Age related semen parameters and ICSI pregnancy outcomes of 8046 men in Turkey over a 9-year period.

The effect of paternal age on fertility remains unclear. This retrospective study aims to examine the impact of male age on semen parameters and the reproductive outcomes of men admitted to an infertility center over a 9-year period. A total of 8046 patients were included in the study. Men were divided into four age groups. The groups were evaluated for semen parameters and reproductive outcome. The 21-30 year group presented lower sperm concentrations in comparison to those aged 31-40 and 41-50, yet shared a similar concentration to those over 50 years of age. Moreover, grades A and B decreased significantly in men aged over 50 years. The highest progressive motility and normozoospermia were observed in the age group 31-40 years while men over 50 years of age had the highest rates of asthenozoospermia and oligoasthenozoospermia. Furthermore, live birth results were reported in 5583 of the patients who underwent intracytoplasmic sperm injection (ICSI) and were found highest between 31-40 years of age. To our knowledge, this is the largest study in Turkey focusing on male age-related semen parameters and ICSI pregnancy outcomes. The study demonstrates that age is a significant factor for semen quality and live birth.

Melatonin improves fertilization rate in assisted reproduction: Systematic review and meta-analysis.

BACKGROUND: Melatonin is a hormone produced by the pineal gland and it has antioxidant properties. AIM: This study aimed to evaluate the effects of melatonin on assisted reproductive technologies through a systematic review and a meta-analysis. MATERIALS AND METHODS: Search strategies were used in PubMed and in other databases covering the last 15 years. After screening for eligibility, 17 articles were selected for the systematic review. For the meta-analysis statistics, two groups were formed, the treatment group (with melatonin) and the control group (without melatonin) for various assisted reproduction outcomes. RESULTS: The main results were that no statistical differences were found concerning the clinical pregnancy outcome (p = 0.64), but there was a statistical difference with respect to Mature Oocytes (MII) (p = 0.001), antral follicle count (p = 0.0002), and the fertilization rate (p ≤ 0.0001). CONCLUSIONS: Melatonin had beneficial effects such as the improvement in the fertilization rate, although the authors did not obtain significance in the clinical pregnancy rate.

Gonadotropin-Releasing Hormone (GnRH) Agonist Protocol Improves Pregnancy Outcomes During In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Treatment in Young Infertile Women: A Retrospective Study.

Objective The objective of this study was to determine if gonadotropin-releasing hormone agonist (GnRH-a) or gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in young infertile women improve their pregnancy outcomes. Methodology We retrospectively reviewed the records of 876 young infertile women aged 20-35 years who underwent fresh embryo transfer in IVF/ICSI cycles. The data were collected from their initial visits to the reproductive medicine center of the Second Affiliated Hospital of Zhengzhou University between January 2019 and December 2022. We divided them into two groups according to the controlled ovarian hyperstimulation (COH) protocols: GnRH-a (n = 580) and GnRH-ant (n = 296). The primary outcome assessed in this study was the live birth rate. The secondary observation indicators included the total dose and duration of gonadotropin (Gn), total embryo transfer, day three (D3) embryo transfer, total two pro-nuclei (2PN) cleavage count, number of fertilizations, and implantation rate. Results The live birth rate had no clinical significance (P > 0.05). The total dose and duration of Gn stimulation in the GnRH-ant group were lower than in the GnRH-a group (P  < 0.05). The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer, and mature oocytes in metaphase II (MII) of D3 embryos in the GnRH-a group were higher than those in the GnRH-ant group (P  < 0.05). The clinical pregnancy rate and implantation rate of the GnRH-a group were higher than those of the control group. Conclusions The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer and MII of D3 embryos, clinical pregnancy, and implantation rates were significantly higher in the GnRH-a protocol group. The total dosage of Gn and duration of Gn stimulation were lower in the GnRH-ant group than in the GnRH-a group. These findings provide the basis for the selection of the COH protocol in normal Chinese ovarian response patients undergoing IVF/ICSI.

