Intracytoplasmic Sperm Injection Research Articles

Long-Term Impact of Infertility and Assisted Reproductive Technology on Cardio-Renal Health in Sweden

Abstract Background The use of Assisted Reproductive Technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), is rising in Europe. These treatments involve high doses of hormones to increase oocyte collection. While most safety studies in women have focused on cancer risks, the association with cardio-renal diseases remains under-explored. This study examines whether the use of ART is linked to coronary ischemic disease (CHD), stroke, brain hemorrhage, other cerebrovascular diseases, chronic kidney disease, and aortic aneurysm/dissection, while also exploring the association between infertility and these conditions. Methods A nationwide cohort study was conducted using Swedish national registries, following all nulliparous women who gave birth between 1982 and 2002 until the end of 2017. Descriptive statistics and inverse probability weighted Kaplan-Meier curves to adjust for body mass index, maternal age, country of origin, smoking, and year of delivery, were used to compare 1) women who conceived with or without ART, 2) women who used IVF or ICSI respectively to women with known infertility that conceived without ART, and 3) women with and without known infertility. Results Compared to all other women, women undergoing ART were at elevated risk for CHD, stroke, and other cerebrovascular diseases, but after adjustment for underlying risk factors, including infertility, no substantial differences were seen. As a group, women with known infertility were at elevated risk of CHD and stroke, also after adjustment for known background factors. Conclusions Data suggest that the use of ART does not increase the long-term risk of cardio-renal diseases. Nonetheless, infertility itself is associated with a higher risk of CHD and stroke. Key messages • Infertility, more so than the use of ART, is linked to elevated risks of CHD and stroke. • Preventive measures for these conditions should be considered for women with infertility.

REPRODUÇÃO ASSISTIDA: DESAFIOS E AVANÇOS DAFERTILIZAÇÃO IN VITRO E INSEMINAÇÃO ARTIFICIAL COM PERSPECTIVAS ATUAIS E FUTURAS

Assisted human reproduction (AHR) is a set of medical techniques that enable human reproduction with assistance, contributing to cases of infertility, advanced age, same-sex couples, independent gestation, and family planning. The main techniques are artificial insemination and in vitro fertilization (IVF). This exploratory-descriptive study investigates the challenges faced by these couples, as well as recent advancements and future perspectives of these techniques. The analysis includes a review of recent literature, focusing on advancements such as improved ovarian stimulation protocols and embryo selection, as well as the impact of emerging technologies. The study also addresses the variable success rates, procedure costs, and ethical issues involved. It is expected that ongoing innovations will improve success rates, reduce risks, and enhance the accessibility of these treatments. Currently, the technique of intracytoplasmic sperm injection (ICSI) is widely used. Despite the challenges, AHR has enabled infertile couples to realize their dream of parenthood. With scientific and technological advancements, it is anticipated that AHR techniques will continue to evolve to benefit more and more couples wishing to have children.

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

BackgroundAnti-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.MethodsIn 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.ResultsA 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.ConclusionAMH 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.

Clinical outcomes of round spermatid injection versus intra-cytoplasmic sperm injection: The potential role of hormonal pretreatment in male patients with non-obstructive azoospermia.

Round spermatid injection (ROSI) into oocytes offers men with non-obstructive azoospermia (NOA) the opportunity to have biological offspring in cases where mature spermatozoa are not detected. However, the clinical outcomes of ROSI remains poor. This study compares the outcomes of ROSI with intracytoplasmic sperm injection (ICSI) and investigates the effect of hormonal pretreatment. This retrospective cohort study enrolled infertile couples undergoing either ROSI or ICSI at the reproductive center in Taipei Veterans General Hospital. The administration of selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors in male patients were collected. Relevant hormonal markers and biochemical parameters were determined. The outcomes of ROSI and ICSI were assessed based on fertilization rate, implantation rate, and live birth rate. A total of 36 couples were recruited in the ROSI group, whereas 39 couples were recruited in the ICSI group for the analysis. Patients in each group demonstrated similar characteristics, except for a higher proportion of male patients in the ROSI group who were pretreated with anastrozole. The fertilization rate and implantation rate were similar between ROSI and ICSI groups after adjusting for confounding variable. The live birth rate was significant lower in the ROSI group (8.3%) than in the ICSI group (30.8%) before and after adjusting for confounding variable. ROSI demonstrated fertilization and implantation rates comparable to those of ICSI for male patient with NOA undergoing testicular sperm extraction surgery. Further studies evaluating the effect of anastrozole administration on ROSI outcomes are warrant.

