bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Donation: The UK Experience
Authors: Herbert Mary
Published: January 2024

Mutations in mitochondrial DNA (mtDNA) are inherited exclusively from our mothers and can cause a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of the mitochondrial genome from the nuclear DNA genome may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Such technologies involve transplantation of the nuclear DNA from the egg of an affected woman to an enucleated egg from an unaffected donor. Nuclear genome transplantation can be performed either before or after fertilisation. The latter involves transfer of pronuclei, which separately contain the maternal and paternal genomes. In parallel with legal and regulatory reform to permit therapeutic application of so called “mitochondrial donation” techniques in the UK, we have conducted preclinical studies to test the safety and efficacy of pronuclear transplantation (PNT). In 2017 Human Fertilisation and Embryology Authority (HFEA) approved the cautious use of PNT in the UK and granted the first licence for its therapeutic application in 2018. I will discuss the scientific, legal, and regulatory hurdles in the path from proof of concept to translation of mitochondrial donation to clinical treatment.
The Decline and Fall of Human Fertility
Authors: Aitken John
Published: January 2024

Over the last half century, the world has seen a steep decline in fertility in virtually every country on Earth, with the result that most advanced industrialized societies now have fertility rates that are well below replacement levels (conventionally set at 2.1 children per woman). This decline in fertility has been particularly marked in the Tiger economies of Southeast Asia but is essentially ubiquitous, even in populous nations such as India and China. These trends mean that, in the short term, advanced industrialized nations such as Australia can only prop up their ageing, flagging populations by encouraging record levels of immigration. Ultimately, however, we need to address this issue by addressing the causes of global fertility decline, not its consequences. This decline is being driven by increasing prosperity through the mediation of a range of social factors, the most powerful of which is the education of women and an accompanying shift in life’s purpose away from procreation. In addition, environmental and lifestyle factors are also having a profound impact on our fecundity, particularly in the male where increasing prosperity is associated with an exponential rise in the incidence of testicular cancer and a secular decline on semen quality and testosterone levels. On a different time scale, we should also recognize that the reduced fertility rates associated with the demographic transition are lessening selection pressure on high fecundity genotypes. The retention of poor reproductive genes within the human population is also being exacerbated by the increased uptake of assisted conception therapy. If we continue to rely on the latter to solve all of infertility’s woes, the growth of the ART industry may ultimately reach a scale where it serves to reduce human fertility still further, leading our species into an infertility trap.
Using Evolutionary Genomics to Discover Hormones and Receptors
Authors: Hsueh Aaron J.
Published: January 2024

All human genes have undergone hundreds of millions of years of evolution to have today’s sequences and associated functions. At the same time, ligands and receptors have also undergone co-evolution. Evolutionary methods can be used to find ligands and receptors that have not yet been discovered, leading to new clinical diagnoses and treatments.

This talk will deal with:

1. From the perspective of homologous genes and paralogous genes, the co-evolution of the glycoprotein hormone family, including FSH, LH, TSH, and hCG together with their receptors. 2. Create clinically useful long-acting FSH based on the evolutionary approach. 3. Use the evolution method to find five orphan LGR receptors, followed by the identification of receptors for the ligands, relaxin and INSL3, as well as the ligand for LGR4. 4. Use evolutionary methods to discover a new human placental hormone (placensin) and a new gonadal hormone in fish (gonacin), both with important metabolic functions. 5. Does the chicken or the egg come first during evolution? Which came first, the ligand or the receptor?
Breakthrough or Fake News in Reproductive Medicine: Tips to Tell the Difference
Authors: Legro Richard
Published: January 2024

Reproductive Medicine has been a field full of false starts, over-hyping or misrepresentation of study results and fraud. This lecture will explore the history of some of the most egregious events, discuss the current status, review the internet and social media influences, and propose ways to deflate overinflated claims of interventions or individual outcomes.
Can We Really Make a Difference in Reducing Miscarriage?
Authors: Coomarasamy Aravinthan
Published: January 2024

Many miscarriages occur due to chromosomal problems, and may not be preventable. But there are many miscarriages that result from the loss of euploid embryos. Why are these pregnancies lost? Where is the problem, and what can be done? There is a pervasive and harmful idea that miscarriages are nature’s way of dealing with an abnormal pregnancy, and therefore they cannot really be prevented, and we do not need to try to prevent them. This idea ignores the fact that there are several steps that can be taken to reduce the risk of miscarriage. This lecture asks the questions: what can a woman or couple do to reduce their risk of miscarriage? What can a healthcare provider do to reduce the risk of miscarriage? What is evidence? What are the limitations in the evidence? The recently updated evidence-based NICE, RCOG and ESHRE guidelines form the foundation of this lecture.
COVID-19 and Reproduction: An Experience from Wuhan
Authors: Qiao Jie
Published: January 2024

The history of human social development is also the history of human struggle against infectious diseases. Up to now, COVID-19 pandemic worldwide has not ended yet, but since the early stage of the epidemic, the public and scientists have been very concerned about the impact of the virus on fertility.

