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1.
Front Endocrinol (Lausanne) ; 15: 1378635, 2024.
Article En | MEDLINE | ID: mdl-38737550

Objective: The objective of this study is to investigate the factors that influence the live birth rate (LBR) of the first single euploid frozen-thawed blastocyst transfer (FBT) cycles after preimplantation genetic testing for structural rearrangements (PGT-SR) in couples with balanced chromosomal translocations (BCT). Design: Single center, retrospective and observational study. Methods: A total of 336 PGT-SR and the first single euploid FBT cycles between July 2016 and December 2022 were included in this study. The patients were divided into two groups according to the live birth outcomes. The parameters of the study population, controlled ovarian stimulation cycles, and FBT cycles were analyzed. Multivariable binary logistic regression was performed to find the factors that affected the LBR. Results: The percentage of blastocysts at developmental stage Day 5 compared to Day 6 (51.8% vs. 30.8%; P<0.001) and with morphology ≥BB compared to

Cryopreservation , Embryo Transfer , Live Birth , Pregnancy Rate , Preimplantation Diagnosis , Translocation, Genetic , Humans , Female , Pregnancy , Retrospective Studies , Adult , Embryo Transfer/methods , Male , Preimplantation Diagnosis/methods , Birth Rate , Fertilization in Vitro/methods , Pregnancy Outcome , Blastocyst , Ovulation Induction/methods
2.
Front Endocrinol (Lausanne) ; 15: 1379109, 2024.
Article En | MEDLINE | ID: mdl-38737557

Introduction: The impact of the obesity pandemic on female reproductive capability is a factor that needs to be investigated. In addition, the link between endometrial thickness and in vitro fertilization (IVF) outcomes is contentious. Goal: Our goal was to analyze the association among endometrium development, hormone levels, embryo quality, clinical pregnancy, anamnestic parameters, and body mass index (BMI) in women receiving IVF treatment. Patients and methods: 537 participants undergoing IVF/ICSI cycles with successful oocyte retrieval were enrolled. Subjects were divided into four BMI based groups: underweight (UW; n=32), normal weight (NW; n=324), overweight (OW; n= 115), obesity (OB; n=66). Anthropometric and anamnestic parameters, characteristics of stimulation, endometrial thickness on the day of hCG injection, at puncture, at embryo transfer, FSH, LH, AMH, partner's age and the semen analysis indicators, embryo quality, clinical pregnancy, were recorded and analyzed. Support Vector Machine (SVM) was built to predict potential pregnancies based on medical data using 22 dimensions. Results: In accordance with BMI categories, when examining pregnant/non-pregnant division, the average age of pregnant women was significantly lower in the UW (30.9 ± 4.48 vs. 35.3 ± 5.49 years, p=0.022), NW (34.2 ± 4.25 vs. 36.3 ± 4.84 years, p<0.001), and OW (33.8 ± 4.89 vs. 36.3 ± 5.31 years, p=0.009) groups. Considering FSH, LH, and AMH levels in each BMI category, a statistically significant difference was observed only in the NW category FSH was significantly lower (7.8 ± 2.99 vs. 8.6 ± 3.50 IU/L, p=0.032) and AMH (2.87 ± 2.40 vs. 2.28 ± 2.01 pmol/L, p=0.021) was higher in pregnant women. There were no further statistically significant differences observed between the pregnant and non-pregnant groups across any BMI categories, especially concerning endometrial development. Surprisingly, BMI and weight correlated negatively with FSH (r=-0.252, p<0.001; r=-0.206, p<0.001, respectively) and LH (r= -0.213, p<0.001; r= -0.195, p<0.001) in the whole population. SVM model average accuracy on predictions was 61.71%. Discussion: A convincing correlation between endometrial thickness development and patients' BMI could not be substantiated. However, FSH and LH levels exhibited a surprising decreasing trend with increasing BMI, supporting the evolutionary selective role of nutritional status. Our SVM model outperforms previous models; however, to confidently predict the outcome of embryo transfer, further optimization is necessary.


