FSH Values Research Articles

8265 Premature Ovarian Insufficiency in Pediatric Cancer Patients: a 10-Year Rady Children's Hospital Experience

Abstract Disclosure: M. Robinson: None. L. Meller: None. M.E. Patterson: None. Objective: To highlight the occurrence of premature ovarian insufficiency in cancer patients treated at a children’s hospital and to determine which patient characteristics or treatment modalities are associated with ovarian failure and subsequent recovery of ovarian function. Study design: A retrospective chart review. Setting: Rady Children’s Hospital San Diego. Subjects and Methods: Between August 2011 and August 2021, the cases of 36 patients with cancer and ovarian failure were reviewed. Data collected included type of cancer, age at diagnosis, types of chemotherapy used in treatment, whether a bone marrow transplant or radiation was part of the treatment plan, peak FSH value and age when this occurred, peak AMH value, whether GnRHa treatment was used, type of hormone replacement therapy used, and whether there was recovery of ovarian function. Results: The most common type of cancer identified in this group of patients was acute lymphoblastic leukemia (ALL) (13, 36.1%). The mean age of diagnosis was 8.5 ± 4.3 years and the mean age of peak FSH value was 12.6 ± 2.8 years. Nearly all patients (97.2%) were treated with alkylating agents as part of their chemotherapy regimen and 72.2% received some form of radiation. Most patients (26, 72.2%) also received some form of hormone therapy, most commonly transdermal hormone therapy (13, 36.1%) or oral contraceptive pill (10, 27.8%), and 15.8% of patients were treated with the GnRHa Lupron. Fertility planning was offered or discussed in 36.1% of patients. Ten patients (27.8%) were noted to have some degree of recovery in their ovarian function. Age at diagnosis and type of cancer treatment were significant predictors of recovery in multivariate regression modeling. Specifically, each year older in age was associated with a 30% decrease in odds of recovery (OR: 0.7, CI: 0.5-0.95, P = 0.035), and treatment with an alkylating agent without transplant was associated with a 3-fold increase in odds of recovery (OR: 3, CI:2.7-564, P = 0.007). Conclusion: This retrospective review demonstrates that, while uncommon, POI can occur in pediatric cancer survivors, emphasizing the importance of educating patients on the potential long-term effects of cancer treatment and routine surveillance for these complications. This study also confirmed that recovery of ovarian function is possible in these patients, especially when diagnosed at a younger age, so continued monitoring is essential. Presentation: 6/3/2024

7802 A Review of 21 Cases of Kallmann Syndrome

Abstract Disclosure: T. Kashima: None. M. Ishimaru: None. E. Tanimoto: None. S. Fukui: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. M. Igarashi: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. Kallmann syndrome is the most common form of hypogonadotropic hypogonadism. The incidence is estimated to be 1 in 10,000 birth boys and 1 in 50,000 birth girls. The goals of treatment for childhood puberty are to induce the progression of secondary sexual characteristics close to physiological sexual maturity, to improve psychosocial problems caused by delayed puberty, and to achieve fertility. Methods.Twenty-one patients (fifteen males and six females) with a diagnosis of Kallmann syndrome who visited our Department between August 2004 and November 2023 were included in the study. The electronic medical records were reviewed retrospectively. Results.The median age at first visit was 15 years and 11 months (13 years and 3 months to 17 years and 7 months). The chief complained were secondary sexual characteristics not yet developed, olfactory disturbance, amenorrhea, decreased growth rate, and micropenis. Three adults had symptoms of Kallmann's syndrome and were seen for close examination. 6 had a history of hearing loss. Family history included 2 cases of hypogonadotropic hypogonadism and a sibling with Sjogren-Larsson syndrome. 9 cases had genetic testing, including KAL1, KAL2, FGF8, IL17D, 1 case each, and 2 gene variants of CHD2.At the time of initial examination, the median testicular volume in males was 1.0 mL (1.0-3.0 ml). Five of the six female patients had no breast enlargement.Endocrine examination revealed that the mean basic LH and LHRH test peak values were 0.25 and 3.40 mIU/mL, respectively; the mean basic FSH and peak FSH values were 0.91 and 4.47 mIU/m, respectively; the mean testosterone level in males was 0.09 ng/mL; and the mean estradiol level in females was 5.58 pg/mL.For the 20 patients, excluding children, gonadotropins (HCG+rFSH) for men and estrogen patches for women were both started at low doses and titrated up to Kaufman therapy in women. Median age at initiation of treatment was 16 years and 5 months (14 years and 1 month to 18 years and 6 months). Bone density increased after the start of treatment. One patient diagnosed with micropenis in infancy was treated with testosterone for micropenis at 2 years and 5 months. Two male patients had a baby with their partners. Discussion.The age of diagnosis (age of first examination) is considerably older than the average age of onset of secondary sexual characteristics, so it is necessary to educate the public so that patients can be examined earlier. The patient's fertility was partially confirmed, and a smooth transition to adult/reproductive medical care can be expected through earlier intervention. Presentation: 6/1/2024

COVID-19 and Female Fertility: An Observational Prospective Multicenter Cohort Study: Upholding Reproductive Rights in Emergency Circumstances.

