Assisted Reproductive Technology Practice Research Articles

Paternal Age Amplifies Cryopreservation-Induced Stress in Human Spermatozoa.

The global fall in male fertility is a complicated process driven by a variety of factors, including environmental exposure, lifestyle, obesity, stress, and aging. The availability of assisted reproductive technology (ART) has allowed older couples to conceive, increasing the average paternal age at first childbirth. Advanced paternal age (APA), most often considered male age ≥40, has been described to impact several aspects of male reproductive physiology. In this prospective cohort study including 200 normozoospermic patients, 105 of whom were ≤35 years (non-APA), and 95 of whom were ≥42 years (APA), we assessed the impact of paternal age on different endpoints representative of sperm quality and cryopreservation tolerance. Non-APA patients had superior fresh semen quality; DNA fragmentation was notably increased in APA as compared to non-APA individuals (21.7% vs. 15.4%). Cryopreservation further increased the DNA fragmentation index in APA (26.7%) but not in non-APA patients. Additionally, APA was associated with increased mtDNAcn in both fresh and frozen/thawed sperm, which is indicative of poorer mitochondrial quality. Cryopreservation negatively impacted acrosome integrity in both age groups, as indicated by reduced incidences of unreacted acrosome in relation to fresh counterparts in non-APA (from 71.5% to 57.7%) and APA patients (from 75% to 63%). Finally, cryopreservation significantly reduced the phosphorylation status of proteins containing tyrosine residues in sperm from young males. Therefore, the present findings shed light on the effects of paternal age and cryopreservation on sperm quality and serve as valuable new parameters to improve our understanding of the mechanisms underlying sperm developmental competence that are under threat in current ART practice.

Legal and ethical challenges in assisted reproductive technology practice in Ghana

Objective: Infertility remains a global challenge, with assisted reproductive technology (ART) progressively gaining relevance in developing countries, including Ghana. However, associated ethico-legal challenges have not received the needed policy attention. This study explored the legal and ethical challenges of ART practice in Ghana.Design: The study employed an exploratory phenomenological approach to examine ART in Ghana, focusing on ethics and law governing this practice.Participants: Respondents were ART practitioners, managers, facility owners, representatives of surrogacy/gamete donor agencies, and regulatory body representatives.Methods: A semi-structured interview guide was used to collect data. The in-depth interviews were audiotaped, and responses transcribed for analysis through coding, followed by generation of themes and sub-themes, supported with direct quotes.Results: It emerged that there are no ethical and legal frameworks for ART practice in Ghana, and this adversely affects ART practice. Ethical challenges identified border on informed consent, clients’ privacy and clinical data protection, gamete donation issues, multiple gestations, single parenting, and social and religious issues. The legal challenges identified include the non-existence of a legal regime for regulating ART practice and the absence of a professional body with clear-cut guidelines on ART practice. In the absence of legal and ethical frameworks in Ghana, practitioners intimated they do comply with internationally accepted principles and general ethics in medical practice.Conclusion: There are no regulations on ART in Ghana. Legal and ethical guidelines are essential to the provision ofsafe and successful ART practices to protect providers and users. Governmental efforts to regulate Ghana need to beprioritized.

Demographic distributions and clinical results of assisted reproduction techniques in Turkey in 2019: a descriptive survey.

The aim of this study was to describe characteristics and outcomes of assisted reproductive technology (ART) cycles performed in 2019 in Turkey. One-hundred and sixty-five ART centers in Turkey were invited to submit data. The survey was sent to center directors via e-mail with anonymous links by Qualtrics™. The survey involved questions about their patient characteristics, clinical practices, and outcomes. Forty-one (24.8%) centers responded to e-mails, and data gathered from 25 centers was included in the analyses. In 25 centers, 18,127 fresh or frozen transfers were carried out during the study period, of which 7796 (43.0%) were fresh and the rest were either frozen (45.2%) or embryo transfers (ET) with preimplantation genetic testing (PGT) (11.8%). The live birth rate per ET was as 30.6%, 40.1%, and 50.7% in fresh, frozen and PGT cycles, respectively. A single embryo was transferred in 65.3% of all transfers and singleton live births comprised 86.1% of all deliveries. For cycles with intrauterine insemination, 1407 were started in 2019, and 195 clinical pregnancies, 150 live births with 19 multiple pregnancies occurred. A total of 1513 ART cycles were initiated for foreign patients. Russia (29.6%), Germany (7.4%), Iraq (4.6%), Uzbekistan (3.1%), and Syria (1.4%) were the top five countries with most patients coming to Turkey for ART. The survey results are in parallel with the reports of international institutions and organizations. With repeated editions, the data collected with annual surveys can be used to inform ART practices in the coming years.

