RESUMEN
Assisted reproductive technologies (ARTs) are performed worldwide in the equine industry to produce genetically valuable foals. Among them, ovum pick up (OPU) combined with intra-cytoplasmic sperm injection (ICSI) can now be more efficient than embryo transfer (ET) under optimal conditions. However, OPU is not a benign procedure for the mare and the process is costly. Improved efficiency is therefore in the interest of everyone, maximizing mare welfare and optimizing economics for the client. One of the key factors of success is the antral follicle count (AFC) at the time of OPU and subsequently the number of oocytes obtained. Variations in AFC are reported between individuals and between geographical areas. This leads to a significant increase in numbers of embryos produced per session in some countries compared to others, independent of the laboratory efficiency. This article revisits the basics of folliculogenesis involved in establishment of the antral follicle population and explores work in other species given the paucity of equine research in this area. The aim of the review is to elucidate interesting areas of further research that could generate essential information for clinicians and clients about the management and selection of the donor mare for OPU and potentially identify pharmacological targets for manipulation.
Asunto(s)
Folículo Ovárico , Técnicas Reproductivas Asistidas , Caballos/fisiología , Animales , Femenino , Técnicas Reproductivas Asistidas/veterinaria , Oocitos/fisiología , Inyecciones de Esperma Intracitoplasmáticas/veterinaria , Inyecciones de Esperma Intracitoplasmáticas/métodos , Transferencia de Embrión/veterinaria , Transferencia de Embrión/métodos , Recuperación del Oocito/veterinaria , Recuperación del Oocito/métodos , EmbarazoRESUMEN
Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.
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Tasa de Natalidad , Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Recuperación del Oocito , Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Humanos , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Adulto , Recuperación del Oocito/métodos , Inducción de la Ovulación/métodos , Estudios Retrospectivos , Embarazo , Estudios de Casos y Controles , Fertilización In Vitro/métodos , Síndrome de Hiperestimulación Ovárica/prevención & control , Síndrome de Hiperestimulación Ovárica/epidemiología , Nacimiento Vivo/epidemiología , Índice de Embarazo , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Taiwán/epidemiología , Inyecciones de Esperma Intracitoplasmáticas/métodosRESUMEN
This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.
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Transferencia de Embrión , Fertilización In Vitro , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Femenino , Embarazo , Adulto , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Estudios Retrospectivos , Masculino , Criopreservación/métodos , Resultado del Embarazo , Infertilidad Femenina/terapia , Índice de EmbarazoRESUMEN
BACKGROUND: Data sciences and artificial intelligence are becoming encouraging tools in assisted reproduction, favored by time-lapse technology incubators. Our objective is to analyze, compare and identify the most predictive machine learning algorithm developed using a known implantation database of embryos transferred in our egg donation program, including morphokinetic and morphological variables, and recognize the most predictive embryo parameters in order to enhance IVF treatments clinical outcomes. METHODS: Multicenter retrospective cohort study carried out in 378 egg donor recipients who performed a fresh single embryo transfer during 2021. All treatments were performed by Intracytoplasmic Sperm Injection, using fresh or frozen oocytes. The embryos were cultured in Geri® time-lapse incubators until transfer on day 5. The embryonic morphokinetic events of 378 blastocysts with known implantation and live birth were analyzed. Classical statistical analysis (binary logistic regression) and 10 machine learning algorithms were applied including Multi-Layer Perceptron, Support Vector Machines, k-Nearest Neighbor, Cart and C0.5 Classification Trees, Random Forest (RF), AdaBoost Classification Trees, Stochastic Gradient boost, Bagged CART and eXtrem Gradient Boosting. These algorithms were developed and optimized by maximizing the area under the curve. RESULTS: The Random Forest emerged as the most predictive algorithm for implantation (area under the curve, AUC = 0.725, IC 95% [0.6232-0826]). Overall, implantation and miscarriage rates stood at 56.08% and 18.39%, respectively. Overall live birth rate was 41.26%. Significant disparities were observed regarding time to hatching out of the zona pellucida (p = 0.039). The Random Forest algorithm demonstrated good predictive capabilities for live birth (AUC = 0.689, IC 95% [0.5821-0.7921]), but the AdaBoost classification trees proved to be the most predictive model for live birth (AUC = 0.749, IC 95% [0.6522-0.8452]). Other important variables with substantial predictive weight for implantation and live birth were duration of visible pronuclei (DESAPPN-APPN), synchronization of cleavage patterns (T8-T5), duration of compaction (TM-TiCOM), duration of compaction until first sign of cavitation (TiCAV-TM) and time to early compaction (TiCOM). CONCLUSIONS: This study highlights Random Forest and AdaBoost as the most effective machine learning models in our Known Implantation and Live Birth Database from our egg donation program. Notably, time to blastocyst hatching out of the zona pellucida emerged as a highly reliable parameter significantly influencing our implantation machine learning predictive models. Processes involving syngamy, genomic imprinting during embryo cleavage, and embryo compaction are also influential and could be crucial for implantation and live birth outcomes.