Vitamin D levels in couples undergoing In vitro Fertilization: Lack of Association with Embryo Quality or Pregnancy Rates.

OBJECTIVE: To investigate the potential impact of vitamin D serum levels of couples going through in vitro fertilization in terms of embryo quality and pregnancy rates. DESIGN: Retrospective cohort study SETTING: Fertipraxis, private human reproduction center on Rio de Janeiro, Brazil. SUBJECTS: 267 couples who underwent intracytoplasmic sperm injection between January 2017 and March 2019. EXPOSURE: The couples were categorized into four groups based on 25OH vitamin D levels measured at the beginning of the stimulation protocol: Group 1 with levels ≥ 30 ng/mL for both women and men; Group 2 with levels < 30 ng/mL for both; Group 3 with women < 30 ng/mL and men ≥ 30 ng/mL; and Group 4 with women ≥ 30 ng/mL and men < 30 ng/mL. MAIN OUTCOME MEASURES: We consider quantity and quality of embryos during the cleavage and blastocyst stages as primary outcomes. Correspondingly, clinical pregnancy rate was regarded as a secondary outcome. RESULTS: Our findings revealed no significant correlations between the studied VD groups and the evaluated outcomes. This includes quantity and quality of embryos during the cleavage and blastocyst stages, as well as clinical pregnancy rate. Primary analysis revealed a small but statistically significant difference in the duration of controlled ovarian stimulation between group 1 and group 2 (p=0.035; CI=0.07 - 3.04) and between group 1 and group 3 (p=0.040; CI=0.05 - 3.23). CONCLUSION: The present study found no correlation between the studied VD levels and quantity and quality of cleavage or blastocyst stage embryos, nor did it show any impact on clinical pregnancy rates. Further well designed, prospective studies are warranted to determine whether and how vitamin D affects reproductive outcomes.

The impact of assisted reproductive technologies on ADHD: A systematic review and meta-analysis.

BACKGROUND: The escalating utilization of assisted reproductive technology (ART) in response to global infertility rates has spurred research into its complications. Short-term and long-term outcomes have been extensively studied, particularly the neurological concerns surrounding attention-deficit/hyperactivity disorder (ADHD) among ART-conceived children. This study aims investigate the association between ART and ADHD. METHODS: Medline, Embase, Scopus, and Web of Science databases were searched through April 4, 2023. Cohort, case-control, and cross-sectional studies were eligible for inclusion. primary summary measures included the unadjusted relative risk (RR) and adjusted hazard ratio (HR) with 95 % confidence intervals. Both fixed-effects and random-effects models were utilized for meta-analysis data pooling to determine the overall effect size. The onset of ADHD in children conceived through ART compared to those conceived naturally. RESULTS: The systematic search yielded 8 studies with 10,176,148 individuals included in the meta-analysis. The meta-analysis revealed a pooled RR of 0.93 (0.68-1.26) for cohort studies and a pooled RR of 0.97 (0.41-2.29) for cross-sectional studies, along with a pooled HR of 1.08 (1.03-1.13) for ADHD in the ART group compared to the non-ART group. CONCLUSION: While this study identifies some potential association between ART and ADHD, the limited effect size and inherent heterogeneity underscore the need for cautious interpretation.

Exploring the benefit of different methods to perform assisted hatching in the ART laboratory: A narrative review.

