Iris Har-Vardi

Seasonal variations of human sperm cells among 6455 semen samples: a plausible explanation of a seasonal birth pattern

OBJECTIVE To compare the different sperm parameters according to season of the year on sperm production day and the season 70 days prior (during spermatogenesis). STUDY DESIGN Retrospective Andrology Laboratory data comparison. A total of 6455 consecutive semen samples were collected as part of the basic fertility evaluation of 6447 couples. According to sperm concentration, the samples were classified as Normozoospermic or Oligozoospermic and analyzed in relation to the season. RESULTS The sperm concentration and percentage of fast motility showed a significant decrease from spring toward summer and fall (P < .001) with recovery noticed during the winter. As well, the highest percentage of normal sperm morphology was observed during the winter months. CONCLUSION Seasonal sperm pattern seems to be a circannual-rhythmic phenomenon. The winter and spring semen patterns are compatible with increased fecundability and may be a plausible explanation of the peak number of deliveries during the fall.

Increased plasma cell-free DNA is associated with low pregnancy rates among women undergoing IVF-embryo transfer

This prospective repeated measures study was designed to examine the cell-free DNA (cfDNA) concentrations during ovarian stimulation and the relationship between cfDNA concentration and pregnancy rates in women undergoing IVF-embryo transfer. The study examined 37 women undergoing IVF treatment in an IVF unit in a university medical centre in southern Israel. cfDNA concentrations were measured by a direct fluorescence assay, pregnancy rates were identified by plasma β human chorionic gonadotrophin (HCG) concentrations and verified by vaginal ultrasound to determine gestational sac and fetal heart beats. Throughout the IVF cycle, at the three time points measured, the mean concentration of plasma cfDNA among all participants did not statistically significantly change. However, on the day of βHCG test in patients undergoing IVF-embryo transfer, plasma cfDNA concentrations were statistically significantly higher among women who did not conceive in comparison to those who conceived. Plasma cfDNA may reflect the presence of factors which interfere with embryo implantation. Further research is required to determine the usefulness of cfDNA as a biomarker of IVF outcome and to examine the underlying pathologies as potential sources for increased plasma cfDNA concentrations. Cell-free DNA (cfDNA) is particles of DNA which are released from the cell nucleus and are found in high concentrations during a variety of illnesses and injuries. This study was designed to examine the cfDNA concentrations during IVF treatment and the relationship between cfDNA concentration in the bloodstream and pregnancy rates in women undergoing IVF. This study examined 37 women in treatment at the IVF unit of the University Medical Centre in southern Israel. cfDNA concentrations in the bloodstream were measured at three time points by a direct test. Pregnancy rates were identified by pregnancy hormone concentrations in the bloodstream and verified by vaginal ultrasound to determine a pregnancy sac and fetal heart beats. Throughout the IVF cycle, at the three time points measured, the average concentration of cfDNA among all participants did not change. However, on the day of the pregnancy test, blood cfDNA concentrations were significantly higher among women who were not pregnant in comparison to those who were. Plasma cfDNA may reflect the presence of factors which interfere with embryo implantation. Further research is required to determine the usefulness of cfDNA as a biological marker of IVF outcome and examine underlying illnesses and problems as potentials sources for increased cfDNA concentrations.

Morphological embryo assessment: reevaluation.

OBJECTIVE To assess whether the pronuclear score and embryo nuclear scoring have an additive value to day 2 morphology criteria in the prediction of the implantation rate (IR). DESIGN Retrospective clinical study. SETTING IVF Unit, Soroka University Medical Center. PATIENT(S) Analysis of all homogenous IVF fresh embryo transfers from 2008-2010. INTERVENTION(S) Morphological evaluation of pronuclear scoring, embryo nuclear scoring, and day 2 embryo morphology scoring on embryos obtained from IVF or intracytoplasmic sperm injection (ICSI) cycles. MAIN OUTCOME MEASURE(S) Implantation rate of homogeneous transfers. RESULT(S) No statistical association was found between the pronuclear scoring system (Z) and IR. The pronuclear score Z3 had a significantly better performance than Z1, Z2, and Z4 (IR = 25.2%, 22%, 21.4%, and 11.8%, respectively). Assessment of the second day embryo morphology scoring (index [IDX]) was found to associate with IR. IDX1, IDX2, IDX3, IDX4, and IDX5 had an IR of 36.1%, 28%, 21.9%, 14.2%, and 0, respectively. The nuclear scoring including: 1 nucleus in all blastomeres, 1 nucleus in part of the blastomeres, no visualization, and multinucleation showed high association with IR = 32.7%, 22.9%, 14.8%, and 9.1%, respectively. The effect of the nuclear scoring on IR was lost in a multivariable analysis that included day 2 embryo morphology scoring. CONCLUSION(S) Our results suggest that there is no additive value in grading the zygote on day 1 or embryo nuclear scoring on day 2 to day 2 embryo morphology for the prediction of IR.

Monozygotic twins following blastocyst transfer: a report of two cases

Several studies have shown an increased risk for monozygotic twinning after fertilization treatments. We present the clinical and sonographic characteristics of two monozygotic twin cases following blastocyst transfer. It is suggested that delayed transfer of the embryo in the blastocyst stage is a contributing factor to monozygotic twinning.

