Biomedical subjects

Christel Hydén-Granskog

Publications and source records attributed to Christel Hydén-Granskog.

6 recordsLinked to original sources

PubMed2006

Elective single embryo transfer in women aged 36-39 years.

BACKGROUND: The elective single embryo transfer policy is the only effective strategy known to minimize the risk of multiple pregnancy. However, little is known about its applicability to women older than 35 years. METHODS: Analysis was carried out on 1224 fresh IVF/ICSI cycles with embryo transfer and 828 frozen embryo transfer (FET) cycles of women aged 36-39 years. In the fresh cycles, 335 elective single top quality embryo (eSET), 110 elective single non top quality embryo (nt-eSET), 194 compulsory single embryo (cSET) and 585 double embryo transfers (DET) were carried out. RESULTS: Pregnancy rate/embryo transfer (33.1 versus 29.9%) and live birth rate (26.0 versus 21.9%) in fresh cycles did not differ significantly between the eSET and the DET groups. However, women in the eSET group had a higher cumulative pregnancy rate (54.0% versus 35.0%) and a higher cumulative live birth rate (41.8% versus 26.7%, P < 0.0001) compared with those in the DET group. The cumulative multiple birth rate in the eSET group was 1.7%, whereas in the DET group it was 16.6% (P < 0.0001). CONCLUSIONS: The eSET policy can be applied also to patients aged 36-39 years, reducing the risk of multiple birth and increasing the safety of assisted reproduction technique (ART) in this age group.

Adult↗

PubMed2004

Single embryo transfer in clinical practice.

The high incidence of multiple pregnancies is the main reason for adverse treatment outcome in assisted reproduction. A good strategy to avoid multiple pregnancies is elective single embryo transfer and cryopreservation of spare embryos. Important factors in an elective single embryo transfer programme are good counselling of the patients and the selection of embryos with high implantation potential. In the infertility clinic at Helsinki University Central Hospital the elective single embryo transfer programme was started in 1997 and in 2000 the transfer policy turned to single embryo transfer as primary option. In 2003 60% of fresh transfers were elective single embryo transfers and 66% of frozen transfers were single embryo transfers. It has been shown that an elective single embryo transfer programme can be adopted in daily practice and that it decreases the multiple pregnancy rate, in our programme to around 7% with acceptable overall pregnancy and delivery rates. In Finland the increased use of single embryo transfer has reduced the proportion of multiple births. Finally, a good cryopreservation programme is essential to achieve a good cumulative delivery rate without multiple pregnancies.

Cryopreservation↗

PubMed2003

Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures.

BACKGROUND: The reduction of multiple pregnancies by using elective single embryo transfers (eSET) requires critical and careful selection of the embryo for transfer. The current study was undertaken to assess whether early cleavage could be used as a marker of embryo competence in eSET procedures. METHODS: The study included analysis of 178 eSET procedures. All embryos were checked for early cleavage at 25-27 h post insemination or ICSI. The embryos that possessed two cells at 25-27 h post insemination or ICSI were designated as 'early cleavage' (EC) embryos and those that had not yet cleaved were classified as 'no early cleavage' (NEC) embryos. Selection of the embryo for transfer was based on embryo morphology and growth rate on day 2 and not early cleavage. Clinical parameters were compared between 72 EC and 106 NEC single embryo transfers. RESULTS: A significantly higher clinical pregnancy rate was observed after transfer of EC (50%) than NEC (26.4%) embryos. CONCLUSIONS: The current study provides compelling evidence that EC embryos possess significantly higher developmental competence than NEC embryos.

Adult↗

PubMed2003

Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells.

