The Roles of GDF-9, BMP-15, BMP-4 and EMMPRIN in Folliculogenesis and In Vitro Fertilization.

Growth differentiation factor 9 (GDF-9) contributes to early ovarian development and oocyte survival. Higher concentrations of GDF-9 in follicular fluid (FF) are associated with oocyte nuclear maturation and optimal embryo development. In in vitro fertilization (IVF), GDF-9 affects the ability of the oocyte to fertilize and subsequent embryonic development. Bone morphogenetic protein 15 (BMP-15) is involved in the regulation of ovarian function and affects oocyte development. During IVF, BMP-15 contributes to the formation of competent blastocysts. BMP-15 may play a role in embryo implantation by affecting endometrial receptivity. Bone morphogenetic protein 4 (BMP-4) is involved in the regulation of follicle growth and development and affects granulosa cell (GC) differentiation. In relation to IVF, BMP-4 is important for embryonic development, influences cell fate and differentiation, and plays a role in facilitating embryo-endometrial interactions during the implantation process. Extracellular matrix metalloproteinase inducer (EMMPRIN) is associated with ovulation and follicle rupture, promotes the release of mature eggs, and affects the modification of the extracellular matrix of the follicular environment. In IVF, EMMPRIN is involved in embryo implantation by modulating the adhesive properties of endometrial cells and promotes trophoblastic invasion, which is essential for pregnancy to occur. The purpose of the current article is to review the studies and recent findings of GDF-9, BMP-15, BMP-4 and EMMPRIN as fundamental factors in normal follicular development and in vitro fertilization.

Understanding the Role of Female Genital Tract Microbiome in Recurrent Implantation Failure.

The realization of the role of the microbiome of the female reproductive tract in health and disease has opened numerous possibilities for the scientific examination of the intertwining role between the human host and its microbiota. The imbalance in the composition of the microbial communities of the vagina and uterus is now recognized as a risk factor for many complications in pregnancy and according to the data from numerous studies, it is possible for this imbalance to play a crucial role in creating a hostile endometrial environment, and therefore, contributing to the etiology of recurrent implantation failure. Nevertheless, our current understanding of these complicated biological phenomena is far from complete, and in the future, there needs to be a systematic and thorough investigation of the diagnosis and therapy of this condition. This will enable scientists who engage in the field of assisted reproduction technologies to accurately identify and cure women in whom dysbiosis hinders the achievement of a healthy pregnancy.

Association of Obesity with Telomere Length in Human Sperm.

Background: Telomere attrition and mitochondrial dysfunction are two fundamental aspects of aging. Calorie restriction (CR) is the best strategy to postpone aging since it can enhance telomere attrition, boost antioxidant capacity, and lower the generation of reactive oxygen species (ROS). Since ROS is produced by mitochondria and can readily travel to cell nuclei, it is thought to be a crucial molecule for information transfer between mitochondria and cell nuclei. Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). Telomere damage results from mitochondrial failure, whereas nuclear DNA remains unaffected. This research aims to investigate potential associations between these three variables and how they might relate to body mass index. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, male participants who were categorized into three body mass index (ΒΜΙ) groups-normal, overweight, and obese-had their sperm samples tested. Results: For both the normal and overweight groups, our results show a negative connection between relative telomere length and ΒΜI. As an illustration of a potential connection between mitochondrial health and telomere maintenance, a positive correlation was found for the obese group. Only the obese group's results were statistically significant (p < 0.05). More evidence that longer telomeres are associated with lower mitochondrial content can be found in the negative connection between telomere length and mitochondrial content in both the normal and overweight groups. However, the obese group showed a positive association. The data did not reach statistical significance for any of the three groups. These associations may affect sperm quality since telomere length and mitochondrial concentration are indicators of cellular integrity and health. Moreover, the ratio of mtDNA to nDNA was positively correlated with the relative telomere lengths of the obese group, but negatively correlated with the normal and overweight groups. In every group that was studied, the results were not statistically significant. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome compared to the nuclear DNA in sperm. Conclusions: Essentially, the goal of our work is to determine whether mitochondria and telomere length in human sperm interact. Understanding these connections may aid in the explanation of some male infertility causes and possibly contribute to the creation of new treatment modalities for problems pertaining to reproductive health. The functional implications of these connections and their applications in therapeutic settings require further investigation.