Currently available research data points to COVID-19-related multi-organ system damage. This study aims to evaluate the impact of SARS-CoV-2 on the reproductive health, that is, plasma levels of FSH, LH, estradiol, AMH, and antral follicular count, of women undergoing level II ART techniques. This is a multicenter, prospective, and observational study by the reproductive medicine centers of Palermo's Ospedali Riuniti Villa Sofia-Cervello Hospital and Vanvitelli University. From September 2022 to March 2024, 203 patients aged 24-43 were enrolled, all with diagnosed infertility and a history of SARS-CoV-2 infection. Symptomatic women, patients testing positive for HIV or other liver viruses, and patients with a history of ovarian cancer or who had taken gonadotoxic drugs were excluded. Plasma measurements of FSH, LH, estradiol, AMH, and antral follicular count were performed before and after infection. The analysis accounting for the concentration of anti-Müllerian hormone (AMH) before and after COVID-19 infection shows an average concentration decrease from 1.33 ng/mL before SARS-CoV-2 infection to 0.97 ng/mL after infection. Average decrease after infection was -27.4%; average reduction of 1 follicle (95% CI: from -0.74 to -1.33) was reported following SARS-CoV-2 infection. Levels of E2 before and after SARS-CoV-2 infection did not vary significantly. Average FSH and LH levels before and after SARS-CoV-2 infection pointed to an increase. SARS-CoV-2 infection damages female reproductive health, causing significant reductions in AMH (-27.4%) and AFC (-1 antral follicle) values and an increase in FSH (+13.6%) and LH (+13.4%) values. No effect on E2 levels was reported. The pandemic has also affected the ability of infertile patients to access ART procedures, and that calls for a novel, updated blueprint designed to enhance our preparedness in the event that similar circumstances should occur again.

Luteinizing Hormone Variability in Polycystic Ovary Syndrome: A Comparative Analysis

An endocrine with metabolic condition known as Polycystic Ovarian Syndrome (PCOS) affects women who are of reproductive age, women with PCOS are a condition often associated with dysregulation of the hypothalamic-pituitary axis. A Cross-sectional study, the study included 88 patients who visited the outpatient clinic in total. These individuals were split up into two groups. All females are assessed the status of obesity by the body mass index (BMI), [BMI= weight (kg) / height (m)²], LH, FSH, Estradiol and Testosterone levels measured by ELISA technique. There was no discernible variation in BMI between groups A and B. (P ≥ 0.456), The patients' mean FSH and LH values were 5.06 mIU/ml and 5.47 mIU/ml, compared with group B mean that equal to 6.05 mlU/ml, 18.91mlU/ml respectively. Serum testosterone was slightly elevated in group B that was (41.19 ± 5.16 ng/dL), and (39.53 ± 4.98 ng/dL) in group A. Moreover, the level of estradiol (E2) in group A was 79.45ng/dL while in group B the level was 72.65 ng/dL there are no significant difference between two groups. The study found conflicting evidence regarding the impact of high LH levels on oocyte quality, fertilization, and pregnancy outcomes in PCOS patients. According to the research, ovarian theca cells from PCOS patients may be more effective than normal theca cells at converting androgenic precursors to testosterone. While ovulatory dysfunction in PCOS is linked to reduced estradiol production, the study indicates that ovarian tissue may still contribute to circulating estradiol levels in affected women.

The intratesticular artery resistive index as a predictor of spermatogenesis: A prospective study.

With the objective to assess the correlation between the resistive index of intratesticular artery as predictor of spermatogenesis this case control study was conducted. A Prospective study conducted during period April 2021 to March 2023. Total 50 patients, with oligoasthenozoospermia taken as cases and other 50 men with normal sperm count taken as controls. History taken & clinical examination, Semen analysis, hormonal evaluation & Color Doppler ultrasonography of scrotum done. Resistive Index of testicular arteries was obtained. Cases and controls were compared. The age of the study group ranged between 21 and 40 years. Among the cases maximum patients 23 out of 50 and among controls with maximum number 21 out of 50 patients were belonged to age group 26-30 years.The mean semen volume for the cases & controls was 2.76 ± 0.44 ml and 3.32 ± 0.54 ml respectively. The Mean sperm concentration in the cases & controls was 14.33 million/ml & 84.8 million/ml. Mean Type A sperm motility was 20.82% ± 7.86 in cases and 54.96% ± 5.41 in controls. The mean testicular volume in cases was 18.36 ± 0.75 & in controls was 18.39 ± 0.62 ml. Hormonal evaluation done in both cases and controls and mean value of FSH in cases and controls was 7.57 ± 2.34 and 6.27 ± 3.55 respectively (p-value = 0.036). Mean value of Resistive Index (PSV - EDV)/PSV) in cases and controls were found 0.63 ± 0.32 and 0.53 ± 0.37 respectively (p-value = 0.001). The intratesticular artery resistive index can be utilized as valuable predictive marker to indicate spermatogenesis.

Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35years, 198 embryos) and AMA (≥ 35years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

A Case Report of Bardet Biedl Syndrome in a Patient from Pakistan who Presented with Osmotic Symptoms associated with Diabetes Mellitus

Background: The primary features of Bardet Biedl syndrome (BBS) are characterized by retinal degeneration, central obesity, post-axial polydactyly, intellectual impairment, hypogonadism, and renal anomalies. The secondary clinical features are syndactyly, delay in the achievement of developmental milestones, diabetes insipidus, diabetes mellitus, congenital heart disease and liver involvement. It is diagnosed when a patient has either four primary or three primary and two secondary clinical features and the management depends upon those predominant features. Case presentation: A 12-year-old boy presented with polyuria, polydipsia and polyphagia. His developmental milestones were delayed and had syndromic features on physical exmination. Ultrasound of the abdomen and pelvis showed mild right-side hydronephrosis. His BMI was 28 and HbA1c was 18.3%, and values of LH and FSH were decreased. As a result, he was diagnosed with a case of BBS. He was commenced on insulin therapy with Insulin Regular (Human Insulin)and Insulin NPH (Human Insulin). Conclusion: Patients presenting with polyuria, polydipsia, polyphagia along with the presence of syndromic features, should be assessed for BBS as osmotic symptoms associated with diabetes mellitus can be initial clinical presentation of BBS. Its management depends upon the signs and symptoms of the patient. Various options including weight loss, exercise, oral hypoglycemic drugs, and insulin are available to treat diabetes mellitus in BBS. Some cases can have very high levels of HbA1c on initial presentation, which may require insulin without trying oral hypoglycemic drugs to treat diabetes mellitus in BBS.

Testicular histopathology and follicular stimulating hormone to predict fertility in nonobstructive azoospermia.

To examine the ability of testicular histopathology in Non-obstructive azoospermia (NOA) in predicting sperm retrieval rate (SR), sperm quality and assisted reproductive technology success. A retrospective study recruited clinically diagnosed NOA patients between 2007 and 2015. Testicular biopsy and conventional sperm extraction (TESE) were done concomitantly. Correlation between pathological categories, SR rate, sperm quality and success of intracytoplasmic sperm injection (ICSI) was studied. FSH was measured as a predictor of fertility. One hundred eighteen patients were recruited. Histopathological classification was hypospermatogenesis (HS) 45 (38%), maturation arrest (MA) 22(19%), Sertoli cell only syndrome (SCOS) 34 (29%) and normal spermatogenesis (NS) 17 (14%). FSH value was above normal level in 34 (76%) of HS, 19 (86%) of MA, 32 (94%) of SCOS and 5 (29%) of NS. Positive SR was obtained in 108 (92%) patients. The highest SR rate was seen in NS group 100% and the lowest was in SCOS 26 (77%). The worst sperm quality was found in SCOS as type C represents 46%, followed by MA 40% and HS 24%. Patients had ICSI following TESE had variable success rate as success of ICSI was seen (9/15) for HS, (0/7) for MA, (5/15) for SCOS and (8/9) for NS. FSH is strongly correlated to SR, quality of sperm and success of ICSI as positive SR in normal FSH patients was obtained in 28 (100%) of normal FSH, 70 (97%) of high FSH and 10 (56%) of double high FSH (p value < 001). The success of ICSI significantly correlates with FSH value as normal FSH has 77% success ICSI rate, high FSH (52%) and double high FSH (0%) (p value < 0.001). Testicular biopsy and histopathology findings in NOA are strongly correlated SR rate, quality of sperms, and success of ICSI. FSH is a strong noninvasive predictor of fertility in NOA patients.

Ameliorating Effects of Arsenic-Induced Toxicity On The Histology Of Vagina And Reproductive Hormones Of Female Sprague Dawley Rats

Objective: To find out the toxic effects of arsenic on the histology of the vagina and reproductive hormones of female Sprague Dawley rats. Methods: 60 female Sprague Dawley rats were divided into control group A and experimental group B with 30 rats in each group. The gross weight of all the rats was checked before and at the end of the experiment. After one week of acclimatization, the control group was administered 10ml of distilled water by oral gavage daily for 14 days and the experimental group was administered 4µg of sodium arsenite dissolved in 10ml of distilled water by oral gavage daily for 14 days. After being euthanized by chloroform inhalation on day 15, blood from each rat was drawn by a single intra-cardiac puncture and stored for biochemical analysis. After that, rats were sacrificed and the whole reproductive tract was removed and vaginal sections were prepared and stained with hematoxylin and eosin (H&amp;E ). The histological parameters were analyzed by using Image J software. Whereas, biochemical parameters e.g. serum LH and FSH levels were analyzed by ELISA. Results: After exposure to a low dose of arsenic administered for a short period, the gross weight of rats, weight of reproductive tract, height of vaginal epithelium and serum FSH and LH values were significantly reduced in experimental animals as compared to control animals with p-value &lt; 0.05. Conclusion: Low dose of arsenic given via contaminated drinking water for a short period is very toxic to the female reproductive tract which is evident by the histological changes in the vagina and deranged hormonal profile of female Sprague Dawley rats. Keywords: Arsenic, FSH, Free radicals, LH, Oxidative stress, Vagina.

