FSH Levels Research Articles

The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status.

Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic-pituitary-gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.

Establishment of a predictive nomogram for clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer

To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer. We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer, who were randomly divided into a training dataset (60%) and a testing dataset (40%). Using univariate analysis, multiple logistic regression analysis, and LASSO regression analysis, we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer. We employed an integrated learning approach that combined GBM, XGBOOST, and MLP algorithms for optimization of the model performance through parameter adjustments. The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age, Gn initiation dose, number of assisted reproduction cycles, and number of embryos transferred. The variables included in the LASSO model selection included female age, FSH levels, duration and initial dose of Gn usage, number of assisted reproduction cycles, retrieved oocytes, embryos transferred, endometrial thickness on HCG day, and progesterone level on HCG day. The nomogram demonstrated an accuracy of 0.642 (95% CI: 0.605-0.679) in the training dataset and 0.652 (95% CI: 0.600-0.704) in the validation dataset. The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725 (95% CI: 0.680-0.770) in the training dataset and 0.718 (95% CI: 0.675-0.761) in the validation dataset. The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. Post-hoc analyses of prospective cohort studies. Clinical research center. Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.

Increase in Testosterone Levels and Improvement of Clinical Symptoms in Eugonadic men With a Prolactin-secreting Adenoma.

Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Retrospective case-control longitudinal study at a tertiary referral center. From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P = .02 and P = .0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P = .0028 and P = .0088, respectively). LH and FSH levels also increased in PSPA-nt men (P < .05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P < .05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range.

PREVALENCE OF POLYCYSTIC OVARIAN SYNDROME AMONG YOUNG WOMEN WHO ATTENDED TERTIARY CARE HOSPITAL, VISAKHAPATNAM

Objective: The present study aimed to determine the prevalence of PCOS among young adults attended to medical OP in a Tertiary care teaching hospital. Materials: It is a retrospective study conducted in a Tertiary care teaching hospital, Visakhapatnam using existing records in the Department of Obstetrics and Gynaecology. The study was conducted from July 2021 to July 2023. The study population includes young adults of age in between 18-30 y. PCOS was defined by Rotterdam's criteria having presence of any two of the three features. Hormonal assays were conducted using immunoradiometric assay for TSH, LH, FSH. Results: Majority of the PCOS cases 39% were reported in the age group of 26-30 Y. Among the 100 cases reported, the majority of them are reported with menstrual irregularity 62%. However, it was identified from the results that the mean values of cholesterol and triglycerides levels are quite higher suggested hyperlipidemia. The hormonal levels of TSH, LH and FSH were normal. Conclusion: Although the overall frequency of PCOS is low and evaluating PCOS in young adults can be difficult, the condition is becoming more common at this age. Changes in lifestyle are essential at this age to avoid long-term metabolic and reproductive issues.

The relationship between follicle-stimulating hormone and metabolic dysfunction-associated fatty liver disease in men

ObjectivesThe present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males.MethodsData from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD.ResultA total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age.ConclusionsOur findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

Protective Role of Evolvulus Alsinoides Linn. on Chemical Induced Prostatitis in Male Albino Rats

“Evolvulus alsinoides Linn. (Vishnu Kiranti) plant is widely used as antibacterial and anthelmintic, anti-stress and anti-amnesic and a good memory tonic”.The present this study aimed to investigate the protective role of Evolvulus alsinoides L.on the inflammatory effects of AlCl3 induced prostatitis in rat model.Prostatitis was induced in male Wistar rats (n=24) treated with AlCl3 for 12 weeks. Following prostatitis induction, the rats were randomly assigned to one of four treatment groups: normal control (NC-group), prostatitis (AlCl3-group), Evolvulusalsinoides methanolic extract (EAME group), and AlCl3+EAME group. The animals were giventheir routinediets throughout the study period. The parameters including Reproductive hormones, inflammatory markers and Prostate Specific Antigen (PSA), were evaluated.The histopathological changes in the prostate were also studied. The results showed that there was a significant (p&lt;0.05) reduction in PSA levels and a significant (p&lt;0.05) increase in reproductive hormones, including LH, FSH, Progesterone, Testosterone, and Estradiol levels, in groups fed with EAME. The study concluded that the EAMEhad aneffective anti-inflammatory property, and histological examinations revealed a significant improvement in the prostatic histoarchitecture of groups fed EAME. Our research findings suggest that EAME is beneficial in the prevention and treatment of nonbacterial prostatitis.

Experience and andrological follow-up after testicular tissue cryopreservation

Research questionWhat is the experience and mid- and long-term andrological health follow-up of (pre)pubertal males who have undergone testicular tissue freezing (TTF)? DesignThis single-centre longitudinal retrospective cohort study reports on the mid- and long-term andrological health follow-up of (pre)pubertal males and young adults who underwent TTF for fertility preservation between January 2007 and December 2018. Medical characteristics and questionnaire data collected more than 18 months after TTF were analysed. ResultsThirty-six patients were revisited during a medical follow-up consultation. During follow-up after TTF, 72.7% of patients could not recollect their counselling consultation prior to TTF but 42.4% of them found information about the TTF process useful and sufficient. Parents’ or legal guardians’ feedback was more positive about the counselling consultation and the TTF process. After TTF and treatment, the majority of patients (76.9%) who provided a semen sample had non-obstructive azoospermia. Higher serum concentrations of FSH and LH and lower serum concentrations of inhibin B were associated with non-obstructive azoospermia compared with patients with oligozoospermia (P = 0.0182, P = 0.0245 and P = 0.0140 respectively). During cancer treatment, about half of pubertal patients reported sexual dysfunction, decreasing to approximately 20% after treatment. However, two patients had children using sperm donation and one patient had a child through natural pregnancy. ConclusionsThe involvement of parents or legal guardians is crucial in the decision-making process for fertility preservