Biomedical subjects

P Sjöblom

Publications and source records attributed to P Sjöblom.

At least 19 recordsLinked to original sources

PubMed2001

Clinical outcome of treatment cycles using preimplantation genetic diagnosis for structural chromosomal abnormalities.

OBJECTIVES: To explore oocyte recovery, embryo quality, the number of transferable embryos and pregnancy rate after preimplantation genetic diagnosis (PGD) in patients with structural chromosomal aberrations. METHODS: PGD was performed in seven couples with Robertsonian translocations (Rob), eight couples with reciprocal translocations (Rec), two couples with inversions and one couple with a deletion. A total of 43 treatment cycles were carried out. RESULTS: A total of 14.2 oocytes per cycle were retrieved. Fertilisation and cleavage rates were 63% and 58%, respectively. Of the biopsied embryos 20% were transferable. Comparison of the Rob and Rec group revealed no significant differences in number of oocytes, fertilisation or cleavage rates. The number of transferable embryos after biopsy was significantly higher in the Rob group than in the Rec group. When embryo transfer (ET) was performed the pregnancy rate did not differ between the Rob and the Rec groups. Twenty-eight embryo transfers (one or two embryos) were carried out leading to eight clinical pregnancies (29% per ET): two twins, four singletons, one miscarriage and one ectopic pregnancy. All the children are carriers of balanced chromosomal aberrations. CONCLUSION: An acceptable pregnancy rate can be achieved among couples with structural chromosomal abnormalities.

Adult↗

PubMed2001

Reduced developmental potential in oocytes from women with endometriosis.

PURPOSE: To study retrospectively the outcome of intracytoplasmatic sperm injection (ICSI) in women with endometriosis compared with women with no known female infertility factor. METHODS: All couples treated with ICSI because of male infertility plus verified endometriosis (n = 26) and all couples treated with ICSI because of male infertility only (n = 125) during the period January 1995 to June 1999 were included. Data were collected from patient files and ICSI protocols. RESULTS: The time to complete down regulation was significantly longer (p = 0.0108), the dose of FSH significantly higher (0.0247), the day for oocyte pickup significantly later (p = 0.0091), and the cleavage rate of oocytes significantly lower (p = 0.0011) in women with endometriosis compared with controls. There was no significant difference in implantation rate or pregnancy rate between the groups. CONCLUSIONS: Women with endometriosis presented significantly reduced follicular response and oocyte cleavage rate, two mechanisms that might be related to a disturbed oogenesis.

Adult↗

PubMed2000

Semen retrieval and analysis in men with myelomeningocele.

The introduction of advanced assisted reproduction technologies (ART) has created opportunities for the treatment of infertility among patients with myelomeningocele (MMC). The aim of this study was to assess the possibility of semen retrieval and to analyse the semen quality in men with MMC. Nine men, aged 22 to 39 with MMC participated in the study. Two participants were able to achieve unassisted ejaculation. Vibratory stimulation was unsuccessfully attempted in the remaining seven participants who then underwent electroejaculation under general anaesthesia. In total, enough spermatozoa for intracytoplasmic spermatozoa injection were retrieved from five participants. In four cases, no spermatozoa were observed in the ejaculates. Testicular biopsies, however, revealed spermatogenesis, and thus a reproductive potential, in one of these men. Therefore, in six of the nine men with MMC, fatherhood seemed possible with modern ART, despite the semen quality generally being very poor.

Adult↗

PubMed2000

Tissue differences but limited sex steroid responsiveness of c-fos and c-jun in human fibroids and myometrium.

