Monash IVF showcase expertise at Fertility Society Australia FSA Annual Conference - | IVF Treatment | Monash IVF Australia

Monash IVF showcase expertise at Fertility Society Australia FSA Annual Conference

The FSA Annual Conference 2015 recently held in Canberra (13-16 September) is an Annual Scientific Program that supports and showcases scientific research in the field of reproductive medicine. The 2015 program included over 100 clinical and scientific sessions and was attended by over 1,000 Australian and International delegates.

The expertise of Monash IVF was featured throughout the event; represented by a number of key staff and clinicians who presented findings of original research projects designed to improve patient outcomes, and the ultimate advancement of the industry.

We congratulate the FSA, our staff, clinicians and peers on a successful week and for contributing to the promotion of excellence in research and education. A summary of the Monash IVF presentation abstracts are below:   

ART Treatment effects on βHCG levels

Phillippa CLEMENTS1, Kelli SORBY1, Vivien MacLACHLAN1, Tiki OSIANLIS1
1 Monash IVF, Melbourne, Australia

Aim: To determine whether the type of ART treatment affects βHCG levels.

Method: Retrospective analysis of 4718 fresh and frozen ART cycles from 2011-2015 and HCG levels day 15 to 17 post oocyte retrieval or ovulation. ART treatment types investigated included fresh and frozen (FET) transfer cycles and insemination method. Fresh ICSI cycles were further analysed according to day of transfer and stimulation type. Donor, surrogate, and multiple pregnancy cycles were excluded.

Results: There were significantly different βHCG levels on day 15 or day 17 post oocyte
retrieval/ovulation (as occurs when day 16 falls on weekends), compared with day 16 (d15 242 IU/L cf. d17 354 IU/L cf. d16 569 IU/L, P=0.0001); all further analyses utilised day 16 results (N=2913) only.
Insemination method influenced βHCG with levels being higher in IVF cycles compared to ICSI cycles (351 IU/L cf. 319 IU/L, P= 0.04). This effect of insemination method was negated in stimulated FET cycles (353 IU/L cf. 364 IU/L, P=0.72); conversely βHCG levels were higher in ICSI over IVF embryos in natural FET cycles (408 IU/L cf. 352 IU/L, P=0.007). Interestingly, HCG levels were significantly higher with cleavage stage embryo transfers compared to blastocyst transfers (334 IU/L cf. 313 IU/L,
P=0.04). Down Regulation and Antagonist stimulations showed no significant difference in βHCG levels (337 IU/L cf. 318 IU/L, P=0.14).

Conclusion: ART treatment type seems to have a significant effect on HCG levels and should be taken into consideration when interpreting results. Further investigations are required to elucidate the underlying mechanisms.

The role of microRNAs in the embryo-endometrial dialogue

Carly CUMAN1,2,3, Michelle VAN SINDEREN1,3, Kelli SORBY1,2,3, Tiki OSIANLIS2,3, Luk ROMBAUTS2,3, Eva DIMITRIADIS1,3
1 Hudson Institute of Medical Research, Clayton, Victoria, 3168
2 Monash IVF, Clayton, Victoria, 3168
3 Monash University, Clayton, Victoria, 3800

Aim: Differentiate microRNA (miR) profiles of blastocyst culture media (BCM) from embryos that successfully implanted compared to those that failed to implant. Furthermore, we aim to demonstrate miR uptake by human endometrial epithelial cells (HEEC) and investigate the role microRNAs play in the embryo-endometrial dialogue in facilitating successful implantation.

Method: microRNAs were isolated from BCM containing blastocysts resulting in a successful clinical pregnancy (Implanted) or from blastocysts that failed to implant (Non-implant; no biochemical or clinical indications). Control blastocyst culture media was also used to exclude miRs present in the media prior to culture. Real-time miR PCR arrays were utilized and adhesion was investigated using a HTR8 spheroid-HEEC co-culture model.

