Infertility Therapy Research Articles

Therapy of ovarian dysfunction in cows in the conditions of farms of the udmurt republik

Increasing the reproductive qualities of animals is the main task of dairy farms. Replacement of the main breeding stock with young animals, often leads to the fact that young animals, being exposed to ovarian diseases, undergo a longer recovery time and reduce the effectiveness of artificial insemination. This work highlights the issue of infertility of cows in specific farms, under certain feeding and housing conditions. The aim of the work was to develop a system therapy of infertility of cows with ovarian diseases.The experiment was conducted in two farms of Uvinsky district of the Udmurt Republic, with the formation of six groups of animals in each farm for each individual disease. In particular, the main diseases were ovarian hypofunction and ovarian follicular cysts. Six schemes of ovarian therapy were developed.During a gynecological examination, hypofunction of the ovaries was found in 14% of cows in the SPK "collective farm Udarnik" and in 18% of cows in OOO "Riko-Agro". Follicular ovarian cysts were found in 10% of cows in the SPK "collective farm Udarnik" and in 12% of cows in LLC "RikoAgro". During the experiment, the activity of the manifestation of sexual characteristics in cows was monitored. At the same time, it was found that with hypofunction of the ovaries, all experimental cows came into heat only according to scheme No. 2. This scheme includes drugs such as Surfagon and ASD-2fr emulsion. and Tetravit. In the treatment of follicular ovarian cysts, attention was paid to the regression of cysts. The greatest amount of cyst regression (100%) was achieved using scheme No. 5, which includes Metrostim, Fertagon and Estrofan. As a result of the work, we found that in the case of ovarian hypofunction, the most effective treatment regimen included Surfagon, ASD-2fr. and Tetravit. The rate of cow fecundation was over 67% of cows in both farms on the first insemination. With follicular ovarian cysts the greatest efficiency of therapy was achieved using the scheme including Metrostim, Fertagon and Estrofan.Fertilization of cows at the first insemination after therapy was also more than 80%. For the purpose therapy of these diseases, we recommend to use schemes including the above mentioned drugs.

Male Hypogonadism Significantly Increases the Risk of Perinatal Birth Complications: Retrospective Analysis of US Claims Data

ABSTRACT Introduction Hypogonadism is common in men with male factor infertility and hormone therapies may improve semen parameters and pregnancy rates in affected men. However, compared to paternal factors such as advanced age, male infertility or obesity, it is uncertain whether hypogonadism itself impacts perinatal birth outcomes and complications. Objective This study evaluates the association between male hypogonadism and perinatal birth complications in the United States. Methods We performed a retrospective analysis of the IBM MarketScan™ Commercial Claims and Encounters database between 2011-2017. We identified birth records using birth or pregnancy-related major diagnostic categories associated with persons age 0. Fathers were considered to be adult (> 18) male individuals with the same family identifier as the neonates listed as either the primary insurance beneficiary or spouse. Birth records were excluded if there was no family identifier or the father was unable to be linked. For each birth, we recorded whether they were preterm, diagnosed as low birth weight, or diagnosed with birth defects. For the fathers linked with each birth record, we determined paternal age, hypogonadism status, geographic region, and other associated comorbidities. Births were stratified based on whether the father had hypogonadism or not and we performed univariate tests for variation. Additionally, we conducted a multivariate logistic model of birth complication (preterm, low weight, or growth defect) against father's age, hypogonadism status, and paternal comorbidities. Results Between 2011 and 2017, paternal hypogonadism was found in 3.97% of fathers among 468,546 birth records. In contrast, no paternal hypogonadism was found in 96.03% of fathers among 468,546 birth records. Overall, our study reveals that paternal hypogonadism is positively associated with perinatal birth complications (odds ratio (OR) 1.10; 95% CI: 1.06, 1.13). Additionally, low birth weight was found in 46, 96% of birth among 196,607 birth records with paternal hypogonadism, follow by preterm birth with 7.64% of birth among 26,886 birth records with paternal hypogonadism. Conclusions Male hypogonadism was associated with a statistically significant increase in perinatal birth complications. However, these results should be interpreted with caution because patients with male hypogonadism are also likely to have male infertility. For hypogonadism to be considered as a separate risk factor for perinatal birth complications further investigation will be needed. Disclosure No

Transcriptional profiling of β-2M-SPα-6+THY1+ spermatogonial stem cells in human spermatogenesis.

