Reproductive endocrinology

OBJECTIVE:
This study aimed at evaluating the effects obtained by administering 30 mg of micronised dispersible ferric pyrophosphate plus 300 mg of alpha-lactalbumin (MDFP-AL) compared to 80 mg of ferrous gluconate (FG) in pregnant women affected by iron-deficiency anemia (IDA).

PATIENTS AND METHODS:
We considered eligible all second-trimester singleton pregnancies in women affected by IDA. We excluded any other disease, twin pregnancies, any other pharmacologic/nutraceutical treatments (besides folic acid) before/during pregnancy. We randomized patients in two groups: one underwent treatment with 1 tablet of MDFP-AL/day, the other one with 1 tablet of FG/day, for 30 days. We evaluated hemoglobin (Hb), ferritin, red blood cells (RBCs), serum iron, hematocrit (Hct), and side effects at baseline (T0), after 15 days (T1) and 30 days (T2).

RESULTS:
50 women met the inclusion/exclusion criteria. We did not observe significant differences between the two groups for mean age, gestational age at the enrollment and parity. In MDFP-AL group, after 15 days (T1) Hb, ferritin, serum iron and Hct and were significantly improved respect to baseline (T0); after 30 days (T2), all the parameters, including RBCs, were significantly improved respect to baseline (T0). Similarly, in FG group the investigated parameters were improved both after 15 (T1) and 30 days (T2) respect to baseline (T0), although less in percentage terms respect to MDFP-AL group. The side effects rate was 24% in FG group, whereas MDFP-AL group did not show any significant side effect.

CONCLUSIONS:
Overall, MDFP-AL is more effective and safe than FG for the treatment of IDA in pregnant women.

ABSTRACT
Polycystic ovary syndrome (PCOS) is the most common cause of anovulation, infertility and hyperandrogenism, in addition to many long term unfavorable metabolic sequels in women worldwide. The question of whether the presence of polycystic ovary morphology alone, but without other diagnostic criteria of PCOS, is pathological or a normal variant of ovarian morphology is debated. Several studies have been shown abnormal hormonal responses in women who have polycystic ovary morphology alone, in absence of other features of PCOS, during ovulation induction procedures in addition to a provoked androgenic response and insulin resistance. Furthermore, there is a clear evidence of increased anti-Mullerian hormone levels, which can be considered as a surrogate marker of PCOS, in that subset of women. Based on the above, polycystic ovary morphology is obviously not a normal variant, but rather a mild phenotype of PCOS.
KEYWORDS: Polycystic ovary, anovulation, infertility, hyperandrogenism

Il primo libro in lingua italiana dedicato alle conseguenze psicologiche, emotive e relazionali della Sindrome dell'Ovaio Policistico, pensato per le donne con PCOS.

Se soffri di Sindrome dell’Ovaio Policistico, se sei disorientata e confusa dalla quantità di informazioni che trovi online, se senti il bisogno di capire meglio che cosa sia e cosa comporti vivere con questa sindrome, questo libro fa proprio per te.

Partendo dai risultati della ricerca scientifica internazionale, l’autrice ti accompagnerà verso una conoscenza sempre più approfondita della PCOS: capirai cos’è, come si manifesta, a quali specialisti dovresti fare riferimento, quali siano gli errori da evitare e i passi da compiere per stare bene. Soprattutto apprenderai tutte le informazioni necessarie per capire in che modo la PCOS influenzi la tua salute mentale, il tuo benessere emotivo, l’umore, il rapporto con il cibo, la sessualità e le relazioni con gli altri.

Un utile ausilio anche per i professionisti che si occupino di Sindrome dell’Ovaio Policistico in ambito nutrizionale, endocrinologico e ginecologico e che vogliano approfondire le implicazioni psicologiche della PCOS sulla salute mentale e qualità di vita della donna.

Una guida evidence based per conoscere la PCOS a 360 gradi.

"Despite the implication of the name, Polycystic Ovary Syndrome (PCOS) affects not merely the
ovaries, but endocrine system function, psychological health, psychosocial and psychosexual development throughout the lifespan. Up to 10% of pre-menopausal women meet the diagnostic criteria for PCOS, making it the most prevalent endocrine disorder for this population. Common features of PCOS include: polycystic ovaries, irregular or absent ovulation, disruption of the menstrual cycle, hyperandrogenism, insulin resistance, and central obesity. A review of extant literature reveals that as many as 50% of women with PCOS also meet the diagnostic criteria for a mood or anxiety disorder, with a strong correlation between PCOS and bipolar disorder. While such correlation does not equate to causality, some studies suggest that disruption of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes might be the common etiology between the physical manifestations of PCOS and the decreased psychological wellbeing experienced by women with PCOS. Hyperandrogenism is a particular source of concern in psychosocial and gender identity development. Some studies show a significantly higher prevalence of PCOS among lesbian women and female-to-male transsexuals compared to the general population, while heterosexual women with PCOS frequently report feeling “different” or “less feminine” due to hyperandrogenism and infertility. Researchers recommend implementing routine screening of women with PCOS for psychological disorders, and conversely, screening of women with mood disorders for reproductive endocrinological dysfunction."

