Synthetic cyanoacrylic glue in the prevention of post-operative lymphocele after pelvic lymphadenectomy in patients with uterine malignancies: A prospective, single-blind, preliminary study.

OBJECTIVES: Lymphoceles are among the most common post-operative complications of pelvic lymphadenectomy, with a reported incidence of 1% to 29% in gynecology oncology. Several studies evaluated the effectiveness of biological glues on reducing lymphoceles, but no data on gynecological patients are available. We evaluated the effectiveness of cyanoacrylic glues (n-butyl cyanoacrylate) (Glubran 2 - GEM s.r.l., Italy) in preventing lymphocele on 30 patients who underwent pelvic lymphadenectomy for endometrial or cervical cancer. METHODS: Single-blind prospective randomized study. Patients were divided into 2 groups: pelvic lymphadenectomy plus n-butyl cyanoacrylate (treatment group: 44 patients) and pelvic lymphadenectomy without n-butyl cyanoacrylate (control group: 44 patients). Primary endpoint was incidence of pelvic lymphocele in the two groups 30 days after surgery, and evaluated with pelvic ultrasound and RMI examination. Secondary endpoints evaluated drainage volume of lymphorrhea 36, 48, 72 and 96 h after surgery. RESULTS: 15% in the treatment group and 36.6% in the control group had lymphocele 1month after the procedure (p<0.03; RR 0.4 [95% CI 0.152-0.999]). Concerning the secondary outcome in group A the amount of lymphorrhea presented a constant significant decrease during evaluation; on the contrary, in group B, after an initial decrease at 48 h, the amount of lymphorrhea remained unchanged; at all considered times the amount of lymphorrhea resulted significantly greater in controls. CONCLUSION: Intraoperative application of n-butyl cyanoacrylate seems to reduce lymph production after pelvic lymphadenectomy, providing a useful additional treatment option for reducing drainage volume and preventing lymphocele development after pelvic lymphadenectomy.

Transdermal estradiol and oral or vaginal natural progesterone: bleeding patterns.

OBJECTIVE: To evaluate the effects on bleeding pattern of two different doses of natural progesterone (NP) administered per os or per vagina in association with transdermal estradiol in a continuous, sequential estrogen-progestin therapy. METHODS: A prospective, randomized trial was conducted on 100 patients randomized into four groups. Each group received transdermal 17beta-estradiol treatment at the dose of 50 microg/day. Groups A and B received NP per os at the dose of 100 mg/day and 200 mg/day, respectively. Groups C and D received NP per vagina at the dose of 100 mg/day and 200 mg/day, respectively. RESULTS: After 12 cycles of treatment, no significant differences were observed in endometrial thickness between groups, suggesting that all treatments are effective in balancing the effects of estradiol on endometrium. Regarding bleeding control, patients in Groups C and D showed a higher number of episodes of regular bleeding than patients in Groups A and B and fewer episodes of spotting. The better control of bleeding was associated with a higher treatment compliance in patients who received vaginal NP, with a larger percentage of women completing the study. CONCLUSION: Transdermal estrogen replacement therapy combined with 100 mg of micronized NP administered per vagina from the 14th day to the 25th day of each 28-day cycle leads to good cycle control and provides excellent patient satisfaction without serious side-effects. This therapy could be a treatment of first choice in early postmenopausal patients.

Molecular mechanisms involved in GnRH analogue-related apoptosis for uterine leiomyomas.

GnRH agonist therapy is known to reduce uterine leiomyoma volume, although the molecular mechanisms responsible for this effect remain poorly understood. In this study, we have investigated the molecular mechanisms involved in the anti-proliferative effect of a GnRH agonist, leuprolide acetate (LA), in uterine leiomyomas obtained from six patients treated with LA for 3 months before surgery (group B), compared with tumours from six untreated patients (group A). To this end, we have evaluated the expression and the activity of molecules involved in the regulation of cell survival and proliferation. In group B, the total activity of PI3K was reduced by 60% compared with control samples. Furthermore, LA caused a reduction of PKB activation of approximately 50%, measured as serine 473 phosphorylation. In parallel with PKB reduction in LA samples, we observed a 60% reduction in the phosphorylation of its substrate BAD. While Bcl-xL/BAD association was not significantly modified in LA-treated leiomyomas, BAD/14.3.3 interaction was reduced, due to a 50% decreased 14.3.3 expression. In addition, LA was able to reduce the expression of the antiapoptotic proteins FLIP and PED/PEA15 by 70 and 50% respectively, compared with control samples. We next evaluated the activation of MAP kinases in leiomyomas. Activation of p42 and p44 MAP kinase isoforms was increased by 30% in group B. However, the phosphorylation of the transcription factor Elk1 was not increased in a similar fashion in LA-treated leiomyomas compared with group A. Thus, these data suggest that LA reduction of leiomyoma volume is mediated at least in part by a decreased activation of the PI3K/PKB survival pathway and by the suppression of antiapoptotic factors.

