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Current research fails to adequately inform about the differential use of available levonorgestrel-releasing intrauterine systems (LNG-IUSs) in real life. Aim of our study was to compare the characteristics, satisfaction, continuation rates, and adverse effects between users of the high-dose LNG-IUS (52 mg) and of the low dose LNG-IUS (13.5 mg and 19.5 mg).A prospective cohort study was performed in two Services for Family Planning in normal menstruating women with the inclusion of all new prescriptions of LNG-IUS for contraception. Women were followed for a mean of 9.1 ± 2.6 months after placement.109 women (mean age of 39.8 ± 8.7 years old) were included, 69.7% using a high dose LNG-IUS and 30.3% using a low dose LNG-IUS. Women with a low dose LNG-IUS were significantly younger, thinner, more nulliparous, with fewer vaginal deliveries and C-sections, with a lower menstrual flow length and with more previous use of short-acting reversible contraceptives (We have shown a clear differential use of available LNG-IUS in clinical practice, both as baseline characteristics and as different outcomes, primarily for bleeding patterns. However, all these systems were associated with a very high rate of satisfaction and continuation.

Many women experience negative feelings during menstrual bleeding. Aim of the study was to evaluate the attitudes of Italian women towards menstrual bleeding, their desire to reduce its frequency and knowledge of the existence of methods capable of achieving such an objective. An internet-based anonymous questionnaire has been sent to women willing to fill it in through different social media (Instagram, WhatsApp, Facebook, Twitter). The survey evaluated, objective parameters such as number of pads, use of painkillers, duration of period and pain intensity. Judgement towards period and knowledge about methods to reduce frequency and amount of menstrual flow were analysed. 1072 Women aged 18 − 40 years, answered the survey. The level of education of responders was high, with 61.7% having a university degree. 27.5% of respondents viewed positively the occurrence of a menstrual period. Ideal frequency of menstrual cycles was considered 3 months and the perfect duration was considered to be 3 days. Half of the respondents ignored the existence of methods to suppress menstruation or reduce its frequency. 52% of participants stated that they would not use a contraceptive method because they considered it not ‘natural’. In our sample, in spite of the discomfort reported by half of the women interviewed, menstruation was considered positively by one fourth as because confirm their fertility. The majority of women did consider bleeding every month a healthy, but they preferred a three-monthly frequency. Knowledge of contraceptive methods capable of reducing the frequency of menstrual bleeding was scarce.

Introduction: Following a historical overview, the effect of different contraceptive methods on vaginal microbiome has been reviewed and summarized.Areas covered: Effects of combined hormonal contraceptives (oral or vaginal) and of progestin only (injectable and implantable), intrauterine devices/systems (copper- or levonorgestrel-releasing), on vaginal microbiome. In addition, mention is made of vaginal rings releasing antiviral drugs and lactic acid.Expert opinion: The vaginal microbiota (VM) is unique in that it is normally dominated by Lactobacillus species providing a degree of protection against infections; this however may vary, depending on the species and strains of Lactobacillus. Bacterial Vaginosis represents the most common dysbiosis of the VM and its prevalence can be influenced by use of contraception. Available evidence indicates that, under the influence of oral or systemically administered female sex hormones, there is apromotion of vaginal eubiosis, with aprevalence of ahealthy VM in which Lactobacilli predominate.

Uterine fibroids are the most common gynecological disorder, classically requiring surgery when symptomatic. Although attempts at finding a nonsurgical cure date back to centuries, it is only around the middle of the last century that serious attempts at a medical treatment were carried out. Initially, both progestins and estrogen-progestin combinations have been utilized, although proof of their usefulness is lacking. A major step forward was achieved when peptide analogs of the GnRH were introduced, first those with superagonist properties and subsequently those acting as antagonists. Initially, the latter produced side effects preventing their routine utilization; eventually, this problem was overcome following the synthesis of cetrorelix. Because both types of analogs produce hypoestrogenism, their use is limited to a maximum of 6 months and, for this reason, today they are utilized as an adjuvant treatment before surgery with overall good results. Over the last decade, new, nonpeptidic, orally active GnRH-receptor blockers have also been synthesized. One of them, Elagolix, is in the early stages of testing in women with fibroids. Another fundamental development has been the utilization of the so-called selective progesterone receptor modulators, sometimes referred to as "antiprogestins". The first such compound to be applied to the long-term treatment of fibroids was Mifepristone; today, this compound is mostly used outside of Western Countries, where the substance of choice is Ulipristal acetate. Large clinical trials have proven the effectiveness of Ulipristal in the long-term medical therapy of fibroids, although some caution must be exercised because of the rare occurrence of liver complications. All selective progesterone receptor modulators produce unique endometrial changes that are today considered benign, reversible, and without negative consequences. In conclusion, long-term medical treatment of fibroids seems possible today, especially in premenopausal women.