SummaryMale infertility is responsible for approximately half of all cases of reproductive issues. Spermatogenesis originates in a small pool of spermatogonial stem cells (SSCs), which are of interest for therapy of infertility but remain not well defined in humans. Using multiparametric analysis of the side population (SP) phenotype and the α-6 integrin, THY1, and β-2 microglobulin cell markers, we identified a population of human primitive undifferentiated spermatogonia with the phenotype β-2 microglobulin (β-2M)−SPα-6+THY1+, which is highly enriched in stem cells. By analyzing the expression signatures of this SSC-enriched population along with other germinal progenitors, we established an exhaustive transcriptome of human spermatogenesis. Transcriptome profiling of the human β-2M−SPα-6+THY1+ population and comparison with the profile of mouse undifferentiated spermatogonia provide insights into the molecular networks and key transcriptional regulators regulating human SSCs, including the basic-helix-loop-helix (bHLH) transcriptional repressor HES1, which we show to be implicated in maintenance of SSCs in vitro.

Clinical utility of serum 17-hydroxyprogesterone as a marker for medical therapy for male infertility: recommendations based on clinical scenarios.

Traditional serum hormone testing in the evaluation of male infertility consists of testosterone, follicle-stimulating hormone, luteinizing hormone, and estradiol. Based on these values, medical therapy is often initiated in an attempt to increase intratesticular testosterone levels and, in turn, promote spermatogenesis. While this hormone panel provides serum testosterone levels, it does not evaluate intratesticular testosterone, obviously an important factor that is critical for spermatogenesis. 17-hydroxyprogesterone (17-OHP) is an intermediate in the steroidal pathway of cholesterol to testosterone conversion that has recently demonstrated promise as an accurate serum biomarker for intratesticular testosterone. At present, 17-OHP has not been widely adopted as a clinical tool in the evaluation of male infertility, which likely stems, in part, from a lack of concrete indications for its use. In this review, we present five commonly encountered scenarios of male infertility where the utilization of 17-OHP has aided in the management and provided a more personalized approach to treatment.

Follicle-stimulating hormone modestly predicts improvement in semen parameters in men with infertility treated with clomiphene citrate.

Clomiphene citrate is a commonly prescribed empiric medical therapy for male infertility, but outcomes data and response rates remain incompletely understood. We retrospectively reviewed our single-institutional experience of infertile men prescribed clomiphene. Clomiphene treatment in the final cohort of 140 men was associated with a modest increase in median sperm concentration from 2.2 to 2.5million/ml (p<0.001). A total of 46/140 (33%) of men upgraded according to World Health Organization concentration categories. Clomiphene treatment in 26/113 (23%) of previously ineligible men became eligible for intrauterine insemination. Using both univariate and multivariable regression, pre-treatment follicle-stimulating hormone was inversely associated with change in semen concentration with clomiphene treatment. On binary logistic regression, follicle-stimulating hormone level was inversely related to World Health Organization concentration category upgrade (p=0.01). Unfortunately, 17/140 (12%) of men paradoxically worsened on clomiphene, but no predictors for this could be identified. In summary, clomiphene citrate confers a clinically relevant but modest benefit in a subset (1/3rd ) of infertile men, particularly those with lower pre-treatment follicle-stimulating hormone levels. Men with elevated follicle-stimulating hormone over 15IU/ml are less likely to benefit from treatment and should be counselled on other relevant treatment alternatives.

