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Biomedical subjects

C De Geyter

Publications and source records attributed to C De Geyter.

At least 19 recordsLinked to original sources
PubMed2006

Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: a randomized open-label study.

OBJECTIVES: To establish whether transdermal continuous hormone replacement therapy (HRT) with estrogen/progestogen provides adequate long-term endometrial protection in postmenopausal women over a period of 96 weeks. METHODS: This multicenter, randomized, open-label, parallel-group study evaluated the endometrial effects and overall safety and tolerability of a transdermal matrix patch delivering estradiol (E2) 50 microg/day and norethisterone acetate (NETA) 140 microg/day (Estalis; patches applied twice weekly without intermediate breaks) and a once-daily oral comparator (Kliogest; one tablet containing E2 2 mg/NETA 1 mg) in postmenopausal women. A total of 406 women with an intact uterus, aged 44-69 years, were randomized in the 48-week core phase of the study, and 239 continued into the 48-week extension phase. Subjects were randomized in the ratio 3 : 1 to transdermal or oral E2/NETA treatment. RESULTS: No cases of endometrial hyperplasia or endometrial cancer were reported with either treatment during the core or extension phase. Both treatments were generally well tolerated, with most adverse events (>90%) being mild to moderate, although minor differences in the tolerability profile were observed between treatments. CONCLUSIONS: Continuous combined transdermal HRT with E2/NETA shows no evidence of an increased endometrial hyperplasia or endometrial cancer risk over a 96-week period.

Administration, Cutaneous↗
PubMed2005

Comparative birth weights of singletons born after assisted reproduction and natural conception in previously infertile women.

BACKGROUND: The possible interference of assisted reproduction techniques (ART) with epigenetic reprogramming during early embryo development has recently sparked renewed interest about the reported lower birth weight among infants born as a consequence of infertility treatments. However, the latter finding so far has relied on the comparison of the birth weight of infants conceived with ART to general population data. A more appropriate comparison group should involve pregnancies in infertile women after natural conception. Therefore, we compared neonatal birth weight data of infants born after various ART treatments, including intrauterine insemination (IUI), with those of previously infertile women achieving pregnancy after sexual intercourse. METHODS: Between August 1996 and March 2004 the data of all infertile women presenting in the infertility unit of the University Women's Hospital of Basel, Switzerland, were collected prospectively, adding up to 995 intact pregnancies and deliveries. The birth weight of all infants resulting from 741 singleton pregnancies were analysed with regard to the patients' characteristics, the occurrence of complications during pregnancy and the type of infertility treatment with which the pregnancies were achieved. RESULTS: Comparison of duration of pregnancy and birth weight of infants born after infertility treatment confirms a shorter pregnancy span and a lower mean birth weight in infants born after IVF and ICSI. If women with pregnancies after ART deliver before term, neonatal birth weight is significantly lower. CONCLUSIONS: There is a specific effect of ART, mainly IVF and ICSI, on both shortening the duration of pregnancy and lowering neonatal birth weight. Both these parameters seem to be interrelated consequences of some modification in the gestational process induced by the infertility treatment. Freezing and thawing of oocytes in the pronucleate stage had a lesser impact on pregnancy span and on neonatal birth weight.

Adult↗
PubMed2005

Membrane translocation and oligomerization of hBok are triggered in response to apoptotic stimuli and Bnip3.

hBok is a human pro-apoptotic member of the Bcl-2 family. By fluorescence in situ hybridization and in silico analysis, hBok was found to be located on chromosome 2q37.3. Its expression was detected in various organs and several hormonally regulated cancer cells. Expression of hBok was shown to be upregulated in estrogen-dependent breast cancer by estrogen deprivation and in myocardial cells during hypoxia. Confocal laser scanning microscopy examinations and subcellular fractionation studies showed that hBok was distributed in both the cytosol and intracellular membranes of healthy cells. Upon overexpression of hBok or stimulation of apoptosis, hBok became integrated into the membrane. Furthermore, apoptosis and oligomerization were promoted by BH3-only proteins, such as Bid, Bnip3 and p53, but prevented by BFL-1. hBok was found to interact with Bnip3. Our findings suggest that functional BH3-only proteins facilite the oligomerization and insertion of hBok into the membrane to activate it.

Amino Acid Sequence↗
PubMed2002

Three-dimensional dynamic MR-hysterosalpingography; a new, low invasive, radiation-free and less painful radiological approach to female infertility.

