Microfluidics as an emerging paradigm for assisted reproductive technology: A sperm separation perspective.

Millions of people are subject to infertility worldwide and one in every six people, regardless of gender, experiences infertility at some period in their life, according to the World Health Organization. Assisted reproductive technologies are defined as a set of procedures that can address the infertility issue among couples, culminating in the alleviation of the condition. However, the costly conventional procedures of assisted reproduction and the inherent vagaries of the processes involved represent a setback for its successful implementation. Microfluidics, an emerging tool for processing low-volume samples, have recently started to play a role in infertility diagnosis and treatment. Given its host of benefits, including manipulating cells at the microscale, repeatability, automation, and superior biocompatibility, microfluidics have been adopted for various procedures in assisted reproduction, ranging from sperm sorting and analysis to more advanced processes such as IVF-on-a-chip. In this review, we try to adopt a more holistic approach and cover different uses of microfluidics for a variety of applications, specifically aimed at sperm separation and analysis. We present various sperm separation microfluidic techniques, categorized as natural and non-natural methods. A few of the recent developments in on-chip fertilization are also discussed.

Comparative efficacy of different growth hormone supplementation protocols in improving clinical outcomes in women with poor ovarian response undergoing assisted reproductive therapy: a network meta-analysis.

Growth hormone (GH) has a long-standing history of use as an adjunctive therapy in the treatment of poor ovarian response (POR), but the optimal dosage and timing remains unclear. The aim of this study was to evaluate and compare the efficacy of different GH supplementation protocols through a network meta-analysis (NMA) and determine the optimal treatment protocol. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. Databases including PubMed, Web of Science, Cochrane Library and Embase were searched until June 2023. A total of 524 records were retrieved in our search, and 23 clinical studies comprising 4889 cycles were involved. Seven different GH protocols were identified. Results showed that compared to the control group, daily administration of 4-8 IU of GH during the follicular phase of the stimulation cycle had the best comprehensive therapeutic effects on improving the number of retrieved oocytes, mature oocytes, endometrial thickness, and reducing gonadotropin requirements in POR patients undergoing assisted reproductive therapy, with a relatively brief treatment duration and a moderate total GH dose. Subgroup analysis demonstrated that this protocol could significantly improve the clinical pregnancy rate of POR patients in the randomized controlled trials (RCT) subgroup and the African subgroup. Therefore, its clinical application is suggested. Besides, the potential advantages of long-term GH supplementation protocol (using GH for at least 2 weeks before oocyte retrieval) has merit for further research. Rigorous and well-designed multi-arm RCTs are needed in the future to confirm the conclusions drawn from this study.

Moral justification for the use of 'add-ons' in assisted reproductive technology: experts' views and experiences.

RESEARCH QUESTION: What factors do assisted reproductive terchnology (ART) providers take into account when they make decisions about offering 'add-ons'? DESIGN: A qualitative analysis of interviews with 31 ART professionals, focusing on their views and experiences in relation to add-ons, including the factors that are considered when doctors make decisions about their use. RESULTS: The participants reported that a range of considerations are taken into account when it comes to justifying the use of a particular add-on in a given circumstance, including the likelihood of benefit and harm, patients' perceived psychological needs and preferences, and organizational expectations. Importantly, patient preferences, psychological factors and low risk of harm appear to be stronger motivations than increasing the likelihood of a live birth or the desire to innovate. CONCLUSIONS: These findings suggest that it cannot be taken for granted that add-ons and innovation are closely linked. One possible response to this would be regulatory reform; for example, only allowing 'unproven' add-ons to be used in the context of formal scientific evaluation. Alternatively, it could be made clear that add-ons that are not undergoing formal evaluation have more in common with other therapies lacking a clear evidence base, such as complementary and alternative medicines, than with conventional medical practice. Practices in relation to add-ons may also require a focus on the responsibilities of corporations, and the standards applying to purveyors of consumer goods and services.

A Systematic Review of Autoimmune Oophoritis Therapies.

