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Biomedical subjects

M Dirnfeld

Publications and source records attributed to M Dirnfeld.

At least 19 recordsLinked to original sources
PubMed2004

Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium.

p27 is a cyclin-dependent kinase (CDK) inhibitor whose specific late G(1) destruction allows progression of the cell across the G(1)/S boundary. The protein is ubiquitinated by S-phase kinase-interacting protein-2 (Skp2) following its specific phosphorylation, and is subsequently degraded by the 26s proteasome. There is a direct relationship between low level of p27 and rapid proliferation occurring in several benign states and in many malignancies. In the glandular cells of the normal endometrium, the level of p27 is exceedingly low during the proliferative phase, whereas it is markedly increased during the secretory phase. The expression of p27 in endometrial carcinoma is very low but has been found to increase following treatment with progesterone. However, estrogen exposure is considered as a major risk factor in developing endometrial cancer. The implications of the high dose of estrogen and progesterone induced during IVF treatment are still unknown. We have examined the expression of p27 and Skp2 as well as of Ki67 proliferation marker by using endometrial extracts and cells from normal endometrium, from ovarian hyperstimulated patients, and from endometrial carcinoma patients. The expression of p27, Skp2 and Ki67 was found to be similar in both normal secretory endometrium and endometrium from ovarian hyperstimulated patients. In striking contrast, p27 is significantly lower while Skp2 and Ki67 are significantly higher in the endometrial carcinoma and in endometrium from the proliferative phase compared with their normal secretory counterpart tissue.

Biopsy↗
PubMed2004

ART in recurrent miscarriage: preimplantation genetic diagnosis/screening or surrogacy?

Recently, assisted reproductive techniques have been used to prevent further miscarriages in women with recurrent miscarriage. One approach uses either screening or diagnosis of embryonic chromosomes prior to embryo replacement [preimplantation genetic screening (PGS)/preimplantation genetic diagnosis (PGD)]. The second approach involves surrogacy. However, PGS/PGD assumes that the embryo is chromosomally abnormal, and that the mother should receive a chromosomally normal embryo. Surrogacy assumes that the embryo is normal and that the maternal environment needs to be substituted. This article examines the place of both techniques in different types of recurrent miscarriage, and tries to give guidelines as to which technique is preferable depending on the likelihood of an embryonic chromosome aberration. In repeated fetal aneuploidy or in the older patient, PGS or PGD are preferable. However, with high numbers of miscarriages, or in autoimmune pregnancy loss, surrogacy is preferable. In the light of recent work, it is uncertain which treatment mode is indicated in balanced parental chromosome aberrations. In conclusion, both techniques have a place, but probably only in those patients with a poor prognosis in whom assisted reproductive techniques will be shown to improve the subsequent live birth rate above the spontaneous rate.

Abortion, Habitual↗
PubMed2004

The impact of cigarette smoking on zona pellucida thickness of oocytes and embryos prior to transfer into the uterine cavity.

BACKGROUND: Smoking has been reported to promote infertility. The zona pellucida plays an important role in fertilization and implantation. We report, for the first time, the effect of cigarette smoking on zona pellucida thickness of oocytes and embryos as one of the factors that may interfere with fertility. METHODS: This study comprised 169 women, grouped according to their smoking habits: 31 active smokers, whose husbands do not smoke; 44 active smokers, whose husbands smoke; 65 passive smokers, because of smoking husbands and 29 non-smokers (women and husbands). Zona pellucida thickness was measured prospectively on printed photos of 903 oocytes and 456 embryos. RESULTS: The zona pellucida thickness of oocytes and embryos of non-smoking women was significantly thinner than those of active and passive smokers. However, no significant differences were observed in the natural ability of the zona pellucida to become thinner after 48 h in culture. CONCLUSIONS: Our study demonstrates that active and passive cigarette smoking increases the zona pellucida thickness of oocytes and embryos. Our findings also show that active and passive smoking has no significant effect on the thinning mechanism of the zona pellucida, which implies that it is independent of the initial zona pellucida thickness.

Adult↗
PubMed2003

Analyzing factors affecting the success rate of frozen-thawed embryos.

