Infertility Therapy Research Articles

EXPRESS: Effectiveness of stem cells therapy for male infertility restoration: a systematic review.

Cell therapy has emerged as a prominent leader in regenerative medicine, offering potential solutions for various disorders, including infertility. The half of all infertility cases are related to male factors. The objective of this study is to systematically summarize the existing knowledge regarding studies on stem cell-based therapy for the regeneration of impaired spermatogenesis. Initial searching was performed through main databases (e.g., PubMed, Scopus, Cochrane Library, Embase) until December 2023. Articles conducted on stem cell transplantation into the testis of infertile models were considered. The titles and abstracts of articles were carefully evaluated and screened by independent authors. Non-related articles were deleted. The desired outcomes about infertility treatment after stem cell transplantation were attentively evaluated in the final selected articles. In the primary search, 3237 published studies were identified. Finally, 39 studies were included based on the eligibility criteria. In all studies except for two articles, all the outcomes considered, including germ cells/spermatogonia stem cell differentiation, spermatogenesis restoration, defective testicular tissue regeneration, improved sperm quality parameters and hormonal levels, as well as increased expression of fertility-related markers and fertility rate, were observed after stem cell transplantation. Transplantation of stem cells, especially MSCs could be a safe and effective method for the treatment of male infertility patients, such as azoospermic cases. Further research to investigate the efficiency of different stem cells sources, providing nutrient conditions for the isolation and differentiation of stem cells, and exploring the paracrine effects of MSCs in male infertility therapy, could be useful.

Mesenchymal stem cells and mesenchymal stem cell-derived exosomes: attractive therapeutic approaches for female reproductive dysfunction.

Infertility is a reproductive health problem in the male or female reproductive system. Traditional assisted reproductive technology (ART) has been unable to solve various cases of infertility for years. Clinical researchers have sought to treat infertility using new methods that are more effective and noninvasive than the old methods. Recently, Mesenchymal stem cells (MSCs) and MSCs-derived Exosomes (MSC-Exos) via paracrine activity play an important role in treating various causes of infertility and improving pregnancy outcomes. In this review, we focus on the roles of MSCs and MSC-Exos cell therapy in female infertility in the different types of female reproductive disorders.

Chronic inflammation drives epididymal tertiary lymphoid structure formation and autoimmune fertility disorders.

Understanding the epididymal immune cell landscape dynamics aids in developing targeted therapies for infertility and contraception.

Inherited infertility: Mapping loci associated with impaired female reproduction

Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 control individuals from the Finnish population cohort FinnGen, we unveil a landscape of genetic factors associated with the disorder. Our recessive analysis identified a low-frequency stop-gained mutation in TATA-box binding protein-like 2 (TBPL2; c.895A>T [p.Arg299Ter]; minor-allele frequency [MAF]= 1.2%) with an impact comparable to highly penetrant monogenic mutations (odds ratio [OR]= 650, p= 4.1×10-25). While previous studies have linked the orthologous gene to anovulation and sterility in knockout mice, the severe consequence of the p.Arg299Ter variant was evidenced by individuals carrying two copies of that variant having significantly fewer offspring (average of 0.16) compared to women belonging to the other genotype groups (average of 1.75 offspring, p= 1.4×10-15). Notably, all homozygous women who had given birth had received infertility therapy. Moreover, our age-stratified analyses identified three additional genome-wide significant loci. Two loci were associated with early-onset infertility (diagnosed before age 30), located near CHEK2 and within the major histocompatibility complex (MHC) region. The third locus, associated with late-onset infertility, had its lead SNP located in an intron of a long non-coding RNA (lncRNA) gene. Taken together, our data highlight the significance of rare recessive alleles in shaping female infertility risk. The results further provide evidence supporting specific age-dependent mechanisms underlying this complex disorder.

12404 Infertility Therapy Costs for Women Following Hysteroscopic Adhesiolysis (HA) Compared to Those With No and Other Previous Uterine Surgery

12404 Infertility Therapy Costs for Women Following Hysteroscopic Adhesiolysis (HA) Compared to Those With No and Other Previous Uterine Surgery

Pharmacological therapies for male infertility.

