In Vitro Fertilization Outcomes Research Articles

Прогнозирование исходов программ экстракорпорального оплодотворения с использованием модели машинного обучения «Случайный лес»

Currently, in vitro fertilization (IVF) with embryo transfer is the main method of treatment of all forms of infertility, but successful cases ending in pregnancy still account for only a third of all cycles performed. It is necessary to take into account many parameters and investigate the connections between them in order to properly evaluate the results of IVF. Over the past decades, a number of IVF prediction models have been developed with the aim at assessing the outcomes in individual cases, but, given the generally poor prognostic capacity, only a few of them have proven to be clinically significant. This study aimed to create nonlinear IVF outcomes prediction models and identify the most significant factors affecting the said outcomes. Using a database containing information on more than 700 indicators of 7004 women aged 18 to 45 years who participated in the IVF program in Russia from 2010 to 2020, we trained a random forest model that predicted pregnancy in the IVF cycle with ROC-AUC = 0.69. This paper describes 20 most successful predictors of the resulting model and interprets their contribution to the prognosis. Of these, body mass index (BMI) and the number of received and fertilized oocytes have been covered in the scientific literature previously as predictors of IVF outcomes, but other parameters, such as anamnestic data, previous participation in an IVF program (number of cases and their results), as well as serum concentration of AMH, rarely appear in foreign prognostic models.

#53 : Pregnancy Outcome After Hydrosalpinx Aspiration in In-Vitro Fertilization Cycle

Background and Aims: Hydrosalpinx is a severe manifestation of tubal disease-causing infertility in women. It has an adverse effect on the outcome of in vitro fertilization (IVF), reducing live birth rate (LBR) by 50% compared to other tubal factors. Laparoscopic salpingectomy can effectively improve IVF outcome but is contraindicated in some women. It can also be expensive and is not without complications. Ultrasound-guided hydrosalpinx aspiration is a cheaper, less invasive procedure alternative to salpingectomy. It has been shown to improve clinical and ongoing pregnancy rates compared to patients with no aspiration. However, the published literature on the effectiveness of hydrosalpinx aspiration is equivocal. Method: This retrospective study aimed to evaluate the outcome of minimal stimulation (mild) IVF cycles wherein the women underwent hydrosalpinx aspiration prior to embryo transfer at a private fertility clinic in the Philippines. Results: A total of 98 IVF cycles satisfied the inclusion criteria. The average patient age was 35.22 ± 4.57 and average duration of infertility was 5.87 ± 3.70 years. The biochemical pregnancy rate was 48% and the clinical pregnancy rate was 39.8%. Live birth rate was 35.7%, which is comparable to that of mild IVF patients without hydrosalpinx. There was a negative correlation between patient age and biochemical pregnancy rate, clinical pregnancy rate, and LBR, however, the correlations were statistically insignificant (Pearson correlation, P = 0.081, 0.197, and 0.344, respectively). Binary logistic regression analyses showed that age, infertility type, infertility factor, basal hormone levels, and number of eggs retrieved were not predictive of the success of IVF among the women in the study. Conclusion: Our results show that hydrosalpinx aspiration is a safe and effective option in improving pregnancy and live birth rates in women undergoing mild IVF.

#295 : Comparison of In Vitro Fertilization in Couples with HIV Infection with Negative Viral Load Versus Non-Infected Couples: A Case-Control Study

Background and Aims: The development of Advanced Reproductive Technology (ART) changes many aspects and perspectives towards reproductive health. Current in vitro fertilization (IVF) protocols reduce the risk of Human Immunodeficiency Virus (HIV) transmission to their partners and offspring. This study compares IVF outcome in couples in which at least one partner is HIV positive with negative viral load versus couples in which neither partner is diagnosed with HIV. Method: A total of 100 couples undergoing IVF were categorized into two groups. HIV-positive with negative viral load group in which at least one partner is infected (n = 50) and non-HIV group in which neither partner is diagnosed with HIV (n = 50) are collected from medical record in our center during the same period. The main outcomes were total oocyte retrieved, normal fertilized egg or 2 pronucleus (2PN) one day after fertilization and good quality embryos based on number of embryos that transferred and frozen for IVF procedure. Differences between groups were determined statistically using the Mann-Whitney test. Results: There is a significant difference between HIV-positive with negative viral load groups compared to non-HIV groups in terms of total oocyte retrieved (p = 0,005) and normal fertilized egg one day after fertilization (p = 0.017). There is no significant difference in the number of good quality embryos (p = 0.076) between two groups. Conclusion: The data suggested that couples with HIV-positive women have poorer total oocyte retrieved and normal fertilized egg outcome compared to non-HIV couple. HIV infection might affect success rates of IVF treatments.

