Sexological and traumatic aspects in reproductive difficulties: a psychometric study on couples seeking help for infertility.

PURPOSE: To investigate the impact of infertility in gender differences on psycho-traumatological, sexological, relational and emotional aspects and gender differences in couples requiring assisted reproductive treatment. METHODS: 151 couples were recruited with a mean age of 36.7 ± 4.8 years for women and 39.8 ± 6.6f or men. 43% of women and 34% of men had already received the diagnosis of infertility. To recruited subjects was administered the following psychometric tests: Sexological and Emotional in Infertility questionnaire (SEIq), Arizona Sexual Experience Scale (ASEX), the Orgasmomether and the International Trauma Questionnaire (ITQ). RESULTS: There was a significant difference in traumatic symptoms between men and women (t = 5,859, p < 0.05). Gender differences were found in the sexological dimension of the SEIq (t = 7,858, p < .001) and in the total ASEX score (t = 3,979, p < .001). Specifically, significant correlations emerged between the ASEX domains and the emotional and sexological aspects related to infertility only in women. The reaction to the diagnosis was negatively correlated with the emotional area of ​​the couple (r = -0.683, p < .001) and positively with the couple relationship (r = 0.815, p < .001). Multiple regression revealed that the overall functioning of the couple, rather than the single scales, is the main predictor of sexuality (R2 = 0.77). CONCLUSION: A clear impact of infertility on the couple's psycho-traumatological, psycho-sexological and relational aspects emerged. It could be useful to promote targeted support interventions on the most compromised areas of couple functioning in assisted reproductive centers.

Characterization of epidermal growth factor-like domain 7 (EGFL7) expression in normal endometrium and in the endometrium of women with poor reproductive outcomes.

STUDY QUESTION: Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the preparation of the endometrium for implantation and could its dysregulation be implicated in poor reproductive outcomes? SUMMARY ANSWER: EGFL7 is highly expressed in the endothelium and glandular epithelium throughout the menstrual cycle; it is upregulated by stromal cells in secretory phase and appears strongly reduced in endometrial biopsies and isolated stromal cells of women with unexplained recurrent pregnancy loss (uRPL) and recurrent implantation failure (RIF). WHAT IS KNOWN ALREADY: The secreted factor EGFL7, originally identified as a gene primarily expressed in endothelial cells, is also expressed by the mouse blastocyst and by mouse and human trophoblast cells. It regulates trophoblast migration and invasion by activating NOTCH1 signaling. NOTCH1 has been demonstrated to play a fundamental role in endometrial receptivity and its dysregulation may be involved in selected pregnancy complications characterized by altered endometrial receptivity, such as uRPL. STUDY DESIGN, SIZE, DURATION: This is an exploratory study for which 84 endometrial biopsies were collected from normally fertile women, as well as from women with uRPL and RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS: Samples were collected from women in both the proliferative and secretory phases of the menstrual cycle and stratified into three sub-groups according to the patient clinical history: 20 fertile women (8 in proliferative and 12 in secretory phase), 41 women with uRPL (6 in proliferative and 35 in secretory phase), and 27 women with RIF (8 in proliferative and 19 in secretory phase). Immunohistochemistry, real-time PCR, and western blot analyses were performed to study the expression of EGFL7 and NOTCH1, as well as the NOTCH target genes. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis of spatial and temporal distribution of EGFL7 in endometrial biopsies from fertile women revealed higher levels of EGFL7 in samples from the secretory phase compared to proliferative phase. The expected expression of EGFL7 in endothelial cells was shown as well as the novel, not previously reported, expression in endometrial glands and stromal cells. EGFL7 was significantly reduced in the endometrium of women with uRPL and RIF in the secretory phases and this was associated with a downregulation of the NOTCH1 signaling pathway. Human recombinant EGFL7 was able to activate the NOTCH1 signaling pathway in endometrial stromal cells (EndSCs) obtained from fertile women but not in cells from uRPL or RIF patients. EndSCs from fertile women and decidualized in vitro for three days showed an upregulation of EGFL7 expression, whereas cells obtained from women with uRPL and RIF and decidualized in vitro did not. LIMITATIONS, REASONS FOR CAUTION: This study was conducted with a relatively small number of patient samples. Although results are highly reproducible and consistent, additional observations from multicentric cohorts would strengthen the relevance of the data. Moreover, this is an in vitro study, which might only partially represent the in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrate for the first time that EGFL7 is new player involved in decidualization and provide new insights into the pathophysiology of selected implantation defects and early pregnancy complications. Our studies have revealed that alterations in EGFL7 expression and the consequent dysregulation of NOTCH signaling are potential underlying causes of RIF and uRPL. Our results might have therapeutic relevance, as the EGFL7/NOTCH pathway may represent a potential target for medical intervention. STUDY FUNDING/COMPETING INTEREST(S): This study has been supported by the Grant for Fertility Innovation 2017 (Merck KGaA). There are no competing interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Management of male factor infertility: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS) : Endorsing Organization: Italian Society of Embryology, Reproduction, and Research (SIERR).

