A Simon

Hebrew University of Jerusalem, Yerushalayim, Jerusalem District, Israel

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Publications (56)161.17 Total impact

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    ABSTRACT: To describe our 2-year experience with preimplantation genetic diagnosis (PGD) for carriers of mutations in the genes BRCA1 and BRCA2, the dilemmas incurred and the lessons learned. We collected data on those carriers of BRCA1/2 mutations who applied for PGD counseling and who decided to proceed. We describe the PGD procedures that were conducted and their outcome. Ten carriers of BRCA1/2 mutations applied for PGD counseling, seven were healthy, and three were BC survivors. Eight women needed in vitro fertilization (IVF) because of coexisting infertility. After counseling, six opted for the procedure and five of them underwent PGD for the BRCA mutation. In one of these PGD, fluorescence in situ hybridization (FISH) analysis for chromosomes 21, X and Y was also performed. Three women conceived, each in the first treatment attempt. One of them gave birth to twins, the second to a singleton and the third is currently pregnant. During the pregnancies, dilemmas concerning PGD confirmation were discussed. PGD is an acceptable reproductive option for BRCA mutation carriers, especially for those who require IVF due to fertility problems. Discussion of this option should be carried out with sensitivity, taking into account the age of the woman, her health, fertility status and emotional state. Confirmatory prenatal diagnosis may not always be encouraged.
    Prenatal Diagnosis 05/2009; 29(5):508-13. DOI:10.1002/pd.2232 · 3.27 Impact Factor
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    ABSTRACT: Human embryonic stem cells (hESCs) suitable for future transplantation therapy should preferably be developed in an animal-free system. Our objective was to develop a laser-based system for the isolation of the inner cell mass (ICM) that can develop into hESC lines, thereby circumventing immunosurgery that utilizes animal products. Hatching was assisted by micromanipulation techniques through a laser-drilled orifice in the zona pellucida of 13 abnormal preimplantation genetic diagnosed blastocysts. ICMs were dissected from the trophectoderm by a laser beam and plated on feeders to derive hESC lines. eight ICMs were isolated from nine hatched blastocysts and gave rise to three hESC lines affected by myotonic dystrophy type 1, hemophilia A and a carrier of cystic fibrosis 405 + 1G > A mutation. Five blastocysts that collapsed during assisted hatching or ICM dissection were plated whole, giving rise to an additional line affected by fragile X. All cell lines expressed markers of pluripotent stem cells and differentiated in vitro and in vivo into the three germ layers. These hESC lines can serve as an important model of the genetic disorders that they carry. Laser-assisted isolation of the ICMs may be applied for the derivation of new hESC lines in a xeno-free system for future clinical applications.
    Human Reproduction 01/2008; 23(1):46-53. DOI:10.1093/humrep/dem351 · 4.57 Impact Factor
  • A Tsafrir · A Simon · A Revel · B Reubinoff · A Lewin · N Laufer
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    ABSTRACT: Older women comprise an increasing portion of patients entering assisted reproduction programmes. This study is a retrospective summary of the files of all patients aged 40 years and older at advent of IVF, between 1995 and 2004, in the authors' centre. In all, 381 women underwent 1217 initiated treatment cycles. Embryo transfer was performed in 62.6% of initiated cycles. Success rates declined with each year after age 40; pregnancy and delivery rates were 13.9 and 9.1% at age 40 and 2.8 and 0.7% at age 45. There were no deliveries at an older age. Logistic regression analysis showed the following factors were independently and significantly related to higher pregnancy rates: younger age, lower dose of gonadotrophins, greater number of mature follicles, endometrial thickness, and number of embryos transferred; prior pregnancy did not influence success. Retrieving more than four oocytes increased pregnancy rates in all women over 40. Transferring 3 embryos or more increased pregnancy rates in all ages, but reached statistical significance only in women aged 40-41 (P < 0.000). It is concluded that in women between 40 and 41 years of age, ovarian response is a major determinant of success, but not in women older than that. Unrealistic expectations may be avoided if accurate data are provided regarding delivery rates per year after age 40.