Cryopreservation of human spermatozoa or testicular tissue for fertility preservation

Loss of reproductive capacity due to treatments for malignant or non-malignant diseases or even as aresult of diseases themselves significantly impacts patients' quality of life. Cryopreservation of sperm from ejaculate is awell-established procedure for preserving the fertility of these patients and thus improving their quality of life in the long term. If cryopreservation of sperm from ejaculate is not possible, either because ejaculation cannot occur or no sperm can be found in the ejaculate, the preferred treatment option is (microsurgical) testicular sperm extraction (mTESE). Testicular sperm and ejaculated spermatozoa can be cryopreserved and later used for intracytoplasmic sperm injection (ICSI) treatment. The use of cryopreserved sperm for fertility treatment does not carry an increased risk of malformations in the offspring. If gonadotoxic therapy is necessary in pre- or early pubertal boys, the only option to preserve fertility in the long term is to cryopreserve spermatogonial stem cells from testicular tissue as part of the Androprotect© network. This is an experimental approach which has been available since 2012 acrossGermany and which is accompanied by intensive scientific work ( www.androprotect.de ).

A method for determining potential parental contamination: linkage disequilibrium-based log-likelihood ratio analysis for IVF-PGT

BackgroundAt present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.MethodsIn this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.ResultsWith IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.ConclusionsIn this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

Progestin-primed ovarian stimulation outcomes in in-vitro fertilization (IVF) – 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.

Study on the influence of the sY1192 gene locus in the AZFb/c region on sperm quality and pregnancy outcome.

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.

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.

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

BackgroundMelatonin, 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.MethodsWe 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.ResultsOur 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).ConclusionsMelatonin levels in DOR patients may impact embryo quality, offering insights into potential DOR pathogenesis and opportunities to enhance treatment outcomes in these patients.

Genetic diagnosis and outcomes of intracytoplasmic sperm injection in South Chinese patients with congenital bilateral aplasia of the vas deferens

BackgroundObstructive azoospermia commonly is caused by CBAVD(Congenital Bilateral Aplasia of the Vas Deferens), mainly due to the cystic fibrosis transmembrane conductance regulator (CFTR) and adhesion G protein-coupled receptor G2(ADGRG2) mutations. The genetic landscape for Chinese CBAVD patients is unclear, leading to debates over genetic screening, counseling, and assisted reproduction strategies. This study investigates the prevalence of CFTR and ADGRG2 mutations in a southern Chinese cohort of CBAVD patients and evaluates the impact of CFTR mutations on intracytoplasmic sperm injection (ICSI) outcomes.ResultsCFTR mutations were identified in 71.4% (30/42) of CBAVD patients, with a total of 36 CFTR mutation sites across 13 types identified, including two novel mutations. A novel ADGRG2 mutation was also detected. Betweenthe CFTR mutation-CBAVD group and the non-CBAVD OA group, a significant difference was observed only in the 2 Pronuclei(2PN) rate (79.5% vs 86.2%, P = 0.0065), while fertilization rates, pregnancy rates, miscarriage rates, and live birth rates showed no significant differences. Between the CFTR mutation-CBAVD group and the CBAVD group without CFTR mutation, there were no significant differences in fertilization rates, 2PN rates, pregnancy rates, miscarriage rates, or live birth rates.ConclusionChinese CBAVD patients primarily exhibit mutations in the CFTR and ADGRG2 genes. Therefore, targeted gene testing for CFTR and ADGRG2 is more suitable compared to WES for CBAVD patients. Considering that the genetic factors of approximately 30% of CBAVD patients remain unknown, it is recommended to perform massive parallel sequencing for patients who test negative for CFTR and ADGRG2 gene screening. Despite these genetic factors, ICSI outcomes were not adversely affected, except for the 2PN rate. However, genetic counseling remains crucial for Chinese CBAVD patients before undergoing assisted reproduction.

