Search PubMed⌕ Search

Biomedical subjects

B A Lieberman

Publications and source records attributed to B A Lieberman.

At least 37 records · Page 2Linked to original sources

A prospective, longitudinal study of emotions and relationships in in-vitro fertilization treatment.

Emotional and relationship assessments were completed by 144 couples at intake for in-vitro fertilization (IVF) and 6 months after either the identification of pregnancy or the discontinuation of treatment following three unsuccessful cycles. Women also completed emotional assessments at the time of pre-oocyte recovery and post-embryo replacement within each treatment cycle. At intake, women were more anxious than their partners and comparative norms, and were less positive than men about their marital and sexual relationships. Initial emotional assessments were not related to subsequent pregnancy, but at follow-up those who were pregnant were less depressed and more positive about their relationships. Within treatment cycles scores for women were higher after embryo replacement and the failure of pregnancy. First and last treatment cycles were associated with greater anxiety. High levels of confusion and bewilderment found during the initial cycle may indicate the need for better pretreatment information. Services must recognize the presence of high anxiety at intake and provide psychological care for those identified as particularly distressed. Emotional difficulties after failure of IVF treatment can be considered to be iatrogenic effects, and psychological services should be provided to minimize any negative psychological consequences of treatment.

Adult↗

A prospective evaluation of cryopreservation strategies in a two-embryo transfer programme.

A total of 364 consecutive patients requesting in-vitro fertilization (IVF) treatment were divided randomly into two groups. In the first group, two embryos in the original IVF cycle were allowed to divide prior to transfer, with any remaining embryos being cryopreserved at the pronucleate (PN) stage. In the second group, all the embryos were allowed to divide to the early cleavage (EC) stage, and the best two replaced; any suitable remaining embryos were frozen at the 2- to 4-cell stage. A total of 134 cycles (36.8%) fulfilled the study criteria for a fresh embryo replacement and supernumerary embryos cryopreserved. In the PN group, 72 out of 182 (39.6%) patients had a fresh embryo replacement accompanied by embryo cryopreservation, which was not significantly different from the EC group (62/182; 34.1%). The livebirth rate per fresh embryo transfer in the EC group (17/62; 27.4%) was significantly higher than that for the PN group (8/72; 11.1%; P < 0.05). Embryo survival following thawing was similar for the PN (96/129; 74.4%) and EC (79/102; 77.4%) stages. Although not significant, the livebirth rate following the transfer of thawed embryos was higher in the PN group (11/44; 25.0%) than in the EC group (4/38; 10.5%). Following one fresh and two freeze-thaw embryo replacements, the observed cumulative viable pregnancy rates were comparable for patients in both the PN (40.2%) and EC (41.1%) groups.

Adult↗

Children conceived by in vitro fertilisation after fresh embryo transfer.

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.

Cerebral Palsy↗

The estrogen receptor activity cycle: dependence on multiple protein-protein interactions.

The estrogen steroid hormone receptor (ER) is a member of a family of related hormone-inducible transcriptional regulators. The function of these receptors is dependent on multiple protein-protein interactions with other cellular polypeptides. These contacts regulate the four steps in the receptor "life cycle": synthesis and nuclear transport, priming/storage, activation, and recycling. Each of these steps is mediated by the formation of distinct protein complexes and results in a temporal and spatial regulation of ER activity. This review focuses on the cellular proteins that interact with the ER, and the role that these interactions are believed to play in the regulation of ER.

Animals↗

Cellular mechanisms which distinguish between hormone- and antihormone-activated estrogen receptor.

The use of reverse genetics has permitted a definition of the structural features within estrogen receptor required for its productive association with the transcription apparatus. These sequences, transactivation function 1 (TAF1) in the amino terminus and TAF2 at the carboxyl terminus, display distinct transcriptional functions. Using specific receptor mutations it has been shown that on some promoters both TAF1 and TAF2 are required for maximal transcriptional activity, whereas on others, additional factors bound to the target promoter can functionally substitute for TAF1 or TAF2. Estrogen functions as an ER agonist by promoting functional synergism between TAF1 and TAF2. Conversely, 4-OH-tamoxifen inhibits TAF2 activity and functions as an antagonist in cell contexts where TAF2 is required. Alternatively, if a 'TAF2 function' is supplied by another factor, 4-OH tamoxifen can manifest ER agonist activity. These data indicate that alterations in the cellular expression of proteins which mimic TAF1 or TAF2 activity can have a profound effect on the pharmacology of ER modulators. Thus the identification of the cellular proteins which interact with ER and its TAF regions will allow a definition of the mechanism used by the cell to distinguish between hormone- and antihormone-activated estrogen receptor.

Animals↗

Use of buserelin and low-dose human menopausal gonadotropin for in vitro fertilization in women at risk of ovarian hyperstimulation syndrome.