Wuhan, China is the first city to be hit by the COVID-19 epidemic in China. More than 344 medical teams (totaling 42000 medical team members) from other provinces in China concentrated their efforts to rescued Wuhan at that time. Regarding maternal health, the government, medical institutions, and experts strived to play their respective roles. They promptly announced the designated hospitals provide medical services for uninfected or suspected/infected pregnancy women; tried their best to ensure the demand and safety of medical treatment for pregnant and postpartum women; actively conducted scientific research on pregnant women and health status of offspring.

Looking back on COVID-19 epidemic prevention and control in the past few years, we have gained a lot of experience and lessons. For example, all of us should strengthen the connections between various departments of the country, improve urban governance in response to major infectious diseases, accelerate the development of science and technology as well as enhance international cooperation.

In the future, we will continue to coexist with pathogenic microorganisms on this Earth. Hope every battle against infectious diseases can promote us to have a deeper understanding of nature, technology, and social development, and accumulate more experience to support survivors live a better life.
Automation in the Lab-Advances and Opportunity to Improve Outcomes
Authors: Liow Sweelian
Published: January 2024

The workload of an IVF laboratory can vary depending on the size and capacity of the facility and the number of ART cycles. Some of the common tasks and responsibilities of the IVF laboratory include, semen analysis, sperm preparation, oocyte retrieval, ICSI, embryo culture, transfer and freezing, and quality control and documentation. The workload can be demanding as each step requires careful attention, adherence to protocols, and coordination with other team members. Advances in technology have provided opportunities to automate some processes in the IVF laboratory that can greatly improve efficiency, accuracy, and consistency of processes, leading to improved outcomes. However, we should be mindful to maintain a balance between automation and the expertise of skilled embryologists.
New Technologies to Improve Embryo Assessment
Authors: Dunning Kylie
Published: January 2024

Embryo quality is a key factor in determining whether an IVF cycle will result in a live birth. Current approaches for assessing embryo quality are subjective (morphology) or invasive (biopsy) and are not always predictive of live birth. Development of an accurate and non-invasive method to assess embryo quality would likely improve IVF success.

We have taken a different approach towards developing a non-invasive diagnostic for embryo quality: optical imaging. We use low levels of light to illuminate the embryo and obtain spatial information on cell metabolism as well as biophysical properties of the embryo. Here I will present our work showing that hyperspectral imaging – captures natural autofluorescence emitted by the embryo – can be used to accurately discriminate between euploid and aneuploid mouse blastocysts (inner cell mass). Importantly, we show that this form of imaging is safe: compared to embryos that were not imaged, hyperspectral imaged embryos had similar, and not significantly different, pregnancy and implantation rates, with offspring weight at weaning also comparable.

Another potential optical approach to assess embryo quality is digital holographic imaging. To date, little attention has been paid to the physical parameters of an embryo and whether these could be markers of embryo quality. One such physical parameter is refractive index. We have shown that digital holographic microscopy is able to measure very small changes in refractive index between good and poor-quality mouse embryos.

Importantly, these optical approaches occur in the absence of stains or exogenous tags. Used alone, or in combination, such optical approaches may prove beneficial in developing to an accurate, non-invasive diagnostic for embryo quality.
When Should We Recommend Egg Freezing and When Is It Too Late?
Authors: Manalo Eileen
Published: January 2024

Social oocyte freezing (SOF), a fast-growing field in ART is the elective cryopreservation of one’s own oocytes at a younger age when oocytes are of higher quality with the goal of prolonging a woman’s childbearing opportunity without any urgent medical reasons.

The optimum age for SOF is said to be below the age of 35 years ( ASRM , 2013 ; ESHRE , 2012 ). SOF in women above 35 years of age is associated with lower post-thaw survival rates, a lower live birth rate per thawed oocyte, and an increased overall cost per livebirth as more cycles of oocyte freezing and thawing may be required. Beyond 42 years of age, SOF is unlikely to result in a livebirth due to suboptimal response to stimulation and a higher cycle cancellation rate ( ASRM , 2013 ; Doyle, et al. , 2016 ; Wennberg, et al. , 2019 ). The number of oocytes needed to freeze varies widely between studies but should be individualized according to the woman’s ovarian reserve as well as the IVF center’s own success rate data ( Teo, et al. , 2021 ).

The utilization rate of frozen oocyte is low, ranging from 6 to 15%. The main reasons cited are a) women not wanting to start a family without a partner; b) preference for natural conception and, c) refusal to use a sperm donor ( Hammarberg, et al. , 2017 ).