OBJETIVO

Com essa unidade, o objetivo é apresentar o funcionamento do sistema endócrino e o controle que ele exerce sobre os processos reprodutivos. Logo, o estudante com-preenderá que os processos endócrinos de um organismo não podem estar dissociados do que ocorre com o restante do organismo nem das alterações do entorno. Por essa razão, o sistema endócrino e o sistema nervoso se comunicam entre si, formando em seu conjunto o sistema neuroendócrino.

Sendo assim, o intuito desse trabalho é descrever as funções dos órgãos endó-crinos mais importantes relacionados a reprodução, assim como o papel dos principais hormônios produzidos em cada um desses.



•___INTRODUÇÃO

Os processos reprodutivos requerem uma estreita coordenação entre diferentes ór-gãos do aparelho reprodutivo, além de estarem acompanhados por mudanças metabólicas que permitem a adaptação do animal aos requerimentos de cada etapa dos processos que nele realizam-se. A reprodução deve ser capaz de responder ou ajustar-se as condições externas, como a época do ano, a disponibilidade de nutrientes, além da presença ou au-sência de animais do sexo oposto. Essa coordenação e adaptação são alcançados graças a comunicação endócrina entre diversas células e órgãos.



•___HIPOTÁLAMO

O hipotálamo é um órgão central do sistema neuroendócrino. Está constituído por uma região do sistema nervoso central estrategicamente localizado para receber informa-ção de todos os órgãos dos sentidos; direta ou indiretamente recebe projeções provenien-tes da retina, dos bulbos olfatórios primários e secundários, o ouvido, a pele e os órgãos internos. Ademais, o hipotálamo possui receptores hormonais, receptores para substân-cias como a glicose e os ácidos graxos, barorreceptores para registrar a pressão sanguínea, e os termo-receptores para a temperatura corporal.

Pode-se afirmar que o hipotálamo conhece o que está acontecendo dentro e fora do organismo, e consequentemente encontra-se em uma posição específica para tomar decisões transcendentais na vida do animal. Além disso, o hipotálamo regula funções vitais como a fome, a sede e o sono. Também é um órgão encarregado de regular uma função que é essencial para a sobrevivência de qualquer espécie que nada mais é do que a reprodução e a perpetuação da espécie.



Apesar de sua grande importância, o hipotálamo representa uma pequena porcen-tagem de massa encefálica. É constituído por núcleos que são grupamentos de neurônios especializados. A maioria dos núcleos são bilaterais, situados um de cada lado do tercer ventrículo que é uma cavidade pequena que contém líquido cerebrospinal que ocupa o centro do hipotálamo. Em alguns casos os neurônios estão mais dispersos, ao qual em lugar de se denominar núcleos se alcunha de áreas hipotalâmicas (figura 1).

Background: Penile length-for-age nomograms in prepubertal boys may aid in early recognition of endocrine and genetic disorders associated with abnormal phallic size. There are scarce data on the penile length measurements in children beyond the neonatal period and there is a lack of such a nomogram for Asian Indians. Materials and methods: Of the boys who were admitted in our ward or seen in the outpatient setting for genitalia-unrelated surgical problems, 20 consecutive boys were included in each of the following ten age slots (total of 200 subjects): 0e1, 1e2, 2e3, 3e4, 4e5, 5e6, 6e7, 7e8, 8 e9, and 9e10 years. Their stretched penile length (SPL) measurements were used to establish the normal range (mean AE 2 SD) of penile length-for-age in prepubertal Indian boys. Mean AE 2.5 SD was also calculated to define the cut-offs for micropenis and macropenis, respectively, in each age group. Results: A rapid increase is seen in penile length up to 4 years of age. A much slower increase is implied thereafter. Conclusion: This study provides reference values of penile lengths for Asian Indian boys aged 0 e10 years.

Background: Episiotomy is the surgical enlargement of the vaginal orifice by an incision on the perineum during the last part of the second stage of labour or delivery. Episiotomy, incision of the perineum at the time of vaginal childbirth, is a common surgical procedure experienced by women. This study is done to compare use of restrictive episiotomy and routine episiotomy in primigravidae undergoing vaginal birth. Methods: This is a prospective cohort study designed to analyse the outcome of the restrictive use of episiotomy in comparison to routine use of episiotomy. Total 100 primigravidae women reporting to labour room in spontaneous labour/induction of labour were included and two cohorts were formed. Both the cohorts were evaluated during labour, immediate postpartum period and first postnatal day and data was tabulated and analysed. Results: Vaginal and paraurethral tears were noted in 14% primigravidae in the routine episiotomy group and 22.22% in the restrictive episiotomy group with no statistically significant association. Number of cases sustaining perineal tear in restrictive group was 15.55% and extension of episiotomy in the routine group was 26% with no statistically significant association. Requirement of suturing was far less in restrictive group (20%) as compared to routine group (100%), as 64.45% of the patients in restrictive group delivered with an intact perineum. The restrictive use of episiotomy does not prolong the second stage of labour and has requirement of significantly less pain relief compared to the routine group. Complication rate was higher in the routine group and perineal laceration and pain severity, was less in restrictive episiotomy group. However, neonatal complications were similar in the two groups. Conclusions: This study identified fair to good evidence suggesting that immediate outcomes following routine use of episiotomy are no better than those of restrictive use. Indeed, routine use is harmful to the degree that some proportion of women who would have had lesser injury instead had a surgical incision

