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Biomedical subjects

S Lindenberg

Publications and source records attributed to S Lindenberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

DNA strand breaks in human spermatozoa: correlation with fertilization in vitro in oligozoospermic men and in men with unexplained infertility.

BACKGROUND: The purpose of this study was to examine the correlation between DNA strand breaks in human spermatozoa and semen quality, fertilization rate and IVF outcome. METHODS: A total of 50 men suffering from unexplained infertility and 50 men with oligozoospermia undergoing IVF treatment entered a prospective study. Sperm samples were assessed according to the WHO manual and for the presence of DNA strand breaks in spermatozoa. The study was blinded for the technician involved in assessment of DNA strand breaks. IVF was carried out according to a long down regulation protocol using GnRH, FSH and hCG. The ova were inseminated with 200,000 spermatozoa/ml. Embryos were transferred on day 2 after fertilization with a maximum of three embryos. RESULTS: This study demonstrates a negative correlation between the proportion of spermatozoa having DNA strand breaks and the proportion of oocytes fertilized after IVF. CONCLUSION: The number of human spermatozoa with DNA strand breaks is a good predictor for fertilization rate in couples suffering from unexplained infertility and undergoing IVF treatment.

Adult↗
PubMed2000

The role of DNA strand breaks in human spermatozoa used for IVF and ICSI.

BACKGROUND: The objective of this study was to determine the incidence of spermatozoa with DNA strand breaks in four clinically different groups of infertile couples, and to correlate DNA damage with other semen analysis parameters, as well as fertilization rates and IVF outcome. METHODS: One group consisted of 75 men where the female partners had a tubal obstruction, Group A. Fifty sperm samples were collected from men in unexplained infertile couples, Group B. Fifty men with oligozoospermia and IVF made up Group C. Finally, 61 men with oligozoospermia and where ICSI was performed made up Group D. Sperm samples were assessed according to the WHO manual and for the presence of DNA strand breaks in spermatozoa. The study was blinded for the technician involved in the assessment of DNA strand breaks. IVF was carried out according to a long down regulation protocol using GnRH, FSH and hCG. Embryos were transferred on day 2 after fertilization with a maximum of three embryos. RESULTS: This study demonstrated a negative correlation between the proportion of spermatozoa having DNA strand breaks and the proportion of oocytes fertilized after IVF (p<0.01). Furthermore, the number of spermatozoa with DNA strand breaks was important for the pregnancy rate in the group of unexplained infertile couples. After ICSI no association was found between spermatozoa with DNA strand breaks and fertilization rates (p>0.05). CONCLUSION: DNA strand breaks in human spermatozoa impairs fertilization in both unexplained infertile couples and those with oligozoospermia and IVF. However, after ICSI, this impact of DNA strand breaks were not seen. This creates a specific indication and treatment for this new diagnosed group of otherwise unexplained infertile men.

Adult↗
PubMed2000

Apoptosis in human cumulus cells in relation to maturation stage and cleavage of the corresponding oocyte.

BACKGROUND: The purpose of this study was to determine the incidence of apoptosis in cumulus cells, and correlate these findings with the maturation stage, fertilization rate and embryo score of the corresponding oocyte, in couples undergoing ICSI due to a male factor. METHODS: The study group consisted of 21 couples where ICSI was performed. The total number of oocyte-cumulus complexes retrieved was 164. Sperm samples were assessed according to the WHO manual, morphology according to the strict criteria and for the presence of apoptosis. The degree of apoptotic DNA fragmentation was determined using the free 3'OH DNA termini in situ with chemically labeled and unlabeled nucleotides. The study was blinded for the technician involved in the assessments of apoptosis in the cumulus cells, apoptosis and morphology in spermatozoa. Ovarian hyperstimulation was carried out according to a long down regulation protocol using GnRH, recFSH and hCG. A maximum of 3 embryos were transferred on day 2 after ICSI. RESULTS: This study demonstrated that the incidence of apoptosis was significantly higher in cumulus cells from germinal vesicle and metaphase I oocytes compared to cumulus cells from metaphase II oocytes (p<0.0001). Non-fertilized metaphase II oocytes showed significantly higher incidence of apoptosis in cumulus cells compared to fertilized metaphase II oocytes (p=0.0082). Furthermore, apoptosis in spermatozoa had an impact on the embryo score (p=0.0087). CONCLUSION: Comparing apoptosis in cumulus cells with maturity of the corresponding oocytes, a significantly higher degree was found related to immature oocytes. Apoptosis in cumulus cells from human metaphase II oocytes impaired the fertilization rate. The degree of fragmentation in the embryo might be correlated to apoptosis in the spermatozoa.