With the use of relatively safe IVF techniques and success rates similar to that of fresh oocytes, SOF has become an acceptable reproductive option for women today to extend their reproductive ability to achieve parenthood using their own eggs. It is, however, expensive and more than one cycle of oocyte freezing may be required to improve its efficacy. Thorough counselling must be done to advise women regarding the lack of robust evidence on its efficacy, long-term risks, and costs.
Sperm DNA Fragmentation: Causes, Effects and Relevance in IVF Outcomes
Authors: Chan David YL
Published: January 2024

Sperm DNA fragmentation, characterized by damaged or broken DNA strands within sperm cells, has been recognized as an important factor in male infertility and poor ART outcome. This lecture aims to provide an overview of the causes, effects, and relevance of sperm DNA fragmentation in in vitro fertilization (IVF) outcomes and look into the latest evidences from the literatures.

Causes: Sperm DNA fragmentation can result from various factors, including oxidative stress, advanced paternal age, lifestyle factors such as smoking and excessive alcohol consumption, environmental exposures, genotoxic agents, and underlying genetic abnormalities. These factors can induce DNA damage during sperm development, during the transit of sperm through the male reproductive tract or during the storage of the sperm in epididymis.

Relevance in IVF Outcomes: The assessment of sperm DNA fragmentation has emerged as a valuable tool in evaluating male infertility and predicting IVF success. Several methods, including the sperm chromatin structure assay (SCSA), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), comet assay, and other commercial detection kits, are available to measure sperm DNA fragmentation. Previous small cohort studies have demonstrated that higher levels of sperm DNA fragmentation are associated with lower pregnancy rates, decreased embryo quality, and an increased risk of pregnancy loss in IVF cycles. Therefore, incorporating sperm DNA fragmentation analysis into the routine assessment of male infertility can aid in optimizing treatment strategies and improving IVF outcomes.

Recent evidences: Latest large clinical studies showed a limited association to IVF outcome. The DFI remains controversial as a predictive tool. Nonetheless, sperm DNA fragmentation is still believed to be a significant factor affecting male fertility and IVF outcomes. Further research is warranted to explore the mechanisms underlying DNA fragmentation, develop standardized assessment methods, and explore potential interventions to mitigate the adverse effects of sperm DNA damage on IVF success.
Ovarian Tissue Freezing in Cancer Patients - Transplantation and IVM
Authors: Stern Kate
Published: January 2024

Ovarian tissue cryopreservation (OTC) and subsequent grafting (OTG) is an innovative fertility preservation option, particularly for those patients who cannot delay treatment or are pre-pubertal. Unlike mature oocyte cryopreservation, OTC provides potential multiple opportunities for conception given the large supply of oocytes at immature stage. OTG is increasingly recognised as being successful in re-establishing fertility for women who have had gonadotoxic treatment, with over 200 live births documented worldwide from either spontaneous or assisted conception. However, establishing accurate clinical pregnancy rates and livebirth rates associated with IVF treatment after grafting is somewhat difficult as most studies publish pregnancy rates per patient rather than per transfer. Accurate information is important to assist patients with expectation management of numbers of cycles required to conceive and with outcomes, given this type of treatment is more labour-intensive than straightforward IVF. For patients with haematological cancers and with ovarian cancer there is a risk of tumour cell transmission and therefore strategies are required to allow use of the tissue and/or the gametes without conferring this risk. In-vitro-maturation offers the potential for healthy pregnancy and livebirth without the risk of grafting, and development of this technology will allow a robust and realistic fertility treatment strategy. However, how to successfully effect the initial phase of follicle development from primordial phase, termed the in-vitro-growth phase, is still eluding researchers. Mastery of this will allow substantial expansion of the follicle pool.
How Far Should We Investigate the Male Causes in Unexplained Infertility?
Authors: Novero Virgilio
Published: January 2024

According to a recent report by the Guideline Development Group of the ESHRE, the definition of Unexplained Infertility (UI) is ‘infertility in couples with apparently normal ovarian function, fallopian tubes, uterus, cervix and pelvis, age [Formula: see text]40 years and with adequate coital frequency; and apparently normal testicular function, genito-urinary anatomy and a normal ejaculate.’ This is anchored with the ICMART definition of infertility, where couples should have at least 12 months of regular, unprotected sexual intercourse before investigations are initiated.

Since Unexplained Infertility is a diagnosis by exclusion, apart from evaluating female causes, it seems important that in evaluating male contributions to the UI, all necessary tests need to be carried out. Unfortunately, there are no robust standardized methods for establishing etiologic diagnosis in the male partner and that in some patients, underlying sperm dysfunction may not be detected during a routine assessment of the ejaculate, which may appear to be normal using the 2021 WHO standards. It is possible that some adverse reproductive outcomes that have been identified during medical and reproductive history examination may require the use of further tests procedures specified in the latest WHO manual to assess sperm function. However, these tests have a research status only or are not regarded for routine use in clinical practice until sound evidence is developed. These tests include testicular imaging, anti-sperm antibodies, sperm DNA fragmentation, sperm chromatin condensation, sperm aneuploidy screening, serum hormone testing, semen HPV testing, and semen microbiology testing all of which were found not routinely indicated based on current evidence when semen was found to be normal using the WHO 2021 semen standards.

