Improve Fertility Outcomes Research Articles

The Impact of Laparoscopic Treatment on Fertility Outcomes in Patients with Severe Endometriosis

Background: Endometriosis, a prevalent gynecological disorder affecting women of reproductive age, is a significant cause of infertility, especially in severe cases involving extensive adhesions, endometriomas, and deep infiltrating lesions. In Bangladesh, the delay in diagnosis and limited access to advanced treatments, including laparoscopic surgery, poses challenges to improving fertility outcomes for women with severe endometriosis. Objective: This study aimed to assess the impact of laparoscopic treatment on fertility outcomes in patients with severe endometriosis, particularly in a resource-limited healthcare setting in Bangladesh. Methods: This retrospective cohort study included 78 women with severe endometriosis from tertiary hospitals in Dhaka and Khulna, Bangladesh. All participants had previously experienced unsuccessful in vitro fertilization (IVF) attempts and subsequently underwent laparoscopic surgery between 2015 and 2024. Data collection involved reviewing primary and secondary data from these tertiary hospitals, including medical records and operative reports, and was supplemented by follow-up interviews for comprehensive analysis. Variables such as patient age, infertility duration, previous IVF cycles, operative findings, and postoperative fertility outcomes were analyzed using SPSS, with statistical significance set at P < .05. Results: The mean age of patients was 34.3 years, and the average duration of infertility was 52.9 months. Post-laparoscopic surgery, 42.3% (33/78) of women successfully delivered, with 7% achieving spontaneous conception. Younger age, fewer prior IVF cycles, and a normal uterine appearance on transvaginal ultrasound were significantly associated with improved fertility outcomes. Salpingectomy was more common among those who delivered (70%), though the removal of ovarian endometriomas did not significantly impact fertility success. Conclusion: Laparoscopic treatment significantly improves fertility outcomes in Bangladeshi women with severe endometriosis, even in a resource-limited setting. Age, normal ovarian function, and uterine appearance were key factors influencing reproductive success. These findings underscore the importance of timely surgical intervention for endometriosis-related infertility, highlighting the need for improved access to laparoscopic surgery in low-resource healthcare systems.

Surgical Technique and Fertility Outcomes: A Comprehensive Review of Open and Laparoscopic Cystectomy in Women of Reproductive Age.

Cystectomy, the surgical removal of ovarian tissue, is commonly performed in women of reproductive age to address conditions such as ovarian cysts, endometriosis, and tumors. The choice of surgical technique, open versus laparoscopic, has significant implications for postoperative recovery and long-term fertility outcomes. This comprehensive review aims to evaluate the current literature on the effects of these two surgical approaches on fertility in women of reproductive age. Open cystectomy, while effective, is associated with larger incisions, increased trauma to surrounding reproductive structures, and a higher incidence of postoperative complications, which may negatively impact future fertility. In contrast, laparoscopic cystectomy offers a minimally invasive option that generally results in less postoperative pain, quicker recovery, and potentially improved fertility outcomes due to reduced damage to surrounding tissues. However, the literature reveals a complex interplay between surgical technique, underlying medical conditions, and individual patient factors that can influence reproductive potential. This review synthesizes key studies comparing the fertility outcomes of both surgical methods, highlighting the need for individualized surgical planning based on each patient's unique circumstances and reproductive goals. Additionally, it discusses the importance of preoperative counseling and multidisciplinary approaches to optimize patient outcomes. Future research is essential to further clarify the long-term fertility implications of open and laparoscopic cystectomy and to refine surgical techniques to enhance reproductive health. This review contributes to the growing body of evidence guiding clinicians in making informed decisions that prioritize the effective treatment of ovarian pathology and fertility preservation.

Revolutionizing Reproductive Medicine: A Comprehensive Literature Review on Mesenchymal Stem Cells and Their Potential in Enhancing Endometrial Receptivity for Improved Fertility Outcomes

Revolutionizing Reproductive Medicine: A Comprehensive Literature Review on Mesenchymal Stem Cells and Their Potential in Enhancing Endometrial Receptivity for Improved Fertility Outcomes

Preconception and Early-Pregnancy Body Mass Index in Women and Men, Time to Pregnancy, and Risk of Miscarriage

