In Vitro Fertilization Protocol Research Articles

O-043 Con

Abstract Dual and/or double trigger improve IVF success - CON The improvement of in vitro fertilization (IVF) outcomes remains a pivotal area of reproductive medicine research, with the dual trigger approach emerging as a significant innovation. This con abstract explores the scientific basis, methodology, and outcomes associated with the dual trigger strategy, juxtaposed with conventional triggering methods in IVF protocols. The dual trigger, incorporating both Gonadotropin-Releasing Hormone Agonist (GnRHa) and Human Chorionic Gonadotropin (hCG), has been posited to improve oocyte maturation, retrieval-, and live birth rates. By scrutinizing recent studies, clinical trials, and meta-analyses, this debate aims to delineate the efficacy, safety, and application scope of this approach. Initial investigations into the dual trigger method have highlighted its potential to ameliorate oocyte quality and maturity, which are crucial determinants of IVF success. The mechanism underlying this improvement involves the simultaneous activation of LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone) receptors, enhancing follicular response and oocyte developmental competence. Studies have demonstrated an increase in the number of mature oocytes retrieved, attributed to the more synchronized and comprehensive follicular stimulation afforded by the dual trigger. This augmentation in oocyte quality and quantity directly correlates with enhanced embryo development profiles, and higher implantation and clinical pregnancy rates. Furthermore, the dual trigger method has shown promise in reducing the incidence of Ovarian Hyperstimulation Syndrome (OHSS), a severe complication of IVF treatments. By leveraging the luteolytic effects of GnRHa, this strategy minimizes the risk associated with exogenous hCG administration, thus offering a safer alternative for patients predisposed to OHSS. The application of the dual trigger in specific patient cohorts, such as those with PCOS or poor ovarian responders, has been underlined, indicating its potential for personalized reproductive medicine. However, the implementation of the dual trigger strategy is not without challenges. Variability in patient response necessitates a highly individualized approach, with precise dosing and timing adjustments to optimize outcomes. The existing literature presents a heterogeneity in study designs, populations, and outcome measures, which complicates the direct comparison of dual trigger efficacy against traditional methods. Furthermore, the long-term safety and potential impacts on offspring warrant further investigation, given the recent adoption of this approach. In conclusion, the dual trigger strategy may offer significant benefits in enhancing IVF outcomes. Its potential to improve oocyte maturity and quality could increase the number of retrievable oocytes and reduce the incidence of OHSS. However, it is important to acknowledge that, while the GnRH agonist trigger combined with a freeze-all strategy eliminates the risk of OHSS in women with PCOS, the dual trigger approach followed by fresh embryo transfer does not. Further research is imperative to refine its application, understand its mechanisms fully, and establish comprehensive guidelines for its use. The promise of the dual trigger approach underscores the importance of continuous innovation and evidence-based practices in enhancing the efficacy and safety of IVF treatments.

O-156 Trophectoderm biopsy for pre-implantation genetic testing (PGT) does not increase rates of placental abnormalities among singleton pregnancies conceived with in-vitro fertilization (IVF)

