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Biomedical subjects

B A Lieberman

Publications and source records attributed to B A Lieberman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Use of human zonae from cryopreserved oocytes in a test to assess the binding capacity of human spermatozoa.

Aged unfertilized oocytes from an assisted conception programme were cryopreserved and then utilized after thawing in a zona-binding assay. Oocytes frozen using dimethyl sulphoxide (DMSO) showed poor survival post-thaw (2/40, 5%) compared to those frozen with propanediol (PROH) (63/134, 47%). When the zonae were exposed to spermatozoa from fertile donors, those frozen with DMSO showed a significantly higher number of bound spermatozoa than did those frozen with PROH (P < 0.002). In both groups, oocytes which failed to survive the freeze-thaw processes had greater numbers of bound spermatozoa than did those which survived (P < 0.05). Oocytes from cases of failed fertilization showed no difference in their rate of sperm binding compared with oocytes from cases in which some fertilization had occurred. Zonae frozen in PROH but which were from oocytes which were not viable after thawing were used to assess the binding of spermatozoa from men who had failed previously to fertilize their partner's oocytes in vitro and spermatozoa from men with poor quality semen and who had elected for treatment by micro-injection sperm transfer. The number of spermatozoa bound to zonae was reduced significantly in both groups compared to a fertile donor.

Cell Adhesion↗
PubMed1993

The detection of antisperm antibodies in serum: a comparison of the tray agglutination test, indirect immunobead test and indirect SpermCheck assay.

Testing for antisperm antibodies (ASAs) is an important part of the work-up of the sub-fertile couple, yet there is little consensus regarding the most appropriate methods. The SpermCheck assay (GSC; Bio-Rad Laboratories Inc., Diagnostics Division, Hercules, CA, U.S.A.) is supplied with wash buffer, controls and bead reagent which detects all three major classes of ASAs (IgA, IgG and IgM) in a single test. This study compared results on a bank of samples using the tray agglutination test (TAT), immunobead test (IBT), GSC and a modified SpermCheck assay to detect a single isotype in each test (SISC). The IBT and SISC showed excellent correlation, with 127/141 (90.1%) tests agreeing. There was an apparent lack of sensitivity to IgM with GSC as 8/15 (53.3%) samples testing positive with IBT and 7/15 (46.7%) testing positive with SISC were negative with GSC. Of the 24 IBT-negatives, seven (29.2%) were positive for TAT, indicating a high incidence of non-immunological agglutination, though this decreased as the TAT titre increased. The proportion of samples testing positive for IBT increased with TAT titre: 3/20 (15.0%) for TAT-negative samples, 6/10 (60.0%) for low titres and 21/24 (87.5%) for high titres. This was also observed when comparing the GSC with TAT. The TAT therefore appears useful as a first-line screen, whilst the inability of the GSC to adequately detect IgM limits its use as an indirect test. Both the IBT and SISC can be used to further investigate the type and class of ASA present.

Agglutination Tests↗
PubMed1993

Assisted conception using buserelin and human menopausal gonadotrophins in women with polycystic ovary syndrome.

OBJECTIVE: To compare the outcome of in vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) cycles in women with or without ultrasound features of polycystic ovary syndrome (PCOS). DESIGN: A consecutive series from January to December 1989. SUBJECTS: Twenty-five women with PCOS scheduled for assisted conception. The controls were 139 women with normal ovaries. SETTING: A single centre specialist fertility unit, Manchester, UK. INTERVENTIONS: Pituitary desensitisation was with buserelin. In the PCOS group ovarian stimulation was with 1 ampoule (75 iu FSH) of hMG/day in 12 women (Group I) and two ampoules/day in 13 (Group II). The controls (Group III) were given two ampoules of hMG daily. Human chorionic gonadotrophin (hCG; 10,000 iu) was given when three follicles measured > or = 20 mm diameter. MAIN OUTCOME MEASURES: Serum oestradiol (E2) concentrations, number of follicles, clinical pregnancies, features of the ovarian hyperstimulation syndrome (OHS). RESULTS: Women with PCOS (Groups I or II) had more follicles > or = 14 mm diameter on the day of the hCG injection (P < 0.005), higher serum E2 concentrations on the day after the hCG (P < 0.05) and more oocytes retrieved (P < 0.05) than the controls. The OHS was more prevalent in those with PCOS (32% versus 6.5%; P < 0.05). The clinical pregnancy rate per embryo transfer (27% versus 22%) or gamete transfer (25% versus 39%) and the rate of spontaneous miscarriage (33% versus 12%) were not statistically different. CONCLUSIONS: The pregnancy rate and outcome of pregnancy following IVF or GIFT in women with or without PCOS are similar. Women with PCOS are at a higher risk of developing OHS.

Adult↗
PubMed1993

Does elective cryopreservation of all embryos from women at risk of ovarian hyperstimulation syndrome reduce the incidence of the condition?