    Reproductive biomedicine online 03/2007; 14(3):348-55. DOI:10.1016/S1472-6483(10)60878-4 · 3.02 Impact Factor
  • Article: P-76
    A. Revel · N. Laufer · C. Ozcan · A. Simon · A. Tsafrir
  • Neurology 03/2006; 66(4):607-8. DOI:10.1212/01.WNL.0000197984.03391.9B · 8.29 Impact Factor
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    T Elram · A Simon · S Israel · A Revel · D Shveiky · N Laufer
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    ABSTRACT: This study sought to assess the efficacy of intravenous immunoglobulin (IVIg) in improving pregnancy rates and outcome, in a select group of patients with repeated IVF failure and human leukocyte antigen (HLA) similarity. Couples suffering from recurrent IVF failure, defined as at least seven attempts at embryo transfer with no successful implantations, who were found to share at least three HLA loci, and a negative cross-match test, were included in the study. The treatment consisted of two 30 g IVIg doses: one before oocyte retrieval, and a second as soon as a fetal pulse was identified on ultrasound. Ten couples comprised the study group. In total, these couples had undergone 98 IVF cycles with no successful pregnancies prior to initiation of the study. Following a total of 18 IVIg courses, seven women conceived, two women twice. Up to date, five women have delivered at least one live fetus, at 27 weeks or later. One woman is currently in the early third trimester of a twin pregnancy, and one woman had a late abortion at 19 weeks. The results suggest that couples with recurrent IVF failure and HLA similarity, may benefit from IVIg treatment.
    Reproductive biomedicine online 01/2006; 11(6):745-9. DOI:10.1016/S1472-6483(10)61694-X · 3.02 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) with prolonged anovulation had resulted in endometrial carcinoma in a 43-year-old woman. Since she and her husband did not share common biological children, they requested fertility preservation. Due to the woman's age, high dose progesterone and postponing surgery were both considered inappropriate. We therefore proposed oocyte retrieval from the ovaries removed by staging laparotomy followed by in vitro maturation and ICSI. Surrogacy could then enable a future pregnancy. Fourteen of 17 (82%) retrieved oocytes matured in vitro. Following ICSI, eight embryos (two at the pronuclear stage and six cleaved) were cryopreserved. To the best of our knowledge, this is the first report of oocyte aspiration, maturation and fertilization from an ovary removed by laparotomy.
    Human Reproduction 08/2004; 19(7):1608-11. DOI:10.1093/humrep/deh241 · 4.57 Impact Factor
  • A Revel · A Safran · N Laufer · A Lewin · B E Reubinov · A Simon
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    ABSTRACT: It is uncertain how long IVF units can keep frozen embryos. Few data exist on success of embryo transfer for embryos that have been cryopreserved for many years. We report the delivery of healthy twins following the transfer of embryos cryopreserved for 12 years. To the best of our knowledge, this is the longest reported successful human embryo freezing.
    Human Reproduction 03/2004; 19(2):328-9. DOI:10.1093/humrep/deh046 · 4.57 Impact Factor
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    ABSTRACT: There are various successful protocols for artificial endometrial preparation, comprising induction of endometrial proliferation with estrogens and secretory transformation with progestins. The aim of this prospective randomized study was to evaluate a simplified approach for endometrial preparation, comparing two constant doses of oral estradiol combined with a novel low-dose vaginal natural progesterone preparation (100 mg Endometrin tablets). Twenty-nine patients were enrolled in the study and divided randomly into two groups. Both groups received oral estradiol tablets from the beginning of menstruation, group A (15 patients) receiving 4 mg/day divided into two doses of 2 mg each, and group B (14 patients) receiving 6 mg/day divided into three doses. Serum estradiol and progesterone and sonographic thickness of the endometrium were measured on the 1st day of menstruation and on the 6th, 11th, 16th and 21st days of the artificial cycle. Following the first 12 days of estradiol priming, with an endometrial thickness of > or = 8 mm, Endometrin vaginal tablets 100 mg were added twice a day for 10 days. On the 21st cycle day, an endometrial biopsy was taken from all patients using Pipelle. In all 29 patients, appropriate changes in estradiol, progesterone and endometrial thickness were observed. Estradiol levels were significantly higher in the 6 mg/day group on days 6 and 11, but no significant difference was noted in serum progesterone level and endometrial thickess between groups. Histological evaluation of endometrial biopsies, on the 21st day, revealed adequate late-secretory endometrium in 14/15 (93.3%) patients of group A and in 13/14 (92.9%) patients of group B. In conclusion, our results demonstrate that an appropriate endometrial secretory transformation may be induced using an economical regimen of fixed low-dose oral estradiol (4 mg/day) and low-dose vaginal progesterone tablets (Endometrin 100 mg twice daily).