PURPOSE: Infertility affects 15-20% of couples and male factors are present in about half of the cases. For many aspects related to the diagnostic and therapeutic approach of male factor infertility, there is no general consensus, and the clinical approach is not uniform. METHODS: In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), endorsed by the Italian Society of Embryology, Reproduction, and Research (SIERR), we propose evidence-based recommendations for the diagnosis, treatment, and management of male factor infertility to improve patient and couple care. RESULTS: Components of the initial evaluation should include at minimum medical history, physical examination, and semen analysis. Semen microbiological examination, endocrine assessment, and imaging are suggested in most men and recommended when specific risk factors for infertility exist or first-step analyses showed abnormalities. Full examination including genetic tests, testicular cytology/histology, or additional tests on sperm is clinically oriented and based on the results of previous investigations. For treatment purposes, the identification of the specific cause and the pathogenetic mechanism is advisable. At least, distinguishing pre-testicular, testicular, and post-testicular forms is essential. Treatment should be couple-oriented, including lifestyle modifications, etiologic therapies, empirical treatments, and ART on the basis of best evidence and with a gradual approach. CONCLUSION: These Guidelines are based on two principal aspects: they are couple-oriented and place high value in assessing, preventing, and treating risk factors for infertility. These Guidelines also highlighted that male infertility and in particular testicular function might be a mirror of general health of a man.

Leukocytospermia in late adolescents: possible clinical interpretations.

BACKGROUND: No data are currently available on the implication of amicrobial leukocytospermia in male adolescents. Therefore, the primary aim of this study was to evaluate the prevalence of amicrobial leukocytospermia among non-smoker late adolescents who were exposed to other risky lifestyles for the andrological health. The main andrological clinical features of adolescents with leukocytospermia were also reported. METHODS: This is a cross-sectional study carried out in 80 boys. Each adolescent underwent a physical examination, and to the assessment of sperm conventional parameters, seminal leukocytes concentration and immature germ cell evaluation. A possible correlation between seminal leukocytes and immature germ cells and testicular volume (TV) was tested. RESULTS: The adolescents enrolled in this study had 18.0 ± 0.4 (range 18.1-18.9) years. Unprotected sexual intercourse was referred by 38% of them. Sexual dysfunctions were found in 25% and isolated hypoactive sexual desire in 12.5% of boys. Low TV and penile length in flaccidity were found in 44% and 30% of them, respectively. Only 41% had normozoospermia at the sperm analysis, whereas 19% had isolated oligozoospermia, 15% oligo-asthenozoospermia, and 25% oligo-astheno-teratozoospermia. Leukocytospermia occurred in 25% (20 out of 80) of adolescents. No seminal infection was detected in 19% (15 out of 80) of them. Adolescents with leukocytospermia had lower progressive sperm motility, percentage of normal forms, TV, and a higher percentage of immature germ cells compared to those without leukocytospermia. Semen leukocyte concentration correlated negatively with TV and positively with the percentage of immature germ cells in the ejaculate. CONCLUSION: Leukocytospermia, increased immature germ cell number, and low TV identify a distinct phenotype suggestive of testicular tubulopathy. Primary prevention of male infertility and the counselling for andrological risky lifestyles is mandatory and should be started as early as possible.