In the last decades, to enhance success rates in assisted reproductive technology (ART) cycles, scientists have continually tried to optimize embryo culture and selection to increase clinical outcomes. In this scenario, the application of laser technology has increased considerably worldwide and is currently applied across ART in several ways: for assisted hatching (AH) or thinning of the zona pellucida (ZP), embryo biopsy, to immobilize and select the sperm during intracytoplasmic sperm injection, as well as to induce artificial blastocyst shrinkage before cryopreservation. Laser-AH has been suggested as a procedure to improve embryo implantation: the concept is that drilling holes through or thinning of the ZP could improve the hatching process and implantation. The artificial disruption of the ZP can be performed by different approaches: mechanically, chemically and with the laser, which is one of the most favourable and easy methods to remove part of the ZP and to augment the possibilities of implantation in patients defined as having a poor prognosis of success, or when the ZP is too thick. However, in the current literature, there is not sufficient evidence about the potential risk or impairment that laser utilization might induce on embryo development; therefore, the main aim of the current review is to provide an overview of the existing knowledge on the ZP and the mechanisms of manipulating it to improve the effectiveness of ART. Also, it emphasizes the positive aspect of laser application as a powerful tool that might increase the chance of pregnancy for infertile couples undergoing ART cycles.

Impact of COVID-19 Vaccination on In Vitro Fertilization Outcomes: A Systematic Review.

COVID-19 vaccination, especially vaccines that mimic the structure of the COVID-19 virus (mRNA vaccines), may be wrongly assumed to be disrupting factors affecting in vitro fertilization (IVF) outcome. This study aims to evaluate any significant impact of COVID-19 vaccination in women undergoing IVF to improve vaccine compliance and promote COVID-19 eradication. This was a systematic review study. We searched studies published between 2020 and 2022 using databases such as PubMed, Cochrane, PMC, and CINAHL. Selected studies were carefully analyzed to review the impact of the COVID-19 vaccine on IVF outcomes. Seven retrospective and prospective cohort studies, which involved 3232 female patients undergoing IVF, who also received full doses of COVID-19 vaccinations (mRNA), were included. All studies in the present review showed that despite presenting anti-SARS-CoV-2 antibodies after vaccination, there were no significant differences in IVF outcomes, implantation rates, and pregnancy rates. Contrary to the theory that presumed cross-reactivity between anti- SARS-CoV-2 antibodies and the human syncytin-1 protein could affect syncytiotrophoblast formation and embryo implantation. The present review concluded that COVID-19 vaccination does not result in any detrimental effects on IVF outcomes and is safe for women undergoing IVF treatment. The results of our study are important to tackle misinformation regarding COVID-19 vaccination and infertility that may cause vaccine hesitancy in women of reproductive age.

Fertility outcomes in women undergoing Assisted Reproductive Treatments after COVID-19 vaccination: A prospective cohort study.