Hormonal profile changes under the influence of environmental factors in children residing in the Aral environmental disaster region

BACKGROUND: Since the mid 20th century, the Southern Aral Sea Region is notorious as a region of ecological disaster, where anthropogenic influence led to the desiccation of the Aral Sea. Aridization of these territories is the cause of accumulation of endocrine disrupting chemicals — pesticides and toxic metals in soil and water.&#x0D; AIM: The aim of this study was to assess the changes in hormonal profile under the influence of environmental factors in prepubertal children living at different distances from the epicenter of the Aral ecological disaster.&#x0D; MATERIALS AND METHODS: The study included 58 male children aged 11–13 years. All children from birth lived in two regions of the Aral Sea Region and were divided into two groups depending on their place of residence. The group “North” (unfavorable conditions) consisted of 27 children from Muynak, Kungrad, Karauzyak, Takhtakupyr districts. The “Nukus” group (relatively favorable conditions) included 31 volunteers from Nukus city. All children were determined the concentration of IGF-1 — Insulin-like growth factor 1, GH — growth gormone, TT — total testosterone, E2 — estradiol, FSH — follicle-stimulating hormone, LH — luteinizing hormone, TSH — thyroid-stimulating hormone, TT3 — total triiodothyronine in blood sample. The statistical significance of the differences of the mentioned hormones in children from the “North” and “Nukus” groups was checked using the Mann–Whitney test.&#x0D; RESULTS: This analysis revealed statistically significantly higher values of TT, FSH and LH in children from the “Nukus” group compared to their peers from the “North” group. The concentrations of IGF-1, GH, E2, TTG and T3 in blood plasma in volunteers from both groups were not statistically significantly different.&#x0D; CONCLUSIONS: The environment of the Aral ecological disaster region with increased content of organochlorine compounds, pesticides and heavy metals changes the endocrine status in local prepubertal children. This is expressed in a moderate decrease in the activity of androgens (but not estrogens) and gonadotropic hormones. This research work can be considered as a pilot study, which determines the need for further monitoring of endocrine disorders in children and adults living in negative environmental conditions.

Effect of thymoquinone on NRF2/NF-kB/MAPK pathway in methotrexate-induced rat testis injury.

In this study, we aimed to investigate the protective effect of Thymoquinone (THQ) against testicular damage caused by Methotrexate (MTX). This study consists of 5 groups: Control, Olive oil, THQ, MTX, and MTX+THQ. At the end of the experiment, spermiogram analysis was performed on the rats. In addition, testicular tissues were taken and histopathology, immunohistochemistry, and biochemistry analysis were performed. Biochemical analyses were performed on the serums. According to the results obtained, spermiogram values, Johnson's testicular biopsy score, SOD, CAT, GPx, FSH, LH, and testosterone values were statistically significantly decreased in the MTX group compared to the control group. In the MTX+THQ group, spermiogram values, Johnson's testicular biopsy score, SOD, CAT, GPx, FSH, LH, and testosterone values increased statistically significantly compared to the MTX group. NRF2 and HO-1 immunoreactivity were statistically significantly decreased in the MTX group compared to the control group. In the MTX+THQ group, NRF2 and HO-1 immunoreactivity were statistically significantly increased compared to the MTX group. The level of MDA, which is important in lipid damage, and the level of biochemistry results of TNF-α, IL1-β, and IL-6, which are important markers, and the results of p-NF-kB and P38 immunoreactivity were statistically significantly increased in the MTX group compared to the control group. In the MTX+THQ group, these parameters showed a significant decrease compared to the MTX group. According to these results, it is thought that THQ will play a protective role against infertility caused by chemotherapy-induced testicular damage.

The corrective role of superparamagnetic iron oxide nanoparticles for the genes controlling hypothalamus-pituitary-testis-axis in male obesity-associated secondary hypogonadism.