Serum leptin levels and uterine Doppler flow velocimetry at 20 weeks' gestation as markers for the development of pre-eclampsia.

Altered Doppler flow velocimetry of the uterine arteries during the second trimester is correlated with the risk of developing pre-eclampsia. Serum levels of leptin, a protein regulating body weight and secreted by the placenta, are higher in women with severe pre-eclampsia. We investigated whether alterations of uterine arteries' Doppler flow velocimetry during the early second-trimester scan were accompanied by changes in leptin levels, and whether these changes might be an early risk factor for pre-eclampsia. We retrospectively selected 50 women with altered uterine artery velocimetry at the second-trimester scan who subsequently developed pre-eclampsia (group A) and 100 women who did not develop pre-eclampsia, divided into two groups: 50 women with normal velocimetry at the second-trimester scan (group B) and 50 women with altered velocimetry at the second-trimester scan (group C). Serum leptin levels during the second and third trimesters and bilateral uterine artery resistance index during the second trimester were evaluated. No differences were observed in serum leptin levels in the second trimester among the three groups. During the third trimester, women in group A showed significantly higher serum leptin levels in comparison with women in groups B and C (p < 0.01). Serum leptin levels do not seem to be a useful early marker for the development of pre-eclampsia in the presence of altered uterine blood flow, and may be a late compensatory mechanism or reflect a generalized response of the trophoblast to hypoxic stimuli.

Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study.

In this prospective, controlled, randomized study, we compared the effect of a low-dose 21-day combined oral contraceptive (COC) containing 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GTD) (Group A; n = 19) with an ultra-low-dose 24-day COC containing 15 microg EE and 60 microg GTD (Group B; n = 18) on bone turnover and bone mineral density (BMD) in young, fertile women. Nineteen healthy fertile women were used as untreated controls (Group C). At 3, 6, 9 and 12 months of the study serum osteocalcin (BGP), urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) were measured in all subjects. At baseline and after 12 months BMD was determined at lumbar spine by dual-energy X-ray absorptiometry in all patients. In both Groups A and B, urinary levels of PYD and D-PYD at 6, 9 and 12 months, were significantly reduced in comparison with basal values and with control subjects (p < 0.05). No significant differences in urinary PYD and D-PYD levels were observed between Groups A and B during the entire period of treatment. At 12 months, no statistically significant difference in spinal BMD values was detected between the three groups and in comparison with basal values. The present study suggests that the two COCs could exert a similar positive effect on bone turnover in young postadolescent women, without any significant and appreciable modification of BMD.

Leptin induces mitogenic effect on human choriocarcinoma cell line (JAr) via MAP kinase activation in a glucose-dependent fashion.

Leptin and glucose effect on cell growth has been investigated in the JAr human choriocarcinoma cells. When JAr cells were cultured in the presence of 6m M glucose (LG), proliferation and thymidine incorporation were induced by serum but not by leptin. At variance, at 25m M glucose (HG), proliferation and thymidine incorporation were stimulated by leptin and serum to a comparable extent. HG culturing also enhanced leptin-stimulated insulin receptor substrate 1 (IRS1) and MAPK phosphorylation. Blockage of MAPK activity with PD98059 caused an inhibition of glucose- and leptin-dependent thymidine incorporation. At variance with HG conditions no effects were observed in cells cultured in 6m M glucose upon treatment with PD98059. Neither glucose nor leptin determined a modification in leptin receptors total content. In this study, we provide evidence that in placental cells, leptin, similarly to that observed with insulin, stimulates cell proliferation by inducing the IRS1/MAPK pathway in a glucose-dependent fashion.

[Hormone therapies in pregnancy]. / Terapie ormonali in gravidanza.