Body Mass Index , Endometrium , Fertilization in Vitro , Pregnancy Rate , Humans , Female , Fertilization in Vitro/methods , Pregnancy , Adult , Endometrium/pathology , Prognosis , Obesity , Infertility, Female/therapy , Embryo Transfer/methods , Sperm Injections, Intracytoplasmic , Thinness
3.
Front Endocrinol (Lausanne) ; 15: 1343176, 2024.
Article En | MEDLINE | ID: mdl-38742200

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.


Adenomyosis , Embryo Transfer , Endometrium , Gonadotropin-Releasing Hormone , Infertility, Female , Live Birth , Humans , Female , Gonadotropin-Releasing Hormone/agonists , Adult , Retrospective Studies , Pregnancy , Endometrium/drug effects , Endometrium/pathology , Live Birth/epidemiology , Infertility, Female/therapy , Embryo Transfer/methods , Pregnancy Rate , Birth Rate , Tissue Adhesions , Fertilization in Vitro/methods
4.
Front Endocrinol (Lausanne) ; 15: 1370114, 2024.
Article En | MEDLINE | ID: mdl-38694938

Objective: Despite the developments of in vitro fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure. Methods: We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I2 index was analyzed. Results: We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I2 = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I2 = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I2 = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I2 = 24%], but not on LBR. In addition, >150µg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I2 = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I2 = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I2 = 22%], while ≤150µg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I2 = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I2 = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I2 = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection. Conclusion: G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.


Embryo Implantation , Fertilization in Vitro , Granulocyte Colony-Stimulating Factor , Pregnancy Rate , Humans , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/therapeutic use , Embryo Implantation/drug effects , Pregnancy , Fertilization in Vitro/methods , Embryo Transfer/methods , Randomized Controlled Trials as Topic , Treatment Failure
5.
PLoS One ; 19(5): e0299602, 2024.
Article En | MEDLINE | ID: mdl-38696439

PURPOSE: The purposes of this study were to determine whether biomechanical properties of mature oocytes could predict usable blastocyst formation better than morphological information or maternal factors, and to demonstrate the safety of the aspiration measurement procedure used to determine the biomechanical properties of oocytes. METHODS: A prospective split cohort study was conducted with patients from two IVF clinics who underwent in vitro fertilization. Each patient's oocytes were randomly divided into a measurement group and a control group. The aspiration depth into a micropipette was measured, and the biomechanical properties were derived. Oocyte fertilization, day 3 morphology, and blastocyst development were observed and compared between measured and unmeasured cohorts. A predictive classifier was trained to predict usable blastocyst formation and compared to the predictions of four experienced embryologists. RESULTS: 68 patients and their corresponding 1252 oocytes were included in the study. In the safety analyses, there was no significant difference between the cohorts for fertilization, while the day 3 and 5 embryo development were not negatively affected. Four embryologists predicted usable blastocyst development based on oocyte morphology with an average accuracy of 44% while the predictive classifier achieved an accuracy of 71%. Retaining the variables necessary for normal fertilization, only data from successfully fertilized oocytes were used, resulting in a classifier an accuracy of 81%. CONCLUSIONS: To date, there is no standard guideline or technique to aid in the selection of oocytes that have a higher likelihood of developing into usable blastocysts, which are chosen for transfer or vitrification. This study provides a comprehensive workflow of extracting biomechanical properties and building a predictive classifier using these properties to predict mature oocytes' developmental potential. The classifier has greater accuracy in predicting the formation of usable blastocysts than the predictions provided by morphological information or maternal factors. The measurement procedure did not negatively affect embryo culture outcomes. While further analysis is necessary, this study shows the potential of using biomechanical properties of oocytes to predict embryo developmental outcomes.