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 pandemia Materials 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.

The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation; (b) Changes in cervical mucus characteristics that inhibit sperm penetration and (c) desynchronization of the endometrial picture necessary for implantation.Mechanisms involved in the progestin-induced endometrium desynchronization are individually reviewed for each of the routes of administration and, whenever possible, by individual members of the various families of synthetic progestin derivatives.For contraceptive purposes, progestins are today administered through several routes: orally, as injections, subdermally and via the vagina or the uterine cavity. Given this variety of modalities, their effects may differ, depending on the route of administration, concentration reached at the level of the endometrium and the duration of use. These are characterized by inactivation of the endometrium. Progestin-only contraception provides a safe and effective control of fertility regulation, although, they are associated with the problem of endometrial break through bleeding that may lead to discontinuation. Unfortunately, in spite of a major research effort over two decades, there is not, as yet, an established long-term intervention available to manage bleeding irregularities, making mandatory a deeper understanding of the mechanisms involved is required.

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequen...

Objectives. To evaluate the impact on metabolism, bleeding, and sexual function of Nexplanon, a subdermal implant. Study Design. We recruited women (n=101) receiving the Nexplanon implant at two university centers in Italy between 2011 and 2016 into this prospective, observational, multicenter research trial. Participants completed the Interview for Ratings of Sexual Function (IRSF) and the Female Sexual Function Index (FSFI) questionnaires before and 3 and 6 months after the implant was inserted. In addition, all blood parameters were assessed at these visits. All women were given a menstrual diary card and a pictorial blood assessment chart to record daily any vaginal bleeding. Results. The studied metabolic parameters remained in the normal range, showing no alarming modifications: minimal statistical reductions (in aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides, and activated partial thromboplastin time) and increases (in glucose and prothrombin activity) were observed. Changes in IRSF score over 6 months showed a significant increase in pleasure, personal initiative, orgasm, intensity of orgasm, and satisfaction, and a significant decrease in anxiety and discomfort. Mean Body Mass Index decreased, and the weekly frequency of sexual intercourse increased. Conclusions. Nexplanon showed not only a lower metabolic and bleeding impact, but also important positive effects on sexual function. It expands the range of possibilities for women, 38 and couples, in the modern concepts of sexual and reproductive wellbeing.

In the last decade, the risk benefits ratio of MHT has been evaluated mainly in terms of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these Recommendations is to provide a simple and updated reference on postmenopausal MHT. The term MHT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential (Seq) when progestogen is added to ERT for 10-14 days a month, or continuous combined (CC) when progestogen is administered continuously every day along with a fixed amount of estrogen. MHT also includes Tibolone and the Tissue Selective Estrogen Complex (TSEC).

Following a historical overview, the ovulation-inhibiting effect of various orally administered estrogen-progestin combinations (combined oral contraceptives [COCs]) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Inhibition of ovulation with progestins alone; estrogens alone; various progestins in combination with ethinyl estradiol; various progestins in combination with natural estrogens (estradiol, estradiol valerate, and estetrol). Expert commentary: The original idea to achieve ovulation blockage through the administration of steroid hormones involved the use a progestogen (both progesterone and its synthetic homologous). The ability of a progestin to inhibit ovulation depends on the type of compound and on its dosage and a difference of more than 20-fold in activity exists between compounds utilized today in COCs. Initially, the estrogenic component was present only because it contaminated the first progestin utilized. It was soon found that an estrogen is necessary for proper cycle control. It was also found that the estrogen acts synergistically in inhibiting ovulation. For almost half a century, most COCs contained ethinyl estradiol. Today, also natural estrogens are being employed. Inhibition of ovulation was complete with all early high dose preparations. Decreasing dosage allowed some ovarian activity to occur, occasionally leading to a mature follicle. Even in this situation, defective corpus luteum formation assured contraceptive protection.

Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.

After some 60 years of ever-increasing utilization, hormonal contraception (HC) has made a major impact in the lives of women worldwide. This chapter discusses the different meaning that family planning has taken today in industrialized and in developing countries, the reason being that in the former fertility is almost always at, or below, replacement level, whereas in the latter—with the notable exception of China—it is still well above it.