Autoimmune primary ovarian insufficiency (POI) is a devastating disease with limited clinical guidance. The objective of this systematic review was to identify treatments for autoimmune POI and analyze their efficacy. A comprehensive search of CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science was performed from inception to April 2022. English language publications that evaluated women with autoimmune POI after a documented intervention were included. Animal models of autoimmune POI were also included. Risk of bias was assessed with the SYRCLE's risk of bias tool for animal studies or the NIH Quality Assessment Tool for Case Series as appropriate. Twenty-eight studies were included in this review, with 11 RCTs, 15 case reports, and 2 case series. Seventeen studies were in humans, and 11 were in animal models. No completed RCTs, cohort studies, or case-control studies were identified in humans. In observational human studies, corticosteroids were effective in select patients. In many case reports, adequate treatment of comorbid autoimmune conditions resulted in return of menses, hormonal normalization, or spontaneous pregnancy. In terms of assisted reproductive technologies, there was case report evidence for both in vitro fertilization (IVF) and in vitro maturation (IVM) in women wishing to conceive with their own oocytes. Ovulation induction, IVF, and IVM resulted in a total of 15 pregnancies and 14 live births. In animal models, there was additional evidence for stem cell therapies and treatments used in traditional Chinese medicine, although this research may not be generalizable to humans. Furthermore, litter size was not evaluated in any of the animal studies. Additional research is needed to establish the efficacy of current treatments for autoimmune POI with a controlled experimental design and larger sample size. Additionally, there is a critical need to develop novel therapies for this condition, as understanding of its pathophysiology and  available tools to modulate the immune response have progressed.

Bibliometric and Visual Analysis of the Research Status and Knowledge Structure of Assisted Reproductive Therapy for Patients with Premature Ovarian Insufficiency.

Objective: A large proportion of patients undergoing assisted reproductive therapy (ART) suffer from premature ovarian insufficiency (POI). The knowledge structure, research hotspots, and research trends related to ART for patients with POI are still unclear and have not been systematically summarized. We aimed to analyze the research status of ART for patients with POI and deeply explore its knowledge structure and research trends. Our findings may provide treatment recommendations for clinicians and guidance for researchers in further research. Methods: The PubMed database for publications on ART for patients with POI was searched. The Bibliographic Item Co-occurrence Matrix Builder (BICOMB) obtained the Co-word matrix and co-occurrence matrix. The H-index method was used to extract high-frequency main Medical Subject Headings (MeSH) terms/subheadings. Then we used software such as graphical clustering toolkit (gCluto), Microsoft Excel, Ucinet and NetDraw to carry out the biclustering analysis, strategic diagram analysis and social network analysis of the major MeSH terms/subheadings. Results: The high-frequency major MeSH terms/subheadings were analyzed by biclustering, strategic diagram, and social network analyses. A total of 431 articles from 1983 to 2023 were retrieved. Analysis showed that a total of 176 journals published relevant papers, including FERTILITY AND STERILITY, ranking first. In addition, we extracted 20 high-frequency major MeSH terms/subheadings. We grouped them into five categories: cryopreservation of oocyte and ovarian tissue, oocyte donation, in vitro activation (IVA) of primordial follicles, overview of therapy for patients with POI, therapy of iatrogenic POI. Within these five categories, there were 4, 4, 3, 4, and 5 major MeSH terms/subheadings, respectively. The major MeSH terms/subheadings were evenly distributed, and no particular group had a particular central tendency. Conclusion: The therapy of Iatrogenic POI is in the core position of research and is becoming increasingly mature. Oocyte donation and IVA of primordial follicles are the trends of future research. This study is helpful to understand the current research status, knowledge structure, and research trends of ART for patients with POI, and provide reference for improving ART for patients with POI in the future. Our study may guide clinicians to apply more established research to treat patients, which may lead to better treatment outcomes for patients. At the same time, we also suggest that researchers can conduct research in the field of future research trends, which may lead to greater research results.

Parents' experiences of life after medicalised conception: a thematic meta-synthesis of the qualitative literature.

BACKGROUND: Medicalised Conception (MAC) assists many couples to achieve pregnancy worldwide. As the impact of MAC has been linked to increased pregnancy-specific anxiety and parenting difficulties, this review aimed to explore parental experiences of pregnancy and early parenting following MAC, identifying parents' psychological, social and health needs. METHOD: Five databases were searched systematically from inception to March 2023. Identified articles were screened for eligibility against the inclusion criteria and the results were analysed using thematic synthesis. The Critical Appraisal Skills checklist was employed to appraise methodological quality. RESULTS: Twenty qualitative studies, drawing on a total of 19 participant samples, were included in this review, most with samples with history of subfertility. The findings were synthesised into three main themes (consisting of seven subthemes): 1) The vulnerable parent: fear, doubt, uncertainty, 2) the stark realisation of the parental dream, 3) psychosocial needs and support. Parents lacked a sense of safety during pregnancy and reported acting protectively both antenatally and postnatally. Furthermore, their identity transition was complex and non-linear, influenced by sociocultural context. CONCLUSIONS: Considerable unmet psychosocial needs were identified including the potential for anxiety in pregnancy, the possibility of feeling excluded and marginalised, and a reluctance to share distress and experiences with healthcare professionals. These findings suggest a need for consistent, holistic care, integrating psychological services.

