Patients from across Europe have similar views on patient-centred care: an international multilingual qualitative study in infertility care.

BACKGROUND: International patient centredness concepts were suggested but never conceptualized from the patients' perspective. Previously, a literature review and a monolingual qualitative study defined 'patient-centred infertility care' (PCIC). The present study aimed to test whether patients from across Europe value the same aspects of infertility care. METHODS: An international multilingual focus group (FG) study with 48 European patients from fertility clinics in Austria, Spain, the UK and Belgium, with deductive content analysis. RESULTS: All specific care aspects important to participants from all countries could be allocated to the 10 dimensions of PCIC, each discussed in every FG, including: 'information provision', 'attitude of and relationship with staff', 'competence of clinic and staff', 'communication', 'patient involvement and privacy', 'emotional support', 'coordination and integration', 'continuity and transition', 'physical comfort' and 'accessibility'. Most specific care aspects (65%) were discussed in two or more countries and only a few new codes (11%) needed to be added to the previously published coding tree. Rankings from across Europe clearly showed that 'information provision' is a top priority. CONCLUSIONS: The PCIC-model is the first patient-centred care (PCC) model based on the patients' perspective to be validated in an international setting. Although health-care organization and performance differ, the similarities between countries in the infertile patients' perspective were striking, as were the similarities with PCC models from other clinical conditions. A non-condition specific international PCC model and a European instrument for the patient centredness of infertility care could be developed. European professionals can learn from each other on how to provide PCC.

Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF.

BACKGROUND: Anti-Müllerian hormone (AMH) is increasingly used to quantify ovarian reserve, but it has not yet realized its full clinical potential in assisted reproduction technology. We investigated the possible benefits of using novel, stratified ovarian hyperstimulation protocols, tailored to individual AMH levels, compared with conventional stimulation. METHODS: Retrospective data were collected from 769 women (first cycle of IVF, using fresh embryos), in a UK tertiary care unit: 346 women using conventional stimulation protocols; 423 women treated under new AMH-tailored protocols. RESULTS: Embryo transfer rates increased significantly (79-87%: P= 0.002) after the introduction of AMH-tailored stimulation protocols. Pregnancy rate per cycle started and live birth rate also increased significantly compared with conventionally treated women (17.9-27.7%, P= 0.002 and 15.9-23.9%, P = 0.007, respectively). Moreover, in the AMH group, the incidence of the ovarian hyperstimulation syndrome (OHSS) fell significantly (6.9-2.3%, P = 0.002) and failed fertilization fell from 7.8 to 4.5%. The cost of fertility drug treatment fell by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group. GnRH antagonist protocols, introduced as part of AMH-tailored treatment, may have contributed to the observed improvements: however, within the AMH-tailored group, the live birth rate was not significantly different between agonist and antagonist-treated groups. CONCLUSIONS: Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.

Update in endometriosis and IVF.

The impact of endometriosis on in vitro fertilization (IVF) has been the subject of numerous publications, although a number of critical issues related to the management of affected patients remain unsolved. Accurate assessment of the effect of this disease on IVF outcome requires an appraisal of the diagnostic limitations, the consequences of surgical and hormonal management of endometriosis and the potential impact of both disease and IVF on feto-maternal well-being. We have addressed all these aspects by attempting an overview of the literature of the last decade and we present an update which may be useful regarding the treatment options of subfertile women seeking pregnancy.

Altered glycosylation in peri-implantation phase endometrium in women with stages III and IV endometriosis.

