Fertility Outcomes Research Articles

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.

The Impact of Laparoscopic Surgery on Fertility Outcomes in Patients with Minimal/Mild Endometriosis.

Minimal/mild endometriosis (MME) is independently associated with reduced fecundity rates. In this review article, we discuss the role of laparoscopic surgery in enhancing the fertility outcomes of patients with MME. Laparoscopic management of MME enhances fecundity and increases the chances of spontaneous conception in appropriately selected cases. However, laparoscopy cannot be routinely recommended in asymptomatic patients with the sole purpose of diagnosing and treating potentially present MME. Equally, and based on existing information, the laparoscopic management of MME cannot be routinely recommended prior to in vitro fertilisation (IVF) attempts due to the lack of robust and beneficial evidence. Because an overlap between unexplained infertility and MME cases likely exists, the development of reliable, widely available, non-invasive tests for the diagnosis of MME may revolutionise the management of cases currently classified as unexplained infertility. In a disease as diverse as endometriosis, management decisions should be based on a multitude of factors. Future studies should focus on reporting the outcomes of interventions for MME on fertility and obstetric outcomes, clearly differentiating between disease stages and phenotypes.

Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies.

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.

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.

Weight Regain following Bariatric Surgery and in vitro Fertilization Outcomes

Introduction: The aim of this study was to estimate the time to pregnancy and live birth and evaluate the effect of weight regain in women with a history of bariatric surgery (BS) who underwent in vitro fertilization (IVF) treatments. Methods: This is a retrospective cohort study. All patients with previous BS who underwent IVF treatment in a tertiary university-affiliated hospital between 2013 and 2022 were included. Time to pregnancy and live birth were compared between patients who regained less than or greater than three points of body mass index (BMI) from the nadir weight after BS. Kaplan-Meier curves and log-rank tests were used to compare groups. Results: A total of 78 patients were included in this study. The positive β-hCG, clinical pregnancy, and live birth rates following BS were 89.4%, 78.9%, and 50.8%, respectively. The median time from the beginning of IVF treatments to a positive β-hCG test was 2.97 months (95% CI: 1.04–4.89 months), to a clinical pregnancy was 7.1 months (95% CI: 3.56–10.91), and to a live birth was 20.2 months. Women who maintained their nadir BMI following BS had nearly twice the chance of achieving a clinical pregnancy (HR 1.967, 95% CI: 1.026–3.771, p = 0.042) and were approximately three times more likely to achieve a live birth (2.864, 95% CI: 1.196–6.859, p = 0.018) than those who regained at least three points of BMI. Conclusion: Weight regain after BS is associated with a lower rate of live births and prolonged time to achieve clinical pregnancy and live birth.

Thinking in context: Fibroids-to-uterine volume ratio in pre-surgical fertility evaluation for intramural fibroids

