bluuebunny/crossref_metadata_2025 huggingface dataset:
The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease
Authors: Liyanage Ganesha , Trewin Benjamin P , Lopez Joseph A , Andersen Jane , Tea Fiona , Merheb Vera , Nguyen Kristy , Lee Fiona X Z , Fabis-Pedrini Marzena J , Zou Alicia , Buckland Ali , Fok Anthony , Barnett Michael H , Reddel Stephen W , Marignier Romain , El Hajj Aseel , Monif Mastura , van der Walt Anneke , Lechner-Scott Jeannette , Kermode Allan G , Kalincik Tomas , Broadley Simon A , Dale Russell C , Ramanathan Sudarshini , Brilot Fabienne
Published: January 2024

Background

Myelin oligodendrocyte glycoprotein (MOG) IgG seropositivity is a prerequisite for MOG antibody-associated disease (MOGAD) diagnosis. While a significant proportion of patients experience a relapsing disease, there is currently no biomarker predictive of disease course. We aim to determine whether MOG-IgG epitopes can predict a relapsing course in MOGAD patients.

Methods

MOG-IgG-seropositive confirmed adult MOGAD patients were included (n=202). Serum MOG-IgG and epitope binding were determined by validated flow cytometry live cell-based assays. Associations between epitopes, disease course, clinical phenotype, Expanded Disability Status Scale and Visual Functional System Score at onset and last review were evaluated.

Results

Of 202 MOGAD patients, 150 (74%) patients had MOG-IgG that recognised the immunodominant proline42 (P42) epitope and 115 (57%) recognised histidine103/serine104 (H103/S104). Fifty-two (26%) patients had non-P42 MOG-IgG and showed an increased risk of a relapsing course (HR 1.7; 95% CI 1.15 to 2.60, p=0.009). Relapse-freedom was shorter in patients with non-P42 MOG-IgG (p=0.0079). Non-P42 MOG-IgG epitope status remained unchanged from onset throughout the disease course and was a strong predictor of a relapsing course in patients with unilateral optic neuritis (HR 2.7, 95% CI 1.06 to 6.98, p=0.038), with high specificity (95%, 95% CI 77% to 100%) and positive predictive value (85%, 95% CI 45% to 98%).

Conclusions

Non-P42 MOG-IgG predicts a relapsing course in a significant subgroup of MOGAD patients. Patients with unilateral optic neuritis, the most frequent MOGAD phenotype, can reliably be tested at onset, regardless of age and sex. Early detection and specialised management in these patients could minimise disability and improve long-term outcomes.
Can laboratory HIV and infectious syphilis data inform future pre-exposure prophylaxis use in women in Ontario, Canada?
Authors: Sadeghi Yasamin , Nelson Paul , Sullivan Ashleigh , Allen Vanessa , Hasso Maan , Liu Juan , Tran Vanessa , Tan Darrell H S
Published: January 2024

Objectives

Infectious syphilis has been proposed as an indication for HIV pre-exposure prophylaxis (PrEP) in women. We explored how many women experienced HIV seroconversion after being diagnosed with syphilis in Ontario between 20 April 2010 and 31 December 2021.

Methods

Through deterministic linkage of laboratory data at the Public Health Ontario laboratory, which conducts the vast majority of syphilis and HIV testing in Ontario, we quantified the number of females with positive syphilis diagnoses who subsequently exhibited HIV seroconversion between April 2010 and December 2021. New HIV cases were identified by diagnostic serology or HIV viral load test result of ≥20 copies/mL at least 60 days after the positive syphilis test. We report aggregate numbers of women with new laboratory evidence of HIV infection after their first positive syphilis test.

Results

Among 7957 women with positive syphilis tests during the study period, 6554 (82.4%) had linkable HIV serology tests and 133 (1.7%) ever tested HIV positive. With further linkage to viral load data, the number of women who ever had laboratory evidence of HIV infection increased to 184 (2.3%). However, when restricting to women whose first positive HIV test or HIV viral load occurred after their first positive syphilis test, this number decreased to 34 (0.4%). The median (IQR) time between the positive syphilis test and the first laboratory evidence of HIV was 551 (IQR=226–1159) days.

Conclusion

Although it is clinically appropriate to recommend HIV PrEP to women with syphilis, Ontario surveillance data suggest that the population-level impact of this strategy on the HIV epidemic in Ontario would have been modest during this 11-year period. Future studies should explore additional ways of prioritising women for PrEP.
The Prevalence of PCOS in East Asia
Authors: Li Rong
Published: January 2024