BACKGROUND: Vaccination against Coronavirus-19 disease (COVID-19) was widely administered from 2021 onwards. There is little information on how this vaccine affected fertility after assisted-reproductive-technology (ART). The aim of this study therefore was to determine if COVID-19 vaccination or time-since-vaccination influenced ART outcomes. MATERIALS AND METHODS: In this prospective cohort study, 502 oocyte-retrieval-cycles and 582 subsequent embryo- transfer-cycles were grouped based on COVID-19 vaccine status of the female partner into those with no-exposure, 1-dose and ≥2-dose exposure. Within the exposed cohort, time-since-last-vaccination to embryotransfer- cycle (Ttr) was calculated in days. Main outcomes were mean-total-utilizable-embryos, mean-oocyteutilization- rates and cumulative-ongoing-pregnancy-rates per oocyte-retrieval-cycle, and ongoing-pregnancy and pregnancy-loss-rates per embryo-transfer cycle. The Beta-coefficient (ß) was calculated using linear regression for mean-total-utilizable-embryos and mean-oocyte-utilization-rates and adjusted-odds-ratio (OR) was calculated for cumulative-ongoing-pregnancy-rates, ongoing-pregnancy and pregnancy-loss-rates using binomial logistic regression. Influence of T(tr) on embryo-transfer outcomes was estimated using receiver-operator-curve (ROC) analysis and cut-offs determined that influenced embryo-transfer outcomes. RESULTS: Mean-total-utilizable-embryos and mean-oocyte-utilization-rate per oocyte-retrieval-cycle in no-exposure, 1-dose and ≥2 dose were 2.7 ± 1.8 vs. 2.5 ± 1.9 vs. 2.7 ± 2.0, P=0.78, (ß=0.42, 95% confidence-interval (CI)=0.15 to 0.69) and 21.2 ± 13.2 vs. 25.1 ± 19.0 vs. 26.7 ± 18.8, P=0.08, (ß=3.94, 95% CI=1.26 to 6.23) respectively. Ongoing-pregnancy-rates and pregnancy-loss-rates per embryo-transfer-cycle were 27.3% vs. 24.4% vs. 32.5% (aOR=1.38, 95% CI=0.3-5.6, P=0.52), and 13.6% vs. 13.4% vs. 15.2%, (aOR=0.97, 95% CI=0.18-5.2, P=0.97) respectively. Cumulative-ongoing-pregnancy-rates per oocyte-retrieval-cycle were 36.5% vs. 34.5% vs. 35.5% (aOR=1.53, 95% CI=0.57 to 4.07, P=0.35). Median T(tr) was 146 days (IQR: 80-220). T(tr) negatively affected ongoing pregnancy rates for intervals <60 days (AUC=0.59, 95% CI=0.54-0.66, P<0.01). For T(tr) >60 vs. <60 days, the aOR for ongoing-pregnancy-per-embryo-transfer-cycle was 2.85 (95% CI=1.50-5.46, P<0.01). CONCLUSION: Covid-19 vaccination does not negatively influence embryological-outcomes or cumulative-ongoing-pregnancies after ART-treatments. Duration since vaccination may have a weak negative effect on embryo-transfer-outcomes performed within 60 days.

Preimplantation Genetic Testing for Aneuploidy in In Vitro Fertilization Using Comprehensive Chromosome Screening: A Systematic Review and Meta-Analysis.

The utility of pre-implantation genetic testing (PGT-A) is controversial, with older meta-analyses demonstrating improved pregnancy outcomes, while newer trials have not shown benefit. Therefore, we performed a meta-analysis which aimed to evaluate the benefits of PGT-A using comprehensive chromosome screening (CCS) and its effects on in vitro fertilization (IVF) outcomes among randomized controlled trials (RCTs). We conducted a systematic search to identify RCTs comparing women undergoing PGT-A with CSS with women not undergoing PGT-A, from inception to December 2020. Random effects meta-analysis was utilized to calculate average odds ratios (OR) for clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and miscarriage rate (MR). The heterogeneity of exposure was assessed using Forest plots and I2 statistics. Publication bias was evaluated using Egger's test. Among 1251 citations, seven RCTs met the inclusion criteria. Biopsies of embryos were carried out at various developmental stages, including polar body, day 3, and day 5-6 of culture. Data was analyzed as all studies and blastocyst only. Meta-analysis failed to show improvement in OPRs using PGT-A in the all ages, <35 years old and ≥35 years old age groups. There was also no significant difference in CPRs in any group. The MR decreased with the use of PGT-A (among all biopsy types and among blastocyst biopsies) in the all-ages group, but not when stratifying according to patient age <35 and ≥35 years old. More data regarding the risks and advantages of PGT-A are needed to make a final decision on the value of this intervention in clinical practice. The exact magnitude of the benefit of PGT-A selection cannot be correctly determined until multiple standardized protocol IVF PGT-A trials are conducted.

Association of Working Status with Clinical Pregnancy and Miscarriage among Women undergoing In Vitro Fertilization: Single-Centre Cross-Sectional Study.

