Ottawa Fertility Center

Ottawa, Canada

Ottawa Fertility Center

Ottawa, Canada

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Choi B.,Univfy Inc. | Bosch E.,Instituto Valenciano Of Infertilidad | Lannon B.M.,Boston IVF | Lannon B.M.,Beth Israel Deaconess Medical Center | And 10 more authors.
Fertility and Sterility | Year: 2013

Objective: To test whether the probability of having a live birth (LB) with the first IVF cycle (C1) can be predicted and personalized for patients in diverse environments. Design: Retrospective validation of multicenter prediction model. Setting: Three university-affiliated outpatient IVF clinics located in different countries. Patient(s): Using primary models aggregated from >13,000 C1s, we applied the boosted tree method to train a preIVF-diversity model (PreIVF-D) with 1,061 C1s from 2008 to 2009, and validated predicted LB probabilities with an independent dataset comprising 1,058 C1s from 2008 to 2009. Intervention(s): None. Main Outcome Measure(s): Predictive power, reclassification, receiver operator characteristic analysis, calibration, dynamic range. Result(s): Overall, with PreIVF-D, 86% of cases had significantly different LB probabilities compared with age control, and more than one-half had higher LB probabilities. Specifically, 42% of patients could have been identified by PreIVF-D to have a personalized predicted success rate >45%, whereas an age-control model could not differentiate them from others. Furthermore, PreIVF-D showed improved predictive power, with 36% improved log-likelihood (or 9.0-fold by log-scale; >1,000-fold linear scale), and prediction errors for subgroups ranged from 0.9% to 3.7%. Conclusion(s): Validated prediction of personalized LB probabilities from diverse multiple sources identify excellent prognoses in more than one-half of patients. © 2013 American Society for Reproductive Medicine, Published by Elsevier Inc.


Kim J.Y.,Ottawa Hospital Research Institute | Kim J.Y.,Seoul National University | Xue K.,Ottawa Hospital Research Institute | Xue K.,Nanjing Medical University | And 8 more authors.
Endocrinology | Year: 2013

In the present study, we have investigated the cellular mechanisms of androgen-induced antral follicular growth arrest and the possible involvement of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) in this process, using a chronically androgenized rat model. We hypothesize that hyperandrogenism induces antral follicle growth arrest via the action of chemerin and ovarian structural changes, resulting from granulosa cell and oocyte apoptosis and theca cell survival. Dihydrotestosterone (DHT) treatment resulted in increased expression of chemerinandCMKLR1in antral follicles, absence of corpus luteum, and increased atypical follicles. Addition of chemerin to follicle cultures induced granulosa cell apoptosis and suppressed basal, FSH- and growth differentiation factor-9- stimulated follicular growth. DHT down-regulated aromatase expression and increased active caspase-3 contentandDNAfragmentation in granulosa cells in vivo. These changeswereaccompanied by higher phosphatase and tensin homolog and lower phospho-Akt (Ser473) content in antral follicles and higher calpain expression and down-regulation of cytoskeletal proteins in atypical follicles, which were constituted predominantly of theca cells. DHT also activated granulosa cell caspase-3, decreased X-linked inhibitor of apoptosis protein, poly(ADP-ribose) polymerase, and phospho-Akt contents and induced apoptosis in vitro, responses readily attenuated by forced X-linked inhibitor of apoptosis protein expression. These findings are consistent with our hypothesis that antral follicular growth arrest in DHT-treated rats results from increased chemerin expression and action, as well as changes in follicular cell fate and structure, which are a consequence of dysregulated interactions of pro-survival and pro-apoptotic modulators in a cell-specific manner. Our observations suggest that this chronically androgenized rat model may be useful for studies on the long-term effects of androgens on folliculogenesis and may have implications for the female reproductive disorders associated with hyperandrogenism. © 2013 by The Endocrine Society.


Wang Q.,University of Ottawa | Wang Q.,Ottawa Hospital Research Institute | Leader A.,University of Ottawa | Leader A.,Ottawa Hospital Research Institute | And 4 more authors.
Endocrinology | Year: 2013

