Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.

FSH is a glycoprotein hormone consisting of two peptide subunits. The role of FSH in folliculogenesis is well known: to stimulate the formation of a large pre-ovulatory follicle that, because of its FSH-dependent maturation, is capable of ovulation and forming a corpus luteum in response to the mid-cycle surge of LH. FSH is widely used in ovarian stimulation for assisted reproduction techniques. Ovarian stimulation protocols combine the use of human menopausal gonadotrophin, urinary FSH or recombinant FSH with gonadotrophin-releasing hormone (GnRH) agonists or antagonists in order to increase oocyte number and to avoid premature LH surge. Recently, the availability of recombinant LH has permitted new stimulation protocols, combining recombinant FSH, recombinant LH and GnRH antagonists. Due to the limitations of the new Italian law in terms of the number of oocytes that can be fertilized, protocols with a softer ovarian stimulation are now considered, reducing risk of ovarian hyperstimulation syndrome, multiple pregnancies and emotional and physical burdens on the patients. Long-acting FSH preparations are also under clinical study. Knowledge of the stereochemical three-dimensional structure of FSH and its receptor will allow the study of new non-peptide orally administered molecules that fit the FSH receptors.

No abstract

Genetic factors may influence the timing of menopause. Premature ovarian failure (POF) has recently been identified as a genetic entity, but no genetic data are available on early menopause (EM). We investigated 36 patients with EM (age of menopause between 40 and 45 years of age) using cytogenetic and pedigree analysis. In 30 patients of this study the EM was idiopathic and 15 subjects (50%) had a familial condition of EM or POF. Pedigree analysis revealed a dominant pattern of inheritance of EM through maternal or paternal relatives. Our data reveal that POF and EM patients show the same genetic features and we postulate that these conditions may be a variable expression of the same genetic disease.

BackgroundThe aim of the present randomised controlled non-inferiority trial is to test whether in women with compromised ovarian reserve requiring in vitro fertilisation, a protocol of ovarian stimulation using exclusively clomiphene citrate performs similarly to a regimen with high doses of gonadotropins.MethodsWomen with day 3 serum FSH > 12 IU/ml on at least two occasions or previous poor response to hyper-stimulation were recruited at four Italian infertility units. Selected women were allocated to clomiphene citrate 150 mg/day from day 3 to day 7 of the cycle (n=145) or to a short protocol with GnRH agonist 0.1 mg and recombinant FSH 450 IU daily (n=146). They were randomised by means of a computer-generated list into two groups. The study was not blinded. The main outcome of the study was the delivery rate per started cycle.ResultsThe study was interrupted after the scheduled two years of recruitment before reaching the sample size. 148 women were allocated to clomiphene citrate and 156 to the short protocol with high doses of gonadotropins; 124 and 125 participants were analysed in the groups, respectively. Women allocated to high doses of gonadotropins retrieved more oocytes and had a higher probability to perform embryo-transfer. However, the chances of success were similar. The delivery rate per started cycle in women receiving clomiphene citrate and high-dose gonadotropins was 3% (n=5) and 5% (n=7), respectively (p=0.77). The mean estimated cost per delivery in the two groups was 81,294 and 113,107 Euros, respectively. No side-effects or adverse events were observed.ConclusionsIn women with compromised ovarian reserve selected for in vitro fertilisation, ovarian stimulation with clomiphene citrate or high-dose gonadotropins led to similar chances of pregnancy but the former is less expensive.Trial registrationTrial registered on http://www.clinicaltrials.gov (NCT01389713)