Blastocyst , Embryonic Development , Fertilization in Vitro , Oocytes , Humans , Blastocyst/physiology , Blastocyst/cytology , Female , Oocytes/physiology , Oocytes/cytology , Adult , Biomechanical Phenomena , Fertilization in Vitro/methods , Embryonic Development/physiology , Prospective Studies
6.
Front Endocrinol (Lausanne) ; 15: 1352522, 2024.
Article En | MEDLINE | ID: mdl-38699386

Background: For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. Methods: This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. Results: For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). Conclusions: For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.


Body Mass Index , Medroxyprogesterone Acetate , Ovulation Induction , Pregnancy Outcome , Pregnancy Rate , Humans , Female , Pregnancy , Ovulation Induction/methods , Adult , Retrospective Studies , Medroxyprogesterone Acetate/administration & dosage , Progestins/administration & dosage , Fertilization in Vitro/methods , Dose-Response Relationship, Drug
7.
Mol Biol Rep ; 51(1): 621, 2024 May 06.
Article En | MEDLINE | ID: mdl-38709430

BACKGROUND: To investigate the effect of plasma-derived extracellular vesicles (EVs) or conventional medium in fertilization and early embryo development rate in mice. METHODS AND RESULTS: MII oocytes (matured in vivo or in vitro conditions) were obtained from female mice. The extracellular vesicles were isolated by ultracentrifugation of plasma and were analyzed and measured for size and morphology by dynamic light scattering (DLS) and transmission electron microscopy (TEM). By western blotting analysis, the EVs proteins markers such as CD82 protein and heat shock protein 90 (HSP90) were investigated. Incorporating DiI-labeled EVs within the oocyte cytoplasm was visible at 23 h in oocyte cytoplasm. Also, the effective proteins in the early reproductive process were determined in isolated EVs by western blotting. These EVs had a positive effect on the fertilization rate (P < 0.05). The early embryo development (8 cell, morula and blastocyst stages) was higher in groups supplemented with EVs (P < 0.01). CONCLUSION: Our findings showed that supplementing in vitro maturation media with EVs derived- plasma was beneficial for mice's embryo development.


Embryonic Development , Extracellular Vesicles , Oocytes , Animals , Extracellular Vesicles/metabolism , Mice , Female , Oocytes/metabolism , Oocytes/cytology , Fertilization in Vitro/methods , Blastocyst/metabolism , In Vitro Oocyte Maturation Techniques/methods , HSP90 Heat-Shock Proteins/metabolism
8.
Sci Rep ; 14(1): 10569, 2024 05 08.
Article En | MEDLINE | ID: mdl-38719918

Within the medical field of human assisted reproductive technology, a method for interpretable, non-invasive, and objective oocyte evaluation is lacking. To address this clinical gap, a workflow utilizing machine learning techniques has been developed involving automatic multi-class segmentation of two-dimensional images, morphometric analysis, and prediction of developmental outcomes of mature denuded oocytes based on feature extraction and clinical variables. Two separate models have been developed for this purpose-a model to perform multiclass segmentation, and a classifier model to classify oocytes as likely or unlikely to develop into a blastocyst (Day 5-7 embryo). The segmentation model is highly accurate at segmenting the oocyte, ensuring high-quality segmented images (masks) are utilized as inputs for the classifier model (mask model). The mask model displayed an area under the curve (AUC) of 0.63, a sensitivity of 0.51, and a specificity of 0.66 on the test set. The AUC underwent a reduction to 0.57 when features extracted from the ooplasm were removed, suggesting the ooplasm holds the information most pertinent to oocyte developmental competence. The mask model was further compared to a deep learning model, which also utilized the segmented images as inputs. The performance of both models combined in an ensemble model was evaluated, showing an improvement (AUC 0.67) compared to either model alone. The results of this study indicate that direct assessments of the oocyte are warranted, providing the first objective insights into key features for developmental competence, a step above the current standard of care-solely utilizing oocyte age as a proxy for quality.


