Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception.

Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemiaMaterials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented.Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method.Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.

SA1/SA2 cohesion proteins and SIRT1-NAD+ deacetylase modulate telomere homeostasis in cumulus cells and are eligible biomarkers of ovarian aging.

STUDY QUESTION: Are cohesins SA1/SA2 and the NAD-dependent deacetylase SIRT1 involved in telomere homeostasis of cumulus cells and thus eligible as biomarkers of follicular physiology and ovarian aging? SUMMARY ANSWER: SA1/SA2 cohesins and SIRT1 are associated with telomere length in cumulus cells and may be eligible biomarkers of follicular physiology and ovarian aging. WHAT IS KNOWN ALREADY: In somatic cells, cohesins SA1/SA2 mediate sister chromatid cohesion at the telomere termini (for SA1) and along chromatid arms (for SA2). The NAD+-dependent protein deacetylase Sirtuin 1 (SIRT1), which preserves DNA integrity from oxidative stress, may also modulate genome stability and telomere length. STUDY DESIGN, SIZE, DURATION: Collectively 280 cumulus/oocyte complex samples were recovered from a total of 50 women undergoing in vitro fertilization. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulus cells were separated from the oocyte-cumulus complex. DNA and total mRNA were extracted from cumulus cells and assayed for telomere length and for SA1, SA2 and SIRT1 gene expression profiling. Telomere length was determined by quantitave PCR and analyzed relative to the single copy of the housekeeping gene (albumin) to generate a T/S ratio (Telomere/single copy gene). Gene expression levels of SA1, SA2 and SIRT1 mRNA were assayed by quantitative RT-PCR and confirmed by western blotting and immunofluorescent studies (SIRT1). SA1/SA2 and SIRT1 gene expression levels and telomere length analysis of patients/samples were ranked in relation to their clinical setting parameters (BMI, age) and to the number of oocyte retrieved. MAIN RESULTS AND THE ROLE OF CHANCE: SA1 and SA2 transcripts were both detected in all cumulus cells analyzed and the relative amount showed a clear decreasing trend according to the age of patients. A significant increase in SA1 and SA2 was disclosed in high responder women (>6 oocytes retrieved) compared to poor responders (<4 oocytes) (P < 0.05). Furthermore, statistically significant positive correlations were also recorded between the transcripts levels of the two cohesin molecules (r = 0.89; P < 0.05) and, to a lesser extent, between telomere length and SA1 (r = 0.42; P < 0.001) and SA2 (r = 0.36; P < 0.001) mRNA levels. SIRT1 expression was also significantly increased in high responders (>6 oocytes) compared to poor responders. Significant correlations were found between SIRT1 and SA1 (r = 0.69; P < 0.001), between SIRT1 and SA2 (r = 0.78; P < 0.001), and between SIRT1 and telomere length (r = 0.36; P < 0.001). However, in the older patient group (>38 years), SIRT1 mRNA levels were twice as high as the levels recorded in the younger patient cohort (<34 years). Western blot analysis and immunofluorescent studies confirmed the increments in SIRT1 protein levels in patients over 38 years old. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Cumulus/oocyte complexes were retrieved by patients undergoing ovarian stimulation protocol for IVF. We cannot exclude the possibility that different stimulation protocols affect the correlations highlighted in this study. Future investigations should shed light on cumulus cells molecular profile according to different stimulation protocols. WIDER IMPLICATIONS OF THE FINDINGS: The overall results of our study point to the involvement of cohesins SA1/SA2 and SIRT1 deacetylase in telomere homeostasis in cumulus cells and highlight their possible eligibility as biomarkers of follicular physiology and ovarian aging. STUDY FUNDING/COMPETING INTEREST(S): Merck Serono S.P.A Italy sponsored the study with financial support. There are no competing interests to declare.