Obesity is one of the most prevalent and perilous health affairs. Male obesity-associated secondary hypogonadism (MOSH) is one of many of its complexities, which is mounting in parallel with the aggravation of obesity. Magnetic nanoparticles seem to be an advanced favorable trend in multiple biomedical fields. In this study, we explore the therapeutic effects of superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyl cellulose (CMC) on an obese male rat model with MOSH syndrome, comparing their impacts with a well-known anti-obesity medication (Orlistat). 42 male albino rats split into 7 equal groups: 1-negative control: nonobese, untreated; 35 rats fed the high fat-high fructose (HFHF) diet for a period of 12 weeks. Obese rats splitted into 6 equal groups; 2-positive control: obese untreated; 3-obese given Orlistat (30 mg/kg); 4-obese given CMC-SPIONs (25 mgFe/kg); 5-obese given CMC-SPIONs (50 mgFe/kg); 6-obese given CMC-SPIONs(25 mgFe/kg) + Orlistat (30 mg/kg), 7-obese given CMC-SPIONs (50 mgFe/kg) + Orlistat (30 mg/kg); all treatments given orally for 4 weeks. During sacrifice, blood serum and sectioned hypothalamic, pituitary, testicular, and adipose tissues were collected for biochemical and biomolecular assessments. The HFHF diet for 12 weeks resulted in a significant upsurge in body weight, body mass index, serum fasting glucose, insulin resistance, TAG, total cholesterol, and LDL-c; HDL-c was dropped. Serum FSH, LH, and testosterone values declined. A significant disorder in expression levels of genes regulating the hypothalamic-pituitary-testicular-axis pathway. Hypothalamic GnRH, Kisspeptin-1, Kisspeptin-r1, and Adipo-R1 values declined. GnIH and Leptin-R1 values raised up. Pituitary GnRH-R values declined. Testicular tissue STAR, HSD17B3, and CYP19A1 values declined. Adipose tissue adiponectin declined, while leptin raised up. CMC-SPIONs 25-50 mg could modulate the deranged biochemical parameters and correct the deranged expression levels of all previous genes. Co-treatments revealed highly synergistic effects on all parameters. Overall, CMC-SPIONs have significant efficiency whether alone or with Orlisat in limiting obesity and consequence subfertility. CMC-SPIONs act as an incoming promising contender for obesity and MOSH disorders management, and need more studies on their mechanisms.

Fertility and Gonadal Function after First-Line Treatment with Nivolumab-AVD in Hodgkin Lymphoma Patients: An Analysis from the Phase II GHSG Nivahl Trial

Background: First-line treatment of patients with classical Hodgkin lymphoma (HL) with anti-PD1 antibodies in combination with AVD chemotherapy is highly effective across risk-groups. Based on encouraging phase II and ongoing phase III trials, anti-PD1 based first-line treatment may hence soon become a first-line treatment option. To date, no data on fertility and gonadal function after anti-PD1 based first-line HL treatment is available. Herein, we present data on pregnancies and gonadal function in patients treated within the randomized GHSG phase II NIVAHL trial. Methods: NIVAHL enrolled 109 patients aged 18-60 years with first diagnosis of early-stage unfavorable HL to receive either fully concomitant (4xN-AVD; group A) or sequential (4xN, 2xN-AVD, 2xAVD; group B) nivolumab-based 1st-line treatment, each followed by 30Gy involved-site radiotherapy (IS-RT). The primary and final analyses showed excellent efficacy and an acceptable safety profile after 1- and 3-years of follow up; details were previously published (Bröckelmann et al. JAMA Oncol 2020 &amp; JCO 2023). Data on pregnancies and births as well as sexual hormones prior, during and after treatment were collected via standardized case report forms. The cohort for this descriptive analysis included women &amp;lt;40 and men &amp;lt;50 years of age. Results: A total of 87 patients (55% female, 51% treatment group A) with a median age of 25 (range 18-49) were eligible for this analysis. Patient characteristics were well balanced between treatment groups and patients presented predominantly with stage IIA disease (75.3%) and presence of the risk factors ≥3 nodal areas (75%), elevated ESR (44%) and bulky mediastinal disease (20.2%). Cryopreservation prior start of treatment was performed in 39.6% of female and 74.4% of male patients. With a median follow-up (FU) of 41 months, a total of 11 pregnancies were documented (12.6%; 9 in female patients, 2 in partners of male patients). These resulted in 8 documented live births (2 abortions, 1 missing info), with none using assisted reproductive techniques. In female patients, median hormone levels remained relatively stable from baseline to 12-24 months of FU for FSH (4.7 -&amp;gt; 4.3 U/l), LH (6 -&amp;gt; 7.2 U/l) and AMH (2.3 -&amp;gt; 2.8 ug/l) while an increase of estradiol was observed (53.6 -&amp;gt; 102 ng/l). Similar trajectories of largely stable hormone levels were observed when stratifying female patients by age groups (i.e. 18-29 and 30-39 years). Women ≥30 years presented higher median FSH (6.1 vs 4.7 U/l) and lower estradiol values (48.8 vs 53.6 ng/l) compared to younger women at baseline, however, presented with similar median FSH levels at 12-24 months of FU (4.2 and 4.4 U/l, respectively). In male patients, hormone levels also remained stable from baseline to 12-24 months of FU for FSH (4.2 -&amp;gt; 4.2 U/l), LH (4.1 -&amp;gt; 3.9 U/l), testosterone (4 -&amp;gt; 5.6 ug/l) and inhibin B (159.4 -&amp;gt; 180 ng/l). More detailed analyses regarding hormonal trajectories of individual patients and stratifications by treatment group are ongoing and will be presented at the meeting. Conclusion: This analysis of pregnancies, births and sex hormones after first-line HL treatment with N-AVD indicates preserved gonadal function in the majority of both female and male patients.

