Mouse oocyte vitrification with and without dimethyl sulfoxide: influence on cryo-survival, development, and maternal imprinted gene expression.

PURPOSE: Oocytes and embryos can be vitrified with and without dimethyl sulfoxide (DMSO). Objectives were to compare no vitrification (No-Vitr), vitrification with DMSO (Vitr + DMSO), and vitrification without DMSO (Vitr - DMSO) on fresh/warmed oocyte survival, induced parthenogenetic activation, parthenogenetic embryo development, and embryonic maternal imprinted gene expression. METHODS: In this prospective controlled laboratory study, mature B6C3F1 female mouse metaphase II oocytes were treated as: i) No-Vitr, ii) Vitr + DMSO/warmed, and iii) Vitr - DMSO/warmed with subsequent parthenogenetic activation and culture to the blastocyst stage. Oocyte cryo-survival, parthenogenetic activation and embryo development, parthenogenetic embryo maternal imprinted gene expression were outcome measures. RESULTS: Oocyte cryo-survival was significantly improved in Vitr + DMSO versus Vitr - DMSO at initial warming and 2 h after warming. Induced parthenogenetic activation was similar between all three intervention groups. While early preimplantation parthenogenetic embryo development was similar between control, Vitr + DMSO, Vitr - DMSO oocytes, the development to blastocysts was significantly inferior in the Vitr - DMSO oocytes group compared to the control and Vitr + DMSO oocyte groups. Finally, maternal imprinted gene expression was similar between intervention groups at both the 2-cell and blastocyst parthenogenetic embryo stage. CONCLUSION(S): Inclusion of DMSO in oocyte vitrification solutions improved cryo-survival and developmental potential of parthenogenetic embryos to the blastocyst stage without significantly altering maternal imprinted gene expression.

Pregnancy rate and outcome of pregnancies in long-term survivors of Hodgkin's lymphoma.

Thanks to the increased number of young survivors of Hodgkin's lymphoma (HL), management of the pregnancies of women who have a history of exposure to chemotherapies and radiation therapy is becoming increasingly common. Many patients and clinicians are worried that pregnancy after the diagnosis of HL may increase the risk of relapse, despite a lack of empirical evidence to support such concerns. In the present study, we included 89 women diagnosed with HL between 2006 and 2015 under the age of 50 years, who were in complete remission and alive without relapse > 1 year after treatment. We determined the pregnancy rate, time to pregnancy, and the disease-free survival. We found no evidence of significant impairment of the fertility of female HL long-term survivors and no evidence that a pregnancy increases the relapse rate among women in remission from HL. Survivors of HL need to consider a range of factors when deciding on future reproduction.

Dynamics of the development of multiple follicles by early versus late hCG administration in ART program.

OBJECTIVE: To evaluate, in patients stimulated with recombinant FSH and GnRH antagonists, whether triggering the final maturation of oocytes affects IVF outcomes. STUDY DESIGN: Five hundred and six IVF procedures were divided into three groups according to the timing of hCG administration: when at least 2 follicles reached the diameter of 17 mm, at least 2 follicles reached 18 mm and at least 2 follicles reached 20 mm. The main outcome was the number of mature oocyte that was the dependent variable of a multivariate model whose independents were, age, AFC, hCG timing, E2 levels at hCG day, number of follicles in different categories of dimension. Secondary endpoints were to compare fertilization, implantation and pregnancy rates in a multilevel multivariate model whose covariates were age, BMI, AFC, embryo quality and cause of infertility. RESULTS: Timing did not result a statistically significant factor influencing the number of oocytes collected, which was influenced by age, AFC, number of follicles between 12.1 and 15.9 mm and E2 levels. Implantation rate and pregnancy rate appear to be affected only by embryo quality. CONCLUSION: The number of oocytes collected and the probability of pregnancy are not associated with the time of hCG administration.

Optimizing the Ovarian Tissue Cryopreservation in the 'Oncofertility' Institutional Program at an Italian National Cancer Institute.

