Basal FSH concentration as a predictor of IVF outcome in older women undergoing stimulation with GnRH antagonist.

The aim of this study was to determine the value of basal FSH as a predictor of assisted reproduction outcome in women >or=35 years undergoing ovarian stimulation with gonadotrophin-releasing hormone (GnRH) antagonist. A retrospective clinical study was carried out on 83 infertile women, 35-45 years old, divided into three groups according to their day 3 FSH concentration (group A = FSH 10 and <15 mIU/ml, group C = FSH >15 mIU/ml). Patients underwent ovarian stimulation with a GnRH-antagonist protocol. Group A women had significantly higher basal inhibin B concentrations (P < 0.001), lower cancellation rate (P < 0.001), required a significantly lower dosage of recombinant FSH (P < 0.0001) and had significantly higher oestradiol concentration under stimulation compared with the other groups (P < 0.0001). Oocyte and embryo numbers were comparable in all groups, although groups B and C had more low quality embryos compared with group A. The number of metaphase II oocytes and embryos was related to patients' ovarian reserve markers only in group C. Pregnancy and delivery rates were 35 and 22.5% in group A, 22.2 and 16.6% in group B and 5 and 0% in group C. It is concluded that a basal FSH cut-off of 10 mIU/ml seems predictive of ovarian reserve, while basal FSH cut-off of 15 mIU/ml seems predictive of pregnancy potential and probably of oocyte quality.

A novel protocol of ovulation induction with delayed gonadotropin-releasing hormone antagonist administration combined with high-dose recombinant follicle-stimulating hormone and clomiphene citrate for poor responders and women over 35 years.

OBJECTIVE: To evaluate the efficacy of a novel protocol of ovulation induction for poor responders. DESIGN: Prospective, controlled, clinical study. SETTING: Research institute's reproductive unit. PATIENT(S): One hundred forty-five infertile women, aged 27-39 years, candidates for assisted reproductive techniques (ART). INTERVENTION(S): Before undergoing ART, 85 patients received clomiphene citrate, high-dose recombinant human FSH, and a delayed, multidose GnRH antagonist, whereas 60 patients underwent a standard long protocol. MAIN OUTCOME MEASURE(S): Estradiol levels (pg/mL), cancellation rate, oocyte retrieval, embryo score, and fertilization and pregnancy rates. RESULT(S): Patients undergoing the study protocol obtained lower cancellation rates (4.7% vs. 34%) and higher E(2) levels (945.88 +/- 173.2 pg/mL vs. 169.55 +/- 45.07 pg/mL), oocyte retrieval (5.56 +/- 1.13 vs. 3.36 +/- 1.3), and pregnancy (22.2% vs. 15.3%) and implantation rates (13.5% vs. 7.6%) compared with those receiving the long protocol. Age negatively correlated with ovarian response in the latter, whereas the ovarian outcome results were comparable in younger (<35 yrs) and older (>35 yrs) women treated with the study protocol. CONCLUSION(S): The proposed protocol of ovulation induction can be usefully administered in poor responders as well as in aged woman, probably because the delayed administration of GnRH antagonist prevents its adverse effects on ovarian paracrine activity and on oocyte maturation.

Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients.

Two loci for nonsyndromic recessive deafness located on chromosome 21q22.3 have previously been reported, DFNB8 and DFNB10. Recently a gene which encodes a transmembrane serine protease, TMPRSS3 or ECHOS1, was found to be responsible for both the DFNB8 and DFNB10 phenotypes. To determine the contribution of TMPRSS3 mutations in the general congenital/childhood nonsyndromic deaf population we performed mutation analysis of the TMPRSS3 gene in 448 unrelated deaf patients from Spain, Italy, Greece, and Australia who did not have the common 35delG GJB2 mutation. From the 896 chromosomes studied we identified two novel pathogenic mutations accounting for four mutant alleles and at least 16 nonpathogenic sequence variants. The pathogenic mutations were a 1-bp deletion resulting in a frameshift and an amino acid substitution in the LDLRA domain of TMPRSS3. From this and another study we estimate the frequency of TMPRSS3 mutations in our sample as 0.45%, and approximately 0.38% in the general Caucasian childhood deaf population. However, TMPRSS3 is still an important contributor to genetic deafness in populations with large consanguineous families.