Abstract Study question Does trophectoderm biopsy for PGT affect placental pathology? Summary answer Trophectoderm biopsy does not increase rates of placental abnormalities among singleton pregnancies conceived with in-vitro fertilization (IVF). What is known already PGT, routinely performed at the blastocyst stage, is used to screen embryos for aneuploidy, structural rearrangements, and single-gene disorders. The association of ART with abnormal placentation and adverse pregnancy outcomes is known. Whether, in a similar fashion, the disruption of the trophectoderm contributes to increased rates of abnormal placentation, remains unknown. Study design, size, duration Data from 987 singleton livebirths with available placental pathology, who conceived following IVF/±PGT at a single academic fertility center between 01/2004 and 12/2019, were retrospectively reviewed. Placental abnormalities were classified as anatomic, inflammatory, infectious, and vascular (any features of fetal or maternal vascular malperfusion), by one expert perinatal pathologist using the Amsterdam Workshop Consensus definitions. Placental pathology was compared between PGT (n = 76) and non-PGT (fresh and frozen, n = 911) cycles. Participants/materials, setting, methods Primary Outcome Measures: incidence of anatomic, vascular (maternal and fetal side), infectious, and inflammatory placental abnormalities. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using generalized estimating equations regression to adjust for multiple deliveries per patient and for potential confounders [maternal age, body mass index (BMI:kg/m2), race, parity, infertility diagnosis, gestational age, infant gender, hypertensive disorders of pregnancy, IVF and FET protocol]. Main results and the role of chance Patients undergoing PGT were older than the non-PGT group [36.2(3.5) vs. 34.9(3.8) years, p = 0.006] and did not otherwise differ in AMH, BMI, and race. Overall, adjusted (Adj) OR (95%CI) did not reveal any differences between groups in anatomic [0.92(0.82-1.03)], inflammatory [1.03 (0.94-1.14)]), infectious [1.02 (0.9-1.16)], or vascular abnormalities [1.02(0.88-1.18)]. When limiting analysis to blastocyst biopsies/FET cycles only, adjOR did not show any differences in inflammatory [1.01 (0.89-1.13)]), infectious [1.02 (0.88-1.17)], or vascular abnormalities [1.01 (0.84-1.2)] between the PGT and non-PGT group. Interestingly, adjOR (95%CI) revealed lower odds for anatomic abnormalities in the PGT group (0.86 (0.76-0.98), p = 0.021, non-PGT: ref). A sub-analysis of programmed FET cycles revealed persistently lower odds of anatomic abnormalities among the PGT group [adjOR (95%CI): 0.77 (0.67-0.89), p < 0.001, non-PGT: ref]. Among anatomic abnormalities studied in the programmed FET cycles, marginal cord insertion showed a difference between the groups [adjOR(95%CI): 0.83 (0.73-0.95), p:0.007, non-PGT: ref ]. AdjOR(95%CI) showed no differences in inflammatory [ 1.01 (0.87-1.17)], infectious [1.01 (0.86-1.2)], and vascular [0.9 (0.73-1.1)] abnormalities between groups. Limitations, reasons for caution This study is limited by its retrospective nature. Although a large number of IVF placentas was included, the number of patients in the PGT compared to the non-PGT group was smaller potentially limiting our ability to detect subtle differences between groups. Wider implications of the findings Trophectoderm biopsy for PGT does not appear to increase risk for placental abnormalities, a reassuring finding given the increased incidence of abnormal placentation and adverse perinatal outcomes among IVF pregnancies. Trial registration number not applicable

Case Report: The combined effect of endometrial receptivity array and laser assisted hatching on embryo implantation in repeated implantation failure case

This case report describes a couple with nine years of primary infertility and three failed in vitro fertilization (IVF) attempts that showed no reproductive abnormality. Negative results were observed following the conventional IVF protocol. The couple then insisted on laser-assisted hatching (LAH) and endometrial receptivity analysis (ERA). The ERA results showed a specific window for embryo implantation, and accordingly, the treatment was carried out, which resulted in seven good-quality oocytes, leading to the formation of four blastocyst-stage embryos. These embryos were then frozen, single embryo transfer (ET) was performed following the ERA results, and the embryos were successfully implanted. The βhCG level was 245 mIU/mL, indicating that the female had successfully conceived. This case highlights the challenges of a thick zona pellucida and recurrent implantation failure (RIF), defining how a personalized method combining both LAH and ERA could lead to successful implantation.

Rescue intrauterine insemination in women failing to retrieve oocytes at ovum pick-up: report of a case series

PurposeFailure to collect oocytes at the time of oocyte pick-up is an unfavorable outcome of in vitro fertilization (IVF) cycles. In these cases, prompt intrauterine insemination (IUI) could be an option (rescue IUI), but this possibility has been poorly studied.MethodsRescue IUI is routinely offered in our unit in women failing to retrieve oocytes, provided that they have at least one patent tube, normal male semen analysis, and the total number of developed follicles is ≤ 3. We therefore reviewed all oocyte retrievals performed from 2006 to 2022 in our unit to identify these cases. As a comparator, we referred to preplanned IUI performed during the same study period. The 95% confidence interval (95% CI) of proportions was calculated using a binomial distribution model.ResultsRescue IUI was performed in 96 out of 3531 oocyte retrievals (2.7%; 95% CI 2.2–3.3%). Six live births were obtained, corresponding to 6.2% (95% CI 2.3–13.1). All pregnancies were singletons.ConclusionsRescue IUI in women failing to retrieve oocytes is a possible option that may be considered in selected cases. The efficacy is low, but the procedure is simple, and without significant risks. Generalizability to a conventional IVF protocol setting is however limited.