Blastocyst , Machine Learning , Oocytes , Humans , Blastocyst/cytology , Blastocyst/physiology , Oocytes/cytology , Female , Embryonic Development , Adult , Fertilization in Vitro/methods , Image Processing, Computer-Assisted/methods
9.
Reprod Biol Endocrinol ; 22(1): 57, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769525

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.


Fertility , Fertilization in Vitro , Pregnancy Outcome , Propensity Score , Sjogren's Syndrome , Humans , Female , Pregnancy , Adult , Pregnancy Outcome/epidemiology , Fertilization in Vitro/methods , Retrospective Studies , Sjogren's Syndrome/complications , Sjogren's Syndrome/epidemiology , Fertility/physiology , Ovarian Reserve/physiology , Pregnancy Rate , Infertility, Female/therapy , Infertility, Female/epidemiology , Infertility, Female/etiology
10.
Reprod Biol Endocrinol ; 22(1): 56, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769552

BACKGROUND: Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer. METHODS: This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18-38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile. RESULTS: Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28-3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03-4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth. CONCLUSIONS: These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF. TRIAL REGISTRATION: NCT04693624 ( www. CLINICALTRIALS: gov ).


Chorionic Gonadotropin , Fertilization in Vitro , Luteal Phase , Ovulation Induction , Progesterone , Humans , Female , Luteal Phase/blood , Luteal Phase/physiology , Fertilization in Vitro/methods , Adult , Pregnancy , Prospective Studies , Progesterone/blood , Chorionic Gonadotropin/administration & dosage , Ovulation Induction/methods , Pregnancy Rate , Young Adult , 17-alpha-Hydroxyprogesterone/blood , Cohort Studies , Embryo Transfer/methods , Adolescent , Birth Rate , Treatment Outcome , Live Birth/epidemiology
11.
Cells ; 13(10)2024 May 15.
Article En | MEDLINE | ID: mdl-38786061

Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations.


Fertilization in Vitro , Trace Elements , Humans , Female , Trace Elements/blood , Trace Elements/metabolism , Trace Elements/urine , Fertilization in Vitro/methods , Adult , Pregnancy , Single Embryo Transfer , Pregnancy Outcome , Sperm Injections, Intracytoplasmic
12.
Sci Rep ; 14(1): 11689, 2024 05 22.
Article En | MEDLINE | ID: mdl-38778076

We evaluated whether serum stem cell factor (s-SCF) levels just prior to ovulation induction could indicate the ability to develop a top-quality (TQ) blastocyst by day 5. We investigated patients with normal ovarian reserve (NOR), polycystic ovary syndrome (PCOS), diminished ovarian reserve (DOR), or mild endometriosis. Our pilot research suggests a correlation between s-SCF levels and the ability to form TQ blastocysts in patients with mild endometriosis. This significant statistical difference (p < 0.05) was noted between mild endometriosis patients for whom a TQ blastocyst was obtained and those for whom it was not possible, as measured on the 8th day of stimulation and the day of oocyte retrieval. The mean SCF levels in the serum of these women on the 8th day were at 28.07 (± 2.67) pg/ml for the TQ subgroup and 53.32 (± 16.02) pg/ml for the non-TQ subgroup (p < 0.05). On oocyte retrieval day it was 33.47 (± 3.93) pg/ml and 52.23 (± 9.72) pg/ml (p < 0.05), respectively.