Adult↗
PubMed1999

A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU. In subjects of the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (10.6 versus 6.2 oocytes, P < 0.001). The total dose needed to develop at least three follicles with a diameter of > or = 17 mm was significantly lower in the 100 IU treatment group (1114 IU versus 1931 IU, P < 0.001). In the low-dose group, significantly lower serum concentrations of oestradiol, progesterone and FSH were observed at the day of human chorionic gonadotrophin administration. Although more cycle cancellations due to low response were seen in the 100 IU group (n = 24 versus n = 3), the clinical pregnancy rate per started cycle was similar (24.7% in the 100 IU group versus 23.3% in the 200 IU group). In the high-dose group, more side-effects, in particular more cases of ovarian hyperstimulation syndrome, were noted. It is concluded that compared to 200 IU, the use of a 100 IU fixed dose is less efficacious in terms of the number of oocytes retrieved, but more efficient as indicated by a lower total dose.

Buserelin↗
PubMed1999

In-vitro maturation of human oocytes from regularly menstruating women may be successful without follicle stimulating hormone priming.

This prospective randomized study investigated whether the developmental potential of in-vitro matured (IVM) human oocytes is improved by follicle stimulating hormone (FSH) priming before aspiration. Normally cycling women were recruited among couples referred for in-vitro fertilization or intracytoplasmic sperm injection because of male factor and/or tubal disease. In the first experiment, 20 women were randomly allocated to either no stimulation (n = 10) or stimulation for 3 days with rec-FSH (Gonal-F, Serono) at a fixed dose of 150 IU/day from day 3 (n = 10). The oocytes were aspirated when the follicle(s) was observed to be 10 mm and matured in vitro for 36 h. In experiment 2, 12 women received rec-FSH (150 IU/daily) from day 3. In five patients stimulation was given for 3 days and aspiration performed as in the first experiment; the remaining seven patients continued stimulation until follicles were 10 mm in diameter and aspiration was performed 72 h later. All the oocytes were cultured for 48 h. FSH priming did not increase the number of oocytes obtained per aspiration and did not improve on maturation to metaphase II, cleavage rate or embryo development. The implantation potential of IVM embryos may be improved by maturation for 36 h compared to 48 h. In the first experiment, five out of 20 patients (25%) obtained a clinical pregnancy with an implantation rate of 15% (5/33). One has delivered a healthy boy and three pregnancies are ongoing beyond 32 gestational weeks. In the second experiment, an implantation rate of 7% and a single pregnancy (8%) was obtained, with delivery of a healthy girl.

Cytoplasm↗
PubMed1999

DNA strand breaks in human sperm cells: a comparison between men with normal and oligozoospermic sperm samples.

BACKGROUND: The aim of this report was to compare the degree of DNA strand breaks in known normal fertile men to those with oligozoospermia, and evaluate the presence of DNA strand breaks in normal raw sperm, after Percoll and swim-up and following conventional cryopreservation, as all these preparation methods might differ in selection of healthy sperm cells. METHODS: Sperm samples from proven fertile sperm donors (n=20) and infertile men with oligozoospermia (n=33) were tested for the presence of DNA strand breaks in the spermatozoa, by direct immunoperoxidase detection of digoxigenin-labeled genomic DNA. A correlation to other sperm parameters, sperm counts, motility and Krüger's strict criteria was performed. RESULTS: DNA strand breaks were found significantly more often in sperm samples from men with oligozoospermia compared to sperm samples of normal fertile men. The degree of spermatozoa with DNA strand breaks was correlated proportional with the degree of morphological pathological sperm cells judged by Krüger's strict criteria. The percentage of spermatozoa with DNA strand breaks in the samples was not influenced by procedures such as the swim-up technique, Percoll gradients or cryopreservation and thawing. CONCLUSION: DNA strand breaks were found significantly more often in men with oligozoospermia compared to normospermic men. The DNA strand breaks might play an important role for the maturation process of the spermatozoa in the same way as apoptosis is controlling the number of early meiotic germ cells in the testis, and hereby play an important role in advanced fertility treatments (ICSI).

Apoptosis↗
PubMed1999

Sperm morphology and IVF: embryo quality in relation to sperm morphology following the WHO and Krüger's strict criteria.