Assessment of sexual and emotional distress in infertile couple: validation of a new specific psychometric tool.

BACKGROUND: The diagnosis of infertility strongly impacts on psychological and sexological couple health. In this regard, some feelings and psychological states were demonstrated in association with reproductive problems. Depression and anxiety are the most common psychopathologies associated with infertility, although also sexuality is strongly involved in infertility conditions. OBJECTIVES: The aim of this study is to develop a tool to probe and assess the emotional aspects, sexuality, and social relationships of the couple seeking medical care for infertility. MATERIALS AND METHODS: A self-reported questionnaire that we will refer to as SEIq (Sexuality and Emotions in Infertility questionnaire) was constructed and developed and, consequently, administered to 162 heterosexual couples (324 subjects) seeking help for reproductive problems. Hence, we performed a specific statistical analysis to assess and validate this new psychometric tool. RESULTS: About 60% of men and women (both partners in 43% of couples) declare that infertility has changed their life (Q10). Moreover, the incidence of sexual disorder declared by the subjects is quite rare in men (10%) but more frequent in women (29%) (p < 0.01). CONCLUSION AND DISCUSSION: The results of this pilot test show that the diagnosis of infertility impacts on the couple relationship affecting the emotional area, interpersonal relationships, and sexual functions of the couples. Moreover, the SEIq appears a valuable tool to coherently probe and relate sexological, psychological, relational, and emotive aspects in partners and couples facing the infertility diagnosis. The explorative factor analysis of SEIq data allows to understand the women, men, and couples' behavior in our sample, individuating a reduced set of factors, prone to an easier evaluation. On the whole, the psychometric evaluation through SEIq might be suitable for the couples during Assisted Reproductive Technologies treatments.

Do malignant diseases affect semen quality? Sperm parameters of men with cancers.

The advent of modern treatments together with the improvement of the surgical techniques has significantly increased 5-year survival rates of young patients with cancer. Although the deleterious effects of chemotherapy and radiation are well documented, controversies exist about the effect of cancer itself on semen parameters before treatment. We collected data on 236 patients representative of different types of cancers reoffered at our institution for sperm cryopreservation with the aim to correlate the pre-freeze semen parameters with type of cancer, disease stage and with semen quality of 102 fertile and healthy men. The median baseline semen parameters of all our patients with cancer are placed above the 5th percentile of the World Health Organization reference value, but the type of cancer may impact the sperm parameters. In testicular tumours and in Hodgkin lymphoma, we show a semen concentration statistically lower than in the fertile population, while in patients with other cancers, there is no difference with the healthy men. We found no correlation between semen quality and disease stage. Eighty-six per cent of our patients do not have children at the time of semen cryopreservation, and the only established clinical option for preserving fertility of these men is cryopreservation of spermatozoa.

Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study.

The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS.

Influence of preoperative biliary drainage on surgical outcome after pancreaticoduodenectomy: single centre experience.

PURPOSE: Controversy prevails on the impact of preoperative biliary drainage (PBD) on postoperative complications and clinical outcome of pancreatic cancer. We determined whether PBD is associated with increased morbidity and mortality rates after pancreaticoduodenectomy. METHODS: A total of 131 consecutive patients who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were included in this study. Overall, 57 % of jaundiced patients underwent PBD, while 43 % were not drained. The impact of PBD on postoperative morbidity and mortality was evaluated by means of logistic regression analysis. The Kaplan-Meier method was applied to determine the effect of PBD on survival of patients with malignant lesions. RESULTS: Mortality and morbidity rate was 3 % and 54.6 %, respectively. PBD was demonstrated to be the unique predictor of complications (odds ration [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The jaundiced patients who were drained exhibited high frequencies of wound infection (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p < 0.001). In addition, an increased frequency of pancreatic fistula emerged among drained patients compared to those who were not drained (p = 0.036). PBD did not affect survival of patient with malignant lesions. CONCLUSIONS: With the exception of the classical indications, PBD should be carefully evaluated in patients with resectable pancreatic cancer.

