Anat Safran

At what age can human oocytes be obtained

OBJECTIVE To determine whether oocyte retrieval and in vitro maturation (IVM) is effective in girls undergoing fertility preservation before cancer treatment. DESIGN Cohort study. SETTING Tertiary university medical center. PATIENT(S) Patients <or=20 years old before gonadotoxic chemotherapy undergoing ovarian cortex cryopreservation. INTERVENTION(S) Before ovarian cortex cryopreservation, oocytes in all observed follicles were aspirated, matured in vitro, and cryopreserved. MAIN OUTCOME MEASURE(S) Maturation of oocytes. RESULT(S) One hundred seventy-nine oocytes were detected in 17/19 patients (89%) aged 5-20 years. We found 7, 8, and 17 oocytes in patients 5, 8, and 10 years old, respectively. The median number of oocytes per patient was 9 (0-37). Maturation rate was 45/133 oocytes (34%). In total, 81 oocytes were cryopreserved. We cryopreserved 4 of 12 detected, 4 of 9 detected, 1 of 8 detected, and 4 of 9 detected IVM oocytes for patients aged 5-10, 11-14, 15-17, and 18-20 years old, respectively. CONCLUSION(S) Patients undergoing ovarian cryopreservation could benefit from supplementary oocyte aspiration from the cortex. Surprisingly, oocytes were detected even in young premenarcheal girls. The number of oocytes detected, matured, and cryopreserved was not age dependent. Retrieved oocytes can be matured in vitro and cryopreserved. Because no pregnancy has yet resulted from this procedure it should be considered to be experimental. We describe the youngest patients to undergo ovum collection, IVM, and oocyte cryopreservation.

Seasonal variability in fertilization and embryo quality rates in women undergoing IVF

OBJECTIVE IVF-ET provides unique controlled conditions for the study of seasonal influences on the human reproductive process. This study was designed to evaluate the effects of seasonality on fertilization rate, embryo quality, and conception rates. DESIGN A retrospective observational cohort study. A chart review of all individuals undergoing IVF-ET from 1988 to 1991 at our institution was performed. SETTING An assisted reproduction unit at a university-based tertiary medical center. PATIENT(S) 657 women, for a total of 1074 IVF-ET treatment cycles, were evaluated. From this population, we chose 305 women undergoing their first IVF-ET cycle for reasons of pure mechanical infertility. INTERVENTION(S) IVF-ET cycles. MAIN OUTCOME MEASURE(S) Seasonal variability in fertilization rates and quality-A embryo rates, and the correlation with the absolute number of light hours, as well as the influence of temperature, humidity, and other environmental parameters. RESULT(S) A significant seasonal variability in the fertilization rate and the quality-A embryo rate was demonstrated. The highest fertilization and quality-A embryo rates were observed during the spring and the lowest in the autumn. These changes correlated with the absolute number of light hours and its increment over time, but not with the temperature, humidity, or other environmental parameters. CONCLUSION(S) Seasonality seems to have a significant influence on the fertilization process and on the quality of the human embryos that are obtained in vitro, possibly because of the light/dark variations over time. If this finding is confirmed, these seasonal changes should be taken into account when evaluating infertility data and in everyday clinical practice.

The role of uterine straightening by passive bladder distension before embryo transfer in IVF cycles

AbstractPurpose: The present study investigated the effect of bladder distension on in vitro fertilization and embryo transfer (IVF-ET) results. Methods: The study comprised 796 patients after successful transvaginal oocyte pickup and IVF, who, on the basis of bladder filling for ET, were divided into two groups. In group E, 385 patients underwent ET with an empty bladder, and in group F, 411 patients underwent ET with a full bladder. Results: Sixty-four pregnancies were achieved in group E (16.6%), compared to 110 pregnancies in group F (26.8%, P=0.006). A similar pregnancy loss rate was observed in both groups, 13 in group E (20.3%) and 29 in group F (26.4%; P=NS). Conclusions: A significantly higher pregnancy rate was achieved with routine bladder distension before ET, probably attributable to the smooth and easy insertion of the ET catheter.

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.

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. Pediatr Blood Cancer 2007;48:4–9.

Embryonic cultures but not embryos transplanted to the mouse's brain grow rapidly without immunosuppression

Embryos and embryocultures can be successfully transplanted into various bodily organs. However immunosuppression or homogenicity are required for the success of such experimental manipulation. Since the brain is considered immunologically privileged, we transplanted 2-4 cell embryos of C57BL x BALB/c, embryonic stem cells (ES) or embryoid bodies (EB) cultures into the hippocampus of the heterogeneous mouse stock HS/IBg. Both ES and EB cultures developed into an extensive growth, eventually larger than the brain itself, causing the death of the host in less than 29 days. The growth was identified as teratoma, mostly made of immature cells and tissues of diverse origin. Thus, the overall histological picture was that of a malignant teratoma. On the other hand, no embryos were found at any time after the transplantation; apparently, they could not survive in the host brain. The growth rate and the relative lack of rejection suggest that the brain offers a unique medium for ES and EB cultures but, not to embryos.

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.

Embryonic cultures transplanted to the mouse's brain survive and grow rapidly without immunosuppression☆

SURVIVE AND GROW RAPIDLY WITHOUT IMMUNOSUPPRESSION Joseph Yanai 1, Thomas C. Doetschman 5, Neri Laufer 3, Julia Maslaton t Shlomo Mor-Yosef ~, Anat Safran~, Moshe Shani 4, Dov Softer ~and Emanuel A. Winston 1. Ross Lab for Neural Birth Defects Lab Dept. Anatomy & Embryol. t , Pathoi. 2, & Dept. Obst. Gynec 3. Hebrew Univ. -Hadassah Med. Schl,, Jerusalem, Dept. Animal Sci. Volcani Ct~. Israel & Univ Cinc. Ohio, USA 5.