Therapeutic approach for metabolic disorders and infertility in women with PCOS.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10% of women of reproductive age. It generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is defined as a multifactorial pathology, determined by the association of many factors: genetic, endocrine and environmental. The first and most effective treatment of PCOS is to change life-style and lose weight. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. For women with severe hirsutism, the addition of antiandrogens to estrogen-progestin therapy has significantly improved the results. In cases of anovulatory infertility, the drug of first choice is clomiphene citrate, followed by low-dose gonadotropins. Recently, insulin-sensitizing drugs have been widely prescribed for PCOS patients. They are particularly effective in reducing insulin resistance and improving ovulatory performance. Besides insulin-sensitizing drugs, natural substances, such as inositol, seems to have good efficacy, similar to metformin with fewer side effects. New substances that could be used include statins and natural statins, such as monakolin, alone or combined with myo-inositol. These substances do not have side effects and greatly reduce the hyperandrogenic component in these patients.

Genetic, hormonal and metabolic aspects of PCOS: an update.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.

Assembly of a photosynthetic reaction center with ABA tri-block polymersomes: highlights on protein localization.

The reconstitution of the integral membrane protein photosynthetic reaction center (RC) in polymersomes, i.e. artificial closed vesicles, was achieved by the micelle-to-vesicle transition technique, a very mild protocol based on size exclusion chromatography often used to drive the incorporation of proteins contemporarily to liposome formation. An optimized protocol was used to successfully reconstitute the protein in a fully active state in polymersomes formed by the tri-block copolymers PMOXA22-PDMS61-PMOXA22. The RC is very sensitive to its solubilizing environment and was used to probe the positioning of the protein in the vesicles. According to charge-recombination experiments and to the enzymatic activity assay, the RC is found to accommodate in the PMOXA22 region of the polymersome, facing the water bulk solution, rather than in the PDMS61 transmembrane-like region. Furthermore, polymersomes were found to preserve protein integrity efficiently as the biomimetic lipid bilayers but show a much longer temporal stability than lipid based vesicles.

Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds.

This study investigated chromosomal aneuploidies and DNA damage in spermatozoa from male patients contaminated by perfluorinated compounds (PFCs) in whole blood and seminal plasma. Sperm aneuploidy and diploidy rate for chromosomes 18, X and Y were evaluated by FISH; sperm DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling technique coupled to flow cytometry. Our results indicated that PFC contamination was present in 58% of subjects included in the study. A significant increase in alterations of sperm parameters was observed in PFC-positive subjects compared to PFC-negative subjects. As regards the sperm aneuploidy, both disomy and diploidy rates resulted significantly increased in subjects positive for PFC contamination compared to PFC-negative samples. In addition, sperm DNA fragmentation index resulted significantly increased in PFC-contaminated subjects compared to PFC-non-contaminated subjects, with a significant increased level of dimmer DNA fragmentation index. Our results clearly indicate that PFC contamination may detrimentally affect spermatogenesis, disturbing both meiotic segregation and DNA integrity. We could therefore suggest cautions to reduce or eliminate any contact with these compounds because the long-term effects of PFC accumulation in the body are not predictable.

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin.

PURPOSE: The purpose of this study was to evaluate the oxidative stress status (OS) of follicular fluid (FF) and the oocyte quality in women with polycystic ovary syndrome (PCOS) undergoing different ovarian stimulation protocols. METHODS: FF samples were collected after gonadotropin administration in association or not with metformin or D-chiro-inositol (DCI). OS status was then evaluated by checking the follicular fluid protein oxidation profile after specific labeling of aminoacidic free-SH groups, and two-dimensional electrophoresis followed by qualitative and semiquantitative analysis. Oocyte quality was assessed by international morphological criteria. RESULTS: Our data indicated that both treatments, even if to different extent, recovered a significantly high level of free-SH groups in FF proteins of PCOS women clearly indicating a decrease of OS level with respect to that found in FF samples from gonadotropins alone treated women. A higher number of good quality MII oocytes was also observed in DCI (P < 0.05) or metformin (P < 0.05) study groups in comparison to untreated control group. CONCLUSION: A natural supplement and a drug both showed a statistically significant positive effect on follicular milieu by decreasing the oxidative damage on FF proteins, as well as in recovering good quality oocytes.