Maternal endocrine disorders can have detrimental effects on the fetus and the pregnancy can affect the course of a pre-exisiting endocrinopathy or induce the onset of one of these disorders. Therapies for endocrine disorders are not always safe to administer during pregnancy. Before administering any therapy to the mother, the effects on the fetus, the degree of placental trespassing as well as the potential damaging effects must be assessed. An accurate evaluation of the risks/benefits of any drug to be used on the mother is needed, assessing above all a potential theratogenic effect. In this review, the incidence of the main endocrine disorders, their evolution during pregnancy, their effects on mothers and fetuses and new acquisition on the treatment during pregnancy are discussed.

Effects of sex steroid hormones and menopause on serum leptin concentrations.

Leptin is a protein secreted by adipocytes; its circulating levels are correlated to fat mass and it acts on the hypothalamic centers regulating body weight. Leptin may also play an important role in regulating reproductive function. Indeed, ob/ob mice, lacking leptin due to a genetic mutation, are obese and infertile; administration of recombinant leptin to these animals reduces body weight and restores fertility. A sexual dimorphism in serum leptin levels has also been observed, with higher concentrations in women. Studies in vitro seem to indicate that estrogens stimulate leptin secretion, while in vivo studies are extremely discordant. In humans, several studies showed increased, unmodified and decreased leptin levels after the menopause. Furthermore, hormonal replacement therapy (HRT) after the menopause was reported to result in unmodified, increased or decreased leptin levels. It is likely that the effects of postmenopausal hypoestrogenism on leptin levels are masked by the postmenopausal changes in body composition. Indeed, after menopause, there is an increase in body weight, body mass index (BMI) and fat mass with a centralization of fat distribution. Administration of HRT may stop these changes and even restore a premenopausal pattern, leading then to decreased leptin levels.

Conscious sedation versus general anaesthesia for minilaparoscopic gamete intra-Fallopian transfer: a prospective randomized study.

BACKGROUND: Gamete intra-Fallopian transfer (GIFT) is a successful technique for infertile women, and is performed almost exclusively by laparoscopy under general anaesthesia. METHODS: We performed a prospective randomized study of 67 infertile patients to assess the efficacy of minilaparoscopic GIFT under conscious sedation/local anaesthesia (group A) compared with general anaesthesia (group B). Operative and discharge times and pregnancy outcome were evaluated in both groups. RESULTS: Operative time was similar in both groups. The rate of patients discharged 2 h after surgery was significantly higher in group A. The necessity for postoperative analgesics was significantly higher in group B. No significant differences were noted between the two study groups in terms of pregnancy outcome. CONCLUSIONS: Conscious sedation and local anaesthesia will allow us to perform an outpatient minilaparoscopic GIFT without the need for general anaesthesia. The simplicity of the method, and the quicker discharge time in comparison with general anaesthesia, offer a detectable benefit for patients.

[Effects of gonadotropins on oocyte maturation]. / Effetti delle gonadotropine sulla maturità ovocitaria.

The use of exogenous gonadotropins, alone or in association with other drugs, is a useful tool in the treatment of anovulation. The first stages of the follicologenesis are gonadotropin independent up to the preantral stage. The final phase of this process begins when follicles grow faster during the luteal phase of the preceding cycle, the so-called gonadotropin-dependent phase. Recent studies confirmed the central role of FSH in follicular and oocyte maturation, but also re-evaluated the actions of LH, in particular during the first phases of these processes. LH induces the physiological development of the follicle, acting only on a limited number of follicles, while FSH protects against atresia. In the absence of FSH the development will be delayed. It seems obvious that both hormones are necessary, that a stimulation protocol may rely only on FSH, but the addition of LH will render it more physiological.

[Changes of leptin levels in menopause]. / Modificazioni dei livelli sierici di leptina in menopausa.

One of the main advances in the field of metabolic control of body weight and obesity treatment was the identification of the OB protein or leptin, that plays an important role in controlling body weight, signalling to the CNS the amount of body fat. Indeed, leptin levels are positively correlated to indices of body fat, namely total fat mass, percent body fat and body mass index (BMI). This protein may be also the signal that indicates the nutritional status to the reproductive axis. Whether this signal is exerted directly on the gonads or through the neuroendocrine axis is still to be determined. A sexual dimorphism between male and female in serum leptin levels has been observed, with the latter showing higher serum leptin levels. This evidence has led to the hypothesis that estrogens might have a stimulatory role in leptin secretion. To evaluate this hypothesis, several authors have determined serum leptin levels in postmenopausal women that have estrogen levels comparable to those present in men. The results of these studies are contradictory and the aim of this article has been the revision of data present in the literature regarding serum leptin levels in menopause and to correlate them to body composition changes taking place during menopause.