Multiple gestation associated with infertility therapy: a committee opinion

This Committee Opinion provides practitioners with suggestions to reduce the likelihood of iatrogenic multiple gestation resulting from infertility treatment. This document replaces the document of the same name previously published in 2012 (Fertil Steril 2012;97:825-34 by the American Society for Reproductive Medicine).

Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial.

BackgroundWomen with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.Methods and findingsIn this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (−6.6 ± 5.4% versus −0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.ConclusionsA preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.Trial registrationClinicalTrials.gov NCT02432209.

Duration of oral antioxidant therapy in male infertility with increased DNA damage: 3 month versus 6 month

Duration of oral antioxidant therapy in male infertility with increased DNA damage: 3 month versus 6 month

Adenovirus-mediated gene delivery restores fertility in congenitally infertile female mice.

Oogenesis depends on close interactions between oocytes and granulosa cells. Abnormal signaling between these cell types can result in infertility. However, attempts to manipulate oocyte-granulosa cell interactions have had limited success, likely due to the blood-follicle barrier (BFB), which prevents the penetration of exogenous materials into ovarian follicles. Here, we used adenoviruses (AVs) to manipulate the oocyte-granulosa cell interactions. AVs penetrated the BFB and transduced granulosa cells through ovarian microinjection. Although AVs caused transient inflammation, they did not impair fertility in wild-type mice. Introduction of Kitl-expressing AVs into congenitally infertile KitlSl-t/KitlSl-t mutant mouse ovaries, which contained only primordial follicles because of a lack of Kitl expression, restored fertility through natural mating. The offspring showed no evidence of AV integration and exhibited normal genomic imprinting patterns for imprinted genes. These results demonstrate the usefulness of AVs for manipulating oogenesis and suggest the possibility of gene therapies for human female infertility.

Эндометриоз-ассоциированное бесплодие: патогенез и возможности гормональной терапии в подготовке к ЭКО

Objective. Analytical review of the literature on endometriosis-associated infertility, its mechanisms and hormone therapy in preparation for in vitro fertilization (IVF). Endometriosis is considered the most common benign but potentially metastatic gynecological disease and occurs in approximately 10% of women of reproductive age, causing infertility in 40%. Patients with this disease often require the use of assisted reproductive technologies to increase the chances of pregnancy. However, endometriosis interferes with all aspects of the reproductive process and is associated with lower success rates than other indications for IVF. The mechanisms of infertility associated with endometriosis remain largely unknown. Several etiological factors of endometriosis-associated infertility are discussed, ranging from abnormal anatomy and fallopian tube obstruction due to pelvic adhesions to less studied factors such as proinflammatory cytokine responses leading to endometrial receptivity and impaired oocyte quality. Conclusion. To improve IVF outcomes in infertile patients with endometriosis, a long-term (3–6 months) hormone suppressive therapy before the cycle was suggested. Preliminary prescription of dienogest may improve clinical outcomes of pregnancy after IVF in patients with this disease. Dienogest has a favorable effect on both systemic and local inflammatory microenvironment, increases the number and quality of obtained oocytes, high-quality embryos and blastocysts, the rate of clinical pregnancy and live birth, which has been repeatedly shown in studies. Key words: endometriosis, IVF, IVF failure, dienogest, infertility

Tamoxifen as Empirical Treatment in Males with Primary Infertility and Normal Gonadotropic Hormonal Levels: A Prospective Study