Blastocyst , Ovarian Reserve , Stem Cell Factor , Humans , Female , Stem Cell Factor/blood , Adult , Blastocyst/cytology , Ovarian Reserve/physiology , Polycystic Ovary Syndrome/blood , Endometriosis/blood , Oocyte Retrieval , Ovulation Induction/methods , Pilot Projects , Fertilization in Vitro/methods
13.
BMJ Open ; 14(5): e081018, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719320

INTRODUCTION: In recent years, the use of frozen embryo transfers (FET) has rapidly increased following the freeze-all strategy due to the advantages of increased maternal safety, improved pregnancy rates, lower ectopic pregnancy rates and better obstetric and neonatal outcomes. Currently, there is still no good scientific evidence to support when to perform FET following a stimulated in vitro fertilisation (IVF) cycle in the freeze-all strategy. METHODS/ANALYSIS: This will be a randomised controlled trial. A total of 828 women undergoing their first FET following their first stimulated IVF cycle in the freeze-all strategy will be enrolled and randomised into one of the following groups according to a computer-generated randomisation list: (1) the immediate group, in which FET will be performed in the first menstrual cycle following the stimulated IVF cycle; or (2) the delayed group, in which FET will be performed at least in the second menstrual cycle following the stimulated IVF cycle. The primary outcome will be live birth, which is defined as the delivery of any infants at ≥22 gestational weeks with heartbeat and breath. ETHICS/DISSEMINATION: Ethical approval was granted by the Ethics Committee of Assisted Reproductive Medicine at the Shanghai JiAi Genetics & IVF Institute (JIAI E2019-15). Written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04371783.


Cryopreservation , Fertilization in Vitro , Pregnancy Rate , Randomized Controlled Trials as Topic , Humans , Female , Pregnancy , Fertilization in Vitro/methods , Cryopreservation/methods , Adult , Embryo Transfer/methods , Single Embryo Transfer/methods , Live Birth , Time Factors , China
14.
Reprod Biol Endocrinol ; 22(1): 59, 2024 May 22.
Article En | MEDLINE | ID: mdl-38778327

BACKGROUND: Deep learning has been increasingly investigated for assisting clinical in vitro fertilization (IVF). The first technical step in many tasks is to visually detect and locate sperm, oocytes, and embryos in images. For clinical deployment of such deep learning models, different clinics use different image acquisition hardware and different sample preprocessing protocols, raising the concern over whether the reported accuracy of a deep learning model by one clinic could be reproduced in another clinic. Here we aim to investigate the effect of each imaging factor on the generalizability of object detection models, using sperm analysis as a pilot example. METHODS: Ablation studies were performed using state-of-the-art models for detecting human sperm to quantitatively assess how model precision (false-positive detection) and recall (missed detection) were affected by imaging magnification, imaging mode, and sample preprocessing protocols. The results led to the hypothesis that the richness of image acquisition conditions in a training dataset deterministically affects model generalizability. The hypothesis was tested by first enriching the training dataset with a wide range of imaging conditions, then validated through internal blind tests on new samples and external multi-center clinical validations. RESULTS: Ablation experiments revealed that removing subsets of data from the training dataset significantly reduced model precision. Removing raw sample images from the training dataset caused the largest drop in model precision, whereas removing 20x images caused the largest drop in model recall. by incorporating different imaging and sample preprocessing conditions into a rich training dataset, the model achieved an intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94-0.99) for precision, and an ICC of 0.97 (95% CI: 0.93-0.99) for recall. Multi-center clinical validation showed no significant differences in model precision or recall across different clinics and applications. CONCLUSIONS: The results validated the hypothesis that the richness of data in the training dataset is a key factor impacting model generalizability. These findings highlight the importance of diversity in a training dataset for model evaluation and suggest that future deep learning models in andrology and reproductive medicine should incorporate comprehensive feature sets for enhanced generalizability across clinics.


Deep Learning , Spermatozoa , Humans , Pilot Projects , Male , Spermatozoa/physiology , Fertilization in Vitro/methods , Image Processing, Computer-Assisted/methods , Semen Analysis/methods
15.
Reprod Biol Endocrinol ; 22(1): 58, 2024 May 22.
Article En | MEDLINE | ID: mdl-38778410

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.


