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Papers by David Levran

Research paper thumbnail of In vitro fertilization treatment for severe male factor: a comparative study of intracytoplasmic sperm injection with testicular sperm extraction and with spermatozoa from ejaculate

Journal of assisted reproduction and genetics, 1998

Our purpose was to evaluate whether the source of spermatozoa influences the results of intracyto... more Our purpose was to evaluate whether the source of spermatozoa influences the results of intracytoplasmic sperm injection (ICSI) treatment in couples with severe male-factor infertility. A retrospective analysis of 40 cases of ICSI with testicular-retrieved spermatozoa, matched with 40 cases of ICSI with ejaculated spermatozoa, was performed. We included only couples with normoovulatory females younger than 37 years who were matched according to the day of ovum pickup with the patients in the study group. Eighty cycles were analyzed: 40 cycles using testicular spermatozoa and 40 cycles using ejaculated spermatozoa. In 32 (80%) of the 40 ICSI transcutaneous needle aspiration cycles, we obtained enough spermatozoa to inject all the mature oocytes retrieved. In eight (20%) cases there were not enough spermatozoa to inject all the oocytes. Only 76 (54%) of 141 available oocytes were injected in these eight patients. The oocyte fertilization rates were 42% for the study group and 55.5% fo...

Research paper thumbnail of Pregnancies and live births following ICSI with testicular spermatozoa after repeated implantation failure using ejaculated spermatozoa

Reproductive BioMedicine Online, 2008

The use of testicular spermatozoa for IVF/intracytoplasmic sperm injection (ICSI) is currently in... more The use of testicular spermatozoa for IVF/intracytoplasmic sperm injection (ICSI) is currently indicated exclusively for patients with azoospermia, since a favourable outcome is expected even when very few spermatozoa are present in the ejaculate. Here, a series of four couples with long-standing male factor infertility and multiple failed IVF/ICSI cycles are described. In all couples, the use of ejaculated spermatozoa for ICSI resulted in poor embryo quality and repeated implantation failure. Testicular sperm aspiration was performed in subsequent cycles, and testicular spermatozoa were used for ICSI. Embryo implantation and ongoing pregnancies/deliveries were achieved in all four couples. It is postulated that spermatozoa are subjected to post-testicular damage during sperm transport between the seminiferous tubules and epididymis, with the injection of damaged spermatozoa being the cause for repetitive IVF/ICSI failures. In selected patients, the use of testicular spermatozoa for IVF/ICSI should be considered, even when motile spermatozoa can be identified in the ejaculate.

Research paper thumbnail of Zygote intrafallopian transfer may improve pregnancy rate in patients with repeated failure of implantation

Fertility and Sterility, 1998

To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregn... more To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregnancy rates (PRs) in patients with repeated failure of implantation in IVF-ET cycles. A case-control study. Criteria for patient selection included male factor or unexplained infertility, normal uterine cavity, and at least three failures of implantation in IVF-ET cycles in which at least three embryos were placed per transfer. Data on 70 patients who underwent 92 ZIFT cycles are presented. A control group consisted of patients with the same selection criteria who underwent an additional standard IVF-ET cycle during the same time period. Ovulation induction consisted of down-regulation with GnRH analogue followed by ovarian stimulation with FSH and hMG. Intracytoplasmic sperm injection was performed on the oocytes of all patients with male factor infertility. Zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval. Implantation rates and PRs in the ZIFT and control groups were compared. The PRs and implantation rates were significantly higher in the ZIFT group than in the control group: 34.2% (24/70) and 8.7% (29/333) versus 17.1% (12/70) and 4.4% (13/289), respectively (P = 0.002 and P = 0.04). The cumulative conception rate for two ZIFT cycles was 59.3%. Zygote intrafallopian transfer should be considered a beneficial mode of treatment for patients with repeated failure of implantation in IVF and transcervical ET. More prospective randomized studies are needed to support this observation.

Research paper thumbnail of Hysteroscopy in a program of in vitro fertilization

Journal of Assisted Reproduction and Genetics, 1991

Two hundred twenty-four women underwent hysteroscopic evaluation without anesthesia after at leas... more Two hundred twenty-four women underwent hysteroscopic evaluation without anesthesia after at least two failed attempts of in vitro fertilization and embryo transfer. One hundred fifty-three (68%) women were diagnosed as having mechanical infertility, and abnormal hysteroscopic findings were observed in 32 (21%). Forty-one women were diagnosed as having unexplained infer-tility (18%) and six (15%) had abnormal findings with hysteroscopy. Of

Research paper thumbnail of Midazolam-fentanyl sedation in conjunction with local anesthesia during oocyte retrieval for in vitro fertilization

Journal of Assisted Reproduction and Genetics - J ASSIST REPROD GENET, 1992

... Collier M, O'Neill C, Ammit AJ, Saunders DM: Measure-ment of human embryo-derive... more ... Collier M, O'Neill C, Ammit AJ, Saunders DM: Measure-ment of human embryo-derived platelet-activating factor (PAF) using a quantitative bioassay of platelet ... Anaesthesia 1988;43(Suppl):87-89 9. Ben-Shlomo I, Abd-EI-Halim H, Ezry J, Zohar S, Tverskoy M: Midazolam ...