Supplementation with vitamin D improves the embryo quality in in vitro fertilization (IVF) programs, independently of the patients’ basal vitamin D status

PurposeThe study aims to demonstrate the effects of Vitamin D (VD) supplementation, prior to oocyte pick-up within IVF protocols, in women with diverse VD status at the enrollment.MethodsA total of 204 women eligible for intra-cytoplasmatic sperm injection (ICSI) cycles were included in the study and two homogeneous groups were selected from the database. Both group of patients with normal VD baseline level (> 40 ng/ml) and patients with low VD baseline level (< 20 ng/ml) were divided into control group and treatment group. The control group followed the standard procedure. The treatment group was supplemented with vitamin D3 as cholecalciferol in combination with Myo-Inositol, folic acid, and melatonin 3 months before standard procedure, once a day in the evening.ResultsVD levels significantly increased in the study group of low baseline VD, both in serum and in the follicular fluid compared to controls. The treatment induced a significant improvement of the embryo quality in both group of patients considered.ConclusionSupplementation of VD in patients undergoing ICSI procedures significantly improved the number of top-quality embryos compared with the control group, either starting from VD normal baseline values or starting from low values.Trial registration number07/2018.

GnRH agonist trigger in poor prognosis patients undergoing a multicycle approach through DuoStim or consecutive stimulations: a SWOT analysis.

Identify the most recent and significant evidence regarding the ovulation trigger within the framework of a multicycle approach through DuoStim, providing valuable insights for improving treatment strategies in patients with a poor prognosis. The trigger method plays a pivotal role in optimizing in-vitro fertilization (IVF) stimulation, influencing oocyte retrieval and maturation rates, as well as follicle recruitment in consecutive ovarian stimulations such as double stimulation. Decision-making involves multiple factors and, while guidelines exist for conventional stimulation, specific recommendations for the multicycle approach are not well established. The different methods for inducing oocyte maturation underscore the need for personalization of IVF protocols. The GnRH agonist trigger induces rapid luteolysis and establishes favorable hormonal conditions that do not adversely affect the recruitment of consecutive follicular waves in the context of DuoStim. It serves as a valid alternative to hCG in freeze-all cycles. This strategy might enhance the safety and flexibility of ovarian stimulations with no impact on oocyte competence and IVF efficacy.

Premature luteinization and pregnancy outcomes in depot goserelin-downregulated assisted reproductive technology cycles: A cross-sectional study from Ethiopia.

To compare the rate of premature luteinization in depot goserelin-downregulated invitro fertilization (IVF) cycles with other IVF protocols at a teaching hospital in Ethiopia. We conducted a cross-sectional study on the effects of premature luteinization on IVF outcomes at St. Paul's Hospital Millennium Medical College, a tertiary teaching hospital in Ethiopia. Patients who had IVF at this hospital between 2019 and 2020 were included in the study. Patient records were reviewed and collected on Open Data Kit. We used Stata release 15 to analyze the data. A simple descriptive analysis and bivariate analysis were performed as appropriate. A P-value less than 0.05 was considered asstatistically significant. A total of 305 patients (40 cases with premature luteinization and 265 without premature luteinization) were included. There was no difference in the rate of premature luteinization in the depot goserelin long protocol cycles (6.4%), compared to minimal stimulation (14.1%) and antagonist protocols (16.7%), P = 0.19. Embryo transfer was carried out in 27 (67.5%) patients in the premature luteinization group, which was lower than the 86.0% (228/265) in the non-premature luteinization group, P = 0.003. There was no difference in the median number of oocytes retrieved (8.5 [interquartile range 5.0, 13.0] per cycle in the premature luteinization group vs 5.0 [interquartile range 3.0, 10.0] in those without premature luteinization, P = 0.10). A depot goserelin-downregulated long protocol for IVF is a cost-effective and convenient option for controlled ovarian hyperstimulation without increased risk of having premature luteinization compared to antagonist and minimal stimulation protocols.

The administration of long in-vitro fertilization protocol in adenomyosis: case series.