Psychopathological symptoms and their association with the quality of life and the sexual functioning in women affected by systemic scleroderma: a preliminary investigation.

OBJECTIVE: This study aimed to investigate the presence of psychopathological symptoms and the relations of these dimensions with the quality of life and sexual function in a group of women affected by systemic scleroderma. SUBJECTS AND METHODS: Seventy-one women with systemic scleroderma were invited to participate in the study; 65 agreed to participate, while 6 declined. Four questionnaires were administered to the patients: a specific socio-demographic questionnaire, the Symptom Checklist-90-Revised (SCL-90-R), the Female Sexual Function Index (FSFI), and the Quality-of-Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). RESULTS: Of all the participants in this study, 48% of patients showed a clinical score on SCL-90-R Somatization, 45% on depression, and 37% on obsessive-compulsive. As hypothesized, psychopathological symptoms were related to lower quality of life since somatization and depression predicted the total score of health-related quality of life and lower sexual functions, showing a specific effect of depression on sexuality. CONCLUSIONS: Our findings highlighted the presence of an association between psychopathological symptoms and reduced sexual functioning and the associations between somatization and the health-related quality of life dimensions in scleroderma patients. Furthermore, our results sustain the importance of also considering the mental health of patients with systemic sclerosis, within an integrated biopsychosocial care model.

The semen quality of the mobile phone users.

BACKGROUND: The increased use of mobile phones, the media's attention for general health, and the increase of idiopathic male infertility suggest to investigate the possible consequences of an excessive use of mobile phones on semen quality. AIM: To evaluate the conventional and some of the main biofunctional sperm parameters in healthy men according to the different use of the mobile phone. SUBJECTS AND METHODS: All the enrolled subjects in this study were divided into four groups according to their active cell phone use: group A= no use (no.=10 subjects); group B= <2 h/day (no.=16); group C= 2-4 h/day (no.=17); and group D= >4 h/day (no.=20). Among the subjects of the group D (>4 h/day), a further evaluation was made between the "trousers users"(no.=12) and "shirt users"(no.=8), and they underwent semen collection to evaluate conventional and biofunctional sperm parameters (density, total count, morphology, progressive motility, apoptosis, mithocondrial membrane potential, chromatin compaction, DNA fragmentation). RESULTS: None of the conventional sperm parameters examined were significantly altered. However, the group D and the trousers users showed a higher percentage of sperm DNA fragmentation compared to other groups. CONCLUSION: These results suggest that the sperm DNA fragmentation could represent the only parameter significantly altered in the subjects who use the mobile phone for more than 4 h/day and in particular for those who use the device in the pocket of the trousers.

Impact of different typologies of smoking on ovarian reserve and oocyte quality in women performing ICSI cycles: an observational prospective study.

