The effect on clinical results of adding recombinant LH in late phase of ovarian stimulation of patients with repeated implantation failure: a pilot study.

OBJECTIVE: To evaluate the efficacy of recombinant LH (r-LH) addition in the late phase of ovarian stimulation in patients with repeated implantation failure (RIF). PATIENTS AND METHODS: 66 infertile couples undergoing ICSI treatment due to male factor were allocated to group A (33) and to group B (33). Group A (29 subjects) received recombinant FSH (r-FSH) supplemented by r-LH in the late follicular phase starting the same day of GnRH-antagonist (GnRH-ant) administration, and group B (32 subjects) received r-FSH alone. All patients were stimulated with a GnRH-ant flexible protocol starting r-FSH on day 2 of a spontaneous or induced cycle. hCG (10000 IU) was administered by intramuscular route when at least 2 follicles reached 18 mm in diameter. RESULTS: Metaphase II (MII) oocytes with cytoplasmic maturation showed a significant difference in the r-LH group (89.02%) compared to the one with FSH alone (81.15%) (p < 0.01). The number of positive pregnancy test, 14 (48.3%) and 8 (25%), was significantly greater in the r-LH group compared to the group treated with r-FSH alone (p < 0.03). The number of gestational sacs was 20 in the r-LH group vs. 9 in the r-FSH group (p < 0.001). The implantation rate was significantly higher in the r-LH group compared to the r-FSH only group (19% vs. 7% respectively; p < 0.01). Also, a lower abortion rate was found in the r-LH group (21% vs. 37.5% respectively - p < 0.01). CONCLUSIONS: Ovarian stimulation should be personalized because it seems that some subgroups of patients, like those with RIF, reach a better clinical outcome with the addition of r-LH in the advanced follicular phase stimulation.

The use of r-hFSH in treatment of idiopathic male factor infertility before ICSI.

OBJECTIVE: To evaluate the efficacy of pre-treatment of idiopathic oligozoospermic patients with r-hFSH to improve the clinical results of ICSI. PATIENTS AND METHODS: 82 infertile couples due to male factor who attended our center were included in the study. Thirty-six were randomized to the treatment group (group A) and forty-six to the control group (group B). The male partners in group A were treated with recombinant human FSH (r-hFSH; Gonal F®) 150 IU subcutaneously three times a week for a 3-months period. The control group (group B) did not receive any treatment. After the treatment couples of both groups underwent a cycle of ICSI. RESULTS: The fertilization rate was comparable in both groups. However, in the treatment group (group A), the clinical pregnancy rate was significantly higher (42%) compared to the control group (group B) (20%) (p < 0.02). Also, the implantation rate was significantly higher in treatment group (26%) compared to the control (15%) (p < 0.04). Miscarriage rate was lower (15.7%) in the treatment group than in the control (43.7%), and this difference was statistically significant (p < 0.05). CONCLUSIONS: Treatment of idiopathic male factor infertility with r-hFSH before ICSI improves clinical pregnancy rate, increases implantation rate and decreases the early pregnancy loss.

The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2·7-fold increased risk of polycystic ovary syndrome in a Sardinian population.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive. DESIGN: Case-control study aimed at evaluating possible associations between functionally relevant variants of the luteinizing hormone/choriogonadotrophin receptor gene (LHCGR) and PCOS phenotype. PATIENTS: A total of 198 PCOS and 187 non-PCOS women, aged 14-35 years, of Sardinian origin, were referred to the outpatient clinic of the Department of Obstetrics and Gynaecology of the University of Cagliari (Sardinia). PCOS diagnosis was based on the Rotterdam criteria. MEASUREMENTS: We determined the genotype of ins18LQ, S291N and S312N variants at the LHCGR locus. Genotype was related to the presence or absence of PCOS and to several clinical and biochemical characteristics. RESULTS: The presence of at least one 312N allele was strongly associated with PCOS risk (OR, 2·04; 95% CI, 1·32-3·14; χ(2) , 10·47; P = 0·001). 312N homozygosity was associated with a further risk increase (OR, 2·73; 95% CI, 1·25-5·95; χ(2) , 6·65; P = 0·01). The number of ins18LQ alleles was associated with LH serum levels in controls (χ(2) , 8·04, P = 0·017). CONCLUSIONS: For the first time, we have identified a genetic variant that is strongly associated with PCOS in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N genotype at the LHCGR locus in fertile women to assess the risk of PCOS. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at-risk subjects.

Could antispasmodic drug reduce pain during hysterosalpingo-contrast sonography (HyCoSy) in infertile patients? A randomized double-blind clinical trial.