Use of leuprolide acetate plus tibolone in the treatment of severe premenstrual syndrome.

OBJECTIVE: To evaluate the effectiveness of GnRH agonist (GnRH-a) plus tibolone in the treatment of severe premenstrual syndrome (PMS). DESIGN: Prospective, double-blind, placebo-controlled clinical trial. SETTING: Department of Obstetrics and Gynecology, University of Naples Federico II, Naples, Italy. PATIENT(S); Thirty patients affected by severe PMS, aged 23-29 years (mean age +/- SD, 25.3 +/- 2.9 years). INTERVENTION(S): Treatment for two cycles with leuprolide acetate depot (3.75 mg IM for 28 days) in association with tibolone (2.5 mg/d orally) or placebo (1 tablet per day orally). MAIN OUTCOME MEASURE(S): The mean severity of each symptom and sign of PMS was evaluated using a visual analog scale during the last 7 days of each treatment cycle in comparison with the last 7 days of the cycle before treatment. RESULT(S): Mean scores for each of the adverse psychological/physical and positive psychological symptoms were significantly improved during treatment. No statistically significant difference was detected between patients treated with tibolone and placebo. A significantly lower number of hot flushes per day was observed in groups treated with GnRH-a and tibolone in comparison with GnRH-a and placebo. CONCLUSION(S): Tibolone administered in association with GnRH-a does not reduce the therapeutic effect of GnRH-a in women affected by PMS. Tibolone used in association with GnRH-a may provide long-term medical treatment for women with PMS.

Using complete breastfeeding and lactational amenorrhoea as birth spacing methods.

The aim of this study was to evaluate the effectiveness of lactational amenorrhoea and to determine the relationship between extended breastfeeding and the return of fertility. Breastfeeding pattern, basal body temperature, cervical mucus, salivary ferning, vaginal blood discharge, frequency of sexual intercourse, and the presence of ovulation in the first cycle after the resumption of menses with ultrasonography were evaluated in 40 women. All subjects completed the study with only one case of incomplete breastfeeding. No pregnancies were observed. The mean number of feeding sessions and mean interval between sessions decreased significantly (p <0.01) during the first six months postpartum (7.5 +/- 1.3 after 60 days postpartum vs. 5.7 +/- 2.1 after 180 days, and 3.6 +/- 0.8 vs. 5.1 +/- 0.9, respectively). Eight women (20%) menstruated before weaning, but none had an adequate thermal shift, while 32 (80%) had their first vaginal bleeding after weaning with 12 (37.5%) registering an adequate thermal shift. Both basal body temperature and salivary ferning proved to be suggestive of ovarian activity, while mucus characteristics were not reliable in identifying fertile periods. Our study showed that breastfeeding associated with lactational amenorrhoea proved to be a good method of postpartum fertility control. Since the importance of supplementation is still debated, it is recommended that a "complete" breastfeeding program be used.

The importance of user compliance on the effectiveness of natural family planning programs.

Nowadays, there is an increasing interest in natural family planning methods. The biological basis for the application of natural family planning methods is the recognition of ovulation and, more extensively, of the fertile period. Several studies in the past decade have shown the efficacy of these methods and that the main cause of failure was either a conscious departure from the rules of the method or erroneous application of the method. Another problem affecting natural family planning that has been highlighted is the relatively high discontinuation rate. These features are probably due to low compliance in applying the natural family planning rules, which may be too demanding for a number of couples. In this review, there are comments on the application of natural family planning methods, the discontinuation rates and the failure of the method due to mistakes in the studies carried out in the past 15 years. Steps that can be taken to limit mistakes and discontinuity are also addressed.

Serum leptin levels in postmenopausal women: effects of transdermal hormone replacement therapy.

