Raffaella Depalo

The Plasma Homocysteine Levels Are Increased in Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) have several cardiovascular disease risk factors. Since hyperhomocysteinemia is associated with early atherosclerosis, it was postulated that the homocysteine levels are higher in PCOS patients than in control subjects which, therefore, may explain the cardiovascular disease risk. Thirty-five women with PCOS and 20 healthy subjects were studied. Endocrine assays, lipid profile, homocysteine and insulin level determinations, and ultrasound evaluation were performed in all subjects. We found significantly higher mean plasma homocysteine concentrations in patients with PCOS as compared with controls (10.4 ± 4.4 vs. 7.2 ± 1.5 ng/dl; p < 0.003). These data show that in PCOS early atherosclerosis is not exclusively dependent on hyperinsulinemia and elevated lipid profile – PCOS patients are exposed to significantly higher homocysteine levels which might increase the cardiovascular disease risk.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Do uterine fibroids affect IVF outcomes

The effect of myomectomy on implantation and pregnancy rates prior to assisted reproduction treatments is controversial. This study was designed to assess clinical outcomes of IVF cycles in women with uterine fibroids. A retrospective single-centre assessment of clinical outcomes of IVF/intracytoplasmic sperm injection (ICSI) treatments in infertile women in a 4-year span was carried out. All patients underwent detailed transvaginal ultrasound and hysteroscopy to precisely identify presence, location and intracavitary growth of uterine fibroids. Cumulative pregnancy, ongoing pregnancy and live birth rates were considered primary outcome measurements. Fifty-one women with fibroids (97 treatment cycles), 63 patients with previous myomectomy (127 cycles), and 106 infertile women who did not demonstrate fibroids anywhere in the uterus (215 cycles) were considered for the analysis. No significant difference was found for pregnancy and live birth rates between groups. Women with fibroids>4 cm required an increased number of cycles to obtain an ongoing pregnancy, compared with the other groups. The data do not support pre-IVF myomectomy in women with small-to-moderate uterine fibroids, regardless of their location. This represents valuable information in the counselling of women with fibroids before reproductive assisted cycles.

Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles

The effect of elevated body mass index (BMI) on the oocyte quality was investigated in women undergoing in vitro fertilization (IVF) cycles. A total of 268 patients classified on the basis of BMI subject to the first reproductive treatment were included in this study: the normal weight (NW) group consisted of 160 patients with BMI 19–24.9 kg/m2 and the overweight (OW) group consisted of 108 patients with BMI ≥25 kg/m2. All women were treated with a standard long luteal protocol. The oocyte features were classified as extracytoplasmic or cytoplasmic abnormalities. Outcomes were oocyte morphology, embryo quality, fertilization and implantation rates, and the ovarian response to stimulation. A higher percentage of oocytes with granular cytoplasm was found in women with BMI ≥25 (p = 0.04). However, percentages of mature, immature oocytes and germinal vesicle were similar in both groups. No differences were found in fertilization and cleavage rates and percentages of embryo quality. The implantation rate (p < 0.001) was significantly lower in the OW group than in the NW group. The amount of gonadotrophins was significantly higher in OW group (p = 0.003). These findings suggest that the poor reproductive outcome of obese women is influenced by the release of ova with reduced fertilization potential.

Office hysteroscopy in an in vitro fertilization program

Objective. In the present paper we evaluate the incidence of intrauterine pathologies in a population undergoing in vitro fertilization (IVF) treatment. Moreover, we compare the IVF outcome between patients with normal and abnormal uterine findings to determine if office hysteroscopy (OH) is of any clinical significance. Methods. The hysteroscopic findings in 866 consecutive patients were analyzed. The study group included 555 patients at the first IVF attempt and 311 patients with two or more failed IVF cycles. Results. All hysteroscopic parameters were considered normal in 514 cases (59.4%); in 352 cases (40.6%) various pathological conditions were found. Patients were divided into two groups according to the hysteroscopic findings. The implantation and pregnancy rates were similar between the groups. Comparing the clinical outcomes in patients with repeated IVF failure who had hysteroscopy with no pathology and with pathology, we did not find any statistical differences. Conclusions. This study suggests that hysteroscopy as a routine infertility examination should be performed in all patients, owing to the elevated incidence of hysteroscopic pathological findings (59.4%); hysteroscopy also seems to be the best way to repair the uterine cavity when pathological conditions are present. However, performing OH before IVF–embryo transfer is of no significant value in improving pregnancy outcomes.

Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer

Background. The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome. Methods. A total of 136 patients undergoing IVF were included. Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist. GnRH antagonist was administered when the leading follicle reached a diameter of 12–14 mm. GnRH agonist was administered in a long luteal protocol. Results. The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group (p < 0.02 and p < 0.01, respectively). Embryo quality, implantation rate, clinical pregnancy rates, ongoing pregnancy rate and miscarriage rate were similar in both groups. Conclusions. Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment. However, both regimens seem to have similar efficacy in terms of implantation and pregnancy rates. Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed, as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration.

Is the occurrence of the empty follicle syndrome a predictor that a subsequent stimulated cycle will be an unfavourable one

Several hypotheses have been advanced to explain empty follicle syndrome (EFS) but it remains a controversial topic. This paper reports experience with three IVF cycles in which no oocytes were collected. In all cases, an additional IVF cycle was performed. The ovarian stimulation protocol, ultrasound and hormonal surveillance methods, human chorionic gonadotrophin timing and oocyte retrieval technique were similar in all patients. The assessment of additional cycles demonstrated a poor response in terms of oocyte quality, since the number of mature oocytes was low despite the high number of oocytes collected. Thus, the data suggest that in these patients, EFS should be considered as a borderline form of poor response to ovarian stimulation. If this is confirmed, EFS should be a recurrent event and an empty cycle could be a good predictor that a subsequent stimulated cycle will be an unfavourable.

The role of office hysteroscopy in menopause

We evaluated the efficacy of office hysteroscopic treatment of benign intrauterine pathologies using 5F mechanical instruments (scissors, grasping forceps). Subjects were 4863 women who underwent the procedure without analgesia or anesthesia. We treated cervical and endometrial polyps (0.2-3.7 cm), intrauterine adhesions, and anatomic impediments. At 3 months postoperatively, pathology persisted in 364 women (5.6%). Many operative procedures may be performed in the office setting with simple instruments, provided that correct indications are observed.

The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction

Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb.

Intrauterine insemination with recombinant or urinary human chorionic gonadotropin: A prospective randomized trial.

Aim. Our aim was to compare the efficacy and safety of recombinant and urinary human chorionic gonadotropin (rhCG and uhCG, respectively) for the induction of follicle maturation in women undergoing intrauterine insemination (IUI). Methods. Patients were randomized to receive rhCG or uhCG. IUI was carried out 24 h (day 1) and 48 h (day 2) after hCG administration, except for all cases in which ovulation occurred after 24 h. Results. The two treatments were comparable in terms of progesterone levels on day 7 and day 12. Pregnancy rates were comparable between the treatment groups. Of the 64 women who received rhCG, 29.7% became pregnant; there were 16.7% clinical pregnancies and 3.1% biochemical pregnancies per started cycle, and an ongoing pregnancy rate of 93.7% was reported. Of the 61 patients who received uhCG, 24.6% became pregnant; there were 15.9% clinical pregnancies and 1.1% biochemical pregnancies per started cycle, and ongoing pregnancy rate was 92.9%. No adverse effects were noted in either group. Conclusion. The recombinant products can be effectively used instead of urinary products; moreover, apart from the equivalent efficacy in ovulation induction and safety described in this study, it is necessary to consider the advantages provided by the recombinant form