Research paper thumbnail of Neonatal outcome in polycystic ovarian syndrome patients treated with metformin during pregnancy

Journal of Maternal-Fetal and Neonatal Medicine, 2006

The present study aimed to evaluate the effect of metformin exposure during pregnancy on neonates... more The present study aimed to evaluate the effect of metformin exposure during pregnancy on neonates of polycystic ovarian syndrome (PCOS) patients. Neonatal outcomes of 33 women with PCOS treated with metformin during pregnancy were compared to neonatal outcomes of 66 normal healthy women in a retrospective case-control study. The mean birth weight percentile of neonates exposed to metformin in utero during the first trimester was significantly lower than that of neonates delivered to normal healthy matched controls. After controlling for pregnancy complications, this observation became only marginally statistically significant. Although metformin is an attractive option for induction of ovulation in PCOS patients, there is a need for more evidence related to its safety during pregnancy.

Research paper thumbnail of Timing intra-Fallopian transfer procedures

Reproductive BioMedicine Online, 2007

With the gradual decline in the use of zygote intra-Fallopian transfer (ZIFT), current practice i... more With the gradual decline in the use of zygote intra-Fallopian transfer (ZIFT), current practice is to offer ZIFT almost exclusively to patients with repeated implantation failure (RIF). For practical reasons, the procedure is sometimes deferred by 1 day and embryo intra-Fallopian transfer (EIFT) is performed. The aim of the present study was to compare the reproductive outcome of ZIFT versus EIFT. In a retrospective analysis, 176 patients who failed in 7.65 ± 3.7 previous IVF cycles underwent 200 ZIFT and 73 EIFT procedures. Implantation and live birth rates were compared for both groups. Patients in both groups were found comparable for demographic and clinical parameters. Similar numbers of oocytes were retrieved and fertilized in both groups, and 5.2 ± 1.2 zygotes/embryos were transferred. Implantation and live birth rates (10.5 and 26.5% versus 10.9 and 24.7% for ZIFT and EIFT respectively) were comparable. It is concluded that tubal transfer of zygotes and day-2 cleavage stage embryos are equally effective.

Research paper thumbnail of What is the preferred method for timing natural cycle frozen–thawed embryo transfer?

Spontaneous ovulation during a natural menstrual cycle represents a simple and efficient method f... more Spontaneous ovulation during a natural menstrual cycle represents a simple and efficient method for synchronization between frozen embryos and the endometrium. The objective was to compare serial monitoring until documentation of ovulation, with human chorionic gonadotrophin (HCG) triggering, for timing frozen embryo transfer (FET) in natural cycles (NC). In a retrospective study, 112 women with regular menstrual cycles undergoing 132 NC−FET cycles were divided into two groups: group A (n = 61) patients had FET in an NC after ovulation triggering with HCG; group B (n = 71) patients had FET in an NC after spontaneous ovulation was detected. The main outcome measure was the number of monitoring visits at the clinic. Patients in both groups were similar in terms of demographic characteristics and reproductive history. Clinical and laboratory characteristics of fresh and frozen cycles were also found comparable for both groups, as were pregnancy and delivery rates. The number of monitoring visits in group A (3.46 ± 1.8) was significantly lower than in group B (4.35 ± 1.4) (P < 0.0001). In patients undergoing NC−FET, triggering ovulation by HCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome. Ovulation triggering can increase both patient convenience and cycle cost-effectiveness.

Research paper thumbnail of Blastocyst culture and transfer: lessons from an unselected, difficult IVF population

Reproductive BioMedicine Online, 2008

Blastocyst-stage transfer has yielded excellent results in good prognosis IVF patients, but its e... more Blastocyst-stage transfer has yielded excellent results in good prognosis IVF patients, but its efficacy in the general IVF population has not been clearly demonstrated. The objective of this study was to compare cleavage-stage and blastocyst-stage transfer in a mixed, general IVF population. In a prospective, quasi-randomized study, 152 patients underwent 164 treatment cycles. Patients were allocated to cleavage-stage (group 1; n = 94) or blastocyst-stage (group 2; n = 70) transfer. Main outcome measures included implantation, clinical pregnancy and live birth rates. Implantation (11.2% versus 15.5%), clinical pregnancy (34% versus 21%) and live birth rates per transfer (21.3% versus 13.8%) and per started cycle (21.3% versus 11.4%) were all comparable for groups 1 and 2, respectively. Logistic regression analysis revealed that blastocyst culture and transfer reduced the odds for pregnancy in the general IVF population and defined a good prognosis group for blastocyst transfer. Introducing blastocyst culture and transfer to all IVF patients is not advantageous. Blastocyst transfer should be offered primarily to good prognosis patients, and this group should be specifically defined in each clinical set-up.

Research paper thumbnail of Pregnancy Potential of Human Oocytes—The Effect of Cryopreservation

Obstetrical & Gynecological Survey, 1991

In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a r... more In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos? The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos. Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05). The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation.