... Electrochemical Techniques Samuel N. Kikandi, Samira Musah, Kyoungyun Lee, John Hassani, Shawn Rajan, Ailing Zhou, Omowunmi. A. Sadik* ... Res. Toxicol. 2005, 18, 466. [13] J.Karasinski, S. Andreescu, OA Sadik, B. Lavine, Anal. Chem. 2005, 24, 7941. ...

PURPOSE:
To evaluate whether oral myo-inositol supplementation (MI) is able to reduce the amount of gonadotropins (GA) and the length of controlled ovarian hyperstimulation (SL) in both Polycystic Ovarian Syndrome (PCOS) and non-PCOS women undergoing in vitro fertilization (IVF).

METHODS:
We performed a systematic review (PROSPERO ID: CRD42017069439) of randomized controlled trials (RCTs). We searched articles published in English between January 1985 to August 2017, using the combination of the Medical Subject Headings "Inositol" with "Ovulation Induction", "follicle-stimulating hormone, human, with HCG C-terminal peptide", "Reproductive Techniques, Assisted", and "Fertilization in Vitro". We collected data about GA and SL comparing MI to no treatment or D-Chiro-Inositol (DCI) supplementation (controls). A subgroup analysis was performed to evaluate selected outcomes in PCOS and non-PCOS women.

RESULTS:
We included 8 studies embedding 812 participants. We found a reduction in GA (p < 0.00001) and SL (p = 0.0007) in patients receiving MI with respect to controls. MI was effective in both PCOS (p < 0.00001) and non-PCOS women (p = 0.02) in reducing GA; conversely, MI supplementation decreased the SL only in PCOS women (p < 0.00001).

CONCLUSION:
During IVF, MI is effective in both PCOS and non-PCOS women in saving gonadotropins, but reduces efficiently SL only in PCOS women.