TEAS, DHEA, CoQ10, and GH for poor ovarian response undergoing IVF-ET: a systematic review and network meta-analysis.

BACKGROUND: Assisted reproductive technology (ART) has brought good news to infertile patients, but how to improve the pregnancy outcome of poor ovarian response (POR) patients is still a serious challenge and the scientific evidence of some adjuvant therapies remains controversial. AIM: Based on previous evidence, the purpose of this systematic review and network meta-analysis was to evaluate the effects of DHEA, CoQ10, GH and TEAS on pregnancy outcomes in POR patients undergoing in vitro fertilization and embryo transplantation (IVF-ET). In addition, we aimed to determine the current optimal adjuvant treatment strategies for POR. METHODS: PubMed, Embase, The Cochrane Library and four databases in China (CNKI, Wanfang, VIP, SinoMed) were systematically searched up to July 30, 2022, with no restrictions on language. We included randomized controlled trials (RCTs) of adjuvant treatment strategies (DHEA, CoQ10, GH and TEAS) before IVF-ET to improve pregnancy outcomes in POR patients, while the control group received a controlled ovarian stimulation (COS) regimen only. This study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The surface under the cumulative ranking curve (SUCRA) was used to provide a pooled measure of cumulative ranking for each outcome. RESULTS: Sixteen RCTs (2323 women) with POR defined using the Bologna criteria were included in the network meta-analysis. Compared with the control group, CoQ10 (OR 2.22, 95% CI: 1.05 to 4.71) and DHEA (OR 1.92, 95% CI: 1.16 to 3.16) had obvious advantages in improving the clinical pregnancy rate. CoQ10 was the best in improving the live birth rate (OR 2.36, 95% CI: 1.07 to 5.38). DHEA increased the embryo implantation rate (OR 2.80, 95%CI: 1.41 to 5.57) and the high-quality embryo rate (OR 2.01, 95% CI: 1.07 to 3.78) and number of oocytes retrieved (WMD 1.63, 95% CI: 0.34 to 2.92) showed a greater advantage, with GH in second place. Several adjuvant treatment strategies had no significant effect on reducing the cycle canceling rate compared with the control group. TEAS was the least effective of the four adjuvant treatments in most pooled results, but the overall effect appeared to be better than that of the control group. CONCLUSION: Compared with COS regimen, the adjuvant use of CoQ10, DHEA and GH before IVF may have a better clinical effect on the pregnancy outcome of POR patients. TEAS needs careful consideration in improving the clinical pregnancy rate. Future large-scale RCTs with direct comparisons are needed to validate or update this conclusion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022304723.

The Effect of CoQ10 supplementation on ART treatment and oocyte quality in older women.

A significant problem associated with assisted reproductive technologies (ART) is recurrent treatment failure which can be attributed to the age-associated decline in oocyte quality. Co-enzyme Q10 (CoQ10) is an antioxidant and essential component of the mitochondrial electron transport chain. It is reported that de novo CoQ10 production declines with ageing and coincides with age-related decline in fertility, leading to CoQ10 supplementation being advocated to enhance response to ovarian stimulation and improve oocyte quality. CoQ10 supplementation was found to improve fertilization rates, embryo maturation rates and embryo quality when used before and during in vitro fertilization (IVF) and in vitro maturation (IVM) treatment in women aged 31 and over. Regarding oocyte quality, CoQ10 was able to reduce high rates of chromosomal abnormalities and oocyte fragmentation, as well as improve mitochondrial function. Proposed mechanisms of CoQ10 function include restoration of reactive oxygen species imbalance, preventing DNA damage and oocyte apoptosis, as well as restoration of Krebs cycle downregulation from ageing. In this literature review, we provide an overview of the use of CoQ10 in improving the success of IVF and IVM in older women, and additionally assess the impact of CoQ10 on oocyte quality and discuss potential mechanisms of action by CoQ10 on the oocyte.