A prospective, randomised, investigator-blind, controlled, clinical study on the clinical efficacy and tolerability of two highly purified hMG preparations administered subcutaneously in women undergoing IVF.

The aim of this multicentre, prospective, randomised, investigator blind, controlled clinical trial was to evaluate the clinical efficacy and tolerability of a highly purified human menopausal gonadotrophin (hMG) preparation (Merional-HG) when administered to patients undergoing controlled ovarian stimulation (COS) for in-vitro fertilisation (IVF) procedure enrolled in hospital departments. One hundred fifty-seven patients were randomised in two parallel groups: 78 started COS with Merional-HG and 79 with Menopur. Results of the study showed that both highly purified hMG preparations were equivalent in terms of number of oocytes retrieved (primary endpoint: 8.8 ± 3.9 versus 8.4 ± 3.8, p = 0.54). In the patients treated with Merional-HG, we observed a higher occurrence of mature oocytes (78.3% versus 71.4%, p = 0.005) and a reduced quantity of gonadotrophins administered per cycle (2.556 ± 636 IU versus 2.969 ± 855 IU, p < 0.001). Fertilisation, cleavage, implantation rates and the number of positive ß-human chorionic gonadotrophin (hCG; pregnancy) tests and the clinical pregnancy rate were comparable in the two groups. Both treatments were well tolerated. In conclusion, the results of this study support the efficacy and safety of Merional-HG administered subcutaneously for assisted reproduction techniques. Efficiency of Merional-HG appears to be higher due to reduced quantity of drug used and the higher yield of mature oocytes retrieved.

[Evaluation of a new association between insulin-sensitizers and α-lipoic acid in obese women affected by PCOS]. / Valutazione di una nuova associazione tra insulino-sensibilizzanti e acido α-lipoico in donne obese affette da PCOS.

AIM: Polycystic ovary syndrome (PCOS) is a multifactorial pathology affecting 7-10% of the female population. Usually occurs with oligo/amenorrhea, anovulation, hirsutism, polycystic ovaries. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome. It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients. METHODS: Original association between myo-inositol and alpha-lipoic acid, has recently been successfully administered in women with PCOS. The α-lipoic acid is a powerful natural antioxidant and an enzyme cofactor of the mitochondrial respiratory chain, is found to be a substance capable of improving glycemic control in patients with type II diabetes. In our study we compared two groups: group A, treated with metformin (3 g) and group B treated with metformin (1.7 g), myo-inositol and alpha-lipoic acid. RESULTS: The results of this study demonstrated a good efficacy of both treatments, although in the group treated with the combination of metformin/myo-inositol/alpha-lipoic acid improvement in hyperandrogenism, BMI and HOMA index were significantly better. CONCLUSION: Thus, the association metformin/myo-inositol/alpha-lipoic acid represents an excellent therapy choice to suggest to those obese women affected by PCOS who do not want to take hormones and neither to have any severe side effect.

[Evaluation of the myo-inositol-monacolin K association on hyperandrogenism and on the lipidic metabolism parameters in PCOS women]. / Valutazione dell'associazione myo-inositolo-monacolina K sull'iperandrogenismo e sui parametri del metabolismo lipidico in donne con PCOS.

AIM: Polycystic ovary syndrome (PCOS) is a multifactorial pathology affecting 5-10% of the female population. Usually occurs with oligo/amenorrhea, anovulation, hirsutism, polycystic ovaries. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome. It has been demonstrated that by reducing hyperinsulinemia, in particular with the administration of metformin, insulin-lowering agents might improve endocrine and reproductive abnormalities in PCOS patients. METHODS: A new molecule with insulin-sensitizing properties, myo-inositol, has recently been successfully administered in women with PCOS. New associations between natural substances like myo-inositol and other components have been proposed to improve the therapeutical efficacy. Among these substances, the monacolin K, a natural statin appeared to have important actions in cholesterol synthesis. In this article we study the effect of inositol alone and the association between myo-inositol and monacolinin K in the treatment of PCOS with insulin resistance, menstrual irregularities and hirsutism. RESULTS AND CONCLUSION: The results of this study demonstrated a good efficacy of both treatments, although in the group treated with the combination of myo-inositol/monacolin K improvement in lipids and hyperandrogenism were significantly better.

