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Biomedical subjects

Christina Bergh

Publications and source records attributed to Christina Bergh.

At least 19 recordsLinked to original sources
PubMed2007

Effect of rescuing donated immature human oocytes derived after FSH/hCG stimulation following in vitro culture with or without Follicular Fluid Meiosis Activating Sterol (FF-MAS)--an embryo chromosomal and morphological analysis.

PURPOSE: Studies in mice and humans have shown that Follicular Fluid - Meiosis Activating Sterol (FF-MAS) induces meiotic maturation of immature oocytes in vitro. A multicenter, prospectively randomised study evaluated chromosomal status of embryos from FSH/hCG primed human immature oocytes, cultured with or without FF-MAS. METHODS: Denuded immature oocytes (n=365) were randomly allocated into inert control, FF-MAS 5 microM or 20 microM. Seventy +/-2 hours after ICSI on matured oocytes, all cleaved embryos were fixed for fluorescence in situ hybridisation analysis. RESULTS: Only 15% of oocytes resulted in cleaved embryos. GV oocytes matured at significantly lower rates (14% and 7%) in the two FF-MAS groups compared to the inert control group (47%). High rates of chromosomal abnormalities were found in all groups. CONCLUSION: Immature oocytes showed poor development with high rates of embryo chromosomal abnormalities. Exposure to FF-MAS in the concentrations, duration and/or formulation used in this study did not improve the results.

Animals↗
PubMed2007

Membrane progesterone receptor gamma: tissue distribution and expression in ciliated cells in the fallopian tube.

Non-genomic, rapid actions of steroids have long been known, suggesting the possible presence of non-classical steroid receptors. A membrane receptor for progestins (mPR) was recently described in the spotted seatrout, and transcripts of three related receptors (alpha, beta, and gamma) were subsequently identified in other species including human and mouse. To begin exploring the roles of mPRgamma in mammals, we have generated an antibody against this receptor. The specificity of the antibody was demonstrated by both overexpression and RNA interference experiments. Using the antibody, we show that mPRgamma is expressed in female mouse reproductive tissues such as ovary and fallopian tube, and also in the lung and liver of both sexes. Immunohistochemical studies revealed that mPRgamma is associated with the apical membrane of ciliated cells facing the lumen of the fallopian tube. The presence of mPRgamma in ciliated cells of the fallopian tube was also demonstrated in human samples. Rapid effects of progesterone on ciliary beat frequency in the fallopian tube have recently been reported. Together, this suggests a common role for mPRgamma in the regulation of ciliary activity in the fallopian tube and thus gamete transport in mammals. The presence of mPRgamma in lung and liver of mice suggests that the receptor mediates the actions of progesterone outside the reproductive tract as well.

Animals↗
PubMed2006

Estrogen-induced upregulation of AR expression and enhancement of AR nuclear translocation in mouse fallopian tubes in vivo.

Female mice lacking AR display alterations in ovarian and uterine function. However, the biology of AR in the fallopian tube is not fully understood. To gain an insight into potential roles of AR in this tissue, we demonstrated that eCG treatment increased AR expression in a time-dependent manner and subsequent treatment with hCG decreased AR expression in mouse fallopian tubes. This expression pattern was positively associated with 17beta-estradiol and testosterone levels in vivo. Immunohistochemical analysis of fallopian tube epithelial cells revealed that nuclear localization of AR increased in parallel with decreased AR in the cytoplasm following eCG treatment. Moreover, we found that treatment with flutamide upregulated AR expression in immature mice in association with a decrease in serum testosterone levels, whereas the same treatment resulted in downregulation of AR expression in gonadotropin-stimulated mice with concomitant decreases in serum 17beta-estradiol concentrations, suggesting that androgen differs from estrogen in the regulation of AR expression. Furthermore, we demonstrated that DES increased both AR protein expression and nuclear location over a 48-h time course. DHT had rapid effects, with induction of AR expression and translocation at 6 h after injection, but unlike DES it had prolonged efficacy. In addition, we provided direct in vivo evidence that nuclear protein interaction between AR and p21(Cip1), a previously reported AR-regulated gene, was enhanced by gonadotropin stimulation. To our knowledge, this study provides the first demonstration to illustrate that estrogen as a principal regulator may contribute to regulate and activate AR in the fallopian tubes in vivo.

Animals↗
PubMed2006

Pre-ovarian block versus paracervical block for oocyte retrieval.