Effect of and the association between vitamin D and outcomes of assisted reproductive techniques among infertile men and women: protocol for an overview of systematic reviews and meta-analysis.

INTRODUCTION: Vitamin D is associated with many functions of the human reproductive system. Accordingly, it seems that on infertile couples undergoing assisted reproduction technology (ART), treatment outcomes may be affected by the vitamin D. This overview aims to show the effect of vitamin D on infertility treatments outcomes in recent studies by concluding systematic reviews and meta-analyses to achieve a comprehensive result. METHODS AND ANALYSIS: This overview protocol is being reported according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement and was registered in the International Prospective Register of Systematic Reviews. We will include all peer-reviewed systematic reviews and meta-analyses of randomised controlled trials published from inception until December 2022. PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Scopus, Cochrane Central Register of Controlled Trials and Embase will be searched from the time of publication of the first articles onwards with a comprehensive search strategy. Endnote V.X7 software (Thomson Reuters, New York, New York, USA) will be used to store and manage records. The results will align with guidelines in the Cochrane Handbook of Systematic Reviews of Interventions and the PRISMA statement. ETHICS AND DISSEMINATION: This overview will be evaluating the effect of vitamin D status and vitamin D supplementing on results of ART in women and men who are undergoing treatment for infertility. The high prevalence of vitamin D deficiency worldwide and its effects on an important issue such as human fertility might be a very influential factor that leads scientists to strongly recommend its use. However, the more critical concern is that there is no definitive agreement in studies on the relationship between vitamin D and an increased chance of better fertility in men and women undergoing infertility treatment. PROSPERO REGISTRATION NUMBER: CRD42021252752.

Third-party reproduction: a treatment that grows with societal changes.

Third-party reproduction refers to the use of eggs, sperm, or embryos that have been donated by a third person (the donor) to enable individuals or couples (the intended parents) with infertility to have a child. This differs from the traditional father-mother family model with no third parties involved. Third-party reproduction is also used by couples that are unable to reproduce by traditional means, same-sex couples, and men and women without a partner. This has emerged as a treatment option with great success rates in a scene of changing family constellations. Consequently, this therapeutic alternative has become a realistic solution which has brought great satisfaction and happiness to people who otherwise would have not been able to achieve parenthood if these options were not medically and legally available.

Live birth is not the only relevant outcome in research assessing assisted reproductive technology.

In assisted reproductive technology (ART) research, live birth has been generally accepted as an important outcome, if not the most important one. However, it has been reported inconsistently in the literature and solely focusing on live birth can lead to misinterpretation of research findings. In this review, we provide an overview on the definitions of live birth, including various denominators and numerators use. We present a series of real clinical examples in ART research to demonstrate the impact of variations in live birth on research findings and the importance of other outcomes, including multiple pregnancy, pregnancy loss, time to pregnancy leading to live birth, other short and long term maternal and offspring health outcomes and cost effectiveness measures. We suggest that outcome choices in ART research should be tailored for the research questions. A holistic outcome assessment beyond live birth would provide a full picture to address research questions in ART in terms of effectiveness and safety, and thus facilitate evidence-based decision making.

The effect of adding L-Carnitine to the GnRH-antagonist protocol on assisted reproductive technology outcome in women with polycystic ovarian syndrome: a randomized clinical trial.

OBJECTIVE: This study aimed to investigate the effect of adding L-Carnitine to the gonadotropins on ART outcome in frozen-thawed embryo transfer cycles among PCOS women. METHODS: In this randomized clinical trial, 83 patients with PCOS were randomized to either L-Carnitine supplemented (n = 42) or control (n = 41) groups. The L-Carnitine group was given 3000 mg of oral L-Carnitine daily until the final day of ovulation. The numbers of metaphase II (MII) oocytes, 2-pronuclears (2PNs), oocyte maturity rate, fertilization rate, fertilization proportion as well as implantation, chemical and clinical pregnancy rates were compared between the two groups. RESULTS: Even though the duration of stimulation and endometrial thickness were comparable between groups (p > .05), serum estradiol level on the day of oocyte triggering, was significantly higher in the L-Carnitine group compared to the control group (p < .05). In contrast, the number of retrieved and MII oocytes as well as the number of 2PNs and obtained embryos were similar between groups (p > .05). Moreover, oocyte maturity rate (0.85 ± 0.38 vs. 1.02 ± 0.90), fertilization proportion (0.62 ± 0.44 vs. 0.80 ± 0.86), fertilization rate (0.70 ± 0.22 vs. 0.76 ± 0.19) along with implantation rate (18.1 vs. 13.7%), chemical (26.8 vs. 30.7%) and clinical (24.3 vs. 25.6%) pregnancy rates, were all comparable between L-Carnitine and control groups respectively (p > .05). CONCLUSIONS: Our result showed that oral L-Carnitine administration during induction of ovulation among PCOS women could not improve laboratory and pregnancy outcome.

