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1.
Diabetes Metab ; 40(1): 49-55, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24200881

ABSTRACT

AIM: This study explored the association between reduced estimated glomerular filtration rate (eGFR) and microalbuminuria vs. subclinical organ damage in patients with type 2 diabetes. METHODS: Data from middle-aged patients with type 2 diabetes (n=706) treated in primary care were analyzed for microalbuminura, defined as a urinary albumin/creatinine ratio (uACR)≥3.0mmol/mol, and reduced eGFR, defined as<60mL/min/1.73m(2), in relation to blood pressure, pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and lumen diameter (LD). RESULTS: Patients with microalbuminuria had significantly higher 24-h ambulatory systolic blood pressure (ASBP) compared with subjects with uACR<3mg/mmol: 137 vs. 128mmHg (P<0.001). There were no differences in ASBP in patients with eGFR<60mL/min/1.73m(2). However, patients with vs. without microalbuminuria had increased PWV (11.4 vs. 10.1m/s; P<0.001), LVMI (134.4 vs. 118.6g/m(2); P<0.001), LD (7.01±0.93 vs. 6.46±0.74mm; P<0.001) and IMT (0.78 vs. 0.74mm; P=0.047), respectively. The associations between uACR vs. PWV and LVMI were more robust after adjusting for age, diabetes duration, ASBP, HbA1c, LDL-cholesterol, and antihypertensive and lipid-lowering therapy compared with uACR vs. IMT. There were no statistically significant differences in PWV, LVMI or IMT between patients with reduced (<60mL/min/1.73m(2)) vs. normal eGFR. CONCLUSION: Levels of urinary albumin excretion, but not reduced eGFR, were associated with increased arterial stiffness, left ventricular mass and atherosclerosis in patients with type 2 diabetes.


Subject(s)
Albuminuria/metabolism , Atherosclerosis/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Angiopathies/metabolism , Diabetic Nephropathies/metabolism , Glomerular Filtration Rate , Atherosclerosis/etiology , Atherosclerosis/physiopathology , Biomarkers/metabolism , Blood Flow Velocity , Blood Pressure , Carotid Intima-Media Thickness , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/etiology , Diabetic Angiopathies/physiopathology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/physiopathology , Female , Humans , Kidney/physiopathology , Male , Middle Aged , Risk Factors , Surveys and Questionnaires , Ventricular Dysfunction, Left/physiopathology
2.
Cochrane Database Syst Rev ; (1): CD005552, 2007 Jan 24.
Article in English | MEDLINE | ID: mdl-17253562

ABSTRACT

BACKGROUND: Insulin-sensitizing drugs (ISDs) have recently been advocated as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of ISDs versus OCPs in the long-term treatment of women with PCOS. OBJECTIVES: To assess the effectiveness and safety of ISDs versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2005), Cochrane Central Register of Controlled Trials (CENTRAL (Ovid), third quarter 2005), MEDLINE (1966 to September 2005), CINAHL (1982 to September 2005), and EMBASE (1988 to September 2005). References of the identified articles were handsearched, and pharmaceutical companies and experts in the field were also contacted for additional relevant studies. SELECTION CRITERIA: Randomised controlled trials which compared ISDs versus the OCP (alone or in combination). DATA COLLECTION AND ANALYSIS: Performed independently by two review authors. MAIN RESULTS: Six trials were included for analysis, four of which compared metformin versus OCP (104 participants) and two of which compared OCP combined with metformin versus OCP alone (70 participants). Limited data demonstrated no evidence of difference in effect between metformin and the OCP on hirsutism and acne. There was either insufficient or no data on the relative efficacy of metformin or the OCP (alone or in combination) for preventing the development of diabetes, cardiovascular disease, or endometrial cancer. Metformin was less effective than the OCP in improving menstrual pattern (Peto odds ratio (OR) 0.08, 95% CI 0.01 to 0.45). Metformin resulted in a higher incidence of gastrointestinal (Peto OR 7.75, 95% CI 1.32 to 45.71), and a lower incidence of non-gastrointestinal (Peto OR 0.11, 95% CI 0.03 to 0.39), severe adverse effects requiring stopping of medication. Metformin was less effective in reducing serum androgen levels (total testosterone: weighted mean difference (WMD) 0.54, 95% CI 0.22 to 0.86; free androgen index: WMD 3.69, 95% CI 2.56 to 4.83). Metformin was more effective than the OCP in reducing fasting insulin (WMD -3.46, 95% CI -5.39 to -1.52) and not increasing triglyceride (WMD -0.48, 95% -0.86 to -0.09) levels, but there was insufficient evidence regarding comparative effects on reducing fasting glucose or cholesterol levels. AUTHORS' CONCLUSIONS: Up to 12-months treatment with the OCP is associated with an improvement in menstrual pattern and serum androgen levels compared with metformin; but metformin treatment results in a reduction in fasting insulin and lower triglyceride levels than with the OCP. Side-effect profiles differ between the two drugs. There is either extremely limited or no data on important clinical outcomes such as the development of diabetes, cardiovascular disease, or endometrial cancer. There are no data comparing ISDs other than metformin (that is rosiglitazone, pioglitazone, and D-chiro-inositol) versus OCPs (alone or in combination).