BACKGROUND: A pre-ovarian block (POB) technique can be used for pain relief during oocyte retrieval in IVF. The local anaesthetic is deposited in the vaginal wall and between the vaginal wall and the peritoneal surface near the ovary using ultrasound guidance. The aim of this study was to test whether analgesia with POB resulted in improved pain relief compared to paracervical block (PCB). METHODS: A prospective, randomized, multicentre study of POB versus PCB (10 ml of 1% lidocaine each) with 183 patients randomized to POB (n = 96) or PCB (n = 87) was performed. Randomization (via a computer-generated list) was balanced for age, previously completed IVF cycles, degree of anxiety, estimated number of follicles, BMI, premedication and centre. Pain was measured using a visual analogue scale (VAS, 0-100 mm) and given as median values. The primary end-point of this study was overall VAS pain score for both sides during the oocyte retrieval procedure. RESULTS: Overall pain during the entire oocyte retrieval was 22 (POB) and 16 (PCB) (P = 0.42). No differences were found in degree of anxiety, premedication, dose of alfentanil, fertilization rate, number of good-quality embryos or clinical pregnancy rate. CONCLUSIONS: No differences were found in overall pain experienced during the entire oocyte retrieval procedure with POB compared to PCB.

Adult↗
PubMed2006

Derivation of a xeno-free human embryonic stem cell line.

Elimination of all animal material during both the derivation and long-term culture of human embryonic stem cells (hESCs) is necessary prior to future application of hESCs in clinical cell therapy. The potential consequences of transplanting xeno-contaminated hESCs into patients, such as an increased risk of graft rejection [Stem Cells 2006; 24:221-229] and the potential transfer of nonhuman pathogens, make existing hESC lines unsuitable for clinical applications. To avoid xeno-contamination during derivation and culture of hESCs, we first developed a xeno-free medium supplemented with human serum, which supports long-term (>50 passages) culture of hESCs in an undifferentiated state. To enable derivation of new xeno-free hESCs, we also established xeno-free human foreskin fibroblast feeders and replaced immunosurgery, which involves the use of guinea pig complement, with a modified animal-product-free derivation procedure. Here, we report the establishment and characterization (>20 passages) of a xeno-free pluripotent diploid normal hESC line, SA611.

Cell Culture Techniques↗
PubMed2006

Chromosomal integrity maintained in five human embryonic stem cell lines after prolonged in vitro culture.

There have been recent reports of human embryonic stem cell (hESC) lines developing chromosomal aberrations after long-term culture, indicating an unstable genomic status due to the in vitro milieu. This raises concern, since it would limit their use in therapeutics. In this study the chromosomal status of five well-characterized hESC lines, SA002, SA002.5, AS034.1.1, SA121 and SA461, was monitored during long-term in vitro culture. The criteria of defined hESCs were met by all of the five hESC lines (four diploid and one trisomic for chromosome 13). The genomes were screened for chromosomal aberrations and rearrangements using comparative genomic hybridization (CGH), interphase fluorescence in situ hybridization (FISH) and traditional karyotyping on several occasions while in culture. The genomic integrity was shown to be maintained after repeated freeze-thaw procedures and continuous culture in vitro for up to 22 months (148 passages). We discuss the most common de novo chromosomal aberrations reported in hESCs, as well as their possible origin.

Cell Culture Techniques↗
PubMed2006

Depletion of substrates for protein prenylation increases apoptosis in human periovulatory granulosa cells.

Progesterone receptor (PR) stimulation promotes survival in human and rat periovulatory granulosa cells. PR antagonists, Org 31710 and RU 486, both increase apoptosis and decrease cholesterol synthesis in these cells. The decrease in cholesterol synthesis also causes decreased synthesis of other products branching from the cholesterol synthesis pathway, including substrates for protein prenylation. In this study we focus on the link between apoptosis and prenylation in human periovulatory granulosa cells. A decreased cholesterol synthesis and increased apoptosis was verified in experiments with human periovulatory granulosa cells treated with the PR antagonists Org 31710 or RU 486 by measuring caspase-3/7 activity and incorporation of 14C-acetate into cholesterol and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory human granulosa cells using HMG-CoA reductase inhibitors (lovastatin or simvastatin) increased apoptosis, measured as caspase-3/7 activity. The increase in apoptosis caused by simvastatin or Org 31710 was partially reversed by addition of the protein prenylation precursors farnesol or geranylgeraniol. In addition, the prenylation inhibitors FTI R115777 and GGTI 2147 increased apoptosis in these cells. In conclusion our data suggest that PR antagonists increase apoptosis and reduce cholesterol synthesis in periovulatory granulosa cells and that the resulting depletion of substrates for protein prenylation may contribute to the increased apoptosis sensitivity.

