Delphi consensus on the monitoring tools of main individual risk factors for chronic diseases by the company doctor. / Ricerca di consenso Delphi sugli strumenti per il monitoraggio da parte del medico competente dei principali fattori di rischio individuali per malattie croniche.

BACKGROUND: Data on individual risk factors for chronic diseases (smoking, physical activity, body mass) are collected by company physicians in heterogeneous ways. This makes comparisons, researches and evaluations difficult. OBJECTIVES: The aim of the study was to find a consensus on evaluation tools for chronic diseases risk factors and for health promotion programs in workplaces that could be performed by company physicians during their clinical activity. METHODS: A first set of tools, proposed by a working group of occupational physicians in Bergamo, was submitted through the Delphi technique to a national expert panel of 22 persons including recognized national experts in specific fields and occupational physicians skilled in health promotion. RESULTS: In three Delphi rounds, the panel selected a set of tools to monitor the main individual risk factors for chronic diseases (smoking, alcohol, physical activity, nutrition, stress and mental health) as well as general data related to the worker and his job. CONCLUSIONS: The use of these specific tools, collected in a homogeneous format, should be recommended to all Italian company physicians, in particular those who work in WHP-programs, in order to allow analysis, comparison and evaluation of health promotion programs effectiveness at a national level.

Ovarian and adrenal androgens may be useful markers to predict oocyte competence and embryo development in older women.

The aim of this retrospective analysis was to evaluate the association between serum levels of various hormones and in vitro fertilization (IVF) parameters in poor responder patients. Serum levels of anti-Müllerian hormone (AMH), dehydroepiandrosterone sulfate (DHEAS), androstenedione and testosterone were measured before the start of IVF treatment cycle. We found that serum AMH and DHEAS levels were positively correlated with the number of mature oocytes, fertilized oocytes and developed embryos, both in pregnant and in non-pregnant patients. In contrast, we found a positive correlation between serum androstenedione levels and IVF parameters in pregnant, but not in non-pregnant patients. In this latter group, androstenedione levels were positively associated with the number of mature oocytes and were negatively correlated with the number of fertilized oocytes. No correlation was observed with developed embryos. Finally, we reported a negative correlation between serum levels of testosterone and IVF parameters in pregnant women whereas no correlation was observed in non-pregnant patients. Our results suggest that serum AMH and DHEAS could be predictive for oocyte retrieval and embryo development. Moreover, the positive correlation between serum androstenedione levels and IVF parameters in pregnant patients, together with the lack of a consistent correlation in non-pregnant women seem to identify androstenedione as a more predictive marker for pregnancy outcome than testosterone. In addition, in our analysis testosterone shows a negative correlation with IVF parameters.

Ovulation induction and luteal support with GnRH agonist in patients at high risk for hyperstimulation syndrome.

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75-150 UI/day were started on day 2-5, GnRH antagonist was added when the lead follicle was >14 mm and the final trigger was obtained with hCG 250 µg or triptorelin 0.2 mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.

DHEA supplementation positively affects spontaneous pregnancies in women with diminished ovarian function.

The aim of this article is to describe unexpected spontaneous pregnancies in poor responder patients with long-term infertility, when treated with dehydroepiandrosterone (DHEA) supplementation prior to in vitro fertilization (IVF). Our evaluation was carried out in two groups of women. The first group included 39 young women with <40 years, all treated with DHEA because of a previous poor response. The second group included 38 women over 40 years who received DHEA supplementation. Controls for latter group were 24 comparable women who had not been treated with DHEA before the first IVF cycle to evaluate the spontaneous pregnancy rate during preparation to IVF. Three tablets daily of 25 mg micronized DHEA were administered for at least 12 weeks before starting a long stimulation protocol for IVF. Surprisingly, spontaneous pregnancy rate significantly increased after DHEA treatment, allowing to achieve 10 spontaneous pregnancies and 9 spontaneous ongoing pregnancies among young poor responders. Pregnancy rate and ongoing pregnancy rate obtained before starting the IVF cycle were also significantly higher in older women treated with DHEA than in the control group: 21.05% and 13.15% and 4.1% and 0, respectively. Our results show that DHEA supplementation improves the ovarian function in poor responders and in women over 40 years, suggesting that this molecule alone can raise fecundity and fertility treatment success in women with poor prognosis for pregnancy.

IVF-ICSI outcome in women operated on for bilateral endometriomas.

BACKGROUND: The influence of previous conservative surgery for endometriomas on IVF-ICSI outcome is debated. Conflicting information emerging from the literature may be consequent to the fact that endometriomas are mostly monolateral. The contralateral intact ovary may adequately supply for the reduced function of the affected one. To clarify this point, we assess IVF-ICSI outcome in women operated on for bilateral endometriomas. METHODS: Women selected for IVF-ICSI cycles who previously underwent bilateral endometriomas cystectomy were matched (1:2) for age and study period with patients who did not undergo prior ovarian surgery. RESULTS: Sixty-eight cases and 136 controls were recruited. Women operated on for bilateral endometriotic ovarian cysts had a higher withdrawal rate for poor response (P < 0.001). In these patients, despite the use of higher doses of gonadotrophins, the number of follicles (P = 0.006), oocytes retrieved (P = 0.024) and embryos obtained (P = 0.024) were significantly lower. The clinical pregnancy rate per started cycle in cases and controls was 7% and 19% (P = 0.037) and the delivery rate per started cycle was 4% and 17%, respectively (P = 0.013). CONCLUSIONS: IVF outcome is significantly impaired in women operated on for bilateral ovarian endometriomas.