ObjectiveTo explore the utility of the total fibroids-to-uterine volume (FTUV) ratio as a simple, preoperative tool to assist in counseling patients seeking pregnancy who are undergoing myomectomy for intramural (IM) fibroids. Study designThis is an historical cohort study on reproductive-aged patients seeking pregnancy who underwent laparotomic myomectomy for intramural fibroids from January 2017 to December 2021. Only G3 to G5 fibroids, according to the 2011 International Federation of Gynecology and Obstetrics (FIGO) classification, were included. Pre-operative transvaginal ultrasound (TVUS) was performed to measure the volume of intramural myomas (diameter1*diameter2*diameter3*0.52) and to calculate their total volume. The total fibroids-to-uterine volume (FTUV) ratio was calculated as the proportion of the uterine volume occupied by the sum of IM fibroids volumes. ResultsA total of 166 women with pre-surgical TVUS evaluation of IM fibroids were included, with a mean age of 36.22 ± 5.15 years. The FTUV ratio was identified as a positive predictor of clinical pregnancy after surgery (adjOR, 1.04; 95 % CI, 1.02–1.06; p = 0.0001), whereas age showed a negative association (adjOR, 0.90; 95 % CI, 0.83–0.98; p = 0.012). Endometrial cavity distortion prior to surgery was also positively associated with pregnancy post-surgery (adjOR, 3.50; 95 % CI, 1.51–8.08; p = 0.003). Consistent results were found for live births, with the FTUV ratio being a significant positive predictor of live birth after surgery (adjOR, 1.03; 95 % CI, 1.01–1.05; p = 0.001) and age showing a negative association (adjOR, 0.88; 95 % CI, 0.80–0.96; p = 0.004). Parity prior to surgery also positively impacted live birth post-surgery (adjOR, 2.65; 95 % CI, 1.30–5.40; p = 0.007). An FTUV ratio threshold of 53.39 % accurately predicted clinical pregnancy in 68.46 % of cases (sensitivity of 71.70 % and specificity of 66.67 %). For live births, a higher FTUV ratio threshold of 59.21 % predicted outcomes accurately in 69.13 % of cases (sensitivity of 65.85 % and specificity of 70.37 %). ConclusionThe use of the FTUV ratio in pre-operative ultrasound evaluation of IM fibroids may improve counseling for patients desiring to conceive after myomectomy. By providing a personalized assessment of the amount of myometrial volume occupied by fibroids, the FTUV ratio can help predict fertility outcomes after surgery, enabling better-informed decisions and treatment planning.

Anti-Müllerian hormone and fertility in women after childhood cancer treatment: Association with current infertility risk classifications.

To identify childhood cancer survivors (CCSs) at risk of premature ovarian insufficiency (POI) and impaired fertility is important given its impact on quality of life. The aim of this study was to assess ovarian markers and fertility outcomes in adult female CCSs. We used the Swedish and the PanCareLIFE classifications for infertility risk grouping. 167 CCSs, at median age 34.6 years (19.3-57.8) with a median follow-up time of 25.4 years (11.6-41.3), and 164 healthy matched controls were included in this cross-sectional study. We assessed anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), and fertility outcomes. Based on gonadotoxic treatments given, CCSs were categorized into infertility risk groups. The median levels of AMH, AFC and OV were lower in CCSs (1.9 vs. 2.1 ng/ml, 12.0 vs. 13.0, 6.8 vs. 8.0 cm3) compared with controls, although statistically significant only for OV (p = 0.021). AMH levels in CCSs <40 years were lower for those classified as high-risk (p = 0.034) and very high-risk (p<0.001) for infertility, based on the Swedish risk classification. Similarly, AFC was reduced in the high-risk (p<0.001) and the very high-risk groups (p = 0.003). CCSs of all ages showed a trend towards impaired fertility, especially in the very high-risk group. POI was diagnosed in 22/167 CCSs, of whom 14 were in the high- and very high-risk groups. The results according to the PanCareLIFE classification were similar. Both the Swedish and the PanCareLIFE infertility risk classifications are reliable tools for identifying those at risk of reduced ovarian markers and fertility, as well as POI. We recommend fertility preservation counselling for patients receiving highly gonadotoxic treatments (i.e., Cyclophosphamide Equivalent Dose ≥6 g/m2, radiotherapy exposure to ovaries or stem cell transplantation) with follow-up at a young reproductive age due to the risk of a shortened reproductive window.

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.

Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome.

The number of infertile couples undergoing in vitro fertilisation (IVF) has increased significantly. The efficacy of this procedure is contingent upon a multitude of factors, including gamete quality. One factor influencing gamete quality is oxidative stress, which leads to telomere damage and accelerates cellular ageing. Identifying new biomarkers that can predict the success of assisted reproduction techniques is a current relevant area of research. In this review, we discuss the potential role of SIRT1, a protein known to protect against oxidative stress and telomeres, which are responsible for genome stability, as biomarkers of gamete quality and assisted reproduction technique outcomes.