Obesity in women is associated with reduced fertility and an increased risk of miscarriage. These associations might also be present across the full range of body mass index (BMI) categories as well as among men. To investigate the associations of preconception BMI in both partners with time to pregnancy and miscarriage. This population-based prospective cohort study was conducted in Rotterdam, the Netherlands, between August 9, 2017, and July 1, 2021. A total of 3604 women and their partners were included from the preconception period onward with follow-up until birth. The date of analysis was July 12, 2024. Body mass index (calculated as weight in kilograms divided by height in meters squared) measured in preconception or early pregnancy. Fecundability, defined as the probability of conceiving within 1 month; subfertility, defined as time to pregnancy or duration of actively pursuing pregnancy of more than 12 months or use of assisted reproductive technology; and miscarriage, defined as pregnancy loss before 22 weeks of gestation. These measures were assessed using questionnaires and via the obstetric caregiver. The study population for time-to-pregnancy analyses consisted of 3033 episodes among women (median age, 31.6 years [IQR, 29.2-34.5 years]; median BMI, 23.5 [IQR, 21.2-26.5]) and 2288 episodes among men (median age, 33.4 years [IQR, 30.5-36.8 years]; median BMI, 24.9 [IQR, 23.0-27.4]). The study population for miscarriage analyses consisted of 2770 pregnancy episodes among women (median age, 31.5 years [IQR, 28.9-34.3 years]; median BMI, 23.5 [IQR, 21.3-26.7]) and 2189 pregnancy episodes among men (median age, 33.5 years [IQR, 30.4-36.8 years]; median BMI, 25.0 [IQR, 23.0-27.5]). Higher BMI in women and men was associated with lower fecundability: for every unit increase in BMI, fecundability decreased (fecundability ratio [FR]: women, 0.98 [95% CI, 0.97-0.99]; men, 0.99 [95% CI, 0.98-1.00]). Women with overweight (FR, 0.88 [95% CI, 0.80-0.98]) and obesity (FR, 0.72 [95% CI, 0.63-0.82]) had lower fecundability compared with women with normal weight. Compared with normal weight in women, underweight (odds ratio [OR], 1.88 [95% CI, 1.22-2.88]), overweight (OR, 1.35 [95% CI, 1.11-1.63]), and obesity (OR, 1.67 [95% CI, 1.30-2.13]) were associated with increased odds of subfertility. In men, obesity was associated with increased odds of subfertility (OR, 1.69 [95% CI, 1.24-2.31]). Compared with normal weight in women, overweight (OR, 1.49 [95% CI, 1.12-1.98]) and obesity (OR, 1.44 [95% CI, 1.00-2.08]) were associated with increased odds of miscarriage. In this cohort study, BMI outside of the normal category in women and men during the preconception or early-pregnancy periods was associated with time to pregnancy and miscarriage. Optimizing BMI in women and men from the preconception period onward might be an important strategy to improve fertility outcomes.

Luteal Phase Defects and Progesterone Supplementation

Importance: Luteal phase defects (LPDs), or an insufficiency of progesterone production during the luteal phase of the menstrual cycle, have been identified as a potential cause of recurrent pregnancy loss (RPL), but its exact contribution to RPL is not well-defined. In addition, the role of exogenous progesterone supplementation during pregnancy remains controversial. Objective: The goal of this review is to provide an updated, evidence-based summary of LPD, including prevalence and potential pathophysiologic mechanisms, and to explore the current controversies regarding progesterone supplementation for management and treatment of RPL. Evidence Acquisition: A literature review identified relevant research using a PubMed search, Cochrane summaries, review articles, textbook chapters, databases, and society guidelines. Results: Endogenous progesterone plays a crucial role in the first trimester of pregnancy, and therefore, insufficiency may contribute to RPL. However, the precise relationship between LPD and RPL remains unclear. LPD is primarily a clinical diagnosis based on a luteal phase less than 10 days. Although there may be a possibility of incorporating a combined clinical and biochemical approach in defining LPD, the current lack of validated diagnostic criteria creates a challenge for its routine incorporation in the workup of infertility. Moreover, no treatment modality has demonstrated efficacy in improving fertility outcomes for LPD patients, including progesterone supplementation, whose inconsistent data do not sufficiently support its routine use, despite its minimal risk. It is imperative that women diagnosed with LPD should be worked up for other potential conditions that may contribute to a shortened luteal phase. Future work needs to focus on identifying a reproducible diagnostic test for LPD to guide treatment. Conclusions and Relevance: Currently, the perceived relationship between LPD and RPL is challenged by conflicting data. Therefore, patients with an abnormal luteal phase should undergo a thorough workup to address any other potential etiologies. Although supplemental progesterone is commonly used for treatment of LPD and RPL, inconsistent supporting data call for exogenous hormone therapy to be only used in a research setting or after a thorough discussion of its shortcomings.

