Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial.

BACKGROUND: Poor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR. METHODS: In this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction. RESULTS: After the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group. CONCLUSION: AST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis. TRIAL REGISTRATION: Clinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870 , registration date: 2023 March 16.

Immunosuppressants in women with repeated implantation failure in assisted reproductive techniques: a systematic review and meta-analysis.

Objective: To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone. Data source: Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023. Study Selection: Randomized clinical trials and observational studies with the outcomes of interest were included. Data collect: We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy. Data synthesis: Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42). Conclusion: Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure. PROSPERO: CRD42023449655.

A new hormonal protocol supports early development of in vitro-produced embryos after transfer to anoestrus mares.

The present study aimed to evaluate whether primed anoestrus mares are suitable recipients for embryos produced by intracytoplasmic sperm injection (ICSI). Anoestrus was confirmed in four mares and daily doses of oestradiol benzoate (6 mg in total) over 5 days were administered; after 3 days of rest, oral altrenogest was administered at 0.088 mg/kg and embryos (1 to 5 embryos per mare; 15 in total) were transferred 3.5 days after progesterone onset. Uterine lavage was conducted 48 h after transfer. The results revealed an 80% embryo recovery rate, and among the retrieved embryos, 67% showed evident intrauterine development. Hence, ICSI-derived embryos can be successfully transferred to primed anoestrus mares, but more studies are required to ensure further embryo development and foaling.

Role of sperm morphological parameters in the selection of fertilization methods.

To investigate the role of in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in cases with isolated teratozoospermia, and to provide reference for infertile patients to choose a reasonable insemination program. From January 2018 to December 2022, 433 couples received assisted reproductive assistance in the Department of Reproductive Medicine of our hospital. Among them, 81 patients presented isolated teratozoospermia (other sperm parameters were normal). These underwent IVF/ICSI, and differences in embryological data were compared between groups. 60 patients with moderate teratozoospermia went IVF, 11 needed rescue ICSI (R-ICSI, 18.33%), and 49 developed up to the blastocyst stage. 14 patients with severe teratozoospermia went IVF, 2 needed R-ICSI (14.29%), and 12 developed up to the blastocyst stage. There were no statistically significant differences in the proportion of R-ICSI between the two groups. Embryological outcomes were not significantly different between groups. The present results suggest that patients with moderate and severe teratozoospermia can be effectively treated with IVF, being R-ICSI performed when necessary.

Ensemble machine learning models for sperm quality evaluation concerning success rate of clinical pregnancy in assisted reproductive techniques.

This study aimed to investigate the influence of various sperm quality characteristics, including morphology, motility, and count, on the success rates of clinical pregnancy achieved through assisted reproductive technologies (ART) such as in-vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and intrauterine insemination (IUI). The secondary objective was to assess the impact of these sperm parameters on the clinical pregnancy rate that resulted in the detection of a fetal heartbeat during the 11th week of gestation, a crucial milestone in successful ART-derived pregnancies. The researchers employed a retrospective analysis, evaluating data from 734 couples undergoing IVF/ICSI and 1197 couples undergoing IUI across two infertility centers. Exclusion criteria included cases involving donated eggs or sperm, surrogate uteri, and infertile couples with combined male and female factors. Five ensemble machine-learning models were utilized to predict the clinical pregnancy success rates. The Random Forest (RF) model achieved the highest mean accuracy (0.72) and area under the curve (AUC) (0.80), outperforming the other models for both IVF/ICSI and IUI procedures. The Shapley Additive Explanations (SHAP) value analysis revealed that for IUI cycles, all three sperm parameters (morphology, motility, and count) had significant negative impacts on the prediction of clinical pregnancy success. In contrast, for IVF/ICSI cycles, sperm motility had a positive effect, while sperm morphology and count were negative factors. In cycles with 1 to 5 retrieved eggs, sperm motility, and count, they positively affected the clinical pregnancy rate. The study also identified cut-off values for sperm count, with 54 and 35 being the respective thresholds for IVF/ICSI and IUI. Additionally, a significant cut-off point 30 was found for the sperm morphology parameter across all procedures. This study underscores the immense potential of leveraging ensemble machine learning models with traditional sperm quality assessments. This integrated approach can elevate the precision and personalization of clinical decision-making in the field of assisted reproductive technologies, ultimately offering more hope and better outcomes for couples struggling with infertility.