Sex steroids influence the growth of mammalian uterine tissues and the proto-oncogenes c-fos and c-jun have been implicated in the cascade of cellular events induced by the cyclic influence of oestrogen and progesterone. To investigate the role of these proto-oncogenes for fibroid growth their mRNA expression was measured in myometrium and fibroids under different hormonal conditions, using a solution hybridization method. Fibroids and myometrium were collected at surgery from premenopausal, postmenopausal and pregnant women as well as women treated with a gonadotrophin releasing hormone agonist (GnRHa; Goserelin). The phase of the menstrual cycle was determined in all the untreated, premenopausal, non-pregnant women. The mRNA expression of c-fos and c-jun in fibroids was significantly lower than in homologous myometrium. No significant differences in c-fos expression were observed in myometrium, or fibroids, due to menstrual cycle phase, GnRHa treatment, pregnancy or the menopause. The c-jun expression in myometrium from pregnant women without fibroid disease was significantly higher than the corresponding control myometrium from premenopausal, non-pregnant women. These results demonstrate a tissue difference in the expression of c-fos and c-jun between myometrium and fibroids.

Adult↗

PubMed2000

Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions.

The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from women without fibroid disease. Women with menstrual periods were classified according to the phase of the cycle. In tissues from non-treated premenopausal women, IGF-I mRNA expression was significantly higher in fibroids than in myometrium, with no differences related to phase of the menstrual cycle. In post-menopausal women and in GnRH agonist-treated women responding to treatment, similar mRNA expression was seen in myometrium and fibroids but the concentrations were lower than in untreated premenopausal women. The IGF-I mRNA value in fibroids from pregnant women was higher than in any other group and myometrium from pregnant women exhibited higher mRNA expression than myometrium from non-treated premenopausal women. The IGF-I protein was more abundant in fibroids than in myometrium of non-treated premenopausal and of pregnant women and in both tissues the concentration was significantly higher in the group of pregnant women. The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women. High sex steroid concentrations in pregnant and non-pregnant women of fertile age seem to be associated with a higher expression of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the selective growth advantage of these tumours.

Adult↗

PubMed2000

Production of interleukins 1beta, 6 and 8 and tumor necrosis factor alpha in separated and cultured endometrial and endometriotic stromal and epithelial cells.

The production of IL-1beta, IL-6, IL-8 and TNF-alpha was studied in short-time culture of separated stromal and epithelial cells. The cytokine secretion into culture medium was analyzed using immunoassay to evaluate the cytokine protein levels and bioassay to assess the bioactivity of the cytokines. Tissue samples of endometrium and ovarian endometriomas were obtained from 4 patients operated on for clinical reasons. Only IL-8 was found in all samples. IL-1beta and TNF-alpha were detected in the culture medium from most stromal cell samples, but in fewer media from epithelial cell samples. IL-6 was measurable in a few medium samples. Few of the samples displayed a bioactivity. There was no obvious difference between endometrium and endometriotic cell samples besides the production of IL-8 that seems to be lower in endometriotic tissue.

Adult↗

PubMed2000

Highly abnormal cleavage divisions in preimplantation embryos from translocation carriers.

We have developed preimplantation genetic diagnosis (PGD) for carriers of chromosomal abnormalities using fluorescent in situ hybridisation (FISH). Here we present the detailed analysis of 64 biopsied, normally developing embryos obtained from four Robertsonian and three reciprocal translocation carriers in 11 treatment cycles of which four resulted in normal pregnancies (three simplex, one duplex). In order to investigate the degree of mosaicism and segregation mode in the embryos, the primary analysis of the biopsied cells was extended with the analysis of all cells from the non-transferred embryos. The analysis also included a second hybridisation with two additional probes, not involved in the translocation (chromosomes 1 and 9), in order to investigate the overall degree of mosaicism. Seventeen out of 64 analysed embryos were balanced for the chromosomes involved in the translocation and 14 of these were transferred. Forty-seven out of 64 embryos (73%) were mosaic regarding the chromosomes involved in the translocation and alternate segregation mode was the most common mode of segregation. Moreover, we have found a higher degree of mosaicism for the chromosomes involved in translocations as compared to control chromosomes. This difference was more pronounced for the embryos from reciprocal translocation carriers. The results, mechanisms, significance and implications of our findings are discussed.

Biopsy↗

PubMed1999

A high degree of aneuploidy in frozen-thawed human preimplantation embryos.