BACKGROUND: Middle-aged working women represent most patients attending fertility clinics for in vitro fertilization (IVF) treatment. In this study, we aimed to identify the association of women's working status with clinical pregnancy and miscarriage in the first trimester after IVF treatment. MATERIALS AND METHODS: In this single-centre cross-sectional study at a private clinic in Kazakhstan, we reviewed electronic medical records of all IVF with intracytoplasmic sperm injection (ICSI) and fresh embryo transfer (ET) cycles from January 2018 to December 2019 (n=654). 300 cycles in patients with normal ovarian reserve and registered working status of a female partner in the medical records were selected for the analysis. The study's primary outcome measures were clinical pregnancy rates and clinical miscarriage in the first trimester. RESULTS: 204 women were employed, while 96 were not employed before the start of treatment. The mean age of all patients was 32.2 ± 4.8 years, ranging from 23 to 46 years. Two-thirds of working women had office-based occupations employed as doctors, school and university teachers, accountants, clerks, and managers. One-third of the study participants had manual labor jobs, including service positions and plant workers. There was no association between women's working status and clinical pregnancy rate adjusted for age, antral follicle count, history of pelvic adhesiolysis, and embryo development stage at embryo transfer. However, working women had almost five times the risk of the first trimester miscarriage compared to non-working women [adjusted odds ratio (aOR) 4.56, 95% confidence interval (CI): 0.52 to 4.96] adjusted for age and number of retrieved oocytes. CONCLUSION: Women who work before commencing IVF treatment can be reassured of having equal chances of conception following the treatment compared to non-working women. The observed risk of first trimester miscarriage in working women necessitates further research before drawing any conclusions from medical and public health points.

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles.

BACKGROUND: The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. METHODS: The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients' previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. RESULTS: Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles. CONCLUSION: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

Harnessing Artificial Intelligence to Predict Ovarian Stimulation Outcomes in In Vitro Fertilization: Scoping Review.

BACKGROUND: In the realm of in vitro fertilization (IVF), artificial intelligence (AI) models serve as invaluable tools for clinicians, offering predictive insights into ovarian stimulation outcomes. Predicting and understanding a patient's response to ovarian stimulation can help in personalizing doses of drugs, preventing adverse outcomes (eg, hyperstimulation), and improving the likelihood of successful fertilization and pregnancy. Given the pivotal role of accurate predictions in IVF procedures, it becomes important to investigate the landscape of AI models that are being used to predict the outcomes of ovarian stimulation. OBJECTIVE: The objective of this review is to comprehensively examine the literature to explore the characteristics of AI models used for predicting ovarian stimulation outcomes in the context of IVF. METHODS: A total of 6 electronic databases were searched for peer-reviewed literature published before August 2023, using the concepts of IVF and AI, along with their related terms. Records were independently screened by 2 reviewers against the eligibility criteria. The extracted data were then consolidated and presented through narrative synthesis. RESULTS: Upon reviewing 1348 articles, 30 met the predetermined inclusion criteria. The literature primarily focused on the number of oocytes retrieved as the main predicted outcome. Microscopy images stood out as the primary ground truth reference. The reviewed studies also highlighted that the most frequently adopted stimulation protocol was the gonadotropin-releasing hormone (GnRH) antagonist. In terms of using trigger medication, human chorionic gonadotropin (hCG) was the most commonly selected option. Among the machine learning techniques, the favored choice was the support vector machine. As for the validation of AI algorithms, the hold-out cross-validation method was the most prevalent. The area under the curve was highlighted as the primary evaluation metric. The literature exhibited a wide variation in the number of features used for AI algorithm development, ranging from 2 to 28,054 features. Data were mostly sourced from patient demographics, followed by laboratory data, specifically hormonal levels. Notably, the vast majority of studies were restricted to a single infertility clinic and exclusively relied on nonpublic data sets. CONCLUSIONS: These insights highlight an urgent need to diversify data sources and explore varied AI techniques for improved prediction accuracy and generalizability of AI models for the prediction of ovarian stimulation outcomes. Future research should prioritize multiclinic collaborations and consider leveraging public data sets, aiming for more precise AI-driven predictions that ultimately boost patient care and IVF success rates.

METAPHOR: Metabolic evaluation through phasor-based hyperspectral imaging and organelle recognition for mouse blastocysts and oocytes.

