aminotransferase and alanine aminotransferase. Most of our results were supported by data from other studies. The designed controlled human model yielded changes in known biomarkers suggesting that low testosterone has a negative effect on health in young healthy men. [ABSTRACT FROM AUTHOR]

Oocytes are extremely sensitive to radiation and chemotherapy, and premature ovarian failure (POF) is one of the side effects of anti-tumor therapy. The pathogenesis of POF is very complex and still not fully elucidated. A mouse POF model was established after 14 days of cyclophosphamide injection. POF mice presented ovarian atrophy, destroyed follicular structure, a reduction in the number of primordial and mature follicles, and an decrease in the number of corpora luteal along with increased level of follicle-stimulating hormone (FSH), decreased levels of estradiol (E2), and anti-Mullerian hormone (AMH). Additionally, the proportion of bone marrow myeloid-derived suppressor cells (MDSCs) in peripheral blood, spleen, and ovarian tissue increased. MDSCs were mainly distributed around follicles and corpora luteal. Levels of mTOR and p-mTOR increased in ovarian tissue and inhibition of mTOR with rapamycin reduced the aggregation of MDSCs in peripheral blood, spleen, and ovarian tissue. This investigation sheds new light on the modulatory role of mTOR and demonstrates that an increase in MDSC number may play a key role in the pathological reaction during POF. Inhibition of mTOR and reduction of MDSCs in the ovary may represent a novel strategy for the treatment of POF. [ABSTRACT FROM AUTHOR]

Using recombinant DNA technologies, a chimeric gene containing the coding sequences of follicle stimulating hormone (FSH) β-subunit and C-terminal peptide of the human chorionic gonadotrophin (hCG) β-subunit have been designed to generate a new gonadotrophin named corifollitropin alfa (CFA). CFA has longer elimination half-life and slower rate of absorption compared with FSH, which makes CFA a long-acting hormone employed as a substitute of the recombinant FSH (recFSH) in the controlled ovarian stimulation (COS). The purpose of this study is to compare the gene expression profiles elicited by bioequivalent doses of CFA or recFSH in primary cultures of human granulosa cells (hGCs). Gonadotrophins exert their functions by binding FSH receptors (FSHRs), activating signaling pathways that increase the cyclic adenosine monophosphate (cAMP) intracellular content. Bioequivalence has been defined as the dose/duration of gonadotrophin treatment able to promote the same amount of intracellular cAMP. hGCs were treated with different doses of either gonadotrophin and the cAMP was measured after different incubation times to establish the bioequivalence. Results obtained by comparing the bioequivalent treatments, showed that CFA is more effective than recFSH in inducing aromatase gene expression after 6 and 24 h from the initial stimulation in agreement with its long-acting characteristic. [ABSTRACT FROM AUTHOR]

Objective was to evaluate serum anti-Müllerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS® method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS® were significantly higher in PCOS women than controls (p <.001), and they correlated with those measured using the AMH Gen II method. An AMH cutoff value of 42.1 pmol/L distinguished PCOS women from controls with 67% sensitivity and 83% specificity. The PCOS women with three Rotterdam criteria or hyperandrogenism displayed significantly higher AMH levels compared with those with two Rotterdam criteria or normoandrogenism. In PCOS, AMH levels correlated positively with luteinizing hormone (LH), androgen and sex hormone-binding globulin (SHBG) levels and negatively with BMI, abdominal obesity, follicle-stimulating hormone (FSH), fasting glucose and insulin, and insulin resistance. In conclusion, AMH evaluated using the VIDAS® method distinguished PCOS patients from healthy controls relatively well, especially in those with more severe phenotypes. Further studies are needed to establish whether AMH measurements can distinguish PCOS patients with different metabolic risk factors. [ABSTRACT FROM AUTHOR]

Introduction: Originally limited to the assessment of disorders of sex development, anti-Müllerian hormone (AMH) measurement has more recently been extended to several conditions affecting the reproductive axis in males and females. Follicle-stimulating hormone (FSH) regulation of gonadal function has been extensively studied, but its role on AMH production has been explored only recently. Areas covered: We addressed the relationship between FSH action on the gonads and the usefulness of AMH as a marker in conditions affecting the reproductive axis. Expert opinion: Sertoli cells are the most active cell population in the prepubertal testis. Serum AMH is an excellent marker of FSH action on Sertoli cell proliferation and function in patients with hypogonadotropic hypogonadism. Low serum AMH is expected to predict low sperm production and prompts initial FSH treatment followed by human chorionic gonadotropin (hCG) or luteinizing hormone (LH) addition. Gonadotropin treatment may be more effective if installed to mimic the postnatal activation stage of the hypothalamic-pituitary-testicular axis. In females, AMH secretion by small antral follicles is stimulated by FSH. Elevated AMH indicates increased follicle numbers and should be considered as a potential contraindication of gonadotropin treatment in infertile patients due to an increased risk of developing ovarian hyperstimulation syndrome. [ABSTRACT FROM AUTHOR]