The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range.

Demand for second-trimester induced abortions (STIAs) increases in Italy. For these procedures, prostaglandins alone were used until 2010, when mifepristone became available. The present study compares the two modalities, and investigates the reasons for STIAs.The records of all such procedures performed at the Department of Gynaecology, Obstetrics and Urology of the 'Sapienza' University (Rome), between January 2004 and December 2012, and of all those done at the 'San Filippo' Hospital (Rome), between January 2010 and December 2012, were analysed. Data gathered included women's age, obstetric history, reasons for requesting the STIA, gestational age, mode of intervention, and complications if any.During the study period, 353 women requested a STIA. Karyotype or genetic anomalies were the reason for the request in 187 cases (53%), while structural anomalies, both single and multiple, were given as the reason in 158 (45%). In most cases, these anomalies were assessed by ultrasound scan.Few studies have investigated reasons for requesting STIAs. Of all chromosome abnormalities diagnosed in this study, trisomy 21 was the most common (59%) and it was the most frequent reason for requesting pregnancy termination.

The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease. Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral contraceptives (COC) has substantially changed, with new combinations, dosages and mode of administration appearing on the market. Area covered: In a series of articles, recent information on the complex issue of COC risks and benefits will be reviewed in the hope of providing an updated picture. The present article reviews metabolic changes occurring during use of modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), often compared to classic compounds, such as levonorgestrel. Three categories of metabolic effects in healthy women are detailed: on carbohydrates, lipid and bone mineral content. Expert commentary: Overall, the picture is reassuring: the new generations of progestins are basically devoid of androgenic, estrogenic or glucocorticoid related side-effects. This should result in an improved safety profile, although past history teaches us that that large comparative and surveillance studies are required before firm conclusions can be drawn. At any rate, available evidence indicates that metabolic effects of third and fourth generation progestins, especially when they are combined with natural estrogens, are minimal and, if used in healthy women, should not cause concern.

Introduction: The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens.Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture.The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel.Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed.Expert commentary: Overall, the picture is reassuring: the use of natural estroge...

To analyze adherence to an oral contraceptive (OC) regimen and correlate results to participants' socio-demographic and behavioral characteristics.Women were prospectively enrolled and followed for 6 months. At enrollment, subjects were given a card for recording daily pill intake; its completion was checked at 6 months when women completed a self-administered questionnaire.Out of 755 eligible subjects, 704 agreed to participate; 402 women completed 6 months of recording of use of an OC and properly filled the questionnaire. Good adherence was reported by 64% of participants; 20.9% missed one pill and 14.9% missed more than one pill. Mean number of missed pills per subject was 0.59 and mean number of pills delayed for less than 24 h was 1.18. Best adherence to a COC regimen was associated with evening time intake (p = 0.0019). No statistically significant associations of adherence with socio-demographic characteristics were found. Age was only marginally associated with having missed at least one pill.In the present study, a lower number of missed pills were observed than previously reported, but the proportion of missed pills was similar. No association with specific subject characteristics that could serve as markers of increased risk of nonadherence was found.

The aim of the study was to retrieve data on the characteristics and profile of women attending an emergency service (ES) to receive a prescription (mandatory until May 2015) for emergency contraception (EC).In a retrospective study the following data were collected for all women requesting EC between January 2014 and June 2015: demographic characteristics, time between unprotected sexual intercourse (USI) and arrival at the ES, time between the last menstrual period and the USI, and type of EC prescribed. In a prospective study starting January 2015, a questionnaire was administered requesting the following information: reasons for requiring EC, previous EC use, source of knowledge about EC, prior contraception and age at first intercourse.During the whole study period, 1773 women requested EC: their mean age was 26.0 years; 78.5% were Italian; 91.5% were unmarried; 55.2% were still studying and 51.9% had high school education; 61.2% reached the ES within 12 h of the USI; and 42.4% had a USI during days 9-16 of their menstrual cycle. Levonorgestrel was prescribed in 81.4% of women and ulipristal acetate in 17.7%. In the prospective part of the study (382 women), the majority (57.9%) requested EC for condom rupture; 49.5% reported previous use of EC; and 41.6% received information on the subject through friends. The vast majority (83.8%) reported prior use of contraception; in 25.4% the reason for not using it was the absence of a relationship.An exact profile of women requesting EC can help women in their choice of permanent contraception, and help clinicians in counselling women on appropriate contraception.

