High Prevalence of Vitamin D Deficiency in Infertile Women Referring for Assisted Reproduction.

A comprehensive analysis of the vitamin D status of infertile women is the first step in understanding hypovitaminosis impact on reproductive potential. We sought to determine vitamin D profiles of women attending an infertility center and to investigate non-dietary determinants of vitamin D status in this population. In this cross-sectional analysis, a cohort of 1072 women (mean age ± standard deviation 36.3 ± 4.4 years) attending an academic infertility center was used to examine serum 25-hydroxy-vitamin D (25(OH)D) levels in relation to demographic characteristics, seasons and general health risk factors. Both unadjusted and adjusted levels of serum 25(OH)D were examined. Median 25(OH)D concentration was below 30 ng/mL for 89% of the entire year. Over the whole year, 6.5% of patients had 25(OH)D levels ≤10 ng/mL, 40.1% ≤20 ng/mL, and 77.4% ≤30 ng/mL. Global solar radiation was weakly correlated with 25(OH)D levels. At multivariable analysis, 25(OH)D levels were inversely associated with BMI; conversely, 25(OH)D levels were positively associated with height and endometriosis history. Serum 25(OH)D levels are highly deficient in women seeking medical help for couple's infertility. Levels are significantly associated with body composition, seasonal modifications and causes of infertility. Importantly, this deficiency status may last during pregnancy with more severe consequences.

Fertility preservation in female cancer patients: a single center experience.

Advances in cancer treatment allow women to be cured and live longer. However, the necessary chemotherapy and radiotherapy regimens have a negative impact on future fertility. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer treatment and to facilitate fertility preservation, including oocyte and ovarian tissue cryopreservation. These fertility issues are often inadequately addressed, and referral rates to oncofertility centers are low. The aim of this study was to report the 3-year experience of the San Raffaele Oncofertility Unit. A total of 96 patients were referred to the Oncofertility Unit for evaluation after the diagnosis of cancer and before gonadotoxic treatment between April 2011 and June 2014. Of the 96 patients, 30 (31.2%) were affected by breast cancers, 20 (20.8%) by sarcomas, 28 (29.2%) by hematologic malignancies, 13 (13.5%) by central nervous system cancers, 3 (3.1%) by bowel tumors, 1 (1.0%) by Wilms' tumor, and 1 (1.0%) by a thyroid tumor; 47 (49.0%) were referred for oocyte cryopreservation before starting chemotherapy, 20 (20.8%) were referred for ovarian tissue cryopreservation, and 29 (30.2%) were not recruited. The mean time between the patients' counseling and oocyte retrieval was 15 days (range, 2-37 days). The mean time between the laparoscopic surgery and the beginning of treatment was 4 days (range, 2-10 days). The number of patients who were referred increased over time, whereas the rate of patients who were not recruited decreased, showing an improvement in referrals to the Oncofertility Unit and in the patients' counseling and understanding. Our results indicate that an effective multidisciplinary oncofertility team is necessary for prompt referrals and treatment.

Hyperinsulinemia Alters Myoinositol to d-chiroinositol Ratio in the Follicular Fluid of Patients With PCOS.

Myoinositol (MI) and d-chiroinositol (DCI) are 2 stereoisomers and insulin sensitizers. Their physiological ratio differs from tissue to tissue, and they are regulated by an insulin-dependent epimerase whose activity is drastically reduced in conditions of insulin resistance. Based on literature data and on the fact that MI phospholipids are follicle-stimulating hormone (FSH) second messengers, we speculated that patients with polycystic ovary syndrome (PCOS) having hyperinsulinemia, present an enhanced MI to DCI epimerization in the ovary, leading to MI deficiency that impairs FSH signaling, resulting in reduced oocyte quality. In the present study, 20 patients with PCOS and 20 healthy women were enrolled for measurement of MI and DCI levels in their follicular fluid. Follicular fluid samples were taken using a vaginal probe and both MI and DCI were quantified analytically. Results showed that the ratio of MI-DCI dropped from 100:1 in healthy participants to 0.2:1 in patients with PCOS who additionally displayed significantly higher levels of insulin resistance, hyperinsulinemia, and luteinizing hormone. This study is the first one to analyze the misbalance in the MI-DCI ratio in the ovary of patients with PCOS, supporting the concept that maintaining the physiological levels of the 2 stereoisomers is crucial, in restoring the ovarian functionality.

Exposure of embryos to oxygen at low concentration in a cleavage stage transfer program: reproductive outcomes in a time-series analysis.

