bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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.
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.
How to Diagnose Endometriosis to Improve Fertility Treatment
Authors: Hull Mary Louise 
Published: January 2024

There is a 25-50% higher incidence of endometriosis in infertility populations and there is a 30-50% higher incidence of infertility for people with endometriosis with a significantly lower monthly chance of fertility than healthy women (2-10% vs 15-20%). However, because of the need for surgery, endometriosis is often diagnosed after starting ART treatment, with an estimate that 43-63% of those with an unexplained infertility have undiagnosed endometriosis. Diagnosing endometriosis during rather than before infertility treatments reduces the likelihood of reporting a birth and increases the chance of having a high order number of IVF cycles. Our Guest, Dr Matthew Leonardi will describe how specialised endometriosis scans can be used to diagnose endometriosis, including caveats around interpreting scans and the use of MRI. Professor M. Louise Hull will present cases demonstrating how endometriosis imaging diagnostics can improve clinical decision making in fertility practice.
How to Minimize Future Fertility Risks Associated with the Surgical Management of Miscarriage
Authors: Chung Jacqueline 
Published: January 2024

Miscarriage is a distressing event that can have a profound and lasting impact on a woman’s physical and emotional well-being. Although the causes of miscarriage are not always clear, it is estimated that up to 20% of all pregnancies end in miscarriage. After a miscarriage, women may experience a range of emotions, including grief, guilt, and anxiety. In some cases, medical intervention may be necessary to remove any remaining tissue from the uterus, prevent infection, and reduce the risk of complications. Surgical management is often recommended for incomplete or recurrent miscarriage. However, traditional surgical procedures can lead to the development of intrauterine adhesions, which can cause further complications and fertility problems. Intrauterine adhesions occur when scar tissue forms inside the uterus, usually as a result of damage to the uterine lining. This can cause the walls of the uterus to stick together, making it difficult for a fertilized egg to implant and grow, and potentially leading to infertility. To minimize the risk of intrauterine adhesions and preserve future fertility, ultrasound-guided manual vacuum aspiration (USG-MVA) has been developed as an alternative approach to traditional surgical management of miscarriage. USG-MVA is a minimally invasive procedure that involves using a handheld syringe to remove any remaining tissue from the uterus under ultrasound guidance. The use of ultrasound guidance ensures accurate catheter placement, leading to complete evacuation of the uterine contents and minimizing discomfort by reducing the number of suction catheters passes and unnecessary endometrial damage. USG-MVA has been shown to be a safe and effective method for managing miscarriages while preserving future fertility. The procedure is effective and can be performed in an outpatient setting, reducing the need for hospitalization, and minimizing associated costs. Additionally, USG-MVA has been found to have a lower risk of intrauterine adhesions compared to traditional surgical evacuation.
How to Prevent Early Ovulation/Luteinization During an IVF Cycle
Authors: Morimoto Yoshiharu 
Published: January 2024

In ovarian stimulation for artificial reproductive medicine, we sometimes encounter progesterone elevation (PL; Premature luteinization) on the day of ovulation trigger. Higher progesterone levels on the ovulation trigger have been indicated to induce adverse effects in pregnancy and implantation. This effect’s mechanism is considered an asynchrony between the embryo and the endometrium. PL is commonly defined as an elevation of serum progesterone over 1.5 ng/ml; however, the threshold values differ from the studies. PL had been evaluated by several predictors such as a single progesterone level, progesterone/ estradiol ratio, and progesterone/oocyte ratio. Some conditions may easily induce PL. In poor responder patients, a higher dose of FSH is used and that hormonal milieu provides a condition for premature luteinization. The physiological mechanism for PL has been studied; however, it is yet clarified. Since PL occurs during ovarian stimulation, FSH administration may contribute to PL. HCG trigger timing may also be an essential factor in raising progesterone. In the cases of premature luteinization, the freeze-all can be an appropriate means to keep pregnancy possibility. On the other hand, some studies indicate that the low success rates are attributable to the low quality of the embryo, not to hormonal or endocrinological disturbances. In this theory, the freeze-all strategy is not enough for a solution. Concerning impaired endometrium receptivity induced at premature luteinization, it has been reported to cause implantation failure. It has been indicated that PL affects pregnancy and live birth rates. Therefore, we are required to prevent PL by selecting appropriate ovarian stimulation protocol to achieve high pregnancy rates, optimal trigger timing, and use of medications such as corticosteroids or metformin that may prevent PL.
Prevention of OHSS
Authors: Lee Jung Ryeol 
Published: January 2024