Emergency contraception, or postcoital contraception, is a modality of preventing pregnancy after unprotected sexual intercourse or to avert potential contraceptive failure. The controversy revolves around the definitions of pregnancy and induced abortion. If one utilizes the medical definition accepted by the WHO, pregnancy only begins with implantation; therefore, there can be no abortion without a pregnancy and emergency contraception can in no way be equated to an abortion. The problem is that – ethically at least – there is a contention that a new human life begins right after the fertilization process is completed through full syngamy. Thus, using these parameters, it becomes vital to ascertain exactly the mechanism of action of postcoital methods. Emergency contraception exists in two different forms: the hormonal and the intrauterine. Hormonal emergency contraception was first proposed by Yuspe in the form of 100 µg ethynyl oestradiol plus 500 µg levonorgestrel taken twice at a 12-h interval. At t...

Establishing the proportion of fertilized oocytes and early human embryos that proceed to term may help policy makers in their evaluation of when the life of a new human individual begins and in determining the nature of protection to be accorded to it. The rate of spontaneous abortions, although increasing with age, overall does not exceed 15%. However, abortion rates refer only to 'clinical pregnancy', whereas early embryonic loss is more common than generally believed. Evidence of such wastage comes from many sources. Human fecundity rarely exceeds 35% and may be decreasing due to deterioration in semen quality. Embryological studies show that 50% of randomly recovered preimplantation embryos have severe anomalies. The study of sensitive markers of pregnancy, such as human chorionic gonadotrophin, indicates early embryo wastage in the order of 50%. Pregnancy wastage may be a function of the time lapse between ovulation and implantation as the implantation window extends between menstrual cycle days 20 and 24. Finally, data obtained with natural IVF cycles also indicate major losses, with an overall pregnancy rate of 7.2% per cycle and 15.8% per transfer. These data, however, are biased by a high cancellation rate and low oocyte retrieval in natural IVF cycles.

Synthetic compounds can bind to progesterone receptors and these progesterone receptor ligands exhibit a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism. These substances have been classified as antiprogestins or as selective progesterone receptor modulators.There are several hundred selective progesterone receptor modulators available, although only a dozen or so have been evaluated to any significant extent. The best-known selective progesterone receptor modulators are mifepristone (RU 486), asoprisnil (J 867), onapristone (ZK 98299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710.A careful evaluation of existing major review papers and of recently published articles was carried out for the indications under review, focusing not only on mifepristone, but also on those other selective progesterone receptor modulators for which data are available.Outside pregnancy, selective progesterone receptor modulators are used or have been tested clinically for a number of indications in reproductive medicine: as oral contraceptives, alone or in combination with a progestin, to improve cycle control in users of progestin-only contraceptives, as emergency contraceptives, for the medical treatment of uterine fibroids, in cases of endometriosis and premenstrual syndrome and to improve ovarian stimulation prior to in vitro fertilisation. In the authors' opinion, as of today, few applications outside pregnancy seem worthy of large-scale use: emergency contraception and long-term medical management of uterine fibroids and possibly of endometriosis.

A number of synthetic steroids are capable of modulating progesterone receptors with a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism. The best known of these are mifepristone (RU 486), asoprisnil (J 867), onapristone (ZK 98299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710.Outside reproduction selective modulators of progesterone receptors have been under investigation for a large variety of indications, for example in oncology as adjuvants in breast, cervical, endometrial, ovarian and prostate cancer, as well as inoperable meningioma and leiomyosarcoma. In addition, they have been used as antiglucocorticoids. It is therefore useful to review the results obtained in these conditions.A careful evaluation of existing major review papers and of recently published articles was carried out for the indications under review, focusing not only on mifepristone but also on those other selective modulators of progesterone receptors for which data are available.In preliminary studies selective modulators of progesterone receptors had some activity on a number of neoplasias. Their antiglucocorticoid activity has been tested with some success in Cushing's syndrome, several psychiatric conditions (e.g., mood disorders and Alzheimer's disease) and acute renal failure. Finally they are being used in a gene regulator system.