Altered metabolic profiles in male offspring conceived from intracytoplasmic sperm injection

BackgroundWhile 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.MethodsWe 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).ResultsA 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).ConclusionsThe 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.

Comparison of Recombinant Cumulase with Bovine Derived Hyaluronidase for Oocyte Denudation before ICSI in Sibling Oocytes

Assisted Reproductive Technology (ART) with Intra-cytoplasmic Sperm Injection (ICSI) commonly utilizes Bovine-Derived Hyaluronidase for oocyte denudation. The emergence of Recombinant Cumulase as an alternative merit an examination of its impact upon ICSI outcomes. We compared the effects of Recombinant Cumulase and Bovine-Derived Hyaluronidase on oocyte denudation during ICSI, investigating impact upon fertilization rates, blastulation rates, and euploidy rates, aiming to improve clinical practice and optimize ART for patient outcomes. This was a retrospective observational study involving 59 patients undergoing ICSI conducted at First IVF Fertility Centre, Abu Dhabi, United Arab Emirates. Oocytes from each patient were divided one group which employed Recombinant Cumulase, and the other group utilised Bovine-Derived hyaluronidase. Parameters such as age, number of oocytes retrieved, denudation outcomes, and euploidy rates were assessed to determine enzyme impact. Comparative analysis revealed no substantial difference in fertilisation rates or embryo development (blastocyst rate) between recombinant Cumulase and bovine-derived Hyaluronidase. However, the recombinant Cumulase group exhibited significantly higher (p&lt;0.05) rates of normal euploid embryos (Recombinant Cumulase-48.5%; Bovine Derived Hyaluronidase- 38.0%), indicating a potential advantage. However, the results are from small cohort and need to be validated with large sample size. Selecting enzymes for ART procedures is challenging. Although no significant differences were observed in fertilisation rates, the Recombinant Cumulase group treated oocytes exhibited yielding higher normal euploid embryo rates. Not many studies have looked at the Euploidy rates with use of different enzymes for oocyte denudation. Further investigations are essential to refine best practices and advance patient outcomes in assisted reproduction.

Future prospects for the advancement of treatment of men with NOA: focus on gene editing, artificial sperm, stem cells, and use of imaging.

Nonobstructive azoospermia (NOA) affects about 60% of men with azoospermia, representing a severe form of male infertility. The current approach to manage NOA primarily involves testicular sperm retrieval methods such as conventional testicular sperm extraction (c-TESE) and microdissection testicular sperm extraction (micro-TESE). While combining testicular sperm retrieval with intracytoplasmic sperm injection (ICSI) offers hope for patients, the overall sperm retrieval rate (SRR) stands at around 50%. In cases where micro-TESE fails to retrieve sperm, limited options, like donor sperm or adoption, can be problematic in certain cultural contexts. This paper delves into prospective treatments for NOA management. Gene editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9), hold potential for correcting genetic mutations underlying testicular dysfunction. However, these technologies face challenges due to their complexity, potential off-target effects, ethical concerns, and affordability. This calls for research to address key challenges associated with NOA management within the clinical settings. This also necessitate ongoing research essential for developing more sensitive diagnostic tests, validating novel treatments, and customizing current treatment strategies for individual patients. This review concluded that the future of NOA management may entail a combination of these treatment options, tailored to each patient's unique circumstances, providing a comprehensive approach to address NOA challenges.

Correlation of adenomyosis features to live birth rates after the first IVF/ICSI treatment, when using the revised Morphological Uterus Sonographic Assessment group definitions.