Male factor infertility is a multifaceted problem that affects approximately 50% of couples suffering from infertility. Causes of male infertility include endocrine disturbances, gonadotoxins, genetic abnormalities, varicocele, malignancies, infections, congenital or acquired urogenital abnormalities, iatrogenic factors, immunological factors, and idiopathic reasons. There are a variety of treatment options for male infertility, depending on the underlying cause(s). These can include surgical treatments, medical/hormonal therapies, and assisted reproductive techniques (ART), which can be combined with surgical sperm retrieval (SSR) if necessary. In this review article, the pharmacological therapies for male infertility are grouped by their underlying causes. Some of these therapies are targeted and specific, while others are used empirically to treat idiopathic male infertility. This will include treatments to optimize infertility in patients who have hypogonadism, ejaculatory dysfunction, infections, or idiopathic male infertility. Finally, we will provide an overview of the future directions of pharmacological therapies for male infertility. Significance Statement Male infertility is a significant worldwide problem. Detailed knowledge of the pharmacological therapies available will ensure the prescription of appropriate therapy and avoid the use of unnecessary or harmful treatments.

Medical therapy for male infertility.

To provide up-to-date evidence and clinical guidance on the role of medical therapy in the context of hormonal imbalances affecting human spermatogenesis. Compelling evidence has accumulated over the years regarding the role of gonadotropins, selective estrogen modulators, and aromatase inhibitors to either improve or restore spermatogenesis in men with hormonal abnormalities (e.g. hypogonadotropic/hypergonadotropic hypogonadism, hyperprolactinemia) or supraphysiologic levels (e.g. exogenous testosterone/anabolic steroid use). Despite the increasing number of studies being performed, most of the available evidence relies on small nonrandomized studies, mainly in men with hypergonadotropic hypogonadism or with history of exogenous testosterone/anabolic steroid use. As such, the efficacy of medical therapy is highly variable emphasizing the necessity of randomized clinical trials and individualized approaches. This narrative review provides clinical guidance on medical therapies for male factor infertility based on the most up-to-date evidence, focusing on treatments for hormonal abnormalities (either hypogonadotropic or hypergonadotropic hypogonadism and hyperprolactinemia) and supraphysiologic levels (and exogenous testosterone/anabolic steroid use) to improve spermatogenesis.

An evaluation of couples undergoing intrauterine insemination at the BioART Fertility Centre, Johannesburg

Objective: To describe couples who underwent intrauterine insemination (IUI) and determine predictors of successful IUI in low and middle-income countries. Background: Assisted reproductive technology is still largely unavailable or inaccessible in most low and middle-income countries. IUI, which consists of the deposition of processed sperm from the partner or donor into the cavity of the uterus around ovulation time, is one of the oldest methods used and is still widely practiced to this day. Methods: A retrospective descriptive study was done at the BioArt Fertility Centre from January 2019 to June 2021. In total, 451 IUI cycles were analyzed in 273 couples. The main outcome measure was a clinical pregnancy on transvaginal ultrasound 4 weeks post-IUI. Multivariate logistic regression was done to find predictors of successful IUI. Results: The mean male age was 37.15 years (SD ± 5.16), with most male participants having a processed total motile sperm count (PTMSC) of >39×106/mL. The mean female age was 33.51 years (SD ± 4.83). The main etiology of infertility was ovulatory dysfunction (37.7%). The clinical pregnancy rate and the live birth rate per cycle were 12.4% and 11.9%, respectively, for a cumulative pregnancy rate of 21.6% for couples that underwent 3 cycles. The PTMSC, female age, duration of infertility, and follicle size were directly correlated with an increased pregnancy rate (P < 0.05). Conclusion: IUI is an effective choice of therapy for infertility in selected couples, achieving acceptable pregnancy rates for up to 3 treatment cycles, especially in females <40 years with <5 years duration of infertility, and in males with a PTMSC of >39×106/mL.

Relationship Between Anti-Mullerian Hormone (AMH) and Other Influencing Factors with in Vitro Fertilization (IVF) Outcome of Iraqi Infertile Women