Mean number of DNA breakpoints: illuminating sperm DNA integrity and in vitro fertilization outcomes

ObjectiveTo verify the capacity of the mean number of DNA breakpoints (MDB) for evaluating sperm integrity and its relationship with in vitro fertilization (IVF) outcomes. DesignRetrospective cohort study. SettingReproductive center in a tertiary hospital.Patient(s): All men whose female partners underwent IVF from March to October 2022 in the reproductive center. Intervention(s)MDB and DNA fragmentation index (DFI) were used to assess sperm DNA integrity. The patients were stratified into two groups according to MDB and DFI cutoffs: sperm DNA-normal and sperm DNA-impaired. Main outcome measures(1) semen parameters: concentration, progressive motility (PR), MDB and the DFI; (2) IVF outcome measures: two pronuclei (2PN), fertilization rate, fertilization cleavage rate, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, and implantation rate. ResultsSperm MDB had a higher negative correlation with PR compared to the DFI (r=-0.43, P<0.01; r=-0.37, P<0.01, respectively). Sperm MDB did not have a statistical correlation with sperm concentration, while the DFI correlated significantly with concentration (r=-0.17, P=0.07; r=-0.27, P<0.01, respectively). Logistic regression analysis controlling for age and semen concentration demonstrated that an increase in MDB increased the risk of asthenospermia (OR=1.018, 95% CI 1.003-1.034, P=0.02). An increasing DFI also increased the risk of asthenospermia (OR=1.044, 95% CI 1.002-1.087, P=0.04). MDB showed a stronger clinical relevance with sperm PR than the DFI, as indicated by the area under the curve (AUC) (0.754, 95% CI 0.649-0.859, P<0.01 vs. 0.691, 95% CI 0.556-0.825, P<0.01). A threshold of MDB over 0.37 nM was calculated to define sperm DNA-impaired. Comparison of IVF results showed that the high-quality embryo rate (χ2=13.00, P<0.01) was significantly lower in the DNA-impaired group than in the DNA-normal group stratified by MDB, while there were no significant differences in IVF outcomes in DFI-stratified groups. ConclusionMDB are verified to correlate closely with semen PR and may serve as a predictive parameter for IVF outcomes. Rigorous prospective studies are required to explore MDB performance and to further validate and reinforce the potential application of MDB as a parameter for male infertility.

"Meiosis arrester" C-natriuretic peptide directly stimulates oocyte mtDNA accumulation and is implicated in aging-associated oocyte mtDNA loss.

C-natriuretic peptide (CNP) is the central regulator of oocyte meiosis progression, thus coordinating synchronization of oocyte nuclear-cytoplasmic maturation. However, whether CNP can independently regulate cytoplasmic maturation has been long overlooked. Mitochondrial DNA (mtDNA) accumulation is the hallmark event of cytoplasmic maturation, but the mechanism underlying oocyte mtDNA replication remains largely elusive. Herein, we report that CNP can directly stimulate oocyte mtDNA replication at GV stage, and deficiency of follicular CNP may contribute largely to lower mtDNA copy number in invitro matured oocytes. The mechanistic study showed that cAMP-PKA-CREB1 signaling cascade underlies the regulatory role of CNP in stimulating mtDNA replication and upregulating related genes. Of interest, we also report that CNP-NPR2 signaling is inhibited in aging follicles, and this inhibition is implicated in lower mtDNA copy number in oocytes from aging females. Together, our study provides the first direct functional link between follicular CNP and oocyte mtDNA replication, and identifies its involvement in aging-associated mtDNA loss in oocytes. These findings, not only update the current knowledge of the functions of CNP in coordinating oocyte maturation but also present a promising strategy for improving invitro fertilization outcomes of aging females.

Effects of Nobiletin supplementation on the freezing diluent on porcine sperm cryo-survival and subsequent in vitro embryo development

Nobiletin (NOB) is a bioflavonoid compound isolated from citrus fruit peels. The present study aimed to elucidate whether NOB facilitates the porcine sperm cryosurvival and embryo development after in vitro fertilization (IVF). To this end, spermatozoa were diluted and cryopreserved in a freezing extender supplemented with 0 (control), 50, 100, 150, and 200 μM Nobiletin. The kinematic patterns of frozen-thawed (FT) sperm were assessed after 30 and 90 min incubation using a Sperm Class Analyzer (SCA). Viability, acrosome integrity, and mitochondrial membrane potential (MMP) were measured by fluorescence microscopy 30 min after thawing using SYBR-14/PI, PSA/FITC, and R123/PI, respectively. Lipid peroxidation was determined using MDA assay after incubation for 90 min. The addition of 100 μM and 150 μM NOB to the extender significantly improved sperm progressive motility, and acrosome integrity compared to the control group (P < 0.05). The proportion of viable spermatozoa was significantly higher in the 150 μM NOB group. MDA levels were less in 50 μM and 150 μM NOB treated groups compared to the control. In addition, IVF with FT sperm was used to assess the embryo developmental competence. Treatment with 150 μM NOB before cryopreservation increased the cleavage and blastocyst formation rates compared to the control group. Furthermore, the relative expression of POU5F1 and AMPK, genes related to pluripotency and cell differentiation were significantly upregulated in embryos resulting from NOB-treated sperm compared to the control group. These results suggest that Nobiletin is a functionally novel phytochemical to mitigate oxidative stress during the freezing-thawing of porcine spermatozoa as reflected by improved FT sperm quality and IVF outcome.