    Gynecological Endocrinology 04/2002; 16(2):131-6. DOI:10.1080/713603032 · 1.33 Impact Factor
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    ABSTRACT: The objective of this retrospective study, which included 51 men with non-obstructive azoospermia, was to evaluate the predictive value of the results of the first sperm recovery attempt on the probability for sperm recovery in a second attempt. A positive testicular fine needle aspiration (TEFNA) was defined as the recovery of any number of mature sperm. At the first and second TEFNA attempts, mature sperm were recovered in 33 (64.7%) and 25 (49%) of 51 patients respectively. In 23 of the 33 (69.7%) patients with a positive first TEFNA, sperm were recovered at both attempts, whereas in only two of 18 (11.1%) with a negative first TEFNA, sperm were recovered at the second attempt. Our analysis revealed a high predictive value of the first TEFNA for sperm recovery at the subsequent attempt, with a mean positive predictive value of 69.7%, with the highest probability being 90.9% in hypospermatogenesis, 72.7% in Sertoli cell-only pattern, 75% in tubular hyalinization, and the lowest being 28.6% in maturation arrest. The mean negative predictive value was 88.9%, which was high in all categories (80% in Sertoli cell-only pattern and 100% in maturation arrest and tubular hyalinization). A second TEFNA attempt should be offered to all non-obstructive azoospermic patients with a positive first TEFNA. Patients with a negative first TEFNA may undergo a repeated attempt, but a donor sperm back-up is strongly advised.
    Human Reproduction 02/2002; 17(1):139-42. DOI:10.1093/humrep/17.1.139 · 4.57 Impact Factor
  • Reproductive biomedicine online 01/2002; 4:39. DOI:10.1016/S1472-6483(12)60081-9 · 3.02 Impact Factor
  • A Revel · M Klein · M Gomori · A Simon · M Nadjari
    The Journal of the American Association of Gynecologic Laparoscopists 08/2001; 8(3):S59. DOI:10.1016/S1074-3804(01)80196-1 · 1.61 Impact Factor
  • Fertility and Sterility 09/2000; 74(3). DOI:10.1016/S0015-0282(00)00956-0 · 4.59 Impact Factor
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    S J Fasouliotis · A Simon · N Laufer
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    ABSTRACT: To investigate the various methods of evaluation and treatment of patients with a low response to controlled ovarian hyperstimulation in assisted reproductive technologies (ART). Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches. While a universally accepted definition for low responders is still lacking, these patients are reported to represent about 10% of the ART population. Several ovarian reserve screening techniques have been proposed; however, currently the best-characterized and most sensitive screening tools available are the basal day 3 serum follicle-stimulating hormone level and the clomiphene citrate challenge test. When abnormal, these tests allow physicians to counsel patients that their prognosis for conception is poor. Although the presence of a normal result does indicate better long-term chances for conception, on age-related decline in fecundity remains and patient age should still be considered when counseling patients with normal screening results. Several stimulation protocols have been applied in the low-response group with varying success. Recent studies show that the use of a minidose gonadotropin-releasing hormone-agonist protocol may result in significantly decreased cycle cancellations as well as increased clinical and ongoing pregnancies, and thus is proposed as a first-line therapy. Studies evaluating supplementary forms of treatment to the ovulation induction regimen show improved outcome when pretreating with oral contraceptives, whereas there seems to be no benefit from cotreatment with growth hormone or glucocorticoids. Blastocyst culture and transfer and assisted hatching in low responders are still under evaluation, whereas natural cycle in vitro fertilization may be used in cases of repeated failures as a last option before resorting to oocyte donation or adoption. Future possible forms of treatment like in vitro maturation of immature human oocytes, cytoplasm, and nuclear transfer currently are experimental in nature and their efficacy has still to be proven. The evaluation and treatment of low responders in ART remains a challenge. Understanding of the underlying etiology and pathophysiology of this disorder may help the clinician to approach it successfully.
    Journal of Assisted Reproduction and Genetics 09/2000; 17(7):357-73. DOI:10.1023/A:1009465324197 · 1.72 Impact Factor
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    A Simon · A Hurwitz · B S Zentner · Y Bdolah · N Laufer
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    ABSTRACT: Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost.
    Human Reproduction 11/1998; 13(1O):2712-7. DOI:10.1093/humrep/13.10.2712 · 4.57 Impact Factor
  • J S Younis · A Simon · N Laufer
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    ABSTRACT: To gain insight into the physiology of human endometrial development after artificial preparation with estrogen (E) and P, before oocyte donation. Review and analysis of relevant studies published in the last decade, identified through the literature and Medline searches. Oocyte donation represents a unique in vivo experimental model in the human that permits the study of endometrial development under controlled variable conditions. Early studies have shown that adequate endometrial preparation can be achieved by sequential E and P only. The successful implementation of the simplified approach to oocyte donation demonstrated that satisfactory endometrial receptivity is not dependent on incremental administration of E and P and similarly can be achieved by fixed dosages of these steroids. Moreover, numerous clinical oocyte donation studies have shown that both physiologic and supraphysiologic levels of E and P have resulted in good endometrial development and pregnancy rates, underlining the relative insensitivity of the endometrium to extreme hormonal conditions. In addition, it has been clarified that the endometrium is tolerant of some manipulations during the follicular phase. Contrary to morphological studies that demonstrated preservation of endometrial preparation after luteal E depletion, preliminary evidence suggests that the functional capacity of the endometrium could be affected adversely. In contrast to early oocyte donation studies, which indicated a correlation between morphologic integrity and functional capacity of the endometrium, some evidence presented in this review demonstrates that adequate endometrial morphology does not always imply normal endometrial receptivity.