OBJECTIVE: Within the last few years smoking activities, as well as infertility, have increased in Italy, and so has the consumption of alternative cigarette devices among women of childbearing age. The aim of this observational study was to evaluate the impact of the consumption of cigarettes and alternatives devices, such as electronic cigarettes and heat-not-burn (HnB) products, on infertile women performing in vitro fertilization (IVF), in specific on the quality of oocytes retrieved in women performing intracytoplasmic sperm injection (ICSI) cycles. PATIENTS AND METHODS: Prospective observational longitudinal study involving 410 women referring to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, from 2019-2022. All the women enrolled filled out an elaborate questionnaire investigating smoking consumption, before the beginning of ovarian stimulation by antagonist protocol, ovarian pick-up, and subsequent ICSI technique. The outcomes of the study were the evaluation of clinical and ICSI features between the groups of smokers and non-smokers: the number of retrieved oocytes, immature oocytes, and fertilization rate were confronted between the two groups and between cigarette smokers vs. e-cigarette and heat-not-burn (HnB) products smokers. RESULTS: Clinical parameters were comparable between the group of smokers compared to one of the non-smokers, except for anti-Müllerian hormone (AMH), which was statistically lower in smokers (p<0.05). Regarding IVF hormonal stimulations it appears that the total dose of gonadotropin was statistically lower in the non-smoker's group, compared to smokers (1850±860 UI vs. 1,730±780 p<0.05). Regarding ICSI techniques interestingly the number of oocytes retrieved was lower in the smokers' group compared to non-smokers (5.21±0.9 vs. 6.55±3.5, p<0.001), and the number of empty zona pellucida oocytes was statistically higher in the smokers' group (0.51±0.1 vs. 0.2±0.1, p<0.05). On the other hand, the fertilization rate (FR) was statistically higher in non-smokers compared to the smokers' group (72.16±3.05 vs. 68.12±2.21, p=0.03). Out of the 203 smokers, overall, any statistically significant difference, regarding ICSI results, has been found between the group of cigarette smokers, compared to the group of e-cigarettes plus HnB products smokers. CONCLUSIONS: Smoking negatively impacts human fertility, leading to a reduction of ovarian reserve and ovarian quality, which can negatively impact results in women performing ICSI cycles. Despite the limitation of the study, our results underline that consumption of cigarette alternative devices seems to have a similar negative impact on the quantity and quality of oocytes retrieved in ICSI cycles. Clinicians should emphasize the reduction of exposure to harmful substances derived from the combustion of tobacco smoking, as well as alternative devices, in women of childbearing age.

Effect of vardenafil on semen parameters in infertile men: a pilot study evaluating short-term treatment.

BACKGROUND: Severeal in vivo and in vitro studies have been carried out in order to evaluate the efficacy of long-term treatment with phosphodiesterase type-5 (PDE5) inhibitors (PDE5i) on spermatogenesis, but the results are still controversial. AIM: To evaluate the effects of vardenafil on seminal parameters of infertile men after a short-term treatment. MATERIALS/SUBJECTS AND METHODS: A total of 205 male subjects were randomized to receive a single dose of vardenafil 10 mg (73 men, group B), a single dose of vardenafil 10 mg every other day for 15 days (67 men, group C), and no treatment (65 men, group A). Semen parameters were evaluated before and after the end of the treatment in each of group A, B, and C, respectively. Additionally, an IIEF- 5 questionnaire was administered to all patients with erectile dysfunction (ED) before and after each treatment period. RESULTS: The semen parameters in groups B and C has shown a significant increase in percentage forward motility after vardenafil administration as compared with baseline (p<0.001). In group C, we observed an increase in the mean semen volume and an improvement in the mean total sperm concentration (p<0.001) as compared with baseline. CONCLUSIONS: We showed the efficacy of vardenafil in the treatment of ED and, on a large series of infertile patients, the positive effect on sperm motility after a single-dose administration. It also showed that after 15 days of treatment on alternate days is also achieved an improvement in sperm concentration.

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

Bupivacaine 0.5% versus ropivacaine 0.75% wound infiltration to decrease postoperative pain in total thyroidectomy, a prospective controlled study.

AIM: Control of postoperative pain is one of the most important concerns for both the patients and the surgical team. In this regard the efficacy of wound infiltration with local analgesia and the most proper drugs to be used are not settled. We conducted our study trying to investigate this point in a prospective randomized double blinded manner. METHODS: With inclusion criteria of: age (18-65 y), volume <90 mL, first time, no lymph node enlargement and exclusion criteria of: duration >90 min, incision length >10 cm, neck dissection decided during surgery and a postoperative complication within the first 24 hours. Sixty patients planned for total thyroidectomy under general anesthesia were enrolled in the study in three groups with twenty patients assigned randomly to each one: group (A) a control group in which no wound infiltration was done, group (B) in which preoperative wound infiltration with 10 mL bupivacaine 0.5% was done, and group (C) in which preoperative wound infiltration with 10 mL ropivacaine 0.75% was done. Postoperative pain was evaluated by Visual Analogue Score (VAS) with a scale of (0-10) at 1 hour, 4 hours, 8 hours and 16 hours. RESULTS: The postoperative pain experienced by all the patients reached a maximum point at 1 hour postoperatively then started to decrease to be minimal at 8 hours and almost negligible at 16 hours. Ropivacaine group showed a statistically significant decrease in pain perception at 1 hour postoperatively (P=0.028), bupivacaine group showed also a decrease in pain perception at 1 hour but it was not statistically significant. At 4 hours of operation and after; neither ropivacaine nor bupivacaine showed an effect on pain perception. CONCLUSION: The benefit of local wound infiltration with local analgesia in decreasing postoperative pain is limited to a short period after surgery in which the use of ropivacaine 0.75% is recommended over pubivaccaine 0.5%.