Background: One of the most commonly employed medical therapies for idiopathic male infertility are antiestrogens. Tamoxifen as estrogen receptor blockers have been used as empiric treatments for male infertility, acting through blocking estrogen receptor at the hypothalamus and pituitary levels and so preventing the important negative feedback of estrogens to the pituitary and hypothalamus as a result that leading to gonadotropin releasing hormone (GnRH) stimulation and pulsatile release of luteinizing hormone (LH)/follicle-stimulating hormone (FSH). Objective: To assess tamoxifen role in the treatment of men with primary infertility who are normogonadotropic. as it is widely prescribed drug for that purpose as well as to evaluate possible patient’s criteria for a better response to tamoxifen. Methods: One hundred twenty-three patients with idiopathic primary infertility and normal FSH, LH, and testosterone serum levels were enrolled in this prospective study. All patients received 20 mg tamoxifen daily as a single dose for at least 3 months, and semen analysis (total sperm concentration, total number of progressive motile sperms and percentage of normal sperm morphology) as well hormones levels were evaluated, with the values being compared with those before treatment. Results: Overall, there was no statistically-significant improvement in semen parameters 3 months after treatment (P&gt;0.05); however, patients with pretreatment lower normal FSH level of (1.7-6.85 mIU/ml) and those with pretreatment sperm concentration of (five to ten million per ml) showed statistically significant improvement in sperm concentration after tamoxifen therapy (p=0.044 and p=0.012 respectively). Conclusion: Tamoxifen is an acceptable treatment for idiopathic male infertility. A better response can be expected in patients with pretreatment lower normal FSH level of (1.7-6.85 miu/ml) and sperm concentration of 5-10 million per ml. It might be used as first line treatment to enhance sperm concentration, giving its availability and lower cost in comparison to other hormonal therapies. Keywords: Male Infertility, tamoxifen, empirical treatment Citation: Al-Anbary LA. Tamoxifen as empirical treatment in males with primary infertility and normal gonadotropic hormonal levels: A prospective study. Iraqi JMS. 2021; 19(2): 230-236. doi: 10.22578/IJMS.19.2.12

Histology and Cell Biology: An Introduction to Pathology 5th Edition 2020

Linking basic science to clinical application throughout, Histology and Cell Biology: An Introduction to Pathology, 5th Edition, helps students build a stronger clinical knowledge base in the challenging area of pathologic abnormalities. This award-winning text presents key concepts in an understandable, easy-to-understand manner, with full-color illustrations, diagrams, photomicrographs, and pathology photos fully integrated on every page. Student-friendly features such as highlighted clinical terms, Clinical Conditions boxes, Essential Concepts boxes, concept mapping animations, and more help readers quickly grasp complex information.&#x0D; &#x0D; &#x0D; Features new content on cancer immunotherapy, satellite cells and muscle repair, vasculogenesis and angiogenesis in relation to cancer treatment, and mitochondria replacement therapies.&#x0D; &#x0D; &#x0D; Presents new material on ciliogenesis, microtubule assembly and disassembly, chromatin structure and condensation, and X chromosome inactivation, which directly impact therapy for ciliopathies, infertility, cancer, and Alzheimer’s disease.&#x0D; &#x0D; &#x0D; Provides thoroughly updated information on gestational trophoblastic diseases, molecular aspects of breast cancer, and basic immunology, including new illustrations on the structure of the T-cell receptor, CD4+ cells subtypes and functions, and the structure of the human spleen.&#x0D; &#x0D; &#x0D; Uses a new, light green background throughout the text to identify essential concepts of histology – a feature requested by both students and instructors to quickly locate which concepts are most important for beginning learners or when time is limited. These essential concepts are followed by more detailed information on cell biology and pathology.&#x0D; &#x0D; &#x0D; Contains new Primers in most chapters that provide a practical, self-contained integration of histology, cell biology, and pathology – perfect for clarifying the relationship between basic and clinical sciences.&#x0D; &#x0D; &#x0D; Identifies clinical terms throughout the text and lists all clinical boxes in the table of contents for quick reference.&#x0D; &#x0D; &#x0D; Helps students understand the links between chapter concepts with concept mapping animations on Student Consult™ – an outstanding supplement to in-class instruction.&#x0D; &#x0D; &#x0D; Student Consult™ eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, and references from the book on a variety of devices.&#x0D; &#x0D;

Comparative effectiveness of endometriosis-associated infertility therapy

Endometnosis is not a disease of individual organs and systems, but of the whole organism, the treatment of which requires complex action. The effect of all drugs used to treat endometriosis is to suppress growth factors and the development of pathological implants at different levels of the system - from the hypothalamus to target organs. The problem of restoring reproductive function in patients with endometriosis-associated infertility remains very urgent at the present time. This is due to the prevalence of this pathological process - in the structure of female infertility, endometriosis is about 50%.