Research paper thumbnail of Combined gonadotropin releasing hormone agonist/human menopausal gonadotropin therapy (GnRH-a/hMG) in normal, high, and poor responders to hMG

Journal of In Vitro Fertilization and Embryo Transfer, 1991

Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatmen... more Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatment were classified into normal, high, or poor responders. They were routinely offered another cycle with a combination of a gonadotropin releasing hormone agonist and gonadotropin therapy (in order to evaluate whether this combined therapy could improve their response). The gonadotropininduced cycle was compared with the combined therapy cycle. With the combination treatment, in the normal responders the phase of ovarian stimulation was significantly (P < 0.001) prolonged, and the number of follicles and oocytes collected (5.7 +-0.7 vs 3.1 +-0.4) was increased, without any change in serum estradiol level compared to the control cycle. In high responders the number of oocytes was not modified by the combined treatment compared with the control cycle. However, serum estradiol level was significantly (P < 0.005) decreased. The combined therapy did not modify any parameter of response in poor responders. We conclude that the response to combined agonist/gonadotropin therapy is dependent on the patient's own basal response. No improvement in response was expected in poor responders .

Research paper thumbnail of Ovarian stimulation with gonadotropin-releasing hormone (GnRH) analogue improves the in vitro fertilization (IVF) pregnancy rate with both transvaginal and laparoscopic oocyte recovery

Journal of In Vitro Fertilization and Embryo Transfer, 1990

The relative impact of ovarian stimulation protocol and oocyte retrieval technique on success rat... more The relative impact of ovarian stimulation protocol and oocyte retrieval technique on success rates of in vitro fertilization program was studied in 200 patients. Sixtythree patients received gonadotropin-releasing hormone analogue (GnRHa) with human menopausal gonadotropin (hMG), and 137 received hMG only. The GnRHa + hMG protocol resulted in higher pregnancy rates than the hMG-only protocol (19.0 vs 9.5%, respectively; P < 0.01) despite a lower cleavage rate. Oocyte retrieval was performed via laparoscopy in 100 patients and transvaginally in 100 patients. The number of oocytes recovered per cycle was 6.1 + 3.9 with laparoscopy and 7.0 +-3.1 transvaginally. Pregnancy rates were similar for both retrieval techniques (13 and 12%, respectively). A breakdown of these results showed that the advantage for the GnRHa + hMG protocol was not affected by the oocyte retrieval technique. A comparison of simultaneous blood and follicular fluid pH measured every 10 min during laparoscopy and transvaginal oocyte recovery revealed a constant decline in follicular fluid pH during laparoscopy, while no changes were observed during the vaginal procedure. We conclude that the improvement in in vitro fertilization results during the period of our study is due

Research paper thumbnail of The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment

Journal of Assisted Reproduction and Genetics, 1992

A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challe... more A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challenge. Gonadotropinreleasing hormone agonists (GnRHa) have been suggested as a modality for treatment of this condition. In this study, we analyzed the results of 880 in vitro fertilization treatment cycles with respect to modality of ovarian stimulation, degree of hormonal response, and number of oocytes retrieved. In patients with estradiol (E2) levels less than 501 pg/ml on the day of human chorionic gonadotropin administration, 27% pregnancy rate was achieved with clomiphene citrate (CC) combined with human menopausal gonadotropin (hMG), compared to 15.1% (P < 0.005) with hMG alone and 20.8% (NS) with GnRHa and hMG. Pregnancy rates were not lower in these patients compared to patients with higher estradiol levels in the different stimulation protocols, but pregnancy rates were significantly lower in cycles during which three or fewer oocytes were retrieved, compared to those in which four or more oocytes were retrieved (10.8 vs 23.8%; P < 0.0005). In low-retrieval cycles pregnancy rates actually decreased with increasing levels of estradiol. Our results indicate that the number of oocytes retrieved is a better prognostic parameter than E e levels in predicting the outcome of in vitro fertilization treatment and that GnRHa in the long protocol do not seem to be superior to CC combined with hMG for the treatment of poor responders.

Research paper thumbnail of The effect of prolonged cryopreservation on embryo survival

Gynecological Endocrinology, 2002

The purpose of this study was to assess the effects of long-term cryopreservation on the survival... more The purpose of this study was to assess the effects of long-term cryopreservation on the survival and implantation rates of embryos. We performed a matched case-control study comparing 101 women whose embryos were transferred after cryopreservation for 2-9 years, with 101 control women whose embryos were transferred after 6 months or less of cryopreservation. A multiple step-wise logistic regression was performed to determine the independent effect of the duration of cryopreservation, patient age and embryo quality on pregnancy and live birth rates. In the study group, 673 embryos were frozen for 24-108 months and of these 451 were thawed. In the control group, 513 embryos were cryopreserved for up to 6 months and 456 were thawed. The implantation rate was similar (4.5% vs. 5.5%) in both groups. We concluded that the duration of cryopreservation did not adversely affect embryo survival, and prolonged cryopreservation appeared to be a safe treatment option.

Research paper thumbnail of Timing of testicular sperm retrieval procedures and in vitro fertilization–intracytoplasmic sperm injection outcome

Fertility and Sterility, 2001

To compare the outcome of IVF-intracytoplasmic sperm injection (ICSI) using testicular spermatozo... more To compare the outcome of IVF-intracytoplasmic sperm injection (ICSI) using testicular spermatozoa obtained on the day of ovum pick-up (OPU) or on the day before OPU. Retrospective study. An IVF clinic in a university hospital. Forty-seven IVF-ICSI cycles using testicular spermatozoa in 28 couples with the male partner suffering from nonobstructive azoospermia. Sperm retrieval was performed either on the OPU day (23 cycles in 19 patients; group A) or on the day before OPU (24 cycles in 15 patients; group B). Testicular sperm aspiration (TESA) was performed and followed by testicular sperm extraction (TESE) if no spermatozoa could be found. The presence of motile spermatozoa at the time of ICSI and fertilization and clinical pregnancy rates. A similar proportion of motile spermatozoa (60.9% vs. 62.5%), fertilization rate (61.7% vs. 58.9%), and clinical pregnancy rate per transfer (34.8% and 29.2%) were obtained for groups A and B, respectively. Testicular sperm retrieval can be performed on the day before OPU without compromising success. Considerable medical and practical advantages may be offered by further advancement of testicular sperm retrieval procedures to 48 hours before OPU. This approach should thus be further evaluated.

Research paper thumbnail of A computerized model for prediction of repeated implantation failure in IVF-ET

Fertility and Sterility, 2003

graded as "good quality" were derived from zygotes where the ND was 3 or less whereas 11.6% (138/... more graded as "good quality" were derived from zygotes where the ND was 3 or less whereas 11.6% (138/1191) of embryos in the same group developed from ND 4 or more. One thousand and seventy four (88.5%) embryos in Group 2 were derived from zygotes where the ND was Յ3, and 140 (11.5%) of these from NDՆ4 zygotes. In Groups 3, 87.9% embryos (190/216) derived from NDՅ3 zygotes whereas 12.1% embryos (28/216) derived from NDՆ4.

Research paper thumbnail of P-273 Results of round spermatids injection (ROSI) for treatment of defective spermiogenesis

Fertility and Sterility, 1997

Objectives: To determine if embryos cultured for 3 days verses 2 days would increase pregnancy ra... more Objectives: To determine if embryos cultured for 3 days verses 2 days would increase pregnancy rates after transfer to the fallopian tubes. The effects of embryo grade and patient age were also evaluated.

Research paper thumbnail of Incubation with sperm enhances in vitro maturation of the oocyte from the germinal vesicle to the M2 stage

Fertility and Sterility, 1997

To evaluate the effect of sperm in the culture medium on the rate of oocyte maturation in vitro f... more To evaluate the effect of sperm in the culture medium on the rate of oocyte maturation in vitro from the germinal vesicle to the M2 stage. Prospective randomized controlled study. The IVF Unit, Wolfson Medical Center, Holon, Israel. All women in whom oocytes were retrieved at the germinal vesicle stage between December 1995 and March 1996. Oocytes retrieved at the germinal vesicle stage were divided prospectively and randomly into four groups of incubation conditions: group 1, intact germinal vesicle with cumulus; group 2, intact germinal vesicle with sperm cells in the culture medium; group 3, stripped germinal vesicle; and group 4, stripped germinal vesicle with sperm cells. Oocytes were observed 24 hours after retrieval, and the stage of maturation was recorded. Oocytes that reached the M2 stage underwent the intracytoplasmic injection procedure, and the fertilization rate in each group was recorded at 48 hours. Maturation rate from the germinal vesicle to M2 stage and fertilization rate. Each group contained 20 germinal vesicle oocytes. In groups 1 and 2, 2 (10%) and 9 (45%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 1 (5%) and 8 (40%) embryos developed, respectively. The results in group 2 were significantly higher than in group 1. In groups 3 and 4, 6 (30%) and 16 (80%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 5 (25%) and 14 (70%) embryos developed, respectively. Results in group 4 were significantly higher than those in groups 1, 2, and 3. Both methods of oocyte activation (i.e., addition of sperm to the culture medium or removal of the cumulus) enhance oocyte maturation in vitro, but the sperm-incubation method has a more pronounced effect. A combination of both methods leads to an exceptionally high rate of oocyte maturation, followed by a high fertilization rate.

Research paper thumbnail of The effect of coasting on IVF/ICSI outcome

Fertility and Sterility, 2002

Research paper thumbnail of Testicular sperm aspiration and intracytoplasmic sperm injection for persistent infection of the ejaculate

Fertility and Sterility, 1999

To report the successful use of testicular sperm aspiration and intracytoplasmic sperm injection ... more To report the successful use of testicular sperm aspiration and intracytoplasmic sperm injection in the presence of an Escherichia coli-infected ejaculate that previously caused repeated embryo degeneration. Design: Case report. Setting: University medical center.

Research paper thumbnail of In vitro fertilization treatment for severe male factor: a comparative study of intracytoplasmic sperm injection with testicular sperm extraction and with spermatozoa from ejaculate

Journal of assisted reproduction and genetics, 1998

Our purpose was to evaluate whether the source of spermatozoa influences the results of intracyto... more Our purpose was to evaluate whether the source of spermatozoa influences the results of intracytoplasmic sperm injection (ICSI) treatment in couples with severe male-factor infertility. A retrospective analysis of 40 cases of ICSI with testicular-retrieved spermatozoa, matched with 40 cases of ICSI with ejaculated spermatozoa, was performed. We included only couples with normoovulatory females younger than 37 years who were matched according to the day of ovum pickup with the patients in the study group. Eighty cycles were analyzed: 40 cycles using testicular spermatozoa and 40 cycles using ejaculated spermatozoa. In 32 (80%) of the 40 ICSI transcutaneous needle aspiration cycles, we obtained enough spermatozoa to inject all the mature oocytes retrieved. In eight (20%) cases there were not enough spermatozoa to inject all the oocytes. Only 76 (54%) of 141 available oocytes were injected in these eight patients. The oocyte fertilization rates were 42% for the study group and 55.5% fo...

Research paper thumbnail of Pregnancies and live births following ICSI with testicular spermatozoa after repeated implantation failure using ejaculated spermatozoa

Reproductive BioMedicine Online, 2008

The use of testicular spermatozoa for IVF/intracytoplasmic sperm injection (ICSI) is currently in... more The use of testicular spermatozoa for IVF/intracytoplasmic sperm injection (ICSI) is currently indicated exclusively for patients with azoospermia, since a favourable outcome is expected even when very few spermatozoa are present in the ejaculate. Here, a series of four couples with long-standing male factor infertility and multiple failed IVF/ICSI cycles are described. In all couples, the use of ejaculated spermatozoa for ICSI resulted in poor embryo quality and repeated implantation failure. Testicular sperm aspiration was performed in subsequent cycles, and testicular spermatozoa were used for ICSI. Embryo implantation and ongoing pregnancies/deliveries were achieved in all four couples. It is postulated that spermatozoa are subjected to post-testicular damage during sperm transport between the seminiferous tubules and epididymis, with the injection of damaged spermatozoa being the cause for repetitive IVF/ICSI failures. In selected patients, the use of testicular spermatozoa for IVF/ICSI should be considered, even when motile spermatozoa can be identified in the ejaculate.

Research paper thumbnail of Zygote intrafallopian transfer may improve pregnancy rate in patients with repeated failure of implantation

Fertility and Sterility, 1998

To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregn... more To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregnancy rates (PRs) in patients with repeated failure of implantation in IVF-ET cycles. A case-control study. Criteria for patient selection included male factor or unexplained infertility, normal uterine cavity, and at least three failures of implantation in IVF-ET cycles in which at least three embryos were placed per transfer. Data on 70 patients who underwent 92 ZIFT cycles are presented. A control group consisted of patients with the same selection criteria who underwent an additional standard IVF-ET cycle during the same time period. Ovulation induction consisted of down-regulation with GnRH analogue followed by ovarian stimulation with FSH and hMG. Intracytoplasmic sperm injection was performed on the oocytes of all patients with male factor infertility. Zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval. Implantation rates and PRs in the ZIFT and control groups were compared. The PRs and implantation rates were significantly higher in the ZIFT group than in the control group: 34.2% (24/70) and 8.7% (29/333) versus 17.1% (12/70) and 4.4% (13/289), respectively (P = 0.002 and P = 0.04). The cumulative conception rate for two ZIFT cycles was 59.3%. Zygote intrafallopian transfer should be considered a beneficial mode of treatment for patients with repeated failure of implantation in IVF and transcervical ET. More prospective randomized studies are needed to support this observation.

Research paper thumbnail of Hysteroscopy in a program of in vitro fertilization

Journal of Assisted Reproduction and Genetics, 1991

Two hundred twenty-four women underwent hysteroscopic evaluation without anesthesia after at leas... more Two hundred twenty-four women underwent hysteroscopic evaluation without anesthesia after at least two failed attempts of in vitro fertilization and embryo transfer. One hundred fifty-three (68%) women were diagnosed as having mechanical infertility, and abnormal hysteroscopic findings were observed in 32 (21%). Forty-one women were diagnosed as having unexplained infer-tility (18%) and six (15%) had abnormal findings with hysteroscopy. Of

Research paper thumbnail of Midazolam-fentanyl sedation in conjunction with local anesthesia during oocyte retrieval for in vitro fertilization

Journal of Assisted Reproduction and Genetics - J ASSIST REPROD GENET, 1992

... Collier M, O&amp;#x27;Neill C, Ammit AJ, Saunders DM: Measure-ment of human embryo-derive... more ... Collier M, O&amp;#x27;Neill C, Ammit AJ, Saunders DM: Measure-ment of human embryo-derived platelet-activating factor (PAF) using a quantitative bioassay of platelet ... Anaesthesia 1988;43(Suppl):87-89 9. Ben-Shlomo I, Abd-EI-Halim H, Ezry J, Zohar S, Tverskoy M: Midazolam ...

Research paper thumbnail of Neonatal outcome in polycystic ovarian syndrome patients treated with metformin during pregnancy

Journal of Maternal-Fetal and Neonatal Medicine, 2006

The present study aimed to evaluate the effect of metformin exposure during pregnancy on neonates... more The present study aimed to evaluate the effect of metformin exposure during pregnancy on neonates of polycystic ovarian syndrome (PCOS) patients. Neonatal outcomes of 33 women with PCOS treated with metformin during pregnancy were compared to neonatal outcomes of 66 normal healthy women in a retrospective case-control study. The mean birth weight percentile of neonates exposed to metformin in utero during the first trimester was significantly lower than that of neonates delivered to normal healthy matched controls. After controlling for pregnancy complications, this observation became only marginally statistically significant. Although metformin is an attractive option for induction of ovulation in PCOS patients, there is a need for more evidence related to its safety during pregnancy.

Research paper thumbnail of Timing intra-Fallopian transfer procedures

Reproductive BioMedicine Online, 2007

With the gradual decline in the use of zygote intra-Fallopian transfer (ZIFT), current practice i... more With the gradual decline in the use of zygote intra-Fallopian transfer (ZIFT), current practice is to offer ZIFT almost exclusively to patients with repeated implantation failure (RIF). For practical reasons, the procedure is sometimes deferred by 1 day and embryo intra-Fallopian transfer (EIFT) is performed. The aim of the present study was to compare the reproductive outcome of ZIFT versus EIFT. In a retrospective analysis, 176 patients who failed in 7.65 ± 3.7 previous IVF cycles underwent 200 ZIFT and 73 EIFT procedures. Implantation and live birth rates were compared for both groups. Patients in both groups were found comparable for demographic and clinical parameters. Similar numbers of oocytes were retrieved and fertilized in both groups, and 5.2 ± 1.2 zygotes/embryos were transferred. Implantation and live birth rates (10.5 and 26.5% versus 10.9 and 24.7% for ZIFT and EIFT respectively) were comparable. It is concluded that tubal transfer of zygotes and day-2 cleavage stage embryos are equally effective.

Research paper thumbnail of What is the preferred method for timing natural cycle frozen–thawed embryo transfer?

Spontaneous ovulation during a natural menstrual cycle represents a simple and efficient method f... more Spontaneous ovulation during a natural menstrual cycle represents a simple and efficient method for synchronization between frozen embryos and the endometrium. The objective was to compare serial monitoring until documentation of ovulation, with human chorionic gonadotrophin (HCG) triggering, for timing frozen embryo transfer (FET) in natural cycles (NC). In a retrospective study, 112 women with regular menstrual cycles undergoing 132 NC−FET cycles were divided into two groups: group A (n = 61) patients had FET in an NC after ovulation triggering with HCG; group B (n = 71) patients had FET in an NC after spontaneous ovulation was detected. The main outcome measure was the number of monitoring visits at the clinic. Patients in both groups were similar in terms of demographic characteristics and reproductive history. Clinical and laboratory characteristics of fresh and frozen cycles were also found comparable for both groups, as were pregnancy and delivery rates. The number of monitoring visits in group A (3.46 ± 1.8) was significantly lower than in group B (4.35 ± 1.4) (P < 0.0001). In patients undergoing NC−FET, triggering ovulation by HCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome. Ovulation triggering can increase both patient convenience and cycle cost-effectiveness.

Research paper thumbnail of Blastocyst culture and transfer: lessons from an unselected, difficult IVF population

Reproductive BioMedicine Online, 2008

Blastocyst-stage transfer has yielded excellent results in good prognosis IVF patients, but its e... more Blastocyst-stage transfer has yielded excellent results in good prognosis IVF patients, but its efficacy in the general IVF population has not been clearly demonstrated. The objective of this study was to compare cleavage-stage and blastocyst-stage transfer in a mixed, general IVF population. In a prospective, quasi-randomized study, 152 patients underwent 164 treatment cycles. Patients were allocated to cleavage-stage (group 1; n = 94) or blastocyst-stage (group 2; n = 70) transfer. Main outcome measures included implantation, clinical pregnancy and live birth rates. Implantation (11.2% versus 15.5%), clinical pregnancy (34% versus 21%) and live birth rates per transfer (21.3% versus 13.8%) and per started cycle (21.3% versus 11.4%) were all comparable for groups 1 and 2, respectively. Logistic regression analysis revealed that blastocyst culture and transfer reduced the odds for pregnancy in the general IVF population and defined a good prognosis group for blastocyst transfer. Introducing blastocyst culture and transfer to all IVF patients is not advantageous. Blastocyst transfer should be offered primarily to good prognosis patients, and this group should be specifically defined in each clinical set-up.

Research paper thumbnail of Pregnancy Potential of Human Oocytes—The Effect of Cryopreservation

Obstetrical & Gynecological Survey, 1991

In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a r... more In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos? The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos. Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05). The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation.

Research paper thumbnail of Combined gonadotropin releasing hormone agonist/human menopausal gonadotropin therapy (GnRH-a/hMG) in normal, high, and poor responders to hMG

Journal of In Vitro Fertilization and Embryo Transfer, 1991

Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatmen... more Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatment were classified into normal, high, or poor responders. They were routinely offered another cycle with a combination of a gonadotropin releasing hormone agonist and gonadotropin therapy (in order to evaluate whether this combined therapy could improve their response). The gonadotropininduced cycle was compared with the combined therapy cycle. With the combination treatment, in the normal responders the phase of ovarian stimulation was significantly (P < 0.001) prolonged, and the number of follicles and oocytes collected (5.7 +-0.7 vs 3.1 +-0.4) was increased, without any change in serum estradiol level compared to the control cycle. In high responders the number of oocytes was not modified by the combined treatment compared with the control cycle. However, serum estradiol level was significantly (P < 0.005) decreased. The combined therapy did not modify any parameter of response in poor responders. We conclude that the response to combined agonist/gonadotropin therapy is dependent on the patient's own basal response. No improvement in response was expected in poor responders .

Research paper thumbnail of Ovarian stimulation with gonadotropin-releasing hormone (GnRH) analogue improves the in vitro fertilization (IVF) pregnancy rate with both transvaginal and laparoscopic oocyte recovery

Journal of In Vitro Fertilization and Embryo Transfer, 1990

The relative impact of ovarian stimulation protocol and oocyte retrieval technique on success rat... more The relative impact of ovarian stimulation protocol and oocyte retrieval technique on success rates of in vitro fertilization program was studied in 200 patients. Sixtythree patients received gonadotropin-releasing hormone analogue (GnRHa) with human menopausal gonadotropin (hMG), and 137 received hMG only. The GnRHa + hMG protocol resulted in higher pregnancy rates than the hMG-only protocol (19.0 vs 9.5%, respectively; P < 0.01) despite a lower cleavage rate. Oocyte retrieval was performed via laparoscopy in 100 patients and transvaginally in 100 patients. The number of oocytes recovered per cycle was 6.1 + 3.9 with laparoscopy and 7.0 +-3.1 transvaginally. Pregnancy rates were similar for both retrieval techniques (13 and 12%, respectively). A breakdown of these results showed that the advantage for the GnRHa + hMG protocol was not affected by the oocyte retrieval technique. A comparison of simultaneous blood and follicular fluid pH measured every 10 min during laparoscopy and transvaginal oocyte recovery revealed a constant decline in follicular fluid pH during laparoscopy, while no changes were observed during the vaginal procedure. We conclude that the improvement in in vitro fertilization results during the period of our study is due

Research paper thumbnail of The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment

Journal of Assisted Reproduction and Genetics, 1992

A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challe... more A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challenge. Gonadotropinreleasing hormone agonists (GnRHa) have been suggested as a modality for treatment of this condition. In this study, we analyzed the results of 880 in vitro fertilization treatment cycles with respect to modality of ovarian stimulation, degree of hormonal response, and number of oocytes retrieved. In patients with estradiol (E2) levels less than 501 pg/ml on the day of human chorionic gonadotropin administration, 27% pregnancy rate was achieved with clomiphene citrate (CC) combined with human menopausal gonadotropin (hMG), compared to 15.1% (P < 0.005) with hMG alone and 20.8% (NS) with GnRHa and hMG. Pregnancy rates were not lower in these patients compared to patients with higher estradiol levels in the different stimulation protocols, but pregnancy rates were significantly lower in cycles during which three or fewer oocytes were retrieved, compared to those in which four or more oocytes were retrieved (10.8 vs 23.8%; P < 0.0005). In low-retrieval cycles pregnancy rates actually decreased with increasing levels of estradiol. Our results indicate that the number of oocytes retrieved is a better prognostic parameter than E e levels in predicting the outcome of in vitro fertilization treatment and that GnRHa in the long protocol do not seem to be superior to CC combined with hMG for the treatment of poor responders.

Research paper thumbnail of The effect of prolonged cryopreservation on embryo survival

Gynecological Endocrinology, 2002

The purpose of this study was to assess the effects of long-term cryopreservation on the survival... more The purpose of this study was to assess the effects of long-term cryopreservation on the survival and implantation rates of embryos. We performed a matched case-control study comparing 101 women whose embryos were transferred after cryopreservation for 2-9 years, with 101 control women whose embryos were transferred after 6 months or less of cryopreservation. A multiple step-wise logistic regression was performed to determine the independent effect of the duration of cryopreservation, patient age and embryo quality on pregnancy and live birth rates. In the study group, 673 embryos were frozen for 24-108 months and of these 451 were thawed. In the control group, 513 embryos were cryopreserved for up to 6 months and 456 were thawed. The implantation rate was similar (4.5% vs. 5.5%) in both groups. We concluded that the duration of cryopreservation did not adversely affect embryo survival, and prolonged cryopreservation appeared to be a safe treatment option.

