bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Duo-Stimulation is a Time and Cost-Effective Stimulation Method to Increase the Number of Usable Blastocysts and Ongoing Pregnancies
Authors: POHL Nyssa , WARD Madeleine , DALTON Russell 
Published: November 2022

Background: Duo-stimulation is an ART method whereby a patient undergoes two rounds of ovarian stimulation within a single menstrual cycle; a follicular phase stimulation (FPS) followed by a luteal phase stimulation (LFS) a . Previous studies have indicated that adoption of the duo-stimulation method increases the occurrence of at least one euploid blastocyst from 42% to 65.5% within a single ovarian cycle b . Additional benefits of the duo-stimulation method include both time taken to achieve similar results and, in Australia, cost a . Aim: To determine the efficacy of LPS oocyte collections, as part of a duo-stimulation cycle, in relation to; stimulation, egg collection and utilization parameters, as well as pregnancy outcomes from subsequent FET cycles. Method: A retrospective analysis of all LPS collections as part of a duo-stimulation cycle and subsequent FET cycles undertaken at Ballarat IVF between November 2016 and April 2021 was performed. Results: 129 duo-stimulation cycles were started, (FPS egg collection), with 118 of these progressing to a LPS collection. The average number of oocytes collected was similar with 4.8 eggs collected from FPS egg collections and 4.9 oocytes from LPS collections. Embryo utilization rates were increased in a LPS collection compared to an FPS collection, at 36.09 and 38.04 respectively. Ongoing pregnancy rates from subsequent FET cycles were also increased when embryos created from an LPS collection were transferred, 33.3% vs those created from an FPS cycle 30.6%. Conclusion: Egg collections performed after an LPS as part of a duo-stimulation cycle are a clinically effective method to procure more usable embryos in a short period of time. The duo-stimulation method will be of increasing benefit to those women of advanced maternal age, poor responders or undergoing fertility preservation for medical reasons. The biggest benefit to patients undergoing this method is cost related; when taking into account medicare rebates, undertaking two egg collections as part of a duo-stimulation cycle is a significantly more affordable option for patients in comparison to undertaking two subsequent stimulation cycles, with similar clinical outcomes.
The Effectiveness of Intra-Uterine Platelet Rich Plasma Infusion for Improving Endometrial Thickness and Pregnancy Outcomes: A Pilot Study Analysis
Authors: POHL Nyssa , DALTON Russell 
Published: November 2022

Background: Platelet rich plasma (PRP) is well researched and utilized in many medical fields to increase angiogenesis, tissue healing and regeneration a . Recent studies have reported that intra-uterine PRP infusions when used during frozen embryo transfer (FET) cycles, can similarly affect endometrial proliferation, resulting in decreased cycle cancellation rates and improved endometrial thickness and pregnancy outcomes in women with thin linings b , c Aim: To establish if intra-uterine PRP infusions can increase endometrial thickness and improve pregnancy rates in women with a history of thin endometrial lining. Method: An analysis of all PRP infusions and their FET cycles undertaken at Ballarat IVF between November 2020 and May 2021 was performed. Patients with a history of thin endometrial lining were offered a PRP infusion from day 6 of their cycle, followed by a second infusion 2-3 days later. Endometrial thickness was measured by ultrasound prior to PRP infusion, post infusion #1/prior to PRP infusion #2, and post PRP infusions, and pregnancy outcomes collected. Results: Thirty patients were offered PRP infusions prior to their FET cycle and all 30 patients received one infusion of PRP. Twenty-six patients went on to receive a 2nd PRP infusion. Twenty-five patients had an FET, only one cycle was cancelled due to poor endometrial thickness. Average Endometrial thickness increased by 0.8mm after each PRP infusion; from 6.2mm prior to PRP infusion, to 7.0mm prior to PRP infusion #2, to 7.8mm post PRP infusions. Clinical pregnancy rates and ongoing pregnancy rates were 48%* and 24%* respectively (*two scans pending: anticipated rates 48% and 28% respectively). Conclusion: Intra-uterine Platelet Rich Plasma infusions prior to a FET appear to offer a safe method to increase endometrial lining in women with a history of thin endometrium, allowing these cycles to proceed to an embryo transfer. Clinical pregnancy rates are increased compared to women who have no history of thin endometrial lining. Despite increased implantation, ongoing pregnancy rates (defined by a fetal heart) are decreased compared to women with no history of a thin lining. A longer-term study on a larger number of patients is required to confirm the effectiveness of this technique on live birth rates.
Mitochondrial Uncoupler BAM15 Ameliorates Associated Metabolic PCOS Traits in a Hyperandrogenic PCOS Mouse Model
Authors: RODRIGUEZ PARIS Valentina , ALEXOPOULOS Stephanie J. , HU Ying , SHAH Divya P. , AFLATOUNIAN Ali , EDWARDS Melissa C. , BERTOLDO Michael J. , GILCHRIST Robert B. , HOEHN Kyle L. , WALTERS Kirsty A. 
Published: November 2022