Adenomyosis is a gynaecological condition characterized by the infiltration of endometrial glands and stroma resulting in ectopic intramyometrial, leading to the generalized enlargement of the uterus. Various cyclical regimens are employed globally to assist infertile women with adenomyosis during in-vitro fertilization (IVF) treatment because there is no consensus regarding the best protocol for managing adenomyosis. The authors reported two cases the administration of long IVF protocol in Adenomyosis with pregnancy outcome. In both cases examined were found that the levels of anti-Mullerian hormone (AMH) were below the 25th percentile. Nevertheless, in both of these cases, the number of oocytes successfully retrieved was more than 5, which may have been influenced by the use of GnRH agonists in previous cycles of long protocol. Both of them were diagnosed with intrauterine pregnancy after transfer embryo. Although there is currently no consensus on the most suitable protocol for adenomyosis cases, the application of a long protocol in both of the aforementioned cases has yielded positive IVF outcomes.

Cumulative live birth rate of in vitro fertilization cycle via progestin-primed ovarian stimulation versus gonadotropin-releasing hormone antagonist protocol in infertile women with normal ovarian reserve: an open-label, randomized controlled trial

This study aimed to evaluate the cumulative live birth rate (cLBR) of progestin-primed ovarian stimulation (PPOS) protocol versus gonadotropin-releasing hormone antagonist (GnRH-ant) protocol for in vitro fertilization (IVF) cycle in infertile women with normal ovarian reserve (NOR). Infertile women with NOR who underwent their first IVF cycle were enrolled in an open-label randomized controlled trial. Patients were randomly assigned 1:1 to receive a freeze-all strategy with delayed embryo transfer (PPOS group, n = 174) and fresh embryo transfer first (GnRH-ant group, n = 174). The primary outcome was the cLBR per aspiration. The cLBR between the PPOS group and GnRH-ant group were comparable (55.75% vs. 52.87%, p = 0.591). A premature luteinizing hormone surge was not observed in the PPOS group, while there were six cases (3.45%) in the GnRH-ant group, but no premature ovulation in either of the groups. The pregnancy outcomes, including implantation rate, clinical pregnancy rate and miscarriage rate, were all comparable. In addition, the number of retrieved oocytes, mature oocytes and viable embryos were similar (all p > 0.05) between the two groups.

Reactive oxygen species signalling in the deterioration of quality of mammalian oocytes cultured in vitro: Protective effect of antioxidants

The in vitro fertilization (IVF) is the first choice of infertile couples worldwide to plan for conception. Besides having a significant advancement in IVF procedure, the success rate is still poor. Although several approaches have been tested to improve IVF protocol, minor changes in culture conditions, physical factors and/or drug treatment generate reactive oxygen species (ROS) in oocytes. Due to large size and huge number of mitochondria, oocyte is more susceptible towards ROS-mediated signalling under in vitro culture conditions. Elevation of ROS levels destabilize maturation promoting factor (MPF) that results in meiotic exit from diplotene as well as metaphase-II (M-II) arrest in vitro. Once meiotic exit occurs, these oocytes get further arrested at metaphase-I (M-I) stage or metaphase-III (M-III)-like stage under in vitro culture conditions. The M-I as well as M-III arrested oocytes are not fit for fertilization and limits IVF outcome. Further, the generation of excess levels of ROS cause oxidative stress (OS) that initiate downstream signalling to initiate various death pathways such as apoptosis, autophagy, necroptosis and deteriorates oocyte quality under in vitro culture conditions. The increase of cellular enzymatic antioxidants and/or supplementation of exogenous antioxidants in culture medium protect ROS-induced deterioration of oocyte quality in vitro. Although a growing body of evidence suggests the ROS and OS-mediated deterioration of oocyte quality in vitro, their downstream signalling and related mechanisms remain poorly understood. Hence, this review article summarizes the existing evidences concerning ROS and OS-mediated downstream signalling during deterioration of oocyte quality in vitro. The use of various antioxidants against ROS and OS-mediated impairment of oocyte quality in vitro has also been explored in order to increase the success rate of IVF during assisted reproductive health management.

Advances in microfluidic technology for sperm screening and in vitro fertilization.