Impact of letrozole co-treatment in an antagonist protocol for IVF/ICSI: a retrospective study.

OBJECTIVE: The present study aimed to investigate the impact of combined use of letrozole in an antagonist protocol during IVF on live birth outcomes and to assess the safety of letrozole in terms of maternal and neonatal complications. METHODS: This retrospective cohort study included women undergoing IVF/ICSI and fresh embryo transfer (ET) treatment with and without letrozole co-treatment from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). The primary outcome was the live birth rate, while the incidences of maternal and neonatal complications were secondary outcomes. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the analyzed outcomes. Sensitivity analysis was performed using a propensity score-based patient-matching (PSM) model, an inverse probability weighting (IPW) model, logistic regression models with women undergoing their first IVF-ET cycle, and subgroup analysis. RESULTS: Of the 4780 women enrolled in the study, 3887 underwent an antagonist protocol for ovarian stimulation, while 893 received letrozole co-treatment. In this cohort, letrozole co-treatment demonstrated comparable live birth rates to the use of antagonist protocol alone (logistic regression: aOR, 0.88; 95% CI, 0.71-1.08; PSM: aOR, 0.97; 95% CI, 0.77-1.22; IPW: aOR, 0.88; 95% CI, 0.71-1.10). Notably, individuals with a body mass index (BMI) exceeding 24 and those with high ovarian response experienced higher live birth rates under the letrozole co-treatment regimen (BMI ≥ 24: aOR, 1.85; 95% CI, 1.14-3.00; high response: aOR, 1.60; 95% CI, 1.02-2.50). Letrozole co-treatment was also associated with decreased risks of gestational diabetes (aOR, 0.34; 95% CI, 0.15-0.69) and small for gestational age (SGA) fetuses (aOR, 0.42; 95% CI, 0.22-0.75) in fresh ET cycles. These finding were robust in both PSM and IPW models. CONCLUSIONS: Our findings suggested that letrozole co-treatment in antagonist protocol for IVF/ICSI was associated with a comparable live birth rate following fresh ET. Further prospective randomized studies are needed to verify our results.

Melatonin levels and embryo quality in IVF patients with diminished ovarian reserve: a comparative study.

BACKGROUND: Melatonin, a hormone found in various bodily fluids and cells, is known for its potent antioxidative, anti-apoptotic, and endocrine regulatory properties. This study aimed to analyze melatonin levels in patients with diminished ovarian reserve (DOR) and its impact on embryo quality. METHODS: We enrolled 85 women who were undergoing in vitro fertilization or intracytoplasmic sperm injection procedures, including normal ovarian reserve (NOR, n = 27), pathological DOR (DOR-Path, n = 25), and physiological DOR (DOR-Phy, n = 33). Melatonin levels in patient serum and follicular fluid were assessed using ELISA, and correlations between melatonin levels and indicators of embryo quality were examined. RESULTS: Our findings indicate that melatonin levels in the follicular fluid and basal serum of the DOR-Path and DOR-Phy groups were lower compared to the NOR group (P < 0.05). However, no significant differences in melatonin levels were found between the DOR-Path and DOR-Phy groups (P > 0.05). Additionally, the concentration of melatonin in the follicular fluid of the NOR group was significantly higher than in their serum (P < 0.001). Lastly, a significant correlation was discovered between melatonin levels in serum and follicular fluid and parameters of ovarian reserve and embryonic development (P < 0.05). CONCLUSIONS: Melatonin levels in DOR patients may impact embryo quality, offering insights into potential DOR pathogenesis and opportunities to enhance treatment outcomes in these patients.

Feasibility of preimplantation genetic testing for aneuploidy on frozen-thawed embryos following conventional IVF insemination.