The use of typologies as heuristic devices in assisted reproductive technology practice: A qualitative analysis of patients and created typologies

Typologies are classification systems often used by people in social settings. Typologies are often developed by people to make sense of complexity and difference (Loeb et al., 2015; Wrede-Sach et al., 2013). In healthcare, patients may use typologies to characterise practitioners (e.g., as empathic or authoritarian) (Timmerman et al., 2021) and different kinds of practices (Senn et al., 2016). They may also be used by practitioners. Semi-structured interviews were conducted with patients and with health care professionals working in the Assisted Reproductive Technology (ART) sector. We identified six typologies that were often drawn upon by healthcare professionals. These are: the patient as consumer; the hopeful patient; the misinformed patient; the expert patient; the demanding patient and the resolved patient. Typologies bring with them some risk being that they may reinforce dominant models of care/methods of operating such as close adherence to protocols; obscure individuality and entrench stereotypes. They may also privilege particular kinds of knowledge and diminish other information which may be important to patients. This paper considers how typologies may be used in the assisted reproductive technology setting by health care practitioners when considering how to care for their patients.

Quarter-Century Experience in Cryopreservation of Human Oocytes by Vitrifi cation. What Has Been Achieved and What is Next?

Cryopreservation of human oocytes by the vitrification has become a part of the daily practice of assisted reproductive technologies to fight an infertility and to preserve the woman's reproductive potential. This literature review covers the results of the studies performed by various scientific schools during 25 years; historical prerequisites for the development of cryopreservation of human oocytes by vitrification; medical and social indices to apply this method, features and complications arising during vitrification of human oocytes. Special attention has been paid to the issues regarding the genetic safety of the method mentioned in respect of the health of future descendants. The paper presents the insight on unsolved tasks in vitrification of oocytes and that of identified ways to overcome the challenges.

Pregnancy by Oocyte Donation: Reviewing Fetal-Maternal Risks and Complications.

Oocyte donation (OD) has greatly improved over the last three decades, becoming a preferred practice of assisted reproductive technology (ART) for infertile women wishing for motherhood. Through OD, indeed, it has become possible to overcome the physiological limitation due to the ovarian reserve (OR) exhaustion as well as the poor gamete reliability which parallels the increasing age of women. However, despite the great scientific contribution related to the success of OD in the field of infertility, this practice seems to be associated with a higher rate of major risky events during pregnancy as recurrent miscarriage, infections and placental diseases including gestational hypertension, pre-eclampsia and post-partum hemorrhage, as well as several maternal-fetal complications due to gametes manipulation and immune system interaction. Here, we will revisit this questioned topic since a number of studies in the medical literature focus on the successful aspects of the OD procedure in terms of pregnancy rate without, however, neglecting the risks and complications potentially linked to external manipulation or heterologous implantation.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Natural cycle frozen embryo transfer: a survey of current assisted reproductive technology practices in the U.S.

Emerging data suggests improved obstetric outcomes with frozen embryo transfer (FET) in an ovulatory or natural cycle (NC-FETs), as compared to programmed endometrial preparation. The objective of this study is to better understand practice patterns and provider attitudes regarding the use of NC-FETs in the United States (U.S.). In this cross-sectional study, an anonymous 22-question survey was emailed to 441 U.S. Assisted Reproductive Technology (ART) clinics to assess the utilization of NC endometrial preparation for FET, protocols used, restrictions to offering NC-FET, and providers' perspectives on advantages and disadvantages of NC-FET. Descriptive statistics were used to analyze survey responses. The survey response rate was 49% (216/441). Seventeen percent of responding clinics did not offer NC-FET. Of the clinics that did not offer NC-FET, 65% had only 1-2 physicians in their practice. Common reasons for not offering NC-FET included "lack of timing predictability for transfer" (81%) and "increased burden on staff/laboratory personnel on holidays and weekends" (54%). Of clinics offering NC-FET, 76% reported < 25% of cycles used the NC for endometrial preparation. Over half (52%) of clinics that offered NC-FET reported having eligibility restrictions for NC-FET. Reported benefits of NC-FET were "patient satisfaction" (18%), "decreased cost of medications" (18%), and "avoidance of intramuscular progesterone" (17%). The attitude towards NC-FET in their clinics was reported as positive by 65% of respondents. NC-FETs are offered by most U.S. ART clinics but are used only in the minority of FET cycles for endometrial preparation, and use is often restricted.

