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Biomedical subjects

Y Gonen

Publications and source records attributed to Y Gonen.

At least 19 recordsLinked to original sources
PubMed1999

Mitogen-activated protein kinase in human eggs.

Mitogen-activated protein (MAP) kinase in human eggs has been investigated by using immunoblotting with both anti-Active MAPK and anti-ERK2 antibodies. The results showed that the main form of MAP kinase was p42ERK2. It was in a dephosphorylated form in oocytes at the germinal vesicle stage, but fully phosphorylated in unfertilised mature eggs. MAP kinase phosphorylation was significantly decreased when pronuclei were formed after intracytoplasmic sperm injection. Neither MAP kinase expression nor activity was detected in morphologically degenerated eggs. Although MAP kinase still existed in early embryos arrested at the 8-cell or morula stages, little, if any, activity could be detected. These data suggest that MAP kinase may play an important role in the cell cycle regulation of human eggs, as in other mammalian species.

Adult↗
PubMed1998

Pregnancy and birth after transfer of embryos that developed from single-nucleated zygotes obtained by injection of round spermatids into oocytes.

OBJECTIVE: To use injection of spermatids into oocytes as a mode of infertility treatment in cases in which spermatozoa are not available. DESIGN: Prospective clinical evaluation and case report. SETTING: In Vitro Fertilization Unit, Herzliya Medical Centers, Herzliya-on-Sea, Israel. PATIENT(S): Thirteen couples with male factor infertility in which the male partner lacked spermatozoa in the ejaculate or testicular biopsy samples. INTERVENTION(S): Round spermatid injection and elongated spermatid injection into oocytes. MAIN OUTCOME MEASURE(S): Evaluation of the rate of two-pronucleated and single-nucleated zygote development. RESULT(S): The rate of two-pronucleated zygote development after round spermatid injection and elongated spermatid injection was relatively low (27% and 36%, respectively). Single-nucleated zygotes develop more frequently after round spermatid injection and elongated spermatid injection (35% and 17%, respectively) than after intracytoplasmic sperm injection with mature spermatozoa. A normal pregnancy and childbirth resulted from the transfer of 4 cleaving embryos, each of which developed from a single-nucleated zygote in a round spermatid injection treatment cycle with ejaculated spermatids. CONCLUSION(S): Embryos derived from single-nucleated zygotes after spermatid conception can be viable and give rise to an ongoing clinical pregnancy and childbirth.

Adult↗
PubMed1998

Monoclonal antibodies against epidermal growth factor prevent outgrowth of mouse embryos in vitro.

The necessity of epidermal growth factor (EGF) in the process of mouse embryo development and outgrowth in vitro was studied. Mouse 4-cell stage embryos were cultured up to spreading stage (outgrowth) in human tubal fluid (HTF) medium alone (control) or with 10 ng/ml EGF and 1:250 diluted monoclonal antibodies against EGF (study groups). Hatching and outgrowth were significantly increased up to 60.9 and 52.4% respectively, while in the control only 33.7 and 20.4% reached hatching and outgrowth respectively. Moreover monoclonal antibodies against EGF significantly inhibited embryo development (P < 0.01). Only 5.8% of the embryos reached the hatching stage and none of them reached the spreading stage. Our results show that EGF is probably involved in the modulation of early embryonic growth and in the initiation of implantation.

Animals↗
PubMed1998

Does glucose affect fertilization, development and pregnancy rates of human in-vitro fertilized oocytes?

The study was conducted to examine whether the presence of glucose in the incubation medium affects fertilization, development and implantation rates of human oocytes of patients who were attending our in-vitro fertilization programme. Harvested oocytes were transferred into one of four different media: human tubal fluid (HTF), P1, M3 and IVF-Universal (IVF-Med). Three of these contained glucose; the fourth (P1), contained no glucose or phosphate ions. In an independent preliminary study, some of the oocytes of each patient were incubated in IVF-Med, which lacks phosphate ions, but not glucose. Comparisons of fertilization rates between media pairs showed differences among all pairs except HTF and M3. When comparing the four study groups, no difference was noticed in embryo development or embryo quality 48 h post-ovum retrieval. A higher development rate was demonstrated in embryos incubated in M3 medium, in comparison with the P1 and IVF-Med embryos after incubation for 72 h. No difference in pregnancy rate was found after embryo transfers of preimplantation embryos which were incubated in one of the following media: HTF, M3 and IVF-Med (seven out of 22, 18 of 54 and 32 of 69 treatment cycles respectively). A lower incidence of pregnancies occurred following transfers of embryos which were incubated in P1 medium (seven pregnancies out of 37 cycles). We suggest that the presence of glucose in the incubation medium enhances implantation potential of in-vitro-developing preimplantation embryos.

