bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Progression from Oocyte to Useable Blastocyst Using Deep Radiomic Signatures: Preliminary Results
Authors: HABIBALAHI Abbas , CULLINAN Rosemarie , TILLIA Liza , DALATI Sarah , MAHBUB Saabah B. , CAMPBELL Jared M. , RIEPSAMEN Angelique , GILCHRIST Robert B. , LEDGER William L. , GOLDYS Ewa M.
Published: November 2022

Background: Oocyte cryopreservation is increasingly used for fertility preservation by young women with cancer prior to chemo/radiotherapy and by single women wishing to defer pregnancy beyond their mid-30’s, thereby avoiding the increased risks of infertility, miscarriage and chromosomally abnormal pregnancy seen as consequences of female ageing. Oocyte cryopreservation is inefficient, with a large number of oocytes being required to give a realistic possibility of even a single pregnancy. We report preliminary data that demonstrate the ability of deep radiomic imaging to predict progression from oocyte to useable blastocyst as a first step towards improving the efficiency of oocyte cryopreservation.

Aim: To develop and apply a deep radiomic signature (DRS) based on an artificial intelligence model to identify oocytes that progressed to useable blastocysts.

Method: 40× brightfield images (n = 45) of human oocytes from 6 patients, taken prior to ICSI using an Olympus DP27 camera and IX73 inverted microscope. An unsupervised deep learning approach was applied to extract informative DRS of oocyte morphology. Unsupervised analysis by a fully blinded operator was conducted to identify data clusters. The data were colour-coded to identify useable (suitable for cryopreservation or transfer) blastocyst formation and a classifier was developed to separate useable blastocysts. This study was approved by the South Eastern Sydney Human Research Ethics Committee (2020/ETH01767).

Results: Blinded analysis identified an effective DRS signature with two separate clusters of oocytes. Oocytes that led to useable blastocysts formed a single cluster which was denser than that from oocytes with no good blastocyst outcome, implying less morphological heterogeneity of the higher quality oocytes. The classifier could successfully distinguish oocytes which did/did not lead to useable blastocysts with strong performance (AUC=0.86).

Conclusion: Our preliminary data demonstrate that non-invasive DRS can be applied to human oocytes, identifying morphological features that predict useable blastocyst formation with high accuracy.
Serum GDF9 and BMP15 as Markers of Ovarian Function in Healthy Women and Women with Polycystic Ovary Syndrome
Authors: RIEPSAMEN Angelique H. , DONOGHOE Mark W. , INDRAN Inthrani R. , LIEN Shelly , HECHTMAN Leah , ROBERTSON David M. , GILCHRIST Robert B. , YONG Eu-Leong , LEDGER William L.
Published: November 2022

Background: The oocyte-secreted factors growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are key regulators of female fertility and are predominantly expressed by oocytes. Recently, methods to quantitate these proteins in serum have demonstrated diagnostic potential. It is unknown if concentrations reflect ovarian and endocrine function, particularly in women with polycystic ovary syndrome (PCOS), where GDF9/BMP15 function is suggested to be aberrant.

Aim: To determine if serum GDF9/BMP15 are associated with ovarian and endocrine parameters, and the ovarian pathologies, PCOM and PCOS.

Method: Women aged 21-45 years (n=381) were from a cross-sectional study at the National University Hospital, Singapore, including healthy volunteers and referrals from gynecological clinics. Transvaginal ultrasound scans, blood tests and questionnaire were performed. Serum GDF9 and BMP15 were assessed relative to ovarian (cycle regularity, ovarian volume, AFC, AMH) and androgenic (testosterone, DHT, androstenedione, DHEAS, SHBG, mFG score) characteristics. PCOM and PCOS were determined using the Rotterdam criteria. Statistical analyses used parametric survival models and Kendall’s tau correlation appropriate for data containing values below the limit of detection.

Results: Serum GDF9 and BMP15 were detectable in 40% and 41% of women, respectively. Serum GDF9 positively correlated with ovarian volume (p=0.02), AFC (p=0.004), and weakly with AMH (p=0.05). Furthermore, irregular menstrual cycles were associated with high GDF9 (p=0.005), and similar, although non-significant associations were seen for BMP15. When stratified into PCOS (n=130), PCOM (n=59), and control (n=192), GDF9 and BMP15 concentrations were not significantly different, and were not associated with the majority of androgenic features of PCOS. However, the relationship between GDF9 and AFC was significantly different between PCOM, PCOS and control women (p=0.02).

Conclusion: These results suggest that serum GDF9 and BMP15 reflect ovarian characteristics but not androgenic characteristics of PCOS, and that the relationships between GDF9 and AFC may be aberrant in women with PCOM/PCOS.
Higher Doses of FSH Used for Superovulation Do Not Adversely Affect Embryonic Ploidy: A Randomised Controlled Trial (Stimulation Resulting in Embryonic Aneuploidy Using Menopur (STREAM) Trial)
Authors: SHYAMSUNDER Akshara , HARDY Tristan , YAZDANI Anusch , POLYAKOV Alex , NORMAN Robert , HART Roger , AGRESTA Franca , ROMBAUTS Luk , BOOTHROYD Clare , CHAPMAN Michael , SWEETEN Prudence , SOMERVILLE Eleanor , JOSE Rachel , WAND Handan , LEDGER William L.
Published: November 2022

Background: High dose gonadotropin stimulation protocols may increase costs, patient discomfort, likelihood of ovarian hyper stimulation syndrome (OHSS), ovarian torsion and increased bleeding after multiple ovarian punctures. In addition, it is possible that high dose stimulation may result in impaired oocyte “quality” with adverse effect of embryonic ploidy. This may negate any benefits seen from a higher oocyte yield after high dose stimulation.