Subject(s)
Contraceptives, Oral, Combined/therapeutic use , Hypoglycemic Agents/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Acne Vulgaris/drug therapy , Cardiovascular Diseases/prevention & control , Endometrial Neoplasms/prevention & control , Female , Hirsutism/drug therapy , Humans , Menstruation Disturbances/drug therapy , Metformin/therapeutic use , Polycystic Ovary Syndrome/complications , Randomized Controlled Trials as Topic
3.
J Assist Reprod Genet ; 23(4): 161-9, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16758346

ABSTRACT

OBJECTIVE: To determine whether ovarian perifollicular blood flow (PFBF) in the early follicular phase (EFP) was associated with treatment outcome. DESIGN: Retrospective longitudinal cohort study. SETTING: Tertiary referral centre/university hospital. PATIENTS: Thirty-four women underwent 37 IVF cycles, which resulted in 35 embryo transfers. INTERVENTIONS: Serial transvaginal scans using power Doppler ultrasound during the follicular phase. Ovarian PFBF of follicles > or =5 mm was subjectively assessed using a modified grading system (grades 0-4). MAIN OUTCOME MEASURES: Ovarian PFBF and pregnancy. RESULTS: Treatment cycles were retrospectively divided into two groups: Group 1 (n=20) had cycles with at least one small (5-10 mm) or medium (11-14 mm) size follicle(s) of high grade (2-4) PFBF on cycle day 5 or 6 or 7; and Group 2 (n=17), had cycles that did not. Group 1 had a significantly higher proportion of high grade large follicles in the late follicular phase (35% vs. 21%) (OR 2.0; 95% CI 1.1-3.7) and higher clinical pregnancy rate (47% vs. 12%) (OR 6.3; CI 1.1-35.7) compared to Group 2. CONCLUSION: High grade ovarian PFBF in the EFP during IVF is associated with both high grade PFBF in the late follicular phase and a higher clinical pregnancy rate.


Subject(s)
Fertilization in Vitro/statistics & numerical data , Follicular Phase/blood , Ovarian Follicle/blood supply , Ovarian Follicle/diagnostic imaging , Ultrasonography, Doppler/methods , Adult , Cohort Studies , Female , Humans , Observer Variation , Regional Blood Flow , Reproducibility of Results , Retrospective Studies , Vagina/diagnostic imaging
4.
J Assist Reprod Genet ; 21(11): 387-95, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15672951