A nexus between the immune and reproductive systems involves, among others, bidirectional effects between gonads and thymus. The human thymus is continuously viewed as the main site of tolerance to auto-antigens that are specifically expressed by T-cells  - along with the macrophages and cytotoxicity, whereas tolerance to tissue-restricted auto-antigens is ascribed to extrathymic (peripheral) mechanisms. The phenomenon of promiscuous expression of tissue-restricted self-antigens by medullary thymic epithelial cells has led to a reassessment of the role of central T-cell tolerance in preventing organ-specific autoimmunity (including the idiopathic infecundity). Both genetic and epigenetic mechanisms account for this unorthodox mode of gene expression.
More empirical studies are required to tackle the immune-reproductive pathways. The following barriers contribute to the unfortunate scarcity of thymic theme in reproductive health scholarship:
(1) being a temporary organ thymus shrinks with puberty, and therefore is erroneously viewed as gradually losing its relations to the HPA axis;
(2) ethical constraints and technical obstacles  in conducting empirical studies on thymus of reproductive age men and women.
Nonetheless, reproductive autoimmune failure can be associated with overall activation of immune system or with immune responses (both innate and adaptive) directed against ovarian antigens. Majority of the antiovarian auto-antibodies target the β-subunit of follicle stimulating hormone (anti-FSH). In female infertility, the expansion of cells responding to low-affinity ligands (allo-antigen) or anomalies in the deletion of high-affinity autoreactive T-cells leading to autoimmune reactions is a possibility to explore.
Infertility and recurrent spontaneous abortion (RSA) are frequently attributed to the immunological disturbance. A deeper insight into apparently unexplained infertility and RSA supports the theory of both alloimmune and autoimmune involvements, in which natural killer (NK) cells and auto-antibodies are the role players.
Successful pregnancy is considered a Th1–Th2 cooperation phenomenon, with a predominantly Th2-type lymphocyte response, together with the emerging role of interleukin (IL)-12, IL-15, and IL-18 and of other unidentified soluble factors dependent on NK cells.
The uterine NK cells comprise the largest population at implantation site, and their activity, characteristics, and abundance suggest that they participate at the decidualization process that induces NK activation and recruitment in each menstrual cycle and vice versa. However, NK cell alteration may be associated with impaired pregnancy, and the modulation in the number of circulating NK cells is most likely to be a primary event rather than an the outcome of active inflammation or autoimmune process in the pathogenesis of immunological infertility. [1]
Studies on animal models suggest on the reduced fecundity of parasites due to the thymus-dependent immunological responses in mice.[2]  Removal of thymus retards the growth of the testes in young guinea pigs.[3] Another study defines the thymus factor (TF) to inhibit the binding activity of 125I-hCG to its testicular receptor. The inhibitory effect of TF on hCG binding is dose related, suggesting a modulation function of TF at the testis receptor level.[4]
Reproductive autoimmune failure syndrome was originally described by Gleicher et al. in 1987, in women with endometriosis, infertility and increased auto-antibodies.[5] Autoimmune mechanisms as well as an increased production of multiple autoantibodies are involved in such infertility disorders as premature ovarian failure (POF), endometriosis, polycystic ovary syndrome (PCOS), unexplained infertility, and repeatedly unsuccessful in vitro fertilization (IVF) attempts and may be responsible for the pathophysiology of preeclampsia or spontaneous abortions.  [7]
The autoimmune infertility might be a polyclonal event featured by immunological defects at the T-cell level which - similarly to classical autoimmune diseases - may manifest itself in abnormal antibody production. [8, 9] However, like state above, most clinical studies are restricted to detecting serum antibodies in determining  autoimmune activation in the infertile couple - due to the technical difficulties.
Yet, thymus performs many roles in immune-related fertility issues. Autoimmune regulator genes (AIREG) influence thymic production of ovarian antigens and prevents autoimmune-mediated premature reproductive senescence. For example, immunemediated ovarian follicular depletion is a mechanism of infertility in mice.[10] Such animal models are important informers as to the mechanism of the ovarian autoimmune disease in women. Thymic expression of the ovarian genes controlled by  the AIREG deem crucial in preventing ovarian autoimmune disease.
It is also established that treatment of patients with chronic prostatitis is complicated by infertility by microwave (460 MHz) action on the area of the thyroid and thymus glands.[11] T-lymphocyte inhibition by human seminal plasma is due to multiple factors, and reduced amounts of these factors may contribute to development and persistence of sperm autoimmunity in the infertile men.[12]
When debating over the immune stress in infertility, no concept is integrate without mentioning the role of relaxin. A peptide of the insulin superfamily, relaxin consists of seven peptides of high structural but low sequence similarity; relaxin-1 (RLN1), 2 (RLN2) and 3 (RLN3), and the insulin-like (INSL) peptides, INSL3, INSL4, INSL5 and INSL6. In females, it is produced by the corpus luteum of the ovary, the breast and during pregnancy, through the placenta, chorion, and decidua. In males, it is produced in the prostate and is found  in the semen.
Discovered more than 75 years prior to the identification of the receptors that mediate  actions of relaxin, there has been however a slow move toward understanding the  role of relaxin – except of the notion of it being a hormone of pregnancy. Yet, relaxin is equipped for many other physiological roles, including vasomotor regulations, or the ability to induce matrix metalloproteinases.
The recent de-orphanisation of four receptors LGR7, LGR8, GPCR135 (SALPR) and GPCR142 (GPR100) that respond to and bind at least one of the three forms of relaxin , allows dissection of this system to determine the precise role of each receptor and enable the identification of new targets for treatment of numerous disease states.
Some studies suggest, that the reduced incidence and severity of rheumatoid arthritis in pregnancy is attributed to the estradiol-17β and relaxin. [13]
Relaxin-3, the newly established member of relaxin peptide family, is produced by GABA-ergic projection neurons in the nucleus incertus (NI), in the pontine periventricular gray matter of the brain. Relaxin-3 is a modulator of stress responses, metabolism, arousal and behavioral activation. It is shown, that relaxin-3 (or INSL7)  is the endogenous ligand for an orphan G-protein-coupled receptor, GPCR135 (aka somatostatin, an angiotensin-like peptide receptor), but it also activates GPCR142. [14] Yet, a definitive role remains elusive due to discrepancies between models and a propensity to investigate pharmacological effects over endogenous function.
Relaxin antagonists may act as contraceptives or prevent the development of breast cancer metastases. Recent research has added considerable knowledge to the signaling pathways activated by relaxin, which will aid our understanding of how relaxin acts in infertility.
During phylogeny and ontogeny, thymus appears as a nodal point between the two major systems of cell-to-cell signaling, between the neuroendocrine and immune systems. The neuroendocrine polypeptide precursors play a dual role in T-cell selection played by the thymic repertoire.
Thymic neuroendocrine-related polypeptides are source of auto-antigens which are presented by the major histocompatible system of thymic epithelium. The intrathymic T-cell education to neuroendocrine self-antigens cannot be strictly counted out in terms of  the antigen presentation by dedicated presenting cells. [15]
Little is known about the role of relaxin in modulating cell-mediated immunity, and acute or chronic thymic atrophy. For the first time in reproductive health scholarship, a putative thymus-gonadal-relaxin  axis is speculated through the pathway presented  in Figure 1):