Polycystic ovary syndrome (PCOS) has emerged as a significant international public health concern in East Asia and around the world. It is characterized by clinical manifestations such as oligo/anovulation, hyperandrogenism, and polycystic ovarian morphology, etc. The pathogenesis of PCOS is complex, involving the interaction of genetic and environmental factors. The prevalence of PCOS in China has reached 7.8% with variation across different regions, occupations, and age groups. Notably, the prevalence of PCOS among Chinese women has been increasing from 2010 to 2020. Similar upward trends in prevalence rates of PCOS have also been observed in other countries. The rise in prevalence is primarily driven by type III PCOS (O+P), while type IV PCOS (H+O+P) has remained relatively stable. PCOS is associated with significant metabolic consequences, including increased risk of impaired glucose tolerance and type 2 diabetes mellitus, atherogenic dyslipidemia, systemic inflammation due to increased secretion of pro-inflammatory factors by adipose tissue, non-alcoholic fatty liver disease, hypertension, and potential coagulation disorders. PCOS affects quality of life and can worsen anxiety and depression either due to its symptoms or due to the diagnosis of a chronic disease. Genetic studies have identified susceptibility loci for PCOS, shedding light on its genetic underpinnings. Treatment aims in PCOS include optimising healthy weight, improving underlying hormonal disturbances, prevention of future reproductive and metabolic complications, and improving quality of life. Effective intervention strategies for PCOS include pharmacological treatments, lifestyle modifications, and surgical treatments.
Optimising IVF Outcomes
Authors: Vuong Lan N
Published: January 2024

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, with an overall prevalence of 5% to 15%, and a frequent cause of infertility. Ovulation disorders are the main cause of infertility for the couples. A range of endocrine and metabolic traits are also associated with PCOS and these include obesity, dyslipidemia, insulin resistance, hyperinsulinism and an increased risk of type 2 diabetes mellitus and cardiovascular disease.

Studies have found that women with PCOS had a higher live birth rate, clinical pregnancy rate and implantation rate, as well as an increased risk of ovarian hyperstimulation syndrome (OHSS), pregnancy complications including miscarriage, preterm delivery, gestational diabetes mellitus and pregnancy-induced hypertension in their first IVF treatment when compared with non-PCOS controls.

During the past three decades, applying IVF for infertility treatment PCOS women has increased significantly, and the landscape of treatment strategies has changed dramatically. GnRH agonist triggering oocyte maturation combined with freeze-all embryos is an effective and commonly used protocol nowadays to achieve good success rate as well as to minimize the risk of OHSS in women with PCOS. Recently, there has been an increasing use of oocyte in-vitro maturation (IVM) for treating infertility in women with PCOS. IVM technique could be considered as an alternative to IVF in centers where it is available. However, strategies to minimize pregnancy complications in women with PCOS remain further studied.
Can AI Improve Imaging Diagnostics?
Authors: Hull Mary Louise
Published: January 2024

The 2016 Cochrane Review identified Magnetic Resonance Imaging (MRI) and Transvaginal Ultrasound scans (TVUS) as the most diagnostic non-invasive test for endometriosis. This led to IMAGENDO, which uses Artificial Intelligence (AI) to model digital data from these two imaging modalities to improve the accuracy of endometriosis non-invasive diagnostics.

The IMAGENDO team have developed a novel, award winning, multimodal approach to improve the sensitivity and specificity of endometriosis imaging. The talk will describe some of the methods used, the impact AI has had on diagnostic accuracy and the challenges faced and yet to be overcome. The likely role of AI in future endometriosis diagnostics will be speculated upon.
Biopsy Procedure and Preparation (Including Biopsy Medium and Biopsy Dish)
Authors: Chang Tiencheng Arthur
Published: January 2024

This lecture is a concise introduction designed to equip participants with essential knowledge and practical skills in performing embryo biopsy for PGT. The workshop emphasizes the significance of procedure and preparation which may impact the blastocyst biopsy and its role in selecting embryos. During the lecture, attendees are introduced to the fundamental steps of the blastocyst biopsy, starting with the optimal time frame for performing the biopsy, followed by techniques for safe and accurate zona drilling without compromising the embryo’s viability, as well as the importance of using a suitable biopsy medium that provides the necessary nutrients and support for the embryo during the biopsy. This lecture also delves into the selection and preparation of the biopsy dish, outlining the key factors to consider and practical tips on maintaining optimal conditions for the embryo within the biopsy dish and minimizing potential stress, to ensure successful outcomes.

The instructor will share experiences and provide valuable insights into troubleshooting potential challenges that may arise during the biopsy process. Participants are encouraged to engage in interactive discussions and following hands-on sessions, allowing for a comprehensive understanding of the procedure, and fostering a collaborative learning environment. In conclusion, this lecture offers a valuable platform for embryologists to enhance their knowledge and skills in performing blastocyst biopsies with precision and confidence.
Zona Opening - The Different Options and Methods
Authors: Liow Sweelian
Published: January 2024

In blastocyst biopsy, zona opening is an essential step to facilitate extraction of a few trophectodermal cells for analysis. The methods of zona opening will be discussed.
Micromanipulator Set-up - Taking Control of This System
Authors: Rose Ryan
Published: January 2024

Embryo biopsy is a precise procedure, demanding adept manipulation skills and the finest instruments to ensure high-quality results. One of the most crucial elements to gain mastery over is the micromanipulator system. In this session attendees will delve into the practical facets of setting up and controlling a micromanipulator within the context of a blastocyst biopsy. The session will also cover the important aspects of system set-up, instrument alignment, and objective positioning, aimed to maximize control, precision, and stability during the biopsy procedure.