In summary, in evaluating male causes in unexplained infertility, there are no robust data to support the recommendation that additional tests about the male reproductive function may routinely be carried out when semen analysis based on the 2021 WHO standard is normal. However, additional tests may be carried out when adverse reproductive outcomes and findings in the medical and reproductive history may require the use of these further tests especially when there are no findings on the female side.
Reproductive Carrier Screening and Its Increasing Importance in Fertility Management
Authors: Delatycki Martin
Published: January 2024

Advances in genetics have had a huge impact on reproductive choices. Reproductive carrier screening has transitioned from testing for a small number of conditions, often ethnically specific, to pan ethnic large panels. The Australian Reproductive Genetic Carrier Screening Project (Mackenzie’s Mission), funded by the Medical Research Future Fund, studied the acceptability and feasibility of offering such a large panel to couples pre pregnancy or in the early stages of pregnancy. Screening of around 1300 genes was offered by healthcare professionals. Education and consent were largely through an online portal. Genomic testing was conducted on self-collected cheek swabs. The study demonstrated that such screening can be offered at scale and that people use the information to inform reproductive decisions.

Another area where genetic advances has played a crucial role in obstetrics is the ability to undertake genomic sequencing to identify the cause for abnormal ultrasound findings. Whereas in the relatively recent past, the only test available to try to identify the cause of add normal ultrasound findings was a banded karyotype on CVS or amniocentesis, now a specific single gene diagnosis can be made in some instances to inform prognosis and better enable couples to make informed reproductive decisions.
Genome Editing Tools to Increase the Efficacy of Mitochondrial Donation
Authors: Herbert Mary
Published: January 2024

Mitochondrial donation (MD) aims to prevent transmission of mtDNA disease by transplanting the nuclear genome from an affected woman’s egg to an enucleated egg from an unaffected donor. The nuclear DNA is transplanted in a karyoplast, which upon fusion with the enucleated donor egg, introduces a small amount of perinuclear mitochondria resulting in heteroplasmy for maternal mtDNA. Under optimal conditions, this accounts for <2% of the mtDNA content of MD embryos. Despite this, [Formula: see text]20% of embryonic stem (ES) cell lines derived from MD embryos exhibit complete reversion to the maternal mitochondrial genome and elevated levels (40–60%) have recently been reported in a baby born following MD treatment for infertility. Thus, currently available MR treatments are regarded as risk reduction, rather than prevention strategies. A major focus of our ongoing research is to bridge this gap by developing techniques to minimise maternal mtDNA in MD embryos. I will present our recent findings from these investigations.
Polygenic Disease and PGT-P - Ethics and Efficacy in Prediction of Disease
Authors: Cedars Marcelle
Published: January 2024

Pre-implantation genetic testing (PGT) began as a method to reduce risk for monogenic disease with known parental risk. PGT-P depends on the accuracy of the polygenic risk scoring (PRS). And susceptibility to a complex disease is multi-factorial. The genetic component is complex and these genetic variants each have a small effect throughout the genome. Environmental factors, as well as rare genetic variations of large effect, play a notable role. Even with more common disorders and large GWAS cohorts, clinical medicine has raised concerns about the predictability, and more importantly, generalizability, of these data. Limited clinical utility has been identified in applying PRS to clinical care except for increased implementation of screening. And positive implications will be harder to document when the diagnostic (in the embryo) is so remote from the actual disease development with many opportunities for environmental influence over the course of a lifetime. Additionally, when selected due to familial risk, the common variants may have limited implication for disease risk in the offspring from the same couple where potential rare genetic variation accounts for a substantial degree of within family risk. Lastly, there are new ethical concerns. For instance, how does application of PGT-P increase social inequity - given both the financial cost of the procedure (which may now require many more cycles to get a “desired” embryo) and the largely Northern European databases utilized for the defining GWAS studies? Will such diagnostics diminish efforts to improve the lives of those remaining in society who are affected? Will lessening the chance for one disorder increase risk for another? And without better understanding of the environmental and epigenetic components, calculating an absolute risk reduction becomes much more difficult so how do you appropriately consent for this procedure. This is particularly true when selecting against several disorders/diseases in the single embryo.
Myomectomy - Choosing the Surgical Approach
Authors: Lee Chyi Long
Published: January 2024

In patients who are desirous of future pregnancy and choose to preserve the uterus, myomectomy is the best surgical option where medical management is not suitable for the patient. Myomectomy was initially performed successfully in 1840 by Amussat and the procedure has evolved from open laparotomy to laparoscopy, hysteroscopy, VNOTES and robotic myomectomy.

The surgical approach in doing myomectomy depends on the type and location of the myoma and the surgeon’s expertise. Minimally invasive surgery has been the preferred approach due to the benefit of shorter hospital stay, lesser postoperative pain, earlier recovery, minimal blood loss and the cosmetic appearance of the scar.

The success of this procedure depends also on the incision technique, enucleation, blood loss prevention by employing hemostatic techniques as well as suturing techniques. Performing myomectomy for a large uterine myoma is a laparoscopic challenge; however, with the use of Lee-Huang point (midpoint between umbilicus and xiphoid) as the primary insertion and camera port, one can easily navigate thru the abdominal cavity in case the uterus is huge obscuring the umbilical port. Laparoscopic Myomectomy can be safely and efficiently performed by experienced laparoscopic surgeons regardless of myoma size, number, and location.

Removal of large myoma specimen from the abdominal cavity through the laparoscope became a challenge after the use of power morcellator was abandoned. To overcome this problem, the large myoma is placed inside an Endo bag and its edges brought extracorporeally through the port site. The myoma is incised in a C-manner using a scalpel to reduce the size. Myoma can also be removed using in-bag morcellation.

Fertility preservation is the long-term aim of doing myomectomy instead of hysterectomy in the management of leiomyoma aside from alleviating symptoms of abnormal uterine bleeding, urinary frequency, and abdominal pain. Thus, every procedure should perform under patient centered concept.
Uterine Septum Surgery
Authors: Li Tin-Chiu
Published: January 2024

The management of uterine septum is a highly controversial subject. There are conflicting reports on the benefits of the procedure. The lecture will attempt to analyse the primary reasons behind the controversy, and put forward a pragmatic, modern approach to the management of uterine septum in women with reproductive failure, including precision in diagnosis, patient selection for expectant vs surgical options, various surgical techniques for different types of septum, recommended post-operative care to ensure optimal outcome, and proposed monitoring in a subsequent pregnancy.
“Three in One”: Why Counselling is Essential in Every Clinic
Authors: Kerner Rebecca
Published: January 2024

In the ever-advancing world of Assisted Reproductive Technology, much of the focus is on the clinical and scientific realms of fertility treatment. However, if we are truly to deliver safe, ethical, and rigorous patient centred care we must include a third factor: the psychosocial implications of treatment. This presentation discusses the crucial inter-play of all three aspects in treatment-clinical, scientific, and psychosocial - and highlights the price we all pay when this is not recognised and put into practice. This session will demonstrate why it is essential for counselling to be integrated into every reproductive treatment clinic, not only for the benefit of patients, but the whole health care team involved. Integrating this trio of knowledge and expertise, is not only essential for patients, it is essential for the whole treating team. What’s more, it is smart for business too.
Building Resilience in Patients Undergoing ART
Authors: Nicholson Helen
Published: January 2024

“The coffee shops I’ve cried in”

Building resilience is part of an individual’s personal growth and development and has long term benefits for clients.

In this presentation Helen will focus on the importance of clients building resilience in their fertility treatment journey. She introduces a social work perspective of the patient context and the sources of difficulty that they may encounter during ART, before discussing resilience.

Helen locates resilience within a human development model; the social-ecological model adapted from the work of Urie Brofenbrenner. She explores how clinics can support clients to build resilience both through the fertility counsellor role and at the multi-disciplinary team/unit level.
Patients Perspective of ART
Authors: Parker Libby
Published: January 2024

After eight years of fertility investigation, attempts, discoveries, challenges, setbacks, pregnancy losses and so many visits to specialists, Libby Trainor Parker finally made the difficult decision to cease fertility treatment and let go of her desire to have a baby. Through her fertility journey, though, she encountered a full spectrum of approach, philosophy, and perspective. Through the patient’s eyes, Libby’s talk will offer some insight into how these encounters contributed to her overall understanding and experience with fertility treatment.
Surgery for Obstructive Azoospermia
Authors: Huang William J.
Published: January 2024

Microsurgical technique in male infertility has progressed significantly since the introduction of intracytoplasmic sperm infection (ICSI) 30 years ago. The searching of sperm available for ICSI becomes the main tasks for reproductive andrologists. At the initial study for patients with azoospermia, it is crucial to differentiate obstructive causes from non-obstructive categories. Testis biopsy is still a gold standard testing method to confirm obstructive azoospermia (OA). For patients with OA, the choice spectrum of treatment is broad. Basically, sperm can be retrieved from anywhere upstream the blocking spot along the male reproductive tract. However, it is not always that infertile couples consider ICSI as their treatment of choice. The choice of treatment should be prioritized according to patients’ concerns. The concerns include age of female partner, the patency of oviducts, the presence of infection in the seminal plasma, DNA fragmentation index of sperm, failure of prior use of downstream sperm for in vitro fertilization (IVF) or ICSI, religious limitation, economical affordability, number of babies expected and techniques available from the surgeons. For techniques view, the surgeons should be equipped with capabilities of techniques for sperm retrieval from the testis (testicular sperm extraction, abbreviated TESE) and epididymis (percutaneous epididymal sperm extraction abb. PESA; or microscopic epididymal sperm aspiration abb. MESA). Besides, techniques of microsurgical anastomosis of vas (vasectomy reversal or vaso-vasostomy) and epididymal tubule (vaso-epididymostomy) after scrotal exploration are also required.

Other special conditions of obstructive azoospermia are also included, such as congenital absence of vas deferens (CBAVD) or causes for dry ejaculation (including diabetes neuropathy, or post retroperitoneal surgery), or obstruction of ejaculatory ducts. Herein, I would like to share the experiences on treatment of various types of obstructive azoospermia, via scrotal exploration and the techniques of epididymovasostomy. Besides, different techniques of sperm retrieval like MESA and TESE are also demonstrated.
How to Improve Clinical Outcome in ROSI
Authors: Tanaka Atsushi
Published: January 2024

In 1996, Tesarik reported the first successful case of ROSI and many successful cases were reported around the world, however very few cases of deliveries were reported. Many doctors began to become doubtful about the usefulness of ROSI and it almost disappeared from the field of ART. Based on recent advances on ROSI research, I think it is now necessary to reconsider the usefulness of ROSI.

There are three issues concerning the extremely low success rate of ROSI. The first is the cytodifferentiation of round spermatid from other round cells. The most difficult cytological differentiation is between spermatogonia and round spermatid. The second is insufficient oocyte activation. Finally, ROSI improvement is being prevented by epigenetic errors. The big difference in ROSI and ICSI is caused by different nuclear proteins. We are now experimenting how to solve those epigenetic errors using histone deacetylase inhibitor.

The first two problems have almost been solved. The only problem we are yet to overcome is the epigenetic abnormality. The big difference between ROSI and ICSI is the different type of nuclear protein. In a round spermatid is histone and in a spermatozoon is protamine. Normal transformation of nucleosomes into nucleoprotamine is generated in normal spermatogenesis.

The characteristics of nuclei of RS are ①incomplete histone-protein transition (incomplete chromatin reprograming), ②active DNA demethylation, then these epigenetic errors affect gene expression. We are now conducting some experiments to solve these problems. The experiment involves the correction of abnormal gene expression by using histone deacetylase inhibitor. However, this method is not yet allowed clinically. I believe these procedures will be allowed for clinical application after accumulation of positive evidence by researchers.
Relative Roles of Metformin and Ovulation Induction Agents
Authors: Wang Rui
Published: January 2024

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. In patients with PCOS, effective ovulation induction agents serve as important first line and second line treatments for anovulatory infertility. High-quality randomised trials are fundamental in evidence-based pyramid to inform systematic reviews, guidelines, and clinical practice. However, in recent years, there has been concerns about the trustworthiness of some published trials on this topic.

In this lecture, a revisit of the role of metformin and ovulation induction agents (letrozole, clomiphene citrate and gonadotrophins) will be provided based on evidence from high-quality and trustworthy randomised trials, systematic reviews, and individual participant meta-analyses. Letrozole is recommended as the first line ovulation induction agent, with combined clomiphene and metformin, clomiphene alone and metformin alone, or gonadotrophins alone as alternatives. From a clinical perspective, it is important to acknowledge that some of these agents (e.g., letrozole and metformin) are considered off-label or unavailable in some countries and it should be communicated with patients during clinical decision making. From a research perspective, there is a need to understand the prevalence of letrozole resistance/failure and to further the role of other agents, alone or in combination, following letrozole resistance/failure.
Establishing Laboratory Benchmarks Beyond 2023
Authors: Blake Debbie
Published: January 2024

It would be fair to say, many of us with scientific minds have a love-hate relationship with Benchmarks and KPIs. Love the aspect that we have clear and measurable targets to aspire to, with formulas and graphs to demonstrate this. Hate the time, resources and rigor required to enter, analyse, present, and rationalise the outcomes - especially when there are so many confounding factors, coupled with the often misdirected scrutiny that can be associated with them. This presentation takes a big picture look at our current practices, some examples of how leading-edge tools can assist in troubleshooting, and a glimpse into the future where we can create more love and less hate, for benchmarks!
Non-ART Treatment of Unexplained Infertility - Waiting, Tubal Flushing, Ovulation Assisting Agents?
Authors: Mahmud Nusrat
Published: January 2024

Unexplained infertility is a common diagnosis affecting 20-25% of couples seeking infertility care. Till now, treatment of unexplained infertility remains empirical as no treatable cause of is identified.

Interestingly the word “Unexplained Infertility” is used where physicians failed to come into conclusion to a diagnosis or failed to identify a detectable cause for couple’s infertility. There are many reasons why the diagnosis of infertility with detectable causes are difficult. It is not taken for granted that even in a well-documented diagnosis, that cause could be the sole reason of infertility.

There is high observer to observer variations in the interpretation of diagnostic findings, sometimes diagnosis of endometriosis is missed and that couple is labelled as unexplained infertility.

Unexplained infertility is inevitably diagnosed by exclusion after routine standard investigations. Unfortunately, a real standardization of the diagnostic workup is still missing.

Management of unexplained infertility is basically empirical as far as the efficacies, safety, cost, and risks of each treatment option regards.

The main problem of treating this couple is disagreement of physicians on the management plan. Failure in implementation of standard practice for treatment leads to over treatment in most of the cases. This practice is mainly accompanied with misdiagnosis of eligible cases of expected management.

Existing guideline for Unexplained Infertility were released from Canadian Fertility and Andrology Society in 2019 and from ASRM in 2022.

Based on these comprehensive guidelines, ESHRE special interest group (SIG) –Reproductive Endocrinology initiated the development of an ESHRE guideline focusing on the diagnosis and therapeutic management of couples with unexplained infertility.

My presentation will be based on the non-ART management of unexplained infertility both expectant and active.
What are the Benefits of Diagnosing Endometriosis Before IVF?
Authors: Tzeng Chii Ruey
Published: January 2024

Endometriosis consists of major five features including inflammation, angiogenesis, MMP activation, adhesion formation and anti-apoptosis which all exhibit adverse effects and severely interfere with embryo implantation. Meta-analysis also shows decreased mean number of eggs retrieved, compromised clinical pregnancy rates and live birth rates in women with endometriosis. Endometriosis impacts on human oocytes by decreased mitochondrial number, reduced mitochondria DNA copy number, and increased the abnormal mitochondrial ultrastructure. The embryo morphokinetics research by time-lapse observation in patients with ovarian endometriosis illustrates delay tM and tB around 2-3 hours compared with the controls. Medical treatment by GnRHa or Dienogest before ET or FET both can induce apoptosis and autophagy of endometriotic tissues and lead to diminished endometriosis related biomarkers Tensin1 etc.) and restores the implantation markers (HOXA 10). Translational clinical studies in IUI or IVF also demonstrated beneficial effects on pregnancy outcomes and decreasing miscarriage rate following GnRHa pretreatment.
Which Systemic Medications Can Improve the Thin Endometrium?
Authors: Vutyavanich Teraporn
Published: January 2024

Transvaginal ultrasound assessment of endometrial thickness and echoic pattern is a part of standard monitoring before embryo transfer. Uterine pathology (adenomyosis, fibroids, and polyps), body habitus, uterine contractions, resolution of the ultrasound machine, inter- and intra-observer variability, and patient tolerance, may affect the accuracy of measurement. There is no exact definition of thin endometrium, and it is still controversial whether thin endometrium negatively affects pregnancy rates after embryo transfer.

Common theoretical causes of thin endometrium include estrogen deficiency, medication such as clomiphene citrate, poor uterine blood flow, uterine fibroids, intrauterine adhesion, previous intrauterine surgery (including curettage), hydro-salpinges, and chronic endometritis. Suggested treatments are 1) Dietary supplements (e.g. L-arginine, and a high-protein diet) to provide protein that the body needs to thicken the endometrium or eat fruits high in nitric oxide (oranges, watermelons, and lemons) to increase blood supply to the uterus; 2) Increase the dose or use alternative routes of estrogen administration; 3) Use vasodilators (e.g. Sildenafil, Pentoxifylline, and low-dose aspirin) to increase uterine blood flow; 4) Hysteroscopy to lyse intrauterine adhesion; 5) Surgery to remove fibroids or hydro-salpinges; 6) Antibiotics to combat subclinical endometritis; 7) Life-style modification (enough sleep to recover and promote optimal tissue growth, and regular exercise to globally increase blood flow in the body); 8) Acupuncture to increase uterine blood flow; and 9) The use of platelet-rich plasma (PRP), granulocyte colony-stimulating factor (G-CSF), and stem cell to stimulate/regenerate endometrial stem cells.

There is minimal evidence to support the use of any specific treatments to improve outcomes in patients with thin endometrium. In frozen embryo transfer, a natural cycle may be considered to avoid iatrogenic thinning of the endometrium. One should consider the cost and possible harm of the treatment before using an adjuvant to improve pregnancy outcomes in patients with a thin endometrium.
Intrauterine Medical Therapies (i.e.: PRP Infusions, G-CSF)
Authors: Wiweko Budi
Published: January 2024

Endometrial thickness is an important and crucial factor that contributed to success rate in IVF. A thin endometrium < 7 mm revealed inadequate endometrial blood flow which will affect the embryo implantation process.

There are a number of intra uterine therapies currently being used to improve chances of implantation such as vaginal sildenafil, GCSF, PRP and stem cell therapy. However, despite these interventions many women with thin or damaged endometrial linings do not respond to these therapies. intrauterine autologous PRP in women with thin lining seems to show promise.

Study in our group about regeneration of endometrial line using 3-D scaffold and self-endometrial cells was addressed particularly for unresponsive thin endometrium cases. Three-dimension acellular scaffolds, amnion bilayer womb patch enriched by autologous endometrial cell were attached into uterine cavity for 14 days.

Endometrial sections indicated that initial biopsy before treatment had undefine histoarchitecture, while 14 days application of womb patch showed some areas had epithelial structure, although not obvious.