Reproductive Outcomes After Hysteroscopic Adhesiolysis in Patients Experiencing Recurrent Pregnancy Loss and Intrauterine Adhesions

ObjectiveThis study aims to evaluate the reproductive outcomes after hysteroscopic adhesiolysis in patients experiencing recurrent pregnancy loss (RPL) combined with intrauterine adhesions (IUA). DesignSingle-center retrospective cohort study. SettingInternational referral hospital for women with IUA and RPL. PatientsBetween January 2018 and June 2022, a cohort of 64 women diagnosed with RPL and IUA were studied, with a follow-up period of at least one year after hysteroscopic adhesiolysis. InterventionsAll patients had a diagnosis of IUA from the diagnostic hysteroscopy and were treated with hysteroscopic adhesiolysis, utilizing intraoperative ultrasound monitoring as required. Main MeasurementsLive birth rate and menstrual pattern change (subjective assessment) after hysteroscopic adhesiolysis. ResultsIn our cohort, 59.38% (38/64) achieved pregnancy following hysteroscopic adhesiolysis, with 92.11% (35/38) conceiving within two years of the procedure. The miscarriage rate was recorded at 17.19% (11/64), and the live birth rate stood at 42.19% (27/64). Throughout the extended follow-up period, 64.06% (41/64) of the patients reported increased menstrual blood volume and improvements in menstrual patterns posthysteroscopic adhesiolysis. Univariate analysis indicated that being aged ≥35 years (p = .026), having a history of infertility (p = .003), the presence of moderate or severe IUA (p = .023), and experiencing menstrual improvements postsurgery (p = .001) were independent predictors of live birth. Multivariate analysis further identified that women with a history of infertility had a reduced chance of live birth following hysteroscopic adhesiolysis (p = .008), while those who reported menstrual pattern improvements postoperatively had an increased probability of achieving a live birth (p = .031). ConclusionsOur findings indicate that RPL and IUA patients without prior infertility and showing menstrual pattern improvement after hysteroscopic adhesiolysis, are more likely to achieve live births. Standardized hysteroscopic treatment, postoperative antiadhesion care, and early pregnancy planning are key to improving fertility outcomes in these patients.

Hysteroscopic metroplasty: Ultrasound parameters to optimize fertility benefits?

IntroductionMetroplasty is a procedure used by some teams to correct certain uterine anomalies to improve fertility outcomes. Our goal was to evaluate hysteroscopic metroplasty in the management of nulliparous and infertile patients with a uterine anomalies. Material and methodsWe conducted a single-center, retrospective, observational study of women who underwent hysteroscopic metroplasty for infertility between January 1, 2015 and December 31, 2019. The primary endpoint was the occurrence of a live birth at 18 months post-surgery. The secondary endpoint was to identify predictive factors for the success of the procedure, in particular ultrasound criteria, and live-birth rate during total follow up. ResultsWe included 43 nulliparous patients with an average of 5.2±-2.4 years of primary infertility, including 84.2 % patients who had at least one IVF cycle prior to the surgery. The mean age was 37±5 years. The post-surgery live-birth rate was 27.9 % at 18 months and 53.5 % during the total postoperative follow-up (mean follow-up 4.5 ± 1 years). Pregnancies were obtained spontaneously after surgery for 8/28 (28.6 %) patients who were undergoing assisted reproduction technology before surgery. No intra- or postoperative complications were recorded. We did not identify any predictive ultrasound factors, pre- or postoperatively, for a live birth at 18 months post-surgery. DiscussionHysteroscopic metroplasty appears to improve the chances of a live birth in a population of nulliparous and infertile patients with at least one uterine pathology. Spontaneous pregnancy can occur after hysteroscopic metroplasty. The Congenital-Ultrasound-Malformation-by-Expert ultrasound criteria do not appear to be predictive of post-surgery outcomes.