Evolution of Minimally Invasive and Non-Invasive Preimplantation Genetic Testing: An Overview.

Preimplantation genetic testing (PGT) has become a common supplementary diagnοstic/testing tοol for in vitro fertilization (ΙVF) cycles due to a significant increase in cases of PGT fοr mοnogenic cοnditions (ΡGT-M) and de novο aneuplοidies (ΡGT-A) over the last ten years. This tendency is mostly attributable to the advancement and application of novel cytogenetic and molecular techniques in clinical practice that are capable of providing an efficient evaluation of the embryonic chromosomal complement and leading to better IVF/ICSI results. Although PGT is widely used, it requires invasive biopsy of the blastocyst, which may harm the embryo. Non-invasive approaches, like cell-free DNA (cfDNA) testing, have lower risks but have drawbacks in consistency and sensitivity. This review discusses new developments and opportunities in the field of preimplantation genetic testing, enhancing the overall effectiveness and accessibility of preimplantation testing in the framework of developments in genomic sequencing, bioinformatics, and the integration of artificial intelligence in the interpretation of genetic data.

Embryo Transfer Procedural Parameters Do Not Predict IVF Cycle Outcome.

BACKGROUND: this study aims to assess the effect of embryo transfer (ET) performance parameters of a technical nature on IVF outcome. METHODS: A total of 1417 ETs from a single IVF center were included in this prospective observational study. The parameters investigated were as follows: the presence of cervical mucus post catheter withdrawal, the presence of blood, catheter reload, the employment of a tenaculum and stylet, catheter resistance as experienced by the physician and patient discomfort. RESULTS: When ET performance parameters were associated with clinical outcomes on a singular level, none of the ET parameters presented with any statistical significance. The evaluation of covariates indicated that the number and the quality of transferred embryos, as well as maternal age, exerted a statistically significant effect on clinical outcomes. In a multivariate analysis, only the presence of mucus along with significant catheter resistance presented with statistical significance; however, when adjusting for covariates, this combination showed no statistically significant effect on clinical outcomes. CONCLUSIONS: the results indicate that the time-consuming process of recording and analyzing ET performance parameters fails to offer any additional value in predicting the cycle's outcome, while factors like embryo quality and number, as well as maternal age, seem to be the sole robust predictive factors of an IVF cycle.

The impact of cryopreservation on both sperm HPV-negative and positive subtypes.

It is well known that various human papillomavirus (HPV) genotypes are present in semen specimens. Also, it has been demonstrated that sperm parameters are negatively affected when HPV infection is present in the sperm sample. Besides all these, the effect of cryopreservation on HPV sensitivity and resistance is not known. The aim of the present study is to evaluate first the prevalence of HPV and secondly to elucidate whether cryopreservation of sperm HPV-positive samples has any effect on the viability of HPV. For this purpose, a cohort of 78 sperm specimens was used from a respective number of patients. After giving informed consent, semen analysis was performed. Each sperm sample was divided into four equal aliquots. The first one (fresh) was evaluated for the prevalence of HPV, while the other three aliquots were cryopreserved by adding an equal quantity of cryoprotectant and plunged into the LN. Each of the three aliquots was thawed 3, 6, and 12 months later, respectively, so as to evaluate whether there is a time-resistance period of HPV prevalence. HPV infection was found to be in eleven sperm samples, demonstrating a 14.1% (11/78) HPV prevalence. Among the HPV-positive samples, six of them were high-risk and the remaining were low-risk genotypes. Moreover, the high-risk fresh samples demonstrated higher motility values than the low-risk samples (60% ± 2.7 vs 45.6% ± 3.7, p < .05), while semen volume in the high-risk samples was significantly lower than the respective volume in the low-risk samples (2.26 ± 0.2ml vs 3.5 ± 0.6ml, p < .05). Interestingly, cryopreservation of the HPV-positive samples resulted in the sustainability and time-resistance of HPV in all high-risk HPV-positive samples, something that was not the case with the low-risk HPV-positive samples. Conclusively, sperm samples infected with high-risk HPV, demonstrate lower sperm parameters and time-resistance activity during cryopreservation.