Objective: Intracytoplasmic sperm injection (ICSI) is commonly employed in preimplantation genetic testing (PGT) to minimize the risk of foreign sperm DNA contamination. Cryopreserved embryos from patients with recurrent miscarriage or repeated implantation failure, who have undergone conventional in vitro fertilization (IVF), can be thawed and biopsied for PGT. Therefore, we aimed to assess the accuracy and effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) on frozen embryos using conventional IVF (c-IVF) insemination methods. Methods: From January 2021 to November 2023, our center conducted 107 thawed cryopreserved embryo biopsy cycles to screen for PGT-A. Among them, 58 cycles used c-IVF insemination, and 49 used ICSI insemination. Basic patient clinical information, laboratory data, PGT test results, and clinical outcome data were collected. To minimize the confounding effects of patient characteristics and embryo quality on PGT-A outcomes, clinical outcomes, and contamination assessment, these variables were included in the analysis. We then evaluated the blastocyst euploidy rate, clinical outcomes, and accuracy of PGT-A results between the two groups and analyzed potential contamination in the c-IVF insemination group. Results: A total of 320 blastocysts underwent PGT-A testing, with 179 blastocysts from c-IVF insemination and 141 from ICSI insemination. Considering participants' baseline characteristics and embryological outcomes, no significant differences were found between the two groups regarding infertility type, average age, body mass index, percentage of PGT-A indications, or quality of embryonic development. Regarding PGT-A results, all 320 biopsy samples were successfully analyzed, showing no statistical variance in chromosomal euploidy, abnormality, or mosaicism rates between the two insemination methods. No parental contamination was detected in the c-IVF insemination group. When assessing clinical outcomes, parameters such as biochemical pregnancy, clinical pregnancy, and miscarriage rates did not exhibit significant discrepancies between the two groups, and no misdiagnoses were reported during the study period. Conclusion: Embryo transfer and PGT-A results are not affected by potential parental contamination in frozen-thawed embryos conceived via c-IVF. PGT-A guided embryo transfer in thawed embryos conceived by c-IVF is a viable and clinically effective approach.

Analysis of the Factors Affecting the Male-Female Sex Ratio of Babies Born through Assisted Reproductive Technology.

BACKGROUND: Until now, the sex ratio in a population is believed to be relatively stable with no male/female preponderance. There has been an increasing amount of evidence to suggest that assisted conception may significantly impact on sex ratio (SR). Several factors have been suggested to affect SR such as parental variables (paternal race, maternal age, and body mass index-(BMI), methods of fertilisation (in-vitro fertilisation/intracytoplasmic sperm injection), stage of embryo transfer (cleavage/blastocyst), type of IVF cycle (fresh/cryopreserved), medications used for controlled ovarian stimulation, poor sperm motility, and even culture media. OBJECTIVES: This study aims to investigate the potential impact of the different ART procedures on sex ratio. It will also explore the relationship between paternal race, maternal age and body mass index BMI on sex ratio. METHODS: A retrospective cohort study from January 2017 to December 2023. Participants were women who had successful ART and delivery at Ninewells Assisted Conception Unit (NACU) Dundee and ART centre of Lagos University Teaching Hospital, Nigeria. RESULTS: Overall, 294 (66.2%) of the case records and 150 (33.8%) were evaluated from NACU and LUTH respectively. More male infants 244 (66.8%) were delivered following pregnancies conceived with blastocyst embryo stage transfer when compared with female infants which stood at 121 (33.2%). Concerning cleavage embryo stage transfer, 56 (70.9%) were in favour of female newborns while males accounted for 23 (29.1%). CONCLUSION: The study revealed that there is an increase in the proportion of male babies born following certain assisted conception techniques such as blastocyst stage embryo transfer and IVF while more female babies were born when cleavage stage embryos were transferred or when ICSI was used as a method of fertilisation.

