N Dean

McGill University, Montréal, Quebec, Canada

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Publications (38)97.76 Total impact

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    ABSTRACT: Intrauterine insemination (IUI) is a commonly used treatment for infertility. Optimal timing of insemination is achieved either by ultrasound monitoring of follicular growth followed by the administration of human chorionic gonadotropin (hCG) or by the detection of a luteinizing hormone (LH) surge through urinary LH testing (uLH). However, in cycles where follicular growth is monitored, there is a possibility of a premature LH rise which may affect the outcome of treatment. The objective of the current study was to determine the frequency of spontaneous LH surges in ultrasound-monitored IUI cycles. One hundred IUI cycles were followed for this prospective cohort study. In combination with ultrasound monitoring, uLH testing was performed twice daily. A serum LH test was performed in the case of an inconclusive uLH test result. IUI was performed either on the day after a positive LH test or, if the diameter of the dominant follicle reached 18 mm and the LH test was still negative, 36 hours after ovulation triggering by administration of hCG. Of the 87 analyzed cycles, 19 (21.8%) exhibited a premature LH surge as detected by urine testing. Eleven further cycles had an inconclusive urine result, and in six of these (6.9% of cycles) the result was confirmed positive by serum LH testing, giving a total of 25 cycles (28.7%) experiencing a premature LH surge. A considerable proportion of patients undergoing ultrasound-monitored IUI cycle had a spontaneous LH surge before ovulation triggering was scheduled. This could affect pregnancy rates following IUI.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 12/2011; 33(12):1248-52.
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    ABSTRACT: Seminal antisperm antibodies (ASAs) have been associated with male infertility and a reduced probability of achieving a spontaneous pregnancy. However, the impact of ASAs on reproductive outcomes after assisted reproductive technologies (ARTs) remains controversial. We sought to further examine the relationship between ASAs and reproductive outcomes after in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI). We conducted a retrospective study of consecutive IVF and IVF/ICSI cycles where the male partner had had direct ASA testing in the six months preceding the ART cycle. We examined the relationship between semen parameters (sperm concentration, motility, strict morphology, ASA levels [by direct mixed agglutination reaction and expressed as the percentage of spermatozoa with IgG or IgA antibodies]) and reproductive outcomes (fertilization and clinical pregnancy rate) after IVF and IVF/ICSI. There was no significant relationship between direct ASA levels and reproductive outcomes after IVF and IVF/ICSI. Similarly, we found no significant relationships between sperm parameters (concentration, motility, strict morphology) and reproductive outcomes after IVF and IVF/ICSI. Clinical pregnancy rates were not significantly different in ASA-positive (>50% of sperm coated with ASAs) compared with ASA-negative samples (42% vs. 52% respectively, odds ratio: 1.45 (95% CI 0.63, 3.30, P>0.05). The data indicate that ASAs in semen are not associated with reproductive outcomes (fertilization and clinical pregnancy rate) after IVF or IVF/ICSI.
    Journal of Reproductive Immunology 01/2011; 88(1):80-4. · 2.34 Impact Factor
  • Reproductive Biomedicine Online - REPROD BIOMED ONLINE. 01/2010; 20.
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    ABSTRACT: The efficiency of in vitro maturation (IVM) techniques is suboptimal compared with controlled ovarian stimulation combined with IVF cycles, and studies are needed to identify factors that predispose IVM cycles to success or failure. We compared the outcome of IVM cycles with different dominant follicle (DF) size at oocyte retrieval following hCG priming. IVM was performed in 160 patients with polycystic ovaries (171 cycles). We administered 10,000 IU hCG s.c. 35-38 h before oocyte collection when endometrial thickness reached at least 6 mm. IVM cycles were retrospectively analyzed according to DF diameter as follows; Group 1: DF diameter <or=10 mm, Group 2: between 10 and 14 mm, Group 3: >14 mm. RESULTS A positive correlation was observed between DF size and number of in vivo matured oocytes collected (Group 1, 2 and 3 = 6.9, 10.6 and 15.1%, respectively). The rates of IVM, fertilization and embryo development were similar among the sibling immature oocytes collected from the three groups. However, clinical pregnancy rate in Group 2 (40.3%) was higher than Group 3 (17.1%) (P < 0.05). Moreover, implantation rates in Groups 1 (13.6%) and 2 (14.3%) were higher than Group 3 (4.9%) (P < 0.01). Our results suggest that oocyte collection in IVM cycles should be performed when the DF is 14 mm diameter or less. Sibling immature oocytes may be affected detrimentally if a DF >14 mm is present at oocyte collection.