Aim: To determine the proportion of euploid blastocysts resulting from higher versus lower dose ovarian stimulation protocols.

Method: Multicentre randomised controlled trial recruiting 57 women who were treated with ovarian stimulation using either 150 or 300 IU Menopur per day. In Vitro Fertilisation (IVF) or Intracytoplasmic Sperm Injection (ICSI) were performed according to individual unit protocol and embryos were cultured to blastocyst stage. A trophectoderm biopsy was performed for preimplant action genetic testing for aneuploidy.

Results: The number of oocytes obtained from women randomised to 150 IU Menopur was between 3–17 (mean=9), whereas the number of oocytes obtained from women randomised to 300 IU Menopur was between 3–24 (mean=11). There was a positive linear relationship between serum AMH concentration and oocyte yield in both the 150 & 300 IU Menopur groups (R=0.3359, R2=0.1129 & R=0.3741, R2=0.1399). 63% of blastocysts were euploid in the 150 IU Menopur group and 75% in the 300 IU Menopur group (p=0.17).

Conclusion: The higher dose ovarian stimulation protocol did not significantly increase the number of oocytes retrieved, nor did the higher dose protocol reduce the proportion of euploid embryos created. This study does not support the hypothesis that use of higher doses of gonadotropin for ovarian stimulation results in a reduction in the proportion of euploid embryos obtained after IVF.
Individualised versus Standard FSH Dosing in Predicted Poor Responders Undergoing IVF: A Randomised Controlled Trial
Authors: LIU Xitong , SHI Juanzi , MOL Ben W , LI Wentao
Published: November 2022

Background: Poor responders usually lead to detrimental effects on IVF outcomes due to low oocyte number and quality which further result in low pregnancy outcomes and increased chance of cycle cancellation. Clinicians often individualise the FSH dose using ovarian reserve tests (ORT), including antral follicle count (AFC). However, it is unclear whether individualised FSH dosing improves clinical outcomes.

Aim: To understand if there is a difference in live birth rates between individualised or standard FSH dosing in poor responders?

Method: Between March 2019 and April 2020, we performed a single center, parallel, open-label randomised controlled trial. Women referred for their first IVF/ICSI cycle, [Formula: see text]43 years of age, AFC[Formula: see text]10 were approached. Eligible women were randomised either to individualised or standard FSH dosing. In the individualised group, women with AFC 1-6 were assigned to 300IU/day, while women with AFC 7-9 were assigned to 225IU/day. In the standard group, women were assigned 150IU/day. The primary outcome was live birth attributable to the first ART cycle within 18 months of randomization.

Results: A total of 661 women were randomised, 328 to the individualised group and 333 to the standard group. The live birth rate (follow up still ongoing) was not significantly different between the two groups [49.1% (161/328) vs 42.3% (141/333), RR: 1.16 (95%CI, 0.98-1.37), P=0.082]. The cumulative ongoing pregnancy rate for individualised versus standard dosing was 53.0% (174/328) versus 47.4% (158/333), respectively [RR: 1.12 (95%CI, 0.96-1.30), p=0.150]. The multiple pregnancy rate also did not differ between individualised and standard dosing [5.49% vs 5.71%, RR: 0.96 (95%CI, 0.51-1.80), p=0.903]. Individualised dosing reduced the occurrence of poor response compared to standard dosing [31.1% vs 48.6%, RR: 0.64 (95%CI, 0.53-0.78), p[Formula: see text]0.001].

Conclusion: The individualised dosing strategy led to lower rates of poor response, but it did not result in significantly higher ongoing pregnancy rates.
Can We Identify Subgroups in Which ICSI is Cost-Effective Over IVF: A Secondary Analysis of a Randomised Clinical Trial
Authors: MOL Ben W. , VUONG Lan N. , LUU Tam M. , PHAM Toan D. , HO Tuong M. , HA Anh N. , TRUONG Binh T. , PHAN Anh K. , NGUYEN Dung P. , PHAM Thanh N. , PHAM Quan T. , WANG Rui , NORMAN Robert J. , DANG Vinh Q.
Published: November 2022

Background: The use of intracytoplasmic sperm injection (ICSI) has increased substantially worldwide, primarily in couples with non-male factor infertility. We recently published the results of a large randomised controlled trial (RCT) comparing ICSI and IVF showing no significant improvement of ICSI over IVF in couples with normal semen concentration and motility. Here, we assess the cost-effectiveness of ICSI in these couples, with additional attention for subgroups.

Aim: To assess the effectiveness and cost-effectiveness of ICSI versus IVF in relation to sperm morphology.

Method: We performed a cost-effectiveness alongside a randomised clinical trial comparing ICSI and IVF. Between 16th March 2018 and 12th August 2019, we had randomized 1,064 couples (532 to ICSI vs 532 to IVF) in two centres in VietNam. After comparing the difference in life birth rate, we calculated the incremental cost-effectiveness ratio as the additional cost to establish one live birth. We also looked at (cost-)effectiveness in subgroups by the baseline characteristics treatment-indication, ovarian response, total-motile-count and sperm-morphology.