Association of ‘normal’ early follicular FSH concentrations with unexpected poor or suboptimal response when ovarian reserve markers are reassuring: a retrospective cohort study

Research questionAre basal FSH measurements, when elevated within its normal range, useful for assessing overall ovarian response and predicting unexpected poor or suboptimal ovarian response? DesignRetrospective cohort study of ovarian stimulation cycles. ResultsA total of 1058 ovarian stimulation cycles (891 first, 167 repeated) were included. Anti-Müllerian hormone (AMH) values were categorized into four (0 to ≤0.6, >0.6 to ≤1.2, >1.2 to ≤3.0, >3.0 to ≤6.25 ng/ml) and basal FSH levels into four groups (<25th percentile: >3.5 to 6.1 IU/ml; 25–75th percentile: >6.1 to ≤8.5 IU/ml; >75–90th percentile: >8.5 to ≤9.9 IU/ml; >90th percentile: >9.9 to ≤12.5 IU/ml). Including only first cycles, a significant independent effect of basal FSH on retrieved cumulus–oocyte complex (COC) count was seen for all basal FSH categories (>90th, >75 to ≤90th, >25 to ≤75th compared with ≤25th percentile, P < 0.001, P = 0.001 and P = 0.007, respectively), when adjusted for age, body mass index (BMI), AMH, antral follicle count (AFC), starting dose and gonadotrophin type. Including only first cycles, patients aged 35 years or older with AFC of 5 or above and AMH 1.2 ng/ml or above, showed significantly higher odds of unexpected poor or suboptimal response if they had higher basal FSH values. Most prominently in the above 90th percentile group (OR 8.64, 95% CI 2.84 to 28.47 compared with <25th percentile) but lower categories (>25th to ≤75th percentile: OR 3.04, 95% CI 1.42 t 6.99; >75th to ≤90th percentile: OR 3.47, 95% CI 1.28 to 9.83 compared with ≤25th percentile) also showed a significant association after adjusting for age, AMH, BMI, AFC, dose, and gonadotrophin type. In patients with a second cycle, an increase in FSH levels in the second round compared with the first was associated with fewer retrieved COCs (estimate: –0.44, 95% CI –0.44 to –0.05, P = 0.027). This effect was adjusted for changes in age, FSH, AFC, starting dose, stimulation duration and change in medication type. ConclusionsBasal FSH is independently associated with overall ovarian response. Moreover, it is associated with unexpected poor or suboptimal response in patients, who would fulfill POSEIDON group 2 criteria after oocyte retrieval.

Effect of preconditioning of human umbilical cord mesenchymal stem cells with hydrogen peroxide on the therapeutic potential of MSCs in the cyclophosphamide -induced premature ovarian failure mice model.

Exposure of stem cells to sublethal levels of hydrogen peroxide (H2O2) can prevent oxidative stress-induced apoptosis. In the present study, the effects of H2O2 preconditioning on the therapeutic potential of human umbilical vein cord mesenchymal stem cells (hUCV-MSCs) were evaluated in a murine model of premature ovarian failure. Mature mice were divided into 4 groups, and 10 mice were incorporated into each group. The control (Ctrl) group received phosphate buffered saline (PBS) intraperitoneal (IP), and the CTX group was injected IP with cyclophosphamide (CTX). The CTX+MSC group after receiving CTX was injected with a single dose of hUCV-MSCs labeled with CM-DiI intravenously (IV), whereas the CTX+preMSCs group after CTX injection received preconditioned MSCs with H2O2 IV. Seven days later, the mice were euthanized, and their ovaries were removed for histological studies such as H&E staining and the TUNEL assay. Furthermore, the numbers of CM-DiI-labeled hUCV-MSCs in the different regions of the ovary were calculated. FSH and estradiol values in the serum were measured. Our studies showed that CTX caused degenerative changes and follicular loss in the ovary. The number of follicles in the CTX+MSCs and CTX+PreMSCs groups was significantly higher compared to the CTX group. In addition, in the CTX+PreMSCs group, the numbers of different types of follicles were higher than in the CTX-MSC group. Immunohistochemical studies in the CTX+MSCs and CTX+PreMSCs groups showed little evidence of TUNEL positivity compared with the CTX group. Moreover, the apoptotic index decreased in the CTX+PreMSCs group compared to the CTX+MSCs group. Moreover, CM-DiI-labeled MSCs in the ovary in the CTX+pre-MSCs group were higher than in the CTX+MSCs group. Our experiment offers preconditioning as an effective strategy in stem cell therapy to potentiate MSCs' therapeutic efficacy in ovarian function failure.

P-678 Predictive value of intra-cycle FSH measurements for blastocyst euploid rate: a longitudinal cohort study