BACKGROUND: The majority of female cancer patients undergoing anticancer treatments are at risk of experiencing 'cancer treatment-related infertility', which can result in permanent damage to their reproductive prospects. Among the fertility preservation methods, ovarian tissue cryopreservation (OTC) has emerged as an alternative for these patients. The Cancer Institute of Bari initiated a research program to assess the feasibility of OTC. This study compares the viability of ovarian cortical fragments cryopreserved using slow freezing (SF) and ultra-rapid freezing (URF) methods. METHODS: Ovarian cortex biopsies were obtained from 11 fertile women enrolled in our oncofertility service between June 2022 and January 2023. After tissue collection, a histological assessment was performed before cryopreservation. OTC was carried out using both SF and URF methods. Six months later, thawed samples were evaluated for follicle counts and histological integrity. RESULTS: No statistically significant difference was observed in the proportion of intact follicles (means of 31.5% and 73.0% in the SF and URF groups, respectively; p = 0.064). However, there was a significant difference in the number of follicles between the SF group (n = 149) and the URF group (n = 37) (p = 0.046). CONCLUSIONS: We assessed the viability of ovarian cortex after freezing and thawing, focusing on the structural integrity of follicles. Our findings suggest that there are no significant differences between the SF and URF methods.

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.

Sperm head vacuolization affects clinical outcome in ICSI cycle. A proposal of a cut-off value.

OBJECTIVE: To evaluate the relationship between sperm nuclear vacuoles and sperm morphology and to investigate the influence of the rate of spermatozoa with head vacuolization (SVR) in a seminal sample on the clinical outcomes in couples undergoing intracytoplasmic sperm injection. MATERIALS: 26 patients undergoing infertility investigations were included and were divided in two groups according to an SVR ≤ 20,28 % (Group A) or > 20,28 % (Group B), and were investigated to verify the influence of SVR on the fertilization rate, embryo quality, pregnancy and implantation rates. RESULTS: Abnormal spermatozoa with nuclear vacuoles were significantly higher (p < 0.001) than the percentage of normal spermatozoa with nuclear vacuoles. Patients in group A had a percentage of abnormal sperm with nuclear vacuole significantly lower compared to group B (p < 0,001), but there was no difference in the percentage of normal sperm with nuclear vacuoles. Fertilization rates and the number of top quality embryos did not differ between the two groups. The pregnancy and implantation rates were significantly higher in Group A compared to Group B (respectively p < 0,05 and p < 0.001). CONCLUSIONS: For the first time, we propose a cut off value in the proportion of sperms with nuclear vacuolization on the total of sperm in seminal samples, and demonstrate a relationship between SNV and clinical outcomes after ICSI. The SNV rate could be introduced as an easy diagnostic evaluation prior to perform an ICSI cycle.

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/m(2) and the overweight (OW) group consisted of 108 patients with BMI ≥ 25 kg/m(2). 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.

Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated ΔcytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from ß-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of ß-catenin signaling, which were further enhanced by the ΔcytoTrop-2 mutant. This Trop-2/E-cadherin/ß-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.

Semen quality and hormonal levels in infertile patients with varicocele.

OBJECTIVE: Aim of this study was to evaluate the semen quality and the serum concentration of follicle-stimulating hormone (FSH) and Testosterone (T) in infertile patients with and without varicocele. MATERIAL AND METHODS: 365 infertile patients undergoing Assisted Reproduction Tecnique (ART) were retrospectively included in the study. All subject were evaluated by history, physical examination, semen analysis, semen culture, mixed anti-immunoglobulin reaction test (MAR) for demonstration of sperm agglutination antibodies IgG and IgA, serum FSH and T determination. RESULTS: We observed 97 (26.6%) patients affected by varicocele compared to 268 (73.4%) without varicocele. A significant reduced percentage of motile spermatozoa (24.58 +/- 21.68 vs 21.01 +/- 12.62, p < 0.001) and lower sperm concentration (15.50 +/- 23.30 vs 16.50 +/- 15.22, p < 0.001) were observed in patients with varicocele compared to patients without varicocele. No significant differences were observed in sperm vitality between the two population of men with and without varicocele. Serum FSH (10.42 +/- 10.84 vs 9.11 +/- 18.81, p < 0.001) and Testosterone (5.73 +/- 5.97 vs 5.21 +/- 2.43, p < 0.001) levels were significantly higher in patients with varicocele compared to patients without varicocele. Detection of IgG and IgA sperm antibodies were negative in both man with and without varicocele. CONCLUSION: The direct connection between varicocele and infertility is not clear. The data of the present study suggest that the presence of a clinical varicocele rule out fertility in men affecting the hypothalamic pituitary-gonadal axis.

Characterization of endometrial growth in proliferative and early luteal phase in IVF cycles.