ABSTRACT

PURPOSE: This longitudinal study aimed to compare ovarian perifollicular and endometrial blood flow (PFBF and EBF, respectively) during the follicular phase in pregnant and non-pregnant IVF cycles. METHODS: Serial transvaginal scans were performed in 15 subjects undergoing IVF treatment. Both PFBF and EBF were subjectively graded (grades 0-4 for PFBF and grades 1-3 for EBF). After confirmation of clinical pregnancy, the treatment cycles were grouped into 'Pregnant' and 'Non-pregnant' cycles. Ovarian PFBF and EBF were retrospectively compared between the two groups. RESULTS: In pregnant cycles, the proportion of large (> or = 15 mm) follicles with high (24) grade PFBF increased with time throughout the follicular phase, and the proportion of large follicles with poor (0-1) grade PFBF decreased. In non-pregnant cycles these trends were reversed. There was no difference in EBF between the two groups. CONCLUSION: The pattern of ovarian PFBF but not EBF may be predictive of treatment outcome.


Subject(s)
Endometrium/blood supply , Endometrium/diagnostic imaging , Fertilization in Vitro , Ovarian Follicle/blood supply , Ovarian Follicle/diagnostic imaging , Adult , Female , Humans , Longitudinal Studies , Pregnancy , Pregnancy Rate , Retrospective Studies , Treatment Outcome , Ultrasonography, Doppler
5.
Climacteric ; 7(3): 284-91, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15669553

ABSTRACT

OBJECTIVES: To determine any association between hormonal replacement therapy (HRT) usage and breast cancer recurrence and survival rates in women who were premenopausal at the time of diagnosis of breast cancer. METHODS: The study group comprised 524 women who were diagnosed with breast cancer when they were premenopausal. Of these, 277 women reached menopause before recurrence of the disease, being lost to follow-up, or reaching the end of the study. In this group, 119 women took HRT to control menopausal symptoms. The majority took combined continuous estrogen-progestin treatment. Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes, and to death from primary tumor were compared between HRT users and non-users. RESULTS: Women who used HRT after their menopause had an adjusted relative risk of recurrence or new breast cancer of 0.75 (95% confidence interval (CI), 0.29-1.95) compared to that of non-users. The relative risk of death from all causes was 0.36 (95% CI, 0.11-1.16) and that of death from primary tumor was 0.24 (95% CI, 0.05-1.14). CONCLUSION: HRT use in women who were premenopausal at the diagnosis of primary invasive breast cancer is not associated with worse outcomes in terms of breast cancer recurrence or mortality.


Subject(s)
Breast Neoplasms/epidemiology , Estrogen Replacement Therapy/adverse effects , Neoplasm Recurrence, Local/epidemiology , Adult , Breast Neoplasms/etiology , Breast Neoplasms/mortality , Disease-Free Survival , Estrogens/administration & dosage , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/mortality , New South Wales/epidemiology , Premenopause , Progestins/administration & dosage , Retrospective Studies , Risk Factors , Survival Analysis
6.
Prenat Diagn ; 21(9): 781-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11559915

ABSTRACT

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.


Subject(s)
Chromosome Aberrations/diagnosis , Preimplantation Diagnosis , Adult , Chromosome Disorders , Embryo Transfer , Female , Fertilization in Vitro , Heterozygote , Humans , In Situ Hybridization, Fluorescence , Male , Maternal Age , Oocytes/physiology , Pregnancy , Pregnancy Outcome , Pregnancy Rate , Pregnancy, High-Risk
7.
J Assist Reprod Genet ; 18(12): 644-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11808845

ABSTRACT

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.


Subject(s)
Endometriosis/physiopathology , Fertilization in Vitro , Oocytes/physiology , Pregnancy Outcome , Sperm Injections, Intracytoplasmic , Adult , Endometriosis/therapy , Female , Humans , Infertility, Female/therapy , Male , Oligospermia/therapy , Pregnancy
8.
Dev Med Child Neurol ; 42(10): 681-4, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11085296

ABSTRACT

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.


