Moskovtsev S.I.,Andrology Laboratory |
Jarvi K.,Mount Sinai Hospital |
Mullen J.B.M.,Andrology Laboratory |
Cadesky K.I.,LifeQuest Center for Reproductive Medicine |
And 2 more authors.
Fertility and Sterility | Year: 2010
Objective: To compare DNA damage in ejaculated and testicular spermatozoa in patients with previously unsuccessful oral antioxidant treatment. Design: Prospective clinical study. Setting: University-affiliated teaching hospital. Patient(s): Twelve men with persistently high sperm DNA damage. Intervention(s): Evaluation of DNA damage of ejaculated and testicular spermatozoa by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. Main Outcome Measure(s): The DNA damage of ejaculated spermatozoa compared with that of testicular spermatozoa, both samples collected on the day of intracytoplasmic sperm injection. Result(s): Ejaculated spermatozoa showed a threefold higher DNA damage when compared with testicular samples (39.7% ± 14.8 vs. 13.3% ± 7.3). Conclusion(s): Our results indicated that in patients with previously unsuccessful oral antioxidant treatment the retrieved testicular spermatozoa had a lower degree of DNA damage compared with ejaculated sperm collected on the same day. © 2010 American Society for Reproductive Medicine.
Hodes-Wertz B.,New York University |
Grifo J.,New York University |
Ghadir S.,Reproductive Center |
Kaplan B.,Fertility Centers of Illinois |
And 3 more authors.
Fertility and Sterility | Year: 2012
Objective: To determine any beneficial effects of preimplantation genetic screening (PGS) of all chromosomes by array comparative genomic hybridization (aCGH), with either day 3 or blastocyst biopsy, for idiopathic recurrent pregnancy loss (RPL) patients compared with their expected loss rate. Design: Case series report. Setting: Multiple fertility centers. Patient(s): A total of 287 cycles of couples with idiopathic RPL (defined as two or more losses). Intervention(s): PGS was done with day 3 biopsy (n = 193) or blastocyst biopsy (n = 94), followed by analysis with aCGH. Main Outcome Measure(s): Spontaneous abortion rate, euploidy rate. Result(s): A total of 2,282 embryos were analyzed, of which 35% were euploid and 60% were aneuploid. There were 181 embryo transfer cycles, of which 100 (55%) became pregnant with an implantation rate of 45% (136 sacs/299 replaced embryos) and 94 pregnancies (92%) were ongoing (past second trimester) or delivered. The miscarriage rate was found to be only 6.9% (7/102), compared with the expected rate of 33.5% in an RPL control population and 23.7% in an infertile control population. Conclusion(s): Current PGS results with aCGH indicate a significant decrease in the miscarriage rate of idiopathic RPL patients and high pregnancy rates. Furthermore, this suggests that idiopathic recurrent miscarriage is mostly caused by chromosomal abnormalities in embryos. © 2012 by American Society for Reproductive Medicine.
Skeith L.,Ottawa Blood Disease Center |
Skeith L.,University of Ottawa |
Carrier M.,Ottawa Blood Disease Center |
Carrier M.,University of Ottawa |
And 10 more authors.
Blood | Year: 2016
Weperformed a meta-analysis of randomized controlled trials comparing low-molecularweight heparin (LMWH) vs no LMWH in women with inherited thrombophilia and prior late (<10 weeks) or recurrent early (≥10 weeks) pregnancy loss. Eight trials and 483 patients met our inclusion criteria. There was no significant difference in livebirth rates with the use of LMWH compared with no LMWH (relative risk, 0.81; 95% confidence interval, 0.55-1.19; P =.28), suggesting no benefit of LMWH in preventing recurrent pregnancy loss in women with inherited thrombophilia. © 2016 by The American Society of Hematology.
Ben-Meir A.,Mount Sinai Hospital |
Burstein E.,Mount Sinai Hospital |
Borrego-Alvarez A.,Mount Sinai Hospital |
Chong J.,Mount Sinai Hospital |
And 22 more authors.
Aging Cell | Year: 2015
Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age-related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri-phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age-related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte-specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte-specific Pdss2-deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age-associated oocyte deficits causing infertility. © 2015 The Anatomical Society and John Wiley & Sons Ltd.
PubMed | Washington University in St. Louis, McGill University, University of Pennsylvania, TCART Fertility Partners and 2 more.