Results: In the base case, there were per 100 women 3.4 more babies born for an extra cost of €65,600. This translates to €19,294 per extra life birth, which is comparable to the benchmark of €15,000 per live birth.

We did not find significant interaction with any of the baseline characteristics (all P-values for interaction [Formula: see text] 0.05). However, for sperm morphology, in the 458 couples with [Formula: see text]=4% normoform cells, live birth rates were 32.1% versus 32.9% (RR 0.97 (0.75 to 1.27)), while in 201 women with [Formula: see text]4% normoform cells this was 36.2% versus 29.7% (RR 1.22 (0.97, 1.54)). While this would implicate no effectiveness of ICSI in couples with completely normal sperm, in couples with normal total sperm count and motility, those with sperm morphology [Formula: see text]4% would have 6.5 additional babies per 100 women, resulting in a cost-effectiveness of €10,076 per extra life birth.

Conclusion: In couples with completely normal sperm (normal total sperm count, motility and morphology) ICSI does not add anything to the chances obtained with IVF. In couples with a normal total sperm count and motility with abnormal morphology, ICSI could be considered as it seems cost-effective.
Donor Recruitment and Recipient Experience of a Newly Implemented Identity Release Donor Sperm Program
Authors: NOWOWEISKI Sarah , HYLAND Bernadette , OLIVER Laura , HEALEY Martin , OSIANLIS Tiki
Published: November 2022

Background: A shortage of donor sperm exists in Victoria. In combination with COVID-19 affecting cross border reproductive care, the lack of donor availability necessitates increased attention to factors affecting recipient decision making.

Aim: Newlife IVF launched their Identity Release Donor (IR; previously known as clinic recruited) Sperm Program in September 2020. Our aim is to examine donor recruitment and key factors in donor selection in an IR donor sperm program.

Method: Data collected through routine interactions with potential donors and recipients, including donor allocation and reasons for decision making were examined. Qualitative data collected through counselling sessions with recipients were analysed using thematic content analysis.

Results: From September 2020 to May 2021, 308 men responded to an online advertisement requesting more information about our IR program. Of these, 41% (N=126) completed an intake phone call wishing to proceed, however only 7% (N=22) undertook investigative testing. Ultimately 2.5% (N=8) of the initial cohort completed all requirements to date.

To date, 106 recipient women/couples completed the compulsory counseling session and accessed the IR profiles. Seventy-five percent (N=80) selected a donor. Also, 75% stated there was more information in donor profiles than expected, and valued interviewer impressions of donor (international donor profiles). Recipients referred to the ‘letter to the offspring’, a hand-written note by the donor for potential offspring, as providing the most insight and weighed heavily in decision making. Of the 25% (N=26) who have not selected a donor to date, the majority (N=16) were undecided, disliked profiles (N=5), delaying treatment (N=2), or changing clinics (N=3).

Conclusion: A small proportion of men who express interest via an online advertisement, translate to sperm donors. A high proportion of recipients who view donor sperm profiles select a donor and proceed with treatment. Recipients are motivated to learn about a donor and value the donor’s personal connection to a potential donor conceived offspring.
Patient Experience During COVID-19: How the Introduction of Telehealth has Influenced Patient Practices
Authors: NOWOWEISKI Sarah , HEALEY Martin , OSIANLIS Tiki
Published: November 2022

Background: Melbourne underwent one of the strictest lockdowns in the world in 2020, with the swing to telehealth-based appointments, bringing into focus the effectiveness of communication between staff and patients. Due to the ongoing provision of a hybrid model of in-person and telehealth appointments, it is important to learn how this shift in delivery of service has impacted patient experiences.

Aim: To examine patient experiences with telehealth appointments, and to assess any associations between self-reported personality traits and preferred communication method.

Method: Data was collected from a patient satisfaction survey administered in May 2021 (N=127). The patient satisfaction survey consisted of 5-point Likert scale responses regarding specific aspects of IVF care, self-reported personality trait descriptions and qualitative responses. Frequencies and ordinal logistic regression analyses was used to examine associations between personality traits and satisfaction responses.

Results: Overall 80% (N=101) of patients liked the flexibility of telehealth appointments. However 68% (N=87), while understanding the need for telehealth during COVID-19, preferred face to face communication. Exploring self-reported personality traits, patients who described themselves as assertive were more likely to prefer succinct written information, whereas patients who described themselves as anxious and/or shy preferred both verbal and written communication. Patients who described themselves as optimistic, were more likely to rate themselves as pleased with their overall experiences at Newlife IVF and felt emotionally supported during treatment.

Conclusion: Despite shifting to a majority telehealth service provision, most patients reported high levels of satisfaction with communication, and have continued to actively use telehealth since the lifting of lockdown, indicating that it doesn’t introduce significant barriers to patient and clinic communication. Inadvertently, necessary change due to COVID-19 has spontaneously broadened the scope of patient centered care providing further insight into patient preferences. Further exploration into using heuristics to identify links between personality types and mode of communication is warranted.
Pronuclear Differences Between Male and Female Human Zygotes: A Time-Lapse Study
Authors: OREVICH Lee-Sarose , WATSON Kate , ONG Kee , KORMAN Irving , TURNER Ross , SHAKER David , LIU Yanhe
Published: November 2022

Background: Recent time-lapse studies have investigated potential live birth prediction by pronuclei (PN) associated morphometric and morphokinetic measures. Whether there is gender associated difference in such measures is unknown.