The clomiphene citrate challenge test (CCCT) in women with elevated basal FSH: biological significance and predictive value.

OBJECTIVE: The rationale of the clomiphene citrate challenge test (CCCT) is that day 10 serum FSH is influenced by the quality of the recruited oocytes. Biological evidence supporting this assumption is, however, lacking. The aim of this study is to investigate the relationship between results from the CCCT and the quantity and the quality of the recruited oocytes. STUDY DESIGN: Patients selected for in vitro fertilization (IVF) and who were found to have elevated basal FSH (n=114) underwent an IVF cycle using follicles developing during CCCT. Subsequently, a subgroup of patients (n=89) underwent a second cycle receiving high doses of gonadotropins. The main outcome considered was the transfer of viable embryos. RESULTS: During the CCCT cycle, the area under the receiver operating characteristics (ROC) curves for day 3 and day 10 serum FSH to predict embryo-transfer was 0.48 (95% CI, 0.37-0.60) and 0.74 (95% CI, 0.63-0.82), respectively. In the subsequent cycle, the area under the ROC curves for the two variables was 0.58 (0.43-0.72) and 0.58 (0.43-0.72), respectively. CONCLUSIONS: CCCT effectively mirrors the quantity and the quality of the recruited oocytes but its predictive value is low.

The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins.

OBJECTIVE: To clarify whether the presence of ovarian endometriomas is associated with a reduced responsiveness to ovarian hyperstimulation. DESIGN: Observational study. SETTING: University teaching hospital. PATIENT(S): Women selected for in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycles who were found to have unilateral ovarian endometriomas and who did not undergo previous ovarian surgery. INTERVENTION(S): Ovarian hyperstimulation using gonadotropins. MAIN OUTCOME MEASURE(S): Number of codominant follicles (mean diameter >15 mm) in the affected and in the contralateral intact gonads. RESULT(S): Thirty-six patients were enrolled. They underwent 56 IVF-ICSI cycles. The number of codominant follicles in the intact and affected ovaries were 4.0 +/- 2.2 and 3.0 +/- 1.7, respectively (P=.01). This difference corresponded to a mean reduction (95% confidence interval [CI]) of 25% (6%-44%). This deleterious effect was more evident in women with larger cysts, in those with more than one cyst, and in those who were more responsive to ovarian hyperstimulation. CONCLUSION(S): The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins.

Preventing high-order multiple pregnancies during controlled ovarian hyperstimulation and intrauterine insemination: 3 years' experience using low-dose recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists.

OBJECTIVE: To employ protocols of mild ovarian stimulation to prevent an excessively elevated rate of high-order multiple pregnancies. DESIGN: Case series. SETTING: University hospital. PATIENT(S): Six hundred and twenty one consecutive patients undergoing 1,259 controlled ovarian hyperstimulation and intrauterine insemination cycles. INTERVENTION(S): Patients received 50 IU per day of recombinant follicle-stimulating hormone (FSH) starting the third day of the cycle, then a gonadotropin-releasing hormone (GnRH) antagonist on the day in which a follicle > or =13 mm was visualized. Cycles were canceled if three or more follicles > or =16 mm and/or five or more follicles > or =11 mm were detected. MAIN OUTCOME MEASURE(S): Rate of high-order multiple pregnancies. RESULT(S): The clinical pregnancy rate per initiated cycle was 9.2% (95% confidence interval, 7.5-11.1%). The incidence of twins and high-order multiple pregnancies was 9.5% (95% CI, 5.3-16.2%) and 0 (0.0-3.2%), respectively. CONCLUSION(S): In controlled ovarian hyperstimulation and intrauterine insemination cycles, a protocol of 50 IU of recombinant FSH daily combined with the use of GnRH antagonists and a policy of strict cancellation based on echographic criteria are associated with a satisfactory pregnancy rate per initiated cycle and a low risk of high-order multiple pregnancies.

Does laparoscopic removal of nonendometriotic benign ovarian cysts affect ovarian reserve?

