Publications by authors named "Claire Garrett"

10 Publications

  • Page 1 of 1

Reduced live birth rates in frozen versus fresh single cleavage stage embryo transfer cycles: A cross -sectional study.

Int J Reprod Biomed 2020 Jul 22;18(7):491-500. Epub 2020 Jul 22.

Department of Obstetrics and Gynaecology, University of Melbourne, The Royal Women's Hospital, Parkville, Victoria, Australia.

Background: Studies have suggested that embryo-endometrial developmental asynchrony caused by slow-growing embryos can be corrected by freezing the embryo and transferring it back in a subsequent cycle. Therefore, we hypothesized that live birth rates (LBR) would be higher in frozen embryo transfer (FET) compared with fresh embryo transfers.

Objective: To compare LBR between fresh and FET cycles.

Materials And Methods: A cross-sectional analysis of 10,744 single autologous embryo transfer cycles that used a single cleavage stage embryo was performed. Multivariate analysis was performed to compare LBR between FET and fresh cycles, after correcting for various confounding factors. Sub-analysis was also performed in cycles using slow embryos.

Results: Both LBR (19.13% vs 14.13%) and clinical pregnancy (22.48% vs 16.25%) rates (CPR) were higher in the fresh cycle group (p 0.00). Multivariate analysis for confounding factors also confirmed that women receiving a frozen-thawed embryo had a significantly lower LBR rate compared to those receiving a fresh embryo (OR 0.76, 95% CI 0.68-0.86, p 0.00). In the sub-analysis of 1,154 cycles using slow embryos, there was no statistical difference in LBR (6.40% vs 6.26%, p = 0.92) or CPR (8.10% vs 7.22%, p = 0.58) between the two groups.

Conclusion: This study shows a lower LBR in FET cycles when compared to fresh cycles. Our results suggest that any potential gains in LBR due to improved embryo-endometrial synchrony following FET are lost, presumably due to freeze-thaw process-related embryo damage.
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July 2020

Is it possible to apply trial outcomes to a real-world population? A novel approach to External Validity Analysis.

Aust N Z J Obstet Gynaecol 2020 04 22;60(2):284-289. Epub 2019 Nov 22.

Melbourne IVF, Melbourne, Victoria, Australia.

Background: Translation of findings from randomised controlled trials (RCT), the foundation of evidence-based medicine, into clinical practice requires an understanding of relationships between patient characteristics, treatment practices and outcomes. We propose a novel technique, External Validity Analysis (EVA), to evaluate applicability of findings from a large RCT, comparing baseline characteristics, interventions and outcomes between the RCT and a large clinical database.

Aim: To perform EVA of the findings of a randomised controlled trial (ESTHER-1) to a population in an Australian clinic setting. To demonstrate this method, we evaluated the discordance in first cycle follicle-stimulating hormone (FSH) exposure and outcomes between the two populations, to inform clinical practice.

Materials And Methods: In this retrospective, descriptive analysis, we compared practices and outcomes between the follitropin alfa 'conventional' dosing arm of the ESTHER-1 trial and a selected comparable clinic subpopulation of patients who underwent controlled ovarian stimulation using FSH.

Results: Mean FSH exposure was 34% higher in the clinic subpopulation than in the trial subpopulation, resulting in higher average ovarian response without improving the likelihood of clinical pregnancy or live birth.

Conclusions: EVA allowed for the comparison of a trial population with a selected clinic population with similar characteristics. With respect to FSH consumption, this analysis revealed higher exposure to FSH in the clinic setting without a corresponding benefit. The comparison reveals population differences as well as the potential to improve clinical outcomes through a reappraisal of current practices and objectives in gonadotropin dose selection.
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April 2020

A randomised controlled trial of intra-uterine insemination versus in vitro fertilisation in patients with idiopathic or mild male infertility.

Aust N Z J Obstet Gynaecol 2014 Apr 28;54(2):156-61. Epub 2014 Feb 28.

Reproductive Services, Royal Women's Hospital, Carlton, Victoria, Australia; Melbourne IVF, East Melbourne, Victoria, Australia.

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.
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April 2014

Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies.

Fertil Steril 2010 Dec 8;94(7):2674-9. Epub 2010 Apr 8.

Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.

Objective: To determine whether adverse perinatal outcomes are increased in subfertile women.

Design: Cohort study.

Setting: Two tertiary assisted reproductive technologies (ART) centers; Victorian births register.

Patient(s): Records of women who registered with the clinics (1991-2000), but did not have an infant using ART, were linked to the birth register (1991-2004) to identify singleton non-ART births within 5 years of registration (N = 2171). Controls, matched by maternal age and year of infant's birth, were selected randomly from birth records (N = 4363).

Interventions: None.

Main Outcome Measure(s): Adverse obstetric and perinatal outcomes.