BACKGROUND: The aim of this study was to examine the correlation between sperm morphology and embryo quality/IVF outcome. METHODS: The implication of sperm morphology assessment before an IVF cycle was evaluated. A total of 100 IVF couples where the female partner had either tubal factor (n=50) or unexplained infertility (n= 50) entered a prospective study, and sperm samples for the actual cycle were assessed according to the strict criteria and WHO criteria. The study was blinded for the technician involved in sperm morphology analyzing. IVF was carried out according to a long down regulation protocol using GnRH/FSH/hCG and ova were inseminated with 200,000 spermatozoa/ml. Embryos were transferred on day 2 post fertilization in a maximum of three embryos. RESULTS: No significant differences were found between the groups regarding age of the female partner (mean=34.3), no. oocytes retrieved (mean=8.5), fertilization (66.5%), pregnancies (pos. S-hCG/transfer 39.6%) or 'Take home baby rate' (birth rate/transfer 30.0%). As to the score of Krüger's strict criteria and the WHO criteria, we found no correlation between this score and cleavage rate, embryo development or pregnancies. The WHO criteria were found to be a better predictor for fertilization rate than the Krüger's criteria (p<0.002). CONCLUSION: The strict criteria or sperm evaluation according to WHO have no better predictive value for the outcome of routine IVF.

Adult↗
PubMed1999

DNA strand breaks in human spermatozoa: a possible factor, to be considered in couples suffering from unexplained infertility.

BACKGROUND: The aim of this study was to assess the presence of DNA strand breaks and sperm cell morphology in men suffering from unexplained infertility, and to compare these results with normal fertile and oligozoospermic men. METHODS: One fresh sperm sample from proven fertile sperm donors (n=20) and from infertile men with oligozoospermia, (<20 x 10(6)/ml sperm cells) (n=74), and men suffering from unexplained infertility (>20 x 10(6)/ml sperm cells) (n=39) who delivered two sperm samples with 24 hours interval, were tested for the presence of DNA strand breaks in the spermatozoa by direct immunoperoxidase detection of digoxigenin-labeled genomic DNA. Correlations to other sperm parameters, sperm cell counts, motility, activation and Krüger's strict criteria were performed. RESULTS: DNA strand breaks in sperm cell nuclei were found significantly more often in sperm samples from men suffering from unexplained infertility compared to those from normal fertile men, and significantly more rarely compared with sperm samples from men with oligozoospermia. The percentages of normal spermatozoa (Krüger's strict criteria) were significantly lower in samples from men suffering from unexplained infertility compared to those of normal fertile men, but significantly higher compared to those of men with oligozoospermia. No difference was found between first and second day samples used for insemination, as regards DNA strand breaks, sperm cell morphology, total number of motile sperm cells, activation and motility degree. CONCLUSION: The present data suggest that a subgroup of men suffering from unexplained infertility have DNA strand breaks in their sperm cell DNA. This group might suffer from the same malfunction as many men with oligozoospermia, however, their apoptotic activated sites in the testis are different. Delivery of sperm samples with 24 hours interval does not affect any sperm cell counts, CASA, DNA strand breaks or morphology findings in sperm samples from men suffering from unexplained infertility.

Apoptosis↗
PubMed1997

Quality of life and social production functions: a framework for understanding health effects.

Quality of life (QofL) has emerged as a new outcome paradigm. It is now the endpoint in various taxonomies of patient outcomes, in which relationships are modeled amongst biological abnormalities, symptom status, functional status, disability, health perceptions and quality of life. Although current models and taxonomies point at important determinants of QofL, they do not provide a heuristic that guides the conceptualization of QofL and the systematic development of an explanatory theory of how ill health affects QofL. General mechanisms linking ill health, behavior, and QofL are lacking. In this paper we propose social production function (SPF) theory as providing such a heuristic, relating the effects of ill health, the activities that patients engage in to maintain QofL, and QofL itself. This theory basically asserts that people produce their own well-being by trying to optimize achievement of universal human goals via six instrumental goals within the environmental and functional limitations they are facing. Three important notions of SPF theory are: (1) the linkages between goals, needs, and well-being; (2) the distinction between universal needs and instrumental goals; and (3) substitution among instrumental goals, activities and endowments according to cost-benefit considerations, whereby costs refer to scarce resources such as functional capacity, time, effort and money. We will argue that SPF theory meaningfully relates the "biomedical model"-with its focus on pathological processes and biological, physiological and clinical outcomes-to the "quality of life" model, with its focus on functioning and well-being. We describe SPF theory and how SPF theory can be used to: (1) operationally define and measure QofL; (2) clarify persistent measurement problems; and (3) develop an explanatory framework of the effects of disease on QofL. In the discussion section, we address the limitations of the SPF approach of QofL and its relationship with personality.

Activities of Daily Living↗
PubMed1997

Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization.