Results: Real time PCR arrays detected 47 miRs exclusively in media containing a blastocyst; 19 miRs were identified exclusively in the implanted group , 22 miRs in the non-implanted group and 6 miRs in both groups. miR-661, the highest differentially expressed miR in non-implanted BCM was confirmed by individual real time PCR and its presence in human trophectoderm cells confirmed. Overexpression of miR-661 in primary HEECs reduced trophoblast spheroid attachment to the cells, which was demonstrated to be, in part, due to the decreased expression of miR-661 target gene Nectin-1. Furthermore, the addition of miR-661 inhibitor resulted in a corrected phenotype ‘rescuing’ the decreased adhesion observed.

Conclusion: Blastocysts resulting in implantation compared to those that do not implant exhibit a differential expression of miR secretions during in vitro culture. Furthermore our results suggest the blastocyst secretome can adversely affect implantation potential.

Benefits of Blastocyst Transfers for Older Patients

Salonika JALOTA1, Kelli SORBY1, Vivien MACLACHLAN1, Tiki OSIANLIS1,2
1 Monash IVF, Clayton, Australia
2Monash University, Clayton, Australia

Aim: To investigate the effect of embryo stage at transfer on the proportion of clinical pregnancies resulting in live birth.

Method: Retrospective analysis of Monash IVF patients undergoing Fresh and Frozen IVF Cycles with single embryo transfers between 2011 and 2013. Clinical pregnancy was defined as detection of a fetal sac at 6-7 weeks. Multiple pregnancies were excluded due to higher miscarriage rates. Statistical analyses used Fisher’s exact test with p<0.05 considered significant.

Results: A total of 2541 patients met the above criteria with an average age of 34.6 years (range 21-46 years). As expected pregnancy loss increased with age, showing a live birth rate per clinical pregnancy (LBR) of 93.5% in patients under 35 years, steadily decreasing to 89.2% for 36-38 yr, 84.0% 38-40 yr, 72.9% 41-43 yr and finally 64.7% 44-45 yr.
Fresh and frozen embryo transfers showed no statistical difference in miscarriage rates (10.1% vs. 11.3% p=0.368), with equivalent ages being confirmed across the two groups (34.3 years vs. 34.9 years). LBR between cleavage and blastocyst stage transfers for patients <38 yrs showed no statistically significant difference (90.5% vs. 92.9% p=0.138). However, in patients 38 yr miscarriage rates were significantly reduced (p=0.003) with blastocyst stage transfers (17.1%) compared to cleavage stage transfers (28.1%).

Conclusion: Blastocyst transfers have previously been shown to increase clinical pregnancy rates. Our results show older patients with blastocyst transfers have a significantly lower miscarriage rate. Blastocyst transfers for older patients should be considered as a means to increase take home baby rate.

Establishing a clinical service for cryopreservation of reproductive material before cancer treatment: lessons learned over two decades.

Karin HAMMARBERG1, Maggie KIRKMAN1, Kate STERN2,3, Robert McLACHLAN4, 5, 6, Debra GOOK2,3, Beverley VOLLENHOVEN4, Luk ROMBAUTS4, Jane FISHER1
1 Jean Hailes Research Unit, School of Public Health and Preventive Medicine, Monash
2 Melbourne IVF
3 Reproductive Services, Royal Women’s Hospital & Department of Obstetrics & Gynaecology, University of Melbourne
4 Monash IVF Epworth Hospital
5 Andrology Australia
6 Hudson Institute, Monash Medical Centre Clayton

Aim: Fertility preservation for people who need treatment for cancer is a service offered by some assisted reproductive technology (ART) clinics. Formal policies, protocols, clinical practices and governance mechanisms develop in individual services as  laboratory technologies advance. The aim was to investigate and describe the development of fertility preservation clinical practice.

Method: Semi-structured interviews were conducted with health professionals, who were involved in establishing fertility preservation services at Melbourne IVF and Monash IVF or who are currently providing this service. An interview guide was used which addressed current and historical practices, forms of documentation, and the development of service-specific policies in relation to the storage and later use of reproductive material frozen and stored prior to cancer treatment.

