The IMSI procedure improves poor embryo development in the same infertile couples with poor semen quality: A comparative prospective randomized study

<p>Abstract</p> <p>Background</p> <p>Sperm of poor quality can negatively affect embryo development to the blastocyst stage. The aim of this comparative prospective randomized study was to evaluate the role of an intracytoplasmic morphologically selected sperm injection (IMSI) in the same infertile couples included in the programme of intracytoplasmic sperm injection (ICSI) due to their indications of male infertility which had resulted in all arrested embryos following a prolonged 5-day culture in previous ICSI cycles.</p> <p>Methods</p> <p>Couples exhibiting poor semen quality and with all arrested embryos following a prolonged 5-day culture in previous ICSI cycles were divided into two groups: <it>Group 1: IMSI group </it>(n = 20) with IMSI performed in a current attempt and <it>Group 2: ICSI group </it>(n = 37) with a conventional ICSI procedure performed in a current attempt of <it>in vitro </it>fertilization. Fertilization rate, embryo development, implantation, pregnancy and abortion rates were compared between current IMSI and conventional ICSI procedures, and with previous ICSI attempts.</p> <p>Results</p> <p>The <it>IMSI group </it>was characterized by a higher number of blastocysts per cycle than the <it>ICSI group </it>(0.80 vs. 0.65) after a prolonged 5-day embryo culture. There was a significantly lower number of cycles with all arrested embryos and cycles with no embryo transfer in the <it>IMSI group </it>versus the <it>ICSI group </it>(0% vs. 27.0%, p = 0.048). After the transfer of embryos at the blastocyst or morula stage (on luteal day 5) a tendency toward higher implantation and pregnancy rates per cycle was achieved in the <it>IMSI group </it>compared to the <it>ICSI group </it>(17.1% vs. 6.8%; 25.0% vs. 8.1%, respectively), although not statistically significant. After IMSI, all pregnancies achieved by the blastocyst transfer were normally on-going, whereas after ICSI, two of three pregnancies ended in spontaneous abortion. After IMSI, two pregnancies were also achieved by the morula stage embryos, whereas after the conventional ICSI procedure, embryos at the morula stage did not implant.</p> <p>Conclusions</p> <p>The IMSI procedure improved embryo development and the laboratory and clinical outcomes of sperm microinjection in the same infertile couples with male infertility and poor embryo development over the previous ICSI attempts.</p

Small SSEA-4-positive cells from human ovarian cell cultures: related to embryonic stem cells and germinal lineage?

Background: It has already been found that very small embyronic-like stem cells (VSELs) are present in adult human tissues and organs. The aim of this study was to find if there exists any similar population of cells in cell cultures of reproductive tissues and embryonic stem cells, and if these cells have any relation to pluripotency and germinal lineage. Methods and results: Here we report that a population of small SSEA-4-positive cells with diameters of up to 4 μm was isolated by fluorescence-activated cell sorting (FACS) from the human ovarian cell cultures after enzymatic degradation of adult cortex tissues. These small cells – putative ovarian stem cells – were also observed during cell culturing of up to 6 months and more. In general, small putative ovarian stem cells, isolated by FACS, showed a relatively low gene expression profile when compared to human embryonic stem cells (hESCs) and human adult fibroblasts; this may reflect the quiescent state of these cells. In spite of that, small putative ovarian stem cells expressed several genes related to primordial germ cells (PGCs), pluripotency and germinal lineage, including VASA. The PGC-related gene PRDM1 was strongly expressed in small putative ovarian stem cells; in both hESCs and fibroblasts it was significantly down-regulated. In addition, putative ovarian stem cells expressed other PGC-related genes, such as PRDM14 and DPPA3. Most of the pluripotency and germinal lineage-related genes were up-regulated in hESCs (except VASA). When compared to fibroblasts, there were several pluripotency-related genes, which were up-regulated in small putative ovarian stem cells. Similar populations of small cells were also isolated by FACS from human testicular and hESC cultures. Conclusions: Our results confirm the potential embryonic-like character of small putative stem cells isolated from human adult ovaries and their possible relation to germinal lineage

Inhibition of BET proteins and epigenetic signaling as a potential treatment for osteoporosis

