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Ariel Revel

Publications and source records attributed to Ariel Revel.

At least 19 recordsLinked to original sources

Should ovarian cryopreservation be offered to girls with cancer.

Current therapy of childhood cancer makes long-term survival a realistic outcome for most patients. However, some treatment regimens entail a significant risk of infertility. No established method for preservation of female fertility is currently available. Ovarian cryopreservation is an experimental technology that is being offered with increasing frequency to women undergoing cancer therapy. It has not yet been reported in children and adolescent girls. The aim of this review is to stimulate discussion on the possibility of performing ovarian cryopreservation in pre-menarcheal girls in advance of therapies that may induce ovarian failure. We present a multi-disciplinary discussion of the risks and benefits associated with the procedure and propose guidelines for its implementation. We propose that all girls about to receive treatment that has a high risk for infertility be offered consultation about the possibility of ovarian cryopreservation.

Adolescent↗

Endometrial receptivity markers, the journey to successful embryo implantation.

Human embryo implantation is a three-stage process (apposition, adhesion and invasion) involving synchronized crosstalk between a receptive endometrium and a functional blastocyst. This ovarian steroid-dependent phenomenon can only take place during the window of implantation, a self-limited period of endometrial receptivity spanning between days 20 and 24 of the menstrual cycle. Implantation involves a complex sequence of signalling events, consisting in the acquisition of adhesion ligands together with the loss of inhibitory components, which are crucial to the establishment of pregnancy. Histological evaluation, now considered to add little clinically significant information, should be replaced by functional assessment of endometrial receptivity. A large number of molecular mediators have been identified to date, including adhesion molecules, cytokines, growth factors, lipids and others. Thus, endometrial biopsy samples can be used to identify molecules associated with uterine receptivity to obtain a better insight into human implantation. In addition, development of functional in vitro systems to study embryo-uterine interactions will lead to better definition of the interactions existing between the molecules involved in this process. The purpose of this review was not only to describe the different players of the implantation process but also to try to portray the relationship between these factors and their timing in the process of uterine receptivity.

Animals↗

Sibling oocyte submission to IVF and ICSI in unexplained infertility patients: a potential assay for gamete quality.

In order to reduce total fertilization failure in unexplained infertility, sibling oocytes were submitted to both conventional IVF and intracytoplasmic sperm injection (ICSI). Two groups of ICSI embryos were compared in unexplained infertility patients: those derived from ICSI when IVF had failed to fertilize, and those derived from ICSI while their sibling oocytes were fertilized by IVF. The outcome of oocytes fertilized exclusively by ICSI (essential ICSI, n = 749) was compared with those fertilized both by IVF and ICSI (non-essential ICSI, n = 957) in all IVF patients treated for unexplained infertility at the Hadassah Hospital (1999-2002). The latter group was further subdivided into ICSI and IVF embryos. Total fertilization rate was 54%. Fertilization rates by ICSI were lower in the essential ICSI compared with the non-essential ICSI group, at 65 and 73% (P < 0.025). Pregnancy rates per embryo transfer in the essential ICSI group (49%), ICSI derived embryos group (55%) and IVF derived embryos (44%) from the non-essential ICSI group, were similar. Implantation rates were lower in the essential ICSI group as compared with the non-essential ICSI group (21 versus 32% respectively; P < 0.05) and 26% for IVF embryos. In conclusion, essential ICSI was associated with lower fertilization and implantation rates.

Adult↗

Heparanase improves mouse embryo implantation.

