Federica Alagna

PREMATURE OVARIAN FAILURE

Secondary amenorrhoea with elevated gonadotrophins occurring under the age of 40 (premature ovarian failure (POF)), and at the age between 41 and 44 years (early menopause (EM)), respectively, affects 1-2% and 5% of women in the general population. Objective of this study was to evaluate the prevalence of familial cases of POF and EM and to assess the clinical and genetic characteristics of these patients. One hundred and sixty women with idiopathic secondary amenorrhoea before the age of 45 and serum follicle-stimulating hormone (FSH) levels greater than or equal to 40 IU/l were included in the study. Tests performed on patients included complete medical history, pedigrees analysis, clinical pelvic examination, gonadotrophins and thyroid assessment, chromosomal analysis. The 160 patients included in the study showed idiopathic POF (n=130) or EM (n=30). Following pedigree assessment, we were able to identify an incidence of familial cases of 28.5% in the POF group (n=37) and of 50% in the EM group (n=15). POF and EM condition were often present in the same family. There were no differences between POF and EM patients and between familial and sporadic cases regarding age at menarche, personal history, gynaecological history, weight, height and diet habits. There was a statistically significant difference between sporadic and familial cases in age at POF onset: 32.0+/-7.3 years (12-40) compared to 35. 0+/-5.8 (18-40), respectively (P<0.05). The POF and EM families identified showed two or more affected females and transmission through either maternal or paternal relatives; in four families both maternal and paternal transmission was observed. This study suggests that idiopathic POF and EM conditions, differing only in age of menopause onset, may represent a variable expression of the same genetic disease. The different age of menopause onset in these patients may be explained by genetic heterogeneity and/or by different environmental factors. Our results indicate a high rate of familial transmission of the condition. Pedigrees analysis suggests an autosomal or an X-linked dominant sex-limited pattern of inheritance for POF and EM.

Two-year treatment with oral contraceptives in hyperprolactinemic patients.

The aim of this prospective study was the follow-up for 2 years in symptoms, serum prolactin (PRL) levels, and radiological aspects of a group of young patients using oral contraceptives (OC) with hyperprolactinemia. A total of 16 hyperprolactinemic women (eight with idiopathic hyperprolactinemia and eight with pituitary microadenoma) who started OC use were admitted in the study. After 2 years of OC use, the assessable patients showed a nonsignificant decrease in plasma PRL level (26.8 +/- 29.4 micrograms/mL, range 4.2-97.1 micrograms/mL vs 56.3 +/- 31.5 micrograms/mL, range 23.5-144 micrograms/mL). No patient experienced any radiological changes during OC treatment. In conclusion, although the number of observations is limited, the data suggest that after 2 years of follow-up, no harmful effect of OC use was observed in these patients.

Fsh and folliculogenesis : from physiology to ovarian stimulation

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.

Case-Control Study on Risk Factors for Premature Ovarian Failure

Objective of this case-control study was to investigate the potential risk factors for premature ovarian failure (POF). Seventy-three patients with secondary hypergonadotropic amenorrhea and, as control group, 144 women with acute, non-gynecological, non-neoplastic, non-hormone-related diseases were included in the study. Information was obtained on sociodemographic characteristics, gynecological and obstetric data, general lifestile habits, smoking habits and history of selected gynecological and other clinical conditions. A statistically significant association between high education level and POF was found (p = 0.03). Parity was related to a reduced risk of POF and this reduction increased with the number of live births (p = 0.02). No association emerged between POF risk and age at menarche, cycle length and oral contraceptive use. Women with POF could not be distinguished from control women by behavioral and reproductive history, except for lower fertility. The minor influence that reproductive and lifestyle factors have on the occurrence of POF suggests that genetic inheritance plays a more important role.

Developmental Potential of Human Oocytes After Slow Freezing or Vitrification: A Randomized In Vitro Study Based on Parthenogenesis

The aim of the this study was to compare the in vitro developmental competence of parthenogenetically activated oocytes cryopreserved with slow-freezing or vitrification. Supernumerary metaphase II oocytes obtained during in vitro fertilization procedures were randomized to slow freezing or vitrification procedure. After thawing or devitrification, oocytes were parthenogenetically activated and cultured. Survival, activation, development rate, and cell number during culture were compared. The 2 groups showed no significant differences between the rates of parthenogenetic activation, development, good quality parthenotes and blastomere number on day 2 of culture. However, parthenotes from the devitrified oocytes continued cleaving till day 3 in a significantly low proportion (27% vs. 42%). On day 3, the mean number of blastomeres was also lower in vitrification group compared to slow-freezing (4.8 + 1.9 vs. 5.8 + 1.7). In conclusion, parthenogenesis highlights a reduced potential of vitrified oocytes to cleave on day 3 compared with oocytes from slow-freezing.

FIGO Committee for the Ethical Aspects of Human Reproduction and Women’s Health: Ethical Guidelines in the Prevention of Iatrogenic Multiple Pregnancy

Accessible online at: www.karger.com/journals/goi The FIGO Committee for the Ethical Aspects of Human Reproduction and Women’s Health considers the ethical aspects of issues that impact the discipline of obstetrics, gynaecology and women’s health. The following documents represent the result of that carefully researched and considered discussion. This material is not intended to reflect an official position of FIGO but to provide material for consideration and debate about these ethical aspects of our discipline for member organizations and their constituent membership.