Aim: To determine if morphometric and morphokinetic profiles of PN vary between male and female zygotes.

Method: This retrospective study included 94 consecutive autologous single day 5 transfers leading to a singleton live birth (43 males and 51 females) at Monash IVF Gold Coast between January 2019 and March 2020. Timing parameters included 2nd polar body extrusion (tPB2), sperm-originated PN (tSPNa) or oocyte-originated PN (tOPNa) appearance (differentiated by proximity to PB2) and PN fading (tPNF). Morphometrics were evaluated at 8 (stage 1), 4 (stage 2) and 0 hour before PNF (stage 3), measuring PN area (um2), PN juxtaposition, and nucleolar precursor bodies (NPB) arrangement.

Results: Male zygotes had longer time intervals of tPB2_tSPNa than female (4.8±0.2 vs 4.2±0.1 h, p=0.044), but not tPB2_tOPNa and tPB2_tPNF. SPN increased in size from stage 1 through 2 to 3 (435.3±7.2, 506.7±8.0, and 556.3±8.9 um2, p=0.000) and OPN did similarly (399.0±6.1, 464.3±6.7, and 513.8±6.5 um2, p=0.000), with SPN being significantly larger than OPN at each stage (p[Formula: see text]0.05 respectively). However, their relative size difference (SPN-OPN) was similar between male and female zygotes at all 3 stages. More male than female zygotes reached central PN juxtaposition at stage 1 (76.7% vs 51.0%, p=0.010), stage 2 (97.7% vs 86.3%, p=0.048) and stage 3 (97.7% vs 86.3%, p=0.048). Furthermore, more OPN showed aligned NPBs than in SPN at stage 1 (44.7% vs 28.7%, p=0.023). No gender associated differences were detected in NPB alignment in either SPN or OPN (p[Formula: see text]0.05 for each comparison).

Conclusion: Zygotes with different genders display different morphokinetic and morphometric features. Embryo selection using such parameters may lead to unbalanced sex ratio in the resulting offspring.
No, They’re Mine: Who Owns the Embryos?
Authors: PAGE Stephen
Published: November 2022

Background: Disputes between couples who have stored embryos are becoming more and more common. Where has the law come to with who can own or use the embryos- and how can a dispute be resolved to make it clear to a clinic as to who can and cannot use the embryo?

Aim: To set out for practitioners who owns the embryos, or at least the right to possess them- and practical ways to resolve disputes, so that it is clear who has the right to store, use, and discard, and who does not.

Method: A paper would be prepared setting out the law, along with practical tips.

Results: As above.

Conclusion: Clarity will be provided to practitioners so that they are aware of issues that arise when separating couples have embryos in storage- and can act protectively of themselves and of the embryos.
My Vital Cycles™: An Ovulatory-Menstrual Health Literacy Program for the Whole Person
Authors: ROUX Felicity , BURNS Sharyn , HENDRIKS Jacqueline , CHIH Jun
Published: November 2022

Background: A high prevalence of adolescent girls experience ovulatory-menstrual (OM) health difficulties such as painful periods, premenstrual symptoms, irregular cycles and abnormal bleeding patterns. These difficulties are associated with school absenteeism and reduced concentration in class. In addition, there is also an association with mental health challenges such as a negative body image, the onset of eating disorders and non-suicidal self-injury. A review of school-based resources suggests that this stigmatized subject is not only couched in biology, but it can be presented negatively.

Aim: This research project aimed to develop and trial a school-based OM health literacy program that positively addresses the biopsychosocial aspects of the OM cycle.

Method: A Delphi Panel was convened with experts in medicine, education, and public health. Together with a systematic literature review of OM health programs, they informed a draft program to teach adolescent girls and a draft questionnaire to test their OM health literacy. These drafts were reviewed by adolescent girls, parents, teachers and school healthcare professionals in focus groups and one-on-one interviews. The draft questionnaire was then test-retested to establish its validity.

Results: The Delphi Panel validated the content of the draft program. Based on the principles of Positive Education, the program was mapped to the Western Australian curriculum, Nutbeam’s Health Literacy Model and the WHO’s Health Promoting School framework. The focus groups and one-one-one interviews face validated the program and questionnaire, and suggested additional refinements (e.g. website, animations, videos, and the name My Vital Cycles™).

Conclusion: My Vital Cycles™ recognizes the OM cycle as a biopsychosocial phenomenon. It practically addresses common OM health difficulties with the aim of improving OM health literacy using Positive Education principles. The program has been registered for clinical trial.
Multinucleation in the Two-Cell Stage Embryo Matters
Authors: LAZZARO Leah , HEALEY Martin , OSIANLIS Tiki
Published: November 2022

Background: Blastomere multinucleation (MN), defined as the presence of more than one nucleus per cell, in the cleavage-stage embryo, is a well-documented phenomenon 1 . This nuclear anomaly has become more visible with the introduction of time-lapse incubation and an understanding of the potential outcomes of these embryos is necessary to inform decision-making and manage patient expectations.

Aim: To determine rates of blastocyst utilisation and euploidy for embryos with MN at the two-cell stage (MN2) in comparison to mononucleated and binucleated embryos.