We have studied the chromosomal content in 68 normally fertilised freeze-thawed human embryos of good morphology from 34 patients with an average maternal age of 32,6 years. Forty embryos showed post-thaw cellular division and twenty-eight post-thaw cleavage arrest. After spreading of the embryos on microscope slides, analysis of chromosomes X, Y, 15, 16, 17 and 18 was performed using two rounds of fluorescent in situ hybridisation (FISH). According to the results, the embryos were divided into four groups: (I) normal, all nuclei uniformly diploid, (II) diploid mosaics, normal diploid blastomeres in combination with abnormal blastomeres, (III) abnormal, all nuclei abnormal, (IV) chaotic, the chromosome constitution varies randomly from cell to cell. Approximately 25% of the embryos had normal number of the chromosomes tested, while the majority of the embryos were abnormal. Most of the abnormal embryos were diploid mosaics (57%). This was true for the embryos showing cleavage division as well as the embryos showing cleavage arrest. Our data show a slightly higher incidence of abnormal embryos compared to those obtained with FISH in non-cryopreserved embryos and confirm that the majority of preimplantation embryos fertilised in vitro contain abnormal blastomeres. The results, mechanisms, significance and implications are discussed.

Aneuploidy↗

PubMed1999

A cost comparison of infertility treatment for clomiphene resistant polycystic ovary syndrome.

BACKGROUND: The study compares treatment outcome and costs of ovulation induction cycles and in vitro fertilization cycles in infertile women with clomiphene resistant polycystic ovary syndrome. METHODS: Twenty-eight infertile women with clomiphene resistant polycystic ovary syndrome referred to a university clinic were prospectively randomized to ovulation induction or in vitro fertilization. Forty-one ovulation induction cycles and thirty in vitro fertilization cycles were performed. Mann-Whitney U-test was used for between group comparisons and frequencies were compared with Fisher's exact test. RESULTS: More pregnancies per completed cycle were noted in the in vitro fertilization group than in the ovulation induction group. Drug costs were not much higher in the in vitro fertilization group but treatment costs were higher due to the additional costs of ovum pick up and embryo transfer. The cost per pregnancy was about twice as high in the ovulation induction group as in the in vitro fertilization group. The cost per term pregnancy including delivery was 1.6 times higher in the ovulation induction group. CONCLUSION: For a group of obese women with clomiphene resistant polycystic ovary syndrome, in vitro fertilization seems a cost-effective treatment.

Clomiphene↗

PubMed1999

Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization.

Increased androgen concentrations are thought to be detrimental to oocyte quality and reproductive potential. Adjuvant treatment with glucocorticoids has been tried to suppress androgens in women undergoing infertility treatment. In the present study 20 infertile women with polycystic ovary syndrome were prospectively randomized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night, during standard in-vitro fertilization (IVF) treatment. Serum samples for assays of gonadotrophins, steroids and sex hormone-binding globulin (SHBG) were collected before treatment, at down-regulation, and at oocyte retrieval. Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes, the rest according to the clinic's routines. In the placebo group, serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S) did not change between down-regulation and oocyte retrieval, whereas adjuvant prednisolone resulted in a significant decrease. In follicular fluid, adjuvant prednisolone resulted in significantly lower concentrations of DHEA-S as compared to placebo, no other significant differences were found. No significant differences were found in embryo characteristics or pregnancy rates between the groups.

Adult↗

PubMed1999

Cell characteristics and function of two enriched fraction of human luteal cells prolonged culture.

Two subpopulations of steroidogenic cells exist in the corpus luteum of most species. The aims of the present study were to characterize these cells and to study their function during long-term culture. Human corpora lutea from early and late luteal phases were treated by mechanical and enzymatic digestion, followed by density sedimentation. Five distinct cell bands were obtained, two of which produced large amounts of progesterone. These were characterized according to density, size, steroidogenic enzymes, and numbers. More than 75% of cells expressed immunoreactive 3beta-hydroxydehydrogenase (3beta-HSD). Cells of higher density/smaller size were obtained in increasing numbers during the luteal phase and were more numerous compared with large cells. Under basal, human chorionic gonadotrophin (HCG)-, and prostaglandin E(2)-stimulated culture conditions, progesterone synthesis was greater in large cells of the early, but not late, luteal phase. Both cell fractions obtained from late, in contrast to early, luteal phase increased their basal progesterone production during the culture period of 9 days. We conclude that this technique for luteal cell isolation in the human yields two distinct subpopulations of steroidogenic cells, which respond differently to luteotrophic stimuli. We also conclude that cells of late luteal phase readily increase their progesterone synthesis over a period of 9 days, indicating a transition to longevity.