Determining Legal Parentage and Nationality of a Child Born Through Assisted Reproductive Technology: A Comparative Perspective

While procreation through copulation has remained the conventional means for pregnancy and beginning the human family, advances in medical technology has now demonstrated that coitus is no more the absolute process for childbearing. Individuals like infertile couples, single persons, lesbians and gay partners have now resorted to assisted reproductive technology (ART) and surrogacy arrangements in order to start a family. Transcending the hope and joy it offers to these groups of individuals who may have been incapable of having children of their own, this new procreative technology has stirred up a number of ethical and legal questions. The focal aim of the article was to investigate the state of the law for ascertaining the legal parentage and nationality of a child born through ART. Determination of these sensitive issues is vital because of the possibility of a child conceived through ART having more than two parents, especially where surrogacy, donor sperm and donor eggs are involved. The article adopted desk-based and comparative research methods by relying on both primary and secondary sources of information. The various sources of information were appraised and deductions derived from them were presented descriptively. The article revealed inter alia, that in some of the countries examined, ART practice is regulated and the courts, in a number of instances, have been engaged to resolve controversies pertaining to the legal parentage and nationality of children born through ART procedure. But in Nigeria, the practice is unregulated by law and there is dearth of decided cases on the subject. The authors therefore, recommended that in view of the increasing number of individuals turning to ART in Nigeria, including cross-border surrogacy, to build families, there is need for definite ART legislation in Nigeria so as to assist in resolving these problems and other related ones. Nigerian lawmakers could examine similar laws from other foreign jurisdictions and use them as potential guide to fashion out a domestic legislation in Nigeria. The Nigerian courts could also learn from decisions from other jurisdictions so as to know how to determine related cases as they occur in Nigeria.

Survey on the Impact of COVID-19 on the Practice of Assisted Reproduction in Latin America.

To follow the impact of the SARS-CoV-2 pandemic on the practice of assisted reproductive technology in centers reporting to the Latin American Registry during 2020. An internally validated online survey designed on the Survey Monkey platform with a maximum of 20 closed questions was sent via e-mail or WhatsApp to the clinical director of each center reporting to the Latin American Registry of Assisted Reproduction between July and December 2020. The number of centers responding to the survey varied during the six months. The relative contribution of Brazil to all responses was 41.4% to 45%, followed by México (16.2% to 23.8%), Argentina (8.1% to 12.6%), Colombia (7.1% to 8.2%), Chile (3.6% to 6.1%) and Peru (4.0% to 4.9%). Most centers reported stopping activities before July 2020 (81%). COVID-19 related symptoms were a criterion on their own to postpone ovarian stimulation (80.1% to 87.7% of centers). Although in July only 76 of 166 centers (45.8%) performed embryo transfers, by October 104 of 109 centers (95.4%) performed them. In survey 6 (December), 78 of 79 centers (98.7%) that had initially closed had already reopened, although 62.3% (61 of 98 centers) still performed 80% or less of their usual number of ART cycles. Most centers modified their clinical practice and applied specific protocols to screen their staff and patients. Suspicion of COVID-19 delayed treatments. Despite a peak of the pandemic, by December most centers were performing all ART treatments, although the number of cycles remained low compared to pre-pandemic numbers.

FHL1 mediates HOXA10 deacetylation via SIRT2 to enhance blastocyst-epithelial adhesion

Recurrent implantation failure (RIF) is a rather thorny problem in the clinical practice of assisted reproductive technology. Due to the complex aetiology of RIF, its pathogenesis is far from fully understood, and there is no effective treatment available. Here, We explored the regulatory mechanism of the four half-domains of LIM domain 1 (FHL1), which is significantly downregulated in the endometrium of RIF patients, in blastocyst-epithelial adhesion. Indeed, FHL1 expression was dramatically increased in normal female mid-secretory endometrial epithelial cells and was abnormally reduced in RIF patients. Furthermore, FHL1 overexpression promoted blastocyst-epithelial adhesion, and interfering with FHL1 expression in the mouse uterus significantly inhibited embryo implantation. Mechanistically, FHL1 did not regulate HOXA10 mRNA expression but increased HOXA10 protein stability and activated HOXA10, thereby promoting its regulation of downstream gene expression and the β3 integrin/FAK pathway. Meanwhile, FHL1 regulates HOXA10 function by increasing HOXA10 deacetylation through enhanced binding of HOXA10 and SIRT2. SIRT2-specific inhibitors can significantly inhibit this effect. In the endometrial epithelial cells of RIF patients, the correlation between FHL1 and HOXA10 and its downstream target genes has also been verified. Finally, our data indicated FHL1 is a regulatory molecule that promotes blastocyst-epithelial adhesion. Altogether, downstream dysfunction due to aberrant FHL1 expression is an important molecular basis for embryo implantation failure in patients with RIF and to provide new potential therapeutic targets.

Quality assurance (QA) for monitoring the performance of assisted reproductive technology (ART) staff using artificial intelligence (AI).

Deep learning neural networks have been used to predict the developmental fate and implantation potential of embryos with high accuracy. Such networks have been used as an assistive quality assurance (QA) tool to identify perturbations in the embryo culture environment which may impact clinical outcomes. The present study aimed to evaluate the utility of an AI-QA tool to consistently monitor ART staff performance (MD and embryologist) in embryo transfer (ET), embryo vitrification (EV), embryo warming (EW), and trophectoderm biopsy (TBx). Pregnancy outcomes from groups of 20 consecutive elective single day 5 blastocyst transfers were evaluated for the following procedures: MD performed ET (N = 160 transfers), embryologist performed ET (N = 160 transfers), embryologist performed EV (N = 160 vitrification procedures), embryologist performed EW (N = 160 warming procedures), and embryologist performed TBx (N = 120 biopsies). AI-generated implantation probabilities for the same embryo cohorts were estimated, as were mean AI-predicted and actual implantation rates for each provider and compared using Wilcoxon singed-rank test. Actual implantation rates following ET performed by one MD provider: "H" was significantly lower than AI-predicted (20% vs. 61%, p = 0.001). Similar results were observed for one embryologist, "H" (30% vs. 60%, p = 0.011). Embryos thawed by embryologist "H" had lower implantation rates compared to AI prediction (25% vs. 60%, p = 0.004). There were no significant differences between actual and AI-predicted implantation rates for EV, TBx, or for the rest of the clinical staff performing ET or EW. AI-based QA tools could provide accurate, reproducible, and efficient staff performance monitoring in an ART practice.

Multicentre study on rates and reasons for treatment discontinuation in patients with remaining cryopreserved embryos

Research questionWhat is the discontinuation rate among patients with remaining cryopreserved embryos in Belgium and what are the reasons for discontinuation? DesignMulticentre, cross-sectional study across 11 Belgian fertility clinics. Patients were eligible (n = 1917) if they had previously undergone an unsuccessful fresh embryo transfer (fresh group) or frozen embryo transfer (FET) (in-between group) and did not start a subsequent FET cycle within 1 year despite having remaining cryopreserved embryos. The denominator was all patients with embryos cryopreserved during the same period (2012–2017) (n = 21,329). Data were collected through an online anonymous questionnaire. ResultsThe discontinuation rate for patients with remaining cryopreserved embryos was 9% (1917/21329). For the final analysis, 304 completed questionnaires were included. The most important reasons for discontinuing FET cycles were psychological (50%) and physical (43%) burden, effect on work (29%), woman's age (25%) and effect on the relationship (25%). In 69% of cases, the patient themselves made the decision to delay FET treatment. In 16% of respondents, the decision to delay FET was determined by external factors: treating physician (9%), social environment (4%), close family (3%) and society (3%). Suggested improvements were psychological support before (41%), during (51%) and after (51%) treatment, as well as lifestyle counselling (44%) and receiving digital information (43%). ConclusionsThe discontinuation rate is remarkably high in patients with remaining cryopreserved embryos who have a good prognosis. Respondents stressed the need to improve the integration of psychological and patient-tailored care into daily assisted reproductive technology practice.

Assisted Reproductive Technology in Western Algeria.

Infertility is a major public health problem that Assisted reproductive technology (ART) helps remedying, allowing infertile couples realizing their parental project. In Algeria, the infertility rate is about 15%. Thereupon, several ART national centers have emerged. The aim of this study is to evaluate the ART activities, provide quantified data to understand the ART practice in western Algeria and compare our results abroad. We conducted a retrospective study on 1930 women treated for an ART at the EL MAWLOUD fertility center in Oran from January 1, 2019 to December 31, 2020. Our study showed the patients' average age as 33.42 and the ICSI as the commonest ART technique in our center with 90% frequency. The pregnancy rate equals 26.59% by insemination in IUI, and 41.25 % by puncture in IVF and ICSI, i.e. an average success rate similar in Europe and USA. This study elucidates the use of ART techniques (2019-2020) in western Algeria. They are satisfactory in our region compared to international data in the literature. However, ART remains embryonic in Algeria, regarding mainly the exorbitant prices of these techniques and the non-reimbursement of this act by the National Social Security Fund, which handicaps couples with medium and low incomes.