After cell treatment, the epithelial had been formed, with high thoracal, rich with vacuoles, had cilia, and more complex with tubing system. The epithelial also expressed E-Cadherin, and the stroma cells had expressed ER, but not the PR. These had indicated patient phase secretion.

This showed that 3d scaffold and self-endometrial cells look promising to improve regeneration of unresponsive thin endometrium.
Normal Fertilized, or Abnormal Fertilized - What is the Line Between Them?
Authors: Liow Sweelian
Published: January 2024

The line between abnormal and normal fertilized oocyte is typically determined by the presence or absence of genetic or chromosomal abnormalities. In general, a normal fertilized oocyte refers to one that is euploid and has undergone successful fertilization resulting in a viable embryo. On the other hand, an abnormal fertilized oocyte is generally aneuploid and may have genetic abnormalities. These abnormalities can occur due to errors during fertilization or genetic mutations inherited from the parents. Preimplantation genetic testing (PGT) can help to identify abnormal embryos, allowing selection of healthy embryos for transfer. It is important to note that the line between normal and abnormal fertilized oocytes can be complex and may not always be clear-cut, as some abnormalities may have varying degrees of impact on development.
Morphokinetics
Authors: Latif Haroon Khan
Published: January 2024

Morphokinetics in IVF refers to the study of embryo development and quality based on the observation of their changing morphology over time. It involves closely monitoring the embryo’s cell division patterns, size, and other features using time-lapse imaging technology. While morphokinetics has shown promise in improving embryo selection based on morphological grading and provides novel kinetic parameters, it also remains surrounded by controversy. The debate on the use of time-lapse includes factors such as ethical concerns, cost and time, over selection of embryos, misinterpretation of data, and limited evidence.

It is argued that there is a lack of strong scientific evidence demonstrating the superiority of morphokinetics over traditional methods of embryo development which includes grading of the embryos using a standardized grading system. The debate has been prolonged by the fact that studies show conflicting results, leading to questions about its reliability.

Moreover, there are also ethical concerns about the time-lapse technology. There has been a long-standing discussion in ART regarding the use of add-ons in a treatment cycle. Time-lapse is often offered as an add-on in some clinics. This raises questions about accessibility, financial burden, risk of giving false hope to the patients, as well as distraction from the core treatment.

In conclusion, the debate regarding the use of morphokinetics in the form of time-lapse imaging remains unsettled mainly due to conflicting data. The controversy will only be resolved as more information will come to light and studies will show concrete evidence of improved ART results credited to the use of morphokinetics.
CRISPR/Cas9 Mediated KO Studies Identified Essential Genes for Fertilization and Oocyte Activation
Authors: Ikawa Masahito
Published: January 2024

CRISPR/Cas9 system has opened a new era for reverse genetics. Taking advantage of the CRISPR/Cas9-mediated approaches, our laboratory has knocked out 421 male reproductive organ-specific genes and analysed their phenotypes in vivo. Surprisingly, even with the highly testis-specific genes (TPM>10 and 10 times higher expression than any other non-reproductive tissues), only one-third is individually essential for male fertility (37/120=30.8%), suggesting that the tissue-specific expression does not necessarily mean essential for physiological functions ( 1 ). Nevertheless, this KO screening approach has allowed us to identify 116 genes essential for male reproductive function. Among them, we recently elucidated the long-sought lumicrine system. Testicular NELL2/NICOL goes through the efferent duct’s lumen and stimulates the ROS1 signalling pathway in the epididymal epithelial cells. Thus, differentiated epididymal epithelial cells secrete proteases such as OVCH2 that mediate sperm ADAM3 trimming and sperm maturation ( 2 - 3 ). Finally, I would like to introduce recent findings on the molecular mechanism of mammalian fertilization ( 4 - 6 ).
The Role of Ethical Advertising of Fertility Services
Authors: Patki Ameet
Published: January 2024

This lecture will highlight the following

Health Care marketing is a big business. Approximately 1 billion USD are spending each year across USA. However, it is important to note that marketing and advertising of treatment modalities are here to stay and can be useful and productive. Health care marketing can help remove stigma of certain ailments like infertility, mental illness, HIV etc. Advertising of services can help to create awareness and offer treatment options. However overzealous advertising or mis information can create false hopes in patients, over treatment by health care professional often leading to abuse of certain treatment options and can put an inherently good treatment into disrepute. Hence Hospitals and clinics need to self-regulate themselves. It is often seen that corporate hospitals in particular tend to promote lucrative and profitable services more rather than day to day health care since that may not be profitable. Celebrity endorsements are also seen in fertility services through partnerships with health care companies. It is important that advertising should not only be for professional to seek new patients but should also offer unbiased recommendations and create social awareness of illness Hence it is important that ethical advertising of fertility services Maintain patient confidentiality and anonymity Make realistic claims and promises Develop policies for advertising We recommend in addition that for accreditation of services by regulatory bodies advertising protocols of clinics should also be scrutinized and be part of the checklist.