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Blastocisto , Implantación del Embrión , Aprendizaje Automático , Donación de Oocito , Humanos , Femenino , Estudios Retrospectivos , Donación de Oocito/métodos , Embarazo , Adulto , Blastocisto/fisiología , Blastocisto/citología , Implantación del Embrión/fisiología , Índice de Embarazo , Fertilización In Vitro/métodos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Transferencia de Embrión/métodosRESUMEN
Context In vitro embryo production in pigs is an important tool for advancing biomedical research. Intracytoplasmic sperm injection (ICSI) circumvents the polyspermy problems associated with conventional IVF in porcine. However, the suboptimal efficiency for ICSI in pigs requires new strategies to increase blastocyst formation rates. Aim To investigate novel methods for assisted activation using the zinc chelator 1,10-phenanthroline (PHEN), and to improve embryo developmental competence and quality of ICSI porcine blastocyst. Methods ICSI embryos were treated with PHEN after or before sperm injection, recording pronuclear formation, blastocyst rate and the expression of SMARCA4, OCT4, SOX2 and CDX2. Key results Neither electrical nor PHEN significantly improves pronuclear formation rates before or after ICSI. Following in vitro culture to the blastocyst stage, no significant differences were observed in developmental rates among the groups. Moreover, the use of PHEN did not alter the total cell number or the expression of OCT4, SOX2 and CDX2 in pig ICSI blastocysts. Conclusions Assisted oocyte activation with PHEN does not affect the preimplantation development of ICSI-derived pig embryos. Implications These results hold significance in refining and advancing the application of assisted oocyte activation techniques. They offer insights into addressing fertility issues and propelling advancements in human and animal reproductive medicine.
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Quelantes , Desarrollo Embrionario , Oocitos , Fenantrolinas , Inyecciones de Esperma Intracitoplasmáticas , Animales , Inyecciones de Esperma Intracitoplasmáticas/veterinaria , Inyecciones de Esperma Intracitoplasmáticas/métodos , Porcinos , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Fenantrolinas/farmacología , Femenino , Quelantes/farmacología , Desarrollo Embrionario/efectos de los fármacos , Blastocisto/efectos de los fármacos , Blastocisto/metabolismo , Zinc/farmacología , Técnicas de Cultivo de Embriones/veterinaria , MasculinoRESUMEN
BACKGROUND: Overweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment. METHODS: This retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome. RESULTS: Letrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17-3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05). CONCLUSION: Letrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.
Asunto(s)
Inhibidores de la Aromatasa , Transferencia de Embrión , Fertilización In Vitro , Infertilidad Femenina , Letrozol , Sobrepeso , Índice de Embarazo , Humanos , Letrozol/uso terapéutico , Femenino , Estudios Retrospectivos , Adulto , Embarazo , Inhibidores de la Aromatasa/uso terapéutico , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Transferencia de Embrión/métodos , Inducción de la Ovulación/métodos , Nacimiento Vivo , China , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
BACKGROUND: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. METHODS: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. RESULTS: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.