[Evaluation of the treatment with D-chiro-inositol on levels of oxidative stress in PCOS patients]. / Valuzione del trattamento con D-chiro-inositolo dui livelli di stress ossidativo nelle pazienti con PCOS.

AIM: Recent studies on the pathophysiology of infertility have shown that oxidative stress (OS) can be one of the causal factors. The OS is, by definition, an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. It seems that oxidative stress plays an important role in almost all phases of human reproduction. In fact, ROS are involved in the modulation of a large spectrum of reproductive functions such as oocyte maturation, ovarian steroidogenesis, corpus luteum functions and are involved in the processes of fertilization, embryo development and pregnancy, but also in some diseases that cause infertility. Polycystic ovary syndrome (PCOS) has recently been associated with increased oxidative stress, often put in relation to the syndrome's typical metabolic disorder. Inositol is an intracellular mediator of insulin, currently much used as a therapeutic agent in PCOS. While its main action takes place via insulin sensitization, little is known about the possible effects of other disorders, such as oxidative stress, associated with PCOS. The purpose of this study was therefore to assess the effect of D-chiro-inositol on the state of oxidative stress in the follicular fluid of women with PCOS. METHODS: Follicular fluids were obtained from women who have turned to the Center for Diagnosis and Treatment of Sterility of Obstetrics and Gynecology of the University Hospital of Siena and Modena diagnosed with PCOS. The women were treated with D-chiro-inositol (500 mg x 2 per day) for 3 months before being subjected to cycles of in vitro fertilization (IVF). The state of oxidative stress was measured by marking of free thiol groups of proteins in the follicular fluid with 3-(N-Maleimidopropionyl)-biocytin. RESULTS: In our study we obtained a lesser presence of free thiol protein groups equal to 77.8% in the follicular fluid of women with PCOS not treated with D-chiro-inositolo, compared to patients who instead have carried out such treatment. CONCLUSION: These results suggest that in PCOS women there is an increase of the oxidation of thiol groups of proteins follicular, correlated to a progressive increase of the oxidative stress and that the administration of D-chiro-inositol in patients with this disease seems to reduce the oxidation of thiol groups.

[Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia]. / Il trattamento con carnitina, acetilcarnitina, L-arginina e ginseng migliora la motilità spermatica e la salute sessuale negli uomini con astenozoospermia.

AIM: Among the factors contributing to male infertility, asthenospermia constitutes both a health and a social problem frequently associated with alterations in sexual function. Studies have shown that acetyl carnitine and L-arginine improve sperm motility and that ginseng enhances libido and sexual performance. This study examined the effect of treatment with carnitine, acetyl carnitine, L-arginine and ginseng in men with idiopathic asthenospermia and altered sexual function. METHODS: The study population was 180 patients with asthenospermia randomly assigned to two groups: group A (90 men) received treatment and group B (90 men) did not. The sperm count was 16.6 ± 3.2 x 106/mL and the total sperm motility was 26.5 ± 3.4%. RESULTS AND CONCLUSION: Sexual satisfaction was measured using the sexual satisfaction index (SSI). At the end of therapy, a significant improvement was observed in progressive sperm motility on spermiogram evaluation and in SSI scores in the treatment group.

Metformin doses and body mass index: clinical outcomes in insulin resistant polycystic ovary syndrome women.