BACKGROUND: Endometriosis is a common cause of infertility and pelvic pain. Lectin histochemistry has shown that glycan expression is a sensitive marker of differentiation in the normal endometrium. Endometrial biopsies were taken during the implantation window from women with subfertility and advanced (stage III and IV) endometriosis to evaluate specific glycans bound by lectins from Dolichos biflorus agglutinin (DBA) and Vicia villosa agglutinin (VVA), which detect related but distinct glycan sequences regulated by progesterone action. METHODS: Endometrial tissue from 12 women with subfertility and advanced endometriosis and 11 healthy controls were taken on days 19-24 of the menstrual cycle and processed into either epoxy resin or paraffin wax. Lectin histochemistry was analysed using light microscopy to quantify the amount of glandular reaction product. RESULTS: There was a significant (P = 0.011) reduction in DBA binding to endometrium from patients with endometriosis compared with controls, which was not seen with VVA (P = 0.135). Three stage IV biopsies and one stage III biopsy completely failed to bind DBA and, of these, three showed moderate glandular binding of VVA. DBA and VVA binding differed significantly (P= 0.0039) in the endometriosis specimens whereas in controls no significant difference was detected (P = 0.812). CONCLUSION: Secretory phase glycosylation in women with advanced endometriosis differs from that in healthy women with a reduction in fucosylated N-acetylgalactosamine sequences bound by DBA. Shorter VVA-binding glycans are not significantly affected. In addition to indicating abnormalities of epithelial differentiation, these findings may be directly relevant to implantation failure, as blastocyst attachment requires a critical interaction with the epithelial glycocalyx.

Managing the complications associated with assisted reproductive technologies.

Delaying conception has increased the demand on assisted reproduction. Currently, more than 1% of children are conceived through assisted reproductive technologies (ART) worldwide and this number is likely to continue increasing. Like any other medical intervention ART is associated with both short-term and long-term complications. The major short-term complications include ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. OHSS is difficult to predict, but meticulous preventive strategies and protocols are being developed that may limit it. Most of the morbidities in children born after ART are related to multiple pregnancies. New laboratory methodologies may allow the transfer of fewer embryos to maintain satisfactory live birth rates while reducing the risk of multiple pregnancies. In vitro fertilization may be associated with a slight increased risk for birth defects. Analysis of possible risks from these techniques is confounded by factors of underlying parental subfertility, fertility treatments and multiple births. The long-term sequelae remain largely undetermined. All outcomes of ART, including pregnancy rates and adverse complications, need to be compared with standard non-ART when deciding the appropriate course of treatment. The importance of counselling should never be ignored in any treatment decision.

Implantation, clinical pregnancy and miscarriage rates after introduction of ultrasound-guided embryo transfer.

The purpose of this study was to compare the reproductive outcome of ultrasound-guided (USG) embryo transfers versus clinical touch embryo transfers. A statistically powered retrospective analysis of women undergoing fresh and frozen embryo transfers in a National Health Service-based tertiary referral centre in the Department of Reproductive Medicine, St Mary's Hospital, Manchester was carried out. A total of 1723 embryo transfers were included in the analysis. The implantation rate was significantly higher in the USG embryo transfer group compared with the non-USG embryo transfer group (fresh: 19.9 versus 9.5%, P < 0.0001; frozen: 13.1 versus 7.3%, P < 0.0004). The clinical pregnancy rate was also significantly higher in the former group (fresh: 26.9 versus 12.5%, P < 0.0001; frozen: 15.6 versus 8.9%, P < 0.0015). For the frozen embryos, the miscarriage rate was significantly elevated among the USG embryo transfer group [unadjusted rate ratio (RR) = 1.65, 95% CI: 1.04, 2.62], but this was of borderline significance when the model was adjusted for the potential confounders (adjusted RR = 1.56, 95% CI: 0.997, 2.45). There was no difference in the ectopic pregnancy rates between the two groups. The findings of this study show that the practice of USG embryo transfer is associated with statistically higher implantation and clinical pregnancy rates in IVF.

Polycystic ovary syndrome: pathophysiology, molecular aspects and clinical implications.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age (5-10% prevalence) and the most common cause of anovulatory infertility. A recent consensus has led to the formulation of unifying diagnostic criteria for PCOS. It is multifactorial and polygenic in nature. Although the ovary is central to the pathogenesis of PCOS, however neuroendocrine, ovarian and metabolic dysfunctions play a significant role in the pathophysiology. Short- and long-term consequences of the syndrome have been the focus of much interest. The association of PCOS with hyperandrogenism, hyperinsulinemia and insulin resistance is known and some of the putative molecular aspects are established. Menstrual abnormalities (oligo- or amenorrhea), subfertility, obesity and symptoms of androgen excess are often the main reasons for early referral, whereas diabetes, cardiovascular disease and endometrial cancer represent a clinical finding later in life. It is plausible that appropriate specialist medical management improves the wellbeing of women with PCOS.