BACKGROUND: The objective of this study was to investigate whether laparoscopic excision of nonendometriotic benign ovarian cysts is associated with a significant injury to ovarian reserve. METHODS: Women selected for IVF-ICSI cycles who previously underwent laparoscopic excision of a monolateral nonendometriotic benign ovarian cyst were retrospectively identified. The operated ovary and the contralateral intact gonad of the same patient were compared in term of basal ovarian volume before initiating ovarian stimulation and number of dominant follicles at the time of human chorionic gonadotropin administration. Non-parametric Wilcoxon Rank test was used to investigate differences between the two ovaries. RESULTS: Seventeen cases were recruited. The numbers of dominant follicles were 4.6 +/- 2.5 and 2.7 +/- 2.4 in the control ovary and in the previously operated ovary, respectively (p = 0.01). This drop corresponded to a mean reduction of 42% (95% confidence interval: 10-74%). Basal volumes of the intact and the operated gonads were 5.7 +/- 3.3 and 3.4 +/- 2.3 cm3 respectively (p = 0.01), corresponding to a mean reduction of 39% (95% confidence interval: 12-66%). CONCLUSIONS: Laparoscopic excision of nonendometrioid benign ovarian cysts is associated with a significant injury to ovarian reserve.

Effectiveness of sonohysterography in infertile patient work-up: a comparison with transvaginal ultrasonography and hysteroscopy.

OBJECTIVE: The aim of this comparative study was to evaluate the accuracy of transvaginal ultrasonography (TVU), sonohysterography (SHG) with sterile saline solution compared to hysteroscopy in the diagnosis of intrauterine pathology in a population of infertile patients before an in vitro fertilization (IVF) program. PATIENTS/METHODS: 98 infertile patients with a mean age of 33.9 years (range 27-41) underwent TVU assessment and SHG with sterile saline solution immediately followed by hysteroscopy. RESULTS: The clinical findings obtained by TVU, SHG and hysteroscopy were compared. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TVU and SHG compared to hysteroscopy were calculated. The TVU sensitivity and specificity compared with hysteroscopy were 91 and 83% respectively. Using TVU, a 9.2% false positive rate (9 cases) and a 5.1% false negative rate (5 cases) were detected compared to hysteroscopy. The TVU PPV and NPV were 85.4 and 90% respectively. SHG yielded better results: sensitivity and specificity when compared to hysteroscopy were 98 and 94% respectively. The SHG PPV and NPV were 95 and 98% respectively. Accuracy of SHG was significantly better than TVU considering all intrauterine pathologies and polyps. CONCLUSION: In experienced hands, SHG is an easy, safe, and well-tolerated alternative to diagnostic hysteroscopy in the initial evaluation of uterine cavity infertile patients.

Reproductive prognosis in male patients with azoospermia at the time of cancer diagnosis.

OBJECTIVE: Fertility status evaluation in patients found azoospermic at the time of malignancy diagnosis. DESIGN: Case series follow-up. SETTING: University Hospital Sperm Banking service. PATIENT(S): Male cancer patients found azoospermic between 1986 and June 2000. INTERVENTION(S): Patients were interviewed about their reproductive history and were invited for a free semen analysis. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) and percentage of patients with viable spermatozoa in the ejaculate. RESULT(S): Sixty-five patients were enrolled; 16 were lost at follow-up, 7 died, and 42 were followed to the end of the study. The median (range) time of follow-up for the 42 remaining patients was 9 years (2-14 years). Seventeen patients had wanted to father a child; 12 had a child (71%, 95% confidence interval [CI] 48%-88%). Semen analysis results were available in 11 patients. Resumption of spermatogenesis was documented in 9 cases (82%, 95% CI 53%-97%). CONCLUSION(S): Spontaneous fertility recovery is frequent in patients who are azoospermic at the time of cancer diagnosis.

Sperm banking and rate of assisted reproduction treatment: insights from a 15-year cryopreservation program for male cancer patients.

BACKGROUND: Semen cryostorage remains the only proven method to preserve fertility in men with cancer. However, the necessity and the justification of banking spermatozoa have been questioned because it has been reported that only a small percentage of patients are referred for assisted reproductive technologies using frozen semen. METHODS: A 15-year cryopreservation program involving 776 men with malignant diseases who were referred to the study institution for semen cryopreservation before proceeding with chemotherapy and/or radiotherapy was reviewed. Data regarding cancer diagnosis, age, semen quality, and use of frozen semen were analyzed. RESULTS: Sperm banking was not performed for 90 of the 776 subjects (11.6%) because of azoospermia. Sperm quality was reduced in men with testicular carcinoma. To date, 36 of the 686 patients who had banked spermatozoa (5.2%) have attended the clinic for assisted conception treatments using frozen spermatozoa. Cumulative rates related to the use of frozen semen at 4, 8, and 12 years were 4.5%, 8.7%, and 11.8%, respectively. Relevant factors demonstrated to be significantly associated with a lower probability of using frozen material were a younger age at the time of cryostorage and a diagnosis of testicular carcinoma. CONCLUSIONS: The rate of referral for assisted reproductive techniques in patients who have banked their semen is low but tends to rapidly increase extending the length of follow-up. The cumulative percentage of use is at least above 10% but a longer follow-up is required to draw definitive conclusions. A diagnosis of testicular carcinoma is associated with a lower rate of use when compared with other cancers. Cancer 2003;97:1624-9.