ALWAYS ICSI? A SWOT analysis.

PURPOSE: Intracytroplasmatic sperm injection (ICSI) is a common procedure used to improve reproductive results, even among couples without male factor infertility. However, the evidence available is still uncertain on the possible advantages and deficiencies that this procedure may have in patients with no formal indication for ICSI. METHODS: A SWOT (strengths, weaknesses, opportunities, threats) analysis examines the possible advantages and deficiencies of performing ICSI in these patients with no formal indication. RESULTS: The evidence suggests that ICSI is not justified for non-male factor infertile couples requiring in vitro conception. One of the major strengths associated to the procedure is the virtual elimination of cases further complicated by total fertilization failure and a combination between IVF and ICSI on sibling oocytes has been advised in the literature. Greater technical difficulties, higher costs and performing an unnecessary invasive technique in some cases represent some of the weaknesses of the procedure, and questions regarding safety issues should not be ruled out. CONCLUSION: Despite the widespread use of ICSI in patients without a formal diagnosis of male factor infertility, evidence demonstrating its effectiveness in this population is still lacking. Additional large and well-designed randomized controlled trials are needed to clarify definitive indications for ICSI in non-male factor infertility.

Hysteroscopic septum resection and reproductive medicine: A SWOT analysis.

Hysteroscopic septum resection in women with unfavourable reproductive and clinical outcomes has become common practice worldwide to improve reproductive results. No clear evidence on the possible advantages and drawbacks of this procedure has been published. In this opinion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Currently, no level 1 published evidence supports uterine resection in women with septate uterus. Clinical evidence from the studies analysed matches the more recent guidelines and suggests an improvement in reproductive outcomes after hysteroscopic resection of the septum, particularly in infertile women and women who have experienced recurrent miscarriages. In a patient with no history of infertility or prior pregnancy loss, it may be reasonable to consider septum incision after counselling about the potential risks and benefits of the procedure. Published clinical data in favour of the intervention, however, are based on studies with important methodological limitations. In this situation, the clinician and patient should reach an agreement together, based on the pros and cons of this intervention. Well-designed randomized controlled trials are required to confirm the clinical benefits and cost-effectiveness of this procedure.

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial.

OBJECTIVE: Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN: We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS: A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS: We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS: A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS: Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.

Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome.

Treatment with insulin-sensitizing agents is a relatively recent therapeutic strategy in women with polycystic ovary syndrome (PCOS) and insulin resistance. The key areas addressed in this review include PCOS and the development of type 2 diabetes mellitus and gestational diabetes, as well as the use of insulin-sensitizing agents, particularly metformin, in the management of infertility in obese and non-obese PCOS women. Treatment with metformin in PCOS women undergoing IVF and the use of metformin during gestation will be discussed. The challenge for the health care professional should be the appropriate utilization of pharmacotherapies to improve insulin sensitivity and lower circulating insulin levels resulting in beneficial changes in PCOS phenotype. Further research into the potential role of other insulin-sensitizing agents, such as pioglitazone and rosiglitazone, in the treatment of infertile women with PCOS is needed.

Nuevos avances en el Síndrome de ovarios poliquísticos / New aspects of polycystic ovarian syndrome

El síndrome de ovarios poliquísticos o anovulación hiperandrogénica continúa siendo una entidad mal definida que abarca un espectro amplio de pacientes. La disrgulación enzimática y el hiperinsulinismo constituyen los mecanismos responsables de la mayor parte de las alteraciones que acompañan a esta enfermedad. En la actualidad ambos trastornos parecen tener un trasfondo genético.Los criterios diagnósticos siguen siendo ambiguos y limitados a la clínica, las determinaciones hormonales y la ecografía transvaginal. A las modalidades terapéuticas clásicas se han añadido nuevos antiandrógenos más potentes como la flutamida, fármacos que mejoran la sensibilidad a la insulina o las gonadotrofinas recombinantes cuando existen deseos gestacionales (AU)

Safety and effectiveness of hormonal postcoital contraception: a prospective study.