Aneuploidy , Blastocyst , Deep Learning , Preimplantation Diagnosis , Humans , Retrospective Studies , Female , Preimplantation Diagnosis/methods , Adult , Pregnancy , Blastocyst/cytology , Genetic Testing/methods , Fertilization in Vitro/methods
16.
Birth Defects Res ; 116(5): e2349, 2024 May.
Article En | MEDLINE | ID: mdl-38778782

BACKGROUND: To describe and conclude the in vitro fertilization (IVF) results of patients with X chromosome abnormality. METHODS: A retrospective case series was conducted. According to the number of normal X, patients were allocated into two groups: Group A (patients with only a normal X, while other X has any types of abnormalities) and Group B (patients have two or more normal X chromosomes). Clinical data, including basic information, fertility information, and IVF outcomes, were collected. RESULTS: Fourteen patients with X chromosome abnormality were included, among which 13 patients underwent a total of 29 cycles. Patients in Group B had five successful pregnancies and three live births, while no patient in Group A had a clinical pregnancy. Furthermore, the blastocyst formation rate and incidence of pregnancy were significantly lower in Group A (Z = -3.135, p = .002; Z = -2.946, p = .003, respectively). When controlled covariates, the karyotype of one normal X was also a risk factor for both blastocyst formation rate and success pregnancy (ß = .820, 95% confidence interval [CI] = 0.458-1.116, ß = .333, 95% CI = 0.017-0.494, respectively). CONCLUSIONS: Our results revealed that women with only one normal X might suffer from worse IVF outcomes, mainly blastocyst formation rate, compared with those who had two or more normal X, including mosaic Turner syndrome and 47,XXX.


Chromosomes, Human, X , Fertilization in Vitro , Pregnancy Outcome , Humans , Female , Pregnancy , Fertilization in Vitro/methods , Adult , Chromosomes, Human, X/genetics , Retrospective Studies , Sex Chromosome Aberrations , Blastocyst/metabolism , Live Birth/genetics , Turner Syndrome/genetics , Pregnancy Rate
17.
Medicine (Baltimore) ; 103(18): e37886, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701292

INTRODUCTION: Resistant ovary syndrome (ROS) represents a rare reproductive endocrine disorder that is predominantly associated with infertility, characterized by heightened endogenous gonadotropin levels in the presence of a normal ovarian reserve. Patients with ROS typically exhibit a poor response to exogenous gonadotropins during controlled ovarian stimulation (COS). Due to the absence of a universally accepted effective COS protocol, this study aims to contribute to the existing body of literature by detailing 2 successful pregnancies achieved through conventional in vitro fertilization (c-IVF) in patients with ROS, and through retrospective analysis, seeks to elucidate the factors contributing to the successful ovarian stimulation in these cases, with the ultimate goal of establishing clinical guidelines for ROS management. PATIENT CONCERNS: The central challenge addressed in this study pertains to the effective induction of oocyte maturation during c-IVF COS in ROS patients. DIAGNOSIS: The study focuses on 2 infertile women diagnosed with ROS who sought to conceive via c-IVF. INTERVENTIONS: The patients were subjected to a COS protocol involving pituitary downregulation followed by ovarian stimulation using recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin (HMG), preceded by 3 cycles of hormone replacement therapy (HRT) pretreatment. OUTCOMES: The proposed protocol elicited a favorable ovarian response, culminating in the retrieval of numerous mature oocytes and the development of multiple viable embryos via c-IVF, ultimately leading to successful live births post-embryo transfer. CONCLUSIONS: Our study suggests that the outlined COS protocol may serve as a viable treatment option for ROS patients aspiring to conceive through c-IVF, thereby potentially expanding the therapeutic repertoire for this challenging condition.