Evidence-based approach for the use of ultrasound in the management of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy, affecting 5-10% of women in the reproductive age group, with a wide spectrum of phenotypes. The cardinal features are hyperandrogenism, ovulatory dysfunction and/or polycystic ovary (PCO) appearance. Three major diagnostic criteria for PCOS have been proposed by the National Institute of Health (NIH 1990), the Rotterdam European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine sponsored PCOS Consensus Workshop Group (ESHRE/ASRM 2003) and the recent task force of the Androgen Excess Society (AES 2006). The PCO appearance is not a prerequisite for the diagnosis of PCOS. The aim of this review was to assess the available evidence in order to highlight the role of ultrasound in the diagnosis and management of PCOS. The evidence supports positive correlation between ultrasound features and biochemical indices of PCOS suggesting that ultrasound could play a role in prediction of PCOS severity and prognosis. Recent advances in ultrasonography resulted in a change of emphasis on the relative importance of total ovarian volume, follicle number and ovarian stromal changes in the diagnosis of PCO. In particular, ovarian stromal area/total area (S/A) ratio seems to have the most efficient diagnostic performance for hyperandrogenism. Three-dimensional (3D) ultrasound is a relatively new imaging modality that has the potential to improve the sensitivity and specificity of ultrasound without adding much to the practical management of the syndrome. In addition to its role in the definition of PCO, ultrasound is helpful to predict fertility outcome in patients undergoing treatment.

Pinopode expression during human implantation.

Implantation failure is considered the major impediment to successful in vitro fertilization pregnancy rate. Despite recent advances in reproductive medicine, the role played by uterine receptivity in contributing to human infertility remains unclear. Several clinical studies suggest the importance of blastocyst implantation in a narrow window of uterine receptivity, between 6 and 8 days after ovulation. This brief and precise period, called "implantation or nidation window", lasts less than 48 h and coincides with the formation of large and smooth projections, called "pinopodes", on the apical membranes of the endometrial epithelial cells. Pinopode expression appears to advance or retard depending on the hormonal treatments and an individual's particular response. This displacement can be followed through endometrial biopsy and scanning electron microscopy (SEM). Therefore, pinopode expression could be considered a useful biological marker to assess endometrial receptivity and to locate the implantation window.

[Influence of anthropometric parameters on bone mineral density. Correlations with age and sex]. / Influenza dei parametri antropometrici sulla densità osseo. Correlazioni con età e sesso.

BACKGROUND: The aim of the study is to analyse the relationship between bone mineral density (BMD) and some anthropometric parameters such as body weight and height, body mass index, age and sex. METHODS: This study has been carried out between January 1997 and March 2000 in 2839 patients, subdivided into 2679 women (mean age 63.2 +/- 11 years; range: 26-86 years) and 160 men (mean age 58.9 +/- 16.1 years; range: 20-95 years), at the Climatric Unit of the University of Catania The assessment of BMD was measured using a DEXA densitometer method (TurboScan p-DXA, NIM, Verona, Italy). In all patients with high risk for osteoporosis and bone fractures, a statistical analysis of the variance (ANOVA), in order to point out the predictivity of these parameters. RESULTS: The results of the measurements have confirmed a strong relationship between BMD values and sex, age and body constitution. CONCLUSIONS: On the basis of these results, the importance is stressed of diagnostic, instrumental and laboratory investigations for all patients with and without normal body constitution, in order to analyse the bone mineral status and establish an appropriate preventive therapy.

Controlled ovarian hyperstimulation regimens: a review of the available evidence for clinical practice. Produced on behalf of the BFS Policy and Practice Committee.

