MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein ...encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells.
Abstract The aim of this study was to evaluate the influence of maternal age and oestradiol concentrations on blastocyst development and live birth rates in natural cycle IVF–embryo transfer. This ...observational study included 397 natural cycles with IVF–embryo transfer for female infertility with embryo transfer on day 5. The cycles were divided into two groups according to the woman's age (<39 and ≥39 years of age), and into two groups according to oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration (0.4–0.49 nmol/l and 0.5–1.2 nmol/l). Comparison between the cycles in younger versus older age groups showed significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (55 versus 29%, 23 versus 3% and 13 versus 2% respectively) ( P < 0.001). Comparison between cycles with lower versus higher oestradiol concentrations showed no significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (47 versus 49%, 18 versus 18%, and 11 versus 10% respectively). Advanced maternal age negatively predicts the success of natural cycle IVF, while low oestradiol concentrations on the day of HCG administration (ultrasound criteria fulfilled) do not negatively predict blastocyst development and success of natural cycle IVF.
Elastase–inhibitor complex was assessed by immunoassay in the seminal plasma of 312 men attending the outpatient infertility clinic. Using receiver operating characteristic (ROC) curve analysis, ...elastase at the cut-off value of ≥290 ng/ml was shown to be efficient (sensitivity 79.5%, specificity 74.4%) in the detection of genital tract inflammation as defined by leukocytospermia (>1×106 leukocytes/ml). The prevalence of increased elastase in 292 infertile men was significantly higher (34%) as compared with that (5%) observed in 20 fertile men (P = 0.02). Moreover, high elastase concentration (≥290 ng/ml) was observed in 66 of the 264 men (25%) without leukocytospermia. A significant positive correlation was found between elastase concentration and patient age (r = 0.202, P < 0.0001) and the number of leukocytes (r = 0.330, P < 0.0001). A negative correlation was found between elastase concentration and semen volume (r = –0.146, P = 0.01) and the percentage of spermatozoa with single-stranded DNA (r = –0.194, P = 0.024), but there was no correlation between elastase and sperm reactive oxygen species production. A higher seminal elastase concentration was significantly associated with tubal damage in female partners (P < 0.001). After norfloxacine antibiotic therapy, decrease in elastase concentration was observed in 15 (25%) of the 60 treated patients. Tubal damage in the partner negatively affected the response to antibiotic therapy. In conclusion, granulocyte elastase is a reliable screening test for silent genital tract inflammation of the couple. The elastase–inhibitor complex may have a protective effect in reducing sperm DNA denaturation.
This is the first study evaluating whether oocyte development and fertilization competence are related to intrafollicular concentration of cholesterol, meiosis-activating sterols and progesterone, ...after human chorionic gonadotrophin (HCG) administration of women with polycystic ovarian syndrome (PCOS). The concentration of follicular fluid meiosis-activating sterol (FF-MAS) significantly increased in the periovulatory period from 10–14 to 34–38h after HCG administration, while the concentration of testis meiosis-activating sterol (T-MAS) decreased, suggesting a HCG-dependent inhibition of sterol Δ14-reductase. There was no correlation between follicular lanosterol, FF-MAS, T-MAS, and progesterone concentrations and the presence or absence of MII oocytes. Interestingly, free cholesterol level was significantly lower and FF-MAS/cholesterol and progesterone/cholesterol ratios significantly higher in follicles containing MII oocytes compared to follicles from which oocytes were not retrieved. Yet, fertilization and embryo quality did not correlate with follicular sterols. This knowledge should be beneficial for the implementation of protocols for in vitro maturation process, usually used in PCOS patients.
BACKGROUND: The aim of this study was to evaluate the role of blastocyst culture in patients with azoospermia. METHODS: In 98 cycles embryos were cultured for 2 days and in 128 cycles for 5 days to ...reach the blastocyst stage; a maximum of two of the most developed embryos were transferred in each group. RESULTS: There was a negative correlation between a high (≥20 IU/l) male serum FSH and embryo development, manifested as embryos not reaching the morula stage on day 5 (r = 0.387; P < 0.05). After prolonged culture, 23% of embryos reached the blastocyst stage. The pregnancy rates per transfer, and the abortion rates were approximately the same in the day 2 group and the day 5 group (20 versus 20% and 19 versus 18% respectively). After blastocyst transfer, a high clinical pregnancy rate (55%) and a low abortion rate (6%) were achieved, whereas the transfer of arrested embryos provided a low pregnancy rate (2%) and a high abortion rate (100%). If only blastocysts had been transferred on day 5, the clinical pregnancy rate per started cycle would have been approximately the same in both groups (13 versus 16%). CONCLUSIONS: Blastocyst formation is a good indicator of clinical results after ICSI with testicular sperm.