Results: In all 13 individuals were interviewed representing fertility specialists (3), andrologists (2), embryologists/scientists (4), counsellors (2) and administrative staff (2). Essential aspects of optimal clinical practice relating to fertility preservation before cancer treatment were identified. In broad terms they related to the move from experimental to clinical procedures; communication between oncology and ART specialists; managing patients’ expectations; implementing protocols, systems and data bases; and maintaining contact with patients.

Conclusion: Fertility preservation in the context of cancer treatment requires a dedicated multidisciplinary team. The most detailed knowledge of the development of practice and protocols is held by the staff who worked in an organisation during the period when clinical services were introduced. The findings can inform clinical practice guidelines for fertility preservation for people diagnosed with cancer. 

Risk of Ectopic Pregnancy in ART Births Linked to Endometrial Thickness.

Luk ROMBAUTS1,2,3, Caroline MOTTERAM1
1 Monash IVF, Melbourne, Australia
2 Monash Health, Melbourne, Australia
3 Dept O&G, Monash University, Melbourne, Australia

Introduction: We have previously shown that increased endometrial combined thickness (ECT) raises the risk of placenta previa following ART. The cause of this association remains unclear, but it is possible that increased ECT is a surrogate marker for subendometrial hypercontractility causing the embryo(s) to be dislodged after replacement. If this hypothesis is correct, then ECT should also predict ectopic pregnancy (EP) risk following ART. ART is indeed a significant risk factor for EP but an adequate explanation for this association remains elusive. The aim of this study was to investigate whether ECT independently predicts EP risk after ART.

Methods: Observational study of ectopic pregnancy rate in 11,618 fresh or frozen embryo transfer cycles between 01/01/2006 and 20/01/2015 in a private IVF unit. The dataset was analysed using binary logistic general estimating equations (SPSS v22.0) to calculate odds ratios for EP adjusted for known confounders (aOR).

Results: A total of 112 cases of EP (1%) were reported. Compared with an ECT of <7mm the risk of EP was two- and four-fold lower respectively for cycles in which the ECT was 7-12mm (aOR 0.46; 95%CI: 0.29-0.73) and >12mm (aOR 0.27; 95%CI: 0.10-0.77). Tubal infertility increased EP risk twofold. In a subanalysis including stimulated cycles only, oocyte number nor maximum estradiol levels were independently linked with EP risk.

Conclusions: Increased ECT is associated with lower risk of EP, while placenta previa risk is higher with increased ECT. A possible explanation for both observations may be that increased ECT increases the fundus-to-cervix contraction waves. 

PGS – Is age all that matters?

Kelli SORBY1, Canny SUGIANA1, Tiki OSIANLIS1,2
1 Monash IVF, Clayton, Australia
2Monash University, Clayton, Australia

Aim: To determine whether factors beyond age, including previous treatment attempts, number of oocytes retrieved and embryos suitable for biopsy, are related to embryo euploidy rates.

Method: Retrospective analysis of 1029 blastocysts undergoing preimplantation genetic screening (PGS) at Monash IVF. Statistical analyses used Fisher’s exact test with p<0.05 considered significant.

Results: The number of oocytes retrieved, taking age into account, appeared to have no effect on euploidy rate with 4 and 20 oocytes displaying rates of 55.6% and 55.4% respectively, and no significant differences seen in the intervening groups. Similarly, the number of blastocysts available for biopsy did not influence euploidy rate, with 50.4% euploid where <4 blastocysts were biopsied and 53.6% when 4 embryos were available (p=0.35). This held true regardless of the number of embryos chosen as the threshold. Interestingly, a compound effect of age and number of embryos suggests that a lower number of embryos available for biopsy, specifically in younger patients, may be associated with a lower euploidy rate. Patients with a higher number of treatment cycles unexpectedly displayed a higher euploidy rate (1-5 cycles 47.2% vs >5 cycles 61.9% euploid, p<0.0001). Importantly, this effect was consistent regardless of age.