Potential for Offspring with Varicocele and Pcos

Infertility affects a significant portion of couples worldwide, with 30% of cases attributed to male factors, 30% to female factors, 30% to both partners, and 10% to unknown causes. This study focuses on two common causes of infertility: varicocele in men and Polycystic Ovary Syndrome (PCOS) in women. Varicocele, characterized by the enlargement of veins within the scrotum, disrupts spermatogenesis by increasing testicular temperature, leading to poor sperm quality. PCOS, affecting 5-10% of women of reproductive age, is marked by excessive androgen levels, irregular menstruation, and obesity, significantly raising the risk of infertility. Through case studies and literature review, this research highlights the potential for individuals with varicocele or PCOS to achieve pregnancy with appropriate treatment. The study aims to explore the specific examination and treatment processes required for these conditions and to provide insights into improving fertility outcomes for affected individuals.

Comparison of clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with or without concurrent vas-deferens obstruction.

Microsurgical vasoepididymostomy is an effective surgical method for treating epididymal obstructive azoospermia but the surgical outcomes can be affected in some non-vasectomized epididymal obstructive azoospermia patients with concurrent vas-deferens obstruction. This study aimed to explore the clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas-deferens obstruction. Retrospective study. To explore the clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas-deferens obstruction, aiming to identify predictive factors for concurrent vas-deferens obstruction and evaluate the efficacy of microsurgical vasoepididymostomy in patients with epididymal obstructive azoospermia and concurrent short-segment vas-deferens obstruction. A retrospective analysis of 225 epididymal obstructive azoospermia cases was conducted at the First Affiliated Hospital of Fujian Medical University from November 2016 to March 2023. All patients underwent a comprehensive preoperative evaluation. During surgery, the vas deferens were assessed to determine the presence and extent of obstruction. Depending on the obstruction length, either a standard microsurgical vasoepididymostomy was performed, or the obstructed segment was resected followed by microsurgical vasoepididymostomy. If the remaining length post-resection was insufficient for anastomosis, the procedure was discontinued. Data on patient clinical characteristics, operative findings, and outcomes were collected and analyzed. Logistic regression was used to identify predictive factors for concurrent vas-deferens obstruction, and comparative analysis assessed patency and pregnancy rates between patients with and without concurrent vas-deferens obstruction. Of the 225 patients in the study, 77 (34.22%) presented with epididymal obstructive azoospermia and concurrent vas-deferens obstruction. Logistic regression analysis revealed that "the history of epididymitis" was a significant predictive factor for epididymal obstructive azoospermia patients with concurrent vas-deferens obstruction (odds ratio=9.06, p<0.001). The average length of vas deferens obstruction amenable to microsurgical vasoepididymostomy post-resection was 1.31±0.54cm (range from 0.50 to 2.50cm). In contrast, cases unsuitable for microsurgical vasoepididymostomy presented an average obstruction length of 15.26±5.79cm (p<0.001). The patency rates were 82.17% in epididymal obstructive azoospermia patients without concurrent vas-deferens obstruction and 74.14% in those with concurrent vas-deferens obstruction. The pregnancy rates followed a similar trend, at 34.11% and 34.48%, respectively. These differences were not statistically significant (p>0.05 for both). However, epididymal obstructive azoospermia patients with vas-deferens obstruction exhibited a decreased likelihood of bilateral microsurgical vasoepididymostomy (p<0.001). Our study identifies a noticeable occurrence of concurrent vas-deferens obstruction in non-vasectomized epididymal obstructive azoospermia patients, with approximately one-third of the cases (34.22%) exhibiting vas-deferens obstruction during surgical interventions. Notably, a small fraction (6.67%) of these individuals chose not to proceed with any microsurgical vasoepididymostomy, even on one side, due to the extensive length of the obstruction. Through logistic analysis, we have demonstrated that "the history of epididymitis" is a critical predictive factor for the presence of vas-deferens obstruction, underscoring its significance in preoperative evaluations.Furthermore, our research confirms that microsurgical vasoepididymostomy is still an effective treatment for epididymal obstructive azoospermia patients with concurrent short-segment vas-deferens obstruction, achieving significant patency and favorable pregnancy rates compared to those patients without vas-deferens obstruction. These insights are pivotal for enhancing surgical strategies and improving fertility outcomes in this patient cohort.

Endometriosis: A Comprehensive Exploration of Inflammatory Mechanisms and Fertility Implications.