Melatonin alleviates palmitic acid-induced mitochondrial dysfunction by reducing oxidative stress and enhancing autophagy in bovine endometrial epithelial cells

BackgroundNegative energy balance (NEB) typically occurs in dairy cows after delivery. Cows with a high yield are more likely to experience significant NEB. This type of metabolic imbalance could cause ketosis, which is often accompanied by a decline in reproductive performance. However, the molecular mechanisms underlying NEB have yet to be fully elucidated. During excessive NEB, the body fat is extensively broken down, resulting in the abnormal accumulation of non-esterified fatty acids (NEFAs), represented by palmitic acid (PA), within the uterus. Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells (BEECs), while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs remains poorly understood. Melatonin (MT) is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species (mitoROS). However, little is known as to whether MT could ameliorate the damage incurred by BEECs in response to PA and the molecular mechanism involved.ResultsAnalysis showed that 0.2 mmol/L PA stress increased the level of cellular and mitochondrial oxidative stress, as indicated by increased reactive oxygen species (ROS) level. In addition, we observed mitochondrial dysfunction, including abnormal mitochondrial structure and respiratory function, along with a reduction in mitochondrial membrane potential and mitochondrial copy number, and the induction of apoptosis. Notably, we also observed the upregulation of autophagy proteins (PINK, Parkin, LC3B and Ubiquitin), however, the P62 protein was also increased. As we expected, 100 μmol/L of MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function. Meanwhile, MT pretreatment reversed the upregulation of P62 induced by PA and activated the AMPK-mTOR-Beclin-1 pathway, contributing to an increase of autophagy and decline apoptosis.ConclusionsOur findings indicate that PA can induce mitochondrial dysfunction and enhance autophagy in BEECs. In addition, MT is proved to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria by upregulating autophagy pathways, thereby safeguarding the mitochondrial pool and promoting cellular viability. Our study provides a better understanding of the molecular mechanisms underlying the effect of an excess of NEB on the fertility outcomes of high yielding dairy cows.

The Impact of Lead Exposure on Fertility, Infant Mortality, and Infant Birth Outcomes

The Impact of Lead Exposure on Fertility, Infant Mortality, and Infant Birth Outcomes

Effects of cyclophosphamide administration on ovarian dysfunction in pediatric patients with connective tissue diseases: A systematic scoping review.

This systematic scoping review assess the effect of cyclophosphamide (CY) administration during childhood on ovarian function in patients with juvenile-onset connective tissue diseases. A MEDLINE database search was conducted using terms related to CY, juvenile-onset connective tissue diseases, and ovarian function. Studies were included if they met specific criteria. The search, conducted on 28 November 2023, yielded 3328 references. After a two-stage screening process, six observational studies on systemic lupus erythematosus patients were included. All studies had a high risk of confounding bias, as none adjusted for confounding variables. Two studies assessing clinical ovarian dysfunction found no clear difference between CY and non-CY groups. However, statistical differences were observed in hormonal profiles. Decreased ovarian reserve was more frequent in CY-exposed patients. Two studies showed significantly higher follicle-stimulating hormone (FSH) levels in the CY group, while one showed a trend towards higher FSH levels without statistical significance. This review suggested that CY use in childhood may not conclusively have clinically significant effects on ovarian function. Further investigation needed on CY's effect on hormonal levels, fertility, and pregnancy outcomes.

Growth factor-loaded ovarian extracellular matrix hydrogels promote in vivo ovarian niche regeneration and enhance fertility in premature ovarian insufficiency preclinical models