Apoptosis↗
PubMed2006

Ophthalmological findings in children born after intracytoplasmic sperm injection.

PURPOSE: To investigate visual function and ocular morphology in children born after intracytoplasmic sperm injection (ICSI) and compare them with visual function and ocular morphology in matched children born after spontaneous conception. METHODS: A total of 137 children born after ICSI and 159 control children were examined at the age of 5 years in a blinded study. The two groups were matched for age, gender and maternal age. The children underwent a detailed ophthalmological investigation by an ophthalmologist and an orthoptist. RESULTS: A total of 90.4% of the ICSI children had a visual acuity (VA) in the better eye of >or= 0.8, compared with 93.7% of the controls (NS). No significant differences were found between ICSI children and controls with regard to hyperopia, myopia, astigmatism, heterotropia, stereoscopic vision and convergence. One child with Goldenhar syndrome and one with Marcus Gunn syndrome were observed in the ICSI group. One child in the ICSI group was treated for retinopathy of prematurity. CONCLUSION: In this limited study group, no significant differences in visual function and/or ocular morphology were found between children born after ICSI and matched control children at the age of 5 years.

Case-Control Studies↗
PubMed2005

Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis.

BACKGROUND: Transfer of several embryos after IVF results in a high multiple birth rate associated with increased morbidity and high costs for the neonatal care. In a previous randomized trial we demonstrated that a single embryo transfer (SET) strategy, including one fresh single embryo transfer and, if no live birth, one additional frozen-thawed SET, resulted in a live-birth rate that was not substantially lower than after double embryo transfer (DET) but markedly reduced the multiple birth rate. METHODS: We compared costs for maternal health care and productivity losses and paediatric costs for the SET and DET strategies. In addition, maternal and paediatric outcomes between the two groups were compared. RESULTS: The SET strategy resulted in lower average total costs from treatment until 6 months after delivery. There were a few more deliveries with at least one live-born child in the DET group. The incremental cost per extra delivery in the DET alternative was high, 71 940. The rates of prematurely born and low birthweight children were significantly lower with the SET strategy. There were also markedly fewer maternal and paediatric complications in the SET group. CONCLUSIONS: The SET strategy is superior to the DET strategy, when number of deliveries with at least one live-born child, incremental cost-effectiveness ratio and maternal and paediatric complications are taken into consideration. The findings do not support continuing transfers of two embryos in this group of patients.

Adult↗
PubMed2005

Single embryo transfer: a mini-review.

This paper provides a concise review of single embryo transfer (SET) in cycles using fresh embryos as well as in cycles using frozen-thawed embryos. Relevant studies were identified by a computerized search in PubMed for the period 1995-2004. The pregnancy rates, delivery rates and multiple pregnancy/birth rates were evaluated after fresh or frozen embryo transfer as well as cumulative delivery rates after fresh and frozen SET. The results of four randomized controlled trials (RCT) and seven observational studies using fresh embryo transfers are analysed. No RCT with SET in freezing-thawing cycles was identified, while one observational study was identified. The effects of a change in the rules from the National Board of Health and Welfare in Sweden in 2003 regarding the implementation of SET in Sweden are summarized.

Cryopreservation↗
PubMed2005

Genetics and assisted reproduction technology.

In the past 20 years, a significant improvement has been shown in the treatment for infertility in both women and men through the development of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Only donated sperm could be previously used for treatment; now oocytes can also be donated. Furthermore, the combination of IVF and ICSI with advanced genetic methods has made preimplantation genetic diagnosis possible for many genetic conditions. These methods enable genetic testing of the early human embryo by using only a single cell, one blastomere biopsied from the embryo, as the sample from which the diagnosis of many chromosome rearrangements and other inherited diseases can be made. It has also been established that a considerable proportion of infertility is caused by genetic defects, which have several implications for infertility treatment. The purpose of this review is to give a concise introduction on how genetics is involved in assisted reproduction technology to specialists who may not be working in this particular field of gynecology, but who would need some knowledge of this for proper care of their patients.

Female↗
PubMed2004

Electro-acupuncture versus conventional analgesia: a comparison of pain levels during oocyte aspiration and patients' experiences of well-being after surgery.