Decrease in cell free DNA levels following participation in stress reduction techniques among women undergoing infertility treatment

This pilot study examined differences in plasma cell free DNA (CFD) levels based on practice of stress reduction techniques among 14 women undergoing in vitro fertilization (IVF) and embryo transfer (ET) treatment who had higher than normal levels of plasma CFD before beginning IVF treatment. Wilcoxon nonparametric tests were used to examine the significance of the rate of decline in CFD levels between the time points in each of the groups. A paired sample t-test examined the changes in CFD levels among each participant in each of the groups separately. We found that women who engaged in these techniques had reduced plasma CFD, below what is considered elevated in comparison to those who did not practice. High plasma CFD levels have been associated with IVF failure. Stress reduction techniques may facilitate physiological changes that lead to the reduction of plasma CFD levels.

Differential transcriptional control of the H-2K and H-2D loci of the major histocompatibility complex in fibrosacoma cells

In this study we demonstrate a differential transcription of H-2K and H-2D class-I genes in two different tumor cell clones; one is highly metastatic (IE-7) and the other is not metastatic (IC-9), both derived from the same fibrosarcoma, T-10, induced in an (H-2b x H-2k)F1 mouse. The expression of the two parental H-2K alleles is transcriptionally suppressed in both of these clones. In addition the IC-9 clone does not transcribe also the H-2Dk allele. Our data rule out the possibility that this suppression results from enhanced RNA degradation, impaired polyadenylation, DNA rearrangement, or changes in DNA methylation within these genes. Interferons (IFN) are known to enhance MHC expression by acting on a consensus IFN responsive element present in the promoter region of MHC genes. However, IFN-gamma, which is the most potent IFN in this respect, failed to activate the expression of the silent MHC genes in our cells. This finding may reflect a defect within the promoter region of these genes or changes in their chromatin structure.

Antioxidants and Polyphenols: Concentrations and Relation to Male Infertility and Treatment Success

Oxidative stress is induced by reactive oxygen substances (ROS) that are known to affect male fertility. The aims of this study were to prospectively investigate and characterize total antioxidant and specifically polyphenols concentrations and their relations to sperm quality and fertility treatment success. During their infertility treatment, sixty-seven males were prospectively recruited to this study. After separation of the sperm from the semen sample, the semen fluid samples antioxidants and polyphenols concentrations were determined. Antioxidant concentration was significantly associated with sperm concentration and total motile count. Antioxidants concentration in the group of male with sperm concentration ≥ 15 × 106 was significantly higher than in the group of male with antioxidants concentration < 15 × 106 (830.3 ± 350 μM and 268.3 ± 220 μM, resp., p < 0.001). Polyphenols concentration did not differ between the groups of sperm concentration above and below 15 × 106 (178.7 ± 121 μM and 161.7 ± 61 μM, resp., p-NS). No difference was found between fertilization rates and antioxidants or polyphenols concentrations. This is the first study that reports on polyphenols concentration within semen fluid. More studies are needed in order to investigate polyphenols role in male fertility.

Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment

PurposeThe current research is aimed at finding potential non-invasive bio-markers that will help us learn more about the mechanisms at play in failed assisted reproduction treatment. This exploratory pilot study examined the relationship between cell-free DNA (CFD) in plasma and telomere length in lymphocytes among women undergoing in vitro fertilization (IVF) and compared telomere length and CFD levels to a healthy control group.MethodsBlood of 20 women undergoing IVF was collected at three time points during the IVF cycle. We assessed the relationship between CFD and telomere length as well as controlling for morning cortisol levels. We also collected blood of 10 healthy controls at two time points (luteal and follicular phases of the menstrual cycle) and compared mean telomere length, CFD, and cortisol levels between the IVF patients and healthy controls.ResultsThe results revealed an inverse relationship between CFD levels and telomere lengths at several time points that remained significant even after controlling for cortisol levels. Women undergoing IVF had statistically significant higher levels of CFD and shorter telomeres compared to healthy controls.ConclusionsThe relationship between telomere length and CFD should be further explored in larger studies in order to uncover potential mechanisms that cause both shortened telomere length and elevated CFD in women undergoing IVF.

Changes in the coding sequence of the H-2Dk gene of metastatic cells that might account for immunogenic abnormality of its encoded antigen

In previous studies we have demonstrated that metastatic cells, derived from T-10 fibrosarcoma, express an immunogenically abnormal H-2Dk glycoprotein which is involved in manifesting their metastatic phenotype. In the present study we show that these cells contain a remarkably high level of H-2Dk specific mRNA. Moreover, by cloning cDNA of this gene and analyzing its nucleotide sequence, we found 4 single nucleotide changes. Two of them did not change the encoded amino acids, whereas the others resulted in two amino acid substitutions in the alpha-2 domain of the protein product that might account for its immunogenic abnormality.

The effect of fertility treatment on adverse perinatal outcomes in women aged at least 40 years

To compare perinatal outcomes between spontaneous conception and assisted reproductive technologies (ART) among patients of advanced maternal age.