Pregnancy-associated glycoprotein (PAG) concentrations were measured in buffalo cows starting from day 28 after breeding. Oestrus was synchronized in 10 buffaloes using two injections of 25 mg prostraglandin (PG)F 2a (Lutalyse Ò ) at a 11-day interval. Blood sampling was conducted nearly twice weekly. Results indicated that plasma PAG concentrations in nonpregnant buffaloes were low (<0.20 ng/ml) during the whole experimental period (day 28 to 103), while in pregnant animals plasma PAG levels increased from day 28 (4.48 ± 0.92 ng/ml) until day 41 (27.27 ± 6.74 ng/ml), remaining high (20.71 ± 9.20 ng/ml) until day 103. Progesterone levels were significantly (p < 0.0001) higher in pregnant (3.51-4.80 ng/ ml) than in non-pregnant buffaloes (0.28-1.52 ng/ml). A significant difference (p < 0.0001) in plasma PAG concentrations between pregnant and non-pregnant animals starting at day 28 after breeding suggests that PAG-radioimmunoassay could be suitable for pregnancy diagnosis in buffaloes during this period. In conclusion, PAG test offers the advantages that it requires a single plasma sample for early pregnancy diagnosis as well as the accuracy of the test for the detection of pregnancy as early as day 28.

La investigación que presenta el libro tuvo como objetivo analizar las diferencias entre las decisiones económicas bajo riesgo y en contexto social durante las fases ovulatoria y lútea del ciclo menstrual. El enfoque utilizado fue el empírico analítico, con alcance comparativo, diseño no experimental y de tipo transversal. El muestreo fue probabilístico, con una muestra de 100 mujeres de la Universidad de Antioquia entre los 18 y 24 años, con ciclos menstruales regulares y sin uso de métodos anticonceptivos hormonales. Los instrumentos utilizados fueron: encuesta sociodemográfica, cuestionario sobre el ciclo menstrual, Juego de loterías de Holt y Laury y el Juego del ultimátum. Entre los resultados se encontró que las mujeres presentaban aversión al riesgo sin importancia de la fase del ciclo menstrual, y en las decisiones económicas sociales, no hubo diferencias significativas entre los grupos. La investigación permitió concluir que no hubo diferencias en la toma de decisiones entre los grupos de la fase ovulatoria y la fase lútea. La discusión de los resultados se desarrolla a la luz de la teoría evolutiva y la teoría económica.

The differentiation and development of the testis in the lizard Calotes versicolor was studied histologically and histoenzymatically from the day of oviposition (stage 27) to 2 months after hatching. The study reveals the appearance of the gonadal component as a genital ridge at stage 27. The first sign of testis differentiation is observed at stage 33, which displays a well-developed medulla consisting of seminiferous cords comprising Pre-Sertoli cells. The sex differentiation of the embryonic gonads occurs at stage 34. At this stage, seminiferous cords of the testis are prominent and extensive with many pre-Sertoli cells and few spermatogonia. The interstitial space consists of immature fibroblast-type Leydig cells. Pre-Sertoli cells of the seminiferous cords differentiate into Sertoli cells with a triangular nucleus becoming apparent around stages 36–37. The fibroblast-like Leydig cells differentiate into round matured Leydig cells at stage 40. Quantitative estimation of germ cells reveals that the number of germ cells increases in individual gonads, and in 5-day-old hatchling's, this number multiplies by manifold. Spermatogonia show reductional division in the testis of 1-day-old hatchlings. Histochemical localization of D 5-3b-HSDH and G-6-PDH activity appears in the seminiferous cords (medulla) of the testis after sexual differentiation (stage 36), indicating that the embryonic medulla is the site of steroidogenesis and not the cortex in C. versicolor. This study also suggests that morphological differentiation of the gonad precedes detectable steroidogenesis in this species. In 10-day-old hatchling's, D 5-3b-HSDH activity is seen in the interstitial cells of the testis, which, however, is not detected in the seminiferous tubules. The intensity of the enzyme activity remains more or less the same in the testis up to 10 days after hatching and begins to increase thereafter. The increase in steroidogenesis parallels the progressive post-hatching increase of the interstitial/Leydig cells.