Premature ovarian insufficiency (POI) means menopause before 40 years of age affecting about 1 % of women. Approaches based on cell therapy and the paracrine effects of stem cells or bioproducts such as platelet-rich plasma have been proposed, but concerns remain about undesired systemic effects, as well as the need to optimize delivery methods through bioengineering methods. This study explores the efficacy of decellularized bovine ovarian cortex extracellular matrix (OvaECM) hydrogels alone and as a growth factor (GF) carrier (OvaECM+GF) in a chemotherapy-induced POI murine model. In vitro assays showed a gradual release of GF from the OvaECM sustained for two weeks. Chemotherapy drastically reduced follicle numbers, but OvaECM+GF treatment restored pre-antral follicle development. Moreover, this treatment notably regenerated the ovarian microenvironment by increasing cell proliferation and microvessel density while reducing chemotherapy-induced apoptosis and fibrosis. Whole-ovary RNA sequencing and gene set enrichment analysis revealed an upregulation of regeneration-related genes and a downregulation of apoptotic pathways. The OvaECM+GF treatment also yielded significantly better outcomes following ovarian stimulation and in vitro fertilization. After two consecutive crossbreeding cycles, OvaECM+GF-treated mice showed normal reproductive function. This research showcases the biocompatibility and efficacy of OvaECM to reverse POI in mice, setting a foundation to explore innovative bioengineering-based POI therapies. Statement of significancePremature ovarian insufficiency (POI) affects about 1 % of women worldwide, causing early menopause before 40 years old. Current treatments alleviate symptoms but do not restore ovarian function. This study explores an innovative approach using ovarian cortex extracellular matrix hydrogels to deliver growth factors into the murine ovarian niche and reverse POI. In vitro release kinetic assays demonstrated a gradual and sustained release of growth factors. In a POI-induced mouse model, intraovarian injections of the hydrogel encapsulating growth factors restored pre-antral follicle development, increased cell proliferation, reduced apoptosis and fibrosis, and improved ovarian response and in vitro fertilization outcomes. Long-term benefits included larger litter sizes. This innovative technique shows promise in regenerating the ovarian environment and improving reproductive outcomes.

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.

Comparison of the effect of dydrogesterone and natural micronized progesterone for luteal-phase support in assisted reproductive technology cycles: A single-blind randomized clinical trial study.

One of the causes of preterm labor and recurrent abortion is progesterone deficiency in the luteal phase. The aim of the study was a comparison of the effect of oral dydrogesterone and vaginal progesterone for luteal-phase support (LPS) in assisted reproductive technology cycles (ART). This randomized clinical control trial study was conducted on 207 infertile women. Samples were randomly divided into two groups. The first group received a natural micronized vaginal progesterone (MVP) of 400 mg once daily and the second group received dydrogesterone (Duphestone) 20 mg twice daily. Then chemical pregnancy, abortion, and live births were compared in two groups. The results of the study showed that the vaginal form of the drug could increase the chance of pregnancy (positive β-human chorionic gonadotropin) versus the oral form. According to the results of multiple logistic regression analysis after adjusting for other variables, the live birth rate in the vaginal group was more than five times that of the oral group (odds ratio = 5.07; 95% confidence interval = 1.24-20.65; p = 0.023). The vaginal form of the progesterone could increase the chance of pregnancy and the outcome of fertility (live birth). Thus, vaginal progesterone is effective for LPS in women undergoing fresh embryo transfer.

Reproductive Health in Trans and Gender Diverse Patients: Effects of transmasculine gender-affirming hormone therapy on future reproductive capacity: clinical data, animal models, and gaps in knowledge.

Animal studies are needed to inform clinical guidance on the effects of testosterone gender-affirming hormone therapy (T-GAHT) on fertility. This review summarizes current animal models of T-GAHT and identifies gaps in knowledge for future study. Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and pre-pubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations.

Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach

To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality. Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013-2017). A target trial emulation framework was applied to estimate associations. Couples were observed for 9 months or through pregnancy. Clinics that provide reproductive endocrinology and infertility care in the US. Couples seeking infertility treatment. Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D. Live birth and pregnancy loss were ascertained via self-report and medical records. Semen quality was ascertained 6 months after enrollment. Log-binomial regression estimated risk ratios and 95% confidence intervals (CIs). Individual and joint models and effect measure modification by preconception body mass index were considered. Among 2,370 couples, 19.5% of females and 29.9% of males were 25(OH)D deficient. Females with sufficient status had a 28%-higher likelihood of LB than deficient females (95% CI, 1.05-1.56). Female and male 25(OH)D status were associated with LB among those with normal body mass index (sufficient vs. deficient: female adjusted risk ratio [aRR], 1.39; 95% CI, 1.00-1.99; male aRR, 1.51; 95% CI, 1.01-2.25) and among obese female partners (sufficient vs. deficient: aRR, 1.33; 95% CI, 0.95-1.85). Couples whose both partners had higher 25(OH)D status had increased likelihood of LB (both not deficient vs. both deficient aRR, 1.26; 95% CI, 1.00-1.58). No associations were observed with pregnancy loss or semen quality. Similar results were found for all biomarkers except calcium. Preconception vitamin D status and bioavailability impact fertility among couples seeking infertility therapy, likely unrelated to semen quality. Body mass index stratified analyses demonstrated heterogeneous associations. NCT01857310.

