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Casper R.F.,University of Toronto | Casper R.F.,Samuel Lunenfeld Research Institute | Casper R.F.,Toronto Center for Advanced Reproductive Technology | Mitwally M.F.M.,University of Toronto
Clinical Obstetrics and Gynecology | Year: 2011

Clomiphene citrate (CC) is the most commonly used oral agent for the induction of ovulation. It is a nonsteroidal selective estrogen receptor modulator that has predominant antiestrogenic action resulting in long-lasting estrogen receptor depletion. Side effects include antiestrogenic effects systemically and on the endometrium and cervical mucous. Letrozole is a potent, nonsteroidal, aromatase inhibitor, originally used for postmenopausal breast cancer therapy, at present its only registered indication. We hypothesized that letrozole could mimic the action of CC without depletion of estrogen receptors. As there is no estrogen receptor antagonism, antiestrogenic effects such as poor cervical mucus and thin endometrium are not expected with aromatase inhibitor treatment. In addition, because estrogen receptors in the brain are not depleted, normal negative feedback occurs with letrozole and generally results in monoovulation. We and others have demonstrated the success of aromatase inhibition in inducing ovulation in women with polycystic ovarian syndrome. Letrozole may be very effective for ovulation induction and pregnancy in cases of CC resistance. When used together with follicle-stimulating hormone (FSH) injections, letrozole resulted in a significant reduction in the FSH dose needed for controlled ovarian hyperstimulation. Aromatase inhibitors likely increase ovarian sensitivity to FSH, and may be useful in poor responders and in women undergoing ovarian stimulation for in vitro fertilization. The safety of letrozole in pregnancy outcome studies has been demonstrated by examination of spontaneous pregnancy loss, multiple pregnancy rates, and congenital anomalies compared with a control group of infertility patients treated with CC. In addition, new data suggest that CC may result in cardiac anomalies and other birth defects and in low birth weight babies. We believe aromatase inhibitors are acceptable alternatives to CC as first line oral agents for ovulation induction or controlled ovarian stimulation. © 2011 Lippincott Williams & Wilkins. Source


Leung C.,University of Toronto | Lu Z.,University of Toronto | Esfandiari N.,Toronto Center for Advanced Reproductive Technology | Casper R.F.,University of Toronto | Sun Y.,University of Toronto
IEEE Transactions on Biomedical Engineering | Year: 2011

Sperm immobilization is a requisite step in intracytoplasmic sperm injection (ICSI). Conventionally, sperm immobilization is performed manually, which entails long training hours and stringent skills. Manual sperm immobilization also has the limitation of low success rates and poor reproducibility due to human fatigue and skill variations across operators. This paper presents a system for fully automated sperm immobilization to eliminate limitations in manual operation. Integrating computer vision and motion control algorithms, the automated system is able to visually track a sperm and control a micropipette to immobilize the sperm. A robust sperm tail tracking algorithm is developed to locate the optimal position on the sperm tail for sperm immobilization. The system demonstrates: 1) an average sperm tail tracking error of 0.95 μ m; 2) a sperm tail visual tracking success rate of 96%; 3) a sperm immobilization success rate of 88.2% (based on 1000 trials); and 4) a speed of 6-7 s per successful immobilization. © 2011 IEEE. Source


Casper R.F.,Samuel Lunenfeld Research Institute | Casper R.F.,Toronto Center for Advanced Reproductive Technology | Mitwally M.F.M.,Texas Tech University
Fertility and Sterility | Year: 2012

The concept of using aromatase inhibitors in place of clomiphene citrate (CC) for ovulation induction was introduced >10 years ago; a brief history of its development is presented. Its worldwide usage for ovulation induction, including as an adjunct for intrauterine insemination and in vitro fertilization has occurred despite the absence of definitive data of superiority to CC. The results of two ongoing potentially definitive multicenter trials of efficacy and safety of letrozole compared with CC are eagerly awaited. © 2012 by American Society for Reproductive Medicine. Source


Esfandiari N.,Toronto Center for Advanced Reproductive Technology | Esfandiari N.,University of Toronto | De Lamirande E.,McGill University | Gukturk A.,Toronto Center for Advanced Reproductive Technology | And 6 more authors.
Fertility and Sterility | Year: 2014

Objective To investigate the association between seminal hyperviscosity, the extent of semenogelin degradation, and sperm DNA integrity (DNA fragmentation index [DFI] and high DNA stainability [HDS]) in semen from infertile couples. Design Prospective study. Setting University-affiliated fertility center. Patient(s) Twenty-four consecutive infertile couples with moderate or high seminal viscosity (hyperviscosity group) and 25 consecutive infertile couples with normal semen viscosity (control group) undergoing standard IVF. Intervention(s) Semen volume and seminal hyperviscosity, sperm concentration, motility, and morphology, level of semenogelin degradation (by immunoblotting), and sperm chromatin damage (by sperm chromatin structure assay and expressed as %DFI and %HDS) were evaluated. Main Outcome Measures(s) Sperm %DFI and %HDS in the hyperviscosity group and the control group and the relationship between the extent of semenogelin degradation and seminal viscosity. Result(s) Semen volume in couples with moderate and high seminal viscosity was significantly lower as compared with the control group. In addition, total motility and normal morphology were significantly lower in the couples with high seminal viscosity as compared with the control group; however, there were no significant differences in sperm %DFI and %HDS between the hyperviscosity group and the control group. In addition, there was no relationship between the extent of semenogelin degradation and seminal viscosity. Conclusion(s) Our data suggest that seminal hyperviscosity (a posttesticular factor) is not an important cause of sperm DNA damage. Moreover, seminal hyperviscosity is not related to the degree of semenogelin degradation. Copyright © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. Source


Javed M.,Toronto Center for Advanced Reproductive Technology | Esfandiari N.,Toronto Center for Advanced Reproductive Technology | Esfandiari N.,University of Toronto | Casper R.F.,Toronto Center for Advanced Reproductive Technology | Casper R.F.,University of Toronto
Reproductive BioMedicine Online | Year: 2010

Intracytoplasmic sperm injection (ICSI) has resulted in pregnancy and birth for many couples, including those with severe male factor infertility. However, even after ICSI, complete failure of fertilization occurs in 1-3% of cycles. Most cases occur due to low number of mature oocytes, failure of oocyte activation or non-availability of appropriate spermatozoa for injection. Given the significant emotional and financial involvement in assisted reproductive cycles, failure of fertilization in all mature oocytes is a distressful event. It is not predictable. Since follow-up ICSI cycles result in fertilization in 85% of cases, repeated ICSI attempts are suggested. Physicians should counsel patients experiencing repeated failure of fertilization after ICSI cycles about available options including donated oocytes/embryos, donor sperm insemination, adoption or remaining childless if these choices are not acceptable due to religious or ethical reasons. This review discusses the causes and remedies for failed fertilization after clinical ICSI. © 2009, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source

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