The clinical application of Anti-Mullerian Hormone (AMH) measurement has been proposed in the prediction of qualitative and quantitative aspects of assisted reproductive technologies (ART). The aim of this study is to investigate the role of AMH level and other influencing factors in the outcomes of in vitro fertilization (IVF) treatment. The study focused on AMH and its association with infertile women undergoing IVF. The population included in this study was 131 infertile women who sought therapy for infertility at Kamal Al-Samarra'ay Specialized Hospital. They were divided into three groups according to the level of AMH hormone; group A (0.5-1.5 ng/mL, n=52), group B (1.6-4 ng/mL, n=70), and group C (> 4 ng/mL, n=9). Data collection was performed by means of a specially designed questionnaire, independent of demographic data. It included questions related to infertility. Statistical analysis was performed with SPSS 26. Clinical parameters of infertile women, infertility hormones and their relationship with AMH, as well as FMS-like Tyrosine kinase 1 levels, were all investigated. The study findings revealed a significant difference in the concentration of AMH between infertile women (p<0.01). Our analysis further demonstrated that the level of AMH reduces with advancing age in infertile women. Additionally, a positive correlation was observed between the number of oocytes obtained and AMH levels in infertile women. Furthermore, the study found that AMH levels had an effect on clinical pregnancy outcomes. Specifically, the highest success rates for IVF were observed in women with normal AMH levels falling within the ranges of group B (6-4 ng/mL(. Additionally, the study demonstrated significant differences in AMH and TSH levels among infertile groups (p<0.05). Our study concluded that there is a significant correlation between clinical parameters and IVF outcomes, which can provide information for future clinical interventions aimed at improving success rates. Our analysis highlighted the role of FMS-like Tyrosine kinase 1 in infertility, where higher FMS-like Tyrosine kinase 1 levels were associated with higher success rates in IVF. The results indicate that the FMS-like Tyrosine kinase 1 level is a valuable marker for confirming the success or failure of IVF and can help determine the appropriate treatment plan.

The morphological structure of prostate gland under the condition of experimental prostatopathy and after using of cholecalciferol in the different schemes of hypofertility correction

The impact of negative factors, stress, and modern living conditions damages men's health and leads to infertility. Prostatitis is often a cause of hypofertility. It is now shown that vitamin D may play a role in regulating the functioning of reproductive system organs. The aim of the study was to determine the effect of cholecalciferol on the histological structure of the prostate gland in rats with experimental prostatitis and after its application alone or in combination with a prostate protector. Experimental prostatitis was induced by cold intraoperative damage to the prostate gland. To correct prostatitis, vitamin D3 (cholecalciferol) was administered orally at a dose of 4000 IU. The prostate protector (Prostatilen, Pr) and its pharmaceutical composition, as well as vitamin D3, were administered rectally. Rats with modeled prostatitis were divided into groups: EP (cold experimental prostatitis without treatment); EP + seed oil (on the background of experimental prostatitis, animals received a solvent – apricot kernel oil); EP + vit D3 (per os) (on the background of experimental prostatitis, animals received vitamin D3); EP + Pr (rec) (on the background of experimental prostatitis, males were administered Prostatilen per rectum); EP + vit. D3 (per os) + Pr (rec) (on the background of experimental prostatitis, animals received vitamin D3 (per os) and Prostatilen gel (per rectum)); EP + (vit. D3 + Pr) (rec) (on the background of experimental prostatitis, rats were administered Prostatilen gel with vitamin D3 per rectum). Intact animals (Intact group) and sham-operated rats (Control group) were used as controls. Paraffin sections of the prostate gland were stained with hematoxylin, eosin, and Van Gieson's method. In addition to the review microscopy of the ventral lobes of the prostate gland and the isthmus between them, the power of histochemical reactions was measured, the severity of inflammation and fibrosis was assessed, the number of terminal sections of the prostatic glands with a visually unchanged state, with lumen expansion, and with wall destruction was counted, the longitudinal diameter of the acini and the height of the epithelial cells of the prostatic glands were measured. Statistical analysis of the results was performed using the standard software package "Statistica 6.0" with the use of Student's t-test and nonparametric analog of one-way analysis of variance – Kruskal-Wallis test, as well as Mann-Whitney test. It was found that rats with experimental prostatitis exhibit pronounced changes in the morphological structure of the prostate gland. The prostate-protective effect of vitamin D per os at a dose of 4000 IU was established, which reduced the manifestations of atrophic and destructive processes, signs of tissue inflammation, and coarsening of the prostate gland stroma. Signs of fibrosis development in the prostate gland in males of this group were reduced, and the number of destructive changes and the longitudinal diameter of the terminal sections of the prostatic glands of prostate ventral lobe in rats with experimental prostatitis were decreased. Thus, the addition of cholecalciferol to the basic therapy for infertility has a more pronounced corrective effect on the morphological structure of the prostate than the separate use of cholecalciferol and the prostate protector. Combining basic therapy with vitamin D enhances the prostate-protective properties of the latter and is promising for restoring reproductive function overall.