CONTEXTE: Jusqu'à présent, le rapport de masculinité au sein d'une population est considéré comme relativement stable, sans prépondérance masculine/féminine. De plus en plus de preuves suggèrent que la procréation assistée peut avoir un impact significatif sur la sex-ratio (SR). Plusieurs facteurs ont été suggérés pour affecter la SR, tels que les variables parentales (race paternelle, âge maternel et indice de masse corporelle-IMC), les méthodes de fécondation (fécondation in vitro/injection intracytoplasmique de spermatozoïdes), le stade du transfert d'embryon (clivage/blastocyste), le type de Cycle de FIV (frais/cryoconservé), médicaments utilisés pour une stimulation ovarienne contrôlée, mauvaise motilité des spermatozoïdes et même milieux de culture. OBJECTIFS: Cette étude vise à étudier l'impact potentiel des différentes procédures de TAR sur le sex-ratio. Il explorera également la relation entre les variables parentales telles que la race paternelle, l'âge de la mère et l'indice de masse corporelle (IMC) sur le sex-ratio. Méthodes : Une étude rétrospective de janvier 2017 à décembre 2023. Les participantes étaient des femmes qui ont eu un TAR et un accouchement réussis à l'unité de conception assistée de Ninewells (NACU) de Dundee et au centre de TAR de l'hôpital universitaire de Lagos, au Nigeria. RESULTATS: Au total, 294 (66,2 %) des dossiers de cas et 150 (33,8 %) ont été évalués respectivement par le NACU et le LUTH. Un plus grand nombre de nourrissons de sexe masculin, 244 (66,8 %), ont accouché à la suite de grossesses conçues avec transfert de stade embryonnaire de blastocyste, par rapport aux nourrissons de sexe féminin, qui s'élevaient à 121 (33,2 %). Concernant le transfert de stades embryonnaires par clivage, 56 (70,9%) étaient en faveur des nouveau-nés de sexe féminin tandis que les mâles représentaient 23 (29,1%). CONCLUSION: L'étude a révélé qu'il y a une augmentation de la proportion de bébés mâles nés suite à certaines techniques de procréation assistée telles que le transfert d'embryons au stade blastocyste et la FIV, tandis qu'un plus grand nombre de bébés femelles sont nés lorsque des embryons au stade clivage ont été transférés ou lorsque l'ICSI a été utilisée comme méthode de fertilisation. MOTS-CLÉS: Ratio de sexes, ICSI, FIV, Blastocyste, Clivage, Race, IMC, Embryon congelé/frais.

Follitropin Alpha versus Follitropin Beta in IVF/ICSI Cycle: A Retrospective Cohort Study.

Purpose: The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles. Methods: A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups. Results: Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912). Conclusion: Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy.

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study.

BACKGROUND: Obesity poses a significant global health challenge, with profound implications for women's reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients. METHODS: We conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses. RESULTS: Anti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20-30 and 30-35 years. Among women aged 20-35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia. CONCLUSIONS: An age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Erratum: Lower developmental potential of rat zygotes produced by ooplasmic injection of testicular spermatozoa versus cauda epididymal spermatozoa.

J Reprod Dev, Vol. 70, No. 4, p. 255 Table 2 have been corrected. For the bottom of Survived (%) row, the Survived value, which read "69", should be replaced with "86".

Altered metabolic profiles in male offspring conceived from intracytoplasmic sperm injection.

BACKGROUND: While most research has focused on the association between intracytoplasmic sperm injection (ICSI) and neurodevelopmental disorders in children, relatively little attention has been given to its metabolic effects. Previous studies have reported that low serum lipid levels are associated with mental health problems. Our objective was to analyze the impact of ICSI on metabolic alterations compared to their in vitro fertilization (IVF) counterparts in male offspring, as well as its interaction with paternal overweight/obesity. METHODS: We recruited families between January 2006 and December 2017 at the Center for Reproductive Medicine, Shandong University, China. Prospective data of offspring were obtained for body mass index (BMI), blood pressure, glucose, and lipid profile in their 0-11 years old. Linear mixed models were utilized to compute the mean difference and 95% confidence intervals (CI). RESULTS: A total of 14,196 offspring visits were identified. In offspring aged 4-11 years, ICSI-conceived offspring exhibited significantly lower fasting glucose z-scores, total cholesterol z-scores, and low-density lipoprotein cholesterol (LDL-C) z-scores compared with their IVF counterparts (fasting glucose z-score: adjusted mean difference: - 0.13, 95% CI: - 0.23 to - 0.03; total cholesterol z-score: adjusted mean difference: - 0.13, 95% CI: - 0.23 to - 0.02; LDL-C z-score: adjusted mean difference: - 0.12, 95% CI: - 0.22 to - 0.01). Paternal overweight/obesity significantly influenced the relationship between ICSI and metabolic changes in offspring. In offspring born from fathers with overweight/obesity, ICSI-conceived offspring displayed significantly lower fasting glucose and total cholesterol z-scores than their IVF controls (fasting glucose z-score: adjusted mean difference: - 0.20, 95% CI: - 0.32 to - 0.08; total cholesterol z-score: adjusted mean difference: - 0.15, 95% CI: - 0.27 to - 0.02). In offspring born to fathers with normal weight, ICSI-conceived offspring showed significantly lower systolic blood pressure z-scores compared to those conceived via the IVF procedures (adjusted mean difference: - 0.21, 95% CI: - 0.37 to - 0.05). CONCLUSIONS: The findings of this study suggested that ICSI was associated with altered glucose and lipid profiles compared to their IVF controls, characterized by lower fasting glucose z-scores, total cholesterol z-scores, and LDL-C z-scores. Encouraging fathers to reduce their body weight could potentially improve the metabolic health of their ICSI-conceived children.

Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes.

BACKGROUND: Anti-Müllerian hormone (AMH) is a widely used marker for estimating ovarian reserve, and it may predict response to ovarian stimulation. While AMH is considered a stable, cycle-independent marker, studies have shown it can exhibit significant fluctuations based on factors like age, reproductive stage, and menstrual cycle phase. The fluctuations in AMH levels can make it challenging to predict individual responses accurately, particularly when the AMH is not measured in the COS cycle. The aim of this study was to assess the inter-cycle variability of serum AMH levels in two consecutive menstrual cycles and their correlation with response to controlled ovarian stimulation outcome in the latter. METHODS: In this single-centre retrospective cohort study, data of normal and low responder patients who underwent intracytoplasmic sperm injection following a GnRH antagonist cycle at a university hospital infertility clinic between January 2022 and December 2023 were reviewed. Serum AMH levels were measured in the early follicular phase of two consecutive menstrual cycles with Elecsys-AMH Roche® system (Roche Diagnostics, Meylan, France). Correlations between AMH levels and controlled ovarian stimulation outcomes, including total oocyte and mature oocyte (MII) counts, were assessed. The study included normal and poor responder women to maintain data integrity. RESULTS: A total of 79 patients were included in the final analyses. Significant cycle-to-cycle variation in serum AMH levels was observed, with a median variation of 44.3%. Normal responders exhibited a mean change of 0.60 ± 0.46 ng/ml, while poor responders had a mean change of 0.28 ± 0.28 ng/ml. Approximately 20% of patients were reclassified between normal and poor responder categories based on the second AMH measurement. The controlled ovarian stimulation cycle AMH levels showed a stronger correlation with both total oocyte count (r = 0.871, P < 0.001) and MII oocyte count (r = 0.820, P < 0.001) compared to preceding cycle AMH levels. CONCLUSION: AMH levels can exhibit significant variations between consecutive cycles, potentially leading to misclassification of patients. Measuring AMH in the early follicular phase of the COS cycle provides a more accurate prediction of the numbers of total and MII oocytes collected. Consistent and repeated AMH measurements can help clinical decision-making.

Cytoplasmic sperm injection (ICSI) - A systematic review of the literature.

Background: Progestin-primed ovarian stimulation (PPOS) stimulates ovaries to block the premature surge of luteinizing hormone (LH) by using micronized progesterone or a progestin during the follicular phase instead of the conventional gonadotropin-releasing hormone (GnRH) analogues or GnRH antagonists downregulating LH to obtain multi-follicle engagement. Current work aims to assess the influence of progestogen treatment on ovarian stimulation and the ability to control LH surge, its efficacy and suitability in retrieving oocytes, without affecting the embryo quality and its benefit among infertile women long-term outcomes on children compared to standard stimulation protocols. Materials and Methods: The literature review used the randomized control trials published in the Pubmed database from January 2015 to April 2021. To generate the citation list, the following keywords were used: 'progestin-primed ovarian stimulation', 'PPOS', 'micronized progesterone', 'medroxyprogesterone', and/or 'dydrogesterone'. The selected articles analyzed the cohort, intervention, and scheme of the progestin-primed ovarian stimulation protocol in controlled ovarian stimulation (COS) for in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) used in Assisted Reproductive Technologies (ART). Results: Overall we concluded that PPOS for IVF/ICSI in ART results in a higher number of obtained embryos, lower incidence of OHSS, equal duration of stimulation, number of retrieved oocytes, and number of MII oocytes. It is also suggested that long-term safety in children shows no significant difference between the study and control groups. Conclusions: Despite the outcomes of progestin stimulation cycles among all cohorts, we concluded that poor ovarian responders, patients with PCOS, women of advanced age and oocyte donors benefit the most from using PPOS.