PURPOSE: In recent years the infertile population applying for IVF treatments was changed and so the indications for performing intracellular sperm injection (ICSI). The aim of this study was to analyze predicting factors of our thawing cycles. METHODS: From December 1998 to July 2001, 440 consecutive thawing cycles were performed. Patient characteristics were examined. The number of cryopreserved embryos, number of transferred embryos, the timing of cryopreservation (48 h vs. 72 h), and embryo survival rate were analyzed as a possible predictor for pregnancies achievement. RESULTS: Conventional IVF patient's characteristic was significantly different from ICSI population and analysis has been performed for every population separately. In the IVF population the women age, the number of transferred embryos, and timing of cryopreservation were factors significantly influencing the pregnancy rate. Interestingly, in the ICSI population only the number of transferred embryos was found to be a predictive factor. CONCLUSION: ICSI and IVF cycles should be analyzed separately. Not all the factors influencing the success rate in the conventional IVF population are valid in the ICSI population.

Adult↗
PubMed2003

A prospective randomized controlled study of the effect of short coincubation of gametes during insemination on zona pellucida thickness.

A prospective, randomized study was conducted to evaluate the thickness, of zona pellucida (ZP) after brief or standard exposure of human oocytes to spermatozoa, and to determine the correlation between ZP thickness, fertilization rate and embryo quality. The mean ZP thickness 48 h after insemination was found to be significantly less in fertilized oocytes than in non-fertilized oocytes in all treated groups (13.72 +/- 3.0 microns and 15.08 +/- 2.5 microns, respectively; p < 0.007). Zona pellucida thickness correlated positively with embryo quality. Brief exposure of gametes was found to influence ZP thickness. The ZP was significantly thinner after brief and intracytoplasmic sperm injection (ICSI) exposure of oocytes to spermatozoa than after standard in vitro fertilization (IVF). The mean ZP thickness 24 and 48 h after fertilization was significantly greater in standard IVF (16.43 +/- 2.8 microns and 15.22 +/- 2.7 microns, respectively) than in either the brief exposure or ICSI groups (12.78 +/- 2.4 microns and 13.01 +/- 3.5 microns vs. 13.46 +/- 2.2 microns and 13.16 +/- 2.4 microns; p < 0.0001).

Adult↗
PubMed2002

The value of sperm pooling and cryopreservation in patients with transient azoospermia or severe oligoasthenoteratozoospermia.

BACKGROUND: A transient state of azoospermia may occur due to toxic, environmental, infectious or iatrogenic conditions. Finding sperm in the ejaculate of such patients is often unpredictable and may be critical in IVF treatment. In the present study, the approach of pooling and cryopreservation of sperm is evaluated. Cryopreservation was performed in a unique group of patients in whom no sperm had been found in at least one previous sperm examination and in patients diagnosed as suffering from non-obstructive azoospermia in whom, occasionally, sperm were found. METHODS: A total of 157 semen pooling and cryopreservation procedures in 53 patients was performed between January 1998 and December 2000 in our centre. Forty five of these patients underwent an IVF-ICSI treatment during the study period. In 32 patients, fresh sperm were used to perform ICSI. In 13 patients no sperm were available, and the previously frozen sperm were used. RESULTS: Using our pooling system, 13 IVF-ICSI cycles were rescued. In seven patients with a previous testicular biopsy due to azoospermia, sperm cryopreservation was possible. Overall, 13 pregnancies (10 deliveries, two ongoing pregnancies and one missed abortion) were achieved. CONCLUSION: The introduction of semen banking for patients with transient azoospermia may increase the chance of pregnancy using their own sperm.

Adult↗
PubMed2001

Endometrial ablation for the postmenopausal woman.

The postmenopausal woman with abnormal uterine bleeding is considered at risk for developing endometrial neoplasia or one of its precursors. She requires prompt evaluation of the endometrium followed by adequate treatment. In the subgroup of postmenopausal women taking hormone replacement therapy (HRT), the risk of abnormal bleeding is by far higher, is the main reason for discontinuing HRT, and deserves additional attention.