OBJECTIVE: PCOS is the most common endocrinopathy among reproductive age women. Approximately 60% of PCOS women have insulin resistance. While the efficacy of metformin in reducing insulin resistance and decreasing androgen level has been widely validated, there is no agreement on the dose of metformin to be used. PATIENTS AND METHODS: Prospective non-randomized cohort study of 108 insulin resistant, overweight and obese PCOS women, aged between 22 and 35 years. All patients received 1500 mg of metformin (500 mg x 3 times/day) for the first 6 months. At the end of this period, the patients' HOMA index was evaluated. In subjects, who did not demonstrate normalization of the HOMA index, the dose was increased to 2500 mg/day (500 mg at breakfast and 1000 mg at lunch and dinner) for additional 6 months. The hormonal blood profile, fasting insulin and fasting glucose levels, HOMA index, anthropometric assessment, pelvic ultrasound, FAI index and cholesterol were evaluated. RESULTS: Overall results showed a good response to metformin therapy in insulin-resistant PCOS patients with BMI >25, while in patients with higher BMI (31.15 ± 0.40), no normalization of HOMA was found. At the higher dose of metformin, obese patients achieved a good response to therapy, with improvement in BMI, menstrual pattern, cholesterol levels and hyperandrogenism. CONCLUSIONS: Our results demonstrate a correlation between the required dose of metformin, BMI and hyperandrogenism. The dose of metformin should be adjusted to patients' BMI in order to obtain significant results in terms of clinical, metabolic and hormonal responses.

[Low dose oral contraceptives: 30 microg are still used?]. / Contraccettivi a basso dosaggio: quelli contenenti 30 microg sono ancora da prescrivere?

The choice between oral contraceptives (OC) containing 30 or 20 microg of ethinylestradiol (EE) is founded on clinical sign and medical history of the women. Not always a lower dose of EE cause less side effects than an higher dose. Often 20-microg-EE OC induces menstrual cycle alterations and sexual dysfunctions, inducing the women to stop the treatment. Low estrogens concentration have a negative effect on external genital tract, with a consequent vaginal dryness and dispareunia. It is known that OC with 20-microg of EE determine a lower increase of sex hormone binding globulin compared to 30 mg EE and the consequence can be a reduction in antiandrogen effect of OC. OC containing 30 microg of EE have a positive effect on peak in young women, particularly in lean subjects. Moreover, 30 microg of EE induce a better ovarian suppression associated with a lower steroidal production during the week of interruption. Besides, 30-microg-EE OC works well in blocking ovarian cysts formation in women with endocrine dysfunctions like polycystic ovary syndrome or with previous luteal cysts. In conclusion, an OC with 30 microg of EE and an antiandrogen progestin is better than another with 20 microg of EE with the same progestin, because 30 microg of EE have a more powerful antiandrogenic action and guarantee very good cosmetics and endocrine results.

[Is micronutrients supplementation useful in pregnancy?]. / La supplementazione di micronutrienti è utile in gravidanza?

Use of micronutrients in pregnancy appears to be useful in prevention of some pregnancy related pathologies if used continuously before and during all nine months of pregnancy. The assumption of specific micronutrients, with vitamins and mineral salt inside, could be use to correct some deficiencies and prevent the onset of specific pregnancy related diseases. An adequate support of micronutrients can ensure physiological fetal growth contributing to the development of various fetal organs. Besides folic acid administered in appropriate doses (>400 mug), that it is able to prevent some fetal diseases, such as the closure of the neural tube, other vitamins such as vitamin A are very effective in ensuring an optimal state of health of the mother and slowing the growth of uterine myomas.

[Efficacy of Lactobacillus Rhamnosus GR-1 and of Lactobacillus Reuteri RC-14 in the treatment and prevention of vaginoses and bacterial vaginitis relapses]. / Efficacia del Lactobacillus Rhamnosus GR-1 e del Lactobacillus Reuteri RC-14 nel trattamento e nella prevenzione delle recidive nelle vaginosi e nelle vaginiti batteriche.