Endometriosis is a prevalent gynecological disorder characterized by the ectopic growth of endometrial-like tissue outside the uterus. This condition poses significant challenges due to its chronic nature, debilitating symptoms such as pelvic pain and infertility, and substantial impact on quality of life. Central to the pathogenesis of endometriosis are inflammatory mechanisms that perpetuate tissue proliferation, adhesion formation, and immune dysregulation within the pelvic cavity. Inflammation plays a pivotal role in the development and progression of endometriosis, influencing the severity of symptoms and complications associated with the disease. Dysregulated immune responses contribute to the persistence of ectopic endometrial implants, exacerbating pelvic pain and other symptoms experienced by affected individuals. Moreover, the inflammatory milieu created by endometriotic lesions disrupts normal ovarian function, impairs follicular development, and compromises reproductive outcomes, thereby posing challenges to fertility. This review comprehensively explores the inflammatory mechanisms underlying endometriosis and their implications for fertility. Synthesizing current research and clinical insights elucidates the intricate interplay between inflammation, disease progression, and reproductive health outcomes. Understanding these complex interactions is essential for developing targeted diagnostic strategies and optimizing therapeutic approaches tailored to alleviate symptoms and improve fertility outcomes in individuals with endometriosis. Ultimately, this review aims to enhance the understanding of endometriosis pathophysiology, inform clinical practice, and stimulate further research to advance personalized care and management strategies for this challenging condition.

Navigating the Microbial Landscape: Understanding Dysbiosis in Human Genital Tracts and Its Impact on Fertility.

Dysbiosis, an imbalance in microbial communities, significantly impacts the health and functionality of the human genital tract, with profound implications for fertility and reproductive health. This review explores the intricate relationship between genital tract microbiota and reproductive outcomes, highlighting the composition and dynamics of these microbial communities in both females and males. In females, the vaginal microbiota, primarily dominated by Lactobacillus species, is essential for maintaining a healthy vaginal environment, preventing infections, and supporting reproductive functions. In males, the genital microbiota influences sperm quality and reproductive health. Dysbiosis in the genital tract, manifesting as bacterial vaginosis, yeast infections, urethritis, or prostatitis, disrupts these microbial communities, leading to adverse reproductive outcomes such as infertility, pregnancy, and increased susceptibility to sexually transmitted infections. This review delves into the mechanisms through which dysbiosis affects fertility, including alterations in vaginal pH, mucosal immunity, inflammation, sperm viability, and motility. It also evaluates diagnostic methods, clinical implications, and management strategies, including probiotics, prebiotics, antibiotics, antifungal treatments, lifestyle interventions, and emerging therapeutic approaches. By understanding the microbial landscape of the genital tract and its impact on fertility, this review aims to inform targeted interventions that restore microbial balance and enhance reproductive health, ultimately improving fertility outcomes and the potential for healthy pregnancies.

Reproductive Ageing: Declining translational capacity as a potential driver for oocyte meiotic instability.

This point of view article focuses on the potential contribution of defects in protein synthesis (translation) to the incidence of oocyte meiotic failure. We discuss the potential cause of diminished oocyte translation during aging and the impact of these deficits on the function of the meiotic spindle. Errors during female meiosis lead to embryonic aneuploidy and miscarriage and occur with increasing frequency during aging. The underlying molecular changes that drive female meiotic instability remain a subject of debate. Developing oocytes undergo a tremendous increase in cytoplasmic volume over several months of follicle development and rely on long-lived mRNAs and ribosomes accumulated during this growth phase for subsequent meiotic maturation. In this point of view article, we discuss how the unique reliance on stores of long-lived mRNAs and ribosomes may represent an Achilles' heel for oocyte function and how alterations that reduce the translational capacity of oocytes could be a factor significantly contributing to female infertility. Understanding these mechanisms could lead to new therapeutic strategies to improve fertility outcomes.

Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis

BackgroundMale factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy.ObjectiveWe aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis.MethodsWe searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI).ResultsWe included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78–3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23–4.62), tamoxifen (SMD − 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD − 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44–2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo.ConclusionThere is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men.PROSPEROCRD42023430179.