Fertilization in Vitro , Infertility, Female , Ovulation Induction , Humans , Female , Ovulation Induction/methods , Fertilization in Vitro/methods , Adult , Infertility, Female/therapy , Pregnancy , Ovarian Diseases/drug therapy , Follicle Stimulating Hormone/blood , Follicle Stimulating Hormone/administration & dosage
18.
Int J Mol Sci ; 25(9)2024 May 02.
Article En | MEDLINE | ID: mdl-38732193

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.


Carbon , Reproductive Techniques, Assisted , Humans , Carbon/metabolism , Vitamin B 12/metabolism , Fertilization in Vitro/methods , Female , Homocysteine/metabolism , Homocysteine/blood , Folic Acid/metabolism , Dietary Supplements , Choline/metabolism , Zinc/metabolism , Betaine/metabolism , Biomarkers
19.
Ceska Gynekol ; 89(2): 134-138, 2024.
Article En | MEDLINE | ID: mdl-38704226

AIM: The sperm activation method is a modern methodological approach that is used more and more often in practice. The number of studies focused on methods of artificial activation of human sperm motility are constantly increasing. Standard sperm selection methods can fail in some cases, among other things, because very young sperm are isolated that have not yet completed their development. In these cases, artificial stimulation of their movement can have a positive effect and greatly facilitate and faster the process of selecting suitable sperm. Methylxanthines are most often used as activating agents. However, opinions on the safety of using these substances on sperm are not uniform. The aim of the thesis is to present current knowledge about artificial activation of sperm motility for in vitro fertilization and subsequent embryonic development. METHODOLOGY: Research of relevant literature in Web of Science, Scopus, PubMed/Medline databases. RESULTS AND CONCLUSION: The literature analysis shows that this method is safe and effective in the selection of immotile spermatozoa. Scientific studies have been conducted to verify the safety and reliability of this method. The conclusion of these studies is the positive impact of this method of selection, especially in cases of sperm obtained from testicular tissue after method testicular sperm extraction. In these cases, the method of artificial sperm activation facilitated and accelerated the selection of sperm before intracytoplasmic sperm injection. Undamaged spermatozoa, which are immobile due to incomplete maturation, were activated.


Sperm Motility , Humans , Male , Fertilization in Vitro/methods , Spermatozoa/physiology
20.
Thromb Res ; 238: 97-102, 2024 Jun.
Article En | MEDLINE | ID: mdl-38701723

INTRODUCTION: The association between estrogen and hypercoagulability is well-established but little is known about coagulation dynamics during IVF. Our goal was to measure coagulation potential prior to, during, and following an IVF cycle and to investigate differences by conception outcome. MATERIALS AND METHODS: Patients undergoing IVF with fresh embryo transfer at a single academic center using oral contraceptive pills for cycle batching underwent evaluation of thrombin generation using the calibrated automated thrombogram at multiple points during the IVF cycle. Multiple thrombin generation parameters were compared across timepoints and by IVF cycle outcome using ANOVA repeated measures analysis. RESULTS: Of the 17 patients included, 11 conceived. There was a significant increase in peak and total thrombin generation in the entire cohort between the pre-treatment natural follicular phase and following a short course of oral contraceptive pills used for cycle batching. Further increase in these parameters was seen at the time of oocyte retrieval. In the pre-treatment natural follicular phase, patients who conceived had lower peak thrombin generation. There were changes throughout the cycle for factors II, V, VIII, X, XI, XII, antithrombin, and tissue factor pathway inhibitor. Only Factor XI was distinguishable by conception status; values were lower at all visits in patients who conceived. CONCLUSION: Increases in coagulation potential are seen in patients undergoing IVF following a short course of oral contraceptive pills for cycle batching and continue during controlled ovarian hyperstimulation. Those who conceived were seen to have lower peak thrombin generation in the pre-treatment natural follicular phase.


Blood Coagulation , Fertilization in Vitro , Humans , Fertilization in Vitro/methods , Female , Adult , Blood Coagulation/drug effects , Longitudinal Studies , Thrombin/metabolism , Blood Coagulation Tests/methods
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