Type: Journal Article | Journal: Aging cell | Year: 2015
Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age-related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri-phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age-related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte-specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte-specific Pdss2-deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age-associated oocyte deficits causing infertility.
Pankhurst M.W.,University of Otago |
Clark C.A.,Mount Sinai Hospital |
Clark C.A.,LifeQuest Center for Reproductive Medicine |
Zarek J.,LifeQuest Center for Reproductive Medicine |
And 3 more authors.
PLoS ONE | Year: 2016
Circulating Anti-Müllerian hormone (AMH) is derived from the gonads, and is a mixture of the prohormone(proAMH), which does not bind to AMH receptors, and receptor-competent AMH. The functions of a hormone are partially defined by the factors that control its levels. Ovarian reserve accounts for 55~75% of the woman-to-woman variation in AMH level, leaving over 25% of the biological variation to be explained. Pregnancy has been reported to decrease circulatingAMH levels, but the observations are inconsistent, with the effect of pregnancy on the bioactivity of AMH being unknown.We have therefore undertaken a longitudinal study of circulating proAMH and total AMH during pregnancy. Serum samples were drawn at 6'8 gestational time-points (first trimester to post-partum)from 25 healthy women with prior uneventful pregnancies. The total AMH and proAMH levels were measured at each time-point using ELISA. The level of circulating total AMH progressively decreased during pregnancy, in all women (p<0.001). On average, the percentage decline between the first trimester and 36'39 weeks' gestation was 61.5%, with a standard deviation of 13.0% (range 30.4'81.2%). The percentage decline in total AMH levels associated with maternal age (R = -0.53, p = 0.024), but not with the women's first trimesterAMH level. The postpartumtotal AMH levels showed no consistent relationship to the woman's first trimester values (range 31'273%). This raises the possibility that a fundamental determinant of circulatingAMH levels is reset during pregnancy. The ratio of proAMH to total AMH levels exhibited little or no variation during pregnancy, indicating that the control of the cleavage/ activation of AMH is distinct from the mechanisms that control the total level of AMH. © 2016 Pankhurst et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Clark C.A.,Mt Sinai Hospital |
Clark C.A.,LifeQuest Center for Reproductive Medicine |
Davidovits J.,LifeQuest Center for Reproductive Medicine |
Davidovits J.,Hospital for Sick Children |
And 5 more authors.
Blood | Year: 2013
Routine investigation for recurrent pregnancy loss includes measurement of antiphospholipid antibodies under the perception that the lupus anticoagulant (LAC) is prevalent in this population. Our tertiary clinic sees ∼250 new patients with recurrent pregnancy loss annually, in addition to those with systemic lupus erythematosus and/or antiphospholipid syndrome. We measure LAC using a 4-assay panel that expands on the 2 assays recommended by the International Society on Thrombosis and Haemostatis (ISTH) guidelines. Of 2257 patients tested for LAC during a 6-year period, 62 (2.7%) repeatedly tested positive. Only 5 patients (0.2%) had both a history of early recurrent miscarriage and LAC positivity. Patients with LAC had a significantly more frequent history of thrombosis (35.5% vs 2.4%). LAC was absent in an overwhelming majority of women with exclusively early recurrent pregnancy loss but was associated with sporadic stillbirth. Among our panel of assays, none was predominant, and an increasing number of positive assays was associated with an increased history of morbidity. Therefore, our results do not support the ISTH contention that 2 assays are sufficient to identify and describe patients with LAC. We found that a confirmed, repeated LAC was very infrequent even in a high-risk setting. (Blood. 2013;122(3):341-347) © 2013 by The American Society of Hematology.
Pagnoux C.,Sinai University |
Pagnoux C.,University of Toronto |
Mahendira D.,St Michaels Hospital |
Mahendira D.,University of Toronto |
And 3 more authors.
Best Practice and Research: Clinical Rheumatology | Year: 2013
Despite the rarity of vasculitides, fertility and pregnancy outcome in the setting of vasculitis have become a major topic of interest within the past decade. The potential impact of vasculitis therapies, particularly cyclophosphamide, has been examined to some extent, but data are limited on the possible impact of the disease itself on fertility. Ideally, pregnancy should be planned when the vasculitis is in remission. The outcome for mothers and newborns is usually good when vasculitis is known before the pregnancy and is in remission, but every pregnant woman must be monitored by a specialised health-care team consisting of obstetricians specialised in high-risk births and internists/rheumatologists with expertise in managing these rare conditions. Most maternal complications during pregnancy are indeed due to vasculitis damage: hypertension in Takayasu arteritis (TAK) or granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA) with renal insufficiency, asthma or cardiac damage in eosinophilic granulomatosis with polyangiitis (EGPA) and subglottic and/or bronchial stenosis(es) in GPA. Pregnancy loss can occur in about 10% of cases in GPA, up to 20% in EGPA, 20-30% in Behçet's disease and up to 25% in TAK, and several studies found high rates of preterm births, at least with some vasculitides. Vasculitis manifestations in newborns from mothers with known vasculitis are very rare and usually transient. © 2012 Elsevier Ltd. All rights reserved.