Human endometrium has a definite role in implantation, although knowledge about its modifications in the course of IVF cycles is still limited. This study was performed to characterize endometrial growth throughout stimulation treatment in women undergoing IVF cycles, regardless of clinical outcomes. Endometrial growth was longitudinally evaluated by ultrasonography in the first induced ovarian stimulation cycle (717 patients). Acceleration and length of significant growth were used to assess the slope of the growth curve mathematically. Endometrial growth showed a parabolic trend and final thickness was significantly affected by age (P < 0.01). Endometria that tended to overgrowth had a more rapid and longer growth during the whole phase. A similar stimulation treatment was repeated within 6 months of the first one and a second evaluation was carried out to verify whether similar growth occurred. Similar growth was observed in 76% of the patients, with an absolute difference between the two cycles of <4 mm in 84% of cases. The endometrium seems to have an individual intrinsic potential that can be expressed regardless of the stimulation protocol. This supports the hypothesis that individual factors (intrinsic properties of the endometrium) significantly affect endometrial growth.

Apoptosis in normal ovaries of women with and without endometriosis.

The aim of this study was to evaluate the factors predisposing to implants of endometriotic lesions in normal ovarian cortexes of women with and without endometriosis by assessing the expression of pro-apoptotic and anti-apoptotic factors and follicular density. Ovarian biopsies were performed during laparoscopy in 18 patients with endometrioma and in 10 healthy women. Detection of apoptosis was performed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay. p53 and BCL2 proteins were assessed by immunohistochemistry. Quantitative real-time polymerase chain reaction was performed to evaluate BAX , BAK , BCL2 , BCL-XL , survivin and beta-actin ( ACTB ) expression. The p53 protein was positive in a significantly higher number of secondary follicles, whereas the B-cell chronic lymphocytic leukaemia/lymphoma 2 (BCL2) protein was positive in all follicles in unaffected tissue of endometriotic women, compared with the controls. Overexpression of the BCL2 and survivin genes and a decreased BAX and BAK gene expression were observed in the endometriotic group although only the difference in survivin expression was significant (P = 0.016). The BCL2 / BAX ratio showed an increased value in the ovarian cortex in controls compared with endometriosis patients. In conclusion, the reduction of apoptosis in unaffected tissue in women with endometriosis suggests that they may be predisposed to develop endometriosis.

Adipose tissue, metabolic syndrome and polycystic ovary syndrome: from pathophysiology to treatment.

In the last few years, polycystic ovary syndrome (PCOS) has deserved major attention because it is linked to the same cluster of events that promote the metabolic syndrome. This review will point out the relationships between fat excess, insulin resistance and the metabolic syndrome. Adipocytes are actually considered as endocrine cells that synthesize and release molecules (adipokines) that play an endocrine/paracrine role, such as adiponectin, atrial natriuretic peptide, leptin, resistin, tumour necrosis factor alpha (TNFalpha). Metabolic syndrome is a chronic low-grade inflammatory condition in which adipokines play a major role. Isolated adipocytes from women with PCOS express higher mRNA concentrations of some adipokines involved in cardiovascular risk and insulin resistance. However, environmental factors and lifestyle play a major role in determining the appearance of the phenotypes of PCOS. In morbid obese women with PCOS, bariatric surgery decreases bodyweight and fat excess and reverses hyperandrogenism and sterility. In lean or overweight women with PCOS, changes in lifestyle in combination with drugs reducing visceral fat and insulin resistance reverse the symptoms and signs of PCOS. Promising treatments for PCOS seem to be insulin sensitizers such as metformin and glitazones.

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.

Weighing the Impact of Diet and Lifestyle on Female Reproductive Function.

BACKGROUND: In the last years, several scientific societies and expert groups focused on the role played by nutritional factors, lifestyle and excess of body fat in interfering with female reproduction and fertility. In many studies a confounding factor is represented by polycystic ovary syndrome (PCOS) which is one of the major causes of infertility where genetic and family history are certainly playing a role, together with lifestyle and nutritional factors. METHODS: In an attempt to define "the optimal fertility diet", we consider the role played by Mediterranean lifestyle and some macronutrients (animal and vegetable proteins) on ovulatory disorders and female fertility also considering some new visions derived from randomized trials of lifestyle programs in obese infertile women asking for in vitro fertilization or alternative assisted reproduction technologies. RESULTS: Several reports are in favor of an increased consumption of either proteins or low-glycemic index carbohydrates to improve ovulatory disorders and female fertility. In studies concerning infertile women undergoing assisted reproduction, either structured exercise sessions and dietary intervention programs seem to be effective in improving menstrual cycles and fertility as demonstrated by the increased rate of natural conceptions. CONCLUSION: The findings of this review confirm the important impact of Mediterranean diet and lifestyle in preserving and improving fertility. However, epigenetic factors are very important in determining fertility rate, but genetic background and ethnicity are also playing crucial roles.

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.

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.

