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Biomedical subjects

L Hamberger

Publications and source records attributed to L Hamberger.

At least 19 recordsLinked to original sources

Risk factors for ectopic pregnancy in assisted reproduction.

OBJECTIVE: To identify risk factors for ectopic pregnancy (EP) after IVF-ET. DESIGN: Retrospective cohort study. SETTING: In vitro fertilization clinic at a university hospital. PATIENT(S): A total of 725 women who conceived after IVF were studied with regard to background factors, indications for IVF, and factors related to the IVF procedure through review of their medical charts. The rate of EP was 4%, corresponding with 29 EPs, of which 2 were heterotopic. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcome, defined as intrauterine pregnancy or EP. Background factors, indications for IVF, and factors related to the IVF procedure were analyzed for possible correlation with the outcome of EP. Risk factors for EP were identified by logistic regression analysis. RESULT(S): Tubal factor infertility, various previous abdominal surgeries, previous EP or pelvic infection, presence of a hydrosalpinx or fibroid, and type of transfer catheter used showed a positive correlation with EP as outcome. Logistic regression analysis identified two factors with predictive power: tubal factor infertility and previous myomectomy. CONCLUSION(S): Tubal factor infertility was the most prominent risk factor for EP after IVF. Previous myomectomy appeared to be another important risk factor, but this is a new finding that needs to be confirmed by further study.

Adult

Postnatal growth and health in children born after cryopreservation as embryos.

BACKGROUND: There is uncertainty about the health of children born from in-vitro fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal growth and health (up to 18 months) of these children compared with those born after standard IVF with fresh embryos and those from spontaneous pregnancies. METHODS: 255 children from cryopreserved embryos were matched by maternal age, parity, single or twin pregnancy, and date of delivery with 255 children born after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The main endpoint was growth; secondary endpoints were the prevalence of chronic illness, major malformations, cumulative incidence of common diseases, and development during the first 18 months. Growth was assessed by comparison with standard Swedish growth charts and by standard deviation scores. FINDINGS: Growth features were similar for both singletons and twins in the three groups. There were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in the cryopreserved group, standard IVF, and spontaneous groups, respectively (p=0.6 between the cryopreserved and standard IVF group). The prevalence of chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and 16.7% of children with a chronic illness in the cryopreserved group, standard IVF, and spontaneous groups, respectively. INTERPRETATION: The cryopreservation process does not adversely affect the growth and health of children during infancy and early childhood. Minor handicaps, behavioural disturbances, learning difficulties, and dysfunction of attention and perception cannot be ruled out at this age.

Body Height

Financing of IVF/ET in the Nordic countries.

BACKGROUND: The need for calculations of costs of health care has increased during the last few years. When priorities within the national health services in the five Nordic countries are discussed, treatment of infertility is often one of the issues. AIM AND METHODS: The aim of this study was to evaluate cost effectiveness and calculate the proportion of publicly financed in-vitro fertilization/embryo transfers in the Nordic countries. The mean direct and indirect costs of the treatments were calculated in both public and private clinics. The total cost of in-vitro fertilization was calculated and compared with the proportion financed through the national health services in the five countries. RESULTS: The cost analysis showed a direct and indirect cost of 3,300 Pounds per started treatment and 12,700 Pounds per term pregnancy for the whole Nordic material. The publicly financed costs were calculated at 27,342,300 Pounds, which is 66% of the total cost for in-vitro fertilization treatments. When these costs were compared with the total cost of health care in the countries, the proportion used for in-vitro fertilization treatments was between 0.08 and 0.16%. CONCLUSION: It will be difficult for the national health services in the five countries to make large savings by limiting the number of treatments financed within the system.

Costs and Cost Analysis

Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro.