Only 30% of embryos from in vitro fertilized oocytes successfully implant and develop to term, leading to repeated transfer cycles. To reduce time-to-pregnancy and stress for patients, there is a need for a diagnostic tool to better select embryos and oocytes based on their physiology. The current standard employs brightfield imaging, which provides limited physiological information. Here, we introduce METAPHOR: Metabolic Evaluation through Phasor-based Hyperspectral Imaging and Organelle Recognition. This non-invasive, label-free imaging method combines two-photon illumination and AI to deliver the metabolic profile of embryos and oocytes based on intrinsic autofluorescence signals. We used it to classify i) mouse blastocysts cultured under standard conditions or with depletion of selected metabolites (glucose, pyruvate, lactate); and ii) oocytes from young and old mouse females, or in vitro-aged oocytes. The imaging process was safe for blastocysts and oocytes. The METAPHOR classification of control vs. metabolites-depleted embryos reached an area under the ROC curve (AUC) of 93.7%, compared to 51% achieved for human grading using brightfield imaging. The binary classification of young vs. old/in vitro-aged oocytes and their blastulation prediction using METAPHOR reached an AUC of 96.2% and 82.2%, respectively. Finally, organelle recognition and segmentation based on the flavin adenine dinucleotide signal revealed that quantification of mitochondria size and distribution can be used as a biomarker to classify oocytes and embryos. The performance and safety of the method highlight the accuracy of noninvasive metabolic imaging as a complementary approach to evaluate oocytes and embryos based on their physiology.

Factors infl uencing delivery in women with multiple fetus pregnancy.

OBJECTIVE: This paper aims to analyze the factors that can influence the method of childbirth in women with multiple pregnancies. MATERIALS AND METHODS: Retrospective analysis of selected parameters in women with multiple pregnancies who gave birth at the 2nd Clinic of Gynecology and Obstetrics of the Faculty of Medicine (FM), Comenius University (CU) and University Hospital (UH) Bratislava in the years 2010-2022. RESULTS: Between 2010 and 2022, at the 2nd Clinic of Gynecology and Obstetrics of the FM CU and UH in Bratislava, 1.13% of births were multiple pregnancies. After statistical data processing, primiparity appeared statistically significant as a risk of acute caesarean section (C-section); multiparous women had a higher probability to give birth vaginally. Since 2017, the clinic has had a decreasing trend in the number of caesarean sections. Women with an acute caesarean section, in turn had on average a lower pH of both fetuses compared to vaginal delivery. However, the incidence of asphyxia in fetuses was not statistically significantly different. We found no risk factor increasing the likelihood of acute caesarean section for fetus B in twins. CONCLUSION: Multiple pregnancy has a higher morbidity not only for the woman but also for the fetuses. The incidence of multiple pregnancies is influenced by assisted reproduction. Delivery method depends on various factors such as chorionicity, fetal presentation, and history of a previous caesarean section.

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Assisted reproductive technologies (ARTs) are core components of the field of reproductive medicine, encompassing multiple pivotal stages of early development from gamete maturation and fertilization to embryo development. Against the backdrop of a deteriorating trend of global decline in fertility rates, patients with infertility problems increasingly turn to ARTs to realize their dreams of parenthood. However, concomitant with this trend is a growing apprehension regarding the potential adverse effects of ARTs. Herein, we endeavor to discuss several common ARTs procedures utilized in clinical settings and the relevant cutting-edge advancements. The ARTs discussed in the article include in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), biphasic in vitro maturation (biphasic IVM), frozen embryo transfer (FET), preimplantation genetic testing (PGT), non-invasive PGT (niPGT), etc. In addition, we reevaluated their roles within the broader context of assisted reproduction aimed at promoting reproductive health. Additionally, we will delve into the impact of ARTs on the reproductive health of the offspring. By prioritizing the reproductive well-being of both patients and their offspring, the ongoing development and improvement of ARTs to enhance their efficacy and safety will contribute significantly to the advancement of human reproductive health.