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition characterized by endocrine, reproductive and metabolic abnormalities. There is no cure for PCOS and existing treatments are suboptimal. Obesity and adverse metabolic features are prevalent in PCOS patients, but weight loss has a beneficial effect on PCOS features. However, dietary interventions aimed at weight loss are difficult to sustain long-term. Interestingly, recent data from animal studies has shown that a mitochondrial uncoupler, BAM15, is an effective approach to pharmacologically treat obesity and metabolic diseases. Aim: To investigate the efficacy of BAM15 to ameliorate PCOS-traits in a PCOS mouse model. Method: The effect of BAM15 treatment on metabolic and reproductive PCOS features were evaluated in dihydrotestosterone (DHT)-induced PCOS mice fed a standard chow diet ± BAM15 for 10 weeks. Results: As expected, exposure of female mice to DHT induced the PCOS metabolic features of increased body weight (P<0.05), lean mass (P<0.001), increased parametrial and mesenteric fat pad weights (P<0.05) and adipocyte hypertrophy (P<0.05). DHT-induced PCOS mice also exhibited increased HOMA-IR, cholesterol and fasting triglyceride levels and hepatic steatosis (all P<0.05). Conversely, DHT-induced PCOS females treated with BAM15 displayed lowered body weights similar with controls, a significant decrease in parametrial and mesenteric fat depot weights (P<0.05) and reduced adipocyte hypertrophy. Likewise, BAM15 treatment decreased HOMA-IR, cholesterol and fasting triglyceride levels and the degree of hepatic steatosis observed in PCOS females, to levels comparable with control females. Lastly, PCOS mice presented the reproductive PCOS traits of irregular cycles and ovulatory dysfunction, though BAM15 treatment did not improve these PCOS features. Conclusion: These findings demonstrate that the pharmacologic mitochondrial uncoupler BAM15 is able to ameliorate metabolic PCOS features in a PCOS mouse model. These data provide evidence to support BAM15 as a potential innovative therapeutic approach to manage associated metabolic PCOS features.
Is There an Increased Incidence of Aneuploid Embryos in Cases of Obstructive and Non-Obstructive Azoospermia?
Authors: SOLE Sally , WILLATS Elissa , GREEN Mark , ROMBAUTS Luk , KATZ Darren , ZANDER-FOX Deirdre , HORTA Fabrizzio 
Published: November 2022

Background: Current evidence supports that males with low spermatozoa concentrations, as well as obstructive azoospermia (OA) or non-obstructive azoospermia (NOA), present with high rates of aneuploid spermatozoa. This issue could potentially lead to an increased number of aneuploid embryos in subsequent ICSI cycles using surgically retrieved spermatozoa, however, azoospermia is not routinely considered to be a clinical indication for pre-implantation genetic testing for aneuploidies (PGT-A). Aim: To identify the incidence of aneuploid embryos in PGT-A cycles that used testicular spermatozoa extracted through surgical sperm retrieval (SSR). In addition, whether aneuploidy rates differed between embryos fertilised with SSR compared with ejaculated spermatozoa. Method: A retrospective study of OA and NOA patients who underwent SSR between March 2017 and September 2020 and had PGT-A cycles. Next-generation sequencing was employed to detect embryo aneuploidies. Data were compared and analysed using a chi-square test with PGT-A cycles using ejaculated spermatozoa within the same time-period. Results: A total of 57 males underwent SSR, leading to 68 cycles that included the use of PGT-A. A total of 152 embryos with conclusive results identified there to be 57.2% euploid embryos (87/152) and 38.2% aneuploid embryos (58/152) in the SSR group. In comparison, the ejaculated spermatozoa group resulted in 59.2% (2115/3677) euploid embryos and 35.7% (1312/3677) aneuploid embryos. The incidence of aneuploid embryos (38.2%) in the SSR group was not statistically significant [Odds ratio: 1.11 (0.79-1.56) p=0.53]. Importantly, there were no differences for mean maternal age for both study groups (SSR female partners: 36.7 years; ejaculated spermatozoa female partners: 37.1 years; p>0.1). Conclusion: The current outcomes indicate there is not an increased incidence of aneuploid embryos in PGT-A cycles of men who underwent to SSR compared with men using ejaculated spermatozoa.
The Race to Equilibrate
Authors: GLAGE Eve , DEAN Casey , GUNASEGARAN Kavya , SORBY Kelli 
Published: November 2022