OBJECTIVE: To improve mouse embryonic implantation by recombinant heparanase supplementation. Heparanase, an endoglycosidase-degrading heparan sulfate proteoglycan, may have a role in embryonic implantation because of its enzymatic, angiogenic, and adhesive properties. Increasing endometrial receptivity could improve one of the most difficult pathologies in human fertility. DESIGN: Comparison between mouse blastocysts obtained after 24-hour incubation of morulae with or without heparanase. SETTING: Experimental laboratory in a medical center. ANIMAL(S): Mice. INTERVENTION(S): Morulae were flushed from CB6F1 female mice and incubated for 24 hours at 37 degrees C in M16 medium supplemented with 0.1 mg/mL heparanase (n = 203), with albumin (n = 60), or with medium alone (n = 258). MAIN OUTCOME MEASURE(S): Blastocysts were evaluated by heparanase immunostaining (n = 10), activity assay (n = 283), and transfer to foster mice uterine horns (n = 228). The number of implantation sites was compared. RESULT(S): Immunostaining demonstrated that heparanase is constitutively expressed in mouse morulae and blastocyts. Heparanase supplementation resulted in increased staining and enzymatic activity in blastocyts. Implantation rates for the heparanase, M16 medium, and albumin groups, were 36.9%, 17.8%, and 20%, respectively (P<.01). CONCLUSION(S): Heparanase was found to be constitutively expressed by blastocyst-stage embryos. Moreover, the amount of heparanase was markedly increased by incubation of morulae with recombinant heparanase, evaluated by immunostaining and enzymatic activity. Heparanase supplementation resulted in approximately a twofold increase in embryo implantation rate in vivo. Taken together, these data suggest that heparanase is actively involved in embryo implantation.

Animals↗

In vitro fertilization-intracytoplasmic sperm injection success rates with cryopreserved sperm from patients with malignant disease.

OBJECTIVE: To describe the success rate of intracytoplasmic sperm injection (ICSI) using thawed cryopreserved sperm in male cancer patients. DESIGN: Retrospective consecutive study. SETTING: IVF unit in a tertiary university hospital. PATIENT(S): Twenty-one couples treated by ICSI using the frozen-thawed sperm of husbands treated for cancer. INTERVENTION(S): Follow-up of all treatments by ICSI. MAIN OUTCOME MEASURE(S): Pregnancy rate, sperm count, and fertilization rate. RESULT(S): Male patients being treated for cancer froze between one and 29 sperm samples. Post-thaw sperm count ranged from 1 x 10(5) to 106 x 10(6). The mean fertilization rate by ICSI was 60% (range, 33%-100%), and the pregnancy rate was 42%. Twenty-six pregnancies were obtained resulting in 23 children (13 singleton and 10 twins) and eight spontaneous abortions (31%). Delivery was obtained in 12 of the 21 treated couples (57%). The lowest total motile sperm count that resulted in a pregnancy was 1 x 10(5). CONCLUSION(S): Male cancer patients should be encouraged to freeze numerous sperm samples even when sperm count and motility are poor. In these cases, ICSI is a powerful technique compared with intrauterine injection since thawed sperm samples with poor parameters can produce relatively high fertilization rates resulting in normal pregnancies and deliveries. The possibility to repeat treatments even in the face of a limited number of sperm samples appears to be of importance.

Adult↗

How often are endometrial polyps malignant?

OBJECTIVE: Endometrial polyps are a frequent pathology encountered during pelvic sonography and diagnostic hysteroscopies. The true incidence of malignant endometrial polyps is unknown. The estimations range from 0.5 to 4.8%. The objective of this study was to investigate the frequency of malignant endometrial polyps, and to characterize the hysteroscopic image of these polyps. METHODS: The study included 300 consecutive women with endometrial polyps who underwent hysteroscopic polypectomy. Patients' characteristics, operative findings, and pathology reports were analyzed. RESULTS: Four of the 300 endometrial polyps removed by operative hysteroscopy were malignant (1.3%). Patients with malignant polyps were symptomatic peri- or postmenopausal women. All asymptomatic polyps in this series were found to be benign. We could not identify any distinct hysteroscopic feature of malignancy. CONCLUSIONS: Our study shows that about 1.5% of endometrial polyps may be malignant. This finding reinforces the indication for removal of symptomatic endometrial polyps, preferably by a hysteroscopic procedure. The significance of asymptomatic uterine polyps has still to be determined.

Adult↗

Should laparoscopy be a mandatory component of the infertility evaluation in infertile women with normal hysterosalpingogram or suspected unilateral distal tubal pathology?