Subject(s)
Infertility, Male/therapy , Meningomyelocele , Tissue and Organ Harvesting/methods , Adult , Humans , Male , Semen Preservation , Sperm Injections, Intracytoplasmic , Sperm Motility
9.
Mol Hum Reprod ; 6(10): 915-20, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11006320

ABSTRACT

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.


Subject(s)
Insulin-Like Growth Factor I/metabolism , Leiomyoma/metabolism , Menstrual Cycle , Myometrium/metabolism , Adult , Aged , Antineoplastic Agents, Hormonal/pharmacology , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Gene Expression , Gonadotropin-Releasing Hormone/agonists , Goserelin/pharmacology , Humans , Insulin-Like Growth Factor I/genetics , Leiomyoma/genetics , Menopause , Middle Aged , Pregnancy , Progesterone/blood , RNA, Messenger/metabolism
10.
Gynecol Obstet Invest ; 50(1): 1-6, 2000.
Article in English | MEDLINE | ID: mdl-10895019

ABSTRACT

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.


Subject(s)
Endometriosis/metabolism , Endometrium/metabolism , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Adult , Cells, Cultured , Culture Media, Conditioned , Epithelial Cells/metabolism , Female , Humans , Immunoassay , Middle Aged , Stromal Cells/metabolism
11.
Prenat Diagn ; 20(13): 1038-47, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11180227

ABSTRACT

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.


Subject(s)
Cleavage Stage, Ovum , Embryonic Development , Heterozygote , Preimplantation Diagnosis , Translocation, Genetic , Biopsy , Chromosome Aberrations , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 9 , Embryo, Mammalian , Female , Fertilization in Vitro , Humans , In Situ Hybridization, Fluorescence , Mosaicism , Pregnancy
12.
Mol Hum Reprod ; 6(1): 55-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10611261

ABSTRACT

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.


Subject(s)
Estradiol/blood , Follicle Stimulating Hormone/blood , Leiomyoma/metabolism , Myometrium/metabolism , Progesterone/blood , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-jun/genetics , Adult , Aged , Aged, 80 and over , Female , Gene Expression , Humans , Leiomyoma/blood , Leiomyoma/pathology , Menstrual Cycle/physiology , Middle Aged , Myometrium/pathology , Pregnancy , Proto-Oncogene Proteins c-fos/physiology , Proto-Oncogene Proteins c-jun/physiology , RNA, Messenger , Steroids/blood
13.
Hypertens Pregnancy ; 18(1): 73-80, 1999.
Article in English | MEDLINE | ID: mdl-10464001

ABSTRACT

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.


Subject(s)
Hypertension/etiology , Polycystic Ovary Syndrome/complications , Pre-Eclampsia/etiology , Pregnancy Complications, Cardiovascular/etiology , Adult , Birth Weight , Case-Control Studies , Female , Glucose Tolerance Test , Humans , Polycystic Ovary Syndrome/physiopathology , Pregnancy , Pregnancy, Multiple , Retrospective Studies
14.
Mol Hum Reprod ; 5(8): 714-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10421797

ABSTRACT

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.


Subject(s)
Luteal Cells/cytology , Luteal Cells/metabolism , Cell Size , Cells, Cultured , Chorionic Gonadotropin/pharmacology , Culture Media, Conditioned , Female , Humans , Luteal Cells/drug effects , Luteal Phase/metabolism , Progesterone/biosynthesis , Proteins/metabolism
15.
Hum Genet ; 104(5): 376-82, 1999 May.
Article in English | MEDLINE | ID: mdl-10394928

ABSTRACT

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.


Subject(s)
Aneuploidy , Blastocyst , Chromosome Mapping , Fertilization in Vitro , Blastocyst/pathology , Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 16 , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 18 , Cryopreservation , Female , Humans , In Situ Hybridization, Fluorescence , Male , X Chromosome , Y Chromosome
16.
Hum Reprod ; 14(6): 1440-4, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10357955

ABSTRACT

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.