The Effect of Socioeconomic Factors on Maternal Perinatal Depressive Symptoms and the Contribution of Group Prenatal Support as a Preventive Measure.

Background: The European and Greek financial turmoil that began in 2007 has had adverse health consequences. Stillbirth, low birth weight, infant mortality, and maternal suicide have all increased. The purpose of this study was to evaluate whether socioeconomic factors contribute to postpartum blues, and whether psychoprophylaxis with group prenatal education and support may have a beneficial effect. Materials and Methods: The sample study comprised 414 pregnant women equally divided into psychoprophylaxis or standard care. There were six psychoprophylaxis sessions, with two each week lasting 2 hours each in groups of five people at the urban health center of Larissa, Greece. A questionnaire was used for data collection, including (1) closed-type questions about sociodemographic characteristics, and medical and obstetric history; (2) the Hamilton Depression Scale; (3) a Blues Questionnaire; (4) the Holmes and Rahe stressful life events scale; and (5) a scale of effects of the economic crisis. Differences between the two groups and within the groups at different time points were assessed by two-way repeated measures ANOVA tests. Results: Maternity blues scores, depression scores at all time points, life stress event score, and financial difficulty score were all significantly related to each other in both groups at all time points (p < 0.01). The correlation between financial difficulties and depression/maternity blues disappeared after delivery in the intervention group. Financial difficulties, depression, and psychoprophylaxis sessions emerged as independent prognostic factors of maternity blues score, the group variable being most significantly associated with maternal blues. Conclusion: Although financial status as well as depression continued to play a role, the deterrent contribution of psychoprophylaxis was the most important parameter in the final maternity blues prognostic model. The results of our study show a potential for prevention and suggest interesting hypotheses for future interventions.

Smoking Patterns and Anxiety Factors Among Women Expressing Perinatal Depression.

Background: Relationships among perinatal depression occurring a number of weeks before and after childbirth and smoking have been identified. Depression may lead to the inability to abstain from smoking during pregnancy. Objectives: This study aims to determine factors affecting smoking during pregnancy revealing potential relationships between depression and smoking patterns during and after pregnancy. Methods: A total of 206 mothers participated in the study. Data were collected through self-reporting as respondents were asked to answer questionnaires during the 12th week of pregnancy, during the 30th week of pregnancy, after childbirth, and during the period after pregnancy. Relationships between smoking behavior, sociodemographic variables, and feelings of perinatal depression were examined using chi-square test and binary logistic regression analysis. A follow-up investigation has been conducted after 2 years revealing the percentage of women returning to their smoking habits. Results: Smokers before (B = 0.568; p = 0.026) and during pregnancy (B = 1.238; p = 0.009) were more likely to express depression before childbirth. Average daily cigarette consumption before (B = 1.110; p = 0.001) and during pregnancy (B = 1.167; p = 0.002) was associated with depression during pregnancy. Women who smoked during pregnancy reported significantly more depressive symptoms after pregnancy (B = 1.757; p = 0.005) compared with nonsmokers and smokers who abstained during pregnancy. Average daily cigarette consumption during pregnancy (B = 1.402; p = 0.002) affects the expression of depression after pregnancy. Women who smoked before pregnancy (B = 0.568; p = 0.025) and their average daily cigarette consumption before pregnancy (B = 1.465; p = 0.025) were highly associated with the inability to abstain from smoking during pregnancy. However, the knowledge of risks of maternal smoking during pregnancy (B = -1.110; p = 0.001) and medical consult on abstaining (B = -1.238; p = 0.009) reinforced the maternal attempt to quit smoking. The follow-up investigation revealed an elevated amount of women returning to previous smoking patterns. Discussion: Perinatal depression is associated with smoking patterns during pregnancy. Assessment of depression and smoking is needed throughout perinatal period to support the health of women.