“Cocktail” of environmental chemicals and early reproductive outcomes of IVF: The insight from paternal and maternal exposure

BackgroundHumans are exposed to various chemicals, including organophosphate esters (OPEs), phthalates (PAEs), and phenols. The effects on early reproductive outcomes of in vitro fertilization (IVF) remain unclear. MethodsWe recruited 192 women and 157 men who underwent IVF treatment. A total of forty-nine urinary chemicals were detected, including six OPEs, fifteen PAEs, six parabens, two chlorophenols, nine bisphenols, five benzophenones, and six synthetic phenolic antioxidants. We examined the individual and joint effects of parental chemical exposure on early reproductive outcomes. ResultsWe found that certain chemicals were associated with early reproductive outcomes in Poisson regression models. For example, urinary diphenyl phosphate was negatively associated with high-quality embryos in both female (β: −0.12, 95%CI: −0.17, −0.07) and male partners (β: −0.09, 95%CI: −0.15, −0.03). A negative association was found between mixed chemicals and high-quality embryos in Bayesian kernel machine regression, weighted quantile sum regression (β: −0.34, 95%CI: −0.60, −0.07), and quantile-based g-computation model (β: −0.69, 95%CI: −1.34, −0.05) among female partners. Paternal mixture exposure was not associated with early reproductive outcomes. ConclusionsOur results indicated that increased exposure to environmental chemicals was associated with adverse early reproductive outcomes of IVF, especially female partners.

Leukemia Inhibitory Factor, Tissue Factor, Thrombomodulin, P-Selectine, D-Dimer, Thrombin Generation and Procoagulant Phospholipid Dependent Clotting Time Are Predictive for in Vitro Fertilization Outcome. the Prospective Roadmap-IVF Study

Background The link between blood hypercoagulability, endothelial cell activation and infertility or in vitro fertilization (IVF) failure is a puzzling issue. Activation of platelets, endothelial cells and blood coagulation, proinflammatory and angiogenetic potential play important role in implantation and early embryonic development. Biomarkers of cellular hypercoagulability are associated with high risk of IVF failure. Soluble Leukemia Inhibitory Factor (LIF), an interleukin 6 class cytokine expressed in the trophectoderm of the developing embryo is an important regulator in the establishment of pregnancy. Endoglin (Eng), a co-receptor for TGF-β1 and TGF-β3 is implicated in vascular complications of pregnancy and particularly in preeclampsia. Aim: The prospective longitudinal monocentric observational cohort study ROADMAP-IVF, evaluated the synergistic prognostic value of LIF and Eng with the biomarkers of cellular hypercoagulability in predicting the endometrial receptivity of fresh IVF cycles. Materials and Methods. The ROADMAP-IVF enrolled 40 women eligible for IVF with normal blood count, PT, aPTT, Fg, renal and liver function. The control group (CG) consisted of 30 healthy women with history of uncomplicated pregnancies. Exclusion criteria: Use of anticoagulant or antiplatelet agents during the last 30 days before inclusion. Known cardiovascular disease, active cancer. Active corticosteroid treatment. Primary end-point: Echographically documented pregnancy at 7 weeks from implantation. Blood was collected on day 2 (D2) from the natural cycle and 6 days after hormone treatment initiation corresponding to D8 of the cycle. Procoagulant phospholipid-dependent clotting time (PPL-ct), tissue factor (TF), thrombomodulin (TM), von Willebrand factor (vWF) and D-Dimers (DDi) were measured with assays from Diagnostica Stago (Asnieres, France). P- and E-Selectin, LIF and Eng were measured with ELISA. Thrombin generation (TG) with the TF 5 pM PPP-Reagent ® was assessed on Calibrated Automated Thrombogram (Stago, France). The cut-off values for studied biomarkers have been selected on the basis of ROC analysis. Univariate and multivariate logistic regression analysis examined the associations between the biomarkers and the study outcome. Results: 40 women were enrolled in the study. In 11 women pregnancy was confirmed with ultrasound and in 23 women no pregnancy was echographically documented. Age was not significantly different between the IVF (41 ys; range 22 - 48 ys) and the control group (40 ys; range 20 - 46 ys). At D2 and D8 the DDi and LIF were significantly higher in IVFG as compared to the CG. At D2 most of the patients had PPL-ct, DDi and MRI of TG higher than the upper normal limit (UNL). At D8 only TF was significantly increased as compared to the CG. Analytical data are presented in Table 1. Age did not correlate with the levels of the studied biomarkers. Significant correlations (p&amp;lt;0.05) were found between DDi and ETP (r=0.35); TM, TF and P-Selectin (r=0.4) at D2; TF, LIF and Eng (r=0.5) at D2 and D8; P-Selectin and PPL-ct (r=-0.4) at D2; P-Selectin and TM (r=0.4), E-Selectin (r=0.5), LIF (0.4) at D2; E-Selectin and P-Selectin (r=0.5), TF (r=0.3), and LIF (r=0.4) at D2. The ROC analysis showed that IVF failure was associate with DDi increase at D2 (AUC = 0.64); P-Selectin increase at D2(AUC = 0.57) and D8 (AUC = 0.61); TM increase at D8 (AUC = 0.61); TF increase at D8 (AUC = 0.57); LIF increase at D8 (AUC = 0.59); ETP increase at D2 (AUC = 0.67) and D8 (AUC = 0.67); Peak increase at D2 (AUC = 0.64) and D8 (AUC = 0.61). Prolongation of PPL-ct on D8 was predictive for positive pregnancy outcome(AUC 0.64). Conclusion The ROADMAP-IVF study showed that at least one out of four women eligible for IVF present biological evidence of activation of platelets, endothelial cells, blood coagulation or LIF upregulation. Hormone treatment administration does not significantly alter the proinflammatory or the hypercoagulable state. Among the studied biomarkers the levels of LIF, DDi, P-Selectine, TM and TF as well as the status of thrombin generation and PPL-ct showed a significant predictive value for the IVF outcome, particularly when measured at 6 days after hormone treatment administration. These findings will lead to the elaboration of an risk assessment model for IVF failure combining the selected biomarkers of hypercoagulability with LIF.