Ovarian hyperstimulation syndrome (OHSS), perhaps the most serious complication arising from in vitro fertilization (IVF), is rare but life-threatening in some cases. In this lecture, we will first delve into the pathophysiology of OHSS and hallmark features such as hemoconcentration, hypercoagulability, electrolyte imbalances, fluid loss into third space, and renal insufficiency. In addition, clinical vignettes will illustrate some of the most severe cases of OHSS. Next, various methods for identifying patients at high risk of OHSS will be discussed. Available literature indicates that younger age and polycystic ovarian syndrome (PCOS) may be associated with the incidence of OHSS. Ovarian reserve markers such as anti-müllerian hormone (AMH) and antral follicle counts (AFC) have been suggested as useful screening tools. Also, stimulation cycle profiles, such as developing multiple follicles, peak serum estradiol levels, and the number of retrieved oocytes, may aid in identifying those at high risk. To lower the incidence of OHSS, modifying controlled ovarian stimulation (COS) protocols is essential. Evidence suggests that gonadotropin-releasing hormone (GnRH) antagonist protocol is beneficial in reducing the risk of OHSS. Medications such as dopamine agonists, aspirin, and metformin may be associated with lower risk while using clomiphene citrate remains controversial. “Coasting,” which is holding gonadotropins for several days to decrease the OHSS risk, has been suggested as another strategy. Triggering could be done differently using a GnRH agonist. Cycle segmentation by cryopreserving oocytes and embryos is also a feasible option. Close monitoring and early detection of symptoms are essential for prompt intervention and management of OHSS. By implementing preventative measures and closely monitoring patients, physicians may reduce the incidence and severity of OHSS and ensure safer fertility treatments.
Debate 3: Genetically Tested Embryos Expected to Have Mild Adult Disease Should Not Be Transferred
Authors: Yan Junhao , Gabbett Michael 
Published: January 2024

MOTION: For Next generation sequencing (NGS) technology has been widely used in the field of genetic diseases, mainly focusing on the diagnosis of genetic diseases, newborn screening, prenatal screening, preimplantation genetic test (PGT) and other fields such as the treatment of cancer. In the field of reproductive medicine, there are still some issues that engendered controversy about the application of PGT. On one hand, disputes over whether using PGT to treat late-onset diseases is ethical remain. On the other hand, some tested embryos are “available” to transfer, while others are “discarded” embryos that are “unavailable” because they are detected carrying certain genetic flaws. But there are still some embryos biopsied expected to have some genetic abnormality that might or not cause malfunction, including embryos with copy number variant of uncertain significance (VUS), embryos tested with adult-onset genetically anomalousness, embryos of balanced translocation as well as mosaic embryos. So how to dispose of this group of embryos in clinical practice is a hot issue up to now. In this debate, we reviewed the relevant case reports and original research combined with the joint consensus or committee opinion to state our proposition: embryos tested with possible abnormal genetic characteristics and thus expected to have mild adult disease should not be transferred. Parents undergoing PGT may wish to avoid the lifelong concern caused by the chance that their children may develop adult-onset conditions. The transfer of embryos expected to have mild adult disease is contrary to their original intention of seeking PGT treatment. Whether intentional or incidental, the discovery and request for transfer of embryos likely to result in the birth of offspring with health-affecting conditions pose ethical dilemmas for physicians and their staff, patients, and society. MOTION: AGAINST Preimplantation genetic testing provides couples with powerful reproductive choices. The technology allows individuals to avoid giving birth to children with significant health issues and developmental disability. Additionally, serious familial adult-onset conditions, such as predisposition to cancer or dementia, can be screened out of future generations. Polygenetic risk scores will be the next leap in genetic testing technology. This data can used to determine the chances of an embryo developing adult-onset conditions such as cardiovascular disease, diabetes, mental illness and even gout. This presentation argues that there is a limit at which society should stop screening embryos for disease and draws upon practical observations and well-accepted ethical frameworks to support the case.
#77 : A Micro 3D Printed Device for Intracytoplasmic Sperm Injection Removes the Requirement for a Holding Pipette and Reduces Complexity of the Procedure
Authors: Inge Megan , McLennan Hanna , Heinrich Shauna , Blanch Adam , Wallace Samuel , Waite Michael , Love Allison , Gardner David , Thompson Jeremy 
Published: January 2024

Background and Aims: One of the most skilled procedures performed by embryologists is intracytoplasmic sperm injection (ICSI), which takes significant experience to master. Conducting the procedure requires a high level of concentration with training a significant burden on clinical laboratory efficiency. Advancement of a micro 3D printed device to hold oocytes has removed the requirement for a holding pipette, reducing the complexity of the ICSI procedure. This study shows that the microICSIÔ device reduces the technical difficulty of ICSI, improving the speed and precision of the procedure. Method: ICSI was performed conventionally (C-ICSI) and within the microICSIÔ device on abattoir derived porcine denuded oocytes matured in vitro for 39-44 h in NCSU-23 medium containing eCG, hCG, porcine follicular fluid, EGF and insulin. Timing data was captured by video recording for pipette setup and injection time per oocyte for two embryologists and compared between each technique. Oocyte injection time was taken from when a sperm loaded injection pipette was in focus with the oocyte until the injection pipette was removed from the oocyte. Results: Results were compared between C-ICSI and microICSIÔ (Mean ± SD). Pipette setup time was reduced from 278 ± 21 seconds to 109 ± 3 seconds by removing the holding pipette. During the procedure, absence of a holding pipette resulted in embryologists adjusting their hands on average only 3 times during oocyte injection compared to 10 times for C-ICSI when moving between microinjector, pipette and microscope controllers. Oocyte traceability was also improved due to the microICSIÔ device’s numbered array. Embryologist’s injection time was reduced from 42 ± 12 seconds for C-ICSI to 14 ± 5 seconds for microICSIÔ per oocyte. Conclusion: The microICSIÔ device reduces pipette set-up time and the complexity of the ICSI procedure, reducing the time required for oocyte injection by half.