This retrospective study of 1001 in-vitro fertilization (IVF) cycles included a consecutive series of single transfers (n = 341), dual transfers (n = 410) and triple transfers (n = 250) where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. In our 2 day culture system, transfer of 4-cell embryos resulted in a significantly higher implantation rate and pregnancy rate (23 and 49%) compared with 2-cell embryos (12 and 22%) and 3-cell embryos (7 and 15%). Furthermore, the transfer of 4-cell embryos resulted in a significantly higher pregnancy rate compared with embryos that had cleaved beyond the 4-cell stage (28%). The implantation rate (21%) and pregnancy rate (43%) after transfer of embryos of score 1.0 were significantly higher than after transfer of embryos of score 2.0 (14 and 32% respectively). Transferring embryos of score 2.1 resulted in significantly higher implantation rates (26%) and similar pregnancy rates compared with score 1.0. Transferring embryos of score 2.2-3.0 resulted in a significantly lower implantation rate (5%) and pregnancy rate (15%). A striking finding was that embryos of quality score 2.0 had a significantly lower implantation rate compared with embryos of quality score 1.0 and 2.1 and a significantly lower pregnancy rate compared to embryos of quality score 1.0. We also found a lower implantation rate and pregnancy rate when transferring 3-cell embryos. These findings may indicate periods of increased sensitivity to damage during the cell cycle. In conclusion, these results substantiate the idea of the superiority of 4-cell embryos and demonstrate that minor amounts of fragments in the embryo may not be of any importance. These findings may call for a shift when weighing the two main morphological components (quality score and cleavage stage) in the sense that reaching a 4-cell cleavage stage even with the presence of a minor amount of fragments should be preferred to a 2-cell embryo with no fragments.

Adult↗
PubMed1997

Results of intracytoplasmic sperm injection in relation to indication.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) was first introduced as a treatment to couples that were infertile due to severe male factors. Later, the ICSI technic has also been used on other indications like low or no fertilization in previous IVF cycles. METHODS: A total of 262 ICSI cycles performed in 180 patients were reviewed and the results related to the indications. The indications were severely impaired semen quality (182 cycles) or absent or low fertilization in previous IVF attempts (80 cycles). RESULTS: A total of 2298 oocytes were aspirated and 1939 oocytes were injected resulting in 1172 fertilized (60%) and 995 cleaved oocytes (51%). Of these, 547 preembryos were transferred in 240 cycles and 287 preembryos were cryopreserved. We obtained 99 pregnancies (41%/transfer) of which 63 were ongoing pregnancies (26%/transfer). The pregnancy rate was significantly lower (p = 0.025) in couples referred for ICSI due to previously failed IVF (29%/ transfer) compared to couples with impaired semen quality (46%/transfer). Seventy-seven children have been born. Forty-eight healthy children were born from singleton pregnancies with a mean gestational age of 39.8 weeks and an average birthweight of 3561 g. Thirteen sets of healthy twins and one set of healthy triplets were born. In 29 of the 63 ongoing pregnancies amniocenteses were performed and all karyotypes were normal. CONCLUSION: IVF with ICSI gave good clinical results in couples with severe male factor infertility. The technic can also be used in couples with unexplained fertilization failure, but the pregnancy rate may be lower.

Adult↗
PubMed1996

Fertility potential after unilateral orchiopexy: an age independent risk of subsequent infertility when biopsies at surgery lack germ cells.

PURPOSE: We evaluated whether adult fertility potential was better when unilateral orchiopexy was done at ages 2 to 6 years or later, and we identified those at risk for infertility. MATERIALS AND METHODS: Unilateral orchiopexy was performed simultaneously with testicular biopsy in 11 patients 2.8 to 6.8 years old and in 54, 10.0 to 11.9 years old. In adulthood measurement of testicular volume, serum follicle-stimulating hormone, luteinizing hormone and testosterone was done, as well as analysis of semen specimens. RESULTS: At orchiopexy the 2 groups were statistically similar, and statistically similar fertility potentials were found in adulthood. Five of the 65 patients (7.7%, 95% confidence limits 2.5 to 17%) may experience infertility, representing 33% of both groups with less than 1% of the age matched number of spermatogonia per tubular transverse section (approximately no germ cells) in the biopsy specimen at orchiopexy. CONCLUSIONS: Between ages 2 and 12 years the timing of unilateral orchiopexy may vary without an effect on subsequent fertility potential. When biopsy at surgery lacks germ cells, there is an approximately 33% age independent risk of subsequent infertility. Otherwise patients may be fertile after unilateral orchiopexy between ages 2 and 12 years.