OBJECTIVE: To assess the diagnostic benefit of laparoscopy in infertile women with normal hysterosalpingography (HSG) or suspected unilateral pathology on HSG. STUDY DESIGN: Charts of infertile women that underwent complete infertility evaluation between 1996 and 1998 were retrospectively reviewed. Eighty-six patients in whom both HSG and laparoscopy were performed were included in the study. HSG results were compared with laparoscopic findings and the suggested treatment based on HSG results was compared with the treatment plan based on laparoscopic findings. RESULTS: Among 63 patients with a normal HSG or suspected unilateral tubal pathology, who were assigned to ovulation induction and intrauterine insemination (IUI), 60 patients were found to have laparoscopic findings that did not necessitate any change in the original treatment plan. In three patients (4.8%), abnormalities discovered at laparoscopy were of such an extent that a change in the original treatment regimen and referral to in vitro fertilization (IVF) was needed. Among 23 patients with suspected bilateral tubal occlusion on HSG, 16 patients (69.6%) were found to have an abnormal laparoscopy with bilateral tubal adhesions, 6 patients (26%) had unilateral tubal adhesions, and 1 patient (4.3%) had pelvic adhesions with no obstruction. These latter findings led to changes in the original treatment plan of these seven patients from IVF to ovulation induction and IUI. CONCLUSIONS: Laparoscopy may be omitted in women with normal HSG or suspected unilateral distal tubal pathology on HSG, since it was not shown to change the original treatment plan indicated by HSG in 95% of the patients. However, laparoscopy should be recommended in cases with suspected bilateral tubal occlusion on HSG, since it altered the original treatment plan in 30% of the patients from IVF to induction of ovulation with IUI. The reassuring results found in the present study may be related to the low prevalence of pelvic inflammatory diseases and endometriosis in our population.

Adult↗

Mouse embryos generated from frozen-thawed oocytes can successfully survive a second cryopreservation.

BACKGROUND: To determine whether mouse embryos generated from frozen-thawed oocytes can successfully survive a second cryopreservation. METHODS: Immature C57BL6*BALB/c female mice underwent superovulation and the collected oocytes were divided into three groups. Group A oocytes (n = 107) underwent IVF. Group B oocytes (n = 167) underwent IVF and embryos generated were then cryopreserved. Group C oocytes (n = 94) were cryopreserved, thawed and underwent IVF. Two-four-cell stage embryos were re-cryopreserved and thawed. Embryos from all groups were then cultured to the blastocyst stage. RESULTS: Cleavage rates to the 2-4-cell stage were 78, 71 and 46% for groups A, B and C respectively. Blastulation rates from 2-4 cell-stage embryos were 37/83 (45%), 27/118 (23%) and 8/35 (23%) for groups A, B and C respectively. Development to blastocysts was observed in 37/107 oocytes (35%), 27/167 oocytes (16%) and only 8/94 oocytes (9%) for groups A, B and C respectively. CONCLUSION: Oocyte cryopreservation results in reduced fertilization rates. Embryo cryopreservation reduces blastulation rates by half regardless of whether the oocytes were fertilized fresh or frozen-thawed. Nevertheless, embryos generated from cryopreserved oocytes can survive cryopreservation and develop to the blastocyst stage at rates comparable with embryos obtained from fresh oocytes.

Animals↗

Utero-ovarian morphology and blood flow after tubal ligation by the Pomeroy technique.

OBJECTIVES: The objectives of this study were to evaluate ovarian sonographic morphology and pelvic blood flow in patients who had undergone bilateral tubal ligation by the Pomeroy technique. DESIGN: Twenty women who had undergone bilateral tubal ligation during cesarean section by the Pomeroy techniques were compared to 20 matched controls who had undergone cesarean section alone. Ovarian morphology as well as ovarian and uterine pulsatility index (PI), resistance index and peak systolic velocity were evaluated using transvaginal sonography and Doppler velocimetry. RESULTS: Patients post tubal ligation by the Pomeroy technique were found to have a significantly higher rate of polycystic appearance of the ovaries (60% vs. 5%; p < 0.005). Six patients (30%) had post tubal ligation symptoms, as compared to none of the controls. Five of the six symptomatic tubal ligation patients (83%) had ovarian polycystic appearance, which was not significantly different than asymptomatic patients. Ovarian artery PI was significantly higher in symptomatic patients (2.7 +/- 1.9) compared to asymptomatic patients (1.5 +/- 0.9) (p < 0.05). CONCLUSIONS: We therefore conclude that patients post bilateral tubal ligation by the Pomeroy technique may acquire an ovarian polycystic appearance and increased ovarian PI, which may be associated with a tendency to develop post tubal ligation symptoms.