BACKGROUND: The primary aims were to compare the pain-relieving effect and post-operative well-being between electro-acupuncture analgesia (EA) and conventional analgesia (CA) comprising opiates. Further aims were to compare time for mobilization, and costs for time and drug consumption. METHODS: In all, 160 women undergoing IVF were randomized, according to a computer-generated list, to EA or CA. Well-being was evaluated with the State Trait Anxiety Inventory (STAI). Pain and subjective expectations and experiences were recorded on a visual analogue scale (VAS). Time and drug consumption were recorded. RESULTS: Although VAS pain ratings were significantly higher at oocyte aspiration (P < 0.0001) and after retrieval (P < 0.01) in the EA than in the CA group, they were similar 60 min after surgery. Both groups had similar STAI well-being scores. The EA group was significantly less tired and confused than the CA group after oocyte aspiration. No significant differences in time and costs for drug consumption were noted. CONCLUSION: EA cannot generally be recommended as a pain-relieving method at oocyte aspiration but might be an alternative for women desiring a non-pharmacological method. An advantage of EA is less post-operative tiredness and confusion compared with CA.

Acupuncture Analgesia↗
PubMed2004

Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization.

BACKGROUND: The risks of premature birth and perinatal death are increased after in vitro fertilization. These risks are mainly due to the high incidence of multiple births, which relates to the number of embryos transferred. METHODS: We performed a randomized, multicenter trial to assess the equivalence of two approaches to in vitro fertilization with respect to the rates of pregnancy that result in at least one live birth and to compare associated rates of multiple gestation. Women less than 36 years of age who had at least two good-quality embryos were randomly assigned either to undergo transfer of a single fresh embryo and, if there was no live birth, subsequent transfer of a single frozen-and-thawed embryo, or to undergo a single transfer of two fresh embryos. Equivalence was defined as a difference of no more than 10 percentage points in the rates of pregnancy resulting in at least one live birth. RESULTS: Pregnancy resulting in at least one live birth occurred in 142 of 331 women (42.9 percent) in the double-embryo-transfer group as compared with 128 of 330 women (38.8 percent) in the single-embryo-transfer group (difference, 4.1 percentage points; 95 percent confidence interval, -3.4 to 11.6 percentage points); rates of multiple births were 33.1 percent and 0.8 percent, respectively (P<0.001). These results do not demonstrate equivalence of the two approaches in rates of live births, but they do indicate that any reduction in the rate of live births with the transfer of single embryos is unlikely to exceed 11.6 percentage points. CONCLUSIONS: In women under 36 years of age, transferring one fresh embryo and then, if needed, one frozen-and-thawed embryo dramatically reduces the rate of multiple births while achieving a rate of live births that is not substantially lower than the rate that is achievable with a double-embryo transfer.

Adult↗
PubMed2004

Chromosomal abnormality rate in human pre-embryos derived from in vitro fertilization cycles cultured in the presence of Follicular-Fluid Meiosis Activating Sterol (FF-MAS).

BACKGROUND: The objective of the study was to investigate the effect of Follicular-Fluid Meiosis Activating Sterol (FF-MAS) when added to the culture media on the incidence of chromosomal abnormalities and pre-embryo development in human pre-embryos. METHODS: 243 women undergoing IVF/ICSI treatment donated 353 oocytes in a multicentre, prospective, randomized, double blind, four-arm, controlled trial performed at Danish and Swedish public and private IVF centers. Metaphase II oocytes were randomly assigned to: FF-MAS 5 microM, FF-MAS 20 microM, ethanol 0.2% (vehicle control) or water for injection (inert control). The exposure regimen of FF-MAS to the human oocytes was 4 h prior to fertilization by ICSI and 20 h exposure post ICSI. The primary endpoint was the incidence of numerical chromosomal abnormalities. Secondary endpoints were cleavage rate and pre-embryo quality. RESULT: On the pre-embryo level, no significant differences in chromosomal abnormality rate were observed among the four groups. However, the percentage of uniformly normal pre-embryos was significantly lower in the pooled FF-MAS group (5 microM: 12% and 20 microM: 17%) than in the pooled control group (inert control 32% and vehicle control 42%). A high level of mosaicism (41-60%) was found in all groups. At the blastomere level, the percentage of blastomeres categorized as normal was significantly lower in the FF-MAS 5 microM group (41%) and the FF-MAS 20 microM (29%) group versus the inert (52%) and the vehicle (61%) groups. Significantly reduced cleavage and good quality pre-embryo rates were found in both FF-MAS groups. CONCLUSION: FF-MAS increased the rate of aneuploidy and had detrimental effects on cleavage and pre-embryo development, when exposed both before and after fertilization.