Age Factors↗
PubMed1996

Fertility potential after unilateral orchiopexy: simultaneous testicular biopsy and orchiopexy in a cohort of 87 patients.

PURPOSE: We investigated the prognostic value of the number of spermatogonia per tubular cross section in a testicular biopsy specimen obtained at orchiopexy for unilateral cryptorchidism. MATERIALS AND METHODS: A total of 87 consecutive 10 to 12-year-old cryptorchid boys underwent testicular biopsy simultaneously with unilateral orchiopexy. In adulthood 56 of the 87 patients agreed to measurement of serum follicle-stimulating hormone, luteinizing hormone, testosterone and testicular volume, and 54 provided specimens for semen analysis. RESULTS: The number of spermatogonia per tubular cross section correlated to the volume of the operated testis and total testicular volume in adulthood. Serum follicle-stimulating hormone negatively correlated to these volumes, sperm concentration and total sperm count. Contralateral testicular volume correlated to sperm concentration, total sperm count, and percent of living and mobile sperm. When biopsy revealed Sertoli cells only or 1 spermatogonium per 100 tubular cross sections, the age matched number of spermatogonia per tubular cross section was 1% or less. Of these patients 33% later presented with 5 million spermatozoa per ml. or less, no normal motility and generally lower sperm concentrations that those with more than 1 spermatogonium per 100 tubular cross sections (greater than 1%) in the biopsy specimen. When the value was greater than 1%, later sperm quality was not significantly reduced in comparison to that of the general population. CONCLUSIONS: The age matched number of spermatogonia per tubular cross section is significant in regard to fertility potential, and a value of 1% or less (approximately Sertoli cells only) may predict low fertility potential. To our knowledge Sertoli cells only have not been observed before 15 months of life, which makes it logical to treat cryptorchidism before this age even in unilateral cases.

Biopsy↗
PubMed1996

Intracytoplasmic sperm injection does not overcome an oocyte defect in previous fertilization failure with conventional in-vitro fertilization and normal spermatozoa.

A cohort comprising a total of 447 oocyte aspirations due to male factors (n = 258) or to previous fertilization failure by IVF in the presence of normal sperm parameters (n = 189) was studied. We found a significantly reduced implantation and pregnancy rate per transfer in the group with previously failed IVF attempts compared to the male factor group (P < 0.001). No differences were found in age, number of oocytes retrieved, number of embryos transferred or quality of embryos scored at the time of transfer. However, the fertilization and cleavage rates were found to be reduced in the group with previous failed IVF cycles. It is therefore concluded that previous fertilization failure despite normal sperm parameters in an IVF cycle may not be alleviated by the intracytoplasmic sperm injection (ICSI) procedure. These patients might suffer from oocyte defects as well.

Cytoplasm↗
PubMed1995

Ultrastructure of endometrial epithelial cells in a three-dimensional cell culture system for human implantation studies.

PURPOSE: A three-dimensional cell culture system imitating normal uterine endometrium has previously been established. To what degree do cultured epithelial cells retain their morphological characteristics as compared to in vivo material obtained simultaneously from the same tissue donor. RESULTS: We found a high degree of similarity between the in vivo and in vitro situations. The present culture system furthermore imitates the day-to-day morphology of the cycle. CONCLUSIONS: This indicates, that a correct timing of the biopsy tissue is important for future human implantation studies.

Biopsy↗
PubMed1994

Isolation and culture of human endometrial cells in a three-dimensional culture system.

A cell culture system was established in which endometrial stromal cells were embedded in a collagen matrix and separated from the endometrial epithelium by basement membrane material (Matrigel). The epithelium, seeded on top of the collagen matrix, grew in a monolayer. The cultures were evaluated by light microscopy and transmission and scanning electron microscopy. Light and transmission electron microscopy indicated a polarized columnar epithelium in monolayer with basally positioned nuclei. Scanning electron microscopy revealed a confluent epithelium with an abundance of microvilli and cilia, as well as pinopodes on the apical surface. Immunohistochemical staining for cytokeratin confirmed the epithelial origin of the surface cells, and staining for human collagen IV demonstrated its presence underneath the epithelial cells. This culture system represents a three-dimensional system that imitates the normal endometrium.

Biocompatible Materials↗
PubMed1993

[Freezing of human embryos: the first Danish results].

The first human pregnancies reported in Denmark following in vitro fertilization and embryo transfer of frozen and thawn embryos are presented. A total of nine embryo transfers, with a mean of one point eight embryos per transfer, were carried out, resulting in three singleton pregnancies. The benefits for the infertile couple, the ethics and technical aspects are discussed with respect to Danish legislation.

Cryopreservation↗