Moreover, the discussion will touch on the common challenges faced during the set-up process, offering practical solutions, and troubleshooting tips to manage these effectively.
The Timing of Vitrification After Biopsy
Authors: Ezoe Kenji
Published: January 2024

The blastocysts are often vitrified after trophectoderm biopsy to secure the time for transportation to external facilities and diagnosis. Previous studies reported that the time interval from the biopsy to vitrification affected the viability of biopsied blastocysts after warming. Furthermore, the degree of blastocyst re-expansion at vitrification was associated with the survival rate after warming. In this presentation, I will share the summary of previous studies, the results of our recent study, and the optimal timing of vitrification after biopsy.
The Future of Genetic Testing of Embryos
Authors: Handyside Alan
Published: January 2024

It is now over 30 years since the first pregnancies and live births following IVF, embryo biopsy and preimplantation genetic testing (PGT) were reported in 1990, in several couples at risk of having children affected by X-linked diseases (Handyside et al., 1990). Since then, methods for genetic analysis at the single-cell level have evolved alongside the rapid advances in human genetics and sequencing of the human genome. The range of applications has also expanded beyond monogenic diseases to chromosome aneuploidy, structural chromosome rearrangements and other genetic abnormalities. PGT is now practiced world-wide and remains a valuable alternative for at risk couples.

With the development of methods for whole genome amplification, such as multiple displacement amplification (MDA), genome-wide analysis became possible. This has led to the development of microarray or next generation sequencing (NGS) based methods for genome-wide haplotyping of parental chromosomes in embryo samples and enabled universal linkage-based testing for monogenic diseases combined with molecular cytogenetic analysis of chromosome abnormalities. In the future, these methods will become increasingly informative and accurate, and it may be possible to use cell-free DNA in spent culture medium to avoid embryo biopsy.

Handyside AH, Kontogianni EH, Hardy K and Winston RML (1990) Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344, 768
News and Fake News in Investigating Recurrent Pregnancy Loss
Authors: Coomarasamy Aravinthan
Published: January 2024

Women and couples who have had the misfortune of losing pregnancies, particularly multiple pregnancies, would often wish to know why the miscarriages happened. This information is important for them to make sense of the loss, help with closure, and seek treatments to avoid future miscarriages. Healthcare practitioners would want to know the reason for the miscarriages so that they can provide accurate prognostic information and offer targeted treatments to improve future pregnancy outcomes. The deeply felt need for finding reasons for miscarriages has led to the proliferation of multiple tests. But which one are useful? And which ones are fake? Which test results show an association with miscarriage, have prognostic value, and guide treatment? Which ones don’t? This lecture takes an evidence-based lens to these questions to tease apart the real news from fake news.
Surgical Management of Intrauterine Adhesions
Authors: Huang Xiaowu
Published: January 2024

Intrauterine adhesions, also known as Asherman’s syndrome, can have an impact on both reproductive outcomes and gynaecologic symptoms. Surgical management with hysteroscopic lysis of adhesions is the gold standard for treatment.

The following techniques are described in this presentation for cases with severe occlusive cavity and should be performed by experienced surgeons.

1. The use of 3D ultrasound played an important role in the preoperative workup of the patient, it could be used to evaluate the severity of intrauterine adhesion and predict the complexity of the cases. 2. Transabdominal 2D ultrasound guidance can help to delineate the location and extent of the adhesions and reduce the risk of uterine perforation and the formation of false passage. Laparoscopic guidance for severe cases has been advocated for immediate treatment of uterine perforation and minimizing extrauterine trauma. 3. In patients with severe intrauterine adhesion, a “myometrial scoring technique” could be used by bipolar electrode need with score 6 to 8, 4-mm-deep incisions from the fundus to the cervix and a transverse incision at the uterine fundus. Or the “ploughing technique” could be used by scissors, both methods aim to remove the fibrotic tissue, expose any underlying healthy basal endometrial tissue capable of regeneration. It remains to be seen whether “ploughing technique” using cold scissors or a “myometrial scoring technique” by bipolar electrode produces similar or different results, which could only be resolved by RCT in the future. 4. Surgical management offers favourable fertility outcomes and is often successful in restoring menstruation. Endometrial thickness and volume assessed by 3D-TVUS may have important predictive value for pregnancy after hysteroscopic adhesiolysis. 5. Prevention of reformation of adhesions remains challenging and no single method for preventing recurrence has shown superiority.
Genetic Diagnosis in Male Infertility
Authors: Rehman Khaleeq
Published: January 2024

The male factor is responsible for more than half of infertile couples. It is caused by diverse factors. Amongst them, genetic and epigenetic abnormalities are important disorders. Appropriate genetic diagnosis is the key to understanding male factor infertility.

It is interesting to note that genetic abnormalities of any disease vary from one region to another due to ethnic, geographic, and other differences. Our experience with the Pakistani population is similar. We have found novel genetic mutations in familial Idiopathic hypogonadotropic hypogonadism (IHH) specific to our patients. Familial IHH of Pakistan were studied through whole genome sequencing and we found novel mutations in GnRHR, KISS1R, and ANOS1 genes. We have found IHH families with X linked mode of inheritance and novel deletions in the ANOS1 gene that could be prevented by avoiding cousin marriages that are common in Pakistan. Similar results were found for our patients suffering from congenital absent vas deferens. This is why every region needs indigenous research to understand the genetic and epigenetic abnormalities of its population. The current presentation will highlight and discuss further research updates in this area. Today we have high hopes for the future of genetic medicine, but any developments in treatment strategies would require an understanding of the genetic patterns of different populations. It is an uphill task, especially for developing countries, so broadly-based collaborative studies are required with the facilitation of global organisations like “ASPIRE”.
Fundamental Mechanisms of Sperm Production: The Role of Microtubules
Authors: Dunleavy Jessica
Published: January 2024