Conclusion: Unlike previous reports, our large data set shows no detrimental effect of oocyte or embryo number on euploidy rates. Higher euploidy rates in patients with a higher number of previous cycles suggest recurrent IVF failure may not be an indication for pursuing PGS treatment.

Will Freeze all cycles be the norm in the future?

1 Monash IVF, Melbourne, Australia
2 Monash Health, Melbourne, Australia
3 Dept O&G, Monash University, Melbourne, Australia

Basic research, large observational studies and RCTs are now providing growing evidence in support of an elective freeze (eFET) or ‘freeze all’ strategy, not only in terms of achieving higher pregnancy rates but more importantly also in terms of lower maternal and infant morbidity and mortality. Additional RCTs in less selected populations are needed but they will have to prove that the reported health risks are significantly outweighed by higher cumulative pregnancy rates or lower costs. In the absence of such RCTs the major pressures against eFET remain the required up skilling of IVF units, patient preference, restrictive healthcare funding models and government regulation. It is likely that the implementation of eFET will be gradual. The addition of endometrial receptivity tests to the repertoire of tools for clinical decision making, will provide further guidance when to abandon fresh embryo transfers in individual cases.  

Australia incofertility registry: Monitoring referral patterns and the uptake, quality and complications of fertility preservation strategies in Australia and New Zealand.

1 School of Women’s and Children’s Health, Discipline of Paediatrics, UNSW Medicine, University of New South Wales, New South Wales, Australia
2 Sydney Youth Cancer Service, Sydney, New South Wales, Australia
3 Kids Cancer Centre, Sydney Children’s Hospital, Sydney, New South Wales, Australia
4 Melbourne IVF, Victoria, Australia
5 Monash IVF, Geelong, Victoria, Australia
6 Andrology Australia, Victoria, Australia
7 The Kirby Institute, Wallace Wurth Building, University of New South Wales, New South Wales, Australia
8 The University of Melbourne, Victoria, Australia
9 The Royal Children’s Hospital, Victoria, Australia
10 Peter MacCallum Cancer Centre, Victoria, Australia
11 University of Technology Sydney, New South Wales, Australia
12 The Royal Hospital for Women, New South Wales, Australia
13 School of Women’s and Children’s Health, Discipline of Obstetrics & Gynaecology, UNSW Medicine, University of New South Wales, New South Wales, Australia
14 Salesforce Australia, New South Wales, Australia

Improvements in cancer diagnosis and treatment, in children, adolescent and young adults aged 0-25 years has led to significant improvements in survival rates. Unfortunately, fertility can be affected by cancer treatment, however, as survival rates improve there is an expectation that the reproductive health of patients should be preserved whenever possible. A major gap in acute cancer management with implication for all patient’s future fertility is the lack of data and evidence based fertility preservation (FP) and assisted reproductive practices (ART) in this age group, which could give patients  hope for a biological family.

This research project has established the first web-based bi-national multi-site Australasian Fertility Preservation Registry collecting data from 170 cancer and fertility centres.

Outcomes from the research project will monitor uptake, use and complications of FP/ART and document the reproductive potential after treatment by age, diagnosis and treatment. Additionally, we are monitoring the fertility related psychological distress before and after cancer treatment. Finally data from the registry and Medicare on each patient is being used to perform health economics modeling of FP services.

As a direct consequence of this study, cancer and fertility centres are establishing referral pathways and an ANZ Oncofertility Consortium is developing. This will lead to future use of shared evidence based guidelines and resources, teaching and training for multi-disciplinary staff. The outcomes from this research study will assist clinicians to give accurate risk projections for future infertility and reproductive potential and assist clinicians in making recommendations for FP/ART. Results will lead to development of national guidelines for FP strategies and psychosocial support of patients during and after cancer treatment. The health economics study will lead to an application to the Department of Health for Medicare item numbers to be associated with FP strategies in cancer patients leading to equitable access of FP.

Paternal Obesity reduced pregnancy and live birth rates from assisted reproduction therapy as well as fertility, and increases sperm mitochondrial membrane potential and DNA fragmentation: A systematic review and meta analysis.