Percepção sobre o cuidado à perda gestacional: estudo qualitativo com casais brasileiros / Perceptions on pregnancy loss care: a qualitative study with brazilian couples / Percepción sobre la atención a la pérdida del embarazo: estudio cualitativo con parejas brasileñas

Este artigo analisou a percepção e os sentimentos de casais sobre o atendimento recebido nos serviços de saúde acessados em função de perda gestacional (óbito fetal ante e intraparto). O convite para a pesquisa foi divulgado em mídias sociais (Instagram e Facebook). Dos 66 casais que contataram a equipe, 12 participaram do estudo, cuja coleta de dados ocorreu em 2018. Os casais responderam conjuntamente a uma ficha de dados sociodemográficos e uma entrevista semiestruturada, realizada presencialmente (n=4) ou por videochamada (n=8). Os dados foram gravados em áudio e posteriormente transcritos. A Análise Temática indutiva das entrevistas identificou cinco temas: sentimento de impotência, iatrogenia vivida nos serviços, falta de cuidado em saúde mental, não reconhecimento da perda como evento com consequências emocionais negativas, e características do bom atendimento. Os achados demonstraram situações de violência, comunicação deficitária, desvalorização das perdas precoces, falta de suporte para contato com o bebê falecido e rotinas pouco humanizadas, especialmente durante a internação após a perda. Para aprimorar a assistência às famílias enlutadas, sugere-se qualificação profissional, ampliação da visibilidade do tema entre diferentes atores e reorganização dos serviços, considerando uma diretriz clínica para atenção ao luto perinatal, com destaque para o fortalecimento da inserção de equipes de saúde mental no contexto hospitalar.(AU)

This study analyzed couples' perceptions and feelings about pregnancy loss care (ante and intrapartum fetal death). A research invitation was published on social media (Instagram and Facebook) and data collection took place in 2018. Of the 66 couples who contacted the research team, 12 participated in the study by filling a sociodemographic questionnaire and answering a semi-structured interview in person (n=04) or by video call (n=08). All interviews were audio recorded, transcribed, and examined by Inductive Thematic Analysis, which identified five themes: feelings of impotence, iatrogenic experiences in health services, lack of mental health care, not recognizing pregnancy loss as an emotionally overwhelming event, and aspects of good healthcare. Analysis showed experiences of violence, poor communication, devaluation of early losses, lack of support for contact with the deceased baby, and dehumanizing routines, especially during hospitalization after loss. Professional qualification, extended pregnancy loss visibility among different stakeholders, and reorganization of health services are needed to improve the care offered to grieving families, considering a clinical guideline for perinatal grief care with emphasis on strengthening the insertion of mental health teams in the hospital context.(AU)

Este estudio analizó las percepciones y sentimientos de parejas sobre la atención recibida en los servicios de salud a los que accedieron debido a la pérdida del embarazo (muerte fetal ante e intraparto). La invitación al estudio se publicó en las redes sociales (Instagram y Facebook). De las 66 parejas que se contactaron con el equipo, 12 participaron en el estudio, cuya recolección de datos se realizó en 2018. Las parejas respondieron un formulario de datos sociodemográficos y realizaron una entrevista semiestructurada presencialmente (n=4) o por videollamada (n=08). Los datos se grabaron en audio para su posterior transcripción. El análisis temático inductivo identificó cinco temas: Sentimiento de impotencia, experiencias iatrogénicas en los servicios, falta de atención a la salud mental, falta de reconocimiento de la pérdida como un evento con consecuencias emocionales negativas y características de buena atención. Los hallazgos evidenciaron situaciones de violencia, comunicación deficiente, desvalorización de las pérdidas tempranas, falta de apoyo para el contacto con el bebé fallecido y rutinas poco humanizadas, especialmente durante la hospitalización tras la pérdida. Para mejorar la atención a las familias en duelo, se sugiere capacitación profesional, ampliación de la visibilidad del tema entre los diferentes actores y reorganización de los servicios, teniendo en cuenta una guía clínica para la atención del duelo perinatal, enfocada en fortalecer la inserción de los equipos de salud mental en el contexto hospitalario.(AU)

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques.