Spermatogenesis is a feat of unparalleled biological scale and complexity. At any one time, the human testis harbours millions of germ cells in a continuous progression through multiple rounds of mitosis and meiosis, followed by a series of dramatic remodelling events. These processes are the critical determinant of sperm number, morphology, and motility, and 70% of infertile men have abnormalities in one, or more, of these parameters. Testament to its complexity, human spermatogenesis involves the expression of 84% of all protein-encoding genes and is touted as a health ‘canary in the coalmine’, as infertile men as a cohort, die younger than their fertile counterparts. Understanding the mechanisms of sperm production is thus essential, not only in the context of formulating infertility treatments, but also to identify additional health risks for the man and any potential offspring. In addition, sperm research has, and will continue to, shed light on gene function relevant to broad aspects of cell biology, as fertility is often the first, but not the only system, to fail, and may uncover strategies for contraceptive development. Microtubules (MTs) are a key driver of many aspects of sperm production. They form the fundamental machinery of mitosis and meiosis, sperm head shaping, and the sperm tail, in addition to playing roles in intracellular trafficking, including during acrosome biogenesis, and in germ-Sertoli cell adhesion. Through the use of mutant mouse models, our research has revealed the functional diversity of MTs in spermatogenesis is co-ordinated by a diverse suite of MT-associated proteins, including multiple MT-severing proteins from the katanin and spastin families, and the non-canonical tubulins, epsilon and delta. Moreover, we have shown that disruption of this MT regulatory toolbox has catastrophic consequences for sperm production and male fertility.
Cell-Cell Interactions in the Testis that Support Male Fertility
Authors: O’Donnell Liza
Published: January 2024

The testis has two important functions: the production of sperm for fertility and the synthesis and release of androgens, such as testosterone, that maintain sperm production, sexual function, health, and wellbeing. Sperm production takes place within the seminiferous tubules, supported by the somatic Sertoli cells, and is stimulated by gonadotrophins produced by the pituitary and androgens produced by the Leydig cells in the interstitium. Spermatogenesis is a highly complex and co-ordinated process regulated via cell-cell interactions between multiple cell types. Sertoli cells produce many factors, in a cyclic manner, that are required for germ cell development and, in turn, they receive signals from developing germ cells to maintain their function. Regulation of the spermatogenic cycle involves different cell types co-operating to produce a “pulse” of retinoic acid that stimulates immature germ cells to become committed to differentiation. Research in the past decade has shown that Sertoli cells do much more than regulate germ cell development; they maintain the development and function of peritubular myoid cells, the testicular vasculature and the Leydig cells. Sertoli cells send signals to interstitial immune cells to maintain an immunosuppressive environment and deposit thousands of proteins into the interstitium, including spermatid-specific proteins that likely help to promote peripheral immune tolerance. Leydig cells produce testosterone that acts on receptors in Sertoli cells to initiate and maintain spermatogenesis, and in peritubular myoid cells to support germ cell development. Leydig cells exist in a niche with specialised macrophages that can regulate Leydig cell function and steroidogenesis, highlighting that cross-talk between testis cells and the immune system is important for testis function. Defining the specific signals that operate between the different cell types that regulate key testis functions will help to uncover new therapies to support male fertility and testicular testosterone production over the life course.
Investing in Future Fertility: Where is the Best Place to Put Your Country’s Money?
Authors: Tiemann Emily
Published: January 2024

Fertility rates continue to fall across the Asia Pacific Region (APAC), placing pressure on the economy, healthcare systems, and society as a whole. It is not just a question of population size; increasing old-age dependency ratios beg the question of how a diminishing workforce will be able to pay for the services necessary to serve an ageing population. In many countries, it is the women who are expected to shoulder the burden of homecare and childcare duties, even if they are working full time themselves. What can policymakers in APAC countries do in order to help couples achieve the family size they desire and perhaps turn the falling fertility rate around, or at least slow the rate of population decline? And importantly, where should investment be placed to make the biggest impact?

Economist Impact has authored a series of papers, sponsored by Merck, on the issue of low fertility rates in APAC countries. We explored the evidence base and cost-effectiveness for interventions such as workplace policies, parental leave, childcare provision, financial incentives and assisted reproductive technology, and discussed wider cultural and economic issues that may be impeding action.

This presentation will describe the main findings from our previous work, including a recent policy prioritisation “Toolkit” that was designed to be used by policymakers in the region to help inspire the development of policy ideas to address falling fertility rates, and support discussions on where funding should best be targeted. We shall also describe our current research project on the development of a policy “Scorecard”, which compares and contrasts the fertility and family-friendly landscape in countries across APAC, to explore what policies are being implemented in practice in the region, and provide local suggestions for improvement and where funding should be allocated.
Debate 1: All Childless Women Age 32-34 Should Be Offered Egg Freezing
Authors: Boothroyd Clare , Kar Sujata
Published: January 2024

Motion: For

NIL

Motion: Against

In my opinion this is a very radical approach to managing women’s fertility.