The role of clinical and immunological factors in the outcomes of in vitro fertilization procedure in women

The objective: to determine the features of clinical and immunological factors in women undergoing in vitro fertilization (IVF) procedure and to determine a relationship between these parameters and the procedure outcomes.Materials and methods. In the period from 2020 to 2022, 131 patients were examined at the Reproductive Department of the Caspian International Hospital. Of these, 103 (78.6%) are aged 19-35 years, 28 (21.4%) are aged 36-50. Patients were grouped and analyzed based on: IVF success (presence or absence of fertilization), pregnancy (yes, no), and infertility factors. Markers of peripheral blood mononuclear cells (CD16/56 and HLA-DR) were determined in 50 women. The cytokines – interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon-ɣ (IFN-ɣ) were studied in blood serum of 84 patients. All samples were taken at the day of oocyte pick-up. Descriptive statistical methods (mean, standard deviation, median, frequency, percentage, and minimum and maximum), Student-t test and Mann–Whitney U test (for comparisons between two groups) were used while evaluating the study data. Statistical significance was accepted as p&lt;0.05.Results. Female infertility occurred in 49 (37.4%) patients, 82 (62.6%) patients were fertile. There was no significant difference in CD16/56 and HLA-DR levels depending on pregnancy status, IVF outcomes and infertility factors (p&gt;0.05). The levels of IL-1β and IFN-ɣ differed in the blood serum of patients with and without pregnancy (p=0.041 and p=0.037, respectively). Analysis of groups based on infertility factors showed that there were not significant differences (p&gt;0.05) in the levels of CD16/56, HLA-DR, IL-1β, TNF-α and IFN-ɣ between groups. Conclusions. Our study showed that there is an association between serum levels of IL‒1β and IFN-y and successful pregnancy in the IVF procedure. We did not reveal the other relationships between clinical and immunological parameters in women with IVF procedure.

The Role of Reproductive Surgeons/Surgery has Got Rekindled with Plateauing of IVF Results and Advances in Technology: A Comprehensive Narrative Review

Earlier we have reviewed the role of surgery in need for fibroids removal prior to IVF in improving success rates, management of inoperable recurrent endometrioma presenting as severe incapacitating pain following leuprolide acetate depot by aspiration, recurring again at 2 years subsequently for sclerosing therapy presented as a case report updated advances in classification along with re¬productive surgeries in mullerian anomalies. Updated management of oncofertility-does the use of vsels appear practical in the near future in human malignancies replacing cortical tissue and testicular tissue, autologous Platelet Rich Plasma (PRP) probability of it becoming a revolutionary therapy in the field of gynaecology and reproductive endocrinology and infertility, role of surgery in endometriomas and endometriosis, adenomyomas, tubal surgery. Here we have tried to outline how prior to the invention of In Vitro Fertilization (IVF), reproductive surgeries which were believed to be fertility sparing were properly acknowledged, role of reproductive surgeons became obsolete. With the plateauing of IVF result interest has got rekindled with considerable advantages of reproductive surgeries is this field. Additionally, newer instrumentation as well as along with surgical procedure has evoked and made it attractivefor reproductive surgeons for improvementof their expertise with regards to conservation of future fertility as well as train future Reproductive Endocrinology and Infertility specialist (REI) in view of solidifying this field of yielding pregnancies to maximum of infertile cases even in patients having cancer surgeries or earlier cryopreservation of oocytes in say patients with turners syndrome etc.

The Prediction of IVF Outcomes with Autologous Oocytes and the Optimal MII Oocyte/Embryo Number for Live Birth at Advanced Maternal Age.

Background and Objectives: Delayed childbearing in advanced age might be associated with a low prognosis for achieving pregnancy. Therefore, it is important to establish a predictive tool that will optimize the likelihood of a live birth at advanced age. Material and Methods: The retrospective study was conducted at the Ferona Fertility Clinic in Novi Sad (Republic of Serbia), between January 2020 and May 2021. The survey included 491 women aged ≥35 who met the inclusion criteria and who were subjected to an IVF (in vitro fertilization) treatment cycle. Results: The average number of retrieved oocytes, MII (metaphase II) oocytes, and developed embryos significantly decreased in advanced age. Age was also found to have a significant adverse effect on pregnancy and live birth rates. In women aged ≥35, 10/12 MII oocytes or 10/11 embryos are required for reaching an optimal live birth rate/cumulative live birth rate. Optimal CLBR (cumulative live birth rate) per one oocyte was achieved when 9 MII oocyte were retrieved. Conclusions: The study indicates that the cut-off for increased risk is ≥42 year. However, despite low live birth rates, autologous IVF for these women is not futile. An increase in the number of retrieved mature oocytes and a generation of surplus cryopreserved embryos could reinforce LBR (live birth rate) and CLBR. Clinicians should be very cautious in counseling, as autologous IVF may only be applicable to women with good ovarian reserve.

Effect of prior female SARS-CoV-2 infection on IVF outcomes: a prospective cohort study.

The clinical impact of SARS-CoV-2 infection on human reproduction remains controversial. This prospective cohort study aimed to assess the effect of prior female SARS-CoV-2 infection on subsequent in vitro fertilization (IVF) outcomes. A total of 451 women who underwent fresh IVF treatment between December 1, 2022 and April 30, 2023 were included from an academic fertility center. Participants were divided into the infected group if they had a prior COVID-19 history before cycle initiation (n = 252), while the control group were those uninfected (n = 199). The primary outcomes were the number of oocytes retrieved and clinical pregnancy rate after fresh embryo transfer. Multivariate linear and logistic regression analyses were conducted to control for potential confounders. The number of oocytes retrieved (11.4 ± 8.3 vs. 11.6 ± 7.7; P = 0.457) and clinical pregnancy rate (70.3% vs. 73.7%; P = 0.590) were similar between infected and uninfected groups, with a fully adjusted β coefficient of 0 (95% confidence interval [CI]: -0.14-0.13) and odds ratio of 0.64 (95% CI: 0.20-2.07), respectively. Consistently, the two groups were comparable in cycle characteristics as well as other laboratory and pregnancy parameters. In both subgroup analyses and restricted cubic splines, different post-infection time intervals to IVF cycle initiation showed no significant associations with treatment outcomes. Prior SARS-CoV-2 infection in females had no adverse influence on subsequent IVF treatment, regardless of the time interval following infection. Our findings provide reassurance for infected women planning for assisted reproduction. Additional prospective cohort studies with larger datasets and longer follow-up are required to confirm the conclusion.

The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency.

To evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model. After inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneally to 6-week-old ICR mice, the mice were divided into four groups (control, CP, 1 mg/kg GH, and 2 mg/kg GH) with 10 mice in each group. GH was administered a week later for 7 days. Five mice from each group were sacrificed the next day, and their ovaries were collected for histological examination. The remaining mice were superovulated for in vitro fertilization (IVF). The terminal deoxynucleotidyl transferase dUTP-nick end labeling assay was performed to detect apoptosis. Masson's trichrome staining was used to analyze the degree of fibrosis. To quantify angiogenesis, CD31 immunohistochemistry was performed. Angiogenesis-related gene expression profiles were assessed using quantitative reverse transcription polymerase chain reaction. CP induced the loss of non-growing (primordial and primary) follicles while GH significantly protected primordial follicles and increased follicular quality. The CP group showed a decrease in fertilization and blastocyst formation rates in IVF. In contrast, the GH treatment group showed dose-dependent enhanced IVF outcomes. Furthermore, GH treatment decreased apoptosis and stromal fibrosis and increased angiogenesis. Many genes involved in angiogenesis, especially Leptin (Lep), platelet endothelial cell adhesion molecule 1 (Pecam-1), and angiogenin (Ang) were up-regulated in the GH treatment groups. GH treatment may promote the recovery of ovarian function in ovarian insufficiency induced by the administration of CP via decreasing apoptosis and stromal fibrosis and upregulating Lep, Pecam-1, and Ang genes.