Substances with an antifertility activity can be delivered directly into the vagina and the uterus. Indeed, it has been known for decades that the vaginal mucosa is an excellent way through which to deliver a number of compounds to the general circulation. Research and development efforts have concentrated on rings delivering only progestins, or both an estrogen and a progestin. The only combined ring marketed so far releases 15 microg ethynyl estradiol and 120 microg etonogestrel, and has a failure rate between one and two per 100 women-years of use. It has a preset duration of action of 1 month, has to be inserted before day 5 of the cycle, irrespective of the presence of menstrual flow, and withdrawn after 21 days, thereby allowing proper cycle control. Among rings releasing only a progestin, one device releasing progesterone has been marketed; all others are still under development. Unlike other long-term methods, vaginal rings do not require the involvement of a healthcare professional and can be inserted and removed by the user. The first attempt at achieving contraception by inserting a device in the uterus is 100 years old. Half a century later, medicated intrauterine systems were investigated; they are superior to inert devices and today a number of active principles, such as copper and progestogens, have been incorporated and tested when released from an intrauterine device (IUD). Copper-releasing devices last more than 10 years, with cumulative pregnancy rates of between approximately 5 and 3, and cumulative expulsion rates between approximately 12 and 8. With all IUDs, bleeding and pain are the most common reasons for a request to withdraw a device. There is agreement that fertility after removal of a copper-IUD is not impaired. Finally, the overall risk of ectopic pregnancy is reduced in IUD users, compared with using no contraception. The first progestogen-releasing system contained progesterone, had 1-year duration of action and was marketed some 30 years ago; unfortunately, it was shown that failure caused an increase of extrauterine pregnancies. This potentially dangerous effect eventually led to the withdrawal of the device from the market. In the meantime, a device releasing the synthetic progestin levonorgestrel was being developed and has now been successfully marketed; it lasts for a minimum of 5 years and, although absorbed systemically, cyclic function is maintained. The system is one of the most effective methods of contraception available today: large clinical studies indicate a Pearl index of 0.1 per 100 woman-years. Although a postfertilization effect cannot be excluded, in a majority of cases, intrauterine systems act as true contraceptives, preventing fertilization.

SUMMARYUlipristal acetate (UPA) is now recommended as first choice hormonal Emergency Contraception (EC), due to its higher efficacy and similar safety compared to Levonogestrel - EC. Even though all trials demonstrated that the first mechanism of action is inhibition of ovulation, some authors still postulate that a post fertilization effect is also possible, raising the alert on medication and fostering the ethical debate.A Medline database search was performed in order to find recent articles related to UPA’s effects on ovulation, on fallopian tube and on endometrium. We also analyzed the effects on sperm function and pregnancy. All studies conclude that UPA is effective in inhibition of ovulation even when administered shortly before LH peak. The effects on fallopian tube are unclear: according to some authors UPA inhibits ciliar beat through an agonistic effect on progesterone receptors, according to others it antagonizes the progesterone-induced ciliar beat decrease. Concerning the action on endometrium and on embryo implantation most of the studies concluded that low dose UPA used for EC has no significant effect on the decrease of endometrial thickness and on embryo’s attachment, but these results are still matter of debate. Finally recent evidence suggests that UPA modulates human sperm functions while it has no effect on established pregnancy. To date the majority of the evidence concur in excluding a post-fertilization effect of UPA, even though more studies are needed to clarify its mechanism of action.

The term progestogen has been widely utilized to indicate the general class of agents that includes both progesterone and its synthetic analogs, whereas the term progestin refers only to synthetic progestational steroids. The development of progestins has been influenced in a major way by the search for orally active hormonal contraceptives, since it is likely that hormonal contraceptives will continue to utilize a progestin, the only possible alternative being represented by the utilization of antiprogestins. Synthetic progestogens in clinical use today belong to three main chemical families: progesterone derivatives (progesterone, retro-progesterone, 19-norprogesterone and 17alpha-hydroxyprogesterone); gonane and 19-nortestosterone derivatives (norethisterone, levonorgestrel, desogestrel, gestodene, norgestimate); a spironolactone derivative. Biological potency of progestogens varies depending on the end-point measured, usually ovulation inhibition and endometrial transformation; with both these tests, the most active compounds are all gonane derivatives, with a potency over a 100 times that of the natural hormone. When administered in adequate doses, a progestin inhibits fertility by inhibiting ovulation. This action is mainly exerted at the hypothalamic level where, physiologically, progesterone decreases the number of LH pulses. When progestogens are delivered directly to the uterine cavity, their action seems to be purely local. It has been amply proven that--even when administered in doses that do not constantly inhibit ovulation--a progestin can still remain effective as a contraceptive by acting at the level of the cervical mucus and, at least in part, of the endometrium. Progestogens utilized today differ largely in their pharmacokinetics. In general, after intake, these compounds are rapidly absorbed and distributed so that peak serum concentrations are reached between 1 and 4 h. Third-generation progestins (desogestrel, gestodene, norgestimate) have common characteristics: a higher affinity for progesterone receptors than their predecessors, a lower affinity for androgen receptors, a higher selectivity of action, a higher central inhibitory activity, a higher potency at the level of the endometrium, and an overall metabolic neutrality, in terms of effects on lipid and carbohydrate metabolism. In general, progestins can induce two types of adverse effects: changes in lipid metabolism and bleeding irregularities. Whereas the newer compounds seem to have overcome the first of these adverse effects, the second remains untouched: to this day, proper cycle control can only be achieved with combined hormonal contraceptives.