Aged↗
PubMed2001

A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles.

The effect of 100 and 200 IU per day recombinant FSH (rFSH) on numbers of oocytes retrieved and the total dose used in ovarian stimulation before intracytoplasmic sperm injection was investigated in a double-blind, randomized multicentre trial. A total of 91 women was treated with a low-dose protocol and 88 with a high-dose regimen at five centres. For each started cycle, significantly more oocytes were retrieved in the 200 IU group than in 100 IU group (12.0 versus 5.7, P < 0.001); total rFSH consumption was 1121 and 1875 IU in the low- and high-dose groups respectively. Significant variations were noted between centres with regard to numbers of oocytes collected per started cycle, ranging from 2.8 to 7.2 in the 100 IU group and from 9.0 to 19.1 in the high-dose group. Exploratory analyses of secondary outcomes suggested there were no differences in vital pregnancy rates per started cycle (19.2 versus 16.9%) and per embryo transfer (26.2 versus 19.3%) in the low- and high dose groups respectively. There were four hospitalizations due to ovarian hyperstimulation syndrome, all in the 200 IU group.

Adult↗
PubMed2000

Pure follicle-stimulating hormone as an adjuvant therapy for selected cases in male infertility during in-vitro fertilization is beneficial.

OBJECTIVES: Since research has demonstrated the possibility of hormonal therapy for male infertility, we conducted a study to analyze the efficacy of pure follicle-stimulating hormone (pFSH) treatment in patients with idiopathic, severe oligoteratoastheno-spermia (OTA) syndrome, or failed fertilization before referral to an intracytoplasmic sperm injection (ICSI) in an in-vitro fertilization (IVF) program. STUDY DESIGN: A retrospective, clinical study was carried out on 178 men with OTA syndrome. Group I comprised 76 patients selected for treatment with pFSH. Group II comprised 102 men who served as the controls. Pure FSH was administered intramuscularly to the patients in group I. Upon cessation of therapy, an IVF treatment cycle was carried out. RESULTS: After treatment with FSH, sperm motility was the only parameter which significantly improved in Group I (34% vs. 23%, and 15% vs. 24% in the subgroups of Group 1, respectively; P<0.05). In-vitro fertilization pregnancy rates were similar in both groups. The highest spontaneous pregnancy rates were achieved in FSH-treated, severe OTA patients. CONCLUSIONS: Patients with severe male factor infertility may benefit from pFSH in terms of sperm motility, fertilization by IVF and spontaneous pregnancy rates. Selection criteria for FSH treatment are proposed.

Adult↗
PubMed1999

Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization.

OBJECTIVE: To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. DESIGN: A prospective, randomized controlled trial. SETTING: Hospital-based IVF Unit. PATIENT(S): Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. INTERVENTION(S): In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. MAIN OUTCOME MEASURE(S): Ovarian stimulation patterns and IVF outcome. RESULT(S): A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). CONCLUSION(S): Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.

Adult↗
PubMed1999

Dexamethasone supplementation to gonadotropin stimulation for in vitro fertilization in polycystic ovarian disease.

PURPOSE: This study was conducted to determine whether glucocorticoid supplementation for patients with polycystic ovarian disease during ovulation induction with gonadotropins for in vitro fertilization (IVF) therapy is beneficial. METHODS: Seventy-one cycles of patients undergoing first attempts at IVF, with classical polycystic ovarian disease and hyperandrogenemia, who enrolled in the IVF-embryo transfer program, were evaluated retrospectively. In 20 cycles (20 patients) glucocorticoid supplementation was noted and compared to 51 cycles (51 patients) without glucocorticoid as adrenal androgen suppression. Ovaries were stimulated by gonadotropin releasing hormone agonist, human menopausal gonadotropin, and dexamethasone. Ovarian responsiveness and IVF-embryo transfer outcome were analyzed and included the number of follicles > 17 mm in diameter, serum estradiol concentration on the day of human chorionic gonadotropin administration, number of human chorionic gonadotropin ampoules administered, number of oocytes retrieved, percentage of oocytes fertilized, number of embryos transferred, implantation rate, and number of clinical pregnancies and their outcome. RESULTS: The results showed that the pregnancy rate in patients who received glucocorticoid was 22.1%, compared to 26% in the controls (statistically insignificant). The IVF cycle variables studied revealed no statistically significant differences. CONCLUSIONS: Our observations did not support the notion that adrenal androgen suppression by glucocorticoid, or as an adjuvant therapy, is beneficial to patients with polycystic ovarian disease who enrolled in an IVF-embryo transfer program.