Several retrospectively designed studies have shown an association between the presence of hydrosalpinx and impaired implantation and pregnancy rates among in-vitro fertilization (IVF) patients. In the present study we have evaluated the influence of hydrosalpinx fluid on normal human embryo development and implantation. Surplus, donated frozen embryos (n = 183) from IVF patients were used to study the effects on blastocyst development of hydrosalpinx fluid at concentrations of 50 and 100% compared with controls in S2 medium. The fluids were analysed for concentrations of electrolytes, osmolarity, protein content, endotoxin levels, bacterial or fungal contamination, pH and haemoglobin content. There was no difference in blastocyst development in cultures under mineral oil when control cultures (15/42 = 36%) were compared with cultures in 50% hydrosalpinx fluid (32/96 = 33%). The only biochemical parameter which correlated with capacity for blastocyst development was pH in hydrosalpinx fluid/medium (50/50%) after equilibration in 5% CO2 in air. When embryos were cultured in 100% hydrosalpinx fluid the blastocyst development was 14% (5/36) in comparison to control 33% (3/9). The original experiment was repeated in an open culture system without the protection of mineral oil but still in the presence of 50% hydrosalpinx fluid. The rate of blastocyst development was within the same range in the open system. In three separate experiments, the capability of expanded blastocyst to implant on multilayer artificial endometrium was tested. In these experiments, 1/3, 4/5 and 9/9 blastocysts implanted. The present study demonstrates that hydrosalpinx fluid does not generally exert any major negative effects on in-vitro development of human embryos or on the implantation process in vitro.

Adult

Comparison of fertilization, cleavage and pregnancy rates of oocytes from large and small follicles.

Ovarian stimulation for in-vitro fertilization (IVF) causes development of several cohorts of follicles. At the time of oocyte collection, oocytes are thus retrieved from a wide range of follicles of different sizes and developmental stages. A relationship between size of follicles and pregnancy rates has earlier been demonstrated. The aim of the present study was to compare fertilization, cleavage and pregnancy rates between oocytes retrieved from large and small follicles in conventional IVF and intracytoplasmic sperm injection (ICSI). A total of 200 conventional IVF patients and 175 ICSI patients underwent oocyte retrieval where oocytes from both large and small follicles were collected. A follicle with a volume of > or = 2 ml, corresponding to a follicular diameter > or = 16 mm as determined by ultrasound, was regarded as a large follicle. Only one cycle from each patient was included. Fertilization and cleavage rates were calculated per patient for oocytes from large and small follicles. The mean fertilization and cleavage rates for conventional IVF and ICSI cycles were calculated. Comparison of pregnancy rates was performed for patients receiving embryos derived from oocytes of only large or only small follicles. For conventional IVF patients, fertilization rates were 71.4 and 58.1% (P < 0.01, Wilcoxon paired test) for oocytes of large and small follicles respectively. The corresponding cleavage rates were 95.4 and 93.9% respectively. The pregnancy rate for the two groups was 47% (60/127) and 15% (2/13) (P < 0.05, chi2 test). For ICSI patients the fertilization rate was 72.0 and 71.1% for oocytes of large and small follicles respectively. The corresponding cleavage rate was 93.0 and 91.1%. The pregnancy rate in the two groups was 41% (46/113) and 42% (5/12). The results show that oocytes from smaller follicles also yield fertilization and pregnancies, although in conventional IVF to a lesser extent than oocytes from larger follicles. For IVF cycles, a higher proportion of immature oocytes (which are normally not included in the ICSI procedure) in the group of oocytes from small follicles is most probably the explanation for the lower fertilization rate. The decrease in pregnancy rate with oocytes from small follicles in the IVF cycles was not observed in the ICSI cycles. The possibility of evaluating the degree of oocyte maturation prior to fertilization may be an advantage of the ICSI technique. This suggests that the disadvantages of oocytes from small follicles might be overcome by means of ICSI.