Al momento attuale, la ricerca medica in campo contraccettivo presenta alla donna una gamma di scelte ben piů ampia ed efficace rispetto al passato. Questo riguarda sia la contraccezione post-coitale sia i dispositivi intrauterini. Nel nostro paese la forte presenza della chiesa cattolica richiede la necessitŕ di raggiungere una mediazione tra etica e ricerca scientifica.

Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis.Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated.Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion.Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates.

Several selective progesterone receptor modulators (SPRMs) show promise in several areas of medicine and this work has been summarized by us in 2008.Since the publication of our reviews, several developments have taken place in the field of reproductive medicine. The first is emergency contraception (EC). Two SPRMs are clinically utilized today: mifepristone (MFP) and ulipristal acetate (UPA). MFP is available for EC in up to 120 h following unprotected intercourse. A dose of 10 mg is significantly more effective than levonorgestrel (LNG). In a metanalysis of the use of UPA versus LNG up to 72 h after unprotected intercourse, failure rates of 1.4 versus 2.2% were reported. The second is contraception. A daily dose of 2 mg MFP can block ovulation and several MFP regimens are being tested, including a vaginal ring releasing MFP. The third is the preoperative administration in women harboring leiomyomas, where clinical testing of several SPRM has shown that they can decrease uterine leiomyomas' size and substantially reduce uterine bleeding. SPRM can induce unusual, specific endometrial appearances. Many believe that these changes should not cause concern, but the issue remains controversial.SPRMs are very effective in EC and for the preoperative treatment of uterine leiomyomas.

Background The levonorgestrel-releasing intrauterine system (LNG-IUS) was first marketed in 1990 in Finland. Since then, it has been approved in approximately 120 countries throughout the world, with almost 50 million women-years of cumulative experience to date. Its high contraceptive effectiveness and favorable bleeding profile, leading to significant reduction of menstrual bleeding both in women with idiopathic menorrhagia and in those with normal menstrual bleedings, have been the key to the success of the system. At the same time, women need to be provided adequate preinsertion counseling about changes in menstrual bleeding to be expected. In the Italian context, it is important to highlight during counseling that amenorrhea is not harmful but can lead to health benefits such as an increase in iron blood stores and blood hemoglobin concentration. Study Design To evaluate contraceptive efficacy, compliance and the effect of changes in menstrual cyclicity on quality of life and sexuality of the LNG-IUS (Mirena®), 156 women attending the Family Planning Clinic to request contraception were enrolled in the study and inserted with the device. Results Menstrual blood flow decreased in all users, in terms of both quantity and duration; although spotting was present in 93.7% of the women, it disappeared within 6 months in the majority of cases. Amenorrhea occurred in 29.5% of all women, with onset within the first six cycles postinsertion. Data from the EuroQuality of Life-5D and Female Sexual Function Index questionnaires showed improvement in the quality of life, with a decrease in intercourse-related pain and an improvement in sexual desire. Conclusions Although in Italy intrauterine contraception is poorly accepted, once started on LNG-IUS, women found that the device represents a safe and effective contraceptive modality, with valuable noncontraceptive benefits, especially in the presence of heavy or prolonged bleeding.