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Astenozoospermia , Dineínas Axonemales , Secuenciación del Exoma , Infertilidad Masculina , Humanos , Masculino , Astenozoospermia/genética , Astenozoospermia/patología , Dineínas Axonemales/genética , Femenino , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Adulto , Cola del Espermatozoide/patología , Cola del Espermatozoide/ultraestructura , Cola del Espermatozoide/metabolismo , Inyecciones de Esperma Intracitoplasmáticas , Embarazo , Espermatozoides/ultraestructura , Espermatozoides/patología , Dineínas/genéticaRESUMEN
OBJECTIVE: To investigate the effect of the early blastocyst on pregnancy and birth outcomes in patients in vitro fertilization/(early rescue) intracytoplasmic sperm injection-embryo transfer [IVF/(early rescue)ICSI-ET] cycles. METHODS: In this retrospective cohort study, 289 patients with single-blastocyst transfer within IVF/(early rescue)ICSI-ET treatment cycle were included and divided into the early (n = 48, Gardner stage = 1 or 2) and the fully expanded blastocyst (n = 241, Gardner stage ≥ 3) groups. The differences in pregnancy and birth outcomes between the two groups were compared. RESULTS: There was no significant differences between the two groups in baseline indicators, including demographic characteristics and clinical treatment (P> 0.05).The clinical outcomes indicators in the early and the fully expanded blastocyst groups were compared, including the number of transferable embryos on the third day (D3)5.0 (4.0, 6.8) vs. 6.0 (5.0, 8.0) (P = 0.001), the number of remaining embryos frozen per cycle 1.0 (0.3, 2.0) vs. 3.0 (2.0, 5.0) (P<0.001); the number of cycles of unfrozen embryos 13/48 (27.1%) vs. 12/241 (5.0%) (P<0.001); the pregnancy outcome including the clinical pregnancy rate (CPR) 20/48 (41.7%) vs. 129/241 (53.5%) (P>0.05); the live birth rate (LBR)15/48 (31.3%) vs.106/241 (44.0%) (P>0.05). There were no significant differences in birth outcomes, such as gestational week of labor, mode of delivery, neonatal birth weight, height, Apgar score, sex ratio, and birth defects between the two groups (P>0.05).Multivariate binary logistic regression showed the same result, i.e., early blastocyst transfer in fresh cycle was not a risk factor for clinical pregnancy (OR = 0.516, 95% CI = 0.260-1.022) and live birth (OR = 0.521, 95% CI = 0.252-1.079). CONCLUSION: Compared with the fully expanded blastocyst group, the CPR and LBR in the early blastocyst group of the fresh transfer cycles were relatively ideal, and there were no significant differences in birth outcomes and neonatal status between the two groups.
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Blastocisto , Transferencia de Embrión , Fertilización In Vitro , Resultado del Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Embarazo , Femenino , Estudios Retrospectivos , Adulto , Inyecciones de Esperma Intracitoplasmáticas/métodos , Blastocisto/citología , Fertilización In Vitro/métodos , Transferencia de Embrión/métodos , Índice de EmbarazoRESUMEN
PURPOSE: This study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing. METHODS: A retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes. RESULTS: Demographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4. CONCLUSION: For patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.
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Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Folículo Ovárico , Inducción de la Ovulación , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Estudios Retrospectivos , Adulto , Inyecciones de Esperma Intracitoplasmáticas/métodos , Embarazo , Fertilización In Vitro/métodos , Folículo Ovárico/efectos de los fármacos , Inducción de la Ovulación/métodos , Índice de Embarazo , Pronóstico , Antagonistas de Hormonas/uso terapéutico , Resultado del EmbarazoRESUMEN
OBJECTIVE: To examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications. METHODS: Women diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student's t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. RESULTS: A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively). CONCLUSIONS: These findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.