Abstract Study question Can intra-cycle FSH levels measured at baseline, mid-cycle, and on trigger day predict blastocyst euploid rate? Summary answer Repeat measurements of FSH were not useful for predicting the euploid rate of blastocysts after accounting for the effects of female age. What is known already During the follicular phase of ovarian stimulation cycles, blood FSH levels are kept at supraphysiologic levels for a longer period compared to naturally occurring ovulation cycles during which FSH levels recede in response to rising estradiol. Some studies suggested maintaining higher than necessary blood FSH concentrations may have a detrimental effect on embryo quality and ploidy and recommended intra-cycle FSH monitoring. Whether intra-cycle measurements of FSH can be used to predict euploid rate is yet to be determined. Study design, size, duration Retrospective study was performed at tertiary IVF refereral center, including 373 cycles between April 2017 and February 2022. All GnRH (Gonadotropin-Releasing-Hormone) antagonist stimulation cycles using only recombinant FSH were included. Included patients were between 19 and 44 years old and all embryos underwent aneuploidy testing with Next Generation Sequencing using trophectoderm biopsy. Patients with PCOS, surgical sperm extraction, or warmed oocytes were excluded. Participants/materials, setting, methods Patients with primary or secondary infertility and an indication for ovarian stimulation for IVF/ICSI with PGT-A were included. Ovarian stimulation cycles were monitored according to the clinical routine by ultrasound and repeated measurement of FSH, E2, and progesterone at baseline, mid-cycle, and on trigger day. FSH changes were evaluated as delta differences between basal to mid-cycle levels and from mid-cycle to trigger levels. Main results and the role of chance 1,119 intra-cycle measurements of FSH were obtained from 373 cycles of 344 women. The median age of included women was 31 years (IQR:27-34), with AMH levels of 3.28ng/ml (IQR: 2.13-4.24). The euploid rate per fertilized oocyte was analyzed in categories of low (≤33.3%), normal (33.3 to 66.6%), and high (&amp;gt;66.6%). Delta change in serum FSH values from baseline to mid-cycle was not significantly different between groups (median change: 7.6 IU, 7.4 IU, and 6.2 IU; low, normal, and high euploid rate groups, respectively, P = 0.481). Again, delta change in mid-cycle to trigger day FSH was not significantly different between groups either (median change: -0.2 IU, 0.0 IU, 0.6 IU; low, normal, and high euploid rate groups, respectively, P = 0.151). After adjusting for the effect of age, basal FSH values (OR: 1.11, 95% CI:0.91-1.34, P = 0.248), delta FSH change to mid-cycle (OR: 0.99, 95% CI:0.91-1.07, P = 0.951) or delta change to trigger day (OR: 1.14, 95% CI:0.99-1.31, P = 0.067) was not significantly associated with high euploid rates. Performance of age alone compared to age and delta of FSH measurements combined for predicting high euploid rates, as measured with area under the curve (AUC) values, were AUC: 0.63 (95% CI: 0.54-0.71) and AUC: 0.66 (0.58-0.73), respectively (P = 0.369). Limitations, reasons for caution This was a retrospective study including only recombinant FSH cycles and findings represented here may not be generalizable to larger populations. Sample power may not be adequate to detect some effect sizes. Wider implications of the findings We could not demonstrate a direct relationship between euploid rate and delta change in intra-cycle FSH measurements. More studies using more diverse populations and larger sample sizes may be needed to further investigate this association. Trial registration number Not applicable

Analysis of oxidative stress and antioxidative potential in premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is characterized by an early decline in ovarian function, inducing secondary amenorrhea. While the cause of POI has not yet been identified, the function of mitochondria in the ovaries and the cytotoxicity associated with reactive oxygen species (ROS) have been implicated in follicle pool depletion and a decline in follicle quality. Recently developed tests have enabled easy measurement of diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The combination of these two tests is used to comprehensively assess oxidative stress in the blood. To comprehensively assess the oxidative stress of d-ROMs and BAP in POI. Participants were classified into two groups: A POI group of 11 women aged < 40 years examined between January 2021 and June 2022 with a history of secondary amenorrhea for at least 4 mo in our hospital and an FSH value of ≥ 40 mIU/mL; and a control group of healthy women of the same age with normal ovarian function in our hospital. Plasma d-ROMs and BAP were measured in both these groups underwent. Differences between groups were assessed using the t-test. The mean age and mean body mass index (BMI) were 35.8 ± 3.0 years and 20.1 ± 1.9 kg/m2 in the control group and 35.8 ± 2.7 years and 19.4 ± 2.5 kg/m2 in the POI group, respectively. The mean gravidity and parity in control and POI groups were 0.6 ± 0.7 and 0.4 ± 0.5 and 0.6 ± 0.9 and 0.3 ± 0.5, respectively. The two groups did not differ significantly in terms of mean age, BMI, gravidity, or parity. The d-ROMs level was significantly higher in the POI group than in the control group (478.2 ± 58.7 vs 341.1 ± 35.1 U.CARR; P < 0.001); however, the BAP level did not significantly differ between the two groups (2078.5 ± 157.4 vs 2029.0 ± 186.4 μmol/L). The oxidase stress index (d-ROMs/BAP × 100) was significantly higher in the POI group than in the control group (23.7 ± 3.3 vs 16.5 ± 2.1; P < 0.001). Oxidative stress was significantly greater in the POI group than in the control group, suggesting oxidative stress as a factor that can serve as a POI biomarker.