Cell Size↗

PubMed1999

Are women with polycystic ovary syndrome at an increased risk of pregnancy-induced hypertension and/or preeclampsia?

OBJECTIVE: To study whether there is an increased risk of glucose intolerance and hypertensive complications during pregnancy in women with polycystic ovary syndrome (PCOS) and if there is an adverse pregnancy outcome. METHODS: In a retrospective case-control study, pregnancies and neonatal outcome were compared in 33 women with PCOS and 66 women without PCOS. The women were treated at Huddinge University Hospital; antenatal care was given at associated outpatient units. MAIN OUTCOME MEASURES: Blood glucose and blood pressure during the different trimesters. Pregnancy outcome in terms of gestational length, birth weight, and need for neonatal intensive care. RESULTS: No significant differences were found in blood glucose levels between the groups. There were also no differences in blood pressure during the first and second trimester. However, during the third trimester and labor, the PCOS group had a significantly higher blood pressure than the control group. Apart from a tendency toward reduced growth of twins in PCOS mothers, the babies were healthy, overall, with few problems in the neonatal period. CONCLUSIONS: No major differences with regard to perinatal outcome in pregnant women with and without PCOS were found. An increased risk of hypertensive disorders in the third trimester and during labor was demonstrated in the PCOS group. This suggests that in the antenatal care of women with PCOS, attention should focus on blood pressure in order to reduce the risks of morbidity associated with hypertension.

Adult↗

PubMed1998

Application of single-needle blastomere biopsy in human preimplantation genetic diagnosis.

We have tested and subsequently successfully applied a single-needle approach to obtain blastomere biopsies from human preimplantation embryos for preimplantation genetic diagnosis (PGD). The method was first evaluated in a mouse system and shown to be compatible with a high degree of in vitro and in vivo development of biopsied mouse embryos. Furthermore, we showed that biopsied mouse embryos after transfer to recipient mice underwent implantation, normal development and delivery. Litters were followed through puberty and adulthood and shown to be normal with regard to sexual function and also a panel of biochemical and morphological parameters including organ histology. Successful human preimplantation diagnosis, followed by pregnancies and birth of healthy babies, was established with two out of three couples carrying a risk to transmit chromosomal abnormalities leading to severe disease. This is the first report of the successful use of a single-needle approach in human PGD. Considering its simplicity, we conclude that the single-needle approach is an attractive alternative for biopsies in PGD.

Adult↗

PubMed1998

Outcome of IVF in patients with endometriosis in comparison with tubal-factor infertility.

PURPOSE: The aim of this retrospective study was to compare the outcome of in vitro fertilization and embryo transfer in women with endometriosis and a control group with tubal-factor infertility. METHODS: Forty-eight patients with endometriosis underwent 65 cycles of in vitro fertilization and embryo transfer at Huddinge University Hospital. The matched control group with tubal-factor infertility consisted of 98 cycles in 98 patients. These groups were retrospectively analyzed regarding stimulation, fertilization, embryo development, implantation, and pregnancy outcome. RESULTS: The fertilization rate was significantly lower in women with endometriosis, but the cleavage, implantation, and pregnancy rates did not differ. CONCLUSIONS: Our results show that women with endometriosis have a lower fertilization rate compared with women with tubal-factor infertility. However, once the oocyte is fertilized, it seems that the preembryo has a normal chance of implantation, leading to similar pregnancy rates.

Adult↗

PubMed1998

In-vitro fertilization and intracytoplasmic sperm injection in the treatment of infertility after testicular cancer.