Absence of a Legal Framework, a Limitation to the Practice of Surrogacy in Nigeria

Introduction: The human passion for procreation and perpetration of lineage has remained since existence. Surrogacy implies the use of a substitute mother to gestate a pregnancy for another woman and thereafter relinquishes the child/children and any parental entitlement to the child/children to the commissioning parents. It is a veritable option for couples who have not been successful in their efforts to bear children. Objective: to assess the awareness, practice, and limitations to practice of surrogacy in Igbo Ukwu community of Anambra State, South- East Nigeria. Methodology: A descriptive cross-sectional study which involved 200 male and female community members of Igbo Ukwu in Anambra. Sample size of 200 was calculated for the study using the Kish formula for cross sectional studies. Simple random sampling was used in selecting participants who converged in the community square. A structured self-administered questionnaire was employed in gathering information on socio-demographic characteristics, knowledge, practice, and limitations to practice of surrogacy. Data was analyzed using Statistical Packages for Social Sciences (SPSS) version 23.0. Descriptive statistics was used to summarize the results which were presented with the aid of a pie chart, bar chart and frequency tables. The level of significance was set at 95% probability level (p &lt; 0.05) Result: Most of the research participants were within the age group 28 – 37 years (40.0%), with mean age of 25.3+1yrs. The study population comprised mainly of people who had formal education (93.0%). There was high level of awareness of surrogacy arrangement in the studied population (84%). However, the practice of surrogacy was generally poor; only four (4) respondents out of 120 females that participated in the study (3.3%) had acted as surrogate mother. Financial benefit was mainly the reason for accepting surrogacy as noted in 47.8% of research participants, while fear of victimization due to absence of a legal framework (54.3%) and to a lesser extent, culture (27.1%) and religious inclination (28.6%) were the main reasons limiting the practice of surrogacy among the participants Conclusion: There is an obvious disconnect between the level of awareness and practice of surrogacy mainly due to fear of victimization from lack of a legal framework. This calls for a need to institutionalize a legal framework to control assisted reproductive technology practice in Nigeria which will restore the hope and aspirations of the infertile couple in need of surrogacy and other assisted reproductive techniques. Keywords: surrogacy, awareness, practice, limitations, legal framework.

Optimizing embryological aspects of oocyte retrieval, oocyte denudation, and embryo loading for transfer.

Oocyte retrieval, oocyte denudation, and embryo transfer are crucial processes during assisted reproduction technology (ART). Air quality in the ART laboratory, temperature, pH of the media used and the time interval between oocyte retrieval and insemination are all critical factors. Anesthesia is required for oocyte retrieval, however, evidence regarding the potential impact of different methods (general anesthesia, conscious sedation, and local anesthesia) on the clinical outcomes is unclear. The optimal timing of oocyte denudation following retrieval has not been established. Regarding the mechanical denudation process, there is a lack of evidence to demonstrate the safest minimum inner diameter of denuding pipettes used to complete the removal of granulosa cells surrounding the oocytes. During embryo transfer, many clinics worldwide flush the catheter before embryo loading, in an attempt to potentially rinse off any toxic agents; however, there is insufficient evidence to show that flushing the embryo transfer catheter before loading increases the success of ART outcome. Considering the serious gaps in knowledge in ART practice, the aim of this review is to provide an updated overview of the current knowledge regarding the various steps and techniques involved in oocyte retrieval, oocyte denudation, and embryo loading for transfer.

Taking a closer look at the key performance indicators in an assisted reproductive technology laboratory: a guide for reproductive professionals.

Over the years, laboratories performing assisted reproductive technologies have been tasked with a growing number of procedures of increased complexity. New technologies, including hardware and software innovations, are constantly evolving, and evaluated as potential tools to improve laboratory and clinical outcomes. The assisted reproductive technology (ART) laboratory plays a crucial role in fertility treatments and, therefore, it is often under intense scrutiny with regards to performance and success rates. As the reproductive medicine field strives to deliver improved clinical outcomes to patients, in-vitro fertilization (IVF) clinics - including the ART laboratories - are required to monitor their performance and seek improvement in the many different aspects related to patient care. Key performance indicators (KPIs) and benchmarking are important tools to support performance monitoring and quality improvement processes. The concept and potential benefits of KPI utilization is generally accepted. However, its adoption poses some challenges that may discourage ART practices from pursuing it as part of their quality management systems (QMS). Properly selecting and using KPIs will allow laboratories to successfully manage their performance and set up realistic target goals to consistently deliver high rates. Existing literature can guide reproductive medicine professionals to embark on their journey to successfully select, implement, and manage KPI and benchmarking as part of their ART programs. This article discusses the concept and essentials of KPI and benchmarking applied to the ART laboratory, as well as potential challenges and how to overcome them.