Women need ethical, scientific, practical, and doable advice from us as fertility consultants. We shall fail in our duties if we do not give them evidence based yet socially and personally relevant information.

My points against egg freezing as a universal policy are as follows:

1. False sense of security. This by far is the most important reason. Women cannot and should not consider frozen eggs like an insurance policy, which they can use when and where they need. 2. Ethical reasoning suggests such a policy might put pressure on women affected reproductive autonomy. They must plan themselves when, where, how and with whom they wish to bear a child. 3. Such a policy may bring about socioeconomic disparities in the society as not all will have access or afford the cost of egg freezing. 4. Cost of the procedure, long-term freezing then IVF/ET will be very substantial and will put burden on a young upcoming struggling with career woman. 5. Healthcare resource diversion/allocation will be significant, with so many other more important women’s healthcare issues at hand. 6. Normalizing delayed childbirth by way of egg freezing could have massive changes in the demography of the society, also psychological pressure in women in follow this principle leading to regrets later in life.

In the face of these issues, it might be more beneficial to focus on policies that support women to have children when they feel ready–whether that is at a younger or older age—rather than encouraging them to delay childbearing via egg freezing. This could include parental leave policies, affordable childcare, flexible work arrangements, and ensuring access to fertility treatments for those who need them.

Not only policy, but research targeting assisted reproductive technologies aimed towards improving IVF success rates, ovarian rejuvenation, stem cell treatment etc. Will go a long way to satisfy reproductive needs of women of all age groups.
Debate 5: All Women with Recurrent Implantation Failure Should Be Offered PGT-A
Authors: Hardy Tristan , Legro Richard
Published: January 2024

Motion: For

Preimplantation genetic testing for aneuploidy (PGT-A) remains one of the most controversial aspects of reproductive medicine. The benefits of deselection of embryos using PGT-A must be considered according to the clinical situation. Although PGT-A is not the solution for recurrent implantation failure, it remains part of the armamentarium available to ensure patient care is optimised in other aspects.

Motion: Against

NIL
#225 : miR-135b Expression Correlated with Aneuploidy in Trophectoderm from IVF Patients: An Approach to NIR-Invasive Screening for Embryo Quality Assessment
Authors: Mutia Kresna , Bowolaksono Anom , Febri Ririn Rahmala , Iffanolida Pritta Ameilia , Pratama Gita , Harzif Achmad Kemal , Maidarti Mila , Sumapraja Kanadi , Muharam R. , Hestiantoro Andon , Wiweko Budi
Published: January 2024

Background and Aims: MicroRNAs (miRNAs) are abundantly expressed in rapidly growing and undifferentiated cells, for example, embryonic stem cells. This led to the discovery that miRNAs are significantly expressed in human embryos and that intracellular miRNAs expression patterns differ between euploidy and aneuploid embryos. Our study aims to determine the correlation between miR-35b and embryo chromosomal status.

Methods: Thirty-six blastocyst culture media were collected from patients who underwent the In Vito Fertilization (IVF) program followed by Preimplantation Genetic Testing for Aneuploidy (PGT-A) at Dr. Ciptomangunkusumo General Hospital, Jakarta. The trophectoderm cells were biopsied, and half of the spent media culture was evaluated for aneuploidy detection using Next Generation Sequencing (NGS). While the rest of the spent media on day five were analyzed for miR-135b expression using quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). All the data were analyzed using SPSS, and the sensitivity and specificity of the miR-135b were analyzed using the ROC curve.

Results: miR-135b relative expression was detected in blastocyst spent blastocyst media culture and not in culture media without embryo. Based on the average of miR-135b, expression was higher in aneuploidy embryos (7.9(0.01-1-45.57)) than embryos with no aneuploidy detected (0.7(0.003-9.65)) and statistically different with p¡0.05. miR-135 relative expression in spent culture media was 10.72-fold higher in aneuploidy compared with an embryo with a normal chromosome. Based on the validation, the sensitivity value was 71.4%, and the specificity was 68.2%, with a cut-off of the relative expression of miR-135b was 1.185-fold.

Conclusion: miR-135b detected in IVF spent culture media from blastocyst media culture. The significant expression of miR-135b in an aneuploidy embryo makes miR-135b a potential biomarker for predicting the chromosomal quality of blastocyst embryos.
#44 : Effects of Optimum (Optimization of Thyroid, Thrombophilia, Immunity, and Uterine Milieu) Treatment Strategy on Euploid Blastocyst Transfer in Advanced Aged Women with Recurrent Reproductive Failure
Authors: Kuroda Keiji , Horikawa Takashi , Moriyama Azusa , Shiobara Keisuke , Takamizawa Satoru , Kuribayashi Yasushi , Nakagawa Koji , Sugiyama Rikikazu
Published: January 2024

Background and Aims: Does the Optimization of Thyroid function, Thrombophilia, Immunity and Uterine Milieu (OPTIMUM) treatment strategy contribute to improving pregnancy outcomes after single euploid blastocyst transfer (SEBT) in patients with a history of repeated implantation failure (RIF) and/or recurrent pregnancy loss (RPL)?