Method: A retrospective analysis was performed at a single IVF unit, of embryos with known two-cell nucleation status from October 2019 to March 2021. Blastomere nucleation was assessed, via time-lapse monitoring (EmbryoScope; UnisenseFertiliTech), and categorised as mononucleate, binucleate or MN in all fertilised oocytes. Blastocyst utilisation rates (number of embryos frozen+transferred/number of oocytes fertilised) were compared together with euploidy rates in embryos that had preimplantation genetic testing for aneuploidy. Outcomes were modelled using multilevel logistic regression to allow for lack of independence between embryos when grouped by patient and cycle, and adjusted for patient age.

Results: Of the 4388 embryos included in this study, 68% were mononucleated, 14% binucleated and 18% MN. The likelihood of embryos becoming usable blastocysts based on nucleation status at the two-cell stage for mononucleated, binucleated and MN were 63%, 55%(p<0.001) and 35%(p<0.001) respectively. The euploidy rates for mono-, bi- and MN were 45%, 38%(p=0.09) and 31%(p=0.004) respectively. Predictive modeling, with adjusting for age, showed that a mononucleate two-cell embryo has 44% likelihood of becoming a euploid blastocyst, binucleate 36% and MN 28%.

Conclusion: There was a clear reduction in rate of blastocyst utilisation and euploidy in binucleate and a further reduction in MN two-cell stage embryos, in comparison to mononucleate embryos, which should preferentially be prioritised for transfer.
Opportunities and Challenges Arising from the Australian Male Infertility Exposure (AMIE) Study
Authors: BIGGS Sarah , LEWIS Sharon , KENNEDY Joanne , CHAMBERS Georgina , MCLACHLAN Robert , O’BRYAN Moira , von SALDERN Simon , HART Roger , KHASHABA Shadi , LEDGER William , NICOL Christopher , ROMBAUTS Luk , STERN Kate , YAZDANI Anusch , HALLIDAY Jane
Published: November 2022

Background: A four-stream research program, Men and Infertility over the Lifecourse, is funded by the MRFF to address the medical, personal and social cost of idiopathic male infertility. This program includes a national case control study: AMIE. Designing and implementing AMIE poses both opportunities and challenges.
Effects of COVID-19 Quarantine Period on Fertility Patients and IVF Clinic Management Worldwide
Authors: CUTTING Elizabeth , MOL Ben W. , VOLLENHOVEN Beverley , CATT Sally , HORTA Fabrizzio
Published: November 2022

Background: The initial months of 2020 experienced a rapid spread of a new Coronavirus named SARS-2. The World Health Organisation declared a global pandemic on 11th March 2020. Due to the new strain of the virus, little was known regarding COVID-19 and its effects on fertility and pregnancy.

Aim: To explore how fertility clinics and ART treatments proceeded post COVID-19 lockdowns and how this affected fertility patients.

Method: We surveyed fertility clinics world-wide with an online questionnaire through the platform RedCap. The questionnaire contained 33 questions focusing on the differences of country responses to guidelines and regulations. Scientific directors, medical directors and lab managers were contacted via email with the questionnaire link. The questionnaire was approved by Monash Health Human Research Ethics Committee and focused on the initial COVID-19 lockdown.

Results: There were 34 individual country responses, Asia (11), Europe (10), Africa (3), North America (3), Oceania (2) and South America (5). Of the 34 countries, 7 countries did not experience a complete cessation of all procedures. Most countries followed their government health recommendations and clinic policies. IVF/ICSI and frozen embryo transfer (FET) procedures proved to be the most delayed treatments. Sixteen countries reported to have an increase in freeze-all cycles compared to fresh transfers. Patients had to undergo a SARS-CoV-2 test in 50% of countries. Additional counselling for patients during the pandemic was implemented in 22 countries.

Conclusion: During the COVID-19 pandemic most fertility services were suspended, allowing insight into the implications of a shutdown. In conclusion, a protocol for scenarios of this nature would benefit future events. A protocol including increased phycological support, continuation of care, including telehealth and guidelines for prioritizing couples who need treatment most urgently.
The Impact of Covid-19 Travel Restrictions on Gamete Shipping from Australian IVF Clinics
Authors: EVERINGHAM Sam , WHITTAKER Andrea
Published: November 2022

Background: Cross-border surrogacy and egg donor arrangements are an increasingly common means to family building. Establishing patterns of use has always been difficult in relation to Australian patients. Accurate data is stymied by lack of documentation of international third-party reproductive care available to Australian authorities.

Since Australia’s international travel ban came into effect, it is hypothesised that those planning to use cross-border reproductive care have had to rely significantly more on local IVF clinics for services such as sperm freezing, embryo creation and gamete release procedures.

Establishing the increase in gamete shipping as a result of the ban on non-essential travel will improve understanding of the resource impact on Australian IVF laboratories. Such data can also assist policymakers assess the utility of state-based regulations relevant to CBRC.

Aim: Quantify and characterise the impact of the Covid-19-related travel ban on Cross-Border Reproductive Care amongst patients of Australian IVF clinics.

Method: All Australian IVF clinics were invited to provide de-identified data on interstate and international gamete export applications from two 12 month time periods pre and during Covid-19 related international travel lockdowns. Each dataset included: patient age; type of gametes exported; destination country or state; and date gamete release was approved.

Results: Results showed a very significant increase in gamete shipping in the twelve months after Covid-19 travel restrictions were enforced. They illustrate the comparative prevalence of shipping to established and newer destinations during the periods March 2019–February 2020 and June 2020–May 2021. The volume of shipping to the commonest destinations is quantified.