About 18% of reproductive-age adults worldwide are affected by infertility. In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are widely used assisted reproductive technologies (ARTs) aimed at improving clinical outcomes. Efficient and noninvasive selection and isolation of highly motile sperm with intact DNA are essential for the success of IVF and ICSI and can potentially impact the therapeutic efficacy and the health of the offspring. Compared to traditional methods, microfluidic technology offers significant advantages such as low sample consumption, high efficiency, minimal damage, high integration, similar microenvironment, and high automation, providing a new platform for ARTs. Here, we review the current situation of microfluidic technology in the field of sperm motility screening and evaluation and IVF research. First, we focus on the working principle, structural design, and screening results of sperm selection microfluidic platforms. We then highlight how the multiple steps of the IVF process can be facilitated and integrated into a microfluidic chip, including oocyte capture, sperm collection and isolation, sperm sorting, fertilization, and embryo culture. Ultimately, we summarize how microfluidics can complement and optimize current sperm sorting and IVF protocols, and challenges and possible solutions are discussed.

Recurrent failure of ART, thrombosis and thrombophilia

In recent years, the number of risk factors for thrombosis associated with pregnancy has increased substantially due to the active introduction of new medical technologies not used 30 years ago or because their role in emerging thrombosis has not been studied, e.g., during pregnancy after assisted reproductive technologies (ART) particularly in vitro fertilization (IVF). The risk of venous thromboembolic complications (VTEС) related to ovarian hyperstimulation during ART is often overlooked. We present the case of a 37-year-old woman who developed thrombosis of the right internal jugular vein 3 weeks after embryo transfer within the IVF protocol. Ovarian hyperstimulation during hormonal IVF protocols provokes procoagulant changes in the hemostasis and fibrinolysis system able to result in venous and arterial thrombosis. The localization of VTEС typical to ART is more often located in the internal jugular vein being accompanied by neck pain and edema. Thrombosis risk factors should be assessed in all women in the IVF program, and appropriate thromboprophylaxis should be carried out to all high risk subjects.

How does the need for IVF affect pregnancy complications among multiple gestations? The study of a large American population database including almost 100,000 multiple gestations

ObjectiveThis study’s aim is to compare pregnancy outcomes in multifetal gestations that were conceived spontaneously compared to in vitro fertilization (IVF). Few population-based studies have addressed this topic. Study designThis is a retrospective cohort study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) database. Our study cohort included 90,552 multifetal gestations conceived spontaneously and 3219 IVF conceptions, from 2008 to 2014, inclusively. Multivariate logistic regression analyses were performed comparing maternal and neonatal outcomes, whilst adjusting for confounding variables. Subject was conducted using ICD-9 codes for multifetal gestation: 651. X and 76.1 and ICD-9 code for IVF: 23.85. Each pregnancy was included once. Results and conclusionIVF multifetal gestations had increased risk of pregnancy-induced hypertension (aOR 1.31, 95 % CI 1.20–1.43), gestational hypertension (aOR 1.21, 95 % CI 1.04–1.41), preeclampsia (aOR 1.31, 95 % CI 1.19–1.45), gestational diabetes (aOR 1.26, 95 % CI 1.13–1.41) and placenta previa (aOR 1.7, 95 % CI 1.32–2.19). IVF delivery outcomes were more likely complicated by cesarean section (aOR 1.21, 95 % CI 1.10–1.33), preterm premature rupture of membranes (aOR 1.33, 95 % CI 1.16–1.52), chorioamnionitis (aOR 1.71, 95 % CI 1.37–2.14), postpartum hemorrhage (aOR 1.44, 95 % CI 1.26–1.63) and transfusions (aOR 1.48, 95 %CI 1.26–1.74). IVF neonatal outcomes were more likely complicated by small for gestational age (aOR 1.26, 95 % CI 1.12–1.41) and congenital anomalies (aOR 1.82, 95 % CI 1.29–2.57). IVF was not found to increase risks of eclampsia, preterm delivery, operative vaginal delivery, hysterectomy, or intrauterine fetal demise.IVF increased the risk of pregnancy, delivery, and neonatal outcomes in multifetal pregnancies with risks increased from 20 % to 70 %. The role of infertility versus the need for IVF and the type of IVF protocol used should be further evaluated.