Adult

Indications for intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is the latest of several microfertilization techniques that have been utilized predominantly to overcome severe male subfertility, giving fertilization and term pregnancy rates similar to conventional in-vitro fertilization (IVF) (but for other indications). Even though available data on children born after ICSI are very encouraging, the procedure must still be considered as novel and the safety aspect to a great extent unexplored. In our opinion, therefore, ICSI should only be used for specific indications, and in this communication the non-existent, relative and absolute indications for performing ICSI are outlined and discussed. With an apparently normal sperm sample, ICSI should not be used in a first cycle even if only few oocytes are obtained. When there is reason to suspect poor fertilization, ICSI can be used in combination with conventional IVF in a split cycle. This includes cases of 'subnormal' sperm samples, high titres of antisperm antibodies, or following a single cycle of poor fertilization using conventional IVF. Absolute indications for ICSI include two previous fertilization failures with conventional IVF, use of epidiymal or testicular sperm samples, or when only acrosomeless or immotile spermatozoa are available. The fertilization of oocytes prior to preimplantation genetic diagnosis is another absolute indication. It is, however, important to keep in mind that for this novel technique, indications should not be rigid, but remain variable with respect to new findings.

Ciliary Motility Disorders

Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic sperm injection?

During intracytoplasmic sperm injection (ICSI) the whole sperm, including head, midpiece and tail, is injected into the middle area of the oocyte. To find out what happens to the sperm mitochondria after ICSI, we checked the first six children born after ICSI treatment for occurrence of paternal mitochondrial DNA (mtDNA). The difference between maternal and paternal mtDNA in the investigated couples in our study was confined to single-base pair substitutions and we had to rely on restriction enzyme cleavage to differentiate between the mitochondrial genomes of the parents. With this kind of assay we were able to reach a sensitivity of about 0.2% for the paternal mtDNA. However, as uneven partition between tissues of heteroplasmic mtDNA is expected to occur, it would not be unlikely that an enrichment to 0.2% would occur in a given tissue if paternal mtDNA was transmitted by the ICSI procedure. We did not detect this level in the blood in any of the six children.

Adult

Ultrasound in gynecology: endometrium.

With the development and clinical application of transvaginal transducers/probes (TVS) the sonographic imaging of the endometrium was greatly enhanced compared with abdominal ultrasound. Also, the discomfort of a full bladder associated with abdominal ultrasound could be avoided. A shorter distance between probe and target allowed the use of higher frequency transducers, thereby achieving improved imaging. This review will only discuss the use of TVS, but it does not mean that abdominal ultrasound should not or cannot be used when dealing with the postmenopausal uterus. Transvaginal sonography (TVS) provides a valuable tool for the diagnosis of a wide range of gynecological disorders including those of the uterus and endometrium. The ability of TVS to depict the thickness and morphology of the endometrium has been established in both office and hospital settings. This article will discuss and illustrate the clinical and research applications of transvaginal sonography in relation to the endometrium in both symptomatic and asymptomatic postmenopausal women. The article is of particular relevance today given the number of women who are undergoing transvaginal ultrasonography in the absence of symptoms as a part of their routine check ups. There is a paucity of data relating to the management of apparent ultrasound abnormalities in such women. In symptomatic women or for women at risk of developing endometrial pathology, a technique that could reduce the number of biopsy procedures would be of value. Hysteroscopy, dilatation and curettage (D & C) as well as other endometrial sampling methods are all invasive, thus it would be of benefit if a way could be found to assess the endometrium using a relatively non-invasive approach. Such a technique would need to be relatively easy to learn and perform, as well as being well accepted by the patients. We believe that transvaginal sonography fulfills many of these requirements, the following review will attempt to put forward some of the evidence to support this view.

Endometrium

Global importance of infertility and its treatment: role of fertility technologies.