BACKGROUND: The purpose of this study was to propose a new method for imaging the uterine cavity and Fallopian tube patency by three-dimensional dynamic magnetic resonance hysterosalpingography (3D dMR-HSG) and to analyse if, by using a higher viscosity contrast solution, direct visualization of the Fallopian tubes may be achieved by this new technique. METHODS: 10 consecutive infertile women underwent 3D dMR-HSG and conventional HSG as gold standard. 3D dMR-HSG consisted of injection of 20 ml of a gadolinium-polyvidone solution into the uterine cavity while acquiring five consecutive three-dimensional (3D) T1-weighted MR-sequences. RESULTS: In three patients the catheter became dislodged during 3D dMR-HSG. However, in one of these patients the examination was still partially diagnostic. Imaging findings of 3D dMR-HSG showed good correlation with conventional hysterosalpingography and allowed 3D imaging of the uterine cavity and of Fallopian tube patency in 8/10 patients and direct visualization of the Fallopian tubes in 5/7 patients. CONCLUSION: 3D dMR-HSG represents a new and promising imaging approach to female infertility causing less pain and avoiding exposure of the ovaries to ionizing radiation. By using a higher viscosity MR-contrast agent it allows not only visualization of uterine cavity and Fallopian tube patency but also direct visualization of Fallopian tubes.

Adult↗
PubMed2001

Bcl2-L-10, a novel anti-apoptotic member of the Bcl-2 family, blocks apoptosis in the mitochondria death pathway but not in the death receptor pathway.

By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain. The Bcl2-L-10 gene has been assigned to chromosome 15q21.2. Transfection experiments demonstrated that Bcl2-L-10 can block apoptosis induced by interleukin-3 withdrawal and Bax expression, by prevention of cytochrome C release, caspase-3 activation and mitochondrial membrane potential collapse. Bcl2-L-10 cannot block TNFalpha-induced apoptosis. Furthermore, both the BH4 domain and the transmembrane domain of Bcl2-L-10 are necessary for its suppressive action on cell death. Our results demonstrated that Bcl2-L-10 is a newly detected anti-apoptotic member of the Bcl-2 family and that it blocks apoptosis in the mitochondrial death pathway but not in the death receptor pathway.

Amino Acid Sequence↗
PubMed2001

Three-dimensional dynamic MR hysterosalpingography: a preliminary report.

The aim of this study was to evaluate the feasibility of three-dimensional dynamic MR hysterosalpingography (3D MR HSG) for visualization of the cavum uteri and demonstration of bilateral fallopian tube patency as an alternative to conventional hysterosalpingography. Five infertile female patients underwent 3D dynamic MR HSG prior to conventional hysterosalpingography. The MR protocol consisted of axial T1-weighted spin-echo (SE), axial/coronal T2-weighted fast SE (FSE), and 3D MR angiography sequences before, during, and after injection of a diluted gadolinium solution into the cavum uteri via a balloon catheter. Positioning of the catheter was feasible in all patients. In one patient the catheter slipped out during MRI and in one patient the catheter was placed far in the cavum uteri. In three patients catheter position was optimal at the level of the cervical canal. Evaluation of pelvic anatomy, myometrium, and ovaries was possible in all patients on the basis of T1-weighted SE and T2-weighted FSE. Three-dimensional visualization of the dilated cavum uteri was possible in four patients. In these four patients 3D MR HSG also proved bilateral fallopian tube patency which was confirmed in each patient by conventional hysterosalpingography. Three-dimensional MR HSG is feasible and further research should be done to determine if this technique can evolve into an alternative technique to conventional hysterosalpingography with the advantages of no radiation and additional visualization of the uterus wall and ovaries.

Adult↗
PubMed2000

Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women.

OBJECTIVE: To investigate the effect of differences in endometrial thickness and pattern as visualized with present-day high-resolution transvaginal ultrasound equipment on the outcome of assisted reproductive treatment. DESIGN: Prospective cohort study. SETTING: Two large infertility units in university hospitals. PATIENT(S): The endometrial characteristics of 981 patients during 1,600 assisted reproductive treatment cycles were compared with those of 205 untreated women. In addition, abnormal echogenic patterns of the endometrium were characterized histologically in 44 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): The endometrium was significantly thinner in untreated women and women treated with IUI than in women treated with IVF or intracytoplasmic sperm injection. The exponential proliferation of the endometrium was similar in conception and nonconception cycles. The odds for a successful pregnancy were significantly lower in the presence of a thin endometrium in women treated with IUI but not in women treated with the long stimulation protocol for IVF or intracytoplasmic sperm injection. Singleton pregnancies were more common than multiple pregnancies in patients with thin endometria. CONCLUSION(S): The pregnancy rates of assisted reproductive procedures are influenced only marginally by the degree of endometrial proliferation, and treatment should not be canceled because of inadequate endometrial thickness.