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↗
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

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↗
PubMed1993

Outcome of pregnancies inadvertently exposed to gonadotropin-releasing hormone analogues (GnRH-a) in early gestation.

In recent years the down-regulation of pituitary function by GnRH-a, before and during ovarian stimulation for IVF, has been widely used. When GnRH-a are commenced in the luteal phase, it is inevitable that some early human embryos will be exposed. To the best of our knowledge the total number of reported deliveries following exposure is less than 30. We report here a further nine uneventful pregnancies with successful neonatal outcomes and three early miscarriages. It is our belief that the favorable outcome in patients presented here, who inadvertently received GnRH-a in early unsuspected gestation, is related to the use of short-acting analogues (Buserelin nasal spray). This enabled immediate discontinuation of the drug when the presence of pregnancy was suspected. In addition, the routine administration of progesterone supplements is strongly recommended, regardless of the hormonal levels.

Abortion, Spontaneous↗
PubMed1993

Different morphology and proliferative ability of cumulus and granulosa cells originating from cystic follicles aspirated from stimulated in vitro fertilization patients.

OBJECTIVE: To investigate the morphology and proliferative ability of cumulus and granulosa cells (GCs) originating from cystic follicles and normal-sized follicles after ovarian stimulation. DESIGN: Granulosa cells, cumulus cells, and follicular fluid (FF) were aspirated from cystic follicles and normal-sized follicles from the same ovary. Morphology and proliferative ability of cumulus and GCs were assessed by Giemsa stain and thymidine incorporation, respectively. Cell proliferation was assessed in medium or FF originating from cystic follicles or normal-sized follicles. RESULTS: An oocyte was found in 40% of the cystic follicles versus 68% in the normal-sized follicles. Changes in dispersion and adhesion properties were observed in cystic versus normal aspirated corona cumuli complex. Proliferative ability was consistently lower in GCs originating from cystic follicles versus normal-sized follicles. Proliferation of GCs originating from normal-sized follicles or cystic follicles was inhibited or increased when grown in FF from cystic follicles or FF from normal-sized follicles, respectively. Differences in embryo quality were significantly in favor of oocytes originating from normal-sized follicles. Although the fertilization rate of those oocytes appeared to be higher, the difference was not of statistical significance. CONCLUSIONS: Inhibition of GC proliferation in FF from cystic follicles can be reversed by incubating cells in FF from normal-sized follicles. We conclude that factors in the FF may affect cell proliferation.

Cell Division↗
PubMed1993

Functional differentiation in progesterone secretion by granulosa versus cumulus cells in the human preovulatory follicle and the effect of different induction of ovulation protocols.

OBJECTIVE: To investigate P secretion by granulosa cells (GCs) versus cumulus cells derived from human preovulatory follicles. DESIGN: Cells were recovered by aspiration of preovulatory follicles in 44 women participating in an IVF program. Induction of ovulation was performed using clomiphene citrate, hMG and hCG (group I), hMG/hCG (group II), buserelin acetate/hMG/hCG (group III), or Decapeptyl/hMG/hCG (group IV). SETTING: Laboratories of the IVF Unit at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. MAIN OUTCOME MEASURES: Secretion of P was examined after cultures for 96 hours under nonstimulated and hCG stimulated conditions. RESULTS: Progesterone secretion by GCs derived from all four groups was found to be higher compared with the respective cumulus cells. However, although the ratios of P secretion by GCs versus cumulus cells in groups I, II, and III were very similar, a significantly lower value was observed in group IV. The response of GCs to hCG in terms of P secretion was higher with at least one dose of hCG in groups I and IV compared with groups II and III. The response of cumulus cells to hCG was absent regardless of the treatment protocol used in vivo. CONCLUSION: Our results demonstrate that in the human preovulatory follicle, GCs and cumulus cells differ in their capacity to secrete P as well as in their response to hCG. They further suggest that the mode of induction of ovulation affects the relative capacity of GCs and cumulus cells to secrete P and their ability to respond to hCG.