O-058 Newly identified female mutations causing oocyte maturation defect and embryo developmental arrest

Abstract Female infertility is a complex issue affecting a significant number of women. In the United States, among married women aged 15–49 years with no prior births, approximately one in five (19%) were unable to get pregnant after one year of trying. In addition, approximately one in four (26%) women in this group had difficulty getting pregnant or carrying a pregnancy to term. For women under 35 years of age, infertility is defined as a lack of success within one year, while for women aged 35 and older, it is within six months. Various factors, such as genetic, endocrine, physiological, anatomical, and immunological irregularities within the reproductive system, can affect a woman's chances of achieving pregnancy and delivering a healthy child. Among these factors, oocyte maturation is an important prerequisite for successful fertilization and subsequent embryonic development. In Medically Assisted Reproduction (MAR), the meiotic maturation of oocytes is induced by human chorionic gonadotropin (hCG) injection, which mimics the natural endogenous luteinizing hormone (LH) surge during the menstrual cycle. Although it is common for a few oocytes to remain immature despite ovarian stimulation and hCG administration, generally, immature oocytes have the competency to spontaneously mature in vitro. However, oocyte maturation is a sophisticated process involving multiple genes or protein molecules. Therefore, pathogenic variations in the genomic sequence or functional defects in any molecule that affects meiosis may lead to impaired oocyte maturation. While complete failure of all oocytes to mature in vivo is extremely rare, understanding the molecular aetiology of oocyte maturation is crucial for addressing infertility issues related to this process and improving fertility outcomes. The transition from the cleavage to the blastocyst stage often represents a significant bottleneck, with nearly 10% of fertilized eggs arrested at the cleavage stages. Developmental arrest of the preimplantation embryo is characterized by the cessation of cellular division for at least 24 h. Various factors originating from both embryonic and parental sources contribute to arrest of early stage embryo development. The genetic roots of developmental arrest were examined by considering both the parental causes of infertility and factors within the embryo. Examination revealed shared elements, regardless of the source of origin. Chromosomal abnormalities, abnormal preimplantation development, and monogenic variations have been reported to cause embryonic developmental arrests. Recently, deficiencies in oocyte maturation and embryo development have been categorized as part of the oocyte/zygote/embryo arrest (OZEMA) phenotype in the Online Mendelian Inheritance in Man (OMIM) database. A latest extensive review of monogenic causes associated with female infertility identified 23 genes with a total of 27 gene disease relationships (GDRs) for the OZEMA phenotype. Seventeen GDRs were classified as having at least moderate evidence of involvement in OZEMA, in addition to ten GDRs with less substantial evidence. Several additional genes were subsequently identified. This presentation will provide an overview of gene defects linked to the OZEMA phenotype, discuss the current status and future prospects of pre-MAR screening of females with OZEMA, and assess a novel workflow for modern genetic diagnosis to maximize the benefit of the patient.

O-319 A randomised trial of time-lapse imaging of embryos in in-vitro-fertilisation treatment