Uterine fibroids treatment: do we have new valid alternative? Experiencing the combination of vitamin D plus epigallocatechin gallate in childbearing age affected women.

OBJECTIVE: Uterine myomas are the most common benign tumors in females, and at least 25% of affected patients experience symptoms severe enough to need treatment, like heavy hemorrhage, pelvic pain, and infertility. Currently, a non-invasive approach is preferred in women of childbearing age who desire pregnancy. The aim of our study was to determine the effect of oral supplementation with a combination of vitamin D plus epigallocatechin gallate (EGCG) and vitamin B6 in women with myomas. PATIENTS AND METHODS: Between April and December 2020, we enrolled 95 women of childbearing age, afferent to our hospital, displaying at least one myoma with a diameter <4 cm. Patients were divided in two groups: 41 women were treated daily with two tablets of 25 µg vitamin D + 150 mg EGCG + 5 mg vitamin B6 for 4 months; 54 women, representing the control group, received no treatment. Total volume and vascularization of myomas were analyzed ultrasonographically. Bleeding and pelvic pain was also evaluated, as well as patients' quality of life and health through questionnaire Short Form Health Survey (SF-36) and Patient Global Impression of improvement (PGI-I). RESULTS: After treatment myomas' total volume and peripherical vascularization significantly decreased respectively by 37.9% (p<0.001) and 7.7%. On the other hand, we observed an increase in myomas' volume by 5.5 % and of peripherical vascularization by 5% in the control group. The treated group reported an improvement in SF-36 (p<0.001) and PGI-I (85.4%) questionnaire scores. CONCLUSIONS: We demonstrated, in young women who want to preserve fertility, that the combined supplementation of vitamin D, EGCG, and vitamin B6 reduced myomas' volume and improved patients' quality of life, without side effects.

4D-HyCoSy performed in a reproductive center: retrospective analysis of pain perception, complications and spontaneous pregnancy rate after the technique.

OBJECTIVE: Nowadays 4D hysterosalpingocontrast sonography (4D-HyCoSy) represents a primary technique in the evaluation of tubal impairment, with a low rate of pain referred and complications related, but its role in increasing the chance of spontaneous clinical pregnancy in women in childbearing age is still debated. PATIENTS AND METHODS: Retrospective study of 359 women performed 4D-HyCoSy at Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2018-2020. INCLUSION CRITERIA: women attending our IVF (in vitro fertilization) center with at least 1 year of infertility. EXCLUSION CRITERIA: female age over 43 years, previously known severe tubal infertility, suspected anovulation, and semen abnormalities. PRIMARY OUTCOME: evaluation of tubal patency, complications related to technique, and pain perception evaluated thanks to a 10-cm visual analogue scale (VAS) Scale. SECONDARY OUTCOMES: clinical pregnancy rate (PR) after the technique confronted between the group of women with bilateral tubal patency (group A) with the group of monolateral tubal patency (group B) within 30 days and between 30-180 days, and 180 days-1 year from the exam. Time to pregnancy (TTP) and other obstetrical outcomes were evaluated too. RESULTS: The average age of the study's population was 33.3 years. Mean duration of infertility was 2.1 years. Complication rate was 6.4%, and in any case the use of ephedrine was required. 182 (50.6%) women reported absence of pain during the exam (VAS scale value 0) and 131 (36.5%), reported mild pain experience (VAS scale value between 1-4). Spontaneous pregnancy rate was of 29.3% in group A and 30.3% in group B; time to pregnancy was 32 ± 14.7 days in group A and 35 ± 13.1 days in group B. The insurgence of a spontaneous pregnancy was significantly lower for both 4D-HyCosy sub-groups after 30 days following technique respect to 30-180 days and 180 days-1 year following the technique (both p-value < 0.001). CONCLUSIONS: We confirm that 4D-HyCoSy is a safe and user-friendly technique, used as first line assessment of tubal patency of women afferent to a reproductive center. We also reported a positive impact on spontaneous pregnancy rate in women performing 4D-HyCoSy, emphasized within the first following month. This mandatory technique for tubal investigation, has not only a function in the diagnostic assessment of female infertility, but also has a therapeutic role, in young women who desire a pregnancy, avoiding, in some cases, the need of IVF treatments and clinical risks linked, while saving medical and monetary resources.