A century of andrology in Cell & Tissue Research: looking back while moving forward.

This article commemorates the 100th anniversary of the first issue of Cell & Tissue Research (CTR), the longest-running active journal dedicated to cell biology. Reflecting the significant contributions of spermatology and embryology to the early days of cell biology, the majority of articles in CTR's inaugural issue centered on plant and animal sperm cells. A brief synopsis of these articles provides a launching point for revisiting 100years of research on the male germ cells and fertility in humans and animals and offers a perspective on the current state and future directions of the andrology field. Early technological advances in light and electron microscopy enabled descriptive studies that ushered in the era of mechanistic, biochemistry-based inquiry focused on the understanding of physiological sperm processes such as sperm capacitation, acrosomal exocytosis, and sperm-egg interactions. In the last 20years, progress in flow cytometry, cell imaging, and omics revealed new information on sperm proteome, transcriptome, metabolome, and overall phenome of fertile and infertile spermatozoa. Going back to the journal's roots, recent advances in male germ cell isolation, transplantation, modification, and cryopreservation have been discussed on the pages of CTR. Newest trends such as gene editing and artificial intelligence/machine learning are now making inroads into andrological inquiry and assisted reproductive therapy of male infertility.

Qualitative and Quantitative Tests on the Ingredients of Mahkota Dewa (Phaleria macrocarpa) Fruit Extract as an Alternative Therapy for Infertility in Endometriosis

Endometriosis is a gynecological disease with complaints of pain, infertility, or both, up to 35-50%. The fruit extract of Mahkota Dewa (Phaleria macrocarpa) contains antioxidants and anti-inflammatories, has anticancer prospects and is expected to have ingredients as an alternative therapy for treating infertility in endometriosis. To conduct qualitative and quantitative tests on the content of Phaleria macrocarpa fruit extract, which is expected to contain substances that act as an alternative to infertility therapy in endometriosis. Mahkota Dewa (Phaleria macrocarpa) was ripened, and its seeds were extracted using 95% ethanol twice. The results of extracts 1 and 2 were combined and then examined by Thin Layer Chromatography (TLC). The research was conducted at the Pharmacognosy-Phytochemical Laboratory, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia. Qualitative test showed that 95% ethanol extract of Phaleria macrocarpa fruit contains flavonoids, alkaloids, terpenoids, and steroids. Quantitative test using Thin Layer Chromatography (TLC) method obtained a flavonoid content of 131.51-189.89µg/ml, equivalent to quercetin, in 6 repetitions, with a wavelength of 510 nm. Phaleria macrocarpa fruit contained flavonoids, alkaloids, terpenoids and steroids. The level of steroids contained in the fruit extract of Mahkota Dewa (Phaleria macrocarpa) had not been obtained in this study.

Gene regulation and signaling transduction in mediating the self-renewal, differentiation, and apoptosis of spermatogonial stem cells.

Infertility has become one of the most serious diseases worldwide, and 50% of this disease can be attributed to male-related factors. Spermatogenesis, by definition, is a complex process by which spermatogonial stem cells (SSCs) self-renew to maintain stem cell population within the testes and differentiate into mature spermatids. It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility. Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs. In this review, we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal, differentiation, and apoptosis of SSCs, and we illustrate the networks of genes and signaling pathways in SSC fate determinations. We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways. This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.

Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies.

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.

Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach

To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality. Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013-2017). A target trial emulation framework was applied to estimate associations. Couples were observed for 9 months or through pregnancy. Clinics that provide reproductive endocrinology and infertility care in the US. Couples seeking infertility treatment. Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D. Live birth and pregnancy loss were ascertained via self-report and medical records. Semen quality was ascertained 6 months after enrollment. Log-binomial regression estimated risk ratios and 95% confidence intervals (CIs). Individual and joint models and effect measure modification by preconception body mass index were considered. Among 2,370 couples, 19.5% of females and 29.9% of males were 25(OH)D deficient. Females with sufficient status had a 28%-higher likelihood of LB than deficient females (95% CI, 1.05-1.56). Female and male 25(OH)D status were associated with LB among those with normal body mass index (sufficient vs. deficient: female adjusted risk ratio [aRR], 1.39; 95% CI, 1.00-1.99; male aRR, 1.51; 95% CI, 1.01-2.25) and among obese female partners (sufficient vs. deficient: aRR, 1.33; 95% CI, 0.95-1.85). Couples whose both partners had higher 25(OH)D status had increased likelihood of LB (both not deficient vs. both deficient aRR, 1.26; 95% CI, 1.00-1.58). No associations were observed with pregnancy loss or semen quality. Similar results were found for all biomarkers except calcium. Preconception vitamin D status and bioavailability impact fertility among couples seeking infertility therapy, likely unrelated to semen quality. Body mass index stratified analyses demonstrated heterogeneous associations. NCT01857310.