Adult↗

Ovarian tissue banking for cancer patients: is ovarian cortex cryopreservation presently justified?

The effect of chemotherapy and radiotherapy on future fertility is of concern to patients and their families. Whereas sperm banking is commonly performed, female gametes are not so amenable to cryopreservation. One alternative includes postponing cancer treatment to enable ovulation induction and oocyte aspiration. Whenever possible, retrieved oocytes should be fertilized in vitro prior to cryopreservation. Frozen embryos could serve to produce pregnancies if ovarian failure occurs. Donor sperm can be offered to single patients, as frozen-thawed unfertilized oocytes yield poor pregnancy rates. Ovarian cortex cryopreservation should still be considered an experimental technology as no pregnancies have been obtained in humans. Therefore, ovarian cortex banking should be used only for young girls, adolescents and when IVF is contraindicated. Reattachment of ovarian vasculature could prevent ischaemic follicular loss and enable ovarian transplantation in the future. This procedure is currently under investigation in animals. At the present time, we recommend urgent IVF in most patients requesting fertility preservation. Ovarian cryopreservation should be offered when emergency IVF is not possible.

Animals↗

Does hysteroscopy produce intraperitoneal spread of endometrial cancer cells?

Hysteroscopy is the tool of choice for the evaluation of the endometrial cavity, including the assessment of abnormal uterine bleeding (AUB). The combination of endometrial biopsy and diagnostic hysteroscopy could replace dilation and curettage in most patients. However, hysteroscopy might disseminate endometrial cells into the peritoneum, thereby potentially raising the stage and decreasing the survival of a patient with endometrial cancer. The purpose of this article is to explore the dilemma of whether hysteroscopy produces intraperitoneal spread of endometrial cancer cells, and, if the answer is yes, what is the prognostic significance of isolated malignant cells in the peritoneal cavity. We conducted a literature search using MEDLINE using the following key words: hysteroscopy, endometrial carcinoma, and dissemination for the years 1980 through 2001. Retrospective data shows a correlation between fluid-based hysteroscopy and the presence of cancer cells in the peritoneal cavity. It cannot, however, be determined whether positive peritoneal washings are the result of hysteroscopy or whether the endometrial cells are found in the peritoneum as a result of other mechanism. Because no prospective, randomized studies have been performed on the dissemination of cancer cells by diagnostic hysteroscopy, no definite conclusions can be made concerning the risk of diagnostic hysteroscopy. In addition, the prognostic significance of isolated malignant cells in the peritoneal cavity of women with endometrial cancer is unclear. Although there might be an increased risk of peritoneal contamination by cancer cells after hysteroscopy, there is currently no evidence that these patients face worse prognosis than patients who have undergone other diagnostic procedures.

Dilatation and Curettage↗

Hyaluronic acid can successfully replace albumin as the sole macromolecule in a human embryo transfer medium.

OBJECTIVE: To examine the effect on pregnancy and implantation rates when highly purified, fermentation-based hyaluronic acid was the only macromolecule supplement to the transfer medium in a human IVF program. DESIGN: Prospective randomized study. SETTING: In vitro fertilization center in an academic medical institution. PATIENT(S): Eighty patients were included in this prospective randomized double blind study. Inclusion criteria were age </=35 years, the availability of at least three embryos eligible for transfer on day 3 after fertilization, and no more than three previous embryo transfer attempts. INTERVENTION(S): All embryos were cultured in P1 medium containing 10% synthetic serum substitute (SSS) until day 3. Patients were randomly allocated to two groups; in treatment group A (40 patients), embryos were transferred to P1 medium supplemented with 0.5 mg/mL hyaluronic acid for 5-10 min before their intrauterine transfer. In the control group B (40 patients), embryos were transferred, as routinely performed, in P1 medium containing 10% SSS. MAIN OUTCOME MEASURES: Clinical pregnancy and implantation rates. RESULT(S): The mean age of the female partner was 28.7 +/- 3.3 years and 29.7 +/- 3.8 years for groups A and B, respectively. In group A, 103 embryos were transferred and in group B, 97 embryos were transferred for a similar mean number of 2.6 +/- 0.6 and 2.4 +/- 0.5 embryos/transfer, respectively. Twenty-five pregnancies were achieved in group A, and 21 pregnancies in group B. This led to a comparable clinical pregnancy and implantation rates of 62.5% and 34% as compared to 52% and 26.8% for groups A and B, respectively. CONCLUSION(S): Hyaluronic acid can successfully replace albumin as a sole macromolecule in a human embryo transfer medium and result in high pregnancy and implantation rates. The use of this supplement is an important step in the development of human embryo culture media free of blood-derived additives.