Cell Division↗
PubMed2000

Characterization of the interaction of IpaB and IpaD, proteins required for entry of Shigella flexneri into epithelial cells, with a lipid membrane.

Entry of Shigella flexneri into epithelial cells and lysis of the phagosome involve the IpaB, IpaC, and IpaD proteins, which are secreted by type III secretion machinery. We report here the purification of IpaB and IpaD and the characterization of their lipid-binding properties as a function of pH. The interaction of IpaB with the membrane was quite independent of the pH whereas that of IpaD took place only at low pH. To support the data obtained with the purified proteins, we designed a system in which protein secretion by live bacteria was induced in the presence of liposomes, thereby allowing interaction of proteins with lipids directly after secretion and bypassing any purification step. In these conditions, both IpaB and IpaC, as well as minor amounts of IpaA and IpgD, were associated with the membrane and the ratio of IpaB to IpaC was modulated by the pH. The relevance of these results with respect to the dual roles of IpaB, IpaC and IpaD in induction of membrane ruffles and lysis of the endosomal membrane is discussed.

Antigens, Bacterial↗
PubMed2000

Clustering of male infertility in the families of couples treated with intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is an effective treatment modality for male factor infertility, but it could promote the transgenerational transmission of genetic defects causing gametogenic failure. Cytogenetic and molecular techniques permit the diagnosis of some infertility-causing genetic aberrations, but many more probably evade detection with currently available technology. The analysis of the recurrence pattern of infertility in infertile couples' families could define the importance of heritable factors in the pathogenesis of human infertility. We have subjected 621 consecutive infertile couples treated with ICSI in a single institution to a comprehensive genetic workup including documentation of the family history, karyotyping and various DNA tests. In all, 1302 fertile couples served as controls. Of the infertile couples 6.4% were shown to have a fertility problem with a definite genetic basis. Male, but not female fertility problems displayed a distinct pattern of familial aggregation. In addition, the infertile couples had fewer siblings than the fertile controls, a finding compatible with suboptimal fertility already among the infertile couples' parents. In summary, our data indicate that male factor infertility should be considered a potentially heritable condition. The recurrence risk for infertility in the offspring of couples treated with ICSI might be substantial.

Adult↗
PubMed2000

Characterization of an immortalized human granulosa cell line (COV434).

We have investigated the biological characteristics of an immortalized granulosa cell line (COV434), which may be used to study follicular and oocyte maturation in vitro. Granulosa cell function was defined as consisting of three distinct properties: (i) production of 17beta-oestradiol in response to follicle stimulating hormone (FSH); (ii) presence of specific molecular markers of apoptosis enabling the induction of follicular atresia; and (iii) capacity to form intercellular connections with cells surrounding an oocyte. The addition of FSH to the culture medium supplemented with 10% fetal calf serum and 4-androstene-3,17-dione resulted in proliferation of the COV434 granulosa cells and in an increased synthesis of 17beta-oestradiol, indicating the presence of the FSH receptor and cytochrome P450 aromatase in these cells. The receptor for luteinizing hormone (LH) was undetectable. Similar expression of various apoptosis-associated genes was found in COV434 granulosa cells and in granulosa cells of patients stimulated with gonadotrophins for in-vitro fertilization, thus indicating that the immortalized COV434 granulosa cells were able to sustain apoptosis. Multiple intercellular connections were formed during co-culture of COV434 granulosa cells with cumulus cells containing an immature oocyte but not with cumulus cells devoid of an oocyte. Detailed morphological analysis of the intercellular connections with scanning electron microscopy and confocal light microscopy demonstrated the presence of long slender structures. It is concluded that the immortalized human granulosa cell line COV434 may be useful for experimental studies on follicular development.

Apoptosis↗
PubMed1999

[20 years in vitro fertilization: what follows?].