Combined treatment with myo-inositol, alpha-lipoic acid, folic acid and vitamins significantly improves sperm parameters of sub-fertile men: a multi-centric study.

OBJECTIVE: Reduction in motility and number of spermatozoa and change in their morphology are some of the most relevant causes of male infertility. Production of reactive oxygen species may affect motility, morphology and DNA stability of spermatozoa. This study aimed at evaluating the effect of combined treatment with myo-inositol, alpha-lipoic acid, folic acid, betaine and vitamins (namely, Sinopol®) on semen parameters of sub-fertile men. PATIENTS AND METHODS: We recruited 143 sub-fertile men, 26-53 years aged, no-smokers, without any testicular pathologies, with a normal endocrinological/metabolic profile, and no concomitant consumption of drugs. Out of them, 25 patients did not meet study inclusion criteria mainly due to the history of genital diseases that came to light after Sinopol® prescription. Among the 118 men that fulfilled inclusion criteria, 10 (8.4%) patients were lost at follow-up and in 8 (6.8%) cases the partner got pregnant spontaneously. Thus, 100 patients completed the study and semen analysis was performed before and after 90 days of treatment. RESULTS: Semen quality improved after 90 days of treatments, with a statistically significant increase of sperm concentration (p=0.0009), of number of spermatozoa (p=0.0017), of progressive motility (p=0.0047), of total motile sperm count (p=0.0010), and of normal sperm morphology (p<0.0001). CONCLUSIONS: For the first time we reported that a combination of nutraceuticals composed of myo-inositol, alpha-lipoic acid, folic acid, betaine and vitamins improves sperm parameters in sub-fertile men. We are aware that to clarify the clinical relevance of the data studies with larger sample sizes and longer durations are needed, as well as evaluation of myo-inositol and alpha-lipoic acid co-treatment effectiveness in improving the chances to obtain a pregnancy spontaneously or following assisted reproduction.

Controlled, prospective, observational study on the efficiency and tolerability of a combination of potential Nrf2-inducing antioxidants and micronutrients as pre-treatment for ICSI in dyspermic patients with previous failure.