Albumins↗

Protecting female fertility from cancer therapy.

Recent advances in cancer therapy have improved the long-term survival of young cancer patients who are then commonly faced with iatrogenic infertility and premature ovarian failure. Preservation of fertility potential has thus become a major goal and could be realized by preventing ovarian toxicity or by cryopreservation of reproductive cells (i.e. oocytes, embryos) and tissues (i.e. ovarian cortex). GnRH analogs prevent chemotherapy-induced-ovarian-damage in rats, however human results are controversial. Anti-apoptotic agents (i.e. sphingosine-1-phosphate) may present an innovative treatment to prevent oocyte destruction during cancer therapy. Although cryopreservation of mouse oocytes is successful, the results obtained in other mammalian species were worse, probably due to their extreme sensitivity to suboptimal conditions during the process of cryopreservation. This resulted in low oocyte survival and fertilization rates, a high incidence of polyploidy, and poor embryonic developmental ability. Ovarian tissue cryopreservation is currently considered as the optimal procedure for follicle banking. Transplantation offers the best prospect of using frozen-thawed ovarian tissue, since no reliable ovarian in-vitro culture technology exists.

Animals↗

Hysteroscopic treatment of intrauterine lesions in premenopausal and postmenopausal women.

STUDY OBJECTIVE: To compare the safety and efficacy of hysteroscopic surgery in the management of intrauterine lesions in premenopausal and postmenopausal women and, in particular, to investigate whether glycine absorption is different between these populations. DESIGN: Comparative study (Canadian Task Force classification II-2). SETTING: Tertiary care university hospital. PATIENTS: Thirty postmenopausal and 78 premenopausal women with intrauterine polyps or myomas. INTERVENTION: Hysteroscopic myomectomy or polypectomy. MEASUREMENTS AND MAIN RESULTS: One hundred eight procedures were completed successfully by hysteroscopy; in two cases myomectomy was completed in a second operation for a deeply embedded myoma. No major complications occurred in either group. Median operating time, mean glycine absorption, and median postoperative hospital stay were not significantly different between groups. During mean follow-up of 15 months (range 1-39 mo), four women underwent hysterectomy (1 for endometrial cancer, 1 for complex hyperplasia with atypia, 2 for pelvic pain and menorrhagia). CONCLUSION: Hysteroscopic surgery is an effective and safe therapeutic option for intrauterine lesions regardless of a woman's menopausal status.

Adult↗

Investigation of the infertile couple: hysteroscopy with endometrial biopsy is the gold standard investigation for abnormal uterine bleeding.

During the last decade hysteroscopy has become the tool of choice for the evaluation of the endometrial cavity, including for assessment of abnormal uterine bleeding (AUB). Many clinicians would consider that, in most patients, the combination of transvaginal sonography and out-patient endometrial biopsy with diagnostic hysteroscopy could replace the need for dilation and curettage. Hysteroscopy was reported to have sensitivity, specificity, negative predictive value and positive predictive value of 94.2, 88.8, 96.3 and 83.1% respectively, in predicting normal or abnormal endometrial histopathology. The highest accuracy of hysteroscopy was in diagnosing endometrial polyps, whereas the worst result was in estimating hyperplasia. Therefore, since the incidence of focal lesions in patients with AUB is high, it seems that the most beneficial approach is to proceed with hysteroscopy complemented by endometrial biopsy early in the assessment of AUB. Nevertheless, the usage of distension media to flush the uterine cavity raises the concern that when the endometrium harbours pathology, there is the potential risk of retrograde dissemination of malignant cells into the peritoneal cavity. The clinical significance of the dissemination of endometrial cells during hysteroscopy is still undetermined.

Female↗