Data regarding the impact of adenomyosis on the outcomes after invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment are conflicting. Standardized diagnostic criteria are prerequisites for studying a potential association between adenomyosis and IVF/ICSI treatment outcomes. This study aims to examine the cumulative live birth rate (CLBR) after the first IVF/ICSI treatment in women with or without direct or indirect features of adenomyosis, using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions. This was a prospective cohort study of 1037 women aged 25-≤39 years, undergoing their first IVF/ICSI treatment between January 2019 and October 2022. The presence of MUSA features of adenomyosis was assessed prior to treatment start. The CLBR after the first IVF/ICSI treatment was 424/1037 (40.9%, 95% CI, 37.9-43.8) in the total cohort. Women with direct features of adenomyosis had lower CLBR, 25/102 (24.5%; 95% CI, 17.5-31.5) than women without, 399/935 (42.7%; 95% CI, 39.5-45.8), p < 0.001. The adjusted relative risk (aRR) for live birth for women with direct features of adenomyosis compared to women without was 0.62 (95% CI, 0.43-0.88), p = 0.007. Direct features were associated with a higher risk of miscarriage after frozen embryo transfer, aRR 2.88 (95% CI, 1.49-5.57), p = 0.002. Women with indirect features had a lower CLBR [50/188 (26.6%, 95% CI, 20.3-32.9)] than women without [399/935, (42.7%, 95% CI, 39.5-45.8)], aRR 0.58 (95% CI, 0.45-0.75), p < 0.001. For features located in the inner myometrium, the aRR for live birth was 0.29 (95% CI 0.11-0.74), p = 0.010 and for the outer myometrium 2.61 (95% CI 1.42-4.8), p = 0.002. An interrupted junctional zone was the single feature that impacted CLBR the most. The presence of direct or indirect MUSA features of adenomyosis correlates to reduced live birth rates in women undergoing their first IVF/ICSI treatment. Features located in the inner myometrium, particularly an interrupted junctional zone, reduced the chance of live birth the most, whereas location in the outer myometrium was associated with higher chances of live birth. Systematic ultrasound examinations should be considered for women scheduled for IVF/ICSI treatment, for adequate counseling on the chances of successful treatment.

A Scoping Review: Risk of Autism in Children Born from Assisted Reproductive Technology

Background/Objectives: As the incidence of autism spectrum disorder (ASD) and use of assisted reproductive technologies (ART) continue to rise in tandem, their relationship to one another, as well as the general risks of ART, are increasingly being explored. The purpose of this review is to summarize the literature on ASD risk, as well as the risks for other neurological and neurodevelopmental disorders, in children born following the implementation of ART. Methods: Here we review studies published between 2000−2023 that elucidate relationships between ASD and some of the most common forms of ART, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), using fresh vs. frozen embryo transfer. Articles were identified by searching Google Scholar and PubMed databases. Results: Though some studies report adverse neurodevelopmental outcomes in ART-conceived children, such as ASD, attention-deficit/hyperactivity disorder (ADHD), and cerebral palsy, a majority of studies do not show a significant association between ART and neurodevelopmental disorders. Additionally, many confounding factors like multiple and preterm births, underlying infertility, and advanced parental age have been discussed, highlighting the need for studies that effectively control for these confounders. Potential mechanisms implicated in the pathogenesis of ASD, including epigenetic mechanisms of gene expression, that may be related to ART procedures, are also discussed. Conclusion: ART may pose a low additional risk to development of ASD, but confounding factors likely account for most of this risk. Several steps in the process of ART may cause epigenetic changes that are implicated in the development of ASD.

The Effect of the Gonadotropin Dose Increment During Controlled Ovarian Hyperstimulation on Live Birth Rates of POSEIDON Group 3-4 Patients

This retrospective study seeks to explore whether modifying the gonadotropin dose in cases of poor ovarian response during controlled ovarian hyperstimulation contributes to improved live birth rates in Poseidon Group 3-4 patients. The study took place at a tertiary level university. The electronic database spanning 2012-2021 was scrutinized to identify patients with diminished ovarian reserve (DOR) who underwent intra-cytoplasmic sperm injection – embryo transfer (ICSI-ET). Diminished ovarian reserve was determined using the POSEIDON criteria. Patients were categorized into two groups based on whether dose adjustment was implemented during the initial ultrasound assessment in controlled ovarian hyperstimulation (COH). There were 188 patients in the dose adjustment (DA) group and 310 patients in the fixed-dose (FD) group. The demographic parameters were similar between the groups. The started gonadotropin dose was similar in both groups (300 IU). The median dose adjustment on the first control was +75 IU in the DA group. The follicle output rates, follicle to oocyte indexes, and the embryology parameters were comparable between the groups. The positive pregnancy rate was 19.7% (36/188) in the DA group vs. 19.1% (61/310) in the FD Group (p=0.4). The primary outcome of the study; live birth rates were 12% in the DA group vs. 9% in the FD group, and the results were statistically similar (p=0.3). Our research revealed that adjusting the gonadotropin dose in cases of inadequate ovarian response during COH results in comparable live birth rates to those observed in the fixed-dose group. For patients exhibiting an inadequate response, dose adjustment may be deemed necessary.