International audienceHistone modifications are important for maintaining the transcription program. BET proteins, an important class of " histone reading proteins " , have recently been described as essential in bone biology. This study presents the therapeutic opportunity of BET protein inhibition in osteoporosis. We find that the pharmacological BET protein inhibitor JQ1 rescues pathologic bone loss in a post-ovariectomy osteoporosis model by increasing the trabecular bone volume and restoring mechanical properties. The BET protein inhibition suppresses osteoclast differentiation and activity as well as the osteoblastogenesis in vitro. Moreover, we show that treated non-resorbing osteoclasts could still activate osteoblast differentiation. In addition, specific inhibition of BRD4 using RNA interference inhibits osteoclast differentiation but strongly activates osteoblast mineralization activity. Mechanistically, JQ1 inhibits expression of the master osteoclast transcription factor NFATc1 and the transcription factor of osteoblast Runx2. These findings strongly support that targeting epigenetic chromatin regulators such as BET proteins may offer a promising alternative for the treatment of bone-related disorders such as osteoporosis

Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence

background: Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate. methods: For this review, we searched the database MEDLINE (1950 to January 2010) and Google for all full texts and/or abstract articles published in English with content related to oocyte maturation and embryo developmental competence. results: The search showed that alteration of many factors may directly or indirectly impair the competence of maturating oocytes through endocrine and local paracrine/autocrine actions, resulting in a lower pregnancy rate in patients with PCOS. The extra-ovarian factors identified included gonadotrophins, hyperandrogenemia and hyperinsulinemia, although intra-ovarian factors included members of the epidermal, fibroblast, insulin-like and neurotrophin families of growth factors, as well as the cytokines. conclusions: Any abnormality in the extra- and/or intra-ovarian factors may negatively affect the granulosa cell-oocyte interaction, oocyte maturation and potential embryonic developmental competence, contributing to unsuccessful outcomes for patients with PCOS who are undergoing assisted reproduction.Obstetrics &amp; GynecologyReproductive BiologySCI(E)PubMed49REVIEW117-331

Cumulative Delivery Rate after Providing Full Reimbursement In Vitro Fertilization Programme: A 6-Years Survey

Since 1983, Slovenia has been offering well-established, successful, and fully reimbursed IVF programme to infertile couples. On the grounds of data gathered at the Slovenian IVF units we aimed to determine whether the fully accessible IVF treatment system can provide notable success considering cumulative delivery rate (cDR). Longitudinal analysis of getting cDR was performed in 810 IVF cycles of 395 couples who for the first time attended the IVF programme in year 2006 and were followed until year 2012. We calculated the actual and the optimistic cDR. In women aged <38 years the actual cDR was 54% and optimistic DR was 83%, respectively. In women aged ≥38 years the actual cDR was 24 % and optimistic cDR was 27%. These results enable us to report that prospects of the treatment for the women aged <38 years, if they undergo all 6 available IVF cycles, are very positive and quite comparable to the chances of spontaneous conception. Even in older patients it is beneficial to repeat the IVF procedures. Therefore we consider the existing infertility treatment system in Slovenia as an example of good medical practice with high level of beneficence offered to the patients

Non-Invasive Preimplantation Genetic Testing for Aneuploidy and the Mystery of Genetic Material: A Review Article

This review focuses on recent findings in the preimplantation genetic testing (PGT) of embryos. Different preimplantation genetic tests are presented along with different genetic materials and their analysis. Original material concerning preimplantation genetic testing for aneuploidy (PGT-A) was sourced by searching the PubMed and ScienceDirect databases in October and November 2021. The searches comprised keywords such as ‘preimplantation’, ‘cfDNA’; ‘miRNA’, ‘PGT-A’, ‘niPGT-A’, ‘aneuploidy’, ‘mosaicism’, ‘blastocyst biopsy’, ‘blastocentesis’, ‘blastocoel fluid’, ‘NGS’, ‘FISH’, and ‘aCGH’. Non-invasive PGT-A (niPGT-A) is a novel approach to the genetic analysis of embryos. The premise is that the genetic material in the spent embryo culture media (SECM) corresponds to the genetic material in the embryo cells. The limitations of niPGT-A are a lower quantity and lesser quality of the cell-free genetic material, and its unknown origin. The concordance rate varies when compared to invasive PGT-A. Some authors have also hypothesized that mosaicism and aneuploid cells are preferentially excluded from the embryo during early development. Cell-free genetic material is readily available in the spent embryo culture media, which provides an easier, more economic, and safer extraction of genetic material for analysis. The sampling of the SECM and DNA extraction and amplification must be optimized. The origin of the cell-free media, the percentage of apoptotic events, and the levels of DNA contamination are currently unknown; these topics need to be further investigated