FSH Therapy in Male Factor Infertility: Evidence and Factors Which Might Predict the Response.

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10-18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men.

The impact of IVF patients' characteristics on their satisfaction and quality-of-life with overseas treatment: A mixed methods approach.

Recent advances in infertility therapy, such as hormone medication and in vitro fertilization (IVF), have led to an increase in the demand for IVF. North Cyprus is a new medical tourist destination, and this study aimed to discover influential demographic predictors of IVF patients' satisfaction and quality-of-life (QoL) after receiving reproductive IVF services. Two questionnaires on IVF patient satisfaction and QoL were administered to 101 patients who received services in selected IVF clinics. Parametric and nonparametric tests were used for statistical analysis. The results showed that the mean satisfaction level with IVF service introduction and doctor professionalism increased with age, and a maximum satisfaction level was found in older patients. Doctor professionalism was another significant factor for greater satisfaction in older patients than in young patients who underwent IVF treatment. Satisfaction with IVF services was reduced by increasing education levels. IVF services must be managed and provided based on the needs of patients from different demographic backgrounds and efforts must be made to improve satisfaction with fertility services.

P-401 Aging affects endometrial receptivity factors. Can DHEA modulate this age-related effect?

Abstract Study question Identification of age-related gene expression differences of the human endometrium during its receptive period – Dehydroepiandrosterone (DHEA) effects. Summary answer Decrease in expression of OPN and HOXA10, receptivity markers, between increasing female age groups in primary human endometrial cells was presented. DHEA altered gene expression. What is known already The increased infertility noted in the world population, has been related to increasing maternal age. Our previous work points out the role of women’s age in endometrial cell function. Endometrial proliferation and differentiation are two important steps that lead to increased cell receptivity during the window of implantation. Optimal receptivity is achieved also through changes inexpression of several factors throughout the endometrial cycle. It is well known that androgen levels, in the female reproductive system, decrease with increasing age.Therefore, DHEA an androgen precursor, found to be reduced with age is thought to be a candidate for infertility treatment. Study design, size, duration Maternal age has not been previously directly correlated with endometrial receptivity factors. We studied 39 endometrial samples divided in three different women’s age groups (25-35 years, 36-40 years and 41-46years) and changes in the mRNA and protein expression of osteopontin (OPN), CD44 and HOXA10 in human endometrium stromal cells were analyzed, in vitro. DHEA was added on stromal cells (decidualized or not) in order to observe changes in mRNA expression. Participants/materials, setting, methods Pipelle endometrial biopsies (secretory phase) were collected from ovulating, fertile, Caucasian women volunteers aged 25–46 years. Stromal cells were isolated. These samples were divided into three age groups: 25-35 years, 36-40 years and 41-46 years. Protein and mRNA expression of receptivity modulators OPN, CD44 and HOXA10 were analyzed using Real-time PCR and Western blot analysis, respectively. Stromal cells were decidualized in vitrousing bromo-8-cAMP in order to observe DHEA effects. Main results and the role of chance Data presented showed a statistically significant decrease (p ≤ 0.05) in OPN expression levels with increasing age groups. Women included in age group of 41-45y presented a significant downregulation of OPN expression compared to younger age group 25-35y (p ≤ 0.01).CD44 expressiondid not differ with age. Furthermore, a statistically significant decrease (p ≤ 0.05) was evident in HOXA10 expression levels with increasing age. Women belonging to the age group 41-45y expression presented with significant HOXA10 downregulation compared to younger age group 25-35y (p ≤ 0.05). Analysis of OPN protein levels showed that cell-extracted OPN decreased from theage of 33y, while the secreted protein gradually decreased from the age of 38y. CD44 protein expression, similarly to the mRNA expression did not show differences with age. HOXA10 protein expression was found to be decreased mainly after the age of41y. DHEA changed, with statistical significance, the expression of decidualization marker IGFBP and OPN in decidualized stromal cells. Overall, our results support our hypothesis as expected, but we must also consider specific cases where older women have the same results as younger ones and the opposite, so factors that are specific for each individual must be further investigated. Limitations, reasons for caution It must be pointed out that there is a plethora of characterized molecules like cytokines and immune cells that also participate in the optimal receptivity status of the endometrium – leading to a successful implantation procedure – that future studies need to examine, as well, in relation to women’s age. Wider implications of the findings Human endometrial aging can affect embryo receptivity markers and therefore, receptivity. Further investigation of receptivity factors that change with the age could be a useful pool in identifying targets for diagnosis and therapy of human implantation failure. Also, DHEA must be further investigated as a tool for infertility therapy. Trial registration number not applicable