Adult↗
PubMed1993

Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization.

The present study was undertaken to assess whether the increase in serum progesterone concentration following the administration of human chorionic gonadotrophin (HCG) may have predictive value on the in-vitro fertilization (IVF) success rate. Progesterone concentration on the day of HCG administration and the increase in progesterone concentration on the following day were evaluated in 140 consecutive patients undergoing IVF with embryo transfer. Stimulation protocol in all study patients entailed intranasal administration of short-acting gonadotrophin-releasing hormone agonist (GnRHa) buserelin and human menopausal gonadotrophin. A pregnancy rate of 37.2% was achieved when at least three embryos were transferred. The only significant difference between conception and non-conception cycles was found in serum progesterone concentrations after HCG administration (P < 0.01), whereas the mean progesterone concentration on the day of HCG did not differ. No difference in other hormonal or cycle parameters was observed. The increase in progesterone concentration was significantly greater in the group of patients who achieved pregnancy than in the group who did not (2.2 +/- 0.2 versus 1.6 +/- 0.1 ng/ml, respectively; P < 0.01). A critical breakpoint in serum progesterone was arbitrarily determined at 1 ng/ml. An increase in progesterone concentration > or = 1 ng/ml when three or more embryos were transferred was associated with a positive predictive value for pregnancy of 40.4% (sensitivity of 94.7%), whereas a negative predictive value of 86.7% was obtained when this value was < 1 ng/ml. These findings indicate that an adequate rise in serum progesterone following HCG administration provides useful information about the possible outcome of the treated cycle.

Adult↗
PubMed1993

The effect of epidermal growth factor on growth and differentiation of mouse preimplantation embryos in vitro.

The effect of epidermal growth factor (EGF) on embryonic growth, development, attachment and spreading in vitro was studied. EGF was added to 130 embryos at the 4-cell stage; to 128 embryos at the blastocyst stage; and to 147 embryos 24 h following spreading. Development of embryos from the 4-cell to the blastocyst stage, differentiation of the inner cell mass (ICM) and trophectoderm, and the occurrence of attachment and spreading were evaluated. Embryo development was significantly inhibited in cultures supplemented with 100 ng/ml EGF compared to the controls (P < 0.001). Development of 4-cell embryos to blastocysts occurred in 25% of the EGF group compared to 85% of controls. Spreading occurred in 20% of 4-cell embryos and 30% of blastocysts treated with EGF, compared to 80 and 90% of corresponding controls. In embryos developing from the 4-cell stage, massive growth of the ICM and inhibition of the trophectoderm occurred, whereas both ICM and trophectoderm were inhibited by EGF in embryos developing from the blastocyst stage. Following spreading, EGF caused massive growth of the ICM and regression of the trophectoderm. Our preliminary results show that EGF may be involved in the modulation and control of early embryonic growth and differentiation.

Animals↗
PubMed1993

Gamete intrafallopian transfer. An overview.

Gamete intrafallopian transfer involves a direct transfer of both human gametes, sperm and oocytes, into the fallopian tube. Since the first report of a successful pregnancy following the use of this technique by Asch et al in 1984, its role in the treatment of infertile women with patent tubes has been established. Recent data demonstrate a 34.4% clinical pregnancy rate, with the highest pregnancy rate achieved in infertile women due to endometriosis or unexplained infertility.

Aftercare↗
PubMed1991

The impact of sonographic assessment of the endometrium and meticulous hormonal monitoring during natural cycles in patients with failed donor artificial insemination.