Fluctuating asymmetry (FA), a morphological marker of developmental stability, may be related to an individual's biological condition, e.g., health or fertility. The aim of this study was to test if the level of a woman's FA was related to her fertility and reproductive potential as measured by reproductive hormone levels. Fifty-three healthy, non-pregnant, naturally cycling women (mean age = 23.42, SD = 1.85 years), participated in the study, conducted in Wrocław (Poland) in May 2015. Early-follicular phase serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured. FA was calculated based on anthropometric measures of six bilateral body traits, and the composite FA index was used in statistical analyses. No relationship was observed between FA and the levels of FSH, LH, and AMH (p >.05), controlled for potential confounders. However, the level of E2 was positively correlated with FA (p <.05). Thus, in young women, FA was not related to hormones levels related to ovarian reserve, but more symmetrical women had lower E2 levels. As FA is an index of developmental stability, environmental, and genetic stress, the results of the study confirm previous research suggesting that developmental conditions may be related to women's endogenous estrogen levels. [ABSTRACT FROM AUTHOR]

Growing evidence indicates that exposure to widespread, environmental contaminants called endocrine disruptors (EDCs) negatively affects animal and human reproductive health and has been linked to several diseases including infertility. This review aims to evaluate the impact of environmental exposure to endocrine disrupting chemicals [phthalates, parabens, triclosan, bisphenol A (BPA), organochlorine (PCBs) and perfluorinated (PFCs) compounds] on the reproductive potential among women, by reviewing most recently published literature. Epidemiological studies focusing on EDCs exposure and reproductive potential among women for the last 16 years were identified by a search of the PUBMED, MEDLINE, EBSCO and TOXNET literature databases. The results of the presented studies show that exposure to EDCs impacts the reproductive potential in women, measured by ovarian reserve and by assisted reproductive technology outcomes. Exposure to environmental endocrine disrupting chemicals decrease: (i) oestradiol levels (BPA); (ii) anti-Müllerian hormone concentrations (PCBs); (iii) antral follicle count (BPA, parabens, phthalates); (iv) oocyte quality (BPA, triclosan, phthalates, PCBs); (v) fertilization rate (PFCs, PCBs); (vi) implantation (BPA, phthalates, PCBs); (vii) embryo quality (triclosan, PCBs, BPA); (viii) rate of clinical pregnancy and live births (parabens, phthalates). The studies were mostly well-designed and used prospective cohorts with the exposure assessment based on the biomarker of exposure. Considering the suggested health effects, more epidemiological data is urgently needed to confirm the presented findings. [ABSTRACT FROM AUTHOR]

Laboratory tests are an integral part of clinical decision making. Therefore, measurement uncertainty comes into prominence in the context of the accuracy of the laboratory result. This study aims to investigate measurement uncertainty of 14 immunoassay analytes, to compare them with different quality goals and to utilize them in the result interpretation. Measurement uncertainties of 14 immunoassay analytes were estimated by using internal and external quality control data by using Nordtest approach. Expanded uncertainties (U) were compared with allowable total error (TEa%), permissible relative deviation in the external quality assessment (PRDEQA%) and permissible expanded uncertainty for external quality assessment (pUEQAS%). Uncertainties were incorporated into the calculation of reference change values (RCV) and uncertainty adjusted reference intervals. RCVs of 14 analytes were calculated by three different methods reported by Harris, Clinical Laboratory Standards Institute (CLSI), and National Pathology Accreditation Advisory Council (NPAAC). Measurement uncertainties of TSH, estradiol, LH, progesterone, prolactin, and vitamin B12 were within defined allowable limits. Uone-sided FT3 and Uone-sided ferritin exceeded defined TEa% but UFT3 and Uferritin were found below the limits of pUEQAS%. Measurement uncertainties of FT4, cortisol, DHEAS, FSH, testosterone, and folate did not meet the specification limits. Recently defined permissible expanded uncertainty promises new targets to compare estimated measurement uncertainty. Measurement uncertainty should be applied to the laboratory result interpretation within the scope of RCV and reference interval to obviate misdiagnosis. Furthermore, we suggest that laboratories should inform clinicians about the tests with high uncertainties to assist them making the right clinical diagnosis. Abbreviations CLSI: Clinical Laboratory Standards Institute; CV: coefficient of variation; CVA: analytic coefficient of variation; CVG: inter-individual coefficient of variation; CVI: intra-individual coefficient of variation; DHEAS: dehydroepiandrosterone sulfate; FSH: follicle-stimulating hormone; FT3: free triiodothyronine; FT4: free thyroxine; k: coverage factor; LH: luteinizing hormone; LRL: lower reference limit; MD: minimal difference; NPAAC: National Pathology Accreditation Advisory Council; PRDEQA%: permissible relative deviation in the external quality assessment; pUEQAS%: permissible expanded uncertainty for external quality assessment; RCV: reference change value; RCV': uncertainty-adjusted reference change value; TSH: thyroid-stimulating hormone; Rw: within-laboratory reproducibility; RMSbias: root mean square of biases; u(Cref): the uncertainty of nominal values; u(bias): uncertainty component for bias; uc: combined standard uncertainty; TEa%: allowable total error; U: expanded uncertainty; Uone-sided%: one sided estimation of expanded measurement uncertainty using coverage factor "1.65"; URL: upper reference limit. [ABSTRACT FROM AUTHOR]