A Randomized Controlled Trial on the Efficacy and Safety of Low-Dose hCG in a Short Protocol with GnRH Agonist and Ovarian Stimulation with Recombinant FSH (rFSH) During the Follicular Phase in Infertile Women Undergoing ART.

Τhis study aims to investigate whether the addition of low-dose hCG throughout stimulation in infertile women undergoing IVF improves IVF outcome parameters. This is a prospective, multicenter, randomized, double-blind, placebo-controlled, Phase IIIb clinical study, conducted in three university IVF units. We studied whether the addition of 100 IU hCG/day to a short GnRH agonist IVF protocol from the onset of the follicular phase (group 1, n=40) or placebo (group 2, n=41) had any impact on the number of high-quality transferred embryos at day 2 and clinical pregnancy rates. The comparison encompassed descriptive statistics, and univariate and multivariate analyses. Concerning the primary outcomes, we found no differences in both the number of high-quality embryos (≥2) at day 3 [21/40 (52.5%) vs. 14/41 (34.2%), p=0.095] and clinical pregnancy rates [10/40 (25%) vs. 10/41 (24.4%), p=0.949], respectively. Similarly, there were no differences concerning the secondary outcomes preset for this trial. According to the results of the multivariate logistic regression analysis, no significant associations were noted for primary outcomes (clinical pregnancy: adjusted OR=0.89, 95% CI: 0.29-2.75; (≥2 excellent quality embryos at day 3: adjusted OR=0.54, 95% CI: 0.21-1.42, with group 1 set as reference category); similarly, no differences were noted with respect to secondary outcomes, except from the increased odds of ≥2 poor-quality embryos at day 3 occurring in group 2 (adjusted OR= 11.69, 95%CI: 1.29-106.19). The addition of low-dose hCG to a short GnRH agonist protocol for IVF does not improve the number of top-quality embryos and clinical pregnancy rates.

Exercise for perinatal depressive symptoms: A systematic review and meta-analysis of randomized controlled trials in perinatal health services.

BACKGROUND: Exercise improves perinatal depressive (PD) symptoms, but reports call for more robust evidence. This systematic review and meta-analysis aimed at synthesizing evidence exclusively from randomized controlled trials (RCTs) examining the effects of exercise on PD symptoms in women recruited through perinatal health services. METHODS: Nine e-databases and fifteen systematic reviews were searched for relevant RCTs. Exercise-specific tools extracted/coded data. A meta-analysis using a random effects model (Standardized Mean Difference [SMD]) investigated the effects of exercise on PD scores post-intervention. RESULTS: From 285 records, 14 RCTs (2.025 participants) were considered eligible including two RCTs with clinically diagnosed PD women. Exercise showed a statistically significant, small, overall antidepressant effect (SMD = -0.21, 95% CI = -0.31, -0.11, p = 0.0001) with low/non-significant heterogeneity (Q = 17.82, I 2 = 16%, p = 0.27). Only the fail-safe criterion recorded marginally significant publication bias, but trim-fill analysis added no study. Sensitivity analyses increased the overall effect in RCTs showing lower risk of bias or delivering ≥150 min/week moderate intensity aerobic exercise. Subgroup analyses revealed significant antidepressant effects for exercise across various settings, delivery formats, depressive symptoms severities and outcome measures used. Heterogeneity was low/non-significant in all analyses (I 2 ≤ 50%). Hedges' g corrections did not influence the results. LIMITATIONS: Study limitations include the small number of available trials and clinically diagnosed PD samples and the variety of exercise modalities. CONCLUSIONS: Exercise improved PD symptoms, especially in RCTs with lower risk of bias or with ≥150 min/day moderate intensity aerobic exercise interventions. Findings are clinically useful but more RCTs for clinically diagnosed PD women are needed for firmer conclusions.

Why Has Metabolomics So Far Not Managed to Efficiently Contribute to the Improvement of Assisted Reproduction Outcomes? The Answer through a Review of the Best Available Current Evidence.