Alteration of relative telomere length and telomerase reverse transcriptase expression in the granulosa cells of women during aging and assessment of in vitro fertilization outcomes.

Telomere attrition plays a critical role in the reproductive aging process in humans. Telomere length (TL) is typically regulated by telomerase, the main component of which is telomerase reverse transcriptase (TERT). The aim of the present study was to investigate the changes of relative TL (RTL) and TERT expression in granulosa cells (GCs) during aging and its association with reproduction. Clinical data on the frozen‑thawed embryo transfer cycles of older (>35year old) and younger (≤35year old) women from a single center over a 3‑year period were retrospectively analyzed. Preimplantation genetic testing for chromosome aneuploidies in older women during the same period was also analyzed. Following the analysis of the data, several biological characteristics of senescent GCs were explored. In addition, a total of 160women who were undergoing their first fresh cycle of invitro fertilization (IVF) or intracytoplasmic sperm injection were included in the study. GCs were collected from all participants. The changes of RTL and TERT expression in GCs during aging were investigated using quantitative PCR and western blotting. The associations of RTL and TERT with IVF outcomes were also assessed. The clinical data demonstrated that the pregnancy and live birth rates of women aged >35years were ~20% lower than those of women aged ≤35years, and the number of embryos with aneuploidy was 7‑fold of that without euploidy in the older age group. An aging‑induced change in follicle stimulating hormone receptor expression was observed. A shorter TL and increased TERT expression were detected in the older women. A significant inverse correlation between the expression levels of TERT and oocyte yield was identified. However, no association of RTL and TERT with blastocyst formation rate and the probability of clinical pregnancy was detected. It may be concluded that RTL and TERT alterations in GCs are potential determinants of ovarian aging. TERT expression in GCs appears to be a potential biomarker for the prediction of ovarian response, which provides a novel strategy for the assessment of female fertility.

Microscopic Video-Based Grouped Embryo Segmentation: A Deep Learning Approach.

The primary aim of this research is to enhance the utilization of advanced deep learning (DL) techniques in the domain of in vitro fertilization (IVF) by presenting a more refined approach to the segmentation and organization of microscopic embryos. This study also seeks to establish a comprehensive embryo database that can be employed for future research and educational purposes. This study introduces an advanced methodology for embryo segmentation and organization using DL. The approach comprises three primary steps: Embryo Segmentation Model, Segmented Embryo Image Organization, and Clear and Blur Image Classification. The proposed approach was rigorously evaluated on a sample of 5182 embryos extracted from 362 microscopic embryo videos. The study's results show that the proposed method is highly effective in accurately segmenting and organizing embryo images. This is evidenced by the high mean average precision values of 1.0 at anintersection over union threshold of 0.5 and across the range of 0.5 to 0.95, indicating a robust object detection capability that is vital in the IVF process. Segmentation of images based on various factors such as the day of development, patient, growth medium, and embryo facilitates easy comparison and identification of potential issues. Finally, appropriate threshold values for clear and blur image classification are proposed. The suggested technique represents an indispensable stage of data preparation for IVF training and education. Furthermore, this study provides asolid foundation for future research and adoption of DL in IVF, which is expected to have a significant positive impact on IVF outcomes.

The utility of all-freeze IVF cycles depends on the composition of study populations