Before planning an assisted conception treatment cycle, a thorough assessment of the woman's hormone profile and ovarian reserve is essential to aid the decision on the appropriate protocol for controlled ovarian hyperstimulation (COH). There is insufficient evidence to recommend the use of one type of gonadotrophins over another. There is no benefit of luteinising hormone (LH) supplementation in cycles stimulated with follicle stimulating hormone alone in an unselected population. There is some evidence to suggest a potential benefit of LH supplementation in patients with a history of poor ovarian response to stimulation and in those older than 35 years. The long gonadotrophin releasing hormone (GnRH) agonist protocol is the most widely used and is the preferred protocol in the unselected population of women undergoing COH for in vitro fertilisation or intra-cytoplasmic sperm injection. The GnRH antagonist protocol is best used for known or suspected high responders, including women with PCOS, as it reduces the risk of OHSS. There is a lack of robust evidence to suggest that the GnRH agonist protocol is better than the GnRH antagonist protocol in poor responders. The prolonged GnRH agonist protocol is advantageous in women who are undergoing COH due to pelvic endometriosis. Oral contraceptive pill pre-treatment adversely affects the IVF outcome in GnRH antagonist cycles, but not in GnRH agonist cycles.

The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis.

BACKGROUND: It is estimated that there is at least a 2-fold rise in the incidence of monozygotic twinning after assisted reproductive technology compared with natural conception. This can result in adverse pregnancy outcomes. METHODS: We searched MEDLINE, EMBASE and SCISEARCH for studies that estimated the risk of monozygotic twinning and its association with any particular assisted reproductive technique. Monozygotic twinning was defined by ultrasound or Weinberg criteria. A meta-analysis of the proportion of monozygotic twins was performed using both fixed and random effects models. RESULTS: The search revealed 37 publications reporting on the incidence of monozygotic twins after assisted reproductive techniques. Twenty-seven studies met the inclusion criteria and were included in the meta-analysis. The summary incidence of monozygotic twins after assisted conception was 0.9% (0.8-0.9%). The incidence of monozygotic twins in natural conception is 0.4%. Blastocyst transfer and intracytoplasmic sperm injection are associated with 4.25 and 2.25 times higher risk of monozygotic twins. CONCLUSIONS: The risk of monozygotic twins in assisted conception is 2.25 times higher than the natural conceptions. Larger studies reporting on monozygotic twinning following single-embryo transfer or after post-natal confirmation of zygosity with DNA analysis are warranted before definitive conclusions can be drawn and guidelines produced. In order to provide adequate pre-conceptional counselling, it is important to monitor the incidence of monozygotic twins in both natural and assisted conceptions. We suggest building a national multiple pregnancy database based on accurate diagnosis of zygosity.

Stimulated intrauterine insemination (SIUI) and donor insemination (DI) as first line management for a selected subfertile population: the Manchester experience.

PURPOSE: The objective of our study is to investigate the optimum number of stimulated intrauterine insemination (SIUI) or donor insemination (DI) cycles that can be offered to the couples prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in a tertiary referral unit for assisted reproduction. METHODS: This is a retrospective analysis of 408 SIUI and 704 DI cycles performed in a tertiary referral unit for assisted reproduction. SIUI's were performed by controlled ovarian hyperstimulation and ovulation induction followed by insemination 36 h later. DI's were performed in natural or stimulated cycles after thawing frozen donor sperm. The main outcome measured was cumulative live birth rate (CLBR) per couple. RESULTS: A maximum CLBR of 26.1% was achieved after the fourth cycle of SIUI. The CLBR of DI increased to 60.1% in the sixth cycle. CONCLUSIONS: This study, in line with a number of other studies, is unable to demonstrate unequivocally whether increasing numbers of IUI or DI cycles are justified clinically or financially. There is a need for larger datasets from multiple centres along with rigorous randomised trials to compare treatment pathways. Until then, the resources spent on the provision of extra SIUI cycles may be better utilized by early referral to IVF.

Low-dose aspirin for in vitro fertilization: a systematic review and meta-analysis.