OBJECTIVES: To analyse the incidence and factors associated with the ovarian hyperstimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk. DESIGN: Two hundred forty-one consecutive IVF/GIFT cycles from January to December 1989. SETTING: Specialist fertility unit, Manchester, UK. INTERVENTIONS: Pituitary suppression was effected by a daily subcutaneous injection of buserelin (500 micrograms) beginning 7 days before the expected menses. The ovarian stimulation was with variable amounts of human menopausal gonadotrophin. Ovulation was induced with 10,000 i.u. human chorionic gonadotrophin (hCG). From January to May (period A), gametes/embryos were replaced and 2000 i.u. hCG given, irrespective of the serum oestradiol (E2) concentration. From June to December (period B), all the embryos from women with an E2 > 3500 pg/ml on the day of ovulatory trigger were electively cryopreserved. MAIN OUTCOME MEASURES: Serum E2, features of moderate or severe OHS, clinical pregnancies. RESULTS: The OHS occurred in 10/105 (9.5%) and 12/136 (8.8%) cycles in periods A and B, respectively. Fewer women (6% versus 60%, P < 0.05) who had their embryos cryopreserved developed severe OHS compared with women with an E2 > 3500 pg/ml who became pregnant after gamete/embryo transfer in period A. The main factors associated with the development of OHS were serum E2 concentrations > 3500 pg/ml, whether gamete/embryos were replaced and the additional hCG given, the occurrence of a pregnancy and the presence of polycystic ovary disease. CONCLUSION: The elective cryopreservation of all embryos from women with high E2 levels reduced the severity, but not the incidence of symptomatic OHS.

Adult↗
PubMed1993

The constitution of a progesterone response element.

Progesterone receptors (PRs) recognize and bind to DNA in a sequence-specific manner. To define the sequence-specific determinants of PR binding to DNA, we employed a detailed series of target elements and analyzed both PR binding in vitro and PR-mediated activation of a reporter gene in vivo. These elements represent point substitution or insertion mutants of a progesterone response element derived from the mouse mammary tumor virus (MMTV). Substitution of a G for the first T in the 15-base pair (bp) MMTV progesterone response element core sequence, GTTACAAACTGTTCT, increases PR-DNA binding in vitro. All other tested mutations within this sequence either had no effect or decreased PR binding. From these analyses, we infer an optimal PR recognition sequence, -7RGNACANRNTGTNCY+7, composed of hexameric half-sites separated by precisely 3 bp and exhibiting dyad symmetry. Limited substitution of a suboptimal base for an optimal base, as in the wild type MMTV element, can be tolerated, but further suboptimal substitutions significantly decrease binding by PR. The identity of 1 bp within the hexameric half-site, position +/- 5, is unconstrained. Transition mutations, but not transversions, are permitted at position +/- 7. Here the hydrogen bond acceptor of the N-7 position of the purine ring may be involved in receptor recognition, since this feature is shared by the permitted substitutions. Insertion of a single base pair between the half-sites abolishes detectable binding, suggesting that the spatial orientation of the DNA binding domains of the monomeric receptor subunits are fixed by dimerization of the receptor. This pattern of sequence-specific recognition parallels that previously inferred for the glucocorticoid receptor, indicating that the two receptors may be unable to distinguish individual target sites. Each of the mutant response elements was also assessed for its ability to confer progestin responsiveness to a truncated MMTV promoter when introduced into a PR-containing cell line. Elements exhibiting strong receptor binding in vitro were fully inducible, whereas poorly inducible or uninducible elements displayed little or no recognition by receptor in vitro. However, some elements, though poorly bound in vitro, still activated transcription in vivo in response to hormone. In certain cases activation was as good as that seen with the wild type element. Further examination of in vitro receptor binding by this class of mutant elements using higher levels of baculovirus-expressed receptor revealed that many were indeed recognized by receptor, albeit with a lower affinity than the wild type sequence.(ABSTRACT TRUNCATED AT 400 WORDS)

Baculoviridae↗
PubMed1992

Endometrium in in-vitro fertilization cycles: morphological and functional differentiation in the implantation phase.

Secretory differentiation of endometrium after multiple follicular stimulation using gonadotrophin releasing hormone and human menopausal gonadotrophin has been studied both histologically and immunohistochemically in 30 women undergoing in-vitro fertilization treatment. None had embryo transfer. Patients were randomly allocated to receive luteal phase support with a single dose of human chorionic gonadotrophin. The latter failed to produce any significant enhancement of endometrial structure or secretions. Appropriate glandular morphology was present in a greater proportion of those who were successfully stimulated than those who responded poorly. However, defective secretion of the cycle-dependent component studied, using monoclonal antibody D9B1, was demonstrated in two-thirds of cases regardless of the ovarian response. Early vascular maturation in the stroma was a common finding, and was thus considered as a feature of structural modulation of these endometria.