Method: Between January 2019 and May 2022, women aged ≥ 40 years with RIF after three or more embryo transfer using morphology good embryos and/or RPL after two or more clinical pregnancy losses underwent preimplantation genetic testing for aneuploidy (PGT-A) and RIF/RPL testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25-hydroxyvitamin D3, interferon-γ-producing helper-T (Th1) cell, IL-4-producing helper-T (Th2) cell, thyroid-stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 160 consecutive women who underwent SEBT, we compared 127 and 33 women with and without the OPTIMUM treatment strategy, respectively.

Results: RIF/RPL testing identified intrauterine abnormalities in 67 (52.8%), aberrant high Th1/Th2 cell ratios in 38 (29.9%), thyroid dysfunction in 19 (15.0%), and thrombophilia in 24 (18.9%). The clinical pregnancy and live birth rates in the OPTIMUM group was significantly higher than that in the control group (73.9% and 45.5%, respectively; p = 0.005 and 64.7% and 39.4%, respectively; p = 0.01) in women with RIF (Table 1). Whereas there was no significant difference of miscarriage rate in RPL women with and without OPTIMUM (5.5% and 13.3%, respectively; p = 0.58).

Conclusion: In the women aged ≥40 years with RIF who underwent PGT-A, the OPTIMUM treatment strategy improved pregnancy outcomes after SEBT. In RPL, however, both PGT-A with and without OPTIMUM resulted in low miscarriage rates and no significant difference was recognized.
#54 : Patient Tolerability of Local Anesthesia Infiltration of the Vaginal Wall and Parietal Peritoneum During Oocyte Retrieval for Minimal Simulation In-Vitro Fertilization (IVF)
Authors: Perillo Gayla , Mendiola Rudie Frederick , Ong-Jao Ednalyn , Francisco Fides Marie
Published: January 2024

Background and Aims: Oocyte retrieval is a brief and minimally invasive procedure occasionally performed under anesthesia due to pain caused by the aspirating needle puncturing the vaginal skin and ovarian capsule during its manipulation within the ovary. Despite different techniques and regimens examined, there is no conclusion on the preferred method for anesthesia and pain relief for these procedures. The purpose of this retrospective cross-sectional study was to assess patient tolerability of local anesthesia for oocyte retrieval.

Method: Patients undergoing minimal stimulation IVF were included. The average age of the women was 38.51 ± 4.402 (min. 28, max. 49). 3 ml of 2% lidocaine infiltration was done at the vaginal wall and parietal peritoneum just before oocyte retrieval. Participants rated pain levels at three events: during oocyte aspiration (“intra-op”), right after oocyte retrieval (“post-op”), and 15 minutes post-OPU. The pain scale used ranged from 0 to 10, with 0 being “No pain” and 10 being “Worst pain imaginable”.

Results: The average time duration of oocyte retrieval was 7.54 ± 4.57. The average number of follicles aspirated was 4.77 ± 4.04 and the average number of eggs retrieved was 3.62 ± 3.213.

Average pain ratings were as follows: Intra-op: 4.152 ± 2.757 S.D. (min. 0, max. 10); 15-min post-OPU: 2.848 ± 2.662 (min. 0, max. 9), and Discharge: 1.711 ± 2.017 (min. 0, max. 8), respectively. There was significant difference in the average pain felt by patients at the three events (p<0.001).

According to 55 out of 99 participants who willingly answered the survey, 90.9% were willing to use the same sedation method again.

Conclusion: Vaginal wall and parietal peritoneum local anesthesia infiltration helps in making the procedure tolerable for the patient.
#86 : Use of Triptorelin Versus Human Chorionic Gonadotropin as Ovulation Trigger
Authors: Ng Karen , Chung Pui Wah Jacqueline , Cheung Lai Ping
Published: January 2024

Background and Aims: Gonadotropin releasing hormone agonist (GnRH-a) trigger has been shown to be associated with significantly lower risk of moderate or severe ovarian hyperstimulation syndrome (OHSS) when compared among women at high risk of OHSS. However, trigger failure has been shown to occur in 2% of cycles using GnRH-a as trigger. This study aims to review the use of GnRH-a as ovulation trigger.

Method: Retrospective review of records in antagonist cycles from an ART unit in a tertiary hospital from 2017-2021 was performed. Follicles were considered mature when they reach [Formula: see text] 15 mm. Ovulation triggered with urinary human chorionic gonadotropin (uhCG) (5000-10000 IU), recombinant hCG (rhCG) 250 mcg, or triptorelin 0.2 mg when there were [Formula: see text] 3 mature follicles. All embryos obtained from cycles using triptorelin were cryopreserved.

Outcome including the number of oocytes retrieved, the follicle to oocyte index, ovarian hyperstimulation syndrome were reviewed.

Results: 1378 cycles were included. 1089 cycles had uhCG or rhCG as trigger, while 284 cycles had triptorelin as trigger. Women in the triptorelin group were significantly younger with a lower basal follicle stimulating hormone level and a higher antral follicle count (Table 1). In the triptorelin group, the total number of mature sized follicles, estrogen level at trigger, oocytes retrieved, number of blastocysts were significantly higher compared to the hCG group (Table 2). Follicle to oocyte index was significantly higher in the triptorelin group but the proportion of mature oocytes were similar in both groups. There were no cases of trigger failure and OHSS in the triptorelin group, but 30 cases of OHSS, with18 cases early onset, 12 cases late onset, amongst them 10 cases (1%) were severe OHSS) in the hCG group.