Follicular differentiation is a tightly regulated process involving various endocrine, autocrine, and paracrine factors. The biosynthesis of progesterone and estradiol in response to FSH involves the regulation of multiple steroidogenic enzymes, such asp450 cholesterol side-chain cleavage enzyme and aromatase. Here we demonstrated that prohibitin (PHB), a multifunctional protein, inhibits FSH-induced progesterone and estradiol secretion in rat granulosa cells. The mRNA abundances of cyp11a (coding p450 cholesterol side-chain cleavage enzyme) and cyp19 (coding aromatase) were also suppressed by PHB in a time-dependent manner. It is known that a novel adipokine chemerin suppresses FSH-induced steroidogenesis in granulosa cells. Chemerin up-regulates the content of PHB, and PHB knockdown attenuates the suppressive role of chemerin on steroidogenesis. In addition, inhibition of phosphatidylinositol 3-kinase/Akt pathway enhances the suppressive action of PHB, whereas expression of constitutively active Akt attenuates this response. These findings suggest that PHB is a novel negative regulator of FSH-induced steroidogenesis, and its action with chemerin may contribute to the dysregulation of steroidogenesis in the pathogenesis of polycystic ovarian syndrome. Copyright © 2013 by The Endocrine Society.


Wang Q.,University of Ottawa | Wang Q.,Ottawa Hospital Research Institute | Leader A.,Ottawa Hospital Research Institute | Leader A.,University of Ottawa | And 4 more authors.
Journal of Ovarian Research | Year: 2013

Background: Follicular growth and atresia are tightly regulated processes, which involve the participation of endocrine, autocrine and paracrine factors at the cellular level. Prohibitin (PHB) is a multifunctional intracellular protein playing an important role in the regulation of proliferation, apoptosis and differentiation. Here we examined the expression of PHB and its regulation by FSH in vitro and studied the role of PHB in the regulation of apoptosis and steroidogenesis in response to the apoptosis inducer staurosporine (STS) and to FSH, respectively. Methods. Undifferentiated and differentiated granulosa cells were collected from diethylstilbestrol (DES)- and equine chronic gonadotropin (eCG)-primed immature rats, respectively and then cultured with various treatments (FSH, adenovirus infection, STS) according to experimental design. The apoptosis rate, the production of estradiol and progesterone, and the expression of distinct proteins (PHB, caspase-3, phospho- and total Akt) were assessed. Results: PHB is anti-apoptotic and its action is dependent on the differentiated state of the granulosa cells. Data from gain- and loss-of-function experiments demonstrate that PHB inhibited STS-induced caspase-3 cleavage and apoptosis in undifferentiated granulosa cells, but was ineffective in differentiated cells. In contrast, PHB suppresses FSH-induced steroidogenesis and this response is evident irrespective of the differentiated state of granulosa cells. Conclusion: These findings suggest that PHB regulates granulosa cell apoptosis and steroidogenesis in a follicular stage-dependent manner and that the dysregulation of PHB expression and action may be relevant to ovarian dysfunction. © 2013 Wang et al.; licensee BioMed Central Ltd.


Wang Q.,University of Ottawa | Wang Q.,Ottawa Hospital Research Institute | Kim J.Y.,University of Ottawa | Kim J.Y.,Ottawa Hospital Research Institute | And 9 more authors.
Endocrinology | Year: 2012

Polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome associated with follicle growth arrest, minimal granulosa cell proliferation, dysregulated sex hormone profile, hyperthecosis, and insulin resistance. Using a 5α-dihydrotestosterone (DHT)-induced rat model that recapitulates the reproductive and metabolic phenotypes of human PCOS, we have examined the steroidogenic capability of granulosa cells from DHT-treated rats. Gene expression of several key steroidogenic enzymes including p450 side-chain cleavage enzyme (p450scc), aromatase, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenase-17β, and hydroxysteroid dehydrogenase-3β were markedly lower in DHT-treated rats than the controls, although the responsiveness of their granulosa cells to FSH was higher. Expression of the adipokine chemerin and its receptor, chemokine receptor-like 1, was evident in control and DHT-treated rats, with significantly higher ovarian mRNA abundances and protein contents of chemerin and its receptor. Recombinant chemerin decreases basal estradiol secretion in granulosa cells from DHT-treated rats. When the inhibitory role of chemerin on steroidogenesis was further examined in vitro, chemerin suppressed FSH-induced progesterone and estradiol secretion in cultured preantral follicles and granulosa cells. Chemerin also inhibits FSH-induced aromatase and p450scc expression in granulosa cells. Overexpression of nuclear receptors NR5a1 and NR5a2 promotes p450scc and aromatase expression, respectively, which is suppressed by chemerin. These findings suggest that chemerin is a novel negative regulator of FSH-induced follicular steroidogenesis and may contribute to the pathogenesis of PCOS. Copyright © 2012 by The Endocrine Society.