Antibodies, Monoclonal↗
PubMed1992

The use of cryopreserved aged human oocytes in a test of the fertilizing capacity of human spermatozoa.

The use of cryopreserved aged human oocytes in a diagnostic test of sperm fertilizing ability was evaluated. Oocytes arising from assisted conception cycles and showing no signs of fertilization 48 h post-insemination were cryopreserved by one of two methods. An ultrarapid method using dimethyl sulphoxide gave poor post-thaw results, with only 5/69 (7.2%) oocytes surviving. Oocytes frozen by a slow method using propanediol as the cryoprotectant gave better survival rates (359/594; 60%). Fertilization by donor spermatozoa of these thawed oocytes was poor (15/63; 24%) when the zona pellucida was left intact. To improve this, the zona was enzymatically removed using pronase. These zona-free oocytes were then inseminated with spermatozoa from a fertile donor or from men previously exhibiting fertilization failure in an in-vitro fertilization treatment cycle. The fertilization rate in the patient group (41/91; 45%) was significantly lower than in the donor group (16/18; 89%) (P less than 0.02). There was also a significant (P less than 0.03) reduction in the median number of pronuclei per oocyte (2.9 versus 4.5). These results show that aged oocytes can be effectively cryopreserved to establish a bank for use in a test to identify men with impaired sperm fertilizing capacity.

Cell Survival↗
PubMed1992

Clinical and endocrinological changes in women following ovulation induction using buserelin acetate/human menopausal gonadotrophin augmented with biosynthetic human growth hormone.

Biosynthetic human growth hormone added to an ovarian stimulation regime of human menopausal gonadotrophin (HMG) for IVF treatment improves the response of women who were previously resistant. This study investigated the efficacy of growth hormone (GH)/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation. Ten patients (28-36 years, mean 32.5 years) were treated with GH (6 IU/day) plus buserelin/HMG. A control group of 10 women (28-37 years mean 31.0 years) received buserelin/HMG alone. All were given buserelin 500 micrograms and 2 ampoules (150 IU) HMG daily once pituitary suppression had been confirmed. There was no improvement in the GH group as assessed by follicular growth rate or number, oocyte number per woman and pregnancy rate. There was no effect of GH upon the serum oestradiol level and the follicular fluid levels of oestradiol, GH and inhibin. Serum IGF-1 increased significantly during GH administration, returning to pre-treatment levels 2 days after the last dose of GH. Follicular IGF-1 was much higher in the GH-treated group than the controls. Significant correlations were found in the GH-treated group between follicular fluid GH and follicular fluid oestradiol concentrations and between follicular GH and follicular size. Follicular IGF-1 was correlated with the serum IGF-1 concentration on day 8 of the GH/HMG treatment. In conclusion GH/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation increased their serum and follicular IGF-1 concentrations. However, it does not improve the clinical ovarian response or the follicular secretion of oestradiol or inhibin.

Adult↗
PubMed1992

Outcome of treatment subsequent to the elective cryopreservation of all embryos from women at risk of the ovarian hyperstimulation syndrome.

From 1st June 1989 to 31st May 1991, 78 women with a serum oestradiol level greater than 3500 pg/ml on the day of the ovulatory trigger, following pituitary suppression with buserelin and ovarian stimulation with human menopausal gonadotrophins (HMG), had all their embryos electively cryopreserved at the pronucleate stage to minimize the risk of developing ovarian hyperstimulation syndrome (OHS). Treatment with buserelin was continued in the luteal phase. A median of 19 oocytes (range 7-43) was obtained and 12 embryos (range 1-37) frozen per cycle. Twenty-one (27%) women developed OHS (six severe). Women developing OHS had higher (P less than 0.05) serum oestradiol concentrations on the 7th day after oocyte retrieval, compared to those who did not. No differences were found for any of the following criteria: aetiology of infertility, age, total dose of HMG, number of oocytes, fertilization rate or freeze-thaw survival of embryos. Subsequently, 125 frozen-thawed embryo replacements have been undertaken, using buserelin and hormone replacement therapy (HRT) (n = 93) or natural cycles (n = 32). The overall freeze-thaw survival and implantation rates per embryo were 71.8 and 11.7%, respectively. The pregnancy rates in natural cycles (19%) and buserelin/HRT cycles (29%) were not significantly different.

Buserelin↗
PubMed1992

Is continuation of a gonadotrophin-releasing hormone agonist (GnRHa) necessary for women at risk of developing the ovarian hyperstimulation syndrome?