Result(s): After adjusting for confounders, compared with controls, subfertile women had increased odds of hypertension or preeclampsia (adjusted odds ratio [OR] 1.29, 1.02-1.61), antepartum hemorrhage (adjusted OR 1.41, 1.05-1.89), perinatal death (adjusted OR 2.19, 1.10-4.36), low birth weight (adjusted OR 1.44, 1.11-1.85), preterm birth <37 weeks (adjusted OR 1.32, 1.05-1.67) or <31 weeks (adjusted OR 2.37, 1.35-4.13), and cesarean delivery (adjusted OR 1.56, 1.37-1.77). There was weak evidence for increased birth defects (adjusted OR 1.30, 0.98-1.72) and gestational diabetes (adjusted OR 1.25, 0.96-1.63). No increased risk was found for prelabor rupture of membranes, small for gestational age, or postpartum hemorrhage.

Conclusion(s): Subfertile women with singleton births are at increased risk of several adverse outcomes. These risks should be considered during their antenatal care and when analyzing adverse effects of ART.
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December 2010

Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies.

Hum Reprod 2010 Jan 22;25(1):59-65. Epub 2009 Oct 22.

Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Rd, Parkville, VIC 3052, Australia.

Background: The reasons for increased birth defect prevalence following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are largely unknown. Classification of birth defects by pathology rather than organ system, and examination of the role of embryo freezing and thawing may provide clues to the mechanisms involved. This study aimed to investigate these two factors.

Method: Data on 6946 IVF or ICSI singleton pregnancies were linked to perinatal outcomes obtained from population-based data sets on births and birth defects occurring between 1991 and 2004 in Victoria, Australia. These were compared with 20,838 outcomes for singleton births in the same population, conceived without IVF or ICSI. Birth defects were classified according to pathogenesis.

Results: Overall, birth defects were increased after IVF or ICSI [adjusted odds ratio (OR) 1.36; 95% CI: 1.19-1.55] relative to controls. There was no strong evidence of risk differences between IVF and ICSI or between fresh and thawed embryo transfer. However, a specific group, blastogenesis birth defects, were markedly increased [adjusted OR 2.80, 95% CI: 1.63-4.81], with the increase relative to the controls being significant for fresh embryo transfer (adjusted OR 3.65; 95% CI: 2.02-6.59) but not for thawed embryo transfer (adjusted OR 1.60; 95% CI: 0.69-3.69).

Conclusion: Our findings suggest that there is a specific risk of blastogenesis birth defects arising very early in pregnancy after IVF or ICSI and that this risk may be lower with use of frozen-thawed embryo transfer.
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January 2010

Comparison of the frequency of defective sperm-zona pellucida (ZP) binding and the ZP-induced acrosome reaction between subfertile men with normal and abnormal semen.

Hum Reprod 2007 Jul 23;22(7):1878-84. Epub 2007 Apr 23.

Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, 132, Grattan Street, Carlton, Victoria 3053, Australia.

Background: The aim of this study was to compare the frequency of defective sperm-zona pellucida (ZP) binding (DSZPB) and defective ZP-induced acrosome reaction (DZPIAR) in subfertile men (i.e. male partners of infertile couples) with normal and abnormal semen analyses.

Methods: A total of 1030 subfertile men with normal semen analysis (n=255), oligozoospermia (count<20x10(6)/ml, n=136), severe teratozoospermia (strict normal morphology
Results: For the groups of men with normal semen or mild-moderate teratozoospermia, severe teratozoospermia and oligozoospermia, the frequencies of DSZPB were: 13, 21, 29 and 28%, respectively, and in those normal SZPB, DZPIAR were 27, 36, 56 and 68%, respectively. Overall DSZPB and ZPIAR were 36, 49, 68 and 77% for the four groups, respectively. The highest frequencies of defective sperm-ZP interaction were in the oligozoospermia and severe teratozoospermia groups. In the normal and teratozoospermia groups, subjects with a relatively low sperm concentration (20-60x10(6)/ml) had a significantly higher frequency of DZPIAR.

Conclusion: Defective sperm-ZP interaction is a major mechanism of male infertility. DZPIAR is more frequent than DSZPB in subfertile men with either normal or abnormal semen, suggesting that sequential sperm-ZP interaction tests are essential to detect these sperm defects.
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July 2007

Clinical application of sperm-oocyte interaction tests in in vitro fertilization--embryo transfer and intracytoplasmic sperm injection programs.

Fertil Steril 2004 Nov;82(5):1251-63

Department of Obstetrics and Gynecology and Reproductive Services, The Royal Women's Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Objective: To review the clinical value of sperm-oocyte interaction tests for the diagnosis and management of infertility by standard IVF or intracytoplasmic sperm injection (ICSI).

Design: Review of recent publications on relationships among sperm-oocyte interaction tests, sperm characteristics, and results of IVF and determination of frequency of defective sperm-oocyte interaction in infertile men.

Main Outcome Measure(s): Fertilization rates with IVF, sperm characteristics, sperm-zona pellucida (ZP) binding, ZP-induced acrosome reaction (AR), and sperm-ZP penetration.