Hamel M.,Laval University | Dufort I.,Laval University | Robert C.,Laval University | Leveille M.-C.,Ottawa Fertility Center | And 2 more authors.
Molecular Human Reproduction | Year: 2010

Multiple pregnancy represents an important health risk to both mother and child in fertility treatment. To reduce a high twin rate, restriction to one embryo transfer is needed. Morphological evaluation methods for predicting embryo viability has significant limitations. Tight communication exists between the follicular cells (FCs) and the oocyte; therefore, developmental competence may be determined by markers expressed in the surrounding FCs. In this study, cells were recovered on a per-follicle basis by individual follicle puncture. Hybridization analysis using a custom-made complementary DNA microarray containing FC transcripts was performed. Genes expressed in FCs associated with good morphological transferred embryos were identified from follicles associated with a pregnancy outcome (pregnancy group) or no pregnancy (non-pregnancy group). Ten candidates from the Pregnancy group and three from the Non-pregnancy group were validated by quantitative RT-PCR. The best predictors associated with pregnancy were UDP-glucose pyrophosphorylase-2 and pleckstrin homology-like domain, family A, member 1. Genes assessment showed no significant candidate genes associated with non-pregnancy outcome, but GA-binding protein transcription factor b1 showed a tendency to be potentially more expressed in the non-pregnancy group. These markers could be related to granulosa luteinization process and could be used to improve embryo selection for successful single embryo transfer. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.


Doris N.,University of Ottawa | Shabib G.,University of Ottawa | Corbett S.,University of Ottawa | Corbett S.,Ottawa Fertility Center | And 5 more authors.
Contraception | Year: 2014

This case of secondary infertility with an associated intraabdominal levonorgestrel intrauterine system (LNG-IUS) demonstrates the importance of adequate imaging in women with a missing intrauterine contraceptive device and the possible fertility implications of an extrauterine LNG-IUS. © 2014 Elsevier Inc.


Sylvestre E.-L.,Laval University | Robert C.,Laval University | Pennetier S.,Laval University | Labrecque R.,Laval University | And 4 more authors.
Molecular Human Reproduction | Year: 2013

Cross-phylum and cross-species comparative transcriptomic analyses provide an evolutionary perspective on how specific tissues use genomic information. A significant mRNA subset present in the oocytes of most vertebrates is stabilized or stored for post- LH surge use. Since transcription is arrested in the oocyte before ovulation, this RNA is important for completing maturation and sustaining embryo development until zygotic genome activation. We compared the human oocyte transcriptome with an oocyte-enriched subset of mouse, bovine and frog (Xenopus laevis) genes in order to evaluate similarities between species. Graded temperature stringency hybridization on a multi-species oocyte cDNA array was used to measure the similarity of preferentially expressed sequences to the human oocyte library. Identity analysis of 679 human orthologs compared with each identified official gene symbol found in the subtractive (somatic-oocyte) libraries comprising our array revealed that bovine/human similarity was greater than mouse/human or frog/human similarity. However, based on protein sequence, mouse/human similarity was greater than bovine/human similarity. Among the genes over-expressed in oocytes relative to somatic tissue in Xenopus, Mus and Bos, a high level of conservation was found relative to humans, especially for genes involved in early embryonic development. © The Author 2013.


Warraich G.,Ottawa Fertility Center | Vause T.D.R.,Ottawa Fertility Center
Fertility and Sterility | Year: 2015

Objective To report the first case of sextuplets conceived via letrozole during ovulation induction. Design Case report. Setting Private fertility clinic. Patient(s) A 32-year-old female with a history of secondary infertility and polycystic ovary syndrome. Intervention(s) Letrozole, 7.5 mg, on cycle days 3-7 after a progesterone-induced menses. Main Outcome Measure(s) Clinical pregnancy. Result(s) Sexchorionic-sexamniotic pregnancy. Conclusion(s) High-order multiple gestations are possible with letrozole ovulation induction, so patients should be counseled appropriately and follicle monitoring considered. Copyright © 2015 Published by Elsevier Inc. on behalf of the American Society for Reproductive Medicine.


PubMed | Ottawa Fertility Center
Type: Case Reports | Journal: Fertility and sterility | Year: 2015

To report the first case of sextuplets conceived via letrozole during ovulation induction.Case report.Private fertility clinic.A 32-year-old female with a history of secondary infertility and polycystic ovary syndrome.Letrozole, 7.5 mg, on cycle days 3-7 after a progesterone-induced menses.Clinical pregnancy.Sexchorionic-sexamniotic pregnancy.High-order multiple gestations are possible with letrozole ovulation induction, so patients should be counseled appropriately and follicle monitoring considered.

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