Conclusion: The inability of involuntarily infertile patients to travel internationally, rather than halt cross-border reproductive care, has led to a significant increase in update of gamete shipping. This is likely associated with increased utilization of Australian IVF clinics for embryo creation purposes. The high proportion of internationally-shipped gametes going to the US and Ukraine is likely a reflection of the availability of surrogates and donors and the legal frameworks.
Studies of Fertility Smartphone Apps Reveal a Lack of Insight and Scientific Information
Authors: FORD Emmalee , PETERS Alexandra , ROMAN Shaun , MCLAUGHLIN Eileen , BECKETT Emma , SUTHERLAND Jessie
Published: November 2022

Background: Female reproductive health and fertility smartphone applications have grown rapidly into a 400 million dollar “femtech” industry. As such, there has been increased interest in their functions and benefits. Claims of app participation in research is a marketing tool for consumers, however there is little known about the current scope of reproductive health app research and specifically how it is performed and reported.

Aim: This study aimed to determine the nature and extent of the peer-reviewed literature presented on fertility-based apps, to identify the reliability of the information within the apps, and to determine the ability of this information to educate users.

Method: A systematic search of six databases was conducted in April 2020, returning a total of 21,158 records. After duplicate removal, title and abstract screening exclusionary steps, 27 records were reviewed and charted.

Results: Fertility smartphone apps covered a variety of reproductive health themes including contraception, sexual health, and family planning, and used a range of research methodologies including prospective, retrospective and observational. A majority (63%) of the studies on apps specified ovulation windows as the sole information on fertility given to users. Around 52% of studies in the review based fertile window algorithms on stringent menstrual cycle length and variability requirements (typically 20-40 day length; <5 day variability). Furthermore, a third of studies in the scoping review contained authors that were affiliates or developers from an app company, and of these studies, 15% did not have co-authors independent to the app advisory board or employees.

Conclusion: Female reproductive health apps have the potential to fulfil a range of reproductive health needs. However, they currently do so with severe limitations when it comes to the menstrual cycle variability, and they do not adequately succeed in multi-functional capabilities. Furthermore, the scope of information available in apps via the user interface is a major barrier to independent review for accuracy. Our findings support the recommendation for open source sharing of app contents. This would ensure developers are accountable to consumers, healthcare professionals and researchers. This study highlights lack of research evaluating the effectiveness of an app’s contents to translate to knowledge or behaviour change in participants.
Is Cleavage Stage Multinucleation Indicative of Lower Pregnancy Potential in Euploid Blastocysts?
Authors: KELLEY Rebecca L. , CATTRALL Fleur , STOCK-MYER Sharyn , LEE Lisa Y. S. , GARDNER David K.
Published: November 2022

Background: Cleavage stage multinucleation is a morphological assessment IVF labs may use to rank embryos for transfer, as blastocysts that were multinucleated at the 2-cell or 4-cell stage have a lower live birth rate (LBR) compared to blastocysts that were mononucleated 1 . However, when these blastocysts are PGT-A tested, the euploidy rate is similar 2 , indicating that the poorer pregnancy outcomes may not be due to aneuploidy. It is unknown if multinucleation is indicative of a lower likelihood of pregnancy for euploid blastocysts.

Aim: To determine if LBR following transfer of euploid blastocysts is lower when blastocysts were multinucleated at the 2-cell or 4-cell stages.

Method: Retrospective study on 360 euploid blastocysts cultured in the EmbryoScope or EmbryoScope+ between March 2018 and October 2019, and individually transferred. Time-lapse images were retrospectively assessed for multinucleation at the 2-cell and 4-cell stage. A multinucleated embryo was defined as having [Formula: see text] 1 cell with [Formula: see text] 2 nuclei.

Results: Blastocysts that were multinucleated at the 2-cell stage (n=139) had a similar LBR to mononucleated embryos (40.3% vs 41.6%). Multinucleation at the 4-cell stage (n=43) also did not significantly affect LBR (37.2% vs 43.6%). Multivariate logistic regression analysis found no significant effect of multinucleation on LBR. Biochemical pregnancy, clinical pregnancy (fetal heart), and miscarriage rates were also similar between multinucleated and mononucleated embryos.

Conclusion: This study found no evidence that multinucleation at the 2-cell or 4-cell stage influences pregnancy rate in euploid blastocysts. As such, the assessment of cleavage stage multinucleation for PGT-A tested embryos may not be useful in ranking PGT-A tested embryos for transfer. Further work is required with larger numbers of embryos to confirm how the degree of multinucleation may influence LBR.
Improving Interpretation of Biopsies During Microsurgical Testicular Sperm Exploration in Azoospermic Patients: Use of Davidson’s Fluid
Authors: AARON GALEA Laurence , STURROCK Sue , APPU Sree , LANTSBERG Daniel , KATZ Darren
Published: November 2022

Background: Histological interpretation of testicular biopsies in the investigation of infertility in men with azoospermia requires adequate tissue fixation to preserve the nuclear and cytoplasmic detail, as well as the architectural organisation of germ cells in different phases of maturation within seminiferous tubules.

Research Aims/Objectives: The aim of the study was to assess the histomorphological quality of testicular biopsies using Davidson’s fluid (DF) as fixative and compare it to standard 10% neutral buffered Formalin.