Treatment of testicular cancer (TC) may cause infertility due to reduced sperm quality with or without an ejaculation problem. In cases of anejaculation or retrograde ejaculation, spermatozoa can be obtained by transrectal electroejaculation (TE) or testicular sperm extraction (TESE) and used for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In this study, 15 out of 17 couples evaluated for infertility after TC, underwent a total of 21 treatment cycles, resulting in 18 embryo transfers. Spermatozoa were obtained by TE in 16 cycles, by masturbation in three cycles and by TESE in one. In one cycle no spermatozoa were found using TESE. Fertilization and cleavage was achieved by IVF in seven cycles and ICSI in 11 cycles; average fertilization rates of 57 and 55% respectively were observed. Twelve clinical pregnancies occurred, of which 11 have been delivered or are ongoing. The ongoing pregnancy rate was 57% per cycle. These results show that infertility after testicular cancer can be treated effectively with IVF and that ICSI even permits treatment of patients who have severe oligozoospermia.

Adult↗

PubMed1998

A comparison between open and percutaneous needle biopsies in men with azoospermia.

Open testicular biopsy is a classic method of investigation in men with azoospermia. Recently, percutaneous needle biopsy of the testis has been used in attempts to obtain material for histopathological diagnosis in such cases and to retrieve spermatozoa for intracytoplasmic sperm injection (ICSI). To determine whether a 19 gauge (G) and a 21G butterfly needle could be used for percutaneous aspiration of testicular tissue to determine the presence of mature spermatids and assess spermatogenesis, 10 patients (16 testes) and 12 patients (17 testes) underwent 19G or 21G needle biopsy respectively, immediately followed by open testicular biopsy, with both procedures under local anaesthesia. Biopsy with each needle size was compared with open biopsy. With the 19G needle, in the 14 cases where material was obtained there was full agreement with open biopsy regarding the presence or absence of mature spermatozoa, whereas with the 21G needle only nine of the 13 biopsies yielding material were predictive in this respect. Each needle size correlated poorly with open biopsy regarding evaluation of spermatogenesis. We conclude that percutaneous biopsy with a 19G butterfly needle is a quick and reliable method for demonstrating spermatozoa for ICSI. But for a detailed histopathological diagnosis, however, the needle biopsies gave poor results, whereas the material from the open testicular biopsies was assessable.

Adult↗

PubMed1998

Preimplantation genetic diagnosis of a large pericentric inversion of chromosome 5.

We report the first established pregnancy using preimplantation genetic diagnosis in order to avoid chromosomal imbalance in the progeny of a woman carrying a large inversion of chromosome 5. This is also the first time where it has been possible to study the distribution of balanced and unbalanced gametes in a female inversion carrier. In total, 23 embryos were biopsied in two separate treatments and analysed by fluorescent in-situ hybridization. Of these, 10 were unbalanced, nine were balanced and for four the analysis was inconclusive. The diagnostic procedure was performed within 3.5 h. This allowed the biopsied embryos to be transferred the same day as the biopsy was taken (day 3). Two embryos were transferred each time, and in the second treatment a twin pregnancy with two chromosomally balanced fetuses was established. Healthy twins were delivered at 34 weeks of gestation.

Adult↗

PubMed1998

Preimplantation genetic diagnosis of DiGeorge syndrome.

We report the first case of preimplantation genetic diagnosis used in order to avoid chromosomal imbalance in the progeny of a woman mildly affected by DiGeorge syndrome and carrier of a microdeletion of chromosome 22q11.2. In total, seven embryos were biopsied in three separate treatments and analysed by fluorescent in-situ hybridization (FISH). Of these, four were carrying the deletion, two were normal and in one the analysis was inconclusive. The diagnostic procedure was performed within 5 h. This allowed the biopsied embryos to be transferred the same day as the biopsy was taken (day 3). Two embryos were transferred in the third treatment, but no pregnancy was established. Patients with a 22q11 microdeletion, who have a 50% risk of transmitting the deletion to their offspring, can now be offered preimplantation genetic diagnosis using FISH for the detection of a 22q11 deletion.

Adult↗