Background: Early embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study. Objective: Our study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA. Methods: A total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP-MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA. Results: Se concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18-2.52; OR = 2.27, 95% CI: 1.37-3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07-0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant. Conclusion: The levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

Omega-3 fatty acids dietary intake for oocyte quality in women undergoing assisted reproductive techniques: A systematic review.

Dietary intake of omega-3 polyunsaturated fats (PUFAs) may be associated with successful assisted reproductive techniques (ART). However, heterogeneous studies were conducted and opposing results were obtained. This systematic review aims to summarize the evidence on the effect of omega-3 dietary intake on oocyte and embryo quality for a positive ART outcome. The PRISMA 2020 statement was followed and the review protocol was registered with PROSPERO (CRD42021283881). Inclusion and exclusion criteria were: eligible studies examined women undergoing ART cycles whose diet was evaluated for omega-3 intake or experienced an increase in omega-3 compared with women who followed in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) but did not increase the omega-3 intake before the cycle. 5,412 records were identified and five studies were included in the analysis. Two studies focused on sub-fertile or infertile women specifically, yet all women in all studies went through IVF/ICSI procedures. All five studies demonstrated how omega-3 FAs may be beneficial by increasing the positive rate of ART outcomes and embryo quality evaluated according to morphology and morphokinetic parameters. More research focusing on comparable and/or equal outcomes is required to strengthen supporting evidence with the aim to provide valid recommendations for women seeking a pregnancy.

Preconception vitamin D intake and obstetric outcomes in women using assisted reproductive technology: the Japan Environment and Children's Study.

BACKGROUND: In reproductive medicine, vitamin D (VitD) is of particular interest because its deficiency has been linked to various infertility issues. Thus, preconception care, including appropriate VitD supplementation, is essential, especially in women using assisted reproductive technology (ART). Despite the therapeutic benefits of VitD, adverse events due to a high daily intake may influence obstetric outcomes. However, the effects of either low or high preconception VitD intake on obstetric outcomes, including the outcomes in women who used ART, remain unclear. Therefore, the aim of this study was to examine the association between pre-pregnancy daily VitD intake and obstetric outcomes in Japanese women, including those who conceived through ART. METHODS: Data were obtained from the Japan Environment and Children's study database comprising 92,571 women recruited between January 2011 and March 2014 in Japan. Participants were categorized into five quintiles according to pre-pregnancy VitD intake (Q1 and Q5 had the lowest and highest VitD intake, respectively) and stratified according to the use of ART. Multiple logistic regression was performed to identify the effects of pre-pregnancy VitD intake on preterm birth (PTB), low-birth weight infant (LBW), and small for gestational age (SGA). RESULTS: Using Q3 (middle VitD intake) as a reference, our analysis revealed that Q5 (highest VitD intake) showed an increased risk of LBW < 1500 g (adjusted odds ratio [aOR]: 1.09, 95% confidence interval [CI]: 1.00-1.18) and SGA (aOR: 1.26, 95% CI: 1.14-1.39) among women who conceived without ART. Among women who conceived with ART, we found that Q5 (highest VitD intake) showed an increased risk of PTB at < 37 weeks (aOR: 2.05, 95% CI: 1.27-3.31). CONCLUSION: The present study revealed that higher VitD intake before pregnancy may affect perinatal outcomes, particularly in women using ART. Our findings may facilitate personalized preconceptional counseling regarding VitD intake based on the method of conception, especially among women using ART.

Reproductive outcomes of dual trigger with combination GnRH agonist and hCG versus trigger with hCG alone in women undergoing IVF/ICSI cycles: a retrospective cohort study with propensity score matching.