Adult↗
PubMed1999

Shortened exposure of oocytes to spermatozoa improves in-vitro fertilization outcome: a prospective, randomized, controlled study.

A prospective, randomized study of 158 patients undergoing in-vitro fertilization (IVF) and embryo transfer was conducted to evaluate whether a shortened exposure of oocytes to spermatozoa enhances oocyte development, and subsequently influences the IVF outcome. A comparison was made between conventional treatment time and shorter exposure of retrieved oocytes to spermatozoa. Fertilization and cleavage rates, embryo quality, implantation and pregnancy rates in the study group (short exposure) versus controls (standard IVF procedure) were evaluated. Fertilization (56 versus 61%) and cleavage rates (96 versus 92%) were similar in the two groups respectively. However, embryo quality was significantly higher in the study group (P < 0.05). Moreover, the pregnancy and implantation rates were significantly increased (42.4 versus 26% per embryo transfer, and 16 versus 10% respectively; P < 0.05). Our results demonstrated that shorter exposure of oocytes to spermatozoa is superior to the standard time in IVF and may have a favourable effect on implantation rates by improving embryo quality.

Adult↗
PubMed1997

A simplified coculture system with luteinized granulosa cells improves embryo quality and implantation rates: a controlled study.

OBJECTIVE: To investigate the use of a simplified short-term coculture system with luteinized granulosa cells (GCs) in patients with failed IVF-ET. DESIGN: Controlled clinical study. SETTING: IVF unit, Department of Obstetrics and Gynecology, Carmel Medical Center. PATIENT(S): Patients with poor embryo quality in their previous IVF-ET cycles. INTERVENTION(S): Embryos from 40 patients, in which > 50% of the embryos were classified as poor quality in their previous IVF attempts, were grown on autologue GC culture system for a short period (24-48 hours) before being replaced in the uterine cavity. MAIN OUTCOME MEASURE(S): Embryo quality. RESULT(S): Significant decrease in poor quality embryos and increase in the proportion of good quality embryos were observed using a coculture system with autologue human GCs. Pregnancy rates in this groups of patients reached our standard IVF results during the same period. CONCLUSION(S): This study describes a simplified short-term coculture system with human autologue GCs. Poor quality embryos may be rescued to cleave regularly.

Cells, Cultured↗
PubMed1997

Triiodothyronine and follicle-stimulating hormone, alone and additively together, stimulate production of the tissue inhibitor of metalloproteinases-1 in cultured human luteinized granulosa cells.

Thyroid disorders have been frequently associated with menstrual disturbances and impaired fertility. To characterize the nature of thyroid hormone action in the ovary, the direct effects of T3-gonadotropin interactions were investigated in vitro using a culture system of human luteinized granulosa cells in serum-free medium. Although FSH alone was devoid of any significant effect on cell proliferation, it inhibited T3-stimulated cell growth. The electrophoretic profiles of the radiolabeled proteins induced by the different hormonal treatments revealed similarity in overall protein patterns but differences in intensity of labeling. Human CG, alone or combined with T3, had no major influence on the total intensity of labeling compared with control, whereas T3 or FSH alone reduced total labeling intensity but a 30,000 Da protein band was increased. FSH combined with T3 augmented the total intensity of labeling, including the 30,000-Da protein band. Western blot analysis revealed the presence of the tissue inhibitor of metalloproteinases-1 (TIMP-1), mol wt 30,000, known to play a key role in ovarian function. TIMP-1 was dose dependently stimulated by T3 and FSH, and an additive effect was obtained when both hormones were combined. This is the first report of TIMP-1 modulation by FSH in ovarian cells and of an effect by thyroid hormone on TIMP-1 levels. The study shows TIMP-1 induction in human ovarian cells not only by FSH, i.e. via a probable protein kinase A mechanism, but also demonstrates an additional mode of TIMP-1 hormonal induction: via thyroid hormone stimulation, acting by modulation of gene transcription. The present study provides novel data on TIMP-1 hormonal modulation and of direct T3 in vitro ovarian effects that may account for the in vivo indications of a thyroid-ovarian connection.