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Supervivientes de Cáncer , Neoplasias de los Genitales Femeninos , Infertilidad Femenina , Índice de Embarazo , Técnicas Reproductivas Asistidas , Humanos , Femenino , Estudios Retrospectivos , Adulto , Embarazo , Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias de los Genitales Femeninos/terapia , Infertilidad Femenina/terapia , Infertilidad Femenina/epidemiología , Tasa de Natalidad , Nacimiento Vivo/epidemiología , Fertilización In Vitro/métodos , Resultado del Embarazo/epidemiología , Inyecciones de Esperma Intracitoplasmáticas , China/epidemiologíaRESUMEN
BACKGROUND: To quantitatively evaluate the effect of coenzyme Q10 (CoQ10) pretreatment on outcomes of IVF or ICSI in women with diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs). METHODS: Nine databases were comprehensively searched from database inception to November 01, 2023, to identify eligible RCTs. Reproductive outcomes of interest consisted of three primary outcomes and six secondary outcomes. The sensitivity analysis was adopted to verify the robustness of pooled results. RESULTS: There were six RCTs in total, which collectively involved 1529 participants with DOR receiving infertility treatment with IVF/ICSI. The review of available evidence suggested that CoQ10 pretreatment was significantly correlated with elevated clinical pregnancy rate (OR = 1.84, 95%CI [1.33, 2.53], p = 0.0002), number of optimal embryos (OR = 0.59, 95%CI [0.21, 0.96], p = 0.002), number of oocytes retrieved (MD = 1.30, 95%CI [1.21, 1.40], p < 0.00001), and E2 levels on the day of hCG (SMD = 0.37, 95%CI [0.07, 0.66], p = 0.01), along with a reduction in cycle cancellation rate (OR = 0.60, 95%CI [0.44, 0.83], p = 0.002), miscarriage rate (OR = 0.38, 95%CI [0.15, 0.98], p = 0.05), total days of Gn applied (MD = -0.89, 95%CI [-1.37, -0.41], p = 0.0003), and total dose of Gn used (MD = -330.44, 95%CI [-373.93, -286.96], p < 0.00001). The sensitivity analysis indicated that our pooled results were robust. CONCLUSIONS: These findings suggested that CoQ10 pretreatment is an effective intervention in improving IVF/ICSI outcomes for women with DOR. Still, this meta-analysis included relatively limited sample sizes with poor descriptions of their methodologies. Rigorously conducted trials are needed in the future.
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Fertilización In Vitro , Reserva Ovárica , Índice de Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Inyecciones de Esperma Intracitoplasmáticas , Ubiquinona , Humanos , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Ubiquinona/administración & dosificación , Ubiquinona/farmacología , Femenino , Reserva Ovárica/efectos de los fármacos , Embarazo , Inyecciones de Esperma Intracitoplasmáticas/métodos , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Infertilidad Femenina/tratamiento farmacológico , Adulto , Inducción de la Ovulación/métodosRESUMEN
Objective: To construct a repetitive implantation failure (RIF)-related competitive endogenous RNA (ceRNA) regulatory network and validate with clinical samples. Methods: RIF-related long non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) from the high-throughput gene expression omnibus (GEO) database Expression profile data set were obtained to construct a ceRNA regulatory network of lncRNA-miRNA-mRNA. At the same time, weighted gene co-expression network analysis (WGCNA) was used to explore hub genes in the network. This retrospective study collected RIF patients and controls (at least one pregnancy history after assisted conception) who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) for assisted pregnancy from 2020 to 2021 at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. In the endometrial tissue of patients with 1 pregnancy history, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the mRNA expression levels of RIF-related hub genes, and Western blotting and immunohistochemistry were used to verify protein expression levels of vascular cell adhesion molecule-1 (VCAM1). Results: A RIF-related ceRNA regulatory network consisting of 32 lncRNAs, 31 miRNAs and 88 mRNAs was constructed, and 7 RIF-related hub genes were identified using WGCNA. By intersecting 88 mRNAs and hub genes in the ceRNA network, two RIF-related key genes were obtained, i.e., VCAM1 and interleukin-2 receptor α (interleukin-2 receptor α, IL-2RA). In clinical verification, the ages of the control group and RIF group [M (Q1, Q3)] were 26.50 (25.00, 34.00) and 30.50 (25.75, 35.25) years old, respectively (P>0.05). Compared with the control group, the mRNA [0.30 (0.15, 0.42) vs 0.99 (0.69, 1.34), P=0.001] and protein expression [0.44 (0.16, 1.27) vs 2.39 (1.58, 2.58), P<0.001] of VCAM1 in the endometrium of the RIF group were both reduced. Conclusions: This study uses bioinformatics analysis methods to construct a RIF-related ceRNA regulatory network, and it is confirmed through clinical samples that the expression level of VCAM1 in the endometrial tissue of RIF patients is significantly reduced.