The present study was undertaken to determine whether the sonographic characteristics of the endometrium in the proliferative phase of the natural cycle combined with meticulous hormonal monitoring would have an impact on the prediction of conception. Fourteen women with regular ovulatory cycles were examined daily, from day 8 of the cycle, by transvaginal ultrasound through 16 unstimulated cycles. All patients had had at least four previous unsuccessful donor artificial insemination cycles scheduled by basal body temperature records. During the study, donor artificial insemination was meticulously timed by hormonal and sonographic monitoring. Four clinical pregnancies occurred with a success rate of 29% per patient, or 25% per cycle. The endometrial thickness at the mid-proliferative phase (day 8) was significantly smaller in patients who conceived in comparison with patients who failed to conceive (0.33 +/- 0.07 cm vs. 0.59 +/- 0.03 cm; p < 0.01). The endometrial thickness on the day of the luteinizing hormone (LH) peak was not significantly different between the two groups. However, the amount of endometrial growth between day 8 of the cycle and the day of the LH peak was significantly greater in conception than non-conception cycles (0.55 +/- 0.05 cm and 0.24 +/- 0.06 cm; p < 0.01). No difference in hormonal parameters was observed either on day 8 of the cycle or on the day of the LH peak between conception and non-conception cycles. On the day of the LH peak, an endometrium with typical triple line appearance and thickness of 0.6 cm or more was seen significantly more often in conception than non-conception cycles (p < 0.05). No pregnancy occurred with an endometrium < 0.6 cm at the time of ovulation. The presence of the favorable endometrial pattern in the periovulatory phase was associated with a positive predictive value for pregnancy of 50% (sensitivity of 100% and specificity of 67%), whereas the negative predictive value of the hyperechoic pattern at the time of ovulation was 100%. Our data show negative correlation between early growth of the endometrium and pregnancy in unstimulated cycles, suggesting that the amount of endometrial growth during the cycle up to ovulation may have an important role in implantation. The sonographic image of the endometrium in natural cycles provides useful information about the possible outcome of the treated cycle.

Journal Article↗
PubMed1991

A randomized prospective study on the effect of short and long buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response.

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I--long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II--short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P less than 0.01). Cancellation rate was significantly lower in Group I than in Group II (P less than 0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos transferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.

Adult↗
PubMed1991

The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a; decapeptyl) and gonadotropins versus short-acting GnRH-a (buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF).

The efficiency of two ovarian stimulation protocols using different gonadotropin-releasing hormone agonists (GnRH-a) for in vitro fertilization (IVF) was examined and compared with human menopausal gonadotropin (hMG)-only stimulation. Fifty-four patients who had 57 aspiration cycles were treated with protocol 1, which consisted of long-acting GnRH-a D-Trp6 (Decapeptyl Depot) and hMG. Protocol 2 entailed intranasal administration of short-acting GnRH-a (Buserelin) and human menopausal gonadotropin (hMG) in 66 women who underwent 70 aspiration cycles. Fifty-five patients who had 59 ovum pickups (OPU) treated with hMG only served as a control. No differences were observed in cycle parameters and hormonal concentrations among the three groups. The total clinical pregnancy rates per OPU for patients receiving protocols 1 and 2 were 12.3 and 27.1%, respectively (P less than 0.05). The pregnancy loss was significantly lower in protocol 2 than in protocol 1 (26.3 versus 71.4%; P less than 0.05). Our data show superiority of short-acting GnRH-a over the long-acting agents in achievement of pregnancy and its outcome, though neither was significantly different from the hMG-only protocol.

Adult↗
PubMed1991

Effect of follicular aspiration on hormonal parameters in patients undergoing ovarian stimulation.

The effect of follicular aspiration and oocyte retrieval on hormonal parameters was examined in women undergoing ovarian stimulation for in-vitro fertilization (IVF) compared to induced ovulation in women undergoing ovarian stimulation for intrauterine insemination (IUI). Blood samples were collected immediately before and 1 h after oocyte retrieval and 48 h later on the day of embryo transfer in 25 IVF patients and before the insemination and 48 h later in 20 IUI patients. A highly significant fall in serum levels of oestradiol (E2), progesterone (P) and human chorionic gonadotrophin (HCG), (P less than 0.001) was observed in the IVF group 1 h after follicular aspiration. The decline in serum E2 levels was maintained at 48 h. In contrast, there was no significant change in serum E2 levels in the IUI group during 48 h. The immediate decline in E2 levels after follicular aspiration might play a role in preventing ovarian hyperstimulation syndrome.

Chorionic Gonadotropin↗