BACKGROUND: Despite a large number of studies on the selection of trigger drugs, it remains unclear whether the dual trigger with human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonist, compared to the trigger with hCG alone, can improve the reproductive outcome of patients undergoing assisted reproductive technology. Therefore, this study aimed to compare the laboratory and clinical outcomes of dual trigger versus single trigger. METHODS: In this retrospective cohort study, we evaluated 520 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles between July 2014 and September 2020 at the Reproductive and Genetic Center of Integrative Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All patients underwent IVF/ICSI treatment with fresh embryo transfer using the GnRH antagonist protocol. We used propensity score matching to control for confounding variables and binary logistic regression analysis to determine the correlations between trigger methods and pregnancy outcomes. After propensity score matching, 57 cycles from each group were evaluated and compared for laboratory or clinical outcomes in this retrospective cohort study. RESULTS: There was no significant difference in the number of oocytes retrieved, embryos available, top-quality embryos, or the rate of normal fertilization between the dual-trigger and single-trigger protocols, respectively. The incidence of ovarian hyperstimulation syndrome, implantation rate, biochemical pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate, early miscarriage rate, and live birth rate were also similar between the two groups, while the miscarriage rate (37.0% vs. 12.5%, p = 0.045) was higher in the dual-trigger than the single-trigger group. Subsequent binary logistic regression analysis showed that age was a remarkably significant independent predictor of both clinical pregnancy rate (odds ratio = 0.90, 95% confidence interval: 0.84-0.97, p = 0.006) and live birth rate (odds ratio = 0.89, 95% confidence interval: 0.82-0.97, p = 0.005). CONCLUSIONS: Therefore, dual-trigger for final oocyte maturation might increase miscarriage rate, but in terms of the laboratory and other pregnancy outcomes such as clinical pregnancy rate, early miscarriage rate or live birth rate, there was no evidence to show that dual trigger was superior to an hCG-trigger alone for patients undergoing GnRH-antagonist cycles with fresh embryo transfer. TRIAL REGISTRATION: Retrospectively registered.

The Effect of Dietary Patterns on Clinical Pregnancy and Live Birth Outcomes in Men and Women Receiving Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis.

The nutritional status of reproductive-aged couples can have a significant impact on fertility status, but the effect of dietary patterns on pregnancy outcomes in people using assisted reproductive technologies (ARTs) is currently unknown. This review aimed to synthesize the published research investigating the relation between preconception dietary patterns and clinical pregnancy or live birth in men and women of reproductive age undergoing ART. Six electronic databases were systematically searched for original research published between January 1978 and June 2021. Original research reporting on the effect of predefined dietary patterns on either clinical pregnancy and/or live birth rates following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in men and women aged 18-49 y was eligible for inclusion. Studies were assessed for risk of bias according to the Cochrane guidelines. Included studies underwent qualitative and quantitative synthesis using random-effects model meta-analyses. Thirteen studies (12 cohort studies, 1 randomized controlled trial) reporting on 3638 participants (93% female) were included in the review. All studies had a moderate-high risk of bias. In individual studies, maternal adherence to 4 dietary patterns [Mediterranean diet (RR: 1.22; 95% CI: 1.05, 1.43), novel profertility diet (OR: 1.43; 95% CI: 1.19, 1.72), Iranian traditional medicine diet (OR: 3.9; 95% CI: 1.2, 12.8), Dutch national dietary recommendations diet (OR: 1.65; 95% CI: 1.08, 2.52)] was associated with increased likelihood of achieving a clinical pregnancy, while 2 dietary patterns [novel profertility diet (OR: 1.53; 95% CI: 1.26, 1.85), Mediterranean diet (RR: 1.25; 95% CI: 1.07, 1.45)] were associated with increased probability of live birth. Meta-analyses showed an association between adherence to the Mediterranean dietary pattern and live birth across 2 studies (OR: 1.98; 95% CI: 1.17, 3.35; I2 = 29%, n = 355), but no association with clinical pregnancy. As the relation between dietary patterns and ART outcomes is currently inconsistent, higher-quality nutrition research is required to further explore this emerging field of interest (PROSPERO registration: CRD42020188194).

Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients. METHODS: In this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes. RESULTS: According to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates. CONCLUSION: AST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients' GCs. TRIAL REGISTRATION: ClincialTrials.gov Identifier: NCT03991286.

The effect of Myo-Inositol supplement on molecular regulation of folliculogenesis, steroidogenesis, and assisted reproductive technique outcomes in patients with polycystic ovarian syndrome.

RESEARCH QUESTION: The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear. DESIGN: Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3ß-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation. RESULT: Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1. CONCLUSION: Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality.