Infertility Treatment Research Articles

Risks of Long-Term Psychiatric Disease in Women with a History of Primary Infertility: A Historical Cohort Study.

To examine the risks of long-term de novo psychiatric disease in women with primary infertiltiy compared to age-matched referrent women. Retrospective, population-based cohort of 1,001 women with primary infertility and 1,001 age-matched (± 1year) referent women aged 18-50. The "index date" was date of first clinical note for infertility and included visits fromJanuary 1, 1980 to December 31, 1999. Baseline characteristics were collected by chart review. Outcome data was evaluated through December 31, 2020. Primary outcomes were baseline prevalence and de novo rates of subsequent psychiatric disorders including depression, anxiety, bipolar disorder, substance abuse, suicidality, and somatization evaluated by Coxproportional hazards modeling. Among women with primary infertility and referent women, the median duration of follow-up was 23.7years. The risk of de novo psychiatric disorders was not significantly different between groups. Additionally, the risk of de novo psychiatric disorders did not significantly differ between those with isolated male factor versus isolated female factor infertility. Among women with primary infertility, the cumulative incidence of de novo depression and anxietywas significantly higher among women diagnosed with primary infertility in the 1990s compared to the 1980s. Women with primary infertility, in a historical population-based cohort, do not have a significantly different long-term risk of de novo psychiatric diagnoses compared to age-matched referent women. Our findings support the notion that infertility diagnosis and treatment present an acute period of stress and for some psychologic distress, neither of which persist or increase the risk for development of future psychiatric disease.

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.

Optimizing care for MRKH patients: From malformation screening to uterus transplantation eligibility.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with utero-vaginal aplasia is the most severe form of the Müllerian duct anomalies and can be associated with extra-genital abnormalities such as renal or skeletal anomalies, hearing loss, or cardiac defects. The past two decades have witnessed significant advances both in understanding the etiologies of MRKH and in the development of fertility treatments such as uterine transplantation. The present work aimed to determine the rate of women with MRKH syndrome who underwent optimal initial management (after comprehensive malformation assessment) and to establish the rate of patients eligible for uterine transplantation (i.e., those with a vaginal length ≥7 cm without reconstruction using a bowel segment, and an anti-Müllerian hormone level >1.5 ng/mL before 35 years). Cohort study of 85 women with MRKH syndrome consulting in our tertiary center. 62.4% of women with MRKH syndrome had an exhaustive malformative evaluation according to the French guidelines (Protocole National de Diagnostic et de Soin [PNDS]), of which 76.5% had associated malformations (MRKH type II). Pedigree, when available, showed a family history of infertility or a urogenital tract spectrum anomaly in 60% of cases. Concerning the uterine transplantation selection criteria, when evaluated, 22.6% of women had an anti-Müllerian hormone level <1.5 ng/mL and 36% a vaginal length <7 cm. On the 21 women with complete evaluation of both primary and secondary outcomes, 14 of them would be eligible for a uterine transplantation program at the time of consultation according to the main inclusion criteria of uterine transplantation program. Women with MRKH syndrome are often inadequately explored for associated malformations. Early assessment and monitoring of the ovarian reserve is key for fertility preservation, especially in the era of uterine transplantation.

Comparative analysis of the bioaccumulation of bisphenol A in the blood serum and follicular fluid of women living in two areas with different environmental impacts.

Bisphenol A (BPA) is a common contaminant widely used in many industrial sectors. Because of its wide use and dispersion, it can be accumulated in living human bodies through both oral assumption and nondietary routes. BPA exhibits hormone-like properties, falling under the class of endocrine disruptors; therefore, it can alter relevant physiological functions. In particular, in women, it can affect folliculogenesis and therefore reproduction, contributing not only to infertility, but also to endometriosis and premature puberty. We conducted a multicenter study on 91 women undergoing a first in vitro fertilization (IVF) treatment in the Campania region (Southern Italy). We investigated the presence and concentration of BPA in serum and follicular fluids to assess the effects of airborne BPA contamination. The analysis was conducted on 32 women living in a low environmental impact (LEI) area, from the Sele Valley River and Cilento region, and 59 women living in a high environmental impact (HEI) area, the so-called "Land of Fires", a highly contaminated territory widely exposed to illegal waste practices. A higher average BPA content in both blood serum and follicular fluid was revealed in the HEI group when compared with the LEI group. In addition, we revealed higher average BPA content in blood serum than in folliclular fluid in the HEI area, with opposite average content in the two fluids in the LEI zone. In addition, our results also showed a lack of correlation between BPA content in follicular and serum fluids both in the overall population and in the HEI and LEI groups, with peculiar trends in different subsets of women. From our results, we revealed a heterogeneity in the distribution of BPA content between serum and follicular fluid. Further studies are needed to unravel the bioaccumulation mechanisms of BPA in highly polluted and nonpolluted areas.

Helping Patients to Predict and Confirm Ovulation with the Use of Combined Urinary Hormonal and Smartphone Technology: A Proof-of-Concept Retrospective Descriptive Case Series.

Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment (n = 95) or family planning advice (n = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing (n = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation.

Infertility treatment and offspring blood pressure-a systematic review and meta-analysis.

Studies have inconsistently observed that children conceived by IVF or ICSI have higher blood pressure compared to children not conceived by these ARTs. The aim was to perform a systematic review and meta-analysis of blood pressure measures of offspring conceived by ART and those conceived naturally. Resolving the suspicion of ART as a risk factor of higher blood pressure, and therefore of heart disease, has public health and clinical implications. A biomedical librarian searched the Embase, PubMed, and Web of Science databases. Searches were limited to records published in English since 1978. Grey literature was searched. Inclusion criteria were humans born via infertility treatment (vs no treatment) who underwent a blood pressure assessment. Exclusion criteria were non-human participants, non-quantitative studies, absence of a control group, and specialty populations (e.g. cancer patients only). Two reviewers independently screened each record's title and abstract and full text using Covidence, extracted data using Excel, and assessed bias using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for cohort studies. Of 5082 records identified, 79 were included in the systematic review and 36 were included in the meta-analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in ART and non-ART groups. Overall, 34 reports including 40 effect sizes from 25 unique cohorts, compared blood pressure between ART (N = 5229) and non-ART (N = 8509, reference) groups with no covariate adjustment. No standardized mean differences (SMD) in SBP (0.06 per SD of mmHg, 95% CI = -0.05, 0.18) or DBP (0.11, 95% CI = -0.04, 0.25) by treatment were found, but the heterogeneity was considerable (I2=76% for SBP and 87% for DBP). Adjusted analyses were presented in 12 reports, representing 28 effect sizes from 21 unique cohorts (N = 2242 treatment vs N = 37590 non-treatment). Studies adjusted for varied covariates including maternal (e.g. age, education, body mass index, smoking, pregnancy complications), child (e.g. sex, age, physical activity, BMI, height), and birth characteristics (e.g. birth weight and gestational age). Adjusted results similarly showed no SMD for SBP (-0.03, 95% CI = -0.13, 0.08) or DBP (0.02, 95% CI = -0.12, 0.16), though heterogeneity remained high (I2 = 64% and 86%). Funnel plots indicated a slight publication bias, but the trim and fill approach suggested no missing studies. Removal of five studies which adjusted for birth outcomes (potentially over-adjusting for mediators) made no material difference. Type of treatment (e.g. IVF vs ICSI), period effects by birth year (≤2000 vs >2000), offspring age group (<8, 8-14, 15+), or study location (e.g. Europe) did not modify the results. In conclusion, conception by ART was not associated with offspring blood pressure in a meta-analysis, although considerable heterogeneity was observed. Given the increasing number of children born using ART, perpetuating a difference in blood pressure would mean unnecessary risk screening for many children/adults on a population level. At a clinical level, couples considering these reproductive technologies have some reassurance that there is no evidence of strong vascular 'programming' due to the techniques used. PROSPERO No. CRD42022374232.

INFERTILITY AND IVF PREGNANCY: A CROSS-SECTIONAL STUDY AMONG NORTH INDIAN WOMEN

Objective: The aim of the study is to compare the reproductive, perinatal, and neonatal outcomes among women conceived by in vitro fertilization to those females conceived spontaneously. Methods: It is an observational descriptive cross-sectional study. The data were collected for 1 year and 6 months. The study population consisted of 82 term females admitted under the Department of Obstetrics and Gynecology of the hospital nearing termination who conceived after infertility. A semi-structured pre-designed questionnaire was used to collect the data. Results: There was a significant difference in the mean age at conception of the patients who conceived spontaneously versus those who conceived after infertility treatments (p&lt;0.001). The rate of cesarean section was higher in the group with a history of infertility (75%) with the rate being 35.7% in the spontaneous conception group (p=0.038). The neonatal outcomes were not significantly different in the two groups. Conclusion: There is a need to analyze and compare patients on a larger scale, so as to decide if special algorithms are required to treat pregnancies conceived after infertility treatments.

New therapeutic approaches for improving the outcomes of assisted reproductive technologies

Infertility is a global health problem that affects up to 17.5% of the world’s population. The use of assisted reproductive technologies makes it possible to solve this problem; however, it is not adequately efficient in all observed cases. Implantation failure remains a serious and multifaceted problem faced by clinicians in reproductive technology, despite the significant advances that have been made in this area. This review highlights promising studies on medical and invasive intervention methods and their possible combinations, which potentially improve the clinical treatment of implantation failures. Nevertheless, further study is required to assess the effectiveness and safety of each therapeutic approach, which can introduce new prospects in the treatment of infertility and increase the chances of successful implantation and pregnancy.

Progression of corneal thinning and melting after collagen cross-linking for keratoconus.

To study the aetiology, diverse clinical manifestations, therapeutic interventions, and prognoses in patients with corneal thinning after collagen cross-linking (CXL) treatment. a retrospective observational study of all patients presenting with corneal thinning after collagen cross-linking, in a tertiary eye care hospital in south India from 2011 to 2017. Preoperative details were noted. Patients who presented with corneal thinning were subjected to investigative measures to assess thinning, received appropriate management, and underwent follow-up evaluations. Among the 12 patients, 8 were female and 4 were male, all of whom had undergone standard classical CXL. The duration between CXL and corneal melting/thinning onset varied from 5 to 12 years. Notably, among female patients, 2 were pregnant, 2 were lactating mothers, 1 was undergoing in vitro fertilization (IVF) treatment, and 1 had comorbid diabetes mellitus and hyperthyroidism. Clinical examination revealed corneal thinning accompanied by hypopyon in 1 patient, corneal perforation with shallow anterior chamber in 1 patient, and epithelial defect with crystalline deposit in another patient, the remaining patients exhibited corneal thinning. Corneal thinnest corneal thickness measurements ranged from 212 to 351 µm. Treatment approaches included penetrating keratoplasty (PKP) in 2 patients, deep anterior lamellar keratoplasty (DALK) in 1 patient, cyanoacrylate glue application in 1 patient, and awaiting DALK/PKP in three patients, 4 patients showing no signs of increased thinning. The incidence of corneal thinning after collagen cross-linking is less but fulminant, requiring timely and appropriate management to prevent visual complications.

Impact of GnRH antagonist pretreatment on oocyte yield after ovarian stimulation: A retrospective analysis.

The study investigates whether a 3-day pretreatment course with a GnRH antagonist in the early follicular phase has an impact on the number of retrieved COCs in a GnRH antagonist stimulation protocol. This is a retrospective single center crossover study involving women who did not conceive after one GnRH antagonist stimulation cycle ("standard cycle") and proceeded with another GnRH antagonist stimulation cycle preceded by early administration of GnRH antagonist for 3 days ("pretreatment cycle") with fresh embryo transfer or frozen embryo transfer. 430 patients undergoing 860 cycles were included. The mean female age was 34.4 ± 4.8 years. Indications for fertility treatment included unexplained infertility (34.3%), male-factor infertility (33.3%), age (16.9%), PCOS (8.2%), tubal (4.7) and endometriosis (2.6%). All cycles were divided into two groups: group 1 (standard, 430 cycles) and group 2 (pretreatment, 430 cycles). The mean duration of stimulation was similar in both groups (10.3 vs 10.3 days, p = 0.28). The starting dose of gonadotropin (234.9 vs 196.8 IU, p<0.001), total amount of gonadotropin used (2419 vs 2020 IU, p<0.001), the total number of retrieved COCs (10 vs 7.8 p<0.001) and the number of mature oocytes (8 vs 5.8 p<0.001) were significantly higher in group 2 than in group 1. The Generalized estimating equation (GEE) regression analysis showed that the pretreatment strategy had a significant positive effect on the number of COCs (coefficient 2.4, p <0.001 after adjusting for known confounders (age, indication, stimulation dose, type, and duration of stimulation). In conclusion, A 3-day course of GnRH antagonist pretreatment increases the number of COCs obtained after ovarian stimulation.

8764 A Unique Case of Infertility in a Patient with NCCAH

Abstract Disclosure: M. Paravastu: None. R. Patel: None. Background: Non-Classic Congenital Adrenal Hyperplasia (NCCAH) in women often presents with hirsutism, acne, menstrual dysfunction, or infertility. Subfertility in patients with NCCAH can be attributed to menstrual disorders including oligomenorrhea or secondary amenorrhea. We report a unique case in which a patient with NCCAH with consistently normal menstrual cycles is experiencing infertility. Case Description: A 31 y/o female with no PMH was referred to our Endocrinology Clinic for evaluation of Infertility and elevated 17-Hydroxyprogesterone levels (17OHP). Patient has been having trouble conceiving for the past 2 years, no prior successful pregnancies. She started menstrual cycles at age 17, she reports having regular menstrual cycles. Prior to our evaluation, she was seen in Reproductive Endocrinology who completed hormonal and imaging evaluation. Elevated 17OHP: 286ng/dL. Rest of hormonal workup within normal range. Normal Pelvic Ultrasound. Hormonal workup was repeated in our clinic. 17OHP is elevated at 617.01ng/dL. Rest of lab work returned normal with DHEAS:218.9mcg/dL, TSH: 2.826mcUnits/mL, Free Testosterone: 5.4pg/mL, Prolactin:11.7ng/mL, Beta HCG: negative, LH: 13.5mUnits/mL, FSH: 5.3mUnits/mL, Estradiol 79pg/mL. Cosyntropin stimulation test was completed. Baseline AM 17OHP:469.78ng/dL, Baseline Cortisol: 17.9mcg/dL. 17OHP 30 minutes-post:1216.4ng/dL, Cortisol 30 minutes-post: 18.5mcg/dL. 17OHP 60 min-post: 1051ng/dL, Cortisol 60 minutes post:16.4 mcg/dL. Given Inconclusive Cosyntropin stimulation test results, Genetic Testing was recommended. Genetic testing returned positive for NCCAH, patient’s husband is not a carrier of this gene. She was started on Hydrocortisone therapy for treatment of infertility. Shortly after she started on hydrocortisone therapy, patient did successfully conceive, however the pregnancy later resulted in a miscarriage. Conclusion: Subfertility in patients in NCCAH is thought to be due to menstrual irregularities including oligomenorrhea or secondary amenorrhea. We report the first case of a woman with diagnosis of NCCAH who is experiencing infertility despite having normal menstrual cycles. Presentation: 6/1/2024

Investigating the Challenges of Infertility Treatment Development in Centers of Iran University of Medical Sciences and Health Services

Investigating the Challenges of Infertility Treatment Development in Centers of Iran University of Medical Sciences and Health Services

7119 Klinefelter Syndrome in a Tertiary Referral Clinic: A Case Series and Clinical Audit

Abstract Disclosure: J. Luo: None. S. Sarlos: None. R. Giri: None. I. Sim: None. R.I. McLachlan: None. C.A. Allan: None. R. Upreti: None. Background: Klinefelter syndrome, the most common chromosomal disorder in men, remains underdiagnosed in many of those affected. Klinefelter syndrome is associated with hypogonadism and infertility, as well as an increased risk for venous thromboembolism (VTE), cardiometabolic disease, osteoporosis and gynaecomastia in adults. We studied the clinical features and disease associations in a tertiary referral cohort, and audited the care provided. Methods: Following ethics approval, adult patients with Klinefelter syndrome attending a Clinical Andrology Service in a tertiary Australian institution since 1 January 2011 were recruited. A database was established and demographics, aspects of initial diagnosis, ongoing treatments and comorbidities were documented. We audited our care using the European Academy of Andrology 2021 Guidelines for Klinefelter Syndrome. Results: Of 94 patients eligible, 57 patients consented to participation. The median age of diagnosis was 28 years, with the most common karyotype being 47,XXY (74%), followed by mosaic (20%) and higher degree polysomy (6%). Infertility (44%) and hypogonadism (33%) were the most common reasons for diagnosis. Most patients (88%) were treated with testosterone. Five men (11%) had genetic children with seven (18%) having previously attempted surgical sperm extraction. VTE occurred in seven patients (12%), with five on long-term anticoagulation following VTE diagnosis. Cardiovascular risk factor prevalence assessed at a median age of 42 years included increased BMI (72%), hypertension (25%), dyslipidaemia (70%), tobacco use (26%), impaired fasting glucose (11%) and type 2 diabetes (22%), though only one patient had a previous cardiovascular event. Osteopenia and osteoporosis were present in 28% and 4% of patients respectively, though only two patients had minimal trauma fractures. The audit of longitudinal care showed that gynaecomastia status was underreported (42%) in our clinic, whilst assessment and management of other health domains were mostly in keeping with the current recommendations. Conclusions: Klinefelter syndrome diagnosis continues to be delayed until adulthood in many men, with presentations most commonly involving infertility and/or hypogonadism. Our tertiary cohort demonstrates low rates of fertility treatment and success, which is likely multifactorial. There is a high burden of VTE, cardiovascular risk factors and reduced bone density despite testosterone treatment. Low rates of cardiovascular events and fracture may be reflective of a younger cohort as well as more aggressive risk factor management in a sub-specialist service. Gynaecomastia identification, documentation and management are areas for potential improvement. Increased awareness of Klinefelter syndrome and research into its associated risks are essential for standardising care and improving long-term outcomes. Presentation: 6/1/2024

7061 Incidence of Adrenal Crisis In Congenital Adrenal Hyperplasia (CAH) Patients During A Prospective Monitored Long-Term Study Of Modified-Release Hydrocortisone (MRHC) Capsules, (Efmody)

Abstract Disclosure: R.J. Ross: Consulting Fee; Self; Diurnal. D.P. Merke: Research Investigator; Self; Diurnal. A. Mallappa: Research Investigator; Self; Diurnal. W. Arlt: Research Investigator; Self; Diurnal. A. Brac de la Perriere: Research Investigator; Self; Diurnal. A.L. Hirschberg: Research Investigator; Self; Diurnal. J.D. Newell-Price: Research Investigator; Self; Diurnal. A. Prete: Research Investigator; Self; Diurnal. A. Rees: Research Investigator; Self; Diurnal. N. Reisch: Research Investigator; Self; Diurnal. M. Quinkler: Research Investigator; Self; Diurnal. P.A. Touraine: Research Investigator; Self; Diurnal. K. Maltby: Employee; Self; Diurnal. J. Quirke: Employee; Self; Diurnal. N. Aslam: Employee; Self; Diurnal. H. Coope: Employee; Self; Diurnal. J. Porter: Employee; Self; Diurnal. Background: Adrenal crisis is the leading cause of excess mortality in patients with CAH[1]. Retrospective studies report an adrenal crisis incidence of 5-10/100 patient years (PY), with mortality 0.5/100 PY2. Modified-release hydrocortisone (MRHC) capsules, (Efmody), replicate cortisol diurnal rhythm and improve androgen control in CAH compared to standard glucocorticoid therapy2. Here, we report the incidence of adrenal crisis in CAH patients from a prospective study of MRHC in CAH patients. Methods: Patients completing MRHC Ph2 and Ph3 studies were eligible to enter a single-arm, open-label extension study. Study visits occurred at baseline, weeks 4, 12, 24 and 6-monthly thereafter. The primary endpoint was the safety of MRHC over time. Adrenal crisis was defined according to Allolio 20153. MRHC doses were adjusted on the basis of an adrenal insufficiency checklist, and measurement of androstenedione (A4) and 17-hydroxyprogesterone (17-OHP) at 9am and 1pm. Results: 91 patients entered the study, mean age 37 years, 68% female, 32% male. 22 discontinued; 11 at patient request, 5 due to pregnancy, 2 undergoing fertility treatment, 2 at physician/sponsor request, 1 due to an AE (carpal tunnel syndrome), and 1 due to death (myocardial infarction). Median treatment duration was 1500 days, range 0.2 to 5.8 years. Median MRHC dose at study entry was 30mg/day, reducing to 20mg/day from 24-weeks until end of study. Signs and symptoms of adrenal insufficiency due to under-treatment were reported for 41 (45.1%) participants, most frequently fatigue which was reported at some point by 41.8% of all participants. Signs and symptoms of overtreatment were reported for 25 (27.5%) participants, most frequently sudden weight gain which was reported at some point by 16.5% of all participants. Signs and symptoms of both over- and undertreatment occurred predominantly during the first 24 weeks. The study encompassed 357 participant years, and 18 adverse events considered indicative of adrenal crisis occurred in 7 participants, giving an incidence rate of 5.043 adrenal crises / 100 PY. Conclusions: Data from this longest prospectively monitored study in CAH suggest that the incidence of adrenal crisis on MRHC is at the low end of that reported in retrospective studies and the safety profile of MRHC is otherwise similar to immediate release hydrocortisone.

7119 Klinefelter Syndrome in a Tertiary Referral Clinic: A Case Series and Clinical Audit

Abstract Disclosure: J. Luo: None. S. Sarlos: None. R. Giri: None. I. Sim: None. R.I. McLachlan: None. C.A. Allan: None. R. Upreti: None. Background: Klinefelter syndrome, the most common chromosomal disorder in men, remains underdiagnosed in many of those affected. Klinefelter syndrome is associated with hypogonadism and infertility, as well as an increased risk for venous thromboembolism (VTE), cardiometabolic disease, osteoporosis and gynaecomastia in adults. We studied the clinical features and disease associations in a tertiary referral cohort, and audited the care provided. Methods: Following ethics approval, adult patients with Klinefelter syndrome attending a Clinical Andrology Service in a tertiary Australian institution since 1 January 2011 were recruited. A database was established and demographics, aspects of initial diagnosis, ongoing treatments and comorbidities were documented. We audited our care using the European Academy of Andrology 2021 Guidelines for Klinefelter Syndrome. Results: Of 94 patients eligible, 57 patients consented to participation. The median age of diagnosis was 28 years, with the most common karyotype being 47,XXY (74%), followed by mosaic (20%) and higher degree polysomy (6%). Infertility (44%) and hypogonadism (33%) were the most common reasons for diagnosis. Most patients (88%) were treated with testosterone. Five men (11%) had genetic children with seven (18%) having previously attempted surgical sperm extraction. VTE occurred in seven patients (12%), with five on long-term anticoagulation following VTE diagnosis. Cardiovascular risk factor prevalence assessed at a median age of 42 years included increased BMI (72%), hypertension (25%), dyslipidaemia (70%), tobacco use (26%), impaired fasting glucose (11%) and type 2 diabetes (22%), though only one patient had a previous cardiovascular event. Osteopenia and osteoporosis were present in 28% and 4% of patients respectively, though only two patients had minimal trauma fractures. The audit of longitudinal care showed that gynaecomastia status was underreported (42%) in our clinic, whilst assessment and management of other health domains were mostly in keeping with the current recommendations. Conclusions: Klinefelter syndrome diagnosis continues to be delayed until adulthood in many men, with presentations most commonly involving infertility and/or hypogonadism. Our tertiary cohort demonstrates low rates of fertility treatment and success, which is likely multifactorial. There is a high burden of VTE, cardiovascular risk factors and reduced bone density despite testosterone treatment. Low rates of cardiovascular events and fracture may be reflective of a younger cohort as well as more aggressive risk factor management in a sub-specialist service. Gynaecomastia identification, documentation and management are areas for potential improvement. Increased awareness of Klinefelter syndrome and research into its associated risks are essential for standardising care and improving long-term outcomes. Presentation: 6/1/2024

Baby-Making as Federal Policy: Mandating Insurance Coverage for Infertility Treatments Under the Patient Protection and Affordable Care Act

Baby-Making as Federal Policy: Mandating Insurance Coverage for Infertility Treatments Under the Patient Protection and Affordable Care Act

Effects of Planting Density and Nitrogen Fertilization on Growth Traits and Leaf and Wood Characteristics of Three Poplar Clones

A comprehension of the effects planting density and nitrogen (N) fertilization have on the physiological and morphological characteristics of trees is critical for optimizing the require size and characteristics of wood products. We evaluated the growth traits and the leaf and wood characteristics of three clone poplars including Populus simonii × P. nigra ‘Xiaohei’, ‘Xiaohei-14’ and ‘Bailin-3’ under five planting densities (1666, 1111, 833, 666, and 555 tree ha−1) and four N fertilization rates (0, 100, 160, and 220 g tree−1 year−1). The results show that the clone type significantly affected all observed indicators, while planting density and N fertilization treatments had a significant effect on growth traits and leaf characteristics, but not on wood characteristics. Specifically, the clone ‘Bailin-3’ exhibited the largest annual increments in tree height and diameter at breast height (DBH), leaf width, N content, and soluble protein content. A decrease in initial planting density (from 1666 to 555 tree ha−1) led to an increased annual incremental tree height and DBH, regardless of clone type and N fertilization treatment. N fertilization treatment significantly impacted the annual increment in DBH, but not that of tree height. Further, the annual increments in tree height and DBH were positively correlated with leaf width, N content, chlorophyll content, and soluble protein content, and negatively correlated with hemicellulose content. In addition, the chlorophyll and soluble protein contents were identified as the most reliable predictors of the annual increments in tree height and DBH. Our results demonstrate the clone ‘Bailin-3’ with 555 tree ha−1 under 160 g N tree−1 yr−1 showed superior growth traits and leaf characteristics. Thus, it is recommended for future poplar silviculture of larger diameter timber production at similar sites. The results contribute to understanding of the effects of planting density and fertilization on the growth traits and the leaf and wood characteristics of three poplar clones, offering valuable guidance for the sustainable development and long-term productivity of poplar plantations.

Establishment and Characterization of Testis Organoids with Proliferation and Differentiation of Spermatogonial Stem Cells into Spermatocytes and Spermatids.

Organoids play pivotal roles in uncovering the molecular mechanisms underlying organogenesis, intercellular communication, and high-throughput drug screening. Testicular organoids are essential for exploring the genetic and epigenetic regulation of spermatogenesis in vivo and the treatment of male infertility. However, the formation of testicular organoids with full spermatogenesis has not yet been achieved. In this study, neonatal mouse testicular cells were isolated by two-step enzymatic digestion, and they were combined with Matrigel and transplanted subcutaneously into nude mice. Histological examination (H&E) staining and immunohistochemistry revealed that cell grafts assembled to form seminiferous tubules that contained spermatogonial stem cells (SSCs) and Sertoli cells, as illustrated by the co-expression of PLZF (a hallmark for SSCs) and SOX9 (a marker for Sertoli cells) as well as the co-expression of UCHL1 (a hallmark for SSCs) and SOX9, after 8 weeks of transplantation. At 10 weeks of transplantation, SSCs could proliferate and differentiate into spermatocytes as evidenced by the expression of PCNA, Ki67, c-Kit, SYCP3, γ-HA2X, and MLH1. Notably, testicular organoids were seen, and spermatids were observed within the lumen of testicular organoids after 16 weeks of transplantation, as shown by the presence of TNP1 and ACROSIN (hallmarks for spermatids). Collectively, these results implicate that we successfully established testicular organoids with spermatogenesis in vivo. This study thus provides an excellent platform for unveiling the mechanisms underlying mammalian spermatogenesis, and it might offer valuable male gametes for treating male infertility.

A-306 High Sensitivity Capability of an Anti-müllerian Hormone Assay on the Beckman Coulter DxI 9000 Immunoassay Analyzer*, a Next Step Toward Enabling Ovarian Failure Staging?