During the last two decades in-vitro fertilization (IVF) developed on a worldwide scale by increasing numbers of treated couples and by extending the medical indications. Existing treatment protocols have been optimized to such an extent that pregnancy rates over 30% are reached in many treatment units. Further improvements of the pregnancy rate may be achieved with assisted hatching, which is now the subject of a large European multicentric prospective study based on the University of Lausanne. On the other hand, the occurrence of multiple pregnancies, which is the main complication of IVF, may be limited by reducing the number of embryos replaced. Further improvements of treatment efficacy may result from the introduction of new medications, such as recombinant FSH or GnRH-antagonists, allowing for the adaptation of the treatment protocol used to the individual needs of each patient. A treatment protocol combining a GnRH-antagonist and gonadotropins may be particularly valuable in young patients for the purpose of avoiding the ovarian hyperstimulation syndrome. The major disadvantage of these novel medications consists of their increased costs. Therefore, a new treatment strategy is currently developed aiming at shortening the ovarian stimulation in combination of a prolongation of the laboratory phase. The in-vitro maturation of immature oocytes aspirated from small follicles previously primed with recombinant FSH has been shown to be a feasible alternative to the present treatment modalities. Cryopreservation of unfertilized oocytes together with in-vitro maturation may prove to be helpful for women prior to chemotherapy or radiation because of malignant diseases or for patients suffering from incipient ovarian failure. At present, there seems to be no alternative to assisted reproduction although the dominance of this technique may impede the development of more cause-related treatment strategies in infertility.

Embryo Transfer↗
PubMed1999

[Polycystic ovary syndrome--only relevant in reproductive medicine?].

The Polycystic Ovary Disease (PCOD) is one of the most common endocrine disorders in women with a prevalence of 5%. Affected women often consult a gynecologist because of menstrual irregularities, fertility problems or problems of androgen excess. However, PCOD is a metabolic disorder affecting multiple organs. Studies suggest that those women are at risk for developing several complications such as type II diabetes mellitus, hypertension, dyslipidemia and myocardial infarction. The risk to develop endometrial carcinoma is also elevated. To give adequate treatment to women with PCOD, an interdisciplinary approach of gynecologists together with endocrinologists specialized in metabolic and nutritional disorders at the University of Basel is presented. The work-up for diagnosis and assessment of risk factors is outlined. Goal of this interdisciplinary approach is an adequate evaluation of affected patients and their long-term follow-up to test if proposed interventions as weight loss, treatment of hyperinsulinemia, regulation of menstrual cycle and others can avoid long-term sequelae.

Diagnosis, Differential↗
PubMed1998

Low multiple pregnancy rates and reduced frequency of cancellation after ovulation induction with gonadotropins, if eventual supernumerary follicles are aspirated to prevent polyovulation.

PURPOSE: Our purpose was to demonstrate the feasibility of the routine aspiration of supernumerary follicles in infertile patients with imminent polyovulation after ovulation induction with gonadotropins and to examine its effect on the frequency of cycle cancellation and on the (multiple) pregnancy rate. METHODS: The data on 796 treatment cycles, performed between 1989 and 1996 on 410 infertile couples, were analyzed retrospectively. From October 1992, whenever necessary, supernumerary ovarian follicles were selectively aspirated transvaginally under ultrasound guidance to prevent the ovulation of more than three follicles. Thereafter, intrauterine insemination was performed. RESULTS: After the adoption of transvaginal ultrasound-guided aspiration of supernumerary follicles into the treatment protocol in October 1992, the number of canceled cycles (P < 0.0001) and the multiple pregnancy rate (P < 0.01) were significantly reduced compared to those previously. The overall pregnancy rate remained stable. No ovarian hyperstimulation syndrome requiring hospitalization was noted, and no complications resulting from the follicle aspiration were registered. CONCLUSIONS: Transvaginal ultrasound-guided aspiration of supernumerary ovarian follicles increases both the efficacy and the safety of ovulation induction with gonadotropins. Because of the limited equipment required, this method represents an alternative for conversion of overstimulated cycles to more costly alternatives such as in vitro fertilization.

Adult↗
PubMed1998

Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm injection--prevalence, types, sex distribution and reproductive relevance.

Chromosomal abnormalities are thought to be a major contributor to the genetic risks of infertility treatment by intracytoplasmic sperm injection (ICSI). Apart from abnormalities arising de novo, abnormal karyotypes in pregnancies conceived through assisted reproductive technology may be directly derived from predisposing parental aberrations. In a prospective study we have analysed the chromosomes of 868 male and female patients prior to planned ICSI treatment. A total of 33 aberrant karyotypes was diagnosed, corresponding to an abnormality rate of 7.6% per couple or 3.8% per individual studied. Even though male factor infertility was twice as common as female factor infertility in this cohort, 24 of the chromosomal abnormalities were found among the women. Low-level mosaicism for numerical sex chromosome anomalies was diagnosed in 20 individuals, and one patient had the triple X karyotype. With respect to structural chromosomal anomalies, we found six reciprocal and three Robertsonian translocations, two paracentric inversions and one marker chromosome. Many of the aberrations that we diagnosed could be classified as carrying only a small to moderate reproductive risk. Given the high rate of abnormal karyotypes among the female subjects, we suggest that not only the males, but both partners should be routinely karyotyped prior to ICSI.

Adult↗