Methodology: Concurrent testicular biopsies from the same testis from patients undergoing microsurgical testicular sperm exploration (m-TESE) were separately fixed in DF and Formalin and processed for histological examination. Histological parameters including sloughing of cells, cytoplasmic shrinkage of seminiferous tubular cells, nuclear chromatin detail, cytoplasmic graininess and overall clarity of morphological detail were graded on a scale of 0 to 4 (0=none, 1=minimal, 2=slight, 3=moderate, 4=marked). The effect of DF on biopsy diagnoses was assessed by comparison with corresponding Formalin fixed biopsy diagnoses.

Results/Findings: 87 testicular biopsies from 27 patients were examined. DF fixation resulted in significantly less luminal sloughing of cells (1.59±1.34 vs. 3.44±0.83, p = [Formula: see text] 0.00001), less cytoplasmic shrinkage of seminiferous tubular cells (1.58±1.11 vs. 3.11±1.07, p = [Formula: see text] 0.00001), better nuclear chromatin detail (3.06±0.91 vs. 1.92±0.48, p = [Formula: see text] 0.00001), less cytoplasmic graininess (2.11±0.96 vs. 2.86±0.87, p = 0.0014) and better overall clarity of morphological detail than Formalin fixation (3.14±0.69 vs. 2.14±0.58, p = [Formula: see text] 0.00001). The diagnostic concordance between DF fixed and Formalin fixed biopsies was 90.8%.

Conclusions: This study supports the use DF as a superior alternative fixative to Formalin for histological assessment of testicular biopsies.
PGT-M With or Without Triplet Repeat Detection for Fragile X Syndrome
Authors: ROSE Katherine , OSIANLIS Tiki , HEALEY Martin , NOWOWEISKI Sarah , VASUDEVAN Anand
Published: November 2022

Background: Fragile X syndrome (FraX) is the most common single gene cause of intellectual disability. It is caused by an unstable triplet repeat expansion in the Fragile X Mental Retardation 1 ( FMR1 ) gene. Female pre-mutation carriers are at-risk of passing a full-mutation onto their offspring, resulting in intellectual disability. A reproductive option to reduce the risk of having an affected child is Pre-implantation Genetic Testing for a monogenetic condition (PGT-M). Various methods exist to perform PGT-M for FraX.

Aim: To explore the option of PGT-M with and without triplet repeat detection for FraX, consider the potential advantages and disadvantages of each approach, and examine the decision of six couples undertaking PGT-M for FraX through our service.

Method: Patients were offered the choice of two testing methods of PGT-M for FraX. The first was haplotype analysis of markers linked to the FMR1 gene. The second was haplotype analysis of linked markers with simultaneous triplet repeat detection. Advantages and disadvantages of testing with and without triplet repeat detection were identified. Each couple’s clinical history and opinion regarding transfer of pre-mutation embryos were elicited. The couples final decision and reasoning was explored.

Results: Despite differing clinical histories and opinions on whether they would transfer a pre-mutation embryo or not, all six couples decided to proceed with PGT-M for FraX with triplet repeat detection. Reasons given included maximising information, treatment options, and pregnancy rate.

Conclusion: PGT-M for FraX should be offered with triplet repeat detection to improve the robustness of the diagnosis and to maximise patient choice. All couples decided to have PGT-M for FraX with triplet repeat detection which ultimately allows them to consider transfer of a pre-mutation embryo if no unaffected embryos are available for transfer.
Case Report: Successful Pregnancy and Birth of a Healthy Baby with PGT-A for Woman with Advanced Maternal Age
Authors: LEE Shaw Ni Amy , TO Chiou Fen , ONG Mei Jing , WONG Rui Shan , YU Su Ling
Published: November 2022

Introduction: The most common cause of failed implantation and miscarriage is embryonic aneuploidy and the risk of aneuploidy increases significantly with increasing maternal age. Pre-implantation genetic testing for aneuploidy (PGT-A) can be an option to improve the prognosis of women with advanced maternal age by extracting 3-5 trophectoderm cells from Day 5 and Day 6 blastocysts for genetic testing.

Case History: A 37 years old patient tried to conceive for 5 years was recruited into our PGS research study initiated by Ministry of Health in Singapore. She had 3 previous implantation failure and one miscarriage between 2015-2018. The patient had regular menses every 30-35 days. Antral follicle count was 48 and her husband’s semen analysis was normal with Density 87 million/ml, motility 34% and morphology 4%.

Results: Patient underwent an IVF cycle with PGT-A in December 2018 at our IVF Centre. 23 eggs were retrieved, 21 eggs were mature to undergo ICSI and 11 fertilized. The eggs were cultured in EmbryoGen immediately after ICSI and the embryos were transferred to BlastGen on Day 3 for extended culture. A total of 5 embryos were suitable for biopsy, 3 on Day 5 and 2 on Day 6. Embryos were vitrified while waiting for the genetic results. Chromosomal analysis of the biopsied trophectoderm cells was performed using NGS platform. Out of the 5 embryos tested, 2 embryos were euploid, giving 60% aneuploidy rate. One euploid embryo was thawed and transferred in a regulated frozen-thawed cycle in March 2020. The patient became pregnant and delivered a healthy baby boy. She returned in January 2022 to put back the remaining euploid embryo, she was again pregnant.

Conclusion: PGT-A for comprehensive chromosome screening in selecting and transferring euploid embryos in assisted reproduction has an immediate impact on implantation, reduces the rate of clinical miscarriages and results in higher live birth rates.
How Often Does Artificial Intelligence System (Ivy) Select the Same Embryo for Transfer Compared to Selection Based on Traditional Blastocyst Morphology or Time-Lapse Algorithm (KIDScore™D5)?
Authors: LEE Lisa Y. S. , CATTRALL Fleur , KELLEY Rebecca L. , STEVENS John , GARDNER David K.
Published: November 2022

Background: When patients have multiple blastocysts following IVF/ICSI, selection of the most viable blastocyst for transfer can reduce time taken for patients to conceive. An artificial intelligence system, Ivy, has been developed to predict pregnancy from embryo images.