Despite recent advances in ovarian stimulation regimens and laboratory techniques, the pregnancy rate of assisted reproduction remains relatively low. New methods that would potentially improve implantation rates are needed. One proposed strategy involves enhancement of blood flow at the implantation site with the use of low-dose aspirin. We conducted a systematic review and meta-analysis to investigate the effect of low-dose aspirin on likelihood of pregnancy in women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). An electronic search of the literature was conducted targeting reports published over the last 26 years. Only randomized controlled trials (RCTs) comparing aspirin with placebo or no treatment in IVF/ICSI women were included in the meta-analysis. A number of relevant outcomes including pregnancy and live birth (LB) rates were investigated. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Inter-study heterogeneity among the trials was assessed using the Cochran's Q test. Ten RCTs were identified from the literature search, six of which met the criteria for inclusion in the meta-analysis. Clinical pregnancy (CP) rate per embryo transfer (ET) was not found to be significantly different between patients who received low-dose aspirin and those who received placebo or no treatment (RR 1.09, 95% CI 0.92-1.29). None of the other outcomes, including CP per cycle, spontaneous abortion or ectopic pregnancy per CP and LB rate per cycle or ET was found to differ significantly between the compared groups. On the basis of up-to-date evidence, low-dose aspirin has no substantial positive effect on likelihood of pregnancy and, therefore, it should not be routinely recommended for women undergoing IVF/ICSI.

Customised fetal growth chart: a systematic review.

Customised fetal growth chart is used to individualise fetal weight for gestational age by adjusting for physiological variables known to affect birth weight and growth. Compared with the standard population-based growth chart, the customised growth chart allows for better distinction between normal and abnormal smallness and reduces the false positive and false negative diagnosis of fetal growth restriction. The charts are currently being introduced into clinical practice in the West Midlands as well as in several units around the country. A Medline and systematic review search from 1980 to 2004 was performed in order to collect information and evidence on the use of customised growth chart and its effect on perinatal outcome.

Ovarian Leydig cell tumor in a peri-menopausal woman with severe hyperandrogenism and virilization.

The authors report a case of Leydig cell tumor in a 46-year-old woman who first presented with severe clinical hyperandrogenism and associated complex medical history. Investigations revealed markedly raised serum concentrations of testosterone (28.3 nmol/l) and free androgen index (54.4), whereas sex hormone binding globulin, random cortisol, androstenedione, 17-hydroxyprogesterone and dehydroepiandrosterone sulphate concentrations were all within the normal range. Transabdominal ultrasound and computed tomography scan of the pelvis and abdomen showed a slightly bulky right ovary, but no other abnormalities. An ovarian source of androgens was suspected and surgery was arranged. Following a three-year history of defaulting appointments due to agoraphobia, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and intraoperative selective ovarian venous sampling. Histopathological examination revealed a 2 cm Leydig cell tumor within the right ovary. Successful intraoperative ovarian venous sampling demonstrated significantly elevated testosterone levels (>260 nmol/l) from the right ovarian vein. Hyperandrogenaemia normalized post-operatively. The patient showed significant regression of clinical signs and symptoms, including the anxiety disorder. Clinical presentation, biochemistry and imaging modalities should allow to detect androgen-secreting ovarian tumors, while selective venous sampling should be reserved for patients whom uncertainty remains. The present case confirms that androgen-secreting ovarian tumors represent a diagnostic and therapeutic challenge. They have to be considered in the differential diagnosis of severe hyperandrogenism even in peri-menopausal women. Although selective venous sampling is of diagnostic value, however, its impact on future management should be considered on individual basis.

Serum luteinizing hormone, follicle-stimulating hormone and oestradiol pattern in women undergoing pituitary suppression with different gonadotrophin-releasing hormone analogue protocols for assisted reproduction.