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Implantación del Embrión , Fertilización In Vitro , Redes Reguladoras de Genes , ARN Endógeno Competitivo , Femenino , Humanos , Embarazo , Implantación del Embrión/genética , Endometrio/metabolismo , Perfilación de la Expresión Génica , MicroARNs/genética , Estudios Retrospectivos , ARN Endógeno Competitivo/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Inyecciones de Esperma Intracitoplasmáticas , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
BACKGROUND: Non-invasive chromosome screening (NICS) and trophectoderm biopsy preimplantation genetic testing for aneuploidy (TE-PGT) were both applied for embryo ploidy detection, However, the cumulative live birth rates (CLBR) of NICS and TE-PGT in older age groups have yet to be reported. This study aimed to ascertain whether NICS and TE-PGT could enhance the cumulative live birth rates among patients of advanced maternal age. METHODS: A total of 384 couples aged 35-40 years were recruited. The patients were assigned to three groups: NICS, TE-PGT, and intracytoplasmic sperm injection (ICSI). All patients received frozen single blastocyst transfer. Patients in the NICS and TE-PGT groups underwent aneuploidy screening. RESULTS: When compared to the ICSI group, the CLBR was significantly higher in the NICS and TE-PGT groups (27.9% vs. 44.9% vs. 51.0%, p = 0.003 for NICS vs. ICSI, p < 0.001 for TE-PGT vs. ICSI). There were no significant differences in the clinical outcomes between the NICS and TE-PGT groups. Adjusting for confounding factors, the NICS and TE-PGT groups still showed a higher CLBR than the ICSI group (adjusted odds ratio (OR) 3.847, 95% confidence interval (CI) 1.939 to 7.634; adjusted OR 3.795, 95% CI 1.981 to 7.270). Additionally, the cumulative pregnancy loss rates of the NICS and TE-PGT groups were significantly lower than that of the ICSI group (adjusted OR 0.277, 95% CI 0.087 to 0.885; adjusted OR 0.182, 95% CI 0.048 to 0.693). There was no significant difference in the birth weights of the three groups (p = 0.108). CONCLUSIONS: In women 35-40 years old, the CLBR can be increased by selecting euploid embryos using NICS and TE-PGT. For elderly women at high risk of embryonic aneuploidy, NICS, characterized by its safety and non-invasive nature, may emerge as an alternative option for preimplantation genetic testing.
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Aneuploidia , Pruebas Genéticas , Edad Materna , Diagnóstico Preimplantación , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Diagnóstico Preimplantación/métodos , Adulto , Embarazo , Estudios Prospectivos , Pruebas Genéticas/métodos , Nacimiento Vivo , Tasa de Natalidad , Índice de Embarazo , Masculino , Transferencia de Embrión/métodosRESUMEN
IMPORTANCE: Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes. OBJECTIVE: We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis. DATA SOURCES: We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023. STUDY SELECTION AND SYNTHESIS: We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License). MAIN OUTCOMES AND RESULTS: We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m2 [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I2 = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I2 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I2 = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I2 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups. CONCLUSIONS AND RELEVANCE: The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.
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Adenomiosis , Hormona Liberadora de Gonadotropina , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/agonistas , Embarazo , Adenomiosis/tratamiento farmacológico , Fertilización In Vitro/métodos , Índice de Embarazo , Regulación hacia Abajo/efectos de los fármacosRESUMEN
PURPOSE: To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations. METHODS: We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy. RESULTS: The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term. CONCLUSION: Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm.
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Aurora Quinasa C , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Masculino , Aurora Quinasa C/genética , Adulto , Femenino , Embarazo , Mutación , Espermatozoides/anomalías , Heterocigoto , Secuenciación del ExomaRESUMEN
OBJECTIVE: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population. DESIGN: Health economic evaluation study. SETTING: The data needed to construct the model for this study were derived from published studies and other secondary sources in China. PARTICIPANTS: No patients participated in the study. MEASURES: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results. RESULTS: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (ï¿¥29 146.26 (US$4333.17) vs ï¿¥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ï¿¥30 703.02 (US$4564.62) vs ï¿¥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive). CONCLUSION: For the Chinese population, when the monetary value per live birth was greater than ï¿¥65 420 (US$9726) and ï¿¥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials.