Result(s): Sperm defects associated with low sperm-ZP binding or impaired ZP-induced AR and sperm-ZP penetration are the major causes of failure of fertilization when all or most oocytes from a couple do not fertilize in standard IVF. There is a high frequency of defective sperm-ZP interaction in men with oligozoospermia (<20 x 10(6)/mL) and severe teratozoospermia (strict normal sperm morphology < or =5%). Sperm morphology correlates with sperm-ZP binding, and sperm concentration correlates with ZP-induced AR in infertile men with sperm concentrations >20 x 10(6)/mL. Defective ZP-induced AR may cause infertility in up to 25% men with idiopathic infertility. These patients require ICSI despite the normal standard semen analyses.

Conclusion(s): Sperm-oocyte interaction tests are useful for diagnosis of subtle sperm defects that cause infertility in men without severe abnormalities of semen analysis. Pre-IVF diagnosis of these sperm defects will assist in the clinical assignment of patients to treatment with either standard IVF or ICSI.
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November 2004

Flow cytometry and microscopic acridine orange test: relationship with standard semen analysis.

Reprod Biomed Online 2004 Apr;8(4):398-407

Clinical Sciences Centre, Medical Research Council, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

Improved prediction of male fertility requires advances in semen analysis. This study examined the reproducibility and independence of the flow cytometry acridine orange test (FCM-AOT) of sperm chromatin integrity as an assessment of semen quality. The study found that FCM-AOT results are not significantly affected by up to 6 h delay in semen preparation (n = 9) or contamination of semen with moderate concentrations of bacteria (<10(8)/ml E. coli or Staph. epidermidis, n = 14). The variation of replicate measurements within samples was low (%Abnormal alpha(t): SD = 1.4, 95%CI = 4.6, n = 25) and different samples from the same men were mostly within the range of measurement error (n = 35). FCM-AOT variables, in particular %Abnormal alpha(t), displayed significant correlations with motility (r = -0.557), vitality (r = -0.469) and morphology (r = -0.464, n = 201), which are similar in magnitude to those existing between the standard semen variables. Surprisingly, no correlation was found between %Abnormal alpha(t) and the microscopic acridine orange test (M-AOT) (n = 185), suggesting the FCM results are sensitive to a different aspect of sperm quality. In summary, this study confirms that although not totally independent of standard semen analysis or the M-AOT, it is found to be a robust, sensitive and reproducible measure of semen quality, representative of the individual.
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April 2004

Recombinant human zona pellucida proteins ZP1, ZP2 and ZP3 co-expressed in a human cell line.

Asian J Androl 2004 Mar;6(1):3-13

Department of Obstetrics and Gynaecology, University of Melbourne, 320 Victoria Parade, East Melbourne 3002 VIC, Australia.

Aim: To produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests.

Methods: The human embryonic kidney cell line 293T was employed to produce rhZP1, rhZP2 and rhZP3 proteins individually and together by co-expression. Presence of these proteins in the culture medium and cell lysate was assessed by Western blotting analysis. The effect of the recombinant proteins on the human AR was assessed.

Results: RhZP2 and rhZP3 were secreted into the culture medium, whereas rhZP1 was found only in the cell lysate. Interestingly, when all zona pellucida proteins were co-expressed in the same cells, rhZP1 was also secreted into the culture medium. However, despite the presence of all three ZP proteins in sufficient concentration and evidence of heavy glycosylation on gel electrophoresis, biological activity to induce the AR was not observed.

Conclusion: RhZP1, rhZP2 and rhZP3 were successfully expressed in the human embryonic kidney cell line 293T. It appears that an interaction amongst these proteins may be required for release of rhZP1 from the cell. Although this approach is not satisfactory for producing active human ZP proteins, it makes a significant contribution to the understanding of the structural and functional characteristics of the ZP proteins.
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March 2004

Phorbol myristate acetate induces ruffling of the acrosome of human sperm.

Fertil Steril 2002 Jul;78(1):128-36

Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Royal Women's Hospital, Victoria, Australia.

Objective: To determine the effect of phorbol myristate acetate (PMA) on human acrosome morphology and the acrosome reaction.

Design: Controlled experiments on sperm and unfertilized oocytes from volunteers.

Setting: Academic research and teaching tertiary hospital.

Patient(s): Sperm samples were from normospermic men and unfertilized oocytes from IVF patients.

Main Outcome Measure(s): Acrosome morphology was assessed by using transmission and scanning electron microscopy. The acrosome reaction was assessed by using fluorescein-labeled Pisum sativum agglutinin.

Result(s): PMA induced acrosome ruffling, indicated by a marked wavy appearance. A significant correlation was found between PMA-induced ruffling and PMA enhancement of the zona pellucida-induced acrosome reaction. Protein kinase C inhibitors bisindolylmalemide I and sangivamycin had no effect on PMA-induced acrosomal ruffling, but actin polymerization inhibitors cytochalasin B and cytochalasin D significantly decreased PMA-induced acrosomal ruffling. In contrast, bisindolylmalemide I, sangivamycin, cytochalasin B, and cytochalasin D significantly decreased both the zona pellucida-induced acrosome reaction and the PMA enhancement of the zona pellucida-induced acrosome reaction.

Conclusion(s): PMA-induced acrosomal ruffling involves actin polymerization, possibly independent of conventional protein kinase C. Acrosomal ruffling is involved in the PMA augmentation of the zona pellucida-induced acrosome reaction.
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July 2002