PURPOSE: The purpose of the present study was (i) to assess the value of using a low dose of hMG (75 IU/day) to achieve ovarian stimulation in women who have previously shown an exaggerated response to a standard dose of 150 IU human menopausal gonadotropin/day in a desensitization (group I) or flare-up (group II) protocol and (ii) to determine whether the choice of GnRH-a regimen in a subsequent cycle, namely, a desensitization or flare-up protocol, influenced the effectiveness of the low dose of hMG. RESULTS: In group I, 75% (12/16) and 57% (8/14) of the subsequent desensitization and flare-up protocols, respectively, were cancelled because of inadequate ovarian response. Similarly, the cancellation rates in group II were 10 of 10 and 7 of 11 (64%), respectively. The total cancellation rate (groups I and II together) with the desensitization protocol was higher than that using the flare-up protocol (P < 0.05). CONCLUSION: The simple use of a reduced dose of hMG (75 IU/day) for subsequent in vitro fertilization in women to minimize the risk of the development of ovarian hyperstimulation is of limited benefit since a large proportion then shows an inadequate response. This is particularly pronounced with a subsequent desensitization protocol which does not utilize endogenous gonadotropins to initiate follicular development.

Adult↗

The quarantine of fertilized donated oocytes.

The fertilization and subsequent cryopreservation of donated oocytes have enabled the resulting embryos to be quarantined for a minimum of 6 months, and to be thawed and replaced only after the donor has had a second negative human immunodeficiency virus (HIV) test. In the study described here, a total of 39 women had 56 embryo transfers, and 12 pregnancies (21% per transfer) were achieved. The logic of the protocol for minimizing the risk of infection of the recipient, which is in line with that of semen donation, is presented, together with an argument for the feasibility of such an approach.

Adult↗

A double-blind cross-over controlled study to evaluate the effect of human biosynthetic growth hormone on ovarian stimulation in previous poor responders to in-vitro fertilization.

The effect of exogenous human biosynthetic growth hormone (HGH; 12 IU/day; Norditropin, Novo-Nordisk) on the response to ovarian stimulation using a buserelin/human menopausal gonadotrophin (HMG) regimen was assessed in women who had previously shown a 'poor response' in spite of increasing doses of HMG. Forty patients were recruited into a prospective double-blind placebo-controlled study. The serum follicle stimulating hormone (FSH) on day 2-5 of a menstrual cycle (< 10 IU/l) was used to exclude any peri-menopausal candidates. The urinary 24 h GH secretion was normal in all patients. Thirty-three patients completed the study with 21 patients having human chorionic gonadotrophin (HCG) in both arms, thus providing a complete set of placebo control data. Of these 21 patients, the administration of HGH compared to the placebo cycle resulted in increased serum concentrations of fasting insulin on the 8th (median 3.9 versus 5.8 mU/l; P < 0.0005) and 13th (median 4.4 versus 5.8 mU/l; P < 0.05) day of HMG in those cycles receiving HGH. After 8 days of co-treatment with HGH the number of cohort follicles (14-16.9 mm) was significantly increased, but this change was not sustained on the day of HCG administration. No statistical difference in the serum oestradiol on the 8th day of HMG or day of HCG, length of the follicular phase, total dose of HMG used, or the number of oocytes collected was seen between the placebo or HGH cycles. This study demonstrates that HGH does not improve the ovarian response to ovulation induction in previous poor responders.

Adult↗

The screening for cytomegalovirus antibody in semen donors and recipients within a donor insemination programme.

A total of 67 semen donors (62 Caucasian and five non-Caucasian) were tested for the presence of immunoglobulin G antibodies to cytomegalovirus (CMV). Ten (16%) of the Caucasian donors tested positive for CMV, while four (80%) of the non-Caucasian donors were positive. A total of 131 women receiving donor insemination (114 Caucasian and 17 non-Caucasian) were tested. Of these, 43 (38%) of the Caucasian recipients tested positive for CMV, while 16 (94%) of the non-Caucasian recipients were positive. There was a significant association between the incidence of positive tests and the age of the Caucasian recipients.

Adult↗

The acrosome reaction to ionophore challenge test: assay reproducibility, effect of sexual abstinence and results for fertile men.

Since the human acrosome reaction is considered a prerequisite for normal fertilization and the spontaneous acrosome reaction rate is low, laboratory tests using calcium ionophores to induce the acrosome reaction have been devised and applied to the investigation of patients. The introduction of any new laboratory test into routine clinical practice is usually accompanied by the determination of intra- and inter-subject variability within the normal population, and the derivation of reference values to distinguish between affected and unaffected populations. The acrosome reaction to ionophore challenge (ARIC) test was evaluated and found to have (i) intra- and inter-assay coefficients of variation of 10.8 and 18.8% respectively, (ii) a high degree of intra-subject variability for three subjects studied over a 10 week period, (iii) a high degree of inter-subject variability when aliquots of 20 ejaculates of donor semen of proven fertility were tested, and (iv) no effect of length of sexual abstinence on ARIC values. The results of this study suggest that the use of fresh semen samples from subjects of proven fertility for quality control purposes in the ARIC test may be inadequate due to the high degree of intra-subject variability, and that this problem may be overcome by utilizing a frozen quality control sample. The results also suggest that an isolated negative ARIC test is not necessarily indicative of functionally incompetent spermatozoa, and highlight the importance of examination of the normal population prior to the clinical application of such a test.