Hassan W. BAKOS1, Julie A. OWENS2, Michelle LANE1,2 , Jared M. CAMPBELL2
1 Monash IVF Group
2 University of Adelaide, Adelaide, Australia

Aim: To determine the effect of paternal obesity on pregnancy and live birth from assisted reproduction technology (ART), fertility, sperm mitochondrial membrane potential (MMP) and DNA fragmentation.

Method: A systematic review and meta-analysis was undertaken to aggregate studies that have investigated the fertility of obese men (Body Mass Index; BMI30) compared to normal weight men (BMI25). Studies were assessed for methodological quality by two independent reviewers using standardized critical appraisal followed by data extraction and meta-analyses through statistical software JBI-Mastari & RevMan 5. Of 27 articles that met the a priori inclusion criteria, 23 met critical appraisal. 

Results: Clinical pregnancy rate was significantly reduced for couples with an obese male (OR=0.53, 95% CI 0.35 to 0.82, 3 studies, N=438), as well as live birth rate (OR=0.57, 95% CI 0.36 to 0.90, 3 studies, N=1,385). Obese men were significantly more likely to experience infertility (OR=1.66, 95% CI 1.53 to 1.79, 2 studies, N=40,880). Semen parameters results suggested that the reduced reproductive potential may be attributable to increased sperm MMP (SMD=0.91, 95% CI 0.30 to 1.53, 2 studies, N=218) and DNA fragmentation (WMD=3.41%, 95% CI 2.08 to 4.75, 4 studies, N=353).

Conclusion: For the first time a meta-analysis shows clear evidence that paternal obesity is associated with reduced reproductive potential. These novel findings suggest that the assessment of conventional semen parameters may be insufficient to detect the cause of some obese mens’ failure to conceive. Therefore, it may be useful to incorporate sperm MMP and/or DNA fragmentation analysis into their semen assessment. 

Socioeconomic disparities in access to assisted reproductive technologies (ART) in Australia

Georgina M CHAMBERS1, Katie HARRIS1, Alan MACALDOWIE1, Kate TAYLOR2,3, Robert MCLACHLAN2,4,5,6
1 National Perinatal Epidemiology and Statistics Unit, School of Women’s and Children’s Health.
University of New South Wales, Sydney, Australia
2 Australian Fertility Medicine Foundation (AFMF), Sydney, Australia
3 The Nossal Institute for Global Health, School of Population and Global Health, University of
4 Andrology Australia ,School of Public Health and Preventive Medicine, Monash University
5 Monash IVF, Epworth Hospital, Richmond
6 Hudson Institute, Monash Medical Centre, Clayton.

Aim: To investigate if disparities exist in access to ART treatment based on socio-economic status (SES) and level of remoteness.

Method: The proportions of women of reproductive age accessing ART treatment between 2009 and 2012 by Australian postcode were calculated based on information collected from the ANZARD and ABS Estimated Residential Populations. SES was assigned using the ABS Index of Relative Socio-Economic Advantage and Disadvantage. Measures of remoteness were assigned using the ABS Geography Classification Remoteness Structure. A proxy for the underlying need for fertility treatment was represented by average mother’s age at first birth sourced from the AIHW National Perinatal Data Collection. Spatial representation of the data was performed using ArcMap Geospatial software. Generalised Linear Models were constructed to measure the independent effect of SES and Remoteness on access to treatment after controlling for confounders including age and underlying need for fertility treatment.

Results: The spatial maps indicate access to ART is highly correlated with SES nationally and within states. The GLM models indicate a gradient of increasing access with increasing level of advantage. On average, there was 43% increase in the adjusted proportion of women that accessed treatment in the most advantaged SES decile compared with the least advantaged SES decile. 

Conclusion: This is the first study to quantify the impact of SES on access to ART treatment after controlling for age and a proxy for underlying need. It suggests that women in disadvantaged areas who would benefit from ART treatment may not be receiving it.

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