OBJECTIVE: To assess the effectiveness of an antispasmodic drug, hyoscine-N-butylbromide, in reducing pain during hysterosalpingo-contrast sonography (HyCoSy). METHODS: Eight hundred and sixteen patients undergoing HyCoSy were randomized to receive 10 mg hyoscine-N-butylbromide (n = 408) or placebo (n = 408) per os, 30 min before the procedure, in a double-blind randomized controlled trial. Immediately after the procedure, the patient was asked to describe any pain experienced in comparison with pain usually suffered during the menstrual cycle, and the operator assigned a pain score between 0 and 4 as follows: 0 (no reaction or discomfort), 1 (slight pain, less than menstrual pain), 2 (moderate pain, exceeding menstrual cramps but no vasovagal reaction), 3 (vasovagal reaction or pain requiring observation in a hospital) and 4 (vasovagal reaction or pain requiring resuscitation). The primary aim was to estimate the difference in pain score, considered as a categorical value, between the active arm of the trial and the control group. The secondary aim was to evaluate if pain is related to tubal patency. RESULTS: There was no difference in pain score between the hyoscine-N-butylbromide group and the placebo group (P = 0.807). There was a negative correlation between pain and tubal patency, regardless of treatment group (P < 0.0001). CONCLUSIONS: Administration of 10 mg antispasmodic drug hyoscine-N-butylbromide does not reduce pain in patients undergoing HyCoSy.

Low- and standard-estrogen dosage in oral therapy: dose-dependent effects on insulin and lipid metabolism in healthy postmenopausal women.

OBJECTIVE: To evaluate the influences of different doses of daily oral unopposed 17beta-estradiol compared with placebo, both on glucose tolerance and lipid metabolism in healthy postmenopausal women. PATIENTS AND METHODS: Forty-eight normoinsulinemic postmenopausal women were enrolled in the study. Patients were assigned to receive randomly 1 mg (group A) or 2 mg (group B) of oral micronized estradiol therapy daily or to the placebo (group C), for 12 weeks. RESULTS: The low-dose estradiol treatment determined an improvement of the peripheral insulin sensitivity, made evident by a significant increase both in the metabolic index and oral glucose insulin sensitivity index (p < 0.01 and p < 0.05, respectively) as well as a decrease in the homeostasis model assessment-estimated insulin resistance (p < 0.01). Conversely, in the standard-dose group, the metabolic index significantly decreased (p < 0.05), showing a slight deterioration in insulin sensitivity. For lipid metabolism, the 1 mg dose showed a neutral effect, while 2 mg had a beneficial effect on low density lipoprotein cholesterol, but caused an increase in triglycerides (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: The oral low dose of unopposed estradiol therapy had a favorable effect on glycoinsulinemic metabolism in healthy postmenopausal women; however, the standard dose caused a slight but significant deterioration in insulin sensitivity.

Which treatment options should be used in adolescents with polycystic ovary syndrome?

Several studies have hypothesized a peripubertal onset of polycystic ovary syndrome (PCOS). This syndrome affects different pathogenetic pathways and includes endocrine-metabolic abnormalities such as hyperandrogenism, hyperinsulinism and insulin resistance. The therapeutic approaches must be addressed to individualization of therapy, considering the major clinical manifestations of the syndrome during adolescence. While the treatment of hyperandrogenism makes use of different drugs already studied, the debate about the use of insulin sensitizing drugs is still open. It will be more and more necessary to define the phenotypic and genotypic milieu in which all treatments will be as safe and effective as possible.

[Diagnosis of polycystic ovary syndrome]. / Diagnosi della sindrome dell'ovaio policistico.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders among women in reproductive age, but diagnostic criteria used in clinical practice are still controversial. In 1990 the National Institute of HEALTH (NIH) conference on PCOS recommended that diagnostic criteria should include biochemical evidence of hyperandrogenism and ovarian dysfunction (in the absence of non-classical adrenal hyperplasia) without considering the morphological diagnosis of polycystic ovary by ultrasound as an essential part of the diagnosis. In the Rotterdam PCOS workshop of May 2003, however, PCOS is diagnosed when 2 of the following criteria are recognized: oligomenorrhea and/or anovulation, clinical or biochemical signs of hyperandrogenism, ultrasound findings of polycystic ovary. Further-more, it is underlined that the metabolic study is not necessary for PCOS diagnosis, while it is suggested for "at risk patients" (obesity, diabetes, familiar and obstetrical history) with an oral glucose tolerance test (OGTT). A recent study carried out by our group underlined the role of ultrasound parameter, in particular suggesting a ratio between ovarian stroma area and total area of the ovarian section (S/A), with a cut-off of 0.34, as "gold parameter" for PCOS diagnosis, because it shows high sensitivity and specificity (96.3%, 97.0% for the S/A).