Understanding the reasons for infertility and the development of new techniques for its treatment is one of the fields within medicine which has undergone a dramatic development during the last two decades. In the past, gynecologists seemed more successful in the treatment of female problems than urologists and andrologists on the male side, while in the last couple of years this scenario has changed due to the development of both operative procedures to harvest spermatozoa from the epididymis and the testis and the ability to micro-inject single spermatozoa (ICSI) or even spermatides directly into metaphase II oocytes. It should, however, be emphasized that the successful development of in vitro fertilization (IVF) and other assisted reproduction technologies (ART), could not have taken place without the development of diagnostic innovations, such as immunoassays of hormones, high resolution ultrasound and various endoscopic techniques. Today, treatment of the infertile couple is less of a medico-technical problem and more a socio-economic dilemma. This communication is an attempt to summarize the more prominent steps in reproductive medicine during the last decades and one more general conclusion of global relevance which can be drawn, is that less money must be spent on diagnosis and more resources transferred to treatment options.

Cost-Benefit Analysis

Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques.

A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r-hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement.

Adolescent

The relationship between sperm morphology and rates of fertilization, pregnancy and spontaneous abortion in an in-vitro fertilization/intracytoplasmic sperm injection programme.

The morphological normality of a spermatozoon is considered to be an important factor in relation to its ability to fertilize an oocyte. We examined the influence of morphology (strict criteria) on the rates of fertilization, pregnancy and spontaneous abortion obtained following conventional in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in our clinical programme. We found our fertilization cut-off values for conventional IVF to be slightly different from those of the Kruger group (10 and 5%, compared to 14 and 5%). We also found the pregnancy rate per transfer to be as good or better in the groups with < 5% normal forms: 36% of these men had a fertilization rate > 50% using conventional IVF, showing that fertilization capacity is not necessarily impaired even in this 'poor prognosis' group. With the exception of the ICSI group with 5-9% normal forms, the rate of spontaneous abortion in this study was similar to or lower than in our IVF/ICSI programme overall. When the 5-9% normal spermatozoa group was divided into those with teratozoospermia as the only factor and those with additional sperm factors, the increased abortion rate was found in the group with multiple sperm factors (67% spontaneous abortions).

Abortion, Spontaneous

Obstetric and perinatal outcome of children conceived from cryopreserved embryos.

The main purpose of this study was to evaluate the obstetric and neonatal outcome of children conceived from cryopreserved embryos. The medical records of 270 infants (163 singletons, 98 twins and nine triplets) were reviewed and compared with two control populations of children born after in-vitro fertilization (IVF) with fresh embryos and children born after spontaneous pregnancies. The controls were matched according to maternal age, parity, plurality and date of delivery. In the cryopreserved group the gestational age at delivery for singletons was 279 +/- 13 days with birthweight 3476 +/- 616 g; for twins gestational age was 257 +/- 19 days with birthweight 2574 +/- 560 g; for triplets gestational age was 228 +/- 3 days with birthweight 1752 +/- 183 g. The incidence of preterm birth (< 37 weeks gestation) was 5.6% for singletons, 44.9% for twins and 100% for triplets. Seven children had major malformations (2.7%) and perinatal mortality occurred in two children (8/1000). Gestational age at delivery, birthweight, the incidence of malformations and the perinatal mortality were comparable with the two control groups both for singletons and twins. Significantly more singletons in the cryopreserved group were delivered by Caesarean section compared with the spontaneous group. The number of infants with low Apgar score (< 7 at 5 min) and the number of infants admitted to neonatal intensive care units were similar in the cryopreserved and spontaneous groups. In conclusion, the cryopreservation process did not seem to adversely influence fetal development and no increased perinatal risk was found.

Adult

Clinical aspects on the use of preimplantation genetic diagnosis in couples at risk.