Conclusion: GnRH-a trigger is a good candidate as ovulatory trigger in women at risk of OHSS without hampering the laboratory outcome.
#93 : Analysis of 126 Uterine Adenomyosis Patients in 360 Cycles of Art Treatment Over 12 Years and Future Prospects
Authors: Tanaka Atsushi , Nakajima Daisuke , Nagayoshi Motoi , Izumi Tanaka Phar.B. , Yamaguchi Takashi
Published: January 2024

Background and Aims: Adenomyosis has low clinical outcomes and is common among older patients. There are three types of treatment, drug administration and surgery to eliminate or alleviate symptoms, and assisted reproductive technology (ART) to achieve pregnancy. However, there are no uniform selection criteria or priorities. We report the clinical outcome of treatments of uterine adenomyosis in 360 cycles following ART over 12 years and propose future treatment of the condition.

Method: We retrospectively analyzed the clinical pregnancy, live birth, and miscarriage rates of 126 patients with uterine adenomyosis (Ut-Ad) who received ART at our hospital and compared them with non-Ut-Ad individuals as controls.

Results: There were no significant differences in the fertilization rate [70.3%(1316/1872), 69.8%(15570/22309)], cleavage rate [68.9%(1289/1872), 68.5%(15274/22309)] and blastocyst formation rate [42.6%(560/1316), 43.0%(6693/15570)] between the two groups. Ut-Ad group showed significantly lower clinical pregnancy rate, live birth rate and higher miscarriage rate than.

Conclusion: The main factors of lower clinical outcome of ART of Ut-Ad were not clear. Kinetic alteration of uterine wall seems to be caused by ectopic endometrial tissues invasion.
#133 : Hysteroscopy Guided Embryo Transfer, a Newer Approach for Difficult Embryo Transfer
Authors: Singh Pratibha
Published: January 2024

Background: Embryo transfer (ET) is a crucial step in IVF process. Therefore, difficult ET can significantly impact the odds of implantation. We propose that hysteroscopy guided ET might be a feasible alternative to conventional ultrasound guided ET in such cases.

Case Report: This is the case of a 27-year-old woman with six years of primary infertility with severe dysmenorrhoea and menorrhagia. TVS showed a bulky adenomyotic uterus with multiple fibroids primarily in the posterior wall distorting the endometrial cavity and bilateral huge endometriomas. She underwent laparoscopic adenomyomectomy, myomectomy and bilateral Tubo-ovarian mass removal. Subsequently, she underwent IVF with donor eggs after 5 months therapy with long-acting GnRH agonist. Mock ET was attempted but was unsuccessful due to acute anterior flexion of the cervix. So, she was planned for ET under general anaesthesia, but the ET catheter could not be negotiated through the internal os. A 30∘ 3 mm hysteroscope was then inserted through the cervical canal using saline as distension media. Additionally, a small polyp was noted at the internal os blocking the entry of ET catheter. Once the endocervical canal was distended the catheter was negotiated from the side of hysteroscope into the cervical canal and it passed through the internal os easily under direct vision of hysteroscope. The hysteroscope was then withdrawn holding the catheter at its place. Complete evacuation of saline from endometrial cavity was confirmed by trans abdominal USG and a double ET was done under USG guidance. The routine post ET medication protocol was followed. Her Serum [Formula: see text]-hCG result was positive and after an uneventful pregnancy, she delivered healthy twin babies at 35 weeks.

Conclusion: The introduction of hysteroscopy guided ET may be a suitable alternative in cases of difficult ET.
#186 : Ultra-Long Protocol During IVF Outcome in Infertile Women with Endometriosis
Authors: Yulinda Dafi , Regan Louis , Siregar Fahreza Akbar , Jovito Axel , Wiweko Budi
Published: January 2024

Background and Aim: Endometriosis issue with infertility may require ART and long-term GnRH agonist therapy prior to frozen embryo transfer was associated with a greater rate of clinical pregnancy. The aim of the study is to assess pregnancy outcomes in endometriosis patients who have received GnRH-a ultra-long protocol prior to IVF.

Method: A retrospective cohort study was conducted at the Yasmin IVF Center, Dr. Cipto Mangunkusumo General Hospital in Jakarta. The study included all Patients diagnosed with endometriosis and underwent IVF procedure with GnRH-a ultra-long protocol was used for ovarian stimulation from July 2021 to January 2023. Parameters observed were maternal age, body mass index, oocytes retrieved, fertilization rate, blastocyst rate, and pregnancy rate.

Result: There were 12 patients who underwent IVF and received ovarian stimulation with ultra long protocol. The average oocyte retrieved in this study was 12 ± 5,3 with the average fertilization rate was 66,2 ± 18,2. We found a pregnancy rate was 58,3% and total live born child was 3 out of 7 patients (42,8%). We assessed based on the presence of intrauterine gestational sac with fetal heartbeat at ultrasound examination.