Background: Hormonal derangements potentially contribute to the diagnosis of infertility in over 60%-70% of couples investigated. Use of hormonal and antihormonal agents has achieved great success in the treatment of male infertility. Our aim was to investigate the prevalence of hormonal abnormalities in males diagnosed with infertility. Methods: Males diagnosed clinically with infertility and referred from the gynecologic clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu State University Teaching Hospital, and some private hospitals in and around Enugu metropolis were recruited for the study. They were grouped according to whether they had primary or secondary infertility on the basis of the World Health Organization definition. Routine fertility test profiles for the subjects were evaluated, and detailed hormonal assays were analyzed. Results: Of 216 men, 173 (80.1%) were found to have a hormonal imbalance. The mean age was 47.7 ± 3.5 (range 30-55) years for primary infertility and 47.2 ± 6.8 (range 33-61) years for secondary infertility. Patterns of hormonal abnormalities diagnosed amongst the 62 (35.80%) primary infertility subjects included hypergonadotrophic hypogonadism in 39 (62.90%), hypogonadotrophic hypogonadism in 18 (29.03%), and hyperprolactinemia in five (8.07%). Among the 111 (64.2%) cases of secondary infertility, there were 55 (49.55%) cases of hypergonadotrophic hypogonadism, 52 (46.85%) of hypogonadotrophic hypogonadism, and four (3.60%) of hyperprolactinemia. There was no statistically significant difference in the mean values between the two groups (χ 2 , 1.414; P . 0.05) for hormonal indices. Conclusion: The hormonal profile should be considered as the gold standard for diagnosis and management of male infertility.

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

Dem Buch liegt eine Metastudie der Autorin von 2017 zugrunde, in der sie zeigte, dass die Spermienzahl in westlichen Ländern (Nordamerika, Europa und Australien) während der letzten vier Jahrzehnte (1973–2011) um 50–60 Prozent abnahm: von durchschnittlich 99 Millionen Spermien pro Milliliter Ejakulat auf 47. Der Testosteronspiegel sinkt
im Durchschnitt ebenfalls ab – um ein Prozent pro Jahr seit
1982 – während erektile Dysfunktionen und Genderfluidität
zunehmen.

Chronotype describes preferences for functioning at different times of the day. At the onset of puberty, a sharp shift towards eveningness starts, reaching its peak at the end of adolescence, followed by a steady shift towards morningness as the ageing process occurs. Puberty is also the time when sex differences appear, with men being more inclined to eveningness than women, which diminishes around menopause; the described pattern of changes in chronotype leads to the hypothesis that reproductive hormones may be the driving factor behind this conversion. In the present study, we aimed to verify this hypothesis by analysing participants' testosterone, progesterone and dehydroepiandrosterone (DHEA) levels in the three months prior to the study, as indicated by assays in 3-cm hair strands from the scalp. Participants (n = 239) of both sexes also completed the Munich Chronotype Questionnaire. The results showed that in men higher testosterone levels were related to eveningness and less sleep loss, whereas greater sleep loss was associated with lower levels of DHEA. In women, no associations between chronotype and levels of the analysed hormones were found. The results support the hypothesis that testosterone levels play a role in shaping eveningness. We further hypothesised that a possible cause of the higher secretion level of testosterone in men with the evening chronotype is a mechanism to offset the negative consequences of sleep loss.

The aim of this study was to compare the accuracy of the progesterone (P4) and pregnancy associated glycoprotein (PAG) tests for determination of early pregnancy in sheep. Estrus was synchronized in 182 Awassi  Merino ewes and blood samples were collected at Days 0 (day of the insemination), 18, 22, 29, 36, and 50 after arti®cial insemination (AI). Plasma P4 concentrations at Days 0 and 18 were determined by double antibody radioimmunoassay, while PAG concentrations at Days 22, 29, 36 and 50 were determined by a heterologous, double-antibody radioimmunoassay (RIA) using the bovine PAG 67 kDa subunit as tracer and standard and rabbit antiserum raised against a mixture of caprine 55 and 59 kDa PAG subunits as the ®rst antibody. The discriminatory value for diagnosis of pregnancy by the P4 and the PAG-RIA tests was !1 ng/ml. Based on lambing data, the accuracy for diagnosing pregnant (sensitivity) and non-pregnant ewes (speci®city) and predictivity of both tests were calculated. The sensitivity, speci®city, positive and negative predictive values for P4 and PAG tests were 100, 95.4, 81.6, and 100% at Day 18 (P4) and 93.5, 100, 100 and 98.7% at Day 22 (PAG), respectively. For diagnosis of non-pregnant ewes the PAG test had signi®cantly higher speci®city than the P4 test (P < 0:05). It is concluded that ovine pregnancy can be reliably diagnosed at Day 22 after AI by using a heterologous radioimmunoassay of PAG. #