Ever since natural sex hormones have been identified, their structure defined and their synthesis achieved, it became clear that their circulating half-life was too short to allow use in therapy. One of the modalities most thoroughly investigated to prolong their duration of action is to embed them in a polymeric matrix and administer them subcutaneously. Research and development activities of devices to be inserted under the skin have focused upon two modalities: the first utilizes the so-called nonbiodegradable devices, in which the matrix is fixed and the drug is made available through diffusion. In the second, biodegradable devices, the matrix dissolves during the process and both the active compound and the matrix components reach the circulation. Although a number of biodegradable systems have been investigated in the form of polymeric rod or micropellets, so far no system has reached the marketplace. Several matrices have been evaluated: poly(ortho esters), (polylactic-polyglycolic acid)co-polymers, poly-(epsilon-caprolactone). In the case of nonbiodegradable systems, several have been in widespread use for years. The first such system, Norplant 1, consists of six capsules delivering levonorgestrel and lasts a minimum of 5 years; the second, called Norplant 2 (Jadelle), consists of only two rods delivering the same amount of steroid of the first system, for the same duration of time. A third system already on the market is made up of a single rod releasing etonogestrel, the active metabolite of desogestrel, with duration of action of 3 years. Additional systems are still at the premarket stage. Subcutaneous implants have several obvious advantages, first and foremost their duration of action that can extend to at least 5 years, making them especially suitable for family-planning programs in developing countries; in addition, they are user- independent, again a positive feature in certain settings. Among the disadvantages, is a relatively complex insertion procedure that, for older systems, required ad hoc trained personnel and a small incision, clearly a disincentive. Newer devices, however, require a much simpler insertion procedure. Extracting systems is also complex and if a woman is lost to follow-up, implants will remain in the subcutaneous tissue forever.

Emergency contraception (EC), also known as 'the morning after pill', or post-coital contraception, is a modality of preventing the establishment of a pregnancy after unprotected intercourse. Both a hormonal and an intrauterine form are available. Modern hormonal EC, with low side effects, was first proposed by Yuzpe in 1974. More recently, a new regimen, consisting of levonorgestrel administered alone, was introduced and found in clinical trials to be more effective (if taken as early as possible), and associated with less side effects than the Yuzpe regimen, which it has gradually replaced. The WHO developed another regimen based on the use of the selective progesterone receptor modulator (antiprogestin) mifepristone and conducted trials with different dosages. Intrauterine EC was first proposed by Lippes in 1976. It has the advantage of being applicable for almost a week and the disadvantage of a greater complexity. In addition, this modality is solely interceptive, acting by preventing implantation. Pregnancy rates reported following EC using an intrauterine device with more than 300 mm2 of copper are consistently low (0.1-0.2%).

A large number of synthetic compounds known as selective progesterone receptor modulators can bind to progesterone receptors: the ligands exhibit a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism.Only a dozen or so selective progesterone receptor modulators have been tested to any significant extent: among them are mifepristone (RU 486), asoprisnil (J867), onapristone (ZK 98 299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710. Their clinical applications during pregnancy are discussed.A careful evaluation of existing major review papers and recently published articles was carried out focusing on mifepristone, the most widely studied selective progesterone receptor modulator, which was first used for the voluntary interruption of an early gestation. Other selective progesterone receptor modulators, especially those with partial agonist action, have shown little activity during pregnancy in animal models.Besides early and late voluntary interruption of gestation, selective progesterone receptor modulators have been tested in a variety of obstetrical situations: to obtain a ripening of the cervix, for the medical management of early embryonic loss and foetal death, for the induction of labour at term and for the medical treatment of extra-uterine pregnancies. The only applications that seem worthy of large-scale utilisation during pregnancy are voluntary interruption of early and late gestation, medical management of early delayed miscarriage and late foetal demise.

Modern contraceptive technology is more than a technical advance: it has brought about a true social revolution, the 'first reproductive revolution' in the history of mankind. This latter was followed in rapid succession by other major changes in human reproductive strategies. In the human species, sexual activity began to lose its exclusive reproductive meaning at an early stage of its evolution. Human beings must have practiced non-conceptive sex from the outset and therefore must have had a need to avoid, rather than to seek conception during intercourse from time immemorial. The search for methods to control fertility went on for millennia, but a valid solution was only found during the twentieth century, when the population explosion had forever changed the shape of humanity: in only one century the total population of the planet had grown from some 1.6 billion to more than 6 billion. That increase will remain unique in the history of Homo sapiens. At the global level, contraception provided a tool to deal with overpopulation and, in only 50 years, went a long way towards its resolution. However, to solve the problem, national and international family planning initiatives were required. For individuals, contraception also meant a revolution. It allowed sexual intercourse without reproduction. Only 25 years later, in vitro fertilisation permitted childbearing without sexual intercourse. Other advances followed and now cloning, that is, reproduction without the two gametes, looms on the horizon. Such a series of rapid, major changes in human reproductive strategies has confused many. For this reason, a constructive dialogue between sociology and biology is mandatory. Contraception is a powerful tool to promote equity between sexes; it improves women's status in the family and in the community. Avoiding pregnancy during the teens increases opportunities for a young woman's education, training and employment. By controlling their fertility, women get a chance to contribute economically to their household, which in turn may give them a greater share in decision-making. There are other specific areas in which contraception has produced beneficial social effects, first and foremost in reducing the need for induced abortion. It has also helped avoiding sexually-transmitted infections and is a very useful tool for educating youngsters to adopt more responsible sexual behaviors. Interventions in the field of family planning are among the most cost-effective health interventions.