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Análisis Costo-Beneficio , Hormona Liberadora de Gonadotropina , Humanos , China , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Embarazo , Adulto , Fertilización In Vitro/economía , Fertilización In Vitro/métodos , Inyecciones de Esperma Intracitoplasmáticas/economía , Transferencia de Embrión/economía , Transferencia de Embrión/métodos , Economía Farmacéutica , Modelos Económicos , Tasa de Natalidad , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: To investigate the etiology, diagnosis and treatment of 45,X/46,XY mixed gonadal dysgenesis and the patients' clinical characteristics of conception, pregnancy and delivery, with purpose of improving the treatment and pregnancy management of the patients. METHODS: We retrospectively analyzed the clinical data on a pregnant patient with 45,X/46,XY mixed gonadal dysgenesis. RESULTS: Based on the findings of hypoplasia of secondary sexual characteristics, streak gonads, chromosome karyotype incompatibility with social sex, and chromosome aberration in the gonadal tissue, the patient was diagnosed with 45,X/46,XY mixed gonadal dysgenesis, received oocyte donation and intracytoplasmic sperm injection-embryo transfer (ICSI-ET), and achieved a live birth. CONCLUSION: Female patients with 45,X/46,XY mixed gonadal dysgenesis are infertile, but can achieve pregnancy through oocyte donation. However, the incidence rates of pregnancy complications and abnormal delivery are higher in these patients than in normal females. The perinatal outcomes can be improved by efficient treatment and pregnancy management of the patients.
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Donación de Oocito , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Embarazo , Adulto , Inyecciones de Esperma Intracitoplasmáticas/métodos , Nacimiento Vivo , Disgenesia Gonadal Mixta , Transferencia de Embrión , Estudios Retrospectivos , Resultado del Embarazo , Disgenesia Gonadal 46 XYRESUMEN
Background and Objectives: Fertilized zygotes normally display two pronuclei (PN), but abnormal fertilization patterns (0, 1 or >2PN) are observed daily in IVF labs. Multiple PN zygotes (>2) are generally discarded due to an increased risk of aneuploidy. However, the decision to transfer or not transfer 1PN-derived embryos remains controversial. The aims of our study were to analyze the neonatal outcomes of fresh or frozen-thawed embryos derived from 1PN zygotes, and to evaluate the influence of the fertilization method. Materials and Methods: Data were retrospectively collected from cycles performed between January 2018 and December 2022. Fresh cycles were analyzed for the comparative fate of 1PN zygotes (n = 1234) following conventional in vitro fertilization (cIVF; n = 648) or intracytoplasmic sperm injection (ICSI; n = 586), as well as the results of the 64 transfers of 1PN-derived embryos (pregnancy rate (PR) and neonatal outcomes). This pregnancy follow-up was also applied to 167 transfers of frozen-thawed 1PN-derived embryos. Results: In fresh cycles, 46% of the 1PN zygotes in the cIVF group developed into embryos of sufficient quality to be transferred or frozen (day 3 or 5/6). This rate was lower in the fresh ICSI cycles (33%). Blastulation rate was also significantly higher in the cIVF group (44%) in comparison to the ICSI group (20%). The fresh single embryo transfers (32 per group) allowed seven pregnancies in the cIVF group (PR = 21.9%) as compared to four pregnancies in the ICSI group (PR = 12.5%). In the cIVF group, five deliveries of healthy newborns were achieved, but only one in the ICSI group. In frozen/thawed cycles, 36 pregnancies were obtained out of the 167 transfers. A non-significant difference was observed between embryos derived from cIVF cycles (PR = 26%) and ICSI cycles (PR = 16%) with 18 and 8 healthy babies born, respectively. Conclusions: We observed better outcomes for 1PN zygotes in cIVF cycles in comparison to ICSI cycles. Our center policy to transfer good-quality 1PN-derived embryos allowed the birth of 32 healthy babies.