    Human Reproduction 09/2008; 23(12):2680-5. · 4.67 Impact Factor
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    ABSTRACT: Our aim was to evaluate whether extending the interval between human chorionic gonadotrophin (hCG) priming and immature oocyte retrieval increases the oocyte maturation rate following in vitro maturation (IVM). This study was performed retrospectively. IVM was performed on 113 polycystic ovary syndrome patients (n = 120 cycles). Oocyte collection was performed either 35 h (Group 1; n = 76) or 38 h (Group 2; n = 44) after 10,000 IU of hCG priming. Following oocyte retrieval, oocyte maturity was assessed and the remaining immature oocytes were cultured in IVM medium up to Day 2. The number of in vivo matured oocytes collected was significantly higher in Group 2 (13.6%, 114/840 versus 7.3%, 96/1312 in Group 1) (P < 0.01); the oocyte maturation rate after Day 1 was significantly higher (P < 0.01) in Group 2 (46.3 versus 36.0% in Group 1); and clinical pregnancy (40.9 versus 25%) and implantation rates (15.6 versus 9.6%) were better in Group 2 than those in Group 1. The results suggest that extending the period of hCG priming time from 35 to 38 h for immature oocyte retrieval promotes oocyte maturation in vivo and increases the IVM rate of immature oocytes. Therefore, oocyte retrieval after 38 h of hCG priming may improve subsequent pregnancy outcome in cycles programmed for IVM treatment.
    Human Reproduction 06/2008; 23(9):2010-6. · 4.67 Impact Factor
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    ABSTRACT: To compare obstetric outcome and congenital abnormalities in pregnancies conceived after in vitro maturation (IVM), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) with those in spontaneously conceived controls. Data were collected from the McGill Obstetrics and Neonatal Database (MOND). All children were examined and classified in a standard manner. Final data were reviewed 12 months after delivery. Pregnancies by IVM, IVF, and ICSI were compared with those of age- and parity-matched controls. Congenital abnormality, gestational age, birth weight, Apgar scores, cord pH, growth restriction, pregnancy complications, mode of delivery, and multiple pregnancy were compared. A total of 432 children were born from 344 pregnancies after assisted reproductive technology (ART) during the study period (IVM 55, IVF 217, ICSI 160). The observed odds ratios (ORs) for any congenital abnormality were 1.42 (95% confidence interval [CI] 0.52-3.91) for IVM, 1.21 (95% CI 0.63-2.62) for IVF, and 1.69 (95% CI 0.88-3.26) for ICSI. Twin pregnancy (IVM 21%, IVF 20%, ICSI 17%) and triplet pregnancy (IVM 5%, IVF 3%, ICSI 3%) were higher than those in controls (1.7% twins and 0% triplets) (P<.001). Cesarean delivery rates were higher after ART, even in singleton pregnancies (IVM 39%, IVF 36%, ICSI 36%; controls: 26.3%) (P<.05). Apgar scores, cord pH, growth restriction, and pregnancy complications were comparable in all groups. All ART pregnancies are associated with an increased risk of multiple pregnancy, cesarean delivery, and congenital abnormality. Compared with IVF and ICSI, IVM is not associated with any additional risk.
    Obstetrics and Gynecology 11/2007; 110(4):885-91. · 4.80 Impact Factor
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    ABSTRACT: To compare rates of pregnancy loss after oocyte maturation in vitro (IVM), after IVF, and after intracytoplasmic sperm injection (ICSI). Retrospective comparative study. University tertiary-care center for infertility. Women undergoing assisted reproductive technology in a single center. Oocyte maturation in vitro, IVF, or ICSI, as indicated. Biochemical pregnancy, clinical miscarriage, ectopic pregnancy, and late fetal loss. There were 1,581 positive pregnancy tests (120 IVM, 849 IVF, and 612 ICSI). The biochemical pregnancy loss rate did not statistically significantly differ among the groups: 17.5% (21/120) after IVM, 17.0% (144/849) after IVF, and 18.0% (110/612) after ICSI. The clinical miscarriage rate after IVM was 25.3% (25/99), which was statistically significantly different compared with 15.7% (111/705) after IVF and 12.6% (63/502) after ICSI. However, the clinical miscarriage rates in women with polycystic ovary syndrome were statistically similar, at 24.5% (24/98) after IVM and 22.2% (18/81) after IVF. The ectopic pregnancy rates also were statistically similar: 1.0% (1/99) after IVM, 2.3% (16/705) after IVF, and 1.8% (9/502) after ICSI. The late fetal loss rates were similar as well: 1.0% (1/99) after IVM, 2.7% (19/705) after IVF, and 2.9% (14/502) after ICSI. There were no chromosomal abnormalities in the IVM group. There is a higher rate of clinical miscarriage after IVM when compared with IVF and ICSI. This appears to be related to polycystic ovary syndrome rather than to the IVM procedure.