O-242 Why do we need to act NOW?

Abstract In the early 1970s, the Report of Rome represented a powerful wake up call to the world. If the world population would continue to grow the way it did until then, catastrophe was predicted and the future of the planet would be in danger. All attempts should focus on decreasing world population growth. At that time the global total fertility rate (the number of children born per woman) was around 5. Policies were implemented worldwide aiming to reduce the number of children born, and the widespread introduction – at least in the more developed world - of various contraceptive strategies in the 1970s certainly helped to reach this goal. Especially in Western societies, the liberation in women (increased participation in higher education, more focus on work and career, and control over when to start a family if at all) was significantly enhanced, dramatically reducing the number of children born. In this context, it is no surprise that organizations like the European Union or the World Health Organization gave very low priority to fertility care, which would potentially increase the number of children born. For a population to remain stable, approximately 2.1 child needs to be born per woman. At present, in more than 50% of all countries worldwide – mainly the more prosperous ones – the number of children born is below replacement level. It is anticipated that societies below replacement will increase up to 90% of all countries worldwide during the 21th century. Hence, underpopulation - causing distinct society challenges - rapidly becomes of distinct concern to many governments, especially in European countries, China, and Japan. It is a generally recognized human right, in case individuals or couples wish to establish a family. However, historically little attention has been dedicated by policy makers to fertility care, mainly because the justified concerns for overpopulation. However, the incidence of infertility remains around 15% worldwide and treatment options have significantly improved. In addition, demand for fertility care is increasing year by year, especially by single individuals, lesbian or gay couples and other members from the LGBTQ+ community who wish to establish a family. At present, at least 10% of all children born are due to infertility therapies in some wealthy countries. However, access to fertility care varies dramatically due to high cost of treatment and lack of insurance coverage of such treatments in the great majority of countries. At present, governments increasingly introduce so called “child friendly” policies (such as financial compensations, extended pregnancy and parental leave, free child care, tax benefits, etc), aiming to decrease barriers for people who wish to have children. Unfortunately, improved access to fertility care is not yet part of this discussion. Over half a century, family planning strategies exclusively focused on the prevention of unwanted pregnancies aiming to reduce world population growth. However, at present family building strategies (helping people who wish to establish a family) should also be included in future family planning strategies.

Uterus Transplantation: the Translational Evolution of a Clinical Breakthrough.

Women suffering from absolute uterine factor infertility (AUFI), due to either lack of a uterus or one unable to sustain neonatal viability, presented as one of the last frontiers in conquering infertility. Following systematic animal research for over a decade, uterus transplantation was tested as a treatment for AUFI in 2012, which culminated in the first human live birth in 2014. The development of uterus transplantation from mouse to human has followed both the Moore criteria for introduction of a surgical innovation and the IDEAL concept for evaluation of a novel major surgical procedure. In this article we review the important preclinical animal and human studies that paved the way for the successful introduction of human uterus transplantation a decade ago. We discuss this in the context of the Moore criteria and describe the different procedures of preparation, surgeries, postoperative monitoring, and use of assisted reproduction in human uterus transplantation. We review the worldwide activities and associated results in the context of the IDEAL concept for evaluation of surgical innovation and appraise the ethical considerations relevant to uterus transplantation. We conclude that rigorous application of the Moore criteria and strict alignment with the IDEAL concept have resulted in the establishment of uterus transplantation as a novel, safe, and effective infertility therapy that is now being used worldwide for the treatment of women suffering from AUFI.