BackgroundBecause often introduced without proper validation studies, so-called “add-ons” to IVF have adversely affected in vitro fertilization (IVF) outcomes worldwide. All-freeze cycles (embryo banking, EB) with subsequently deferred thaw cycles are such an “add-on” and, because of greatly diverging reported outcomes, have become increasingly controversial. Based on “modeling” with selected patient populations, we in this study investigated whether reported outcome discrepancies may be the consequence of biased patient selection.ResultsIn four distinct retrospective case control studies, we modeled in four cohort pairings how cryopreservation with subsequent thaw cycles affects outcomes differently in good-, average- and poor-prognosis patients: (i) 127 fresh vs. 193 frozen donor-recipient cycles to model best-prognosis patients; (ii) 741 autologous fresh non-donor IVF cycles vs. 217 autologous frozen non-donor IVF cycles to model average prognosis patients; (iii) 143 favorably selected autologous non-donor IVF cycles vs. the same 217 frozen autologous cycles non-donor to monitor good- vs. average-prognosis patients; and (iv) 598 average and poor-prognosis autologous non-donor cycles vs. the same 217 frozen autologous non-donor cycles to model poor vs. average prognosis patients. In best-prognosis patients, EB marginally improved IVF outcomes. In unselected patients, EB had no effects. In poor-prognosis patients, EB adversely affected IVF outcomes. Unexpectedly, the study also discovered independent-of-age-associated chromosomal abnormalities, a previously unreported effect of recipient age on miscarriage risk in donor-egg recipients.ConclusionsIn poor-prognosis patients, EB cycles should be considered contraindicated. In intermediate-prognosis patients EB does not appear to change outcomes, not warranting additional cost and time delays. Therefore, only good-prognosis patients are candidates for EB, though they will experience only marginal benefits that may not be cost-effective.

The efficacy of GnRH agonist trigger followed by hCG add-back in normal responders for fresh embryo transfer: a case-control analysis from Vietnam

Aim: to assess the effects of a dual trigger by gonadotrophin-releasing hormone (GnRH) agonist and low-dose human chorionic gonadotropin (hCG) on in vitro fertilization (IVF) outcomes in women with normal ovarian response.Materials and Methods. This case-control analysis comprised 118 patients who responded normally to ovarian stimulation with a GnRH antagonist protocol at Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between January 2018 and October 2019. Recruitment was achieved through case-control matching: a case (with Dual trigger – group A) was paired with control (with hCG trigger – group B) in a 1:1 ratio. The primary markers of success were the retrieval of oocytes and embryological data, the pregnancy rate, and the incidence of ovarian hyperstimulation syndrome (OHSS).Results. 59 patients in group A and 59 women in group B were recruited. Two groups had comparable patient characteristics and ovarian reserve. The initial dose, total dose, duration of gonadotropin administration, and peak of estradiol level were not statistically different across groups. The number of recovered oocytes (10.3 ± 4.2 vs. 10.0 ± 3.3; p = 0.663), mature oocytes (8.6 ± 3.7 vs.8.1 ± 2.8; p = 0.346), and high-quality embryos (56.2 ± 28.9 vs. 59.8 ± 35.9; p = 0.555) was equivalent. Fertilization, clinical pregnancy, and live birth rates were comparable between the dual trigger and hCG groups. In neither group were any occurrences of OHSS seen.Conclusion. Dual trigger may substitute hCG for final oocyte maturation and fresh embryo transfer in patients with normal responses to GnRH antagonist protocol-induced ovarian stimulation without compromising IVF outcomes.

Fertility and Obstetric Outcomes of Assisted Reproductive Technology (ART) in Women With Adenomyosis Following Gonadotropin-Releasing Hormone Agonist Therapy: A Single-Center Experience.

Adenomyosis is an ambiguous disorder causing a wide variety of implications from dysmenorrhea, heavy menstrual bleeding, and infertility to pregnancy complications. Adenomyosis is associated with altered endocrine and inflammatory milieu, resulting in impaired implantation and reduced fertility potential. It is also associated with increased incidence of obstetric complications such as miscarriage, antepartum hemorrhage, placental mal-position, hypertensive disorders, small for gestational age-intrauterine growth restriction (SGA-IUGR), cesarean section, preterm labor, preterm premature rupture of membranes (PPROM), and neonatal intensive care unit (NICU) admissions. The aim of our study was to investigate the fertility and obstetric outcomes in women with adenomyosis treated with GnRH agonists compared to controls with normal uteri undergoing in-vitro fertilization (IVF) at our center, thereby establishing the role of gonadotropin-releasing hormone (GnRH) agonists in managing sub-fertile women with adenomyosis. We carried out a retrospective cohort study at our hospital to analyze the effects of adenomyosis on IVF and pregnancy outcomes. This study (n=83) involves women with adenomyosis between the ages of 21 and 37 years who were followed up at our center between 2013 and 2022. The controls (n=83) were selected from women who underwent IVF-intracytoplasmic sperm injection (IVF-ICSI) for tubal or mild male factor infertility with normal appearing uterus within the same time frame. Women with adenomyosis were given GnRH agonist as long/ultralong agonist protocol before controlled ovarian stimulation or as down-regulated frozen embryo transfer (FET). The length of suppression was between one and six months based on the size of the uterus and response to treatment. Fertility and obstetric outcomes were analyzed. The implantation rates were found to be equivocal: 54.2% and 53% in the adenomyosis and control groups, respectively (p=0.208). The cumulative live birth rate was 50.6% and 48.2% in the study and control groups,respectively (p=0.341). The biochemical pregnancy rate and the first- and second-trimester miscarriage rates were not significantly different between the group with adenomyosis and the group with normal uterus. The incidence of preterm deliveries and antepartum hemorrhage was found to be significantly increased in the study group. Medical management in women with adenomyosis optimizes the live birth rates giving results at par with the control population.