Aim: To determine the frequency that Ivy selects the same embryo for transfer as morphological assessment or time-lapse algorithm (KIDScore™D5v2).

Method: Data was collected from 100 patients that had [Formula: see text] 2 blastocysts for day 5 fresh single embryo transfer (total n=1319 embryos, cultured in EmbryoScope+). The blastocyst transferred was selected by clinic protocol: a combination of morphology and morphokinetics. Ivy analysed time-lapse images to generate an IVYScore. Four embryologists assessed morphology of one image per embryo using different focal planes. Morphokinetics parameters were annotated to calculate KIDScore.

Results: Embryologists chose the same blastocyst for transfer in 51 out of 100 patients, and only 35.3% of these embryos had the highest IVYscore compared to sibling blastocysts. Compared to KIDScore, Ivy would have chosen the same blastocyst in 61% of the cases. Agreement between all methods was lower when patients had morphologically similar blastocysts (18.2% vs. 50.0%, p[Formula: see text]0.001). Clinical pregnancy rate was 48.0% (n=100), which was similar for blastocysts selected by Ivy (50.0%, n=64), morphology (n=29, 41.4%) or KIDScore (n=74, 45.9%). Further, 44 frozen blastocyst transfers resulted in 14 pregnancies. If IvyScore were to be used instead of clinic protocol, 11 cases would have resulted in an equal or shorter time to pregnancy.

Conclusion: There is limited agreement between methods when patients have multiple blastocysts available for transfer, especially when morphology is similar. Pregnancy rates of Ivy-selected blastocysts were similar to other methods, indicating that Ivy could be used with comparable success, and could even lead to reduction in time to pregnancy. This study is limited by its retrospective nature, and unknown pregnancy potential of blastocysts that were not transferred.
Cell Number on Day 3 of Embryo Development is Associated with Ploidy and Pregnancy Rates
Authors: DAMETTO Gracie , ZANDER-FOX Deirdre , MCPHERSON Nicole , TREMELLEN Kelton , PACELLA-INCE Leanne
Published: November 2022

Selection of a blastocyst for transfer is based on day5/6 morphology with day3 morphology only used if two blastocysts are equal in quality. Day3 assessments are based on cell number and fragmentation with embryos that are developmentally advanced ([Formula: see text]10 cells) being downgraded. After extended development, if [Formula: see text]10 cell embryos are the best quality they are selected for transfer. Thus, the aim of this study was to determine if cell number on day3 has an impact on embryo fate, euploidy rates and pregnancy rates.

Data was retrospectively analysed from 269 women (average age 35.7) undergoing stimulated IVF treatment. Embryos were allocated to one of four categories based on day3 morphological score [Formula: see text]6 cells, 7-9 cells, 10-12 cells and [Formula: see text]13 cells. Results were correlated with embryo fate (vitrification/transfer) and pregnancy rates.

After extended culture embryos with [Formula: see text]13 cells on day 3 were mostly likely to have undergone a fresh transfer (28.1%, p[Formula: see text]0.05) compared with embryos with 7-9 cells and 10-12 cells (13.7% and 14.0%, respectively). Embryos with [Formula: see text]6 cells were least likely to be transferred (5.2%) and vitrified (7.1%). Further, embryos with [Formula: see text]6 cells had the lowest pregnancy rate (12.5%) compared with all other groups (p[Formula: see text]0.05). No differences were observed for embryos with 7-9 cells, 10-12 cells and [Formula: see text]13 cells for vitrification rates (42.3%, 40.5% and 35.1%, respectively) or pregnancy rates (33.5%, 43.5% and 45.8%, respectively). Interestingly, the incidence of euploid embryos was increased in [Formula: see text]13 cell embryos (70.0%, p[Formula: see text]0.05) compared with [Formula: see text]6 cells, 7-9 cells and 10-12 cells (52.0%, 42.6% and 52.5%, respectively).

Results from this study provide evidence that a review on cleavage stage embryo grading protocols which currently downgrades developmentally advanced embryos [Formula: see text]10 cells is warranted as these embryos do not appear to have a negative impact on pregnancy rates and can result in some of the best clinical outcomes.
And Baby Makes Four: Dealing with Throuples
Authors: PAGE Stephen
Published: November 2022

Background: Throuples exist and wish to have children. Their existence challenges existing notions about relationships, parenting and treatment.

Aim: To illuminate what the law says about treatment for those in throuple relationship seeking ART, and to illuminate who is and is not a parent. It may be that all three are the parents, or one of them or two of them. Even if not recognised as a parent, one of the parties seeking and consenting to treatment may nevertheless be liable to the financial burdens of parentage-child support (or damages in lieu) or in case of death a claim on their estate.

Method: To illustrate the legal and practical challenges arising from a refusal to treat or the decision to treat when the intended parents are a throuple. The intent would be to provide a paper illustrating the points, and talking to the paper.

Results: Throuples are in large part protected by anti-discrimination law. The implications for the child and for each of the parties would demand that they obtain legal advice before treatment is offered.

Conclusion: As above.