The aim of this study was to evaluate the effect of sperm single-stranded DNA, detected by acridine orange (AO), and classical sperm parameters on embryonic quality after ICSI.
Before ICSI, the ...spermatozoa of 183 infertile patients with oligo-, astheno-, teratozoospermia (n = 147), or more than one previous unsuccessful conventional IVF attempt (n = 36) were stained by AO to assess the presence of single-stranded DNA. Two days after ICSI, the embryos of 135 patients were scored for morphology, fragmentation included. Embryos of 48 couples were cultured for 4 days to develop to the morula or blastocyst stage. At most 2 embryos were transferred on Day 2 or 4.
When the level of spermatozoa with single-stranded DNA was increased, there was a significantly lower fertilization rate after ICSI. Besides, increased sperm single-stranded DNA resulted in a higher proportion of heavily fragmented embryos on Day 2 (P < 0.05). In patients with an increased level of spermatozoa with single-stranded DNA, a significantly higher number of embryos were arrested in spite of prolonged culturing (P < 0.05). Classical sperm parameters did not affect the quality and developmental potential of ICSI-derived embryos. No correlation was found between the level of spermatozoa with single-stranded DNA, pregnancy rate, and live-birth rate achieved by ICSI, except in patients with 0% of spermatozoa with single-stranded DNA, in whom the pregnancy rate was significantly higher.
Sperm single-stranded DNA provides additional data on sperm functional capacity in terms of fertilization and embryonic quality after ICSI.
Summary
The aim of this retrospective study was to evaluate the efficiency of testicular biopsy and intracytoplasmic sperm injection (ICSI) in patients with aspermia or non‐obstructive azoospermia ...(NOA) after cancer treatment. From 1996 to 2003, 30 men with a history of cancer, affected by aspermia or NOA and without sperm cryopreserved before cytotoxic treatment underwent testicular sperm extraction (TESE). In these men, clinical, hormonal and histological characteristics were compared; 13 underwent 39 TESE‐ICSI cycles using frozen‐thawed testicular spermatozoa (TESE‐ICSI group). In the same period, 31 ICSI cycles were performed in 20 men with aspermia or NOA using ejaculated sperm frozen before cancer treatment (ejaculated sperm‐ICSI group). Fertilization, blastocyst development, pregnancy and miscarriage rates were compared between the groups. Testicular volume, serum follicle‐stimulating hormone level and Johnsen score indicated complete although reduced spermatogenesis in men with aspermia and abnormal spermatogenesis in men with NOA. After TESE, sperm retrieval was positive in 92% of men with aspermia and 58% of men with NOA. In TESE‐ICSI patients with NOA a significantly lower proportion of embryos developed to the blastocyst stage than in patients with aspermia and in those after ICSI with frozen‐thawed ejaculated sperm (23% vs. 43% and 47%, p = 0.03 and p < 0.01 respectively). In all groups the miscarriage rates were high; in patients with aspermia and NOA, characterized by increased age, the miscarriage rate tended to be higher in spite of similar female age and female indications of infertility. In patients affected by aspermia or NOA after cancer treatment and without sperm cryopreserved before treatment, TESE‐ICSI using testicular sperm provide a chance to father a child.
Abstract
PURPOSE: To identify a subgroup of twin-prone women undergoing in vitro fertilization (IVF) with blastocyst transfer. MATERIALS AND METHODS OF INVESTIGATION: In a retrospective cohort study, ...2539 IVF cycles (1334 classical IVF and 1205 intracytoplasmic sperm injection ICSI cycles) in 1641 couples in the 3-year period were included. The cycles resulting in blastocysts were analysed in terms of female age, number of IVF attempts, infertility indication, number of developed blastocysts, and pregnancy, twin pregnancy and abortion rates. RESULTS: Blastocysts developed in 52 % of cycles. The pregnancy rate per blastocyst transfer was 43 % and the twin rate per pregnancy 20 %. We found a negative correlation between twin pregnancy rates, female age and number of IVF attempts, and a positive correlation between twin pregnancy rates and number of developed blastocysts. ICSI compromised blastocyst development without directly affecting pregnancy and twin pregnancy rates. Significantly higher twin pregnancy rates (39 % per pregnancy) were observed in women younger than 34 years who had 3 or more developed blastocysts. DISCUSSION, CONCLUSIONS: The subgroup of twin-prone women undergoing blastocyst transfer is characterized by age < 34 years, and number of developed blastocysts ≥ 3. Elective single blastocyst transfer in these selected women would hypothetically reduce twin pregnancy rates from 20 to 8 % per pregnancy.