Abstract Study question Do time-lapse imaging (TLI) systems used in IVF/ICSI treatment improve live birth either due to undisturbed culture conditions or improved embryo selection or both? Summary answer In women undergoing IVF/ICSI treatment the use of TLI systems does not significantly increase the odds of live birth compared to standard care without TLI. What is known already TLI systems used in IVF treatment have the potential to improve fertility outcomes either due to undisturbed culture conditions or improved embryo selection or both. However, there remains uncertainty about its benefits. Existing reviews and primary studies predominantly report no differences between the use of TLI and conventional methods. However none of the previous trials were adequaltely powered to detect meaningful differences in live birth and the quality of most trials was deemed to be low to very low. Study design, size, duration TILT (Time-lapse Imaging Trial) is a multi-centre, three-arm, parallel-group, double-blind, randomised controlled trial. Participants were randomly assigned in a 1:1:1 ratio to the TLI system for both undisturbed culture and embryo selection (TLI arm), TLI system for undisturbed culture conditions alone (undisturbed culture arm), and standard care without TLI (control arm). From June 2018 to September 2022, we randomised 1575 participants based on a pre-specified sample size to detect an 8.75% difference in live births. Participants/materials, setting, methods We randomised 1575 couples undergoing IVF/ICSI with broad inclusion criteria across seven IVF centres. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, pregnancy loss, and multiple pregnancy. Primary analysis was performed based on the intention-to-treat principle for all participants with primary outcome data available and the effect estimate reported as an adjusted odds ratio (aOR). Pre-specified sensitivity analyses and subgroup analyses for age and method of embryo transfer were performed. Main results and the role of chance We recruited 2191 and randomised 1575 participants. Live birth data were available for 1558/1575 (98.92%) participants. The livebirth rates were 33.7% (175/520) in the TLI arm, 36.6% (189/516) in the undisturbed culture arm and 33.0% (172/522) in the control arm. The aOR was 1.04 (97.5% confidence interval (CI) 0.73 to 1.47) for TLI arm vs control and 1.20 (97.5% CI 0.85 to 1.70) for undisturbed culture vs control. The clinical pregnancy rates were 42.2% (219/519) in the TLI arm, 43.4% (225/518) in the undisturbed culture arm, and 40.9% (212/519) in the control arm. There were no significant differences for TLI vs control arm (aOR 1.06, 95% CI 0.82-1.38) and undisturbed culture vs control arm (aOR 1.11, 95% CI 0.86-1.46). The rates of pregnancy loss between clinical pregnancy and 24 weeks’ gestation were not statistically different when TLI (8.7%, 45/515) and undisturbed culture arms (6.4%, 33/513) were compared with control arm (8.1%, 42/517) with aOR 1.09 (95% CI 0.66-1.77) and 0.76 (95% CI 0.45-1.29) respectively. None of the other secondary outcomes demonstrated significant differences between the arms The findings were similar irrespective of the woman’s age and use of fresh or frozen embryo replacement, and for all sensitivity analyses, for primary and secondary outcomes. Limitations, reasons for caution Although the trial recruitment was delayed by the SARS-CoV-2 pandemic, this did not impact the results as patient populations, clinical care pathways and time-lapse technology remained similar. The remit of this trial did not allow assessment of the influence of TLI systems on embryology laboratory workflow or perform a health-economic analysis. Wider implications of the findings Our trial provides high-quality definitive evidence of no benefit of the use of TLI systems for embryo incubation and selection to improve success rates in women having IVF and ICSI treatment. Trial registration number ISRCTN17792989

P-575 Application of biomarkers in obese infertile women: a genetic tool for a personalized treatment

Abstract Study question Investigate CART and Leptin gene expression, FSH Receptor Asn680Ser polymorphism, and reproductive hormones in patients suffering from obesity under 40, facing infertility, undergoing bariatric surgery. Summary answer The present study proposes that variations in CART, leptin expressions, and the Polymorphism Asn680Ser on the FSH Receptor, may influence the response to IVF treatment. What is known already Obesity, presents a multifaceted challenge with profound implications for fertility, particularly concerning hormonal disruptions in reproductive hormones. Research has shown that Asn680Ser polymorphism of FSH Receptor has a pivotal role in infertility. Notably identified as a singular factor sufficient for infertility, this polymorphism influences the response of the FSH receptor to follicle-stimulating hormone (FSH). Leptin activates the expression of CART neuropeptide, indicating a significant interplay between these two regulatory factors. In ovarian granulosa cells (GCs) of obese patients, elevated CART levels have been observed, with leptin stimulation increasing CART expression and subsequently inhibiting GC aromatase expression and steroidogenesis. Study design, size, duration A total of 29 women were included in the study. An hormonal profile along with a detection of CART and Leptin gene expression was evaluated before and after bariatric surgery. Additionally, the presence or absence of Asn680Ser of FSHR gene was studied. Participants/materials, setting, methods Participants had suffer from obesity and experiencing infertility, with a body mass index (BMI) equal to or greater than 40 kg/m². Only women below 40 were included. Blood samples were collected from all women before surgery and 6 months later. Total RNA was extracted from blood samples. To assess the gene expression of Leptin and CART, we utilized Real-time Polymerase Chain Reaction (RT-PCR). The FSHR polymorphism was detected by using the RFLP method. Main results and the role of chance Following bariatric surgery, a mean reduction in BMI (16.03 kg/m²) was observed in all women, reaching high statistical significance (p &amp;lt; 0.001). The intervention also yielded significant differences (p &amp;lt; 0.001) in hormone levels and gene expressions post-surgery, with FSH, LH, E2, and AMH displaying noteworthy variations. Further investigations explored associations between CART and leptin gene expression before and after the intervention, coupled with the detection of the Polymorphism Asn680Ser on the FSH Receptor. Elevated CART expression before treatment correlated with lower expression after treatment (rs = 0.51, p = 0.005), and a similar significant correlation was noted for leptin (rs = 0.75, p &amp;lt; 0.001). Genetic analysis revealed that 27.6% of patients were homozygous for the polymorphism, 44.8% were heterozygous, and it was absent in 27.6%. An ongoing statistical analysis is realized to establish a potential relationship between the presence/absence of the polymorphism and CART and Leptin expression. Limitations, reasons for caution The study’s limitations encompass a small patient cohort, exclusively pre- and post-bariatric surgery assessments. Expanding the sample to include diverse groups—infertile women with lower BMI and high BMI women without fertility issues—would enhance validity. Furthermore, examining gene expression in all participants one year post-surgery could provide valuable insights. Wider implications of the findings Our results underscores the positive impact of bariatric surgery on BMI decrease and possible link between surgical intervention, genetic markers, and hormonal alterations and consequently with infertility issues. These significant correlations may be applied for personalized therapeutic approaches, offering a valuable genetic tool for improved fertility outcomes in obese individuals. Trial registration number not applicable