Metabolomics emerged to give clinicians the necessary information on the competence, in terms of physiology and function, of gametes, embryos, and the endometrium towards a targeted infertility treatment, namely, assisted reproduction techniques (ART). Our minireview aims to investigate the current status of the use of metabolomics in assisted reproduction, the potential flaws in its use, and to propose specific solutions towards the improvement of ART outcomes through the use of the intervention. We used published reports assessing the role of metabolomic investigation of the endometrium, oocytes, and embryos in improving clinical outcomes in women undergoing ART. We initially found that there is no evidence to support that fertility outcomes can be improved through metabolomics profiling. In contrast, it may be helpful for understanding and appraising the nutritional environment of oocytes and embryos. The causes include the different infertility populations, the difference between animals and humans, technical limitations, and the great heterogeneity in the variables employed. Suggested steps include the standardization of variables of the method itself, the universal creation of a panel where all biomarkers are stored concerning specific infertile populations with different phenotypes or etiologies, specific bioinformatics contribution, significant computing power for data processing, and importantly, properly conducted trials.

Effect of adiponectin on estradiol and progesterone secretion from human luteinized granulosa cells in vitro.

Ιnformation on the role of adiponectin in human ovarian steroidogenesis is limited. The present study aimed to investigate the effect of different doses of adiponectin on the secretion of estradiol and progesterone by human luteinized granulosa cells in culture. Granulosa cells, obtained from women undergoing in vitro fertilization (IVF) treatment, were pre-incubated for 24 h and then cultured for 48 h. Adiponectin was used in 3 doses, i.e., 5, 10, and 100 µg/ml alone and in combinations with FSH (10 and 100 ng/ml). Estradiol and progesterone were measured by radioimmunoassays in culture supernatants at 24 h and 48 h. Adiponectin after 48 h of culture stimulated the secretion of estradiol and, to a lesser extent, progesterone in a dose-dependent manner. FSH showed a variable effect on steroidogenesis. However, when the low dose FSH was combined with adiponectin, estradiol, and progesterone secretion were increased disproportionally to the dose of adiponectin. With the high dose FSH, the positive effect of adiponectin on FSH-induced estradiol secretion was less pronounced, while the effect on progesterone secretion was negligible. This study shows for the first time a stimulatory effect of adiponectin on the secretion of estradiol and progesterone by human luteinized granulosa cells in vitro. It is suggested that adiponectin plays a paracrine role in human ovarian steroidogenesis by sensitizing the granulosa cells to FSH.

Replicating a GWAS: two novel candidate markers for oligospermia in Greek population.

Genome-wide association studies have paved the way for the discovery of new markers regarding many diseases, including male infertility. A previous study on Caucasians highlighted 172 polymorphisms for their putative association with male infertility and we attempted to replicate these findings on our dataset comprising of Greek male individuals (n = 360). We retrieved 59 out of 172 polymorphisms and tested for all association models on 278 normospermic men and 82 patients with an abnormal seminogram, later separated into oligozoospermic and asthenozoospermic groups. Our findings indicate that two SNPs (rs2296225 in KIF17, rs7224496 in SMYD4) are associated with male infertility in the Greek population and have not been recorded in literature as of yet. These novel markers need further validation via additional studies and an increased individual number. All in all, replication studies, possess the power to validate existing polymorphisms found across all population and thus increase both statistical significance as well as identify novel potentially diagnostic markers.

Spontaneous Intraoperative Rupture of a Large Interstitial Pregnancy: Laparoscopic Management.

We present a case of a large interstitial pregnancy which was intraoperatively ruptured, but was eventually laparoscopically treated. The patient experienced 9 weeks of amenorrhea, and a right cornual pregnancy measuring 6 cm was diagnosed. The patient consented on having a minimal surgical treatment, and a laparoscopic right cornuotomy was decided. During surgery, and prior to any manipulation to the uterus, there was a spontaneous rupture of the ectopic which resulted in excessive bleeding. Temporal pressure at the bleeding site and ligation of the superior branches of the right uterine artery allowed for a careful dissection of the right uterine cornua and achieved hemostasis. The surgery proceeded uneventfully thereafter. Although surgical intervention in such cases entails a high risk of hemorrhage, successful completion of the laparoscopy lies on the meticulous preoperative planning and the controlled precise surgical steps during the procedure.