Short-Term Metformin Therapy in Clomiphene Citrate Resistant PCOS Patients Improves Fertility Outcome by Regulating Follicular Fluid Redox Balance: A Case-Controlled Study.

To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Fifty-eight patients aged 23-34 who were planned to have intracytoplasmic sperm injection due to clomiphene citrate-resistant PCOS were included in the study. Participants were divided into two groups according to whether they used metformin or not. While 30 of 58 PCOS patients were using short-term metformin in combination with controlled ovarian stimulation, 28 PCOS patients were not using metformin. Metformin was started in the mid-luteal period and continued until the day before oocyte retrieval at 850 mg twice daily. To determine FF-NF-kB, TAS, TOS and OSI values, a dominant follicle ≥17-18 mm in diameter was selected for aspiration. The number of mature follicles and fertilization rates of the metformin group were significantly higher than those not taking metformin. FF-TOS and OSI of the metformin group were significantly lower than those of the group not receiving metformin. Patients receiving metformin had higher FF-TAS than the group not receiving metformin. FF-NF-kB levels of the metformin group were significantly lower than the group not receiving metformin. Insulin resistance, FF-NF-kB and FF-TOS were negatively correlated with the number of mature oocytes. FF-TAS was positively correlated with the number of oocytes. Short-term metformin treatment in clomiphene-resistant PCOS improves the number of mature follicles and fertilization rates by regulating the intra-follicle redox balance.

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

BackgroundObesity 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.MethodsWe 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.ResultsAnti-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.ConclusionsAn 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.

Neurodevelopmental or behavioural disorders in children conceived after assisted reproductive technologies: A nationwide cohort study

To study differences in risk for drug-treated neurodevelopmental or behavioural disorders in children conceived through assisted reproductive technologies in comparison with children conceived without assisted reproductive technologies and to examine if different treatments alter these risks. Nationwide registry-based cohort study. Liveborn children born in Denmark between 1994 and 2012 after assisted reproductive technologies in comparison to children conceived without assisted reproductive technologies aged 0-7. Conception following assisted reproductive technologies treatment, including in vitro fertilisation, intra-cytoplasmic sperm injection, intrauterine insemination and 'others' comprising frozen embryo transfer, and frozen embryo transfer in both in vitro fertilisation and intra-cytoplasmic sperm injection and testicular sperm aspiration. Prescription of neurodevelopmental or behavioural disorders medication in offspring: Antipsychotics, anxiolytics, antidepressants, antiepileptics, attention deficit hyperactivity disorder medication and hypnotics/sedatives obtained from nationwide registers. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated. The association was examined in different sensitivity analyses, including sibling and mediator analyses. In total, 57,964 (4.7%) children conceived after assisted reproductive technologies and 1,183,070 (95.3%) children not conceived using assisted reproductive technologies were included. The adjusted analysis showed higher odds of prescribing neurodevelopmental or behavioural medication to assisted reproductive technology-conceived children (OR 1.15; 95% Cl 1.09-1.20) compared to other children. Prescription of antipsychotics in assisted reproductive technology-conceived children was the most common association in intrauterine insemination treatments, hypnotics/sedatives with both including in vitro fertilisation and intra-cytoplasmic sperm injection and antiepileptics with 'other' treatments. Birth weight partially mediated the association between assisted reproductive technologies and diminished the odds of neurodevelopmental or behavioural medication use in children conceived using assisted reproductive technologies. Sibling analysis showed no increased risk for the first-born child conceived without assisted reproductive technology vs. the second-born child conceived with assisted reproductive technology and vice-versa. Based on the minor observed effects, a potentially higher increased attentiveness of assisted reproductive technology parents, the demonstrated mediation effect of birth weight and preterm birth on the observed association, and the no effect of the within-mother analysis, we find little evidence for increased risk of neurodevelopmental or behavioural disorders in children conceived using assisted reproductive technologies.