OBJECTIVE: To evaluate serum leptin levels in postmenopausal women who are receiving hormone replacement therapy (HRT) and postmenopausal women who are not receiving HRT with similar body mass index (BMI) to determine whether estrogens exert effects on leptin secretion. DESIGN: Cross-sectional, prospective study comparing serum leptin levels in premenopausal women, postmenopausal women who were not receiving HRT (group A), and postmenopausal women who were receiving HRT (group B). RESULTS: Serum leptin levels were significantly higher in group A in comparison to group B and control women (15.82 +/- 6.6 ng/ml, 8.14 +/- 4.17 ng/ml, and 10.12 +/- 5.48 ng/ml, respectively; p < 0.05). Total fat mass (FM) was found to be significantly higher in untreated postmenopausal women in comparison to the other two groups (22.66 +/- 2.79 kg vs. 19.14 +/- 3.39 kg vs. 18.98 +/- 3.82 kg; p < 0.05). No significant difference was observed in weight, height, BMI, blood pressure, or glucose levels among the three groups. A linear correlation between BMI and serum leptin levels as well as between total FM and serum leptin levels was observed in all groups. No correlation was found between serum leptin levels and months from menopause and months of HRT. CONCLUSIONS: Our results show that serum leptin is increased in untreated postmenopausal women, possibly as a consequence of the increase in FM, and that HRT reduces serum leptin levels to premenopausal values. These data need further investigation by a broader longitudinal study.

[Ovarian drilling in minilaroscopy and local anesthesia in the therapy of polycystic ovarian syndrome]. / Drilling ovarico in minilaparoscopia e anestesia locale nella terapia chirurgica della sindrome dell'ovaio policistico.

BACKGROUND: To evaluate the feasibility of ovarian drilling using minilaparoscopy under local anesthesia and to determine its efficacy in the surgical treatment of polycystic ovarian syndrome. METHODS: Prospective randomized study carried out in an out patient service on 62 women affected by PCOS divided into two groups: 32 patients (group A) underwent bilateral ovarian drilling by minilaparoscopy under local anesthesia and 30 patients (group B) underwent bilateral ovarian drilling by traditional laparoscopy under general anesthesia. RESULTS: Operation times were not different between the two groups. Discharge time was significantly lower in group A in comparison to group B. The rate of patients discharged after 2 hours was significantly higher in group A. The need for additional analgesia was lower in group A in comparison to group B. Serum LH, A and T levels were significantly reduced after surgery in both groups. Pregnancy rate after 1-year follow-up was higher, although not significantly in group A. Ovulation and abortion rates were not different between the two groups. CONCLUSIONS: Ovarian drilling in minilaparoscopy under local anesthesia is a new option for gynecologists, allowing similar therapeutical results to those achieved by traditional laparoscopy, but with the benefits of a less invasive technique that can be carried out in an outpatient service without the need for general anesthesia.

Efficacy of methods for determining ovulation in a natural family planning program.

OBJECTIVE: To evaluate the efficacy in ovulation detection of methods used in natural family planning in comparison with pelvic ultrasonography. DESIGN: Prospective analysis of ovulation detection by natural family planning methods and ultrasonography. SETTING: Natural family planning clinic, Department of Obstetrics and Gynecology, University of Naples "Federico II". PATIENT(S): Forty healthy women who were highly motivated to use natural family planning. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Transvaginal ultrasonographic findings, urinary LH levels, salivary beta-glucuronidase activity, salivary ferning levels and characteristics of cervical mucus, and BBT. RESULT(S): Urinary LH level determination yielded a 100% correlation with the simultaneous ultrasonographic diagnosis of ovulation. Mucus sensations and characteristics yielded a 48.3% correlation when simultaneously evaluated with ovulation. Beta-glucuronidase levels yielded a 27.7% correlation. The salivary ferning test had a 36.8% ovulation-detection rate the day of ovulation, but 58.7% of results were uninterpretable. Body temperature measurements yielded a 30.4% correlation with the simultaneous ultrasonographic diagnosis of ovulation. CONCLUSION(S): Measuring urinary LH levels is an excellent method for determining ovulation. Although variations in mucus characteristics and basal body temperature correlate somewhat with ovulation, the length of the fertile period is overestimated with these methods. The salivary ferning test and measurement of beta-glucuronidase levels are not good methods for home ovulation testing.

PIP: This methodological study aims to evaluate the efficacy of methods used for determining ovulation in a natural family planning in comparison with pelvic ultrasonography. Prospective analysis of ovulation detection methods was conducted with 40 women. Ovulation-detection methods employed in the study include transvaginal ultrasonography, daily morning urinary luteinizing hormone (LH) determinations, determination of salivary beta-glucuronidase activity, salivary ferning test, determination of cervical mucus levels and characteristics, and measurement of rectal or oral basal body temperature. Results revealed a 100% correlation between urinary LH level and ovulation diagnosis obtained from ultrasonographic examination. Other ovulation-detection methods contain the following correlation results: mucus sensations and characteristics, 48.3%; alpha-glucuronidase, 27.7%; and salivary ferning test, 36.8%. These findings draw the researchers to conclude that self-determination of LH levels could be an excellent method in ovulation determination.