Acrosome↗

High ovarian response in Yoruba African women during ovulation induction for assisted conception.

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Embryo Implantation↗

Insulin-like growth factor binding proteins in serum and follicular fluid from women undergoing ovarian stimulation with and without growth hormone.

The effects of supplementary growth hormone (GH) upon insulin-like growth factor binding proteins (IGFBP) in serum and ovarian follicular fluid were investigated in women undergoing buserelin-human menopausal gonadotrophin (HMG) ovulation induction for in-vitro fertilization. IGFBPs were detected by Western ligand blotting (WLB) or radioimmunoassay (IGFBP-3) and were shown in the present study to increase and decrease in patients with diseases of GH excess or deficiency. In the women undergoing treatment for ovulation induction, radioimmunoassay of IGFBP-3 gave results which were consistent with the well-documented GH dependency of this protein, increasing in the serum when GH was administered at the same time as buserelin-HMG. In contrast there were no consistent patterns in the abundance of the IGFBPs in serum and follicular fluid examined by WLB whether or not the patient was receiving GH, and the IGFBPs varied independently of the result obtained by radioimmunoassay. Other studies have shown that during pregnancy a serum protease can dramatically decrease the detection of the IGFBPs on the WLB. However, there was no evidence for a protease in the serum or follicular fluid from these nonpregnant women undergoing ovulation induction. Tissue availability of IGFs is probably regulated by the BPs, so that data would suggest that in normal women, neither ovarian activity nor GH at pharmacological concentrations is the primary regulator of the IGFBPs, which are likely to be regulated by some other factor(s), e.g. nutrition. These data may account for the lack of consistent clinical improvement in studies investigating the hypothesis that supplementary GH during ovulation induction with gonadotrophins would be beneficial.

Blotting, Western↗

The UK Human Fertilisation and Embryology Act 1990--how well is it functioning?

The Human Fertilisation and Embryology Act became law in the UK in 1990, and a statutory body, the Human Fertilisation and Embryology Authority, was established to administer the Act. The opinions of those persons responsible for licensed activity under the Act were canvassed anonymously to assess the initial effect of the Act on their activities, and the administration of the Act by the 'Authority'. The views expressed reflect the opinions of 80% of the 'responsible persons' and are thus likely to be of value to those responsible for administration of the Act and also those planning legislation in this field of human endeavour.

Embryo Research↗

The routine assessment of sperm motility at room temperature and 37 degrees C.

The World Health Organization (WHO) laboratory manual (1992) states that assessment of sperm motility can be performed at either 37 degrees C or room temperature (20-24 degrees C). The motility of spermatozoa in 44 semen samples (22 fresh samples and 22 frozen-thawed samples) was assessed at both of these temperatures and a significant difference in the motility profiles was noted, specifically an increase at 37 degrees C in the percentage (expressed here as median and ranges) of spermatozoa with excellent progressive motility and an overall increase in the percentage with total progressive motility. With fresh samples the excellent progressive motility increased from 41 (19-53) to 54 (30-66) and the overall motility from 58.5 (39-74) to 65.0 (40-79). With the frozen-thawed samples the excellent motility increased from 14 (1-33) to 25 (6-45) and the overall motility from 30.5 (14-51) to 33.0 (16-52). As the WHO laboratory manual was published 'In response to a growing need for the standardisation of procedures for the examination of human spermatozoa' it is proposed that only one temperature for routine analysis should be used, namely 37 degrees C, which may have more physiological relevance and eliminate effects of fluctuations in ambient laboratory temperature.

Humans↗

Supplementary growth hormone treatment of women with poor ovarian response to exogenous gonadotrophins: changes in serum and follicular fluid insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3).

The effects of supplementary growth hormone (GH) treatment upon insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3) concentrations in serum and ovarian follicular fluid were investigated in women undergoing buserelin human menopausal gonadotrophin (HMG) ovulation induction for in-vitro fertilization. Women (n = 40), aged 24-39 (mean 35 years), who showed poor ovarian responses to HMG, were recruited and randomly divided into two groups. Each patient received two cycles of ovulation induction, one with GH (12 IU/day x 12 days/HMG/buserelin) and another with placebo/HMG. Serum IGF-1 increased substantially during the GH treatment and remained significantly higher than the control 2 days after the last GH injection. Serum IGFBP-3 fell steadily during the placebo/HMG treatment and to a nadir on the day of oocyte retrieval (P < 0.05 compared to serum before any treatment). In contrast, IGFBP-3 was increased (P < 0.01) during the GH administration and returned to the control level 2 days after GH injection. Serum oestradiol concentrations on the eighth day of HMG and the day of human chorionic gonadotrophin (HCG) were not significantly different between the two groups. Serum IGF-1 was highly correlated with IGFBP-3 before any treatment (r = 0.433, P < 0.001). This correlation disappeared after buserelin, placebo/HMG treatment in the control group, but it was maintained during GH/HMG treatment (r = 0.343, P = 0.04). Follicular fluid concentrations of GH and IGF-1, not IGFBP-3 or oestradiol, were significantly elevated in the GH-treated women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