Rate of testicular histology failure in predicting successful testicular sperm extraction.

Background: The management of Non-Obstructive (NOA) Azoospermia or Obstructive Azoospermia (OA) patients relies on testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI). In NOA patients the sperm recovery is successful in only 50% of cases and therefore the ability to predict those patients with a high probability of achieving a successful sperm retrieval would be a great value in counselling the patient and his partner. Several studies tried to suggest predictors of a positive TESE (e.g. FSH concentration), but most concluded that diagnostic testicular biopsy (histology) is best. Methods: This is a retrospective analysis of 526 TESE patients. After the extraction of the testis, the resulting sample was immediately given to the embryologist, who examined the tubules for sperm cryopreservation. During the same procedure, a different specimen was destined to the histological analysis. The comparison between the two methodological approaches was carried out through a score. Results: Concordance between TESE and testicular histology outcomes was found in 70,7% of patients; discordance was found in 29,3% of patients. Among the discordance outcomes, in approximately 95% we found at least 1 sperm in the TESE retrieval, while the histology report did not find any spermatozoa or found not enough compared to our evaluation; in only 5% of cases we did not find any spermatozoa or found not enough compared to what was detected in the testicular histology. Conclusion: Based on our experience, to increase diagnostic accuracy, a larger biopsy should be sent to the histopathology laboratory; another option may be to use TESE cell suspension (the same embryologists employ for cryopreservation) for cytological evaluation of spermatogenesis.

Successful Sperm Retrieval and Clinical Pregnancies Following Micro-TESE and ICSI Treatments in Patients with Nonobstructive Azoospermia Due to Various Etiologies.

(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were analyzed between November 2017 and July 2022 in the Reproductive and Genetic Hospital of China International Trust and Investment Corporation-Xiangya (CITIC-Xiangya); (3) Results: The overall SRR was 39.4% (247/627). The SRR according to NOA etiologies were: Y chromosome azoospermia factor c microdeletions (26/46, 56.5%), Klinefelter syndrome (KS), 36/85, 42.4%), idiopathic (110/398, 27.6%), cryptorchidism (20/29, 69.0%), chromosome anomalies (7/13, 53.9%), orchitis (45/50, 90.0%), and cancer (3/6, 50.0%). The SRR were different for spermatogonia arrest (26/96, 27.1%), maturation arrest (76/177, 42.9%), and SCOS (30/80, 37.5%) according to histological examinations. The clinical pregnancy rate was similar among the NOA etiologies. The high-quality embryo rate differed between successful (54.7%) and unsuccessful (40.9%) pregnancies. Moreover, the successfully pregnant women (28.99 years) were younger than the unsuccessfully pregnant ones (30.92 years); (4) Conclusions: The SRR from patients with NOA was associated with the etiology and histological categories, while the clinical outcome was associated with the high-quality embryo rate and the female partner's age.

Relationship between fresh single embryo morphology scores and serum HCG values at 14 days and 14-18-day doubling values.

RESEARCH QUESTION: What is the effect of embryo morphology score on 14-day ß-HCG levels and 14-18-day ß-HCG doubling values, and do they have differences in day-3 embryo or day-5 blastocyst transfers? DESIGN: Retrospective analysis of 4434 fresh cycles of single embryo transfers (SET) with ß-HCG ≥15 mIU/ml on day 14 after transfer via IVF and ICSI. The correlation between embryo morphology score and 14-day ß-HCG was examined. Doubling of 14-18 day ß-HCG was analysed in 2628 cycles to determine correlations with embryo morphology score. RESULTS: In day-3 SET, number of embryonic cells was positively correlated with 14-day post-transfer ß-HCG values (R = 0.076; P = 0.013). No significant correlation was observed between the grade of the transferred embryos and the 14-18-day serum ß-HCG doubling values. In day-5 single blastocyst transfers, the degree of blastocyst expansion, trophoblast cell and inner cell mass (ICM) grades demonstrated a significant positive correlation with 14-day post-transfer ß-HCG (P < 0.001, P = 0.014, P = 0.003). Degree of blastocyst expansion was significantly correlated with 14-18-day ß-HCG doubling values (R = -0.051, P = 0.027). Grades of the ICM and trophoblast cells showed no significant correlation with 14-18-day ß-HCG doubling values. CONCLUSION: In fresh SET, embryo morphology score influences 14-day ß-HCG values in day-3 embryos and day-5 blastocyst transfers. Embryo morphology score in day-3 SET does not affect 14-18-day ß-HCG doubling values. Degree of blastocyst expansion significantly affects 14-18-day ß-HCG doubling values in day-5 blastocyst transfers.