Comparison between the modified long gonadotropin-releasing hormone agonist protocol and the non-downregulation protocol in POSEIDON groups: a propensity score matching retrospective cohort study.

In vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes. This study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group. This study was designed as a propensity score-matched (PSM) retrospective analysis. The study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology. The patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups. Of the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779). The modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients. Level III.

Carbon Monoxide Exposure Does Not Improve The In Vitro Fertilization Rate of Oocytes Obtained from Heterozygous Hmox1 Knockout Mice.

In our experimental study we explored the impact of maternal reduced heme oxygenase-1 (HO-1) gene (Hmox1) expression on the in vitro fertilization (IVF) rate through the use of heterozygous Hmox1 knockout mice models (HET/Hmox1+/ -). Also, we hypothesized a beneficial role of gametes exposure during fertilization to carbon monoxide (CO), one of HO-1 by-products, that might be relevant for the improvement of IVF rates. IVF technique was performed by using oocytes obtained from wild-type (WT) or Hmox1+/ - dams fertilized with WT, Hmox1+/ - or Hmox1-/ - mice-derived sperm. The fertilization step occurred either in a conventional incubator (37°C, 5% CO2) or in an incubator implemented with CO (500 ppm). The superovulation yield of WT and Hmox1+/ - mice and the number of fertilized oocytes was assessed using an optical microscope. The dams' Hmox1 heterozygous knockout neither impact the superovulation yield, nor did influence the fertilization success rate. Moreover, CO exposure during fertilization could not significantly improve the outcome. Our study showed that the maternal Hmox1+/ -condition is not affecting the IVF rate in mice. Furthermore, we discovered that CO exposure cannot be exploited to ameliorate this critical step of the IVF protocol.

Factors Associated with the Efficacy of Mature Oocyte Production after Dual-Trigger Controlled Ovarian Stimulation using A GnRH Antagonist Protocol.

The number of mature oocytes retrieved plays a significant role in determining embryo development and pregnancy outcomes of in-vitro fertilization (IVF). However, studies investigating factors predictive of the efficacy of mature oocyte production (EMOP) after dual-trigger controlled ovarian stimulation (COS) are rare. This study aims to identify key predictors of EMOP during dual-trigger COS with a GnRH antagonist protocol for IVF. This retrospective cohort study included 359 first-time IVF patients undergoing dual-trigger COS with a GnRH antagonist protocol. EMOP was defined as the ratio of MII oocyte count to antral follicle count (AFC). Based on EMOP results, patients were divided into two groups: Group A (EMOP < 70%; n = 232) and Group B (EMOP ≥ 70%; n = 127). Multivariate logistic regression analysis revealed that day-2 follicle-stimulating hormone (FSH), stimulation duration, and total oocyte count were the most significant predictors of EMOP (p < 0.05; odds ratios: 1.637, 3.400, and 1.530, respectively). Receiver operating characteristic analysis demonstrated that total oocyte count < 9.5 (AUC, 0.782; sensitivity, 76.2%; specificity, 69.2%; p < 0.001), and stimulation duration < 9.5 days (AUC, 0.725; sensitivity, 63.5%; specificity, 66.7%; p < 0.001) significantly predicted EMOP < 70%. Stimulation duration combined with total oocyte count exhibited the highest power in predicting EMOP < 70% (AUC, 0.767; sensitivity, 92.3%; specificity, 42.4%). Stimulation duration combined with total oocyte count was identified as the most important factor associated with the efficacy of mature oocyte production during dual-trigger COS in IVF using a GnRH antagonist protocol.

Successful use of HTF as a basal fertilization medium during SEcuRe mouse in vitro fertilization