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Criopreservación , Transferencia de Embrión , Cigoto , Humanos , Estudios Retrospectivos , Femenino , Embarazo , Transferencia de Embrión/métodos , Adulto , Cigoto/fisiología , Criopreservación/métodos , Fertilización In Vitro/métodos , Resultado del Embarazo , Inyecciones de Esperma Intracitoplasmáticas/métodosRESUMEN
Background and Objectives: Although considerable research has been devoted to examining the distinctions between fresh and frozen embryo transfer regarding obstetric outcomes and rates of pregnancy success, there is still a scarcity of thorough analyses that specifically examine neonatal outcomes. The objective of our study was to provide an in-depth analysis of neonatal outcomes that occur after the transfer of fresh and frozen embryos (ET vs. FET) in IVF/ICSI cycles. Materials and Methods: Multiple databases (PubMed/MEDLINE, Cochrane Library, Web of Science, Wiley, Scopus, Ovid and Science Direct) were searched from January 1980 to February 2024. Two reviewers conducted the article identification and data extraction, meeting inclusion and exclusion criteria. The methodological quality was evaluated using the Newcastle-Ottawa Scale (NOS) or the revised Cochrane Risk of Bias Tool. The meta-analysis was performed using RevMan 5.4. Results: Twenty studies, including 171,481 participants in total, were subjected to qualitative and quantitative analyses. A significant increase in preterm birth rates was noted with fresh embryo transfer compared to FET in the overall IVF/ICSI population (OR 1.26, 95% CI 1.18-1.35, p < 0.00001), as well as greater odds of a low birth weight (OR 1.37, 95% CI 1.27-1.48, p < 0.00001) and small-for-gestational-age infants in this group (OR 1.81, 95% CI 1.63-2.00, p < 0.00001). In contrast, frozen embryo transfer can result in macrosomic (OR 0.59, 95% CI 0.54-0.65, p < 0.00001) or large-for-gestational-age infants (OR 0.64, 95% CI 0.60-0.69, p < 0.00001). No significant difference was observed regarding congenital malformations or neonatal death rates. Conclusions: This systematic review confirmed that singleton babies conceived by frozen embryo transfer are at lower risk of preterm delivery, low birthweight and being small for gestational age than their counterparts conceived by fresh embryo transfer. The data support embryo cryopreservation but suggest that elective freezing should be limited to cases with a proven indication or within the framework of a clinical study.
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Criopreservación , Transferencia de Embrión , Fertilización In Vitro , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Transferencia de Embrión/métodos , Transferencia de Embrión/estadística & datos numéricos , Transferencia de Embrión/normas , Fertilización In Vitro/métodos , Embarazo , Femenino , Inyecciones de Esperma Intracitoplasmáticas/métodos , Recién Nacido , Criopreservación/métodos , Resultado del Embarazo/epidemiologíaRESUMEN
This study aimed to explore the relationship between female age and pregnancy outcomes in patients undergoing their first elective single embryo transfer (eSET) of in vitro fertilization (IVF) cycles. The retrospective cohort study encompassed 7089 IVF/intracytoplasmic sperm injection (ICSI) patients of the Reproductive Medicine Center, Henan Provincial Peoples' Hospital of China, from September 1, 2016, to May 31, 2022. Patients all received the first eSET in their IVF/ICSI cycles. A generalized additive model (GAM) was employed to examine the the dose-response correlation between age and pregnancy outcomes, namely the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). Logistic regression model was employed to ascertain the correlation between the CPR/OPR and age. The study cohort has an average age of 30.74; 3843 patients got clinical pregnancy rate of 61.40% and ongoing pregnancy rate of 54.21%. The multiple pregnancy rate of is 1.24%. For patients aged 34 and above, the CPR decreased by 10% for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84-0.96, p < 0.0001). Similarly, the OPR decreased by 16% for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81-0.88, p < 0.0001). Patients aged 35-37 years had an acceptable OPR of 52.4% after eSET, with a low multiple pregnancy rate (1.1%). Pregnancy outcomes were significantly better in blastocyst cycles compared to cleavage embryo cycles, and this trend was more pronounced in older patients. There was a non-linear relationship between female age and pregnancy outcomes in patients undergoing their first eSET cycles. The clinical pregnancy rate and ongoing pregnancy rate decreased significantly with age, especially in women older than 34 years. For patients under 37 years old, single embryo transfer should be prioritized. For patients over 38 years old with available blastocysts, eSET is also recommended.