Artificial oocyte activation improves ICSI outcomes following unexplained fertilization abnormalities.

RESEARCH QUESTION: Is artificial oocyte activation (AOA) effective for patients with unexplained low or no fertilization following IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: All IVF/ICSI cases resulting in total fertilization failure or fertilization rate ≤25% at Ninewells Assisted Conception Unit, Dundee between January 2014 and December 2021 (n = 231) were reviewed contemporaneously. After exclusion of obvious stimulation, egg, sperm and/or assisted reproductive technology laboratory factors, patients with at least one cycle of IVF/ICSI resulting in apparently unexplained fertilization abnormalities were offered research investigations, including sperm immunocytochemistry for phospholipase C zeta (PLCζ) protein expression. This retrospective case-control cohort study evaluated laboratory and clinical outcomes for 39 couples (15 attended for sperm studies research) that subsequently undertook ICSI-AOA with Ca2+ ionophore. RESULTS: Comparing preceding IVF/ICSI and subsequent ICSI-AOA for each patient, the number of eggs collected was similar; however, ICSI-AOA resulted in a significantly improved fertilization rate (57.2% versus 7.1%; P < 0.0001). The uplift for a subset of 10 patients identified with PLCζ deficiency was 66.3% versus 4.6% (P < 0.0001). Overall, ICSI-AOA resulted in a higher number of fresh embryo transfers (94.6% versus 33.3%; P < 0.0001), a significantly higher clinical pregnancy rate (CPR) and live birth rate (LBR; 18.9% versus 2.6%; P = 0.02), a significant increase in cycles with surplus embryos suitable for cryostorage (43.6% versus 0%; P < 0.0001), and increased cumulative CPR (41.0% versus 2.6%; P < 0.0001) and LBR (38.5% versus 2.6%; P < 0.0001). CONCLUSION: AOA is a powerful tool that can transform clinical outcomes for couples experiencing apparently unexplained fertilization abnormalities. PLCζ assays have the potential to be valuable diagnostic tools to determine patient selection for ICSI-AOA, and research efforts should continue to focus on their development.

Increased miscarriage rate is associated with at least four components of metabolic syndrome in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycle.

AIM: This study aimed to investigate the association between the components of metabolic syndrome (MetS) and reproductive outcomes in women with polycystic ovary syndrome (PCOS) undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) embryo transfer cycle. METHODS: This is a retrospective study that included 720 women with PCOS from January 2018 to December 2021. Anthropometric, biochemical, and reproductive data of the study subjects were collected from electronic medical record. Women with PCOS met <3, 3, and >3 criteria of MetS were classified in group 1, 2, and 3, respectively. RESULTS: The miscarriage rate in women with MetS was significantly higher than that in non-MetS group (23.2% vs. 14.2%, p = 0.03). There was a significant increasing trend in miscarriage rate from group 1 to group 3 (p for trend <0.05). The miscarriage rate in group 3 was significantly higher than that in group 1 (29.3% vs. 14.2%, p < 0.05). Logistic regression analyses showed that women with at least four components of MetS (group 3) were independently associated with a high risk of miscarriage, with the odds ratios and 95% confidence intervals for group 2 and 3 versus group 1 were 1.38 (0.67-2.82) and 2.46 (1.06-5.74), respectively (p for trend = 0.04). CONCLUSIONS: PCOS women accompanied with at least four diagnostic criteria of MetS is independently associated with increased miscarriage rate when undergoing their first IVF or ICSI cycle.