Impact of dietary supplements based on L-carnitine on free-radical processes in model systems

Introduction. According to the results of numerous studies and meta-analyses, the effectiveness of male infertility therapy with micronutrients-antioxidants in various variants remains low, especially concerning the increase in live-birth rates and the incidence of clinical pregnancy. This may be due to both the empirical nature of such therapy with an imbalance of ejaculate redox systems, and an overdose of individual ingredients of antioxidant complexes.Purpose of the study. To evaluate the antioxidant activity of complex preparation based on L-carnitine for the treatment of male infertility in an experimental model system.Materials and methods. The dietary supplements «AndroDoz®» («Nizhfarm» JSC, Russian Federation) and «Proxeed® plus» (Sigma-Tau Pharmaceuticals Inc., Italy) were tested. The antioxidant properties of the preparations were determined in vitro by recording chemiluminescence in model systems generating reactive oxygen species using the «LKB-Wallac 1256 chemiluminometer» (Wallac Oy/PerkinElmer®, Finland). Chemiluminescence was evaluated by the light sum and the maximum amplitude of the glow, the antioxidant activity in the biological environment was studied when adding drugs to chicken yolk lipids similar to blood lipoprotein complexes.Results. The introduction of «AndroDoz®» and «Proxeed® plus» into the incubation medium in an amount comparable to the physiological level of L-carnitine in seminal plasma, inhibited the luminescence of the model system. At the same time, if «Proxeed® plus» almost completely inhibited the formation of radicals, then an equivalent dose of «AndroDoz®» reduced the intensity of chemiluminescence by 60%. Approximately in the same proportions, the preparations suppressed the intensity of lipid peroxidation processes in a model system with lipoprotein complexes similar to blood lipids, that is, the antioxidant activity was preserved in the biological environment. A decrease in the value of the chemiluminescence light sum was also found against the background of the use of these dietary supplements, which may indicate their protective effect on biological membranes, including subcellular structures of spermatozoa.Conclusion. The combined dietary supplements used in the study have a high antioxidant potential. The preparation «Proxeed® plus» can completely suppress the processes of lipoperoxidation with the possible development of a deficiency of free radicals that provide vital processes. The preparation «AndroDoz®» has a milder effect on free-radical phenomena probably due to a lower content of active ingredients and a balanced composition, which reduces the risk of complications in the form of an «antioxidant paradox» or reductive stress.

Endocrinopathies and Male Infertility.

Male infertility is approaching a concerning prevalence worldwide, and inflicts various impacts on the affected couple. The hormonal assessment is a vital component of male fertility evaluation as endocrine disorders are markedly reversible causatives of male infertility. Precise hormonal regulations are prerequisites to maintain normal male fertility parameters. The core male reproductive event, spermatogenesis, entails adequate testosterone concentration, which is produced via steroidogenesis in the Leydig cells. Physiological levels of both the gonadotropins are needed to achieve normal testicular functions. The hypothalamus-derived gonadotropin-releasing hormone (GnRH) is considered the supreme inducer of the gonadotropins and thereby the subsequent endocrine reproductive events. This hypothalamic–pituitary–gonadal (HPG) axis may be modulated by the thyroidal or adrenal axis and numerous other reproductive and nonreproductive hormones. Disruption of this fine hormonal balance and their crosstalk leads to a spectrum of endocrinopathies, inducing subfertility or infertility in men. This review article will discuss the most essential endocrinopathies associated with male factor infertility to aid precise understanding of the endocrine disruptions-mediated male infertility to encourage further research to reveal the detailed etiology of male infertility and perhaps to develop more customized therapies for endocrinopathy-induced male infertility.