AIM: The aim of this study was to investigate the efficacy of the use of Lactobacillus rhamnosus GR-1 and of Lactobacillus reuteri RC-14 administrated orally in the treatment and prevention of vaginoses and bacterial vaginitis relapses. METHODS: The study enrolled 50 women in good health, aged between 18 and 48 years, with assessed diagnosis of bacterial vaginosis and vaginitis. The women were randomized in two groups: group A comprised 25 patients with bacterial vaginitis and group B comprised 25 patients with vaginosis. Each patient was administered an antibiotic therapy and subsequently a therapy with Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Dicoflor Elle, Dicofarm, Roma, Italy) with two tablets daily for 15 days. After one week from the end of the therapy all patients have been controlled by vaginal swab and microscopic analysis of vaginal secretion. RESULTS: At the end of the study 46 patients had a complete Lactobacilli recolonization, two patients had no colonization and two dropped out. The results showed that 92% of the enrolled patients benefited from the treatment. CONCLUSION: The results of the present study shows that Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, taken orally, were helpful in vaginosis and bacterial vaginitis treatment and in relapse prevention, as they can re-establish the vaginal ecosystem remarkably.

Efficacy on menopausal neurovegetative symptoms and some plasma lipids blood levels of an herbal product containing isoflavones and other plant extracts.

OBJECTIVES: To assess the efficacy of a product containing isoflavones and other plant extracts (BIO) on whole menopausal symptomatology and plasma lipids profile. METHODS: Multicentre, randomized, double blind, placebo controlled clinical investigation on 125 menopausal women randomly assigned to two groups treated for 6 months with placebo or one tablet daily of an herbal product containing 72 mg/dose of isoflavones of different plants origin and other plant extracts (BIO). Primary end-point: Kupperman Menopause Index (KI) variations; secondary end-point: activity on plasma lipids profile and clinical global impression (CGI) on efficacy and tolerability by investigators and patients. The usual parametric test (paired Student t test) was performed to evaluate the significance. In case of non-applicability of parametric tests, the non-parametric Mann-Whitney U test was used. The differences where considered significant at p<0.05 level. RESULTS: At the end of treatment in both groups KI showed a significant decrease (p<0.001). However, in the BIO group the KI reduction was significantly higher (p=0.0265) than in the placebo group after 4 and 6 months of treatment. In the BIO treated patients the LDL cholesterol showed a borderline but not significant reduction compared to placebo (p=0.0608) and triglyceride (TG) a significant (p=0.0151) decrease compared to placebo. The investigator's and patient's CGI on BIO group where superior as compared to placebo. Clinical tolerability was good in booth groups. CONCLUSION: On the basis of positive effects on KI and lipids profile as well as of good clinical tolerability, BIO can be considered one of the possible alternative therapy for conventional HRT.

[Individualization of low-dose oral contraceptives. Pharmacological principles and practical indications for oral contraceptives]. / Personalizzazione dei contraccettivi orali. Brevi principi farmacologici e indicazioni pratiche nella prescrizione di un contraccettivo orale.