BACKGROUND: Preimplantation genetic diagnosis (PGD) is a new technique which may become an attractive alternative to traditional prenatal diagnosis for couples at risk of getting children with severe genetic diseases. We here report our experience after the first trials in Sweden. METHODS: On day three after fertilization by intracytoplasmic sperm injection (ICSI) one or two blastomeres were biopsied and diagnosed by fluorescence in situ hybridization (FISH). Gender determination was done in two cases where the female in the couples were carrier of a severe X-chromosome bound disease (Wiskott-Aldrich disease or ornithine transcarbamylase deficiency). RESULTS: The first couple got an embryo transfer in each of their two treatment cycles. Two female embryos were transferred in the first cycle and one in the second cycle. The second couple did not get any embryo transfer in their two cycles. No clinical pregnancy occurred. CONCLUSION: With the rapidly improving knowledge about inherited disease and refinement of the IVF techniques, PGD will play an important clinical role in high risk groups within a decade for both mono- and polygenic disorders. Both technical as well as legal and ethical problems have however to be solved before these new techniques can be applied on large scale.

Embryonic Development

A new method to study the process of implantation of a human blastocyst in vitro.

OBJECTIVES: To develop a "miniorgan" culture of human endometrium dated according to the LH peak in order to study the process of implantation of a human blastocyst in vitro. DESIGN: Preliminary results of a more extensive study with the same objectives. SETTING: Hospital-based unit of reproductive health and university-related reproductive research laboratories. PATIENTS: Six apparently healthy women with normal regular menstrual cycles providing endometrial material 4, 5 and 6 days after the LH peak. INTERVENTION: One part of the biopsy was used for histologic dating. The other part was incubated in culture medium RPMI-1640 and exposed to the contact with one to three embryos fertilized in vitro. MAIN OUTCOME MEASURE: Biopsy material before and after incubation was studied by morphometric methods in a light microscope. The histologic changes were recorded by photomicrographs. RESULTS: Implantation of an embryo obtained 4 days after IVF penetrated the lining endometrial epithelium of a biopsy obtained 4 days after the LH peak and kept in vitro for 24 hours. The embryo was placed on the lining epithelium of the endometrium within 3 hours after the biopsy was taken. CONCLUSION: A new method to study the process of implantation of a human embryo in vitro has been described, allowing the embryo to penetrate the lining endometrial epithelium in a biopsy obtained at LH +4/+5.

Blastocyst

Ultrasound studies of vascular and morphological changes in the human uterus after a positive self-test for the urinary luteinizing hormone surge.

The aim of the study reported here was to establish complementary data for changes in uterine size, echogenicity and vascularity during the menstrual cycle relative to a positive self-test for urinary luteinizing hormone (LH) and day 1 of next menses. Thirteen volunteers (aged 23-32 years) with apparently regular menstrual cycles were recruited from the nursing staff. The plan was to examine all women by transvaginal ultrasonography with colour Doppler imaging on day 11 of the menstrual cycle. A urinary LH self-test was to be used daily until a positive result was obtained and the women were to be re-scanned daily until the dominant follicle had ruptured. All women were then to be scanned at least every 48 h (within +/- 2 h of the same time of day) until day 6 of the next menstrual cycle. Matched samples of peripheral blood were taken at the time of each scan for hormone analysis. The main outcome measures were the times of follicular rupture, a positive test result for urinary LH and the start of menses, uterine volume, cavity length, endometrial thickness and grade, pulsatility index (PI), and time-averaged and peak systolic maximum velocities in uterine and radial arteries and in subendometrial vessels. Nine women fulfilled the criteria for an ovulatory cycle, and seven provided data over the complete study. The principal changes relative to a positive urinary LH test were (i) a continued rise in endometrial thickness to days 3 and 4 (this index then remained relatively constant, but the layered appearance was lost) and (ii) a gradual decrease in the uterine arterial PI. There was a significant rise in uterine volume, cavity length and uterine arterial PI around the time of the next menses, and a fall in endometrial thickness and blood velocity in the uterine and radial arteries and subendometrial vessels. The data may have implications for the assessment of reproductive status and the design of future studies on disorders of implantation or menstruation.

Adult