Surrogacy Legislation and Kenya's ART Bill 2019: Reproductive Uhuru (Freedom) A Myth or a Reality for Infertile Citizens?

In 2014, Kenyan parliamentarian Odhiambo Millie MP tabled the Assisted Reproductive Technology (ART) Bill [2019] to regulate assisted reproduction. The Bill restricts surrogacy to married couples only, prohibits payment to surrogates and makes no provision for surrogacy services or its oversight. It is modelled on the United Kingdom's surrogacy laws, although this article confirms the UK's surrogacy laws were intended to discourage surrogacy in the first place, and a Law Commission review shall be published in 2022. In 2007, Thiankolu Muthomi called for Kenyan-designed ART legislation. Kenya's customary woman-to-woman marriage is examined as a taking-off point for technologising Kenya's surrogacy services. The woman-to-woman marriage was constitutionally protected in 2010 and embedded by the enactment of the Protection of Traditional Knowledge and Cultural Expressions Act No. 33 [2016] that promotes the right to cultural expression. This cultural reality should provide the launching pad for a more permissive and auditable surrogacy legislation in Kenya and transferability to sub-Saharan Africa burdened, with the exception of South Africa, by unregulated ART practice.

Optimal individualization of patient-oriented ovarian stimulation in Japanese assisted reproductive technology clinics, a review for unique setting with advanced-age patients.

Ovarian stimulation is a key issue in assisted reproductive technology (ART) treatment. ART practice in Japan is unique with various types of ovarian stimulation protocols, which may contribute to lower pregnancy rates compared to other countries. This review aims to clarify optimal individualized ovarian stimulation for improving the pregnancy rate per one oocyte retrieval cycle in Japan. We performed a literature review to describe ovarian stimulation, classification of infertile women depending on ovarian reserve and response, and Japanese ART data and discussed optimal conventional and mild ovarian stimulation protocols in Japan. According to Japanese ART registry data, the live birth rate of 30-35-year-old women was 32%-37% per ET cycle; therefore, four to five embryos are calculatedly needed when aiming a cumulative live birth rate of ≥80%. Mild stimulation aimed at collecting 5-10 oocytes can be alternative choice as an optimal ovarian stimulation protocol in young women. In 40-year-old women, the live birth rate is 18.8%, resulting in eight or more embryos as necessary. Conventional stimulation must be required in women with advanced age. In poor responders, however, mild stimulation may be sufficient for maximumly extracting their ovarian function. In Japan, mild ovarian stimulation can be selected in patients with a good prognosis and poor responders; however, conventional ovarian stimulation is necessary for women in advanced age.

Identification of long non-coding RNA biomarkers and signature scoring, with competing endogenous RNA networks- targeted drug candidates for recurrent implantation failure

Recurrent implantation failure (RIF) remains a source of frustration and presents challenges to clinicians in the practice of assisted reproductive technology (ART). Long non-coding RNAs (lncRNAs) are increasingly recognised as potential biomarkers in various diseases. In this study, eight differentially expressed lncRNAs (LINC00645, LINC00844, LINC02349, AC010975.1, AC022034.1, AC096719.1, AC104072.1 and DLGAP1-AS3) to distinguish RIF from fertile women were identified by RobustRankAggreg (RRA). A two-lncRNA signature for predicting RIF was established by least absolute shrinkage and selection operator (LASSO) regression, with accuracy confirmed by receiver operating characteristic (ROC) curves. After lncRNA-microRNA-mRNA regulatory networks were established by Cytoscape 3.7.2, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were performed, suggesting that the lncRNA-miRNA-mRNA regulatory networks were associated with biological processes involved in endometrial receptivity. Finally, three putative drugs (miconazole, terfenadine and STOCK1N-35215) for RIF were predicted by a Connectivity Map. In conclusion, we identified eight lncRNA biomarkers and a two-lncRNA signature for predicting RIF, as well as proposing three candidate drugs against RIF by targeting the ceRNA networks.