The contraceptive pill has been a revolution of the last 40 years. In Italy, however, it is much less widely used than in other countries. Explanations for this phenomenon range from religious implications and customs to misinformation and word-of-mouth communication of negative experiences. The oral contraceptive pill is often used to correct menstrual disorders, leading to poor results and side-effects. Recent advances in oral contraception have led to a substantial reduction in doses and side-effects. Low-dose pills contain minimal doses of progesterones and estrogens and ensure good control of the menstrual cycle. Although reduction of ethinyl estradiol (EE) concentrations has reduced the incidence of negative systemic side effects such as water retention, edema and swollen breasts, the low estrogen dose may be associated with spotting and hypomenorrhea or amenorrhea in the long term, as well as dyspareunia due to reduced vaginal trophism, which may induce women to suspend use of the drug. It is also true that only one type of estrogen is used in the pill, albeit at different doses, whereas the progesterone may differ and in many cases is the cause of common side-effects. The choice of progesterone therefore involves not only its effect on the endometrium in synergy with estrogen, but also possible residual androgenic activity which may have negative metabolic repercussions. Indeed, addition of a progesterone, especially androgen-derived, attenuates the positive metabolic effects of estrogen. Two new monophasic oral contraceptives were recently released. They contain 30 microg (Yasmin) or 20 muicrog (Yasminelle) EE and a new progesterone, drospirenone, derived from spirolactone, which has antiandrogenic and antimineralcorticoid activity similar to endogenous progesterone. Like progesterone, the drospirenone molecule is an aldosterone antagonist and has a natriuretic effect that opposes the sodium retention effect of EE. It may, therefore, help to prevent the water retention, weight gain and arterial hypertension often associated with oral contraceptive use. Recent comparative studies recorded weight loss that stabilized after 6 months of treatment with drospirenone/EE. Overweight women may therefore benefit from the formulation with 20 microg EE, whereas the formulation with at least 30 microg EE should be more appropriate for underweight women. Women with slight to moderate acne, the formulation with 30 microg EE has been found to be as effective as 2 mg cyproterone acetate combined with 35 micrig EE (Diane). Menstrual cycle characteristics, however, remain the main factor determining the choice of formulation. Randomised control studies comparing the new formulation with others containing second or third generation progesterones have found similar efficacy in cycle control and incidence of spotting. From this point of view, it is not advisable to prescribe more than 30 microg EE (Yasmin or Yasminelle) for women with normal menstrual cycles, whereas in cases of hypomenorrhea and/or amenorrhea at least this dose of EE plus drospirenone may be used. Women with hypermenorrhea run the risk of spotting if an inappropriate drug is chosen. A solution is to use 30 microg EE/drospirenone from day 5 of the cycle. To control so-called minor side-effects, the dose of EE must be appropriate. In women with premenstrual tension a dose of at least 30 microg EE associated with drospirenone reduces or even prevents symptoms. On the other hand, in cases of chronic headache or headache as a side-effect of oral contraceptive use, a lower dose of estrogen is beneficial, and doses below 20 microg may be used. Although the progesterone component is not considered to affect headache, good results have been obtained with drospirenone, the antimineralcorticoid effects of which reduce blood pressure and improve symptoms. Formulations with 20 microg EE and drospirenone are particularly indicated in women with pre-existing mastodynia, fibrocystic breast manifestations or who develop mastodynia as a side-effect of oral contraceptive use. Since high plasma concentrations of androgens have been recorded in these women, a progesterone with antiandrogen and antiedema activity can be beneficial. Finally, it is worth recalling that monophasic pills with low estrogen doses, such as the formulations mentioned above, ensure good mood control, reducing the depressive symptoms often associated with oral contraceptive use. In conclusion, formulations containing drospirenone are a valid alternative to conventional oral contraceptives for the personalisation of these drugs.

[Association of antioxidants and natural immune activators in the treatment of astheno-teratospermia and abacterial leukocytosis]. / Ruolo di un'associazione tra antiossidanti e stiomlanti immunitari naturali nel trattamento dell'astenoteratospermia con leucocitosi.

AIM: Leukocytes are often present in human seminal plasma and more frequently in infertile men. Leukocytospermia is associated with sperm morphological and functional alterations. Immune cell activation leads to an increase of free radical production, without any antioxidant defence activation. Leukocyte presence during sperm maturation and migration through male genital tract and consequently exposure to reactive oxygen species led to sperm alteration: axonemal, acrosomal and nuclear structure damage, associated with necrosis. In order to evaluate the immune-modulating and antioxidative activity of beta-glucan, fermented papaya and lactoferrin associated with vitamins C and E, we analysed sperm characteristics of selected infertile male with astheno-teratospermia and abacterial leukocytosis. METHODS: We selected 20 patients referred to our Sterility Centre for semen analysis with leukocyte concentration higher than 1x106 cell/mL. Seminal quality evaluation was performed according to WHO guidelines (1999) using Papanicolau and eosin staining, before and after three months of treatment with beta-glucan, papaya, lactoferrin, vitamin C and E. RESULTS: After therapy, seminal analysis showed a significant reduction of leukocyte concentration and an increase of sperm motility and normal sperm morphology. CONCLUSION: Our results suggest that a combined immunomodulating and antioxidant treatment protect sperm cells during maturation and migration through the male genital tract, resulting in a functional rescue demonstrated by the improvement of semen quality.