Abstract Background Measurement of anti-müllerian hormone (AMH) has proven value in the evaluation of ovarian reserve using assays such as the Beckman Coulter Access AMH assay. If improved sensitivity of AMH measurement can be achieved, enhanced clinical utility during the assessment of reproductive aging and ovarian response to enable staging of ovarian failure is possible (Practice Committee of the American Society of Reproductive Medicine 2020, Cappola et al. 2023). The Beckman Coulter DxI 9000 Immunoassay Analyzer* has been designed with new technology that can be leveraged to improve assay sensitivity. Such technological advancements include the new Lumi-Phos PRO chemiluminescent substrate which yields markedly increased signal-to-noise, a new luminometer with increased dynamic range, and improved low-volume pipetting capabilities. Data herein summarize results from analytical verification studies of the Access AMH assay on the DxI 9000 Immunoassay Analyzer. Results demonstrate an example of DxI 9000 technologies enabling sensitivity claims that are up to 20-fold improved. * The official name is DxI 9000 Access Immunoassay Analyzer. Methods A method comparison study was performed based on CLSI guideline EP09c, 3rd ed. to compare results for the Access AMH assay on DxI 9000 to the predicate device, the Access AMH assay on the Access 2 Immunoassay System. Within-laboratory precision was also evaluated following CLSI EP05-A3. Finally, performance at low analyte levels was evaluated following CLSI EP17-A2, and linearity was evaluated following CLSI EP06-Ed2. Results Method comparison of the Access AMH assay on DxI 9000 compared to the Access AMH assay on the Access 2 yielded excellent agreement with a Passing-Bablok slope of 1.02 for N=126 samples. Further, bias estimates for a number of key medical decision points suggest minimal bias (≤ 2%) across the assay range, and minimal non-linearity was observed. 20-day imprecision studies yielded CV’s between 2 and 5% across a broad range of concentrations evaluated. Sensitivity studies yielded estimates of limit of quantitation (LoQ) between 0.001 and 0.003 ng/mL. This represents an approximately 10- to 20-fold improvement in sensitivity claims compared to the AMH assay on the Access 2 and other commercially available automated immunoassay analyzers. Conclusions The data herein present performance data for the Access AMH assay on the DxI 9000 Immunoassay Analyzer. The assay demonstrates excellent accuracy relative to the predicate device, while showing good linearity and imprecision. Of note, the Access AMH assay exhibits exceptional low-end performance on the DxI 9000 analyzer as demonstrated by the ability to enable sensitivity claims that are up to 20-fold improved in comparison to existing immunoassays for the measurement of AMH. The sensitivity capabilities of the Access AMH assay on DxI 9000 suggest an opportunity for the addition of further intended uses for scenarios where extremely low AMH measurements can provide additional value of clinical significance. Further studies are needed to fully understand additional clinical utilities of the Access AMH assay with high sensitivity capability on DxI 9000, including the assessment of reproductive aging for menopause diagnosis or ovarian response for fertility treatment.

Association between infertility and cervical insufficiency in nulliparous women- the contribution of fertility treatment

Pregnancies conceived through assisted reproduction have been associated with increased risks of adverse pregnancy and delivery outcomes, including cervical insufficiency (CI). Despite CI being a significant cause of late miscarriage or preterm birth, there are minimal published data on the associations of infertility (with or without fertility treatment) with CI. This study uses Swedish national health registers to examine the associations between infertility, assisted reproduction and CI in nulliparous women. This population-based case-control study is based on data from Swedish national health registers. Using the information on parity and multiple gestation in the Medical Birth Register, singleton pregnancies of nulliparous women were extracted and linked to the National Patient Register and the National Quality Register for Assisted Reproduction. Using diagnostic codes for CI and procedural codes for cervical cerclage, a total of 2662 CI cases were identified for deliveries in the 21-year period, 1992-2012. A reference group of 26,620 controls were extracted from the population of non-cases using simple random sampling.. Infertility was classified using a woman's report of difficulty conceiving for at least one year. Fertility treatment was assessed through self-reported variables in the Medical Birth Register and fertility treatment registration in the National Quality Register for Assisted Reproduction. On adjusting for maternal characteristics and medical history, infertility was associated with CI, overall (adjusted odds ratio (aOR) ) 1.91 (1.53, 2.39) and in the subgroup of non-users of fertility treatment (aOR) 1.60 (1.21, 2.12), compared to women without infertility. Among women with infertility, pregnancies conceived with the aid of fertility treatment had higher risk of CI than naturally-conceived pregnancies (aOR 1.49 (1.05, 2.10). In the subgroup of women with infertility and no history of miscarriage, the use of fertility treatment was associated with CI (aOR 3.48 (2.02. 5.98)). No association was found between fertility treatment and CI in the pregnancies of women with infertility and a history of miscarriage. From this study, we conclude that CI in nulliparous women is associated with both infertility and its treatment. For infertile women, the risk of CI following fertility treatment was seen only in those with no history of miscarriage, providing crucial information for improving risk assessment and management strategies for preterm birth prevention in populations availing of fertility treatment.