Activins and inhibins are often antagonistic in the regulation of ovarian function. TGFbeta type III receptor, betaglycan, has been identified as a coreceptor to enhance the binding of inhibins to activin type II receptor and thus to prevent the binding of activins to their receptor. In this study we characterized the expression and regulation pattern of betaglycan gene in normal ovaries and sex cord-stromal tumors and in cultured human granulosa-luteal cells from women undergoing in vitro fertilization. Expression of betaglycan mRNA was detected by RT-PCR or Northern blotting in normal ovarian granulosa, thecal, and stroma cells as well as in granulosa-luteal cells. Immunohistochemical analysis revealed positive staining for betaglycan in antral and preovulatory follicular granulosa and thecal cells and in corpora lutea of normal ovaries. Furthermore, betaglycan expression was detected in the vast majority of granulosa cell tumors, thecomas, and fibromas, with weaker staining in granulosa cell tumors compared with fibrothecomas. In cultured granulosa-luteal cells, FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA, as did the protein kinase A activator dibutyryl cAMP and the protein kinase C inhibitor staurosporine. In contrast, the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate had no significant effect on betaglycan mRNA levels. Treatment with prostaglandin E(2) and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation and progesterone secretion dose- and time-dependently. In summary, betaglycan gene is expressed in normal human ovarian steroidogenic cells and sex cord-stromal ovarian tumors. The accumulation of its mRNA in cultured granulosa-luteal cells is up-regulated by gonadotropins and prostaglandin E(2), probably via the protein kinase A pathway. The specific expression and regulation pattern of betaglycan gene may be related to the functional antagonism of inhibins to activin signal transduction in human ovaries.

Activins↗

PubMed2002

Engagement of activin and bone morphogenetic protein signaling pathway Smad proteins in the induction of inhibin B production in ovarian granulosa cells.

In the mammalian ovary cell growth and differentiation is regulated by several members of the transforming growth factor beta (TGF beta) superfamily including activins, inhibins, growth differentiation factors and bone morphogenetic proteins (BMPs). The effects of TGF beta family members are mediated to the target cells via heteromeric complexes of type I and II serine/threonine kinase receptors which activate Smad signaling protein pathways in various cell types. We have previously shown that inhibin B, a hormonally important product from human granulosa cells, is up regulated by activin and BMPs. Here, we report the use of adenoviral gene transfer methodology to manipulate the TGF beta growth factor signaling system in primary cultures of human granulosa cells. These cells are exceedingly difficult to transfect by conventional transfection methods, but were virtually 100% infected with recombinant adenoviruses expressing green fluorescent protein (GFP). Adenoviruses expressing constitutively active forms of the seven known mammalian type I activin receptor-like kinase receptors (Ad-caALK1 through Ad-caALK7) cause activation of endogenous and adenovirally transferred Smad signaling proteins so that Ad-caALK1/2/3/6 and Ad-caALK4/5/7 induced phosphorylation of the Smad1 and Smad2 pathways, respectively. Activin A and BMP-2 activated the Smad1 and Smad2 pathways as well as inhibin B production as did all the Ad-caALKs. Furthermore, overexpression of adenoviral Smad1 and Smad2 proteins without exogenously added ligands induced inhibin B production. The inhibitory Smad7 protein suppressed BMP-2 and activin induced inhibin B production. Collectively, the present data demonstrate that adenoviral gene transfer provides an effective approach for dissecting the TGF beta signaling pathways in primary ovarian cells in vitro and more specifically indicate that the Smad1 and Smad2 pathways are involved in the regulation of inhibin B production by TGF beta family ligands in the ovary.

Activins↗

PubMed2002

Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa-luteal cells.

Insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) have been shown to be involved in ovarian follicular growth/development and steroidogenesis. Recently, a number of low-affinity IGFBP-related proteins (IGFBP-rP) have been characterized. In this study, we investigated the expression of the gene for IGFBP-rP2 (also known as connective tissue growth factor, CTGF) in human granulosa cells in vitro and in vivo. Northern blot analysis demonstrated that IGFBP-rP2 mRNA is expressed in cultured human granulosa-luteal cells obtained from women undergoing an IVF programme. Accumulation of IGFBP-rP2 mRNA was dose-dependently down-regulated by FSH and LH after 24 h treatment (both P < 0.05) in cultured granulosa-luteal cells. The inhibitory effects of gonadotrophins were mimicked by treatment with the protein kinase A activator, (Bu)(2)cAMP. Protein kinase C inhibitor staurosporine reduced, whereas protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) increased, IGFBP-rP2 mRNA accumulation. These results suggest that the inhibitory effects of gonadotrophins on IGFBP-rP2 gene expression may involve signal transduction via both protein kinase A and C pathways. Immunohistochemical analysis revealed positive staining for IGFBP-rP2 in the granulosa and theca cells of normal human ovarian follicles. Corpus luteum and ovarian surface epithelial cells were also positively stained. Modulation of IGFBP-rP2 expression by gonadotrophic hormones may have a role in ovarian follicular development and in the ovulatory process.

Cells, Cultured↗