Exclusive Sertoli Cell Syndrome (ESCS) is a rare condition that has male infertility as its main consequence. It is one of the most serious forms of non-obstructive azoospermia, with a poor reproductive prognosis

Abstract Exclusive Sertoli Cell Syndrome (ESCS) is a rare condition that has male infertility as its main consequence. It is one of the most serious forms of non-obstructive azoospermia, with a poor reproductive prognosis. In some cases, however, such as the type II of the syndrome, sperm can be recovered through testicular puncture and subsequent ICSI, with a 13% success rate. This article aims to report the case of an azoospermic 35-year-old patient, with no other significant changes in complementary exams. 35 years old man with history of primary infertility, he was married since 17 years with normal sexual activity and and average built. Hematologic examination and biochemistry lab data were within normal limits. LH and total testosterone values were also within normal range, together with slightly elevated FSH value (119.88mUI/ml. There was azoospermia in the first semen analysis. Repeated semen analysis, 3 months later, revealed azoospermia. The karyotype of the patient is 46, XY with no Y chromosome micro deletions. Scrotal Color Doppler ultrasound and MRI examinations revealed that both testicles were in the left hemiscrotum. The lower testis had 53×26×43 mm dimensions and the posterosuperior located testis had 27×16×25 mm dimensions. Total abdominal ultrasonic examination revealed no developmental anomaly of urinary system. Family history of the patient revealed that mother and father were cousins no family history of infertility, the picture suggestive a case of sertoli only cell syndrome.

Infertile men with semen parameters above WHO reference limits at first assessment may deserve a second semen analysis: Challenging the guidelines in the real-life scenario.

To investigate which infertile men with semen parameters above WHO reference limits at first semen analysis deserve a second semen test. Data from 1358 consecutive infertile men were analysed. Patients underwent two consecutive semen analyses at the same laboratory. Descriptive statistics and logistic regression models tested the association between clinical variables and semen parameters. A new predicting model was identified through logistic regression analysis exploring potential predictors of semen parameters below WHO reference limits after a previously normal one. Diagnostic accuracy of the new model was compared with AUA/ASRM and EAU guidelines. Decision curve analyses (DCA) tested their clinical benefit. Of 1358, 212 (15.6%) infertile men had semen parameters above WHO reference limits at first analysis. Of 212, 87 (41.0%) had a second semen analysis with results above WHO reference limits. Men with sperm parameters below reference limits at second analysis had higher FSH values, but lower testicular volume (TV) (all p<0.01) compared to men with a second semen analysis above WHO limits. At multivariable logistic regression analysis, lower TV (OR 0.9, p = 0.03), higher FSH (OR 1.2, p<0.01), and lower total sperm count (OR 0.9, p<0.01) were associated with second semen analyses below WHO limits. DCA showed the superior net benefit of using the new model, compared to both AUA/ASRM and EAU guidelines to identify those men with a second semen sample below WHO limits after a previously normal one. Approximately 60% of infertile men with a first semen analysis above WHO limits have a second analysis with results below limits. The newly identified risk model might be useful to select infertile men with initial semen results above WHO limits who deserve a second semen analysis.

New perspectives on fertility in transwomen with regard to spermatogonial stem cells.

Germ cells of transwomen are affected by gender-affirming hormone therapy (GAHT). Fertility will be lost after surgical intervention; thereby, fertility preservation becomes an increasingly imortant topic. This study investigated if the absolute number of spermatogonia in transwomen is comparable at the time of gender-affirming surgery (GAS) to that in pre-pubertal boys. We carried out a retrospective study of testicular tissues from 25 selected subjects, which had undergone a comparable sex hormone therapy regimen using cyproterone acetate (10 or 12.5 mg) and estrogens. As controls, testicular biopsies of five cisgender adult men (aged 35-48 years) and five pre-/pubertal boys (5-14 years) were included. Testicular tissues were immunohistochemically stained for MAGE A4-positive cells, the most advanced germ cell type. The number of spermatogonia per area was assessed. Clinical values and serum hormone values for FSH, LH, testosterone, free testosterone, estradiol and prolactin were determined on the day of GAS for correlation analyses. Round spermatids were the most advanced germ cell type in 3 subjects, 5 had an arrest at spermatocyte stage, while 17 showed a spermatogonial arrest. On average, testicular tissues of transwomen contained 25.15 spermatogonia/mm3, a number that was significantly reduced compared to the two control groups (P < 0.01, adult 80.65 spermatogonia/mm3 and pre-/pubertal boys 78.55 spermatogonia/mm3). Linear regression analysis revealed that testes with higher weight and high LH contained more spermatogonia. Irrespective of treatment dose or duration, spermatogenesis was impaired. Spermatogonial numbers were significantly reduced in transwomen compared to the control groups. When transwomen go through treatment to confirm their gender, their germ cells are affected. They lose their fertility after surgery, so fertility preservation becomes an important topic. We carried out a study looking at tissue from testes of 25 people who had been through the same sex hormone therapy until surgery. Blood samples were also taken. As controls, samples were taken from the testes of cisgender boys and adult men. On average, the samples from the testes of transwomen contained a smaller number of early sperm cells compared to the two control groups. Regardless of the dose or length of hormone treatment, the fertility of transwomen was significantly reduced so that counseling about fertility preservation should be offered before hormone therapy.