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Parkville, Australia

Teh W.T.,University of Melbourne | Stern C.,Reproductive Services | Chander S.,Peter MacCallum Cancer Center | Hickey M.,University of Melbourne
BioMed Research International | Year: 2014

Future fertility is of paramount importance to younger cancer survivors. Advances in assisted reproductive technology mean that young women treated with radiation involving the uterus may require clinical guidance regarding whether to attempt a pregnancy themselves. We performed a review of the literature regarding radiation involving uterus (total body irradiation (TBI) and pelvic radiation), fertility, and pregnancy outcomes to come up with a recommendation for our patients. Limited evidence suggests lower fecundity and an increased incidence of pregnancy complications after uterine radiation. Higher radiation doses and direct uterine radiation both significantly increase the risk of an adverse pregnancy outcome. Uterine radiation doses of <4 Gy do not appear to impair uterine function. Adult TBI data (usually 12 Gy) suggest pregnancy is possible but with lower fecundity and more complications. Although there is no clear data indicating the dose of radiation to the uterus, above which a pregnancy would not be sustainable, we suggest patients receiving >45 Gy during adulthood and >25 Gy in childhood be counselled to avoid attempting pregnancy. There is preliminary evidence that menopausal hormone therapy and a combination of pentoxifylline and tocopherol may improve uterine function following irradiation. © 2014 Wan Tinn Teh et al. Source

Stern C.J.,Royal Melbourne Hospital | Gook D.,Royal Melbourne Hospital | Hale L.G.,Royal Melbourne Hospital | Agresta F.,Royal Melbourne Hospital | And 3 more authors.
Human Reproduction | Year: 2013

Ovarian tissue cryopreservation and transplantation is a form of fertility preservation offered to young women at high risk of losing ovarian function after cancer treatment. While there have been successful births resulting from orthotopic site grafts, we report the first case of an ongoing pregnancy from a heterotopic graft in a patient who had previously undergone bilateral oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two oocytes. These were fertilized with ICSI and two embryos were transferred. Serial ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus, this first demonstration of a pregnancy from a heterotopic graft site provides unequivocal evidence that cryopreservation preserves complete follicle development and that normal ovarian function can occur at a non-ovarian site. This provides optimism for further efforts to assist women who have had oophorectomy and pelvic surgery or radiotherapy, without an appropriate orthotopic site for grafting. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com. Source

Gook D.A.,Reproductive Services | Gook D.A.,University of Melbourne | Edgar D.H.,Reproductive Services | Edgar D.H.,University of Melbourne | And 3 more authors.
Molecular Human Reproduction | Year: 2014

Oxygen concentration during in vitro culture has a significant effect on the physiology of embryos, altering metabolic profile and developmental outcome. Although atmospheric oxygen has been used routinely for the culture of ovarian follicles, oxygen concentration mayalso be critical for follicle growth but the optimal concentration has not been determined. In this study, mechanically isolated primary and secondary follicles (80-140 μm diameter) from adult mouse ovaries were cultured in serum-free conditions for 8 days in either 5 or 20% oxygen to determine growth (follicular diameter), morphology and viability. For each oxygen concentration, half of the mediumwas replaced on Days 2, 4 and 6 or on Day 4 only. In the latter group, metabolic analysis of spent follicular culture media was performed by 1H-NMR. The proportion of viable, growing follicles was significantly (P < 0.0001) higher in 5% than in 20% oxygen (59% versus 8%). Reducing the frequency of medium replacement during culture in 5% oxygen resulted in significantly (P < 0.001) more viable follicles (79 versus 46%). In 20% oxygen, poor follicular viability was observed irrespective of the frequency of medium replacement (8 and 10% respectively). Metabolic profiles showed marked differences in amino acid and carbohydrate utilization with respect to both oxygen concentration and between Days 4 and 8 of development. Metabolites which significantly discriminated between oxygen concentration at both time points were glucose consumption, lactate utilization, alanine, alanyl-glutamine, leucine and proline. In conclusion, the poor in vitro follicular development previously observed in minimal culture conditionsmayreflect the use of 20% oxygen. Frequent medium replenishment is not necessary and does not overcome the detrimental effect of high oxygen on follicle viability. Further optimization of culture conditions would benefit frommetabolic analyses and the use of 5% oxygen should be tested further for impact on functional aspects of follicle culture such as steroid production which is currently unknown. © The Author 2013. Source

Gook D.A.,Reproductive Services | Gook D.A.,University of Melbourne | Edgar D.H.,Reproductive Services | Edgar D.H.,University of Melbourne
Journal of Assisted Reproduction and Genetics | Year: 2011

Previous reports of slow cooling of human mature oocytes have shown a reduced clinical efficiency relative to fresh oocytes. This study reports that equivalent fertilization and implantation rates to those obtained using fresh oocytes and cryopreserved embryos can be achieved with human mature oocytes dehydrated in 1.5 M propanediol and 0.2 M sucrose at 37°C and cryopreserved using slow cooling rates. © 2011 Springer Science+Business Media, LLC. Source

Elzeiny H.,Reproductive Services | Garrett C.,Reproductive Services | Garrett C.,University of Melbourne | Toledo M.,Reproductive Services | And 4 more authors.
Australian and New Zealand Journal of Obstetrics and Gynaecology | Year: 2014

Background The cause of infertility is unexplained or poorly explained in 30-40% of couples undergoing standard investigations, and treatment ranges from expectant management to IUI and IVF. Aims The aim of this study was to compare the clinical pregnancy rates and costs of intra-uterine insemination (IUI) and in vitro fertilisation (IVF) in women where the same ovarian stimulation led to the development of two or three mature follicles. Methods A randomised controlled clinical trial compared the efficacy of IUI and IVF in a tertiary fertility centre (ISRCTN28780587). Primary outcome measures were fetal heart positive pregnancy rate and cost per live birth. The selection criteria were age: females 18-42 years and males 18-60 years, infertility for one year or more, no IVF or IUI for 12 months prior to the trial, and no coital, tubal or ovulatory disorders, oligospermia, untreated endometriosis or contraindication for multiple pregnancy. All women (n = 102) had the same dose FSH stimulation protocol. Those who developed two or three preovulatory follicles were randomised 3:1 to IUI (n = 33) or IVF (n = 10). IUI or IVF was performed 36 h after hCG administration with single or double embryo transfer on day two. Results Clinical pregnancy rates (40% vs 12%, P = 0.04) and live birth rate (40% vs 6%, P = 0.01) were higher for IVF than IUI. The cost per live birth was AU$8735 for IVF compared with $42,487 for IUI. Conclusions This study provides evidence that IVF is more successful and cost-effective than IUI using the same doses of FSH. Further confirmatory studies are required. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Source

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