A clinical trial of the effects of tibolone administered with gonadotropin-releasing hormone analogues for the treatment of uterine leiomyomata.

OBJECTIVE: To evaluate the effects of tibolone therapy in association with GnRH-a on uterine leiomyomata, on climacteric-like symptoms, on bone metabolism, and on the lipid profile. DESIGN: A prospective, randomized, double-blind, placebo-controlled, clinical trial. SETTING: Department of Gynecology and Obstetrics, University of Naples "Federico II," Naples, Italy. PATIENT(S): Fifty women with symptomatic uterine leiomyomata. INTERVENTION(S): Six months of treatment with leuprolide acetate (3.75 mg every 28 days IM) combined with daily placebo tablets (group A) or with 2.5-mg of tibolone per os (group B). MAIN OUTCOME MEASURE(S): Uterine and uterine leiomyomata sizes, lumbar spine bone mineral density, biochemical markers of bone metabolism, lipid profile, and myoma-related symptoms were measured at baseline and after 6 months of treatment. Daily symptom diary in which hot flushes and vaginal bleeding episodes were recorded. RESULT(S): No differences between the 2 groups in uterine and uterine leiomyomata size and myoma-related symptoms were detected. After 6 months of treatment, there were statistically significant changes from baseline in bone mineral density and in biochemical markers of bone metabolism in group A but not in group B. Vasomotor symptoms were significantly lower in group B than in group A. There was a statistically significant increase (P<.01) in serum total cholesterol, high-density lipoprotein cholesterol, and triglycerides in group A after 6 months of treatment in comparison with baseline values. The difference in serum total cholesterol and triglyceride levels after 6 months of treatment in group B was not statistically significant in comparison with baseline values, but was statistically significant in comparison with group A values (P<.01). In group B, levels of high-density lipoprotein cholesterol were significantly lower after 6 months of therapy in comparison with baseline values and in comparison with group A values (P<.01). There were no statistically significant changes at baseline and after 6 months of treatment in the level of low-density lipoprotein cholesterol in either group. CONCLUSION(S): Administration of tibolone in association with GnRH-a reduces vasomotor symptoms and prevents bone loss, without compromising the therapeutic efficacy of GnRH-a alone.

[Underestimation of ovarian pathology. Clinical aspects and medico-legal considerations]. / Sottostima della patologia ovarica. Aspetti clinici e considerazioni medico-legali.

In this review are reported the data regarding medical and gynecological responsibility in case of underestimation of ovarian pathology compared to epidemiological data. It is important to recognize the characteristics of the symptomatology, in general very mild, and the diagnostic tests suitable to detect ovarian masses. Four steps in the management of ovarian masses which may generate errors in the diagnostic and therapeutical process are stressed: the clinical diagnosis phase, the surgical phase, the management of borderline tumors, and the follow-up. It is also highlighted the importance of the concept of the "delay" in the medical action, both diagnostic and therapeutical, and an involvement of the Public Health Service, both in the prevention and the treatment of ovarian lesions, is ipothesized.

An overview on the effectiveness of natural family planning.

Recent years have witnessed important developments in natural family planning (NFP), which is based on the observation of fertile and infertile periods of the menstrual cycle, so that the couple is able to know when sexual intercourse may lead to a pregnancy. A review of the main studies regarding the effectiveness of NFP showed a decrease in the Pearl Index and life table values from the early 1980s to date, indicating that progress both in the teaching and in the application of these contraception, methods has been achieved. The main cause of lack of success seems to be the misapplication of NFP rules, whereas the errors due to the method itself are few. Furthermore, it seems that the symptothermal method might give better results than the ovulation method, even though no comparative study has been carried out, and that the first studies on the lactational amenorrhea method show encouraging results. Finally, it seems that NFP is best suited for 'spacers' of pregnancies, rather than for 'limiters'. Indeed, the former are more likely to show good compliance, since the sexual abstinence periods are limited and an unwanted pregnancy is not regarded as a completely negative event.