A total of 28 women scheduled for in-vitro fertilization used buserelin and human menopausal gonadotrophin (HMG) for ovarian stimulation. One group (I) of 17 women was given human chorionic gonadotrophin (HCG 10,000 IU) to trigger ovulation, but the resulting embryos were electively cryopreserved because of the risk (serum oestradiol greater than or equal to 3500 pg/ml) of developing the ovarian hyperstimulation syndrome (OHSS). Six women continued the buserelin therapy in the luteal phase and eleven did not. In group II (n = 11), the HMG injections were discontinued because of an exaggerated ovarian response and the HCG was omitted. Six of these women continued the buserelin injections until the onset of menses and five did not. In both groups, the ovarian response to induction of ovulation (serum oestradiol concentrations and number of follicles) was similar for those who did or did not continue buserelin therapy. There was no difference in the rate of ovarian quiescence (weekly fall in serum oestradiol concentration following the stimulation) between those women who did or did not continue the buserelin therapy in either group. The serum luteinizing hormone concentrations remained low in all women in both groups. We conclude that the omission of buserelin therapy after discontinuing the HMG in women at risk of developing OHSS does not affect subsequent ovarian quiescence.

Adult↗
PubMed1992

Role of the ovary in the synthesis of placental protein-14.

Women with absent ovarian function provide an opportunity to investigate the ovarian contribution to secretion of placental proteins (PP), such as PP14, in early pregnancy. We present data on serum PP14 levels in 12 women (median age, 30.5 yr; range, 26-37 yr) with premature ovarian failure (POF) who conceived after ovum donation and embryo transfer with exogenous sex steroid support using transdermal (n = 5) or oral (n = 7) estradiol and vaginal (n = 8) or im (n = 4) progesterone. The women were closely monitored throughout early pregnancy, with measurement of serum levels of estradiol (E2), progesterone (P4), and PP14. Levels of E2 and P4 were entirely normal. Levels of PP14 were significantly subnormal (P = 0.008) in all 12 agonadal women compared with levels of PP14 in a control group of women with normal ovarian function between 6-12 weeks gestation. Basal and peak levels for subjects with absent ovarian function were 40 and 124 micrograms/L, respectively. For each week between 6-12 weeks of pregnancy, the mean serum levels of PP14 for women with normal ovarian function were between 706-940 micrograms/L. These observations support the concept that PP14 arises from the ovary in early pregnancy or that factors under the control of the maternal ovary are involved in its production by the endometrium.

Adult↗
PubMed1991

Cryopreservation of human embryos at the pronucleate, early cleavage, or expanded blastocyst stages.

Supernumerary embryos following treatment by IVF or GIFT were cryopreserved at the pronucleate, early cleavage or expanded blastocyst stages. The success of embryo cryopreservation at these stages was evaluated in terms of (i) the proportion of embryos surviving the freeze/thaw procedure; (ii) the proportion of patients reaching embryo replacement; and (iii) the incidence of pregnancy per replacement. Significantly more embryos survived when frozen/thawed at the pronucleate (44/61; 72%) or early cleavage stages (48/80; 60%), than at the expanded blastocyst stage (13/34; 38%). A significantly higher proportion of patients had embryo replacements when embryos were frozen/thawed at the pronucleate (17/19; 89%) or early cleavage stages (21/24; 88%), than at the expanded blastocyst stage (9/17; 53%). Following replacement of frozen/thawed pronucleate and early cleavage stage embryos, clinical pregnancy rates of 8/17 (47%) and 3/21 (14%) clinical pregnancies were achieved, respectively. No pregnancies were achieved following replacement of frozen/thawed expanded blastocysts.

Blastocyst↗
PubMed1991

The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response.

The present study has demonstrated the usefulness of GH in augmenting buserelin acetate/hMG to stimulate the rate of growth of follicles in women regarded as poor responders. The PR achieved was extremely encouraging in a group of patients whose prognosis was otherwise poor. Further studies are required to confirm these preliminary data.

Adult↗
PubMed1991

Serum inhibin as an index of ovarian function in women undergoing pituitary suppression and ovarian stimulation in an in vitro fertilization program.

Serum inhibin concentrations, determined by radioimmunoassay, were measured in women undergoing pituitary suppression with buserelin and subsequently ovarian stimulation with human menopausal gonadotropin (hMG). Three types of treatment cycle were investigated, namely (1) cycles showing a normal ovarian response and resulting in a pregnancy; (2) cycles showing a poor response to the hMG, and (3) cycles previously showing a poor ovarian response but augmented with biosynthetic human growth hormone. Good correlations were seen between serum inhibin concentrations and serum progesterone in the luteal phase prior to buserelin (Rs = 0.68), serum oestradiol on the 8th day of hMG administration (Rs = 0.82) or the day of ovulatory trigger (Rs = 0.78), and the number of follicles greater than or equal to 14 mm on the day of ovulatory trigger (Rs = 0.71). These results show inhibin to be a good index of ovarian function in women exhibiting a range of ovarian responses to stimulation in an in vitro fertilization program.

Adult↗