Gonadotrophin-releasing hormone analogues (GnRH-a) are used widely in controlled ovarian stimulation (COS) cycles for assisted reproduction. At present, there is great debate about the influence of exogenous hormone activity on the hypothalamus-pituitary axis following pituitary desensitization. The objective of this comparative study was to investigate the pattern of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestradiol in women undergoing ovarian stimulation with different GnRH-a preparations. We retrospectively analysed 201 women, aged between 27 and 43 years, who were referred consecutively to our infertility clinic between January 2002 and January 2003. All women had no endocrinopathies or occult ovarian failure as assessed by day-3 hormone profile. Women were enrolled in one of the following COS protocols: depot triptorelin long protocol (n = 38), buserelin long protocol (n = 101) or buserelin short protocol (n = 62). Recombinant FSH was used to induce ovulation. Treatment was monitored by transvaginal ultrasound scan and serum measurement of FSH, LH and oestradiol. Among the women initially included, 30 had cancelled cycles due to poor ovarian response. Serum LH levels were significantly higher in the short-protocol group compared with the long-protocol groups (p < 0.001). The number of follicles, oocyte yield, number of grade-I embryos and fertilization rate were significantly lower in the short-protocol group than in the long-protocol groups. These findings showed that LH concentrations are significantly higher in women undergoing reversible medical hypophysectomy with a GnRH-a short protocol than in women treated with a long protocol. The hypothesis of an LH ceiling is confirmed.

Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate.

Clomiphene citrate (CC) is widely used as first-line treatment for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen citrate (TMX), another non-steroidal selective estrogen receptor modulator, may also be effective on the resumption of ovulation in these women. The aim of this controlled observational study was to compare the efficacy and safety of ovulation induction with TMX versus CC in anovulatory infertile women with PCOS. A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38) with PCOS were studied. Following a spontaneous or progesterone-induced withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg daily of TMX (days 2-5). In case ovulation failed to occur, the dose was sequentially increased to 100 mg daily of CC and 40 mg daily of TMX, respectively. Serum progesterone levels were measured on cycle day 21 to monitor the ovulation pattern. The overall ovulation rate was significantly higher in women who received TMX compared with those who received CC (61/98, 62.2% vs. 60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy rate per ovulatory cycle was higher in the TMX group compared to the CC group (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and there were no side-effects in either group of treatment. Collectively, these data demonstrate that TMX is a safe and effective agent, and a suitable alternative to CC for anovulatory infertility in women with PCOS.

Metformin therapy in the management of polycystic ovary syndrome: endocrine, metabolic and reproductive effects.

Polycystic ovary syndrome (PCOS) is a convergence of multisystem endocrine derangements. Impairment in insulin metabolism is a prominent feature of the syndrome and appears to play a key pathogenetic role precipitating the cascade of other disorders associated with PCOS. Recent studies report that insulin-sensitizing agents, such as metformin, reduce hyperinsulinemia, reverse the endocrinopathy of PCOS and normalize endocrine, metabolic and reproductive functions, leading to the resumption of menstrual cyclicity and ovulation. In this review, we report the most recent evidence regarding metformin usage in women with PCOS.

Endometrial lesions after tamoxifen therapy in breast cancer women.

Tamoxifen, a nonsteroidal antiestrogen with a partial estrogen-antagonist activity, is widely used as a hormonal adjuvant therapy for breast cancer in women with positive receptors for estrogens. Its prolonged administration has been associated with a series of collateral effects, among which the endometrial carcinoma is the most important. The aim of our study was to investigate an eventual correlation between a therapy with tamoxifen and the onset of endometrial lesions. We recruited 228 postmenopausal patients who had been operated on for breast cancer. They were divided into two groups according to the presence of positive or negative estrogen receptors. The group with positive receptors was subjected to hormonal adjuvant therapy by tamoxifen (20 mg/day for 5 years), while the group with negative receptors was not treated. All the patients underwent a hysteroscopic evaluation of the uterine cavity before and after treatment. The follow-up carried out 5 years later showed the presence of a statistically higher risk (p < 0.00001) of endometrial lesions, such as low glandular hyperplasia and polyps, than in the treated patients compared with untreated patients. On the other hand, because there was no onset of endometrial carcinoma, the risk of this kind of lesion turned out to be practically absent. In all the treated patients who did not evidence any endometrial lesions (n = 90) and in all those with negative receptors (n = 104) the endometrium seemed to have an atrophic aspect. In conclusion, according to these data, we believe that hormonal adjuvant therapy by tamoxifen (20 mg/day), associated with a periodic hysteroscopic evaluation, and eventually a directed biopsy of the endometrium in order to keep under control the frequent onset of benign endometrial lesions, does not absolutely seem to increase the risk of endometrial carcinoma.