Subject(s)
Androgens/blood , Fertilization in Vitro , Follicular Fluid/chemistry , Glucocorticoids/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Prednisolone/therapeutic use , Adult , Androgens/analysis , Dehydroepiandrosterone/blood , Dehydroepiandrosterone Sulfate/blood , Estradiol/blood , Female , Humans , Infertility, Female/etiology , Infertility, Female/therapy , Placebos , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/complications , Prednisolone/administration & dosage , Pregnancy , Progesterone/blood , Prospective Studies
17.
Acta Obstet Gynecol Scand ; 78(3): 212-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10078583

ABSTRACT

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.


Subject(s)
Clomiphene/therapeutic use , Fertility Agents, Female/therapeutic use , Fertilization in Vitro/economics , Fertilization in Vitro/methods , Infertility, Female/etiology , Ovulation Induction/economics , Ovulation Induction/methods , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/drug therapy , Cost-Benefit Analysis , Direct Service Costs/statistics & numerical data , Drug Costs/statistics & numerical data , Drug Resistance , Female , Humans , Pregnancy , Pregnancy Outcome/economics , Prospective Studies , Treatment Outcome
18.
J Clin Endocrinol Metab ; 83(11): 4092-6, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9814497

ABSTRACT

The content of estrogen and progesterone receptors (ER, PR) is higher in fibroid tissue than in homologous myometrium, and both receptors seem to be regulated by the levels of circulating sex steroids. Myometrial and fibroid tissues were recovered from women undergoing gynecological operations during different phases of the menstrual cycle and during treatment with an analogue of GnRH (GnRHa). Contents of ER and PR in the tissue cytosol were determined by enzyme immunoassay. The ER levels were significantly higher in fibroid tissue than in homologous myometrium in all the endocrine conditions. During the secretory phase, when luteal progesterone production is prominent, the ER levels in the myometrium and fibroids were lower than during the proliferative phase. During GnRHa treatment, the ER levels in both tissues were similar to those in the proliferative phase but significantly higher than in the secretory phase. The PR levels were also significantly higher in fibroids than in myometrium in all the different endocrine conditions. In both tissues, the PR levels were lower in the secretory phase and during GnRHa treatment, compared with the proliferative phase. Our data suggest that, in these categories of women, both ER and PR are overexpressed in fibroid tissue. Apparently, high progesterone levels down-regulate the ER in both fibroids and myometrium, whereas estrogen mediates the up-regulation of the PR during the proliferative phase. Increased knowledge about the mechanisms by which sex steroids regulate their own receptors in uterine tissues might provide a basis for development of new treatment strategies for women with fibroid disease.


Subject(s)
Gonadotropin-Releasing Hormone/analogs & derivatives , Leiomyoma/drug therapy , Myometrium/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Uterine Neoplasms/drug therapy , Adult , Female , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Leiomyoma/metabolism , Middle Aged , Uterine Neoplasms/metabolism
19.
J Assist Reprod Genet ; 15(9): 530-4, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9822979

ABSTRACT

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.


Subject(s)
Endometriosis/physiopathology , Fertilization in Vitro , Infertility, Female/physiopathology , Pregnancy Outcome , Adult , Embryo Implantation/physiology , Embryo Transfer , Fallopian Tube Diseases/complications , Fallopian Tube Diseases/physiopathology , Female , Humans , Infertility, Female/etiology , Infertility, Female/therapy , Male , Pregnancy , Retrospective Studies , Semen/physiology
20.
Mol Hum Reprod ; 4(9): 871-5, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9783847

ABSTRACT

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.


Subject(s)
DiGeorge Syndrome/diagnosis , DiGeorge Syndrome/genetics , Preimplantation Diagnosis , Adult , Blastomeres/ultrastructure , Chromosome Deletion , Chromosomes, Human, Pair 22/genetics , Embryo Transfer , Female , Fertilization in Vitro , Heterozygote , Humans , In Situ Hybridization, Fluorescence , Pregnancy
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