Monitoring of controlled ovarian stimulation in IVF.

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

Association of ambient PM2.5 and its components with in vitro fertilization outcomes: The modifying role of maternal dietary patterns.

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the "Fruits-Vegetables-Dairy" pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the "Puffed food-Bakery-Candy" pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the "Grains-Tubers-Legumes". Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

Clinical parameters that predict a premature LH rise in patients undergoing ovarian stimulation for IVF.

Background: Normal reproductive function requires adequate regulation of follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion. During ovarian stimulation for in-vitro fertilization (IVF), some patients will demonstrate an early rise in LH despite being treated with a gonadotropin releasing-hormone (GnRH) antagonist, sometimes necessitating cycle cancellation. Previous studies have demonstrated a possible link between a premature LH rise with ovarian response to gonadotropins. We sought to determine what clinical parameters can predict this premature LH rise and their relative contribution. Methods: A retrospective study of 382 patients who underwent IVF treatment at Rambam Medical Center. The patients were stratified into age groups. A model predicting premature LH rise based on clinical and demographic parameters was developed using both multiple linear regression and a machine-learning-based algorithm. Results: LH rise was defined as the difference between pre-trigger and basal LH levels. The clinical parameters that significantly predicted an LH rise were patient age, BMI, LH levels at stimulation outset, LH levels on day of antagonist administration, and total number of stimulation days. Importantly, when analyzing the data of specific age groups, the model's prediction was strongest in young patients (age 25-30 years, R2 = 0.88, p < .001) and weakest in older patients (age > 41 years, R2 = 0.23, p = .003). Conclusions: Using both multiple linear regression and a machine-learning-based algorithm of patient data from IVF cycles, we were able to predict patients at risk for premature LH rise and/or LH surge. Utilizing this model may help prevent IVF cycle cancellation and better timing of ovulation triggering.

Thyroid ultrasonic changes relate to implantation failure in euthyroid women with thyroid autoimmunity undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To determine whether ultrasonic manifestations of Hashimoto's thyroiditis (HT) related to embryo qualities or pregnancy outcomes in women with thyroid autoimmunity (TAI) undergoing in vitro fertilization/intracytoplasmic sperm injection. METHODS: Our study was a retrospective cohort study. A total of 589 euthyroid women enrolled from January 2017 to December 2019. 214 TAI women and 375 control women were allocated in each group according to serum levels of thyroid peroxidase antibodies (TPOAb) and/or anti-thyroglobulin antibodies (TgAb). Basal serum hormone levels and thyroid ultrasound were assessed, embryo qualities, pregnancy outcomes were collected from medical records. Diagnosis of thyroid ultrasound was used for subanalysis. Logistic regression was used to evaluate outcomes of embryo development and pregnancy. RESULTS: Implantation rate was significantly lower in euthyroid women with TAI compared with control group (TAI group: 65.5% vs. Control group: 73.0%, adjusted OR (95% CI): 0.65 (0.44, 0.97), p = 0.04). We further stratified TAI group into two groups: one group with HT features under ultrasound and another group with normal thyroid ultrasound. After regression analysis, TAI women with HT morphological changes had a lower chance of implantation compared with control group (TAI group with HT: 64.1% vs. Control group: 73.0%, adjusted OR (95% CI): 0.63 (0.41, 0.99), p = 0.04), while there was no significant difference on implantation rate between TAI women with normal thyroid ultrasound and control group. Other outcomes, such as embryo qualities and pregnancy rate, were comparable between TAI and control groups. CONCLUSIONS: A higher risk of implantation failure was seen among euthyroid women with TAI, especially women with HT morphological changes under ultrasound. The underlying mechanisms of implantation failure among euthyroid HT patients need further research.

Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome.

Objective: To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods: A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results: A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion: Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.