Antioxidant therapy of male infertility in patients with varicocele

BACKGROUND: The study of the relationship between the presence of varicocele and male infertility is the subject of numerous studies, while many aspects of impaired spermatogenesis remain unclear. It has been established that after surgical treatment of varicocele, fertility is not restored in a significant number of patients. In this regard, the search for new and pathogenetically substantiated methods of treating such patients seems to be very relevant.&#x0D; AIM: To evaluate the effectiveness of antioxidant therapy in spermatogenesis disorders in men with varicocele, prescribed both in combination with surgery and as monotherapy.&#x0D; MATERIALS AND METHODS: Three groups of infertile men with varicocele were observed, who were treated with Speroton (a complex containing folic acid, L-carnitine, zinc, selenium, vitamin E) 1 sachet once a day, the duration of the course was three months. Patients of the first group (n = 43) were prescribed the drug after the Ivanissevich operation, the patients of the second group (n = 37) received antioxidant therapy during three months before the Ivanissevich operation and continued for three months after it. Patients of the third group (n = 21) did not undergo surgery, but received only antioxidant therapy for six months. The results of the combined treatment and conservative therapy with Speroton were compared with the results of treatment of 65 infertile patients who underwent only Ivanissevichs operation.&#x0D; RESULTS: In patients with varicocele with initially pathological parameters of ejaculate, who were prescribed drugs with antioxidant properties in the postoperative period as an adjuvant treatment for 3 months, in 76.7% of cases there was a change in spermogram indicators towards improvement. The most significant changes were observed six months after the operation and subsequent adjuvant therapy. The indicators characterizing sperm motility underwent more noticeable changes. In patients who received only antioxidant therapy for six months, in all cases, there was a statistically significant (p 0.001) improvement in sperm motility, which persisted for six months and exceeded these changes in groups of patients with adjuvant therapy and neo- and adjuvant therapy.&#x0D; CONCLUSIONS: The results obtained allow us to conclude that there is no need for surgical treatment for varicocele in order to treat male infertility, since the operation itself can negatively affect the state of spermatogenesis, and conservative antioxidant therapy leads to better results in infertility treatment than the performed operation or any combination of it with antioxidant therapy.

Redox Regulation to Modulate Phosphorylation Events in Human Spermatozoa.

Significance: Spermatozoa are complex and compartmentalized cells that undergo capacitation, a series of biochemical and morphological changes to acquire the ability to fertilize oocytes. Reactive oxygen species (ROS) have a prominent dual role in capacitation. At physiological levels, ROS regulate numerous cellular processes, including increases of cyclic adenosine monophosphate, calcium, and activation of phosphorylation events needed for capacitation. On the contrary, at high concentrations that do not impair sperm viability, ROS can cause loss of motility and inhibition of capacitation. Higher ROS concentrations promote oxidation of lipids, proteins, and DNA leading to cell death, and these damages have been associated with male infertility. Critical Issues: When incubated under specific conditions, spermatozoa can produce low and controlled amounts of ROS that are not harmful but instead regulate numerous cellular processes, including the phosphorylation of tyrosine, serine, and threonine residues in critical proteins needed for sperm capacitation. Here, we outline the complex redox signaling in human spermatozoa needed to achieve fertility and the role of ROS as physiological mediators that trigger phosphorylation cascades. Moreover, we illustrate the importance of various phosphoproteins in spermatozoa capacitation, viability, and hyperactive motility. Future Directions: Further studies to elucidate the different phosphorylation players during sperm capacitation and acrosome reaction (the regulated exocytotic event that releases proteolytic enzymes allowing the spermatozoon to penetrate the zona pellucida and fertilize the oocyte) are essential to understand how the spermatozoon acquires the fertilizing ability to fertilize the oocyte. This knowledge will serve to develop novel diagnostic tools and therapy for male infertility. Antioxid. Redox Signal. 37, 437-450.