Research paper thumbnail of Timing of testicular sperm retrieval procedures and in vitro fertilization–intracytoplasmic sperm injection outcome

Fertility and Sterility, 2001

To compare the outcome of IVF-intracytoplasmic sperm injection (ICSI) using testicular spermatozo... more To compare the outcome of IVF-intracytoplasmic sperm injection (ICSI) using testicular spermatozoa obtained on the day of ovum pick-up (OPU) or on the day before OPU. Retrospective study. An IVF clinic in a university hospital. Forty-seven IVF-ICSI cycles using testicular spermatozoa in 28 couples with the male partner suffering from nonobstructive azoospermia. Sperm retrieval was performed either on the OPU day (23 cycles in 19 patients; group A) or on the day before OPU (24 cycles in 15 patients; group B). Testicular sperm aspiration (TESA) was performed and followed by testicular sperm extraction (TESE) if no spermatozoa could be found. The presence of motile spermatozoa at the time of ICSI and fertilization and clinical pregnancy rates. A similar proportion of motile spermatozoa (60.9% vs. 62.5%), fertilization rate (61.7% vs. 58.9%), and clinical pregnancy rate per transfer (34.8% and 29.2%) were obtained for groups A and B, respectively. Testicular sperm retrieval can be performed on the day before OPU without compromising success. Considerable medical and practical advantages may be offered by further advancement of testicular sperm retrieval procedures to 48 hours before OPU. This approach should thus be further evaluated.

Research paper thumbnail of A computerized model for prediction of repeated implantation failure in IVF-ET

Fertility and Sterility, 2003

graded as "good quality" were derived from zygotes where the ND was 3 or less whereas 11.6% (138/... more graded as "good quality" were derived from zygotes where the ND was 3 or less whereas 11.6% (138/1191) of embryos in the same group developed from ND 4 or more. One thousand and seventy four (88.5%) embryos in Group 2 were derived from zygotes where the ND was Յ3, and 140 (11.5%) of these from NDՆ4 zygotes. In Groups 3, 87.9% embryos (190/216) derived from NDՅ3 zygotes whereas 12.1% embryos (28/216) derived from NDՆ4.

Research paper thumbnail of P-273 Results of round spermatids injection (ROSI) for treatment of defective spermiogenesis

Fertility and Sterility, 1997

Objectives: To determine if embryos cultured for 3 days verses 2 days would increase pregnancy ra... more Objectives: To determine if embryos cultured for 3 days verses 2 days would increase pregnancy rates after transfer to the fallopian tubes. The effects of embryo grade and patient age were also evaluated.

Research paper thumbnail of Incubation with sperm enhances in vitro maturation of the oocyte from the germinal vesicle to the M2 stage

Fertility and Sterility, 1997

To evaluate the effect of sperm in the culture medium on the rate of oocyte maturation in vitro f... more To evaluate the effect of sperm in the culture medium on the rate of oocyte maturation in vitro from the germinal vesicle to the M2 stage. Prospective randomized controlled study. The IVF Unit, Wolfson Medical Center, Holon, Israel. All women in whom oocytes were retrieved at the germinal vesicle stage between December 1995 and March 1996. Oocytes retrieved at the germinal vesicle stage were divided prospectively and randomly into four groups of incubation conditions: group 1, intact germinal vesicle with cumulus; group 2, intact germinal vesicle with sperm cells in the culture medium; group 3, stripped germinal vesicle; and group 4, stripped germinal vesicle with sperm cells. Oocytes were observed 24 hours after retrieval, and the stage of maturation was recorded. Oocytes that reached the M2 stage underwent the intracytoplasmic injection procedure, and the fertilization rate in each group was recorded at 48 hours. Maturation rate from the germinal vesicle to M2 stage and fertilization rate. Each group contained 20 germinal vesicle oocytes. In groups 1 and 2, 2 (10%) and 9 (45%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 1 (5%) and 8 (40%) embryos developed, respectively. The results in group 2 were significantly higher than in group 1. In groups 3 and 4, 6 (30%) and 16 (80%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 5 (25%) and 14 (70%) embryos developed, respectively. Results in group 4 were significantly higher than those in groups 1, 2, and 3. Both methods of oocyte activation (i.e., addition of sperm to the culture medium or removal of the cumulus) enhance oocyte maturation in vitro, but the sperm-incubation method has a more pronounced effect. A combination of both methods leads to an exceptionally high rate of oocyte maturation, followed by a high fertilization rate.

Research paper thumbnail of The effect of coasting on IVF/ICSI outcome

Fertility and Sterility, 2002

Research paper thumbnail of Testicular sperm aspiration and intracytoplasmic sperm injection for persistent infection of the ejaculate

Fertility and Sterility, 1999

To report the successful use of testicular sperm aspiration and intracytoplasmic sperm injection ... more To report the successful use of testicular sperm aspiration and intracytoplasmic sperm injection in the presence of an Escherichia coli-infected ejaculate that previously caused repeated embryo degeneration. Design: Case report. Setting: University medical center.