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.

Intramural Leiomyomas and Fertility: A Systematic Review and Meta-Analysis.

To evaluate fertility outcomes based on size and number of intramural leiomyomas and outcomes after removal. Online searches: MEDLINE, ClinicalTrials.gov , PubMed, Cochrane Library, and PROSPERO Library from 1994 to 2023. A total of 5,143 studies were identified, with inclusion of 13 study groups. Outcomes for size and number of leiomyomas were reported with clinical pregnancy rates and ongoing pregnancy or live-birth rates. In data sets with maximum leiomyoma diameters of less than 6 cm for study inclusion, women with leiomyomas smaller than 3 cm had lower clinical pregnancy rates than women without leiomyomas, with an odds ratio (OR) of 0.53 (95% CI, 0.38-0.76) and, for ongoing pregnancy or live-birth rates, an OR of 0.59 (95% CI, 0.41-0.86). The ORs for clinical pregnancy rates in women with intermediately-sized leiomyomas (those between 3 cm and 6 cm) were lower than in women without leiomyomas, with an OR at 0.43 (95% CI, 0.29-0.63) and, for ongoing pregnancy or live-birth rates, an OR at 0.38 (95% CI, 0.24-0.59). In data sets without exclusion for women with larger-sized leiomyomas, clinical pregnancy rates were lower for those with leiomyomas smaller than 5 cm compared with those without leiomyomas, with an OR of 0.75 (95% CI, 0.58-0.96). Women with leiomyomas larger than 5 cm showed no differences in clinical pregnancy rate compared with women without leiomyomas, with an OR of 0.71 (95% CI, 0.32-1.58). Although women with a single leiomyoma in any location had no differences in outcomes, those with more than one leiomyoma had lower clinical pregnancy rates and ongoing pregnancy or live-birth rates, with an OR of 0.62 (95% CI, 0.44-0.86) and 0.57 (95% CI, 0.36-0.88), respectively. The clinical pregnancy rate for women undergoing myomectomy for intramural leiomyomas was no different than those with intramural leiomyomas in situ, with an OR of 1.10 (95% CI, 0.77-1.59). Even small intramural leiomyomas are associated with lower fertility; removal does not confer benefit. Women with more than one leiomyoma in any location have reduced fertility.

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis

BackgroundEndometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. This study aimed to analyze the location and expression patterns of poly (ADP-ribose) polymerase 1 (PARP-1), epithelial cell adhesion molecule (EpCAM), and folate receptor alpha (FRα) in endometriosis lesions and evaluate their potential for targeted imaging.MethodsGene expression analysis was performed using the Turku endometriosis database (EndometDB). By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FRα in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis of images to perform a quantitative immunolocalization analysis. Double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as for PARP-1 and FRα, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment.ResultsGene expression analysis revealed that PARP-1, EpCAM, and FOLR1 (FRα gene) are more highly expressed in endometriotic lesions than in the peritoneum, which served as the control tissue. The results of the immunohistochemical study revealed a significant increase in the expression levels of all three biomarkers inside the endometriosis foci compared to the adjacent tissues. Additionally, the double immunofluorescence analysis consistently demonstrated the presence of PARP-1 in the nucleus and the expression of EpCAM and FRα in the cell membrane and cytoplasm.ConclusionOverall, these three markers demonstrate significant potential for effective imaging of endometriosis. In particular, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.