OBJECTIVE: The aim of this study was to evaluate the demographic characteristics of the population attending our hospital requesting postcoital contraception and to determine the effectiveness of the method and its side-effects. METHODS: A total of 503 women asking for postcoital contraception were included in a prospective open trial. After filling in a questionnaire dealing with demographic and contraceptive data, we prescribed an ethinylestradiol-levonorgestrel combination (100 micrograms/500 mg for two doses 12 h apart). RESULTS: Only 487 women were available for analysis of demographic data. A further 77 were excluded because they presented irregular menstrual cycles and 55 cases were lost for follow-up. Mean age was 22.6 +/- 5.25 years and 35.9% of cases came to the center within the first 5 h after unprotected intercourse. Only 18.8% had previously asked for postcoital contraception. Breakage of condom was the most common reason for request (81.9%). Two pregnancies occurred in the remaining 355 women. According to Dixon's method 15.5 pregnancies should be expected being the overall efficacy of 87.14%. There were no serious adverse effects. Nausea and vomiting (16.33%) were the most prevalent and 59% of the users menstruated at the expected time whilst menses were delayed in 6% of the cases. CONCLUSION: The combination of ethinylestradiol and levonorgestrel in low doses is an effective and safe method of postcoital contraception.

The role of matching menstrual data with hormonal measurements in evaluating effectiveness of postcoital contraception.

The effectiveness of postcoital contraception can only be estimated. The most commonly used method of calculation compares the expected pregnancy rate in the exposed population to the resultant pregnancies after treatment. Estimation of the fertile period and the day of ovulation are critical to calculate the expected pregnancies. The aim of this study was to improve the accuracy of calculations by evaluating the hormonal status on the day of contraceptive treatment. A total of 483 consecutive women requesting postcoital contraception was included in a prospective observational trial. A blood sample was obtained at the moment of consultation to measure serum luteinizing hormone, estradiol, and progesterone concentrations. An ethinylestradiol-levonorgestrel combination (100 micrograms/500 mg for two doses, 12 h apart) was then prescribed. The fertile period was estimated according to previous hormonal studies in the normal cycling population. Of 483 women, 64 (13.25%) women were excluded because they presented irregular menstrual cycles and 37 (7.6%) women were lost to follow-up. Two pregnancies occurred in the remaining 382 women. Following Wilcox's and Trussell's methods, 21.1 and 17.75 pregnancies should be expected, yielding an overall treatment effectiveness of 90.52% (95% confidence interval [CI] 62.58%-97.6%) and 88.73% (95% CI 55.93%-97.12%), respectively. Hormonal data were available in 356 women; 303 of whom presented with regular cycles. Hormonal information in this group restricted the number of exposed cases to 88 women. Of the women included in Trussell's method of analysis, only 51 (51.5%; p < 0.05) were at risk using hormonal data. Fifty-six percent (95% CI 34.9%-75.6%) of women with luteinizing hormone levels > 20 IU/L were not between days-1 and +1 of the cycle. Hormonal studies suggest that methods based on pregnancy risk calculated by cycle day do not faithfully reflect the real exposure.

Long-acting repeatable bromocriptine in the treatment of patients with microprolactinoma intolerant or resistant to oral dopaminergics.

OBJECTIVE: To study the efficacy of long-acting repeatable bromocriptine in suppressing abnormal PRL secretion in microprolactinoma patients. To assess the incidence and nature of side effects induced by the product. DESIGN: Longitudinal, open label, noncontrolled. SETTING: Human hyperprolactinemic volunteers in an academic clinical research environment. PATIENTS: Ten patients with radiologically proven microademonas resistant or intolerant to oral bromocriptine were included. INTERVENTIONS: The patients were treated with 50 to 150 mg of long-acting bromocriptine monthly during 6 months. MAIN OUTCOME MEASURE: The serum PRL concentrations and the side-effects were assessed before and after each new injection. RESULTS: Serum PRL levels decreased during the first cycle to normal values in four patients. At the end of the study the PRL levels were normalized in five cases and were only slightly increased in three. One patient was resistant to the treatment. Two among four infertile women became pregnant. In nine patients the accompanying symptoms disappeared after the 2nd month. Adverse events were mild or moderate and circumscribed to the 1st month of treatment. CONCLUSION: The long-acting bromocriptine is both effective and well tolerated and is a good alternative to the oral approach in the management of microprolactinoma patients.