PubMed | McGill University, Ottawa Hospital Research Institute, LifeQuest Center for Reproductive Medicine, University of Ottawa and University of Toronto
Type: Journal Article | Journal: Fertility and sterility | Year: 2016
To evaluate maternal and neonatal outcomes in women with chronic hypertension who conceive using assisted reproductive technologies (ART).Population-based retrospective cohort study.Obstetric hospitals.Singleton pregnancies of at least 20 weeks gestational age to women 18 years and older who delivered a live or stillborn infant between April 1, 2006, and March 31, 2012, categorized as exposed based on a diagnosis of chronic hypertension in the mother predating the index pregnancy.Medically assisted pregnancy including in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI), intrauterine insemination, and ovulation induction.placental-mediated complications of pregnancy (preeclampsia/eclampsia, stillbirth, fetal growth restriction/low birthweight [<10th percentile], or clinically significant placental abruption); secondary outcomes: cesarean delivery (planned/unplanned), prematurity (<37 or <32 weeks), and neonatal death.Our cohort included 807,765 singleton pregnancies. We used log binomial regression to compute the adjusted relative risks of the various outcomes in women with hypertension as compared with healthy women in ART and unassisted pregnancies. When we tested an interaction term between hypertension and ART in multivariate models, women with ART pregnancies were at higher risk of placental-mediated complications than were those with unassisted pregnancies (adjusted risk ratio 1.48; 95% confidence interval, 1.35, 1.56). The risk was even greater in hypertensive women who used ART (adjusted risk ratio 6.77; 95% confidence interval, 4.72, 9.72). Our findings persisted when assessing IVF only and when evaluating nulliparas.Hypertension is more frequent in ART-treated women. Hypertension increases the risk of placental complications, which appear to be compounded in ART versus unassisted pregnancies.
Sterling L.,University of Toronto |
Liu J.,University of Toronto |
Okun N.,Mount Sinai Hospital |
Sakhuja A.,University of Toronto |
And 3 more authors.
Fertility and Sterility | Year: 2016
Objective To determine whether the diagnosis of polycystic ovary syndrome (PCOS) independently predicts increased rates of pregnancy complications relative to control subjects, after adjusting for important confounders. Design Retrospective cohort. Setting Not applicable. Patient(s) A review of all pregnancies after fresh IVF with or without intracytoplasmic sperm injection transfers from December 2006 to 2012 (n = 1,084) identified 394 eligible singleton births (71 women with PCOS; 323 controls without). Intervention(s) Not applicable. Main Outcome Measure(s) Singleton births were assessed for selected adverse pregnancy and birth outcomes. Result(s) Women with PCOS demonstrated a higher risk of developing the following pregnancy complications after adjusting for differences in age, parity, body mass index, and time to conception: gestational diabetes (adjusted odds ratio [AOR] 3.15, 95% confidence interval [CI] 1.35-7.33), hypertensive disorders of pregnancy (AOR 4.25, 95% CI 1.94-9.32), preterm birth <37 weeks (AOR 2.30, 95% CI 1.07-4.97), and large for gestational age >90th percentile (AOR 2.77, 95% CI 1.21-6.35). The increased risk of preterm birth <37 weeks was eliminated after adjusting for development of hypertensive disorders of pregnancy, whereas the increased risk of large for gestational age remained significant after adjusting for gestational diabetes mellitus status. Time to conception did not differ significantly between groups, nor did rates of antepartum hemorrhage, cesarean section, or perinatal mortality. Conclusion(s) Polycystic ovary syndrome independently predicts higher risk of adverse pregnancy outcomes after adjusting for differences in maternal age, parity, body mass index, and time to conception. This new information may be of relevance in counseling and monitoring women with PCOS, although larger prospective studies may be needed to validate our findings. © 2016 American Society for Reproductive Medicine.