Introduction: The adverse effects of pesticides as a result of their indiscriminate use have been a concerned issue in many developing countries. Frequently the use of insecticides during the lifetime of human cannot be avoided and it may result in oxidative damage effects. The pyrethroid insecticides are highly toxic which can cause an array of adverse damaging effects including infertility and birth defects in both humans and animals due to generation of free radicals. Aim: This study is aimed to investigate the effect(s) of pyrethroid pesticides on oxidative stress biomarkers and reproductive hormones in exposed adult Wistar rats. Materials and Methods: A total number of healthy thirty one (31) male Wistar rats were randomly selected for this study and divided into two groups. Nineteen (19) were exposed to 1.2% w/v pyrethroid based insecticides while the remaining twelve (12) were grouped as non-exposed/control. The animals in each group were anesthetized and blood sample was collected from the inferior vena cava after 7, 21 and 41 days of exposure. Plasma levels of total antioxidant status (TAS), malondialdehyde (MDA), reduced glutathione (GSH) and hydrogen peroxide (H 2 O 2) were determined using standard spectrophotometric techniques. Plasma activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were determined using standard spectrophotometric techniques. ELISA was used to determine levels of reproductive hormones (Luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (TEST)). Semen fluid analysis was done immediately after the animal was sacrificed appropriately. One way analysis of variance (ANOVA) was used for comparison within the groups. Spearman correlation was used to test the association between variables and P<0.05 was considered significant. Results: The plasma mean levels of SOD, GPx, CAT, GSH and TAS were significantly decreased while plasma mean levels of MDA and H 2 O 2 were significantly increased from 7 days through 41 days exposure in exposed groups. Similarly, the mean levels of FSH, LH and TEST were significantly decreased from 7 days through 41 days. Conclusion: Pyrethroid by inhalational route causes oxidative stress on Wistar rats exposed and reduction in antioxidant defenses. Inhaled pyrethroids affect sex hormone levels and motility of semen cells, which might lead to infertility.

Background: The physiological mechanism by which bulls stimulate resumption of ovarian cycling activity in postpartum, anovular, suckled cows after calving may involve the concurrent activation of the hypothalamic-hypophysealovarian (HPO) axis and hypothalamic-hypophyseal-adrenal (HPA) axis. Thus, the objectives of this experiment were to determine if characteristics of temporal patterns of cortisol and luteinizing hormone (LH) in postpartum, anovular, beef cows are influenced by acute exposure to bulls. The null hypotheses were that daily, temporal characteristics of cortisol and LH concentration patterns do not differ between cows exposed acutely to bulls or steers. Methods: Sixteen cows were assigned randomly 67 +/-4 (+/-SE) after calving to be exposed to bulls (EB, n = 8) or steers (ES, n = 8) 5 h daily for 9 d (D 0 to 8). Blood samples were collected daily from each cow via jugular catheters at 15-min intervals for 6 h from 1000 to 1600 h each day. The 5-h exposure period began 1 h after the start of the intensive bleeding period. Characteristics of cortisol and LH concentration patterns (mean, baseline, pulse frequency, pulse amplitude, and pulse duration) were identified by PULSAR analyses. Results: Mean cortisol concentrations decreased (P < 0.05) in cows in both treatments from D 0 to D 2. Thereafter, mean cortisol concentrations stabilized and did not differ (P > 0.10) between EB and ES cows. The decrease in mean cortisol concentrations in EB and ES cows from D 0 to D 2 was attributed to cows acclimatizing to intensive blood sampling and handling procedures. Consequently, analyses for characteristics of cortisol and LH concentration patterns included D 2 through 8 only. Cortisol mean and baseline concentrations, and pulse amplitude did not differ (P > 0.10) between EB and ES cows. However, cortisol pulse duration tended to be longer (P = 0.09) and pulse frequency was lower (P = 0.05) in EB than ES cows. LH pulse frequency was greater (P = 0.06) in EB than ES cows. All other characteristics of LH concentration patterns did not differ (P > 0.10) between EB and ES cows. Characteristics of cortisol concentration patterns were not related to characteristics of LH concentration patterns for ES cows (P > 0.10). However, as cortisol pulse amplitude increased, LH pulse amplitude decreased (b1 = -0.04; P < 0.05) for EB cows.

The aim of the study was to arrive at some biochemical and hormonal evidence predicting ovarian polycystic ovaries in women with primary or secondary infertility. Samples were collected at the fertility center laboratories in Sadr Medical City, Najaf, Iraq. The blood was taken for complete blood cell (CBC) testing on the samples. Samples were taken 88 samples (70 of which were samples of women with polycystic ovaries and 18 sample of control women). A serum was then taken for biochemical tests, The hormones LH, FSH, prolactin, Estradiol, Kisspeptin1, Interleukin 37 were measured by ELISA method while lipid profile and total protein by spectrophotometer method. The result showed a significant increase (p<0.05) of Kisspeptin-1 ,Prolactin, cholesterol ,triglyceride ,low density lipoprotein ,very low density lipoprotein, total protein and RBC in women with polycystic ovary disease compared with control group, While significant decrease (p<0.05) of high density lipoprotein and Interleukin-37 in women with polycystic disease compared with control group. And the results showed non-significant (p > 0.05) in both Luteinizing hormone, Follicle stimulation hormone, Estradiol hormone, platelet, WBC. The significant increase in the level of Kisspeptin and some of the biochemical and physiological parameters measured in the present study may provide an indicator of increased infertility in women with ovarian disease.