BACKGROUND: Embryos are exposed to oxygen at a concentration of 2% to 8% under in vivo conditions. Laboratory culture of embryos with oxygen at atmospheric tension impairs embryo metabolism and blastocyst development in several species. Indeed, a high rate of live births after a day 5 transfer has been obtained by lowering oxygen concentration in the incubator atmosphere, thus definitively proving the damaging effect of oxygen at atmospheric tension on late stage development of human embryos. Conversely, the possible beneficial effect of low oxygen tension on assisted reproductive technology (ART) outcomes in a selective cleavage stage transfer program remains controversial. Therefore, the present study validated the hypothesis that oxygen at reduced concentration may improve ART outcomes when cleavage stage embryos are transferred. METHODS: The effect of oxygen at atmospheric versus reduced concentration on laboratory and clinical outcomes of both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles were compared. Evaluation of outcomes included fertilization, cleavage, and implantation rates. Clinical outcomes were also assessed in our analysis. RESULTS: From May 2010 to Mid-October 2010 357 ART cycles (ICSI n = 273 and IVF n = 84) were performed using atmospheric oxygen laboratory incubators while from Mid-October 2010 until March 2011 306 cycles (ICSI n = 224 and IVF n = 82) were carried out under low oxygen concentration. The multi-ovulation protocols were not significantly different between the two study periods. The medical and laboratory staff, the laboratory, and its procedures and the operating room did not differ between the two groups, neither did the culture media. For ICSI procedures, no significant difference in ART outcomes was found between the two culture conditions. For conventional IVF cycles, both fertilization rate (59 +/- 36 vs. 71 +/- 32, respectively) and proportion of embryos obtained (38% vs. 50%, respectively) were significantly improved under low oxygen condition. CONCLUSIONS: Culture of embryos in oxygen at low tension improved ART outcomes during a selective cleavage stage transfer program.

Neonatal morbidity and mortality in intrauterine growth restricted (IUGR) pregnancies is predicated upon prenatal diagnosis of clinical severity.

The objective of this work was to determine whether the prenatal determinates of clinical severity in intrauterine growth restricted pregnancies, established by abdominal circumference measures, correlates with neonatal morbidity and mortality. A total of 336 singleton pregnancies with intrauterine growth restriction were subdivided into group 1 (normal fetal heart rate and pulsatility index of the umbilical artery: 251 cases), group 2 (normal fetal heart rate and abnormal pulsatility index: 50 cases), and group 3 (abnormal fetal heart rate and pulsatility index: 35 cases). Gestational age, birth weight, body mass index, placental weight, and Apgar score were significantly related to the severity of intrauterine growth restriction (P < .001). Neonatal survival was 100%, 96%, and 57% in the 3 groups, respectively (P < .001). Greater than 80% of neonates of group 1 had no complications when compared to group 2 (54%) and group 3 (10%); P < .001. Gestational age was the only independent variable significantly associated with neonatal outcomes. The data confirm that the classification of clinical severity of intrauterine growth restriction based on biophysical parameters is clinically relevant to predict neonatal outcome.

Comparison of fetal and neonatal growth curves in detecting growth restriction.

OBJECTIVE: To evaluate the outcome of intrauterine growth restriction (IUGR) infants with abnormal pulsatility index of the umbilical artery according to the neonatal birth weight/gestational age standards and the intrauterine growth charts. METHODS: We analyzed 53 pregnancies with severe IUGR classified as group 2 (22 IUGR: abnormal pulsatility index and normal fetal heart rate) and group 3 (31 IUGR: abnormal pulsatility index and fetal heart rate). Neonatal birth weight/gestational age distribution, body size measurements, maternal characteristics and obstetric outcome, and neonatal major and minor morbidity and mortality were compared with those obtained in 79 singleton pregnancies with normal fetal growth and pulsatility index, matched for gestational age (appropriate for gestational age [AGA] group). Differences were analyzed with the chi(2) test and the Student t test. Differences between means corrected for gestational age in the different groups were assessed by analysis of covariance test. A P<.05 was considered significant. RESULTS: At delivery, using the neonatal standards, 25 of 53 (47%) IUGR showed a birth weight above the 10th percentile (IUGR(AGA)), whereas in 28, birth weight was below the 10th percentile (IUGR small for gestational age [SGA]-IUGR(SGA)). All body size measurements were significantly higher in AGA than in IUGR(AGA) and IUGR(SGA). Forty-nine of 79 (62%) AGA and 49 of 53 (92%) IUGR were admitted to the neonatal intensive care unit (P<.001). One of 79 (1%) AGA and 6 of 53 (11%) IUGR newborns died within 28 days (P<.02). Major and minor morbidity was not different. CONCLUSION: This study shows that neonatal outcome is similar in IUGR of the same clinical severity, whether or not they could be defined AGA or SGA according to the neonatal standards. Neonatal curves are misleading in detecting low birth weight infants and should be used only when obstetric data are unavailable. LEVEL OF EVIDENCE: II.