    Fertility and sterility 10/2007; 90(3):546-50. · 3.97 Impact Factor
  • Nicola L Dean, Seang Lin Tan, Asangla Ao
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    ABSTRACT: To elucidate the timing and variability of CTG repeat expansion within the human dystrophia myotonica protein kinase (DMPK) gene in early development. Triplet-primed polymerase chain reaction was used to amplify the expanded CTG repeat in oocytes and embryos obtained from myotonic dystrophy 1 (DM1) patients, and a heminested polymerase chain reaction approach was used to amplify the normal CTG repeats in supernumerary IVF embryos. University hospital laboratory. Two DM1-affected females undergoing preimplantation genetic diagnosis who carried different CTG repeats. Also, 61 IVF patients who carried a (CTG)(5-18) and (CTG)(19-37) normal DMPK repeat. None. The degree of expansion of the repeat in the oocytes and embryos compared with the DM1-affected maternal repeat and the size of the (CTG)(19-37) repeat compared with the parental size in IVF embryos. The degree of repeat expansion was greater than the DM1 maternal lymphocyte for two of four oocytes, including a germinal vesicle-stage oocyte and 17 of 20 three-cell to blastocyst stage embryos. A change in the (CTG)(19-37) repeat was seen in 7 (7%) of 95 paternal transmissions but in no maternal transmissions. Because the repeat was already expanded in the immature oocyte, the initial expansion most likely occurs during oogenesis. A variable degree of DMPK(CTG)(n) expansion in the embryo is seen from different mothers. In addition, instability in paternal transmission of normal-range (CTG)(19-37) repeats occurs at the level of the embryo.
    Fertility and sterility 08/2006; 86(1):98-105. · 3.97 Impact Factor
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    ABSTRACT: One form of myotonic dystrophy, dystrophia myotonica 1 (DM1), is caused by the expansion of a (CTG)(n) repeat within the dystrophia myotonica-protein kinase (DMPK) gene located in chromosome region 19q13.3. Unaffected individuals carry alleles with repeat size (CTG)(5-37), premutation carriers (CTG)(38-49) and DM1 affected individuals (CTG)(50-6,000). Preferential transmission both of expanded repeats from DM1-affected parents and larger DMPK alleles in the normal-size range have been reported in live-born offspring. To determine the moment in development when transmission ratio distortion (TRD) for larger normal-size DMPK alleles is generated, the transmission from heterozygous parents with one repeat within the (CTG)(5-18) range (Group I repeat) and the other within the (CTG)(19-37) range (Group II repeat) to human preimplantation embryos was analysed. A statistically significant TRD of 59% (95% confidence interval of 54-64) in favour of Group II repeats from both mothers and fathers was observed in preimplantation embryos, which remained significant when female embryos were considered separately. In contrast, no significant TRD was detected for repeats from informative Group I/Group I parents. Our analysis showed that Group II repeats specifically were preferentially transmitted in human preimplantation embryos. We suggest that TRD, in Group II repeats at the DMPK locus, is likely to result from events occurring at or around the time of fertilisation.
    European Journal of HumanGenetics 04/2006; 14(3):299-306. · 4.32 Impact Factor
  • Fertility and Sterility - FERT STERIL. 01/2006; 85.
  • Article: P-704
    Fertility and Sterility - FERT STERIL. 01/2006; 86(3).
  • Fertility and Sterility - FERT STERIL. 01/2005; 84.
  • Fertility and Sterility - FERT STERIL. 01/2005; 84.
  • Fertility and Sterility - FERT STERIL. 01/2004; 82.
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    ABSTRACT: To investigate whether the consecutive embryo transfer of day 3 embryos and of blastocyst protects against failure to reach embryo transfer and provides additional pregnancies. An embryo transfer was performed on day 3 following which all remaining embryos were cultured to the blastocyst stage for a possible second transfer. One hundred and forty-two patients were selected for extended culture. Thirty-two of these patients did not develop blastocysts in culture, however, there were 12 pregnancies achieved in this group. The consecutive transfer of day 3 embryos and blastocysts can prevent the total loss of a cycle when embryos fail to develop to the blastocyst stage in culture and thereby provide additional pregnancies.