Adult↗
PubMed1994

Growth hormone co-treatment for ovulation induction may enhance conception in the co-treatment and succeeding cycles, in clonidine negative but not clonidine positive patients.

To investigate the effect of co-treatment with growth hormone (GH) for ovulation induction with human menopausal gonadotrophins (HMG) on conception, we compared the pregnancy rate and response to co-treatment with GH versus HMG/human chorionic gonadotrophin (HCG) alone in a prospective, randomized, cross-over protocol of ovulation induction for either in-vivo or in-vitro fertilization (IVF). The main outcome measures were the amount of gonadotrophin used and conception. Co-treatment with GH was associated with a reduction of approximately 30% in gonadotrophin requirement. In 24 clonidine negative patients 14 pregnancies were achieved (58.3%) either in the GH/HMG/HCG cycle or in the succeeding one. GH co-treatment did not generate any pregnancy in eight clonidine positive patients. We conclude that growth hormone may increase the pregnancy rate when combined with HMG/HCG for ovulation induction, not only in the co-treatment cycle but also in the succeeding one. The beneficial, synergistic effect of GH co-treatment was detected in clonidine negative but not in clonidine positive infertile patients.

Adult↗
PubMed1993

Vaginal ultrasonography in patients with postmenopausal bleeding.

Our objective was to define a subset of women with postmenopausal bleeding in whom the accepted practice of endometrial sampling could be safely omitted. Vaginal endosonographic measurements were compared to the histological findings of curettings following diagnostic dilatation and curettage in 129 women with post-menopausal bleeding who were not receiving hormonal therapy. Atrophy was diagnosed in 49%, slight proliferation in 10%, endometrial polyps in 11%, hypoplasia in 12%, and adenocarcinoma in 12%. Endometrial atrophy was associated with a mean sonographic thickness of 2.6 mm of the double layer (range 0-6.5 mm). Of the women with a final histological diagnosis of atrophy, 92% had an endometrial thickness of 3 mm or less. Furthermore, all women with a sonographic endometrial thickness of 3 mm or less had atrophic endometrium (p < 0.0001). An endometrial thickness of 3 mm or less would have reduced the number of dilation and curettage procedures by 45% and no cases of endometrial pathologies would have been missed. In women presenting with postmenstrual bleeding, meticulous scanning of the endometrium can select a group where endometrial sampling can be omitted from the protocol.

Journal Article↗
PubMed1993

A modest increase in serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration may influence pregnancy rate and pregnancy loss in in vitro fertilization-embryo transfer (IVF-ET) patients.

PURPOSE: Our purpose was to study the effect of a modest increase in preovulatory serum progesterone (P4) levels in hyperstimulated patients and its association with pregnancy rate and pregnancy loss following in vitro fertilization (IVF) and embryo transfer (ET). PATIENTS: Only patients with mechanical factor and three transferred embryos were included in the present study. They were divided into two groups according to two critical breakpoints for P4 serum levels on the day of hCG administration: serum P4 below 0.6 ng/ml in 28 cycles (group I) and > 0.6 ng/ml in 80 cycles (group II). SETTING: The setting was the IVF program at Carmel Medical Center, Haifa, Israel. RESULTS: The pregnancy rate per embryo transfer was 53% (15/28) in group I and 10% (8/80) in group II (P < 0.025). Of 15 pregnancies achieved in group I, 14 were ongoing pregnancies, compared to 4 of 8 ongoing pregnancies in group II (P < 0.03). CONCLUSIONS: Our findings suggest that a very modest increase in serum P4 levels on the day of hCG administration is associated with lower pregnancy and ongoing pregnancy rates in IVF-ET.

Adult↗