Pre-pregnancy obesity is not associated with poor outcomes in fresh transfer in vitro fertilization cycles: a retrospective study

PurposeThe impact of body mass index (BMI) on in vitro fertilization (IVF) has been well acknowledged; however, the reported conclusions are still incongruent. This study aimed to investigate the effect of BMI on IVF embryos and fresh transfer clinical outcomes.MethodsThis retrospective cohort analysis included patients who underwent IVF/ICSI treatment and fresh embryo transfer from 2014 to March 2022. Patients were divided into the underweight group: BMI < 18.5 kg/m2; normal group: 18.5 ≤ BMI < 24 kg/m2; overweight group: 24 ≤ BMI < 28 kg/m2; and obesity group: BMI ≥ 28 kg/m2. A generalized linear model was used to analyze the impact of BMI on each IVF outcome used as a continuous variable.ResultsA total of 3465 IVF/ICSI cycles in the embryo part; and 1698 fresh embryo transplanted cycles from the clinical part were included. Available embryos rate (61.59% vs. 57.32%, p = 0.007) and blastocyst development rates (77.98% vs. 66.27%, p < 0.001) were higher in the obesity group compared to the normal BMI group. Also, the fertilization rate of IVF cycles in the obesity group was significantly decreased vs. normal BMI group (normal: 62.95% vs. 66.63% p = 0.006; abnormal: 5.43% vs. 7.04%, p = 0.037), while there was no difference in ICSI cycles. The clinical outcomes of overweight and obesity groups were comparable to the normal group. The gestational age of the obesity group was lower compared to the normal group (38.08 ± 1.95 vs. 38.95 ± 1.55, p = 0.011). The adjusted OR (AOR) of BMI for the preterm birth rate of singletons was 1.134 [(95% CI 1.037–1.240), p = 0.006]. BMI was significantly associated with live birth rate after excluded the PCOS patients [AOR: 1.042 (95% CI 1.007–1.078), p = 0.018]. In young age (≤ 35 years), clinical pregnancy rate and live birth rate were positively correlated with BMI, AOR was 1.038 [95% CI (1.001–1.076), p = 0.045] and 1.037 [95% CI (1.002–1.074) p = 0.038] respectively.ConclusionBeing overweight and obese was not associated with poor IVF outcomes but could affect blastocyst formation. ICSI could help to avoid low fertilization in obese patients. Also, obesity was associated with increased rates of premature singleton births.

Associations between Urinary Concentrations of Disinfection Byproducts and in Vitro Fertilization Outcomes: A Prospective Cohort Study in China.

Experimental studies show that disinfection byproducts (DBPs) can inhibit oocyte maturation, decrease fertilization capacity, and impair embryo development, but human evidence is lacking. We aimed to evaluate the associations between exposure to drinking water DBPs and in vitro fertilization (IVF) outcomes. The study included 1,048 women undergoing assisted reproductive technology (ART) treatment between December 2018 and January 2020 from a prospective cohort study, the Tongji Reproductive and Environmental study in Wuhan, China. Exposure to DBPs was assessed by dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in up to four urine samples, which were collected on the day of both enrollment and oocyte retrieval. Multivariable generalized linear mixed models, accounting for multiple IVF cycles per woman, were applied to evaluate the associations between urinary biomarkers of DBP exposures and IVF outcomes. Stratified analyses were used to explore the potential effect modifiers. The included 1,048 women underwent 1,136 IVF cycles, with 960 (91.6%), 84 (8.0%), and 4 (0.4%) women contributing one cycle, two cycles, and three cycles, respectively. We found that elevated quartiles of urinary DCAA and TCAA concentrations were associated with reduced numbers of total oocytes and metaphase II oocytes and that urinary DCAA concentrations with a lower proportion of best-quality embryos (all p for ). Moreover, elevated quartiles of urinary DCAA concentrations were associated with decreased proportions of successful implantation, clinical pregnancy, and live birth (14%, 15%, and 15% decreases in adjusted means comparing the extreme quartiles, respectively; all p for ). Stratification analyses showed that the inverse associations of urinary TCAA concentrations with multiple IVF outcomes were stronger among women y of age (p for ). Exposure to drinking water DBPs was inversely associated with some IVF outcomes among women undergoing ART treatment. Further study is necessary to confirm our findings. https://doi.org/10.1289/EHP12447.