Conclusion: Ultra long protocol for stimulations in patients with endometriosis have a chance to improve oocytes retrieval, fertilization rate, and pregnancy rate.
#188 : Platelet-Rich Plasma in Patients with In-Vitro Fertilization
Authors: Regan Louis , Yulinda Dafi , Jovito Axel , Siregar Fahreza Akbar , Wiweko Budi
Published: January 2024

Background and Aims: Successful embryo implantation requires the presence of a receptive endometrium, and unsuccessful implantation frequently results from a thin endometrial wall. A new approach of treating thin endometrium, platelet-rich plasma (PRP), has been shown to increase endometrial thickness, vascularity, and implantation rate. The aim of this study is to assess PRP’s efficacy as a treatment for infertile women undergoing in vitro fertilization and its benefit for ART.

Method: This retrospective study data was implemented by collecting 26 infertile women who were sent to the Yasmin IVF Center at the Dr. Cipto Mangunkusumo General Hospital in Jakarta and had a history of unsuccessful implantation.

Results: There were 26 patients who underwent IVF and received PRP infusion prior to FET. The clinical pregnancy rate in this study was 87,5% for women <35 years old and 47% for women >35 years old. The clinical pregnancy rate was determined by dividing the number of fetal poles with a heartbeat seen on the 6-week-old ultrasound by the overall number of transplanted embryos.

Conclusions: Autologous PRP injections have shown a highly effective treatment for RIF and refractory thin endometrium.
#200 : The Impact of Serum Progesterone(P4) Level on the Day of Embryo Transfer on Art Outcome
Authors: Murdia Kshitiz , Bhoi Nihar , Chandra Vipin
Published: January 2024

Background and Aims: Physiologically serum progesterone level fluctuates among different stages of pregnancy. The serum level and tissue level of P4 are poorly correlated and also affected by the route of administration, thus creating a challenge for monitoring. Our goal was to determine whether P4 levels on the day of embryo transfer predict pregnancy outcomes in artificial FET cycles.

Method: This was a prospective cohort study conducted from Feb 2022 to Dec 2022. Around 337 patients who underwent IVF/ICSI, irrespective of single or double frozen embryo transfer in an HRT cycle, were analyzed.

Results: The participant’s mean age was 32.29±4.50 years with a BMI of 24.68±3.82 kg/m2, single embryo transfer vs double embryo transfer was 64(19.0%) vs 273(81.0%) and Serum P4 on day of ET was 28.66±12.51. Pearson’s correlation showed that serum P4 was negatively correlated with BMI (r: -0.131; P = 0.017). The serum P4 grouping was done as per the quartile distribution: Q1: <21.4 ng/ml; Q2: 21.4-27.1 ng/ml; Q3: 27.2-38.1 ng/ml; Q4: [Formula: see text]38.2 ng/ml.

Clinical Pregnancy Rate (CPR), 60.7%(Q1); 68.4%(Q2); 64.5%(Q3); 73.8%(Q4); p=0.312) was not significantly different between a female with serum P4 within different quartiles. Miscarriage rates (2.0%, 1.9%, 3.3%, 1.6%; p=0.935) & Ongoing Pregnancy Rates were (48.3%, 56.6%, 44.3%, and 65.2%, respectively, in each quartile.

Conclusion: The serum level of Progesterone on the day of embryo transfer while using intramuscular formulation in an artificial cycle had no significant impact on the clinical pregnancy rate.
#203 : Amazing Low-Cost IVF/ICSI Induction Protocols in Developing Countries
Authors: Ahmed Sajida Shahnawaz
Published: January 2024

Background and Aims: Basically, main cost of IVF is expensive use of gonadotrophins along with agonist or antagonist which are aimed mainly to avoid premature LH surge. Since LH surge is preceded by estrogen surge and inflammatory reaction, so all theory behind is avoiding estrogen surge by continuous aromatase inhibitors and continues use of anti-inflammatory drugs to avoid inflammatory reaction preceded by ovulation. By this expensive use of agonist and antagonist are completely avoided and at the same time dose of gonadotrophins is minimised.

Method: RCT study conducted on 140 patients from 2011 to 2013. Serial follicular monitoring was done by ultrasonography till the day of LH surge. 140 patients were divided into two groups. The agonist group underwent long GnRH analogue protocol. Other groups received aromatase inhibitors with gonadotrophins & anti-inflammatory agent.

Results:

In group 1:

In 20 patients (10-14) M2 oocytes retrieved with 4-6 embryos at blastocyst stage. 6 patients conceived. 5 ended in full term.

In 40 patients (6-9) M2 oocytes retrieved with 3-5 embryos at blastocyst stage, 8 patients conceived, 6 ended in full term.

In 10 patients (2-6) M2 oocytes retrieved with 0-3 embryos at blastocyst stage. 2 patients conceived & ended in full term.

In group 2:

In 30 patients (6-8) M2 oocytes retrieved with 2-4 embryos at blastocyst stage. 7 patients conceived. 6 ended in full term.

In 40 patients (3-6) M2 oocytes retrieved with 1-4 embryos at blastocyst stage. 9 patients conceived. 7 ended in full term.

Conclusion: Significant differences in gonadotrophins usage in both groups leading to marked economical saving for poor patients. According to results although mean number of oocytes retrieved were higher in group 1, but clinical pregnancy rate remained similar. Limitations are there regarding sample size & random selection of patients.