    Fertility and Sterility 01/1997; 66(6):873-84. · 4.59 Impact Factor
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    ABSTRACT: To assess the potential involvement of cytokines and nitrites in the hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS). A controlled clinical study comparing peritoneal fluid (PF) from patients with severe OHSS and from non-OHSS controls. Women hospitalized with severe OHSS in three tertiary medical centers. Twelve patients with severe OHSS necessitating paracentesis and 20 non-OHSS controls. The criteria for ultrasound-guided paracentesis were tense ascites, hydrothorax, hemoconcentration, or oliguria. Interleukin (IL) 1 beta IL-1 receptor agonist, IL-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) levels in PF were assayed by ELISA; nitrites were measured by the "Griess" reaction. Estradiol and P were determined by RIA. Ovarian hyperstimulation syndrome patients had significantly higher PF IL-6 (3,523 versus 30 pg/mL), TNF alpha (14 versus 4.2 pg/mL), and IL-8 (1,695 versus 900 pg/mL). In the serum, only IL-6 levels were significantly higher (375 versus 11 pg/mL). Conversely, nitrite levels were significantly lower in PF of OHSS patients (0.5 versus 34 nmol/mL). Interleukin 1 levels were higher and IL-1 receptor antagonist levels were lower in OHSS patients, suggesting potentially increased biologic potency of IL-1. These findings suggest that these substances could be involved in mediating the capillary hyperpermeability characterizing this syndrome.
    Fertility and Sterility 08/1996; 66(1):66-71. · 4.59 Impact Factor
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    ABSTRACT: A genetic assay by single blastomere analysis was developed for rhesus (RhD) blood group typing of early cleavage stage embryos. The method, which is based on the simultaneous amplification of an RhD-specific sequence and an internal control in single cells, was applied for the selective transfer of RhD-negative embryos in a family of an RhD sensitized woman and a heterozygote partner. The RhD status of two out of three biopsied embryos was determined. According to their amplified products, both were typed as RhD-negative and transferred to the uterus. Pregnancy was not achieved.
    Molecular Human Reproduction 02/1996; 2(1):60-2. · 3.75 Impact Factor
  • A Simon · N Laufer
    Israel journal of medical sciences 12/1995; 31(11):652-6.
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    ABSTRACT: A randomized prospective study was undertaken to compare low and standard luteinizing hormone-releasing hormone agonist (LHRHa) dosage used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization (IVF). A total of 42 ovulatory patients with mechanical infertility were administered 0.5 mg/day LHRHa (Decapeptyl) from day 21 of their cycles for 14 days. Following down-regulation, patients were randomly allocated to continue with the same dose of LHRHa (22 patients, group A) or to receive a lower dose of 0.1 mg/day LHRHa (20 patients, group B) during folliculogenesis. Luteal phase was supported by daily i.m. progesterone (50 mg) injections and human chorionic gonadotrophin (HCG; 1500 IU) every 4 days. Ovarian response, human menopausal gonadotrophin (HMG) dosage used for induction of ovulation, evidence of premature luteinization, and clinical and laboratory IVF outcome, were compared between groups A and B. The two groups were comparable in respect of: age (32.6 +/- 0.7 and 33.0 +/- 0.9 years), HMG dosage (33.0 +/- 1.6 and 36.0 +/- 2.5 ampoules), day of HCG (11.2 +/- 0.3 and 12.2 +/- 0.4), oocytes/patient (13.3 +/- 1.0 and 12.9 +/- 1.3), fertilization rate (68.5 and 65.2%), cleavage rate (95% for both), pregnancy/embryo transfer (32 and 35%) and implantation rate (10.8 and 10.5%), for groups A and B respectively. There was no evidence of premature luteinization or luteolysis in either group. It was concluded that lowering the dose of LHRHa to 0.1 mg/day during folliculogenesis had no adverse effect on ovarian response or clinical results. However, it had no advantage in reducing the HMG dose used for ovulation induction.
    Human Reproduction 11/1994; 9(10):1813-7. · 4.57 Impact Factor

Publication Stats

683 Citations
161.17 Total Impact Points


  • 1989–2009
    • Hebrew University of Jerusalem
      • Department of Obstetrics and Gynecology
      Yerushalayim, Jerusalem District, Israel
  • 1984–2004
    • Hadassah Medical Center
      • Department of Obstetrics and Gynaecology
      Yerushalayim, Jerusalem District, Israel
  • 1986
    • Shaare Zedek Medical Center
      • Department of Obstetrics and Gynecology
      Yerushalayim, Jerusalem District, Israel