Effect of resistin on estradiol and progesterone secretion from human luteinized granulosa cells in culture.

Information on the role of resistin on steroidogenesis is limited to animal studies. The aim of this study was to investigate the effect of various doses of resistin on estradiol and progesterone secretion from human luteinized granulosa cells in culture. Granulosa cells were obtained from follicular fluid aspirated from 50 women undergoing in vitro fertilization (IVF) treatment. The cells were cultured for 48 h after a 24 h pre-incubation period. The effect of resistin at dosages 1, 10 and 100 ng/ml alone or in combinations with FSH (10 and 100 ng/ml) on steroidogenesis was investigated. Estradiol and progesterone were measured by radioimmunoassays in culture supernatants at 24 h and 48 h. FSH treatment increased both estradiol and progesterone secretion. Resistin suppressed basal estradiol (at 1 ng/ml) and progesterone secretion (at all concentrations tested). When resistin (all concentrations) was combined with FSH (100 ng/ml), it eliminated the stimulatory effect of FSH on the secretion of estradiol and progesterone. This study indicates an inhibitory effect of resistin on the secretion of estradiol and progesterone by human luteinized granulosa cells in vitro. It is likely that this adipokine locally affects ovarian function in women. Abbreviations: 3ß-HSD: 3ß-hydroxysteroid dehydrogenase; CAP1: cyclase-associated protein 1; DCN: decorin; FIZZ: Found in Inflammatory Zones; hCG: human chorionic gonadotropin; IGF1: insulin-like growth factor type 1; IVF: in vitro fertilization; PCOS: polycystic ovary syndrome; RIA: radioimmunoassay; ROR1: receptor tyrosine kinase-like orphan receptor-1; TLR4: Toll-like receptor 4.

The effect of a GnRH antagonist on follicle maturation in normal women.

RESEARCH QUESTION: Ganirelix is a gonadotrophin-releasing hormone (GnRH) antagonist used for the prevention of premature LH surge during ovarian stimulation. What is the impact of ganirelix on follicle maturation in normal women? DESIGN: Ten normally cycling women were investigated during two menstrual cycles, i.e. cycle 1 (control) and cycle 2 (ganirelix). During both cycles, daily blood samples were taken from day 2, while transvaginal ultrasound scans were performed on cycle days 8 and 10 and daily thereafter. During cycle 2, all women were given 0.25 mg/day subcutaneous injections of the GnRH antagonist ganirelix from day 2 until the day of the endogenous LH surge onset in cycle 1. RESULTS: During treatment with ganirelix, serum FSH and oestradiol concentrations remained stable, while those of LH decreased significantly on days 3, 4, 7 and 9 (P < 0.05) compared with controls. Nevertheless, there was no significant within-cycle variation in LH concentrations. From day 10 onwards, no follicle maturation was observed in cycle 2, in contrast to cycle 1. Ovulation occurred in 9 of 10 women in cycle 1. In cycle 2, ovulation was delayed by at least 1 week in eight women. Follicle growth and ovulation occurred in only one woman while on ganirelix treatment. CONCLUSIONS: This study demonstrates for the first time that in normal women dominant follicle selection failed during treatment with ganirelix. As there was a similar gonadotrophin profile in the two cycles, it is suggested that ganirelix interferes with the process of follicle selection by acting in the ovary.

The Effect of Metformin on the Endometrium of Women with Polycystic Ovary Syndrome.

OBJECTIVES: To investigate the effect of metformin on endometrial receptivity in women with polycystic ovary syndrome (PCOS). METHODS: Twenty volunteer women with polycystic ovaries and oligomenorrhea were prospectively investigated. All women were treated with exogenous estradiol and progesterone to simulate a normal menstrual cycle (28-day duration) after GnRH-induced pituitary desensitization. Ten of the women received no other medication (group A, control), while the remaining 10 received metformin (group B, metformin). Endometrial biopsy was performed in all women on day 21 of the 2 simulated cycles. RESULTS: The expression of corticotropin - releasing hormone and urocortin in the endometrium was investigated. There was no significant difference between the 2 groups. A 3-day delay in the secretory maturation of the glandular epithelium relatively to the stroma was observed in 7 out of 10 women of group B (70%) as compared to only 1 out of 10 women of group A (10%, p = 0.02). CONCLUSIONS: It is shown for the first time that metformin administration to women with PCOS did not affect the expression of endometrial receptivity markers but delayed histological glandular maturation. It is suggested that metformin may have an impact on the function of the endometrium in PCOS.