Making More Womb: Clinical Perspectives Supporting the Development and Utilization of Mesenchymal Stem Cell Therapy for Endometrial Regeneration and Infertility.

The uterus is a homeostatic organ, unwavering in the setting of monthly endometrial turnover, placental invasion, and parturition. In response to ovarian steroid hormones, the endometrium autologously prepares for embryo implantation and in its absence will shed and regenerate. Dysfunctional endometrial repair and regeneration may present clinically with infertility and abnormal menses. Asherman’s syndrome is characterized by intrauterine adhesions and atrophic endometrium, which often impacts fertility. Clinical management of infertility associated with abnormal endometrium represents a significant challenge. Endometrial mesenchymal stem cells (MSC) occupy a perivascular niche and contain regenerative and immunomodulatory properties. Given these characteristics, mesenchymal stem cells of endometrial and non-endometrial origin (bone marrow, adipose, placental) have been investigated for therapeutic purposes. Local administration of human MSC in animal models of endometrial injury reduces collagen deposition, improves angiogenesis, decreases inflammation, and improves fertility. Small clinical studies of autologous MSC administration in infertile women with Asherman’s Syndrome suggested their potential to restore endometrial function as evidenced by increased endometrial thickness, decreased adhesions, and fertility. The objective of this review is to highlight translational and clinical studies investigating the use of MSC for endometrial dysfunction and infertility and to summarize the current state of the art in this promising area.

Hypoxia: Role of SIRT1 and the protective effect of resveratrol in ovarian function.

BackgroundOvarian function is closely related to the degree of vascular network development surrounding the ovary. Maternal aging‐related construction defects in this vascular network can cause ovarian hypoxia, which impedes oocyte nutrient supply, leading to physiological changes in the ovaries and oocytes. The anti‐aging gene Sirtuin 1 (SIRT1) senses and adapts to ambient stress and is associated with hypoxic environments and mitochondrial biogenesis.MethodsThe present study is a literature review focusing on investigations involving the changes in SIRT1 and mitochondrial expression during hypoxia and the cytoprotective effects of the SIRT1 activator, resveratrol.Main findingsHypoxia suppresses SIRT1 and mitochondrial expression. Resveratrol can reverse the hypoxia‐induced decrease in mitochondrial and SIRT1 activity. Resveratrol suppresses the production of hypoxia‐inducible factor‐1α and vascular endothelial growth factor proteins.ConclusionResveratrol exhibits protective activity against hypoxic stress and may prevent hypoxia‐ or aging‐related mitochondrial dysfunction. Resveratrol treatment may be a potential option for infertility therapy.

Effect of acupuncture for diminished ovarian reserve: study protocol for a randomized controlled trial

BackgroundDiminished ovarian reserve (DOR) is a condition in which the ovary loses its normal reproductive potential, compromising fertility. Although the prevalence and incidence of DOR is increasing, there are currently no effective treatments for this condition. Acupuncture has been reported as an alternative therapy for female infertility. The purpose of this study is to investigate the effect of acupuncture for women with DOR.Methods/designIn this randomized controlled trial, a total of 120 women with DOR will be randomly assigned to receive either acupuncture or sham acupuncture for 12 weeks. The primary outcome will be determined by the mean change from baseline in the antral follicle count (AFC) at week 12. Secondary outcomes include serum levels of FSH, LH, E2, and AMH, the length of menstrual cycle, and the score of Self-Rating Anxiety Scale (SAS).DiscussionThis study is expected to investigate the effectiveness of acupuncture versus sham acupuncture in improving ovarian reserve for women with DOR.Trial registrationAcupuncture-Moxibustion Clinical Trial Registry ChiCTR1800014988. Registered on 6 February 2018