ObjectiveThe ever-increasing number of genetically engineered mouse models highlights the need for efficient archiving and distribution of these lines. Sperm cryopreservation has become the preferred technique for the majority of these models due to its low requirement of costs, time, and experimental animals. Yet, current in vitro fertilization (IVF) protocols either exhibit decreased fertilization efficiency for the most popular C57BL/6 strain, as recently demonstrated by us, or require costly and difficult-to-prepare media, respectively. As a result, we previously developed SEcuRe, a modified IVF protocol with low costs and high fertilization efficiency. The popular basal fertilization medium, Cook’s® proprietary “Research vitro fert” (RVF), used in this protocol has recently been discontinued. As a result, the application of the SEcuRe approach and other IVF protocols employing this medium has been severely limited.ResultsHere we show that human tubal fluid (HTF), a popular and widely available medium with a known composition, can be used as a basal fertilization medium instead of RVF. Comparison of RVF and HTF during 58 independent SEcuRe IVFs with cryopreserved C57BL/6 sperm revealed equal fertilization and live birth rates. In addition, we demonstrate that HTF has a substantially extended shelf-life by utilizing commercial HTF that was six months past its expiration date, yet did not affect fertilization during IVF or subsequent embryo development. This finding not only increases the economic value of our modified method, but also validates it once more. Our results demonstrate that common, shelf-life extended HTF can be used in SEcuRe IVF in place of now-discontinued RVF medium and ensure the applicability of the method, which we since termed SEcuRe 2.0. Our modified SEcuRe 2.0 strategy will assist researchers to efficiently archive and distribute genetically engineered mouse models in a cost-effective, easily adaptable, and 3R-compliant manner with minimal animal use.

Cost-effectiveness of preimplantation genetic testing for aneuploidy for women with subfertility in China: an economic evaluation using evidence from the CESE-PGS trial

BackgroundThere are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated.ObjectiveTo investigate the cost-effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) versus conventional technology in in vitro fertilization (IVF) from the perspective of the healthcare system in China.MethodsFollowing the exact steps in the IVF protocol, a decision tree model was developed, based on the data from the CESE-PGS trial and using cost scenarios for IVF in China. The scenarios were compared for costs per patient and cost-effectiveness. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings.Main outcome measuresCosts per live birth, Costs per patient, Incremental cost-effectiveness for miscarriage prevention.ResultsThe average costs per live birth of PGT-A were estimated as ¥39230.71, which is about 16.8% higher than that of the conventional treatment. Threshold analysis revealed that PGT-A would need to increase the pregnancy rate of 26.24–98.24% or a cost reduction of ¥4649.29 to ¥1350.71 to achieve the same cost-effectiveness. The incremental costs per prevented miscarriage was approximately ¥45600.23. The incremental cost-effectiveness for miscarriage prevention showed that the willingness to pay would be ¥43422.60 for PGT-A to be cost-effective.ConclusionThe present cost-effectiveness analysis demonstrates that embryo selection with PGT‑A is not suitable for routine applications from the perspective of healthcare providers in China, given the cumulative live birth rate and the high costs of PGT‑A.

Metabolomics analysis of follicular fluid in ovarian endometriosis women receiving progestin-primed ovary stimulation protocol for in vitro fertilization

This study aimed to investigate the metabolite profile and inflammatory state of follicular fluid (FF) in women with stage III–IV ovarian endometriosis (OE) who underwent in vitro fertilization (IVF). A cohort of 20 consecutive patients with OE were recruited and received progestin-primed ovary stimulation (PPOS) protocol (study group), while another 20 OE patients received one-month ultra-long term protocol (control group) for IVF in this prospective, nonrandomized study. FF samples were obtained from dominant follicles during oocyte retrieval, and liquid chromatography-mass spectrometry (LC–MS) was used to investigate the metabolites profile of FF. Results showed that significant increases in the levels of proline, arginine, threonine, and glycine in patients who received PPOS protocol compared to the control group (P < 0.05). A panel of three metabolites (proline, arginine, and threonine) was identified as specific biomarkers of OE patients using PPOS protocol. Additionally, levels of interleukin-1β, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor-α markedly decreased in women who received PPOS protocol compared to the control group (P < 0.05). In conclusion, PPOS protocol regulates the metabolism of several amino acids in the FF, which may play critical roles in the oocyte development and blastocyst formation, and their specific mechanism should be further elucidated.

High estradiol levels during a long agonist IVF protocol are associated with decreased food intake, higher leptin concentrations, and lower levels of high-sensitivity C-reactive protein

PurposeTo study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol.MethodsFifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test.ResultsDuring the stimulation protocol, leptin concentrations elevated (P < 0.001), and energy intake decreased (P = 0.03), while estradiol levels increased (P < 0.001). GLP-1 levels unchanged (P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased.ConclusionNo increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.