Artificial oocyte activation: physiological, pathophysiological and ethical aspects.

Infertile couples with low oocyte yield in combination with abnormal semen parameters may experience intra-cytoplasmic sperm injection (ICSI) failure. An established factor associated with ICSI failure is oocyte activation deficiency (AOD). The latter originates from seminal contributors, such as phospholipase C-zeta (PLCζ) that is not adequate to produce calcium (Ca2+) oscillations for oocyte activation. Apart from this natural activator, other stimulants, such as A23187, ionomycin, strontium chloride or even electric pulses, have been used in embryological laboratories to overcome AOD and ICSI failure. The aim of the present narrative review is to discuss the role of Ca+2 oscillations in oocyte activation and summarize the evidence concerning the use of oocyte activators as agents for artificial oocyte activation (AOA). Studies in humans and animals have emerged many physiological, pathophysiological and ethical aspects of AOA. In conclusion, in mammalian eggs, the cytosolic Ca+2 oscillations derive from a periodic release of Ca+2 from intracellular pools. PLCζ, as well as artificial stimulants, have been used to produce Ca+2 oscillations for AOA. As the latter may increase the risk of epigenetic induced malformations, further studies are required to clarify whether AOA constitutes an effective and safe method to overcome ICSI failure. Abbreviations: AOA: artificial oocyte activation; AOD: oocyte activation deficiency; Ca+2: Calcium; CAMKII: Ca+2/calmodulin-dependent protein kinase II; CICR: calcium-induced calcium-release; DAG: diacylglycerol; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICSI: intra-cytoplasmic sperm injection; InsP3R: inositol-trisphosphate receptor; IP3: inositol 1,4,5-trisphosphate; IVF: in vitro fertilization; MAP: mitogen-activated protein; MII: metaphase II; NADP: nicotinic acid adenine dinucleotide phosphate; NO: nitric oxide; PAWP: post-acrosomal WW-binding domain protein; PIP2: phosphatidylinositol 4,5-bisphosphate; PLC: phospholipase C; PLCζ: phospholipase C-zeta; SOAFs: spermatozoon-released oocyte-activating factors; Sr+2: strontium; TFF: total fertilization failure.

The Effect of Glyphosate on Human Sperm Motility and Sperm DNA Fragmentation.

Glyphosate is the active ingredient of Roundup®, which is one of the most popular herbicides worldwide. Although many studies have focused on the reproductive toxicity of glyphosate or glyphosate-based herbicides, the majority of them have concluded that the effect of the specific herbicide is negligible, while only a few studies indicate the male reproductive toxicity of glyphosate alone. The aim of the present study was to investigate the effect of 0.36 mg/L glyphosate on sperm motility and sperm DNA fragmentation (SDF). Thirty healthy men volunteered to undergo semen analysis for the purpose of the study. Sperm motility was calculated according to WHO 2010 guidelines at collection time (zero time) and 1 h post-treatment with glyphosate. Sperm DNA fragmentation was evaluated with Halosperm® G2 kit for both the control and glyphosate-treated sperm samples. Sperm progressive motility of glyphosate-treated samples was significantly reduced after 1 h post-treatment in comparison to the respective controls, in contrast to the SDF of glyphosate-treated samples, which was comparable to the respective controls. Conclusively, under these in vitro conditions, at high concentrations that greatly exceed environmental exposures, glyphosate exerts toxic effects on sperm progressive motility but not on sperm DNA integrity, meaning that the toxic effect is limited only to motility, at least in the first hour.

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study.

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p = .456 and 15/133 vs. 9/97, p = .624, respectively), nor to the secondary outcomes preset for this study (all p values >.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.