Early skin metastasis of endometrial adenocarcinoma: case report and review of the literature.

A seventy-seven-year-old patient presented with skin metastasis from endometrial adenocarcinoma in a laparotomy scar, seven months after surgery. On reviewing current literature, it was clear that this was an unusual site for metastasis. We review the possible pathologic mechanism of this recurrence, its prognosis, and treatment.

Outcome and long-term effects of pregnancy in women with hyperprolactinaemia.

Twenty-four women with high circulating prolactin became pregnant on 39 occasions, of which 32 ended in delivery. Sixteen patients showed radiological evidence of pituitary tumour, 6 exhibited a normal CT and 2 had an empty sella. The pregnancies were induced in 4 patients after successful pituitary surgery, in 3 after surgery and medical treatment, and in the rest by bromocriptine (16) long-acting repeatable bromocriptine (1) and methergoline (1). No major complications related to hyperprolactinaemia or its treatment were observed during pregnancy in the patients or offspring. Prolactin after pregnancy was lower than before (basal 95 micrograms/l, after 1st pregnancy 38 micrograms/l P < 0.002, after 2nd pregnancy 24 micrograms/l P < 0.005 compared to basal prolactin); this prolactin reduction tended to be greater in the 9 multiparous patients, but did not attain statistical significance, probably because the number of multiparous patients was too small. A new empty sella developed after delivery in 4 women and persisted in another 2, all of which were medically treated; prolactin fell in all 6 cases normalizing in 3; 4 of these patients had undergone two or more pregnancies. The mean period of follow-up from the last pregnancy was 41.6 months (8-101). These data suggest that pregnancy may hasten a tendency to spontaneous improvement of hyperprolactinaemia, and multiparity may be beneficial in this way.

[Serum insulin and androgen concentrations in women with histories of gestational diabetes]. / Concentraciones séricas de insulina y andrógenos en mujeres con antecedentes de diabetes gestacional.

BACKGROUND: There is a certain degree of peripheral cell resistance to insulin in the physiopathology of gestational diabetes. These disturbances may persist following pregnancy giving place to secondary hyperinsulinism. Insulin exerts a trophic action on the ovary and favors the production of androgens. The aim of this study was to verify whether the patients diagnosed of gestational diabetes present androgenic alterations following pregnancy. The existence of a correlation between the values of insulin and androgens was analyzed. METHODS: Fifty-one patients were studied. The study group (n = 297) was composed of patients diagnosed of gestational diabetes during their last week of pregnancy. The control group (n = 24) included patients with normal carbohydrate tolerance. The basal values of insulin, glucose, androstenedione, testosterone and SHBG were determined in a postmenstrual phase. RESULTS: Insulin was found to be higher in the study group (78.1 +/- 32.9 pmol/1 vs 63.0 +/- 27.6 pmol/1) although the differences were not significant. The insulin/glucose ratio was significantly higher in the study group (18.1 +/- 8.0 vs 13.9 +/- 7.7; p less than 0.05). Basal insulin and the insulin/glucose ratio were comparable among the obese and non obese patients of both groups. The remaining parameters studied dit not present any significant differences. No significant associations were observed between the values of insulin and insulin/glucose with the androgenic hormonal parameters. CONCLUSIONS: No elevated androgenic profile was observed in the women with previous gestational diabetes. The use of insulin and insulin/glucose values as indicators of insulin resistance did not demonstrate any correlation with the androgenic parameters.