Adult↗
PubMed2004

A randomized, double-blind, controlled trial of the effect of adding follicular fluid meiosis activating sterol in an ethanol formulation to donated human cumulus-enclosed oocytes before fertilization.

OBJECTIVE: To evaluate the effect of follicular fluid meiosis activating sterol (FF-MAS) in a 0.2% ethanol formulation on chromosomal status and development of preembryos. DESIGN: Multicenter, prospective, randomized, double-blind, five parallel group, controlled trial. SETTING: Public and private IVF-clinics in Denmark and Sweden. PATIENT(S): Two hundred ten women undergoing IVF treatment donated 310 oocytes. INTERVENTIONS(S): FSH/hCG primed cumulus-enclosed oocytes randomized to 4 hours exposure of medium with 0.1, 1, or 10 microM FF-MAS dissolved in 0.2% ethanol, medium with ethanol 0.2%, or medium with water for injection (control) before insemination. MAIN OUTCOME MEASURE(S): Primary: incidence of human preembryos with chromosomal abnormalities. Secondary: fertilization rate, cleavage rate, and preembryo quality after 68 hours of culture. RESULT(S): At the preembryo level, no significant differences in chromosomal abnormality rate were found among any of the groups. At the blastomere level, a significant increased abnormality rate was observed in the ethanol group and the combined FF-MAS groups compared with the control group. No significant differences in fertilization rate, cleavage rate, or preembryo quality were observed among any of the groups and the control group except for a significant reduction in the number of embryos with >or=2 cells at 26 hours in the ethanol group. CONCLUSION(S): No negative effect of FF-MAS was observed. However, addition of ethanol 0.2% to standard IVF-medium with or without FF-MAS for culturing cumulus-enclosed oocytes for 4 hours before insemination increased the chromosomal abnormality rate at the blastomere level. Further studies of FF-MAS in a nonethanol formulation are under way.

Adult↗
PubMed2004

Why do couples discontinue in vitro fertilization treatment? A cohort study.

OBJECTIVE: To investigate reasons for discontinuation of IVF treatment. DESIGN: Prospective, cohort study. SETTING: Center for reproductive medicine at a large university hospital. PATIENT(S): The 450 couples of a cohort of 974 couples who started IVF treatment between January 1996 and December 1997 and did not achieve childbirth. INTERVENTION(S): The reasons for ceasing treatment were evaluated by scrutinizing the medical records for all couples (n = 288) who did not achieve live birth and who did not complete three stimulated IVF cycles. A questionnaire was sent to all patients for whom the reason for discontinuation was not obvious from the medical records (n = 211). MAIN OUTCOME MEASURE(S): Reasons for discontinuing IVF. RESULT(S): Of 450 couples not achieving live birth, 208 completed their subsidized cycles, whereas 242 discontinued IVF. In 192 (79%) of the 242 cases, the reasons for ceasing treatment could be identified from records or questionnaires. The reason for discontinuation was psychological burden in 26%, a poor prognosis in 25%, spontaneous pregnancy in 19%, physical burden in 6%, serious disease in 2%, and other reasons in 7%. CONCLUSION(S): An unexpectedly high percentage of couples who performed IVF discontinued the treatment before the three cycles that were offered to a majority of the couples. A majority of these discontinuations were due to psychological stress. This information is of importance when counseling patients during treatment.

Cohort Studies↗
PubMed2004

Medical follow-up study of 5-year-old ICSI children.

Children born after intracytoplasmic sperm injection (ICSI) are still a matter of concern. The purposes of the present study were to investigate the physical outcome in 5-year-old children born after ICSI and compare them with children born after spontaneous conception. Three hundred singleton children from Belgium, Sweden and the USA, born after ICSI, were matched by maternal age, child age and gender. In one centre, matching was also performed for maternal education. The main end-point was growth. Secondary end-points were general health, e.g. common diseases, chronic illnesses, surgical interventions and physical/neurological examinations. Standard deviation scores assessed growth. Growth assessed as stature at follow-up was similar in the two groups, despite a higher rate of preterm birth and low birth weight in the ICSI children. Common diseases and chronic illnesses occurred at similar rates in both groups. More ICSI children underwent surgical interventions and required other therapy e. g. physiotherapy and dietary therapy. Physical/neurological examinations revealed few abnormalities in either group. In conclusion, infertility treatment by ICSI does not adversely affect growth during childhood. The children's general health seems satisfactory.

Abnormalities, Multiple↗