OBJECTIVE: To evaluate the efficiency of pre-treatment in dyspermic males in IVF couples with a combination of micronutrients, for the purpose of improving the fertilization rate, the implantation rate and the outcome of the pregnancy. PATIENTS AND METHODS: This controlled prospective clinical study was performed in two medically assisted reproduction centers. 59 males with mild oligo-astheno-teratospermia (OAT) were admitted to the study. All of them had a history of previous in vitro fertilization (IVF) attempts with female partners aged < 40 diagnosed having tubal or idiopathic infertility. The subjects upon enrolment underwent a semen test and afterward were treated with alpha lipoic acid and glutathione (Fertiplus SOD®, Idi-Pharma, Catania, Italy) for 4 weeks (short-term). The primary endpoints that were evaluated are the following: fertilization rate (mean fertilization), implantation rate and pregnancy rate. RESULTS: At the end of this study all the males (mean age 39.5 ± 5.1) reported in not having any side effects during the administration of Fertiplus. Their female partners (mean age 34.9 ± 4.5) underwent IVF using the ICSI technique. The number of oocytes retrieved and inseminated was not statistically different in comparison to previous attempts, but with the same number of oocytes treated, the fertilization rate per couple demonstrated statistically significant increase (p<0.001). We did not observe a percentage increase in evolutionary embryos, but we noticed an improvement in embryo quality per individual couple (p<0.001), associated with a net increase in the implantation rate per couple (p<0.001) in terms of clinical pregnancy. The estimated miscarriage risk after treatment was five times lower (p<0.001). CONCLUSIONS: Short-term treatment with micronutrients in dyspermic subjects can improve the reproductive outcome of the IVF procedure.

Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells.

BACKGROUND: Prostate cancer is a disease associated with aging. Also commonly associated with increasing age is a shift in the prooxidant-antioxidant balance of many tissues toward a more oxidative state, i.e., increased oxidative stress. We hypothesize that androgen exposure, which has long been associated with the development of prostate cancer, may be a means by which the prooxidant-antioxidant balance of prostate cells is altered. PURPOSE: Using established prostate carcinoma cell lines, we studied the effect of androgens on various parameters of oxidative state (e.g., generation of hydrogen peroxide and hydroxyl radicals, lipid peroxidation, and oxygen consumption) and antioxidant defense mechanisms (e.g., the glutathione system and catalase). METHODS: The androgen-responsive LNCaP and the androgen-independent DU145 prostate carcinoma cell lines were exposed to 5 alpha-dihydrotestosterone (DHT) and to the synthetic androgen R1881. The cellular proliferation responses were measured by use of a fluorometric assay to quantitate the amount of DNA. The generation of reactive oxygen species was measured by use of 2',7'-dichlorofluorescin diacetate, a dye that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals. Lipid peroxidation was quantitated by use of a chromogen specific for malonaldehyde and 4-hydroxy-2(E)-nonenal. General mitochondrial activity was determined by assaying 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. A Clark-type electrode was used to assess oxygen consumption per cell. Intracellular glutathione concentrations and the activities of catalase and gamma-glutamyl transpeptidase were measured spectrophotometrically. All P values resulted from two-sided tests. RESULTS: DHT at less than 1 to 100 nM (a concentration range encompassing the physiologic levels of DHT considering all ages) and R1881 at 0.1-1 nM concentrations were effective in inducing in LNCaP cells comparable proliferative responses and changes in oxidative stress. In contrast, neither DHT nor R1881 had any effect on the oxidative stress in DU145 cells. The mitochondrial activity in LNCaP cells, as measured by MTT reduction, was significantly elevated above the levels of the untreated controls by DHT (0.1-1000 nM) and R1881 (0.05-1 nM) (P < .001 in both). Oxygen consumption and catalase activity were increased in LNCaP cells in the presence of 1 nM R1881 by 60% and 40%, respectively, over the values in the untreated control cells (P < .03 and P < .01, respectively). The same concentration of R1881 resulted in a decrease in intracellular glutathione concentrations and an increase in gamma-glutamyl transpeptidase activity in LNCaP cells. Treatment with the oxidizing agents H2O2 and menadione produced an increase in gamma-glutamyl transpeptidase activity in LNCaP cells, whereas treatment with the antioxidant compound ascorbic acid (100 mM) reduced the oxidative stress produced in LNCaP cells by 1 nM R1881 and completely blocked the gamma-glutamyl transpeptidase activity. CONCLUSIONS: Physiologic levels of androgens are capable of increasing oxidative stress in androgen-responsive LNCaP prostate carcinoma cells. The evidence suggests that this result is due in part to increased mitochondrial activity. Androgens also alter intracellular glutathione levels and the activity of certain detoxification enzymes, such as gamma-glutamyl transpeptidase, that are important for maintenance of the cellular prooxidant-antioxidant balance.