Analysis of determinants of infertility among women at &lt;i&gt;in vitro&lt;/i&gt; fertilization clinic in Surabaya

In social life and global health, infertility is common. History of abdominal surgery, body mass index (BMI), endometriosis, menstrual history, and polycystic ovarian syndrome (PCOS) have not been fully explained as female infertility factors. This study examined infertility causes at ASHA in vitro fertilization Primasatya Husada Citra (PHC) Hospital Surabaya. This quantitative study was cross-sectional. In May-July 2023, 82 childbearing-age women with infertility issues visited the hospital and completed questionnaires. Description and analysis were performed using the Wilcoxon rank test to evaluate menstrual history, BMI, PCOS, endometriosis, and abdominal surgery history in relation to infertility. Infertility was statistically associated with abdominal surgery history (P=0.008), BMI (P=0.000), endometriosis diagnosis (P=0.000), and PCOS (P=0.000). Women with abdominal surgery, endometriosis, and PCOS had significant infertility. Women’s infertility can be caused by ovulation disorders, tubal and pelvic disorders, or uterine disorders, but one-third of cases are unexplained. Infertility treatment may benefit from addressing abdominal surgery history, BMI, endometriosis, and PCOS. Early intervention and targeted care based on these determinants may improve fertility outcomes and reduce unexplained infertility.

GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells.

Ovarian aging results in reactive oxygen species accumulation and mitochondrial deterioration. During the aging process, GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells. Ovarian aging critically influences reproductive potential, with a marked decrease in oocyte quality and quantity and an increase in oxidative stress and mitochondrial dysfunction. This study elucidates the role of guanine-rich RNA sequence binding factor 1 (GRSF1) in the aging of ovarian granulosa cells (GCs). We observed a significant reduction in GRSF1 within GCs correlating with patient age, utilizing clinical samples from IVF patients. Using an siRNA-mediated knockdown technique, we established that diminished GRSF1 expression exacerbates mitochondrial dysfunction, elevates reactive oxygen species, and impairs ATP production. Furthermore, RNA immunoprecipitation revealed GRSF1's interaction with superoxide dismutase 2 (SOD2) mRNA, a key antioxidant enzyme, suggesting a mechanism whereby GRSF1 modulates oxidative stress. Downregulation of SOD2 reversed the protective effects of GRSF1 overexpression on mitochondrial function. These insights into the role of GRSF1 in ovarian aging may guide the development of interventions to improve fertility outcomes in advanced age.

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries.

Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

The Impact of Conservative Surgical Treatment of Adenomyosis on Fertility and Perinatal Outcomes.

Adenomyosis is a benign condition commonly encountered in patients with infertility. While the definitive surgical management is hysterectomy, conservative surgical management is gaining attention in patients desiring future fertility. This review explores whether the surgical treatment of adenomyosis affects fertility outcomes for patients trying to conceive. The PubMed and Medline databases were searched using the keywords: "adenomyosis", "surgery", "radiofrequency", "infertility", "pregnancy", "sterility", "conception", "miscarriage", and "endometrial receptivity". Abstracts were screened, and relevant articles were selected for review. This review reveals that surgery appears to improve fertility outcomes with or without medical therapy; however, the risk of uterine rupture remains high and the best technique to reduce this risk is still not known. More studies are needed to formulate the best surgical approach for preserving fertility in treating adenomyosis and to establish standardized guidelines.