Thirty-six West African Dwarf (WAD) goats were used to assess the effects of an experimental Trypanosoma congolense infection on their reproductive system. Estrous cycles were synchronised and when confirmed pregnant (n=31), the does were randomly allocated into control and trypanosome-infected groups. After infection, the animals were carefully observed till parturition. Trypanosome infection caused an increase of rectal temperature, a significant

OBJECTIVE: This open-label non-randomized clinical study aimed at evaluating the effects of myo-inositol plus alpha-lac-talbumin in two groups of PCOS women, treated in Mexico and Italy. Alpha-lactalbumin was used being effective in increasing myo-inosi-tol intestinal absorption. This effect is very useful in greatly reducing the therapeutic failure of myo-inositol in some patients (inositol resistant subjects). PATIENTS AND METHODS: The study involved 34 normal weight or overweight patients (14 in Mexico and 20 in Italy), aged 18 to 40 years, with anovulation and infertility > 1 year and insulin resistance diagnosed by HOMA-Index. Patients were administered orally with 2 g myo-inositol, 50 mg alpha-lactalbumin, and 200 µg of folic acid twice a day for 6 months. Controls were the same patients at t0 (baseline). The primary outcome was HOMA-index decrease after 3 and 6 months of treatment. Other parameters monitored were BMI, progesterone, LH, FSH, total testosterone, free testosterone, an-drostenedione, total cholesterol, HDL, LDL, tri-glycerides. RESULTS: Recovery was general, and its relevance was higher when the starting point was further away from the normal range. The most important results were obtained with insulin, HOMA-index, LH, and androstenedione. No significant adverse effects were detected in both groups of patients. CONCLUSIONS: This clinical trial demonstrated for the first time that myo-inositol and alpha -lactalbumin improve important parameters in PCOS patients characterized by different metabolic profiles.

Objective: to evaluate the effects of titanium dioxide microcrystals with covalently bonded silver ions and Aloe Vera extract (TIAGIN ®) on the Vaginal Health Index Score (VHIS) and Female Sexual Function Index (FSFI) in patients with vaginal de-epithelialization.
Materials and methods: we enrolled 45 post-menopausal women with vaginal de-epithelialization, who underwent VHIS evaluation and completed an FSFI test. We recorded their age, age at onset of menopause, parity and Body Mass Index. After this baseline evaluation, patients underwent 30 days of vaginal treatment with one capsule per day of TIAGIN ®. After treatment, all patients were evaluated again using the same methods as the pre-treatment phase.
Results: after treatment there was significant improvement in all VHIS parameters (elasticity, fluid secretion type and consistency, pH, epithelialization of vaginal mucosa, and moisture) and in the total score (p=0.006). Similarly, after treatment there was also a significant improvement in 4 FSFI areas (lubrication, orgasm, satisfaction, and pain) and in the total score (p=0.005). None of the patients reported any local or systemic side effects during treatment.
Conclusions: we observed a significant improvement in both the VHIS and FSFI, which can be considered direct and indirect signs of increased vaginal epithelialization following vaginal treatment with TIAGIN ® .

Discoveries of how social behavior can influence the plasticity of gonadotropin-releasing hormone (GnRH) have revolutionized the field of behavioral neuroendocrinology by providing new insights into the neural mechanisms controlling behavior. In 2000, the neuropeptide gonadotropin inhibitory hormone (GnIH) was discovered and is changing the way we view how the brain mediates reproduction and associated behaviors. GnIH acts as a reproductive ‘pause button’, momentarily inhibiting the activity of the reproductive system. However, how GnIH fluctuates naturally in response to social environment is unknown. We examine how the outcome of competition for limited resources needed for reproduction is associated with GnIH. We experimentally manipulated nesting opportunities for pairs of European starlings (Sturnus vulgaris) and examined brain GnIH mRNA and peptide content, as well as GnRH content and plasma testosterone and corticosterone. By limiting the number of nest boxes per enclosure and thus the number of social pairing and nesting opportunities, we observed that birds which outcompeted others for nest boxes (‘winners’) had significantly fewer numbers of GnIH peptide-producing cells than those without nest boxes (‘losers’) and this relationship changed with breeding stage. GnRH content, testosterone and corticosterone did not vary with nest box ownership. Thus, while birds appeared reproductively capable across treatments, our data indicate that GnIH may serve as a modulator of reproductive behaviors in response to social environment. Additionally, we provide some evidence of the adaptive value of this mechanism.

Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

Captive breeding is a vital conservation tool for many endangered species programs. It is often a last resort when wild animal population numbers drop to below critical minimums for natural reproduction. However, critical ecophysiological information of wild counterparts may not be well documented or understood, leading to years of minimal breeding successes. We collected endocrine and associated ecological data on a critically endangered ectotherm concurrently in the wild and in captivity over several years. We tracked plasma concentrations of steroid stress and reproductive hormones, body condition, activity, and environmental parameters in three populations (one wild and two geographically distinct captive) of ploughshare tortoise (Astrochelys yniphora). Hormone profiles along with environmental and behavioral data are presented and compared. We show that animals have particular seasonal environmental requirements that can affect annual reproduction, captivity affects reproductiv...