    Journal of Assisted Reproduction and Genetics 12/2003; 20(11):461-4. · 1.82 Impact Factor
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    ABSTRACT: To perform preimplantation genetic diagnosis for women carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, it is necessary to ensure that the proportion of mutant mtDNA diagnosed in the biopsied cell gives an accurate indication of the mutant load in the remaining embryo. A heteroplasmic mouse model, carrying NZB and BALB mtDNA genotypes, was used to study the relative proportions of each mtDNA genotype in the ooplasm and first polar body of mature oocytes, and between blastomeres of early cleavage stage embryos. The levels of heteroplasmy varied widely in the gametes compared with the maternal genotype. However, the distribution of the two mtDNA genotypes was virtually identical between the ooplasm and polar body of a mature oocyte, and also between the blastomeres of each 2-, 4- and 6-8-cell embryo. Therefore, the level of heteroplasmy diagnosed from the polar body of an unfertilized oocyte or from a single blastomere of an embryo is representative of the level in the embryo as a whole. Reliable results were obtained from both polar bodies and blastomeres, but the efficiency of diagnosis was greater with blastomeres. We conclude that preimplantation genetic diagnosis is feasible for mtDNA diseases, although it should be approached with caution, as it is possible that transmission of some pathogenic mutations could behave in a different manner.
    Molecular Human Reproduction 11/2003; 9(10):631-8. · 4.54 Impact Factor
  • Human Reproduction 12/2002; 17(11):3003-4; author reply 3004. · 4.67 Impact Factor
  • Nicola L Dean, Asangla Ao
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    ABSTRACT: This review examines the history, present status and future of genetic antenatal diagnosis for the trinucleotide repeat disorders, including Huntington's disease, Fragile X syndrome and myotonic dystrophy. Conventional prenatal diagnosis and the relatively new field of preimplantation genetic diagnosis, which can diagnose an affected embryo before a pregnancy is established, are described. Genetic diagnosis for these late onset diseases has inherent difficulties and many controversies. However, antenatal diagnosis is an important service for an individual with one of these mutations, who wishes to prevent the birth of an affected child.
    Expert Review of Neurotherapeutics 07/2002; 2(4):561-72. · 2.96 Impact Factor
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    N L Dean, S L Tan, A Ao
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    ABSTRACT: Preimplantation genetic diagnoses (PGD) for single gene defects require considerable time and resources for the standardization of polymerase chain reactions that are rapid, sensitive and reliable. Developing tests for the trinucleotide repeat diseases, where the expansion of unstable repeats produces the phenotypes, are particularly complex. One of these disorders is myotonic dystrophy where, at present, diagnosis at the single cell level relies on the detection of the normal alleles from both the affected and unaffected parent. The incorporation of short tandem repeat polymorphisms in the assay can give additional information to improve the accuracy of diagnosis. We have developed a multiplex fluorescent reaction for myotonic dystrophy and one of two closely mapped, highly heterozygous, short tandem repeats (D19S219 and D19S559) on chromosome 19 to reduce the possibility of misdiagnosis due to contamination, act as a control for allelic drop-out and maximize the number of embryos genotyped. This protocol was designed as a general diagnosis for myotonic dystrophy, using the most informative of the two polymorphisms for each couple. Subsequently this approach was used in a PGD treatment cycle.
    Molecular Human Reproduction 10/2001; 7(9):895-901. · 4.54 Impact Factor
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    ABSTRACT: Single-cell polymerase chain reaction (PCR) requires efficient amplification and accurate detection. We compare the accuracy of heteroduplex, fluorescent-fragment, and fluorescent single-strand conformation polymorphism (F-SSCP) analysis as detection systems for analysis of a PCR assay developed for preimplantation genetic diagnosis. A single-cell, fluorescent multiplex PCR assay was developed for the cystic fibrosis delta F508 mutation and the short tandem repeat, D21S11. Detection systems were compared by analyzing blinded PCR products. Amplification rates for cystic fibrosis were 89% by heteroduplex and 91% by fragment analysis, while it was 72% for D21S11 by fragment analysis. No difference in allele dropout was detected for cystic fibrosis by any method (2%). Overall accuracy was high, > 97%, although SSCP was the least accurate. Heteroduplex and fragment analysis proved equal in the diagnosis of a single amplified locus. We determined that fragment analysis allows maximal accuracy of detection and permits analysis of a second loci, controlling for DNA contamination and allelic dropout.
    Journal of Assisted Reproduction and Genetics 10/2001; 18(10):557-65. · 1.82 Impact Factor