Background: While it is well documented that culture in hypoxic conditions produces superior outcomes, the mechanics of establishing such conditions within the embryo’s liquid environment is less clear. It is not uncommon for laboratories, while ‘culturing’ in low-oxygen, to equilibrate dishes in CO2 only environments prior to use, meaning embryos are exposed to high oxygen tension in their media even after placing into the hypoxic environment, but for how long is so far unclear. Aim: To assess the equilibration rate of oxygen within embryo culture media when exposed to hypoxic conditions. Method: A handheld blood gas analyser (EPOC system, ‘BGEM’ cartridges) was used to determine the pO2 of G1+ culture media after exposure to a reduced oxygen environment. Results: Culture media in atmospheric oxygen (with or without the presence of CO2) showed mean pO2 values of 150mmHg. Media fully equilibrated over 24 hours in 5% oxygen fell to approximately 70mmHg. This was well above the theoretically expected value but shown to be consistent across multiple measurements including various dish and incubator types. Initial equilibration to hypoxic conditions occurred relatively rapidly, with dishes undergoing 50% of the required oxygen reduction in only 30 minutes. Within 1.5 hours of exposure 5% O2, media achieved 83% of the required change, with full equilibration reached at approximately 2.5 hours. Pre-equilibration of dishes in 6% CO2 did not appear to affect the oxygen diffusion rate compared with non-equilibrated media. Oxygen exhibited similarly rapid diffusion into culture media when dishes equilibrated at 5% O2 were exposed to atmospheric conditions, with pO2 increasing by 1.46mmHg per minute. Conclusion: The diffusion rate of oxygen appears to be significantly faster than the more widely studied CO2, however, oxygen tension in media still requires greater than 2 hours to reach optimum levels, requiring us to consider oxygen in our equilibration practices.
Investigation into Platelet Rich Plasma (PRP) Infusions Within the Intrauterine Cavity, to Support the Development of Endometrial Lining in Transfer Cycle Patients
Authors: ALCOCK Jenyne , BURMEISTER Dr Lynn , ZHANG Shelley , GLAGE Eve , SORBY Kelli 
Published: November 2022

Background: Poor endometrial lining is classically referenced as <6mm. Patients commencing Embryo Transfer (ET) cycles can experience issues with lining development and require additional therapy supplementation with the aim of increasing lining thickness prior to ET day. PRP is an adjuvant IVF treatment, known as an infusion therapy, for use in uterine lining development support with the specific aim of increasing endometrial lining outcomes for patients prior to ET. Aim: To assess the effectiveness of PRP infusion therapy on lining development for ET cycle patients. Method: Using the TGA approved Alocuro PRP medical device system, 10mls of whole blood is collected via venepuncture, this sample is centrifuged, to produce 3 identifiable layers; Plasma, Buffy coat and Packed red blood cells. The Buffy coat is collected with 1ml of Plasma and administered via Intrauterine Infusion with an Embryo Transfer Catheter set. Patients are offered this procedure based on clinical histories of poor lining outcomes. Retrospective analysis of all patients undertaking PRP infusion, included assessment of uterine thickness, was conducted. Results: A total of 35 records were identified, of these 2 were cancelled prior to administration of PRP and 7 were removed due to incomplete records of Initial Lining measurement or Final Lining measurement. In the remaining cohort of 26 patients, 2 patients demonstrated regression in their lining, while 24 patients recorded an increase in final lining measurement, with a mean increase of 2mm or 28% over initial lining measurements. When compared with their previous cycle, PRP infusion cycles demonstrated a greater increase in lining thickness between scans, 0.82mm and 1.78mm respectively (p=0.018). Conclusion: PRP treatment appears to show potential in the treatment of poor lining development and warrants further study.