To evaluate the reason for requesting emergency contraception (EC), previous use of contraceptive methods and provision route in a Family Planning Clinic in Italy.Women requesting EC were interviewed, through a questionnaire containing questions on demographic characteristics, about their reasons for requesting EC, their prior contraceptive use, their reasons for not using an effective contraceptive method (or possible reasons for its failure) and specifically about the so-called 'provision route' (i.e. whether and where they had previously requested EC receiving a negative response).Almost 70% of all women requesting EC were aged between 18 and 25 years. Some 80% of all women were in a stable relationship with their partner, with fewer than 20% having had an occasional intercourse. The vast majority of women (83%) reported prior use of a modern contraceptive method, i.e. 64% with a condom, 27% for combined oral contraceptives and 1.1% for the intrauterine device (IUD). In addition, 15% of the women had used more than one method (oral pills and condoms). Concerning the reasons for requesting EC, condom breakage or slipping was the most frequently cited (64%), followed by totally unprotected intercourse (28%), failed withdrawal (5%) and forgetting one or more pill (only 1.1%).More than one-third of the women interviewed had previously used an emergency contraceptive modality; although no one did so more than four times. Therefore, it can be inferred that-at least in the present series-EC had not been used as a routine contraceptive method. Finally, it seems clear that in Italy, even in large cities, information about the availability, proper usage and mechanism of action is lacking. This seems due to information being spread by word of mouth between peers and friends, with more formal communication channels lagging behind.

In assisted reproductive technology, three main areas are relevant from a health policy perspective: first, the technical excellence of the services rendered; second, a licensing and monitoring system to control all practitioners and the premises in which they work; and third, legislation to avoid abuse, prevent possible damage to the mother and the child and outlaw techniques unacceptable in a given cultural setting, including mechanisms to ensure the adherence by all to ethical and deontological principles. No one refuses the need to ensure that services offering assisted reproductive technologies adhere to technical excellence and everyone agrees that technical guidelines should exist and should be thoroughly enforced. When it comes to legislating about assisted reproductive techniques and, more specifically, to ruling in favour of limiting the use of existing technology to certain groups and not to others, or to ban altogether individual methods, views are sometimes totally divergent. In countries where legislation is fairly liberal, usually both physicians and the public view legislation with favour; conversely, where a number of restrictions exist, many complain that legislation impairs their ability to offer proper services. The solution seems to be a simple, well-defined, legislative act setting clear principles and providing for the creation of an Authority capable of resolving the myriad of individual problems that invariably arise from applying assisted reproductive techniques. Homo sum et nihil humanum a me alienum puto I am a human being and therefore cannot consider alien to me anything that helps another human being.

The original form of hormonal contraception ("the Pill") has developed into a variety of modalities administered through different routes: oral, intramuscular, subcutaneous, transdermal, intrauterine or intravaginal, and intranasal (abandoned). At present, two separate methods of hormonal contraception exist; one is used to prevent fertilization and the other to prevent pregnancy. From a pharmacological point of view, hormonal methods utilize either a combination of estrogen and progestin or progestin alone. Today all combined methods contain ethynylestradiol, and over the years there has been a substantial reduction in its dosage from almost 80 microg to as low as 15 microg. On the other hand, a variety of progestins are currently utilized that belong to two main chemical families: derivatives of progesterone and derivatives of 19-nortestosterone or gonane. These compounds, developed over a period of 50 years, can be distinguished in four successive "generations". Recent developments include new oral regimens intended to change the 7-day medication-free interval and new commercial preparations; the latter utilize the progestins drospirenone and dienogest. In addition, an oral contraceptive containing chlormadinone has also been marketed. Besides the oral route, contraceptive systems exist or are under development that employ the intramuscular, transdermal and intravaginal routes; they deliver both an estrogen and a progestin. Several patches and vaginal rings are also marketed. A variety of long-acting methods delivering only a progestin are also available. They use the subcutaneous route or are released from an intrauterine system, both of which provide optimal contraceptive protection and, depending on the system, can last up to 5 years (and probably more). Finally, progestin-releasing vaginal rings are under investigation. The second type of hormonal contraception, called "emergency contraception", utilizes progestins and antiprogestins and to be effective should be taken as soon as possible after unprotected intercourse.