Endogenous luteinizing hormone concentration and IVF outcome during ovarian stimulation in fixed versus flexible GnRH antagonist protocols: An RCT.

BACKGROUND: Luteinizing hormone (LH) is essential for normal follicular development and oocyte maturation. In particular, fluctuations of LH during the follicular phase have a significant impact on morphological and functional changes of the oocyte and determine its meiotic status and ability to be fertilized. OBJECTIVE: This prospective randomized controlled trial examined effects of endogenous follicular phase LH levels on oocyte maturity and IVF outcomes in fixed vs. flexible in vitro fertilization. MATERIALS AND METHODS: Normo-ovulatory women age <39 yr (n=213) were randomized to fixed or flexible gonadotrophin-releasing hormone (GnRH) antagonist protocols. Follicular phase LH, estradiol, and progesterone profiles were measured. Oocytes retrieved, implantation rate, and pregnancy rate were compared between the two groups. RESULTS: LH profiles were similar in both protocols. A lower trend of LH values at the end of ovarian stimulation correlated significantly with a higher pregnancy rate, regardless of protocol (p=0.02). Estradiol levels were statistically different with respect to time points within treatment groups (p<0.0001), but not between groups (p=0.43), or pregnancy outcomes (p=0.2595). Progesterone profiles were similar between groups. No differences were found in retrieved oocytes numbers, fertilization rate or embryos obtained. Significantly, younger age and a higher number of antral follicles were correlated with positive results. CONCLUSION: Fixed and flexible GnRH antagonist protocols did not produce an oscillation of endogenous LH values correlated to the outcome of ovarian stimulation.

Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial.

Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets. Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test. Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis. Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function. TRIAL REGISTRATION: EUDRACT Number 2010-020196-23. Registred 14 April 2011.

Performance of different ovarian reserve markers for predicting the numbers of oocytes retrieved and mature oocytes.

OBJECTIVE: To assess the performance of different ovarian reserve tests for predicting the total numbers of oocytes retrieved and mature oocytes. METHODS: A retrospective study was performed on 71 women undergoing their first IVF/intracytoplasmic sperm injection treatment. Basal ovarian reserve screening was performed on days 2-3 of a spontaneous cycle. Patients were down-regulated with the GnRH agonist, whereas ovarian stimulation was carried out with recombinant FSH, starting from day 2 to 3 of the cycle. The main outcome measures were the numbers of oocytes retrieved and mature oocytes. RESULTS: The total number of oocytes was positively correlated with AFC (p<0.0001) and E(2) levels post-GnRH (p<0.004), whereas there was an inverse correlation with age (p<0.0001). The number of mature oocytes also correlated with AFC (p<0.008) and E(2) levels post-GnRH (p<0.009), and inversely with age (p<0.0004). Univariate linear regression of square root of number of oocytes (SQNO) shows that acceptable predictors of number oocytes, based on model significance and R(2) are AFC (R(2)=0.215), age (R(2)=0.24) and E(2) variation (R(2)=0.09). The following model is proposed to predict the number of mature oocytes: ln(MO)=ln(NO)-2.09+0.028 AGE+0.03 BMI. CONCLUSION(S): The number of antral follicles and patient age appear to be good markers of ovarian response in IVF treatments. Additional information is provided by stimulated E(2) levels.

A critical analysis on Italian perinatal mortality in a 50-year span.

BACKGROUND: Perinatal mortality rate is used as an indicator of reproductive health worldwide. In western countries, national mortality registers are usually accurate and reliable. METHODS AND AIMS: We reviewed the data recorded in the past 50 years in Italy on perinatal and infant mortality. Each single class of mortality rate (according to WHO definitions) was assessed on temporal trends allowing a critical speculative analysis, mainly focusing on the last 20 years, in an attempt to evaluate the impact of prenatal diagnosis. RESULTS: Infant mortality rate (IMR) constantly decreased in the study period whereas early neonatal mortality rate progressively diminished in a 5-year comparison till the early 1990s. Perinatal mortality showed a linear negative trend until the 1980s, after which the decrease steadied at about 23% in the following 5-year period. Infant mortality attributable to congenital anomalies throughout a 20-year span (1980-2000) was steady at about 23% although a progressive reduction in general infant mortality was reported. CONCLUSIONS: A higher reduction in neonatal and perinatal mortality rate was found before the wide availability of the ultrasonographic prenatal diagnosis and the introduction of the law on voluntary abortion in Italy. Given these data, it seems that advances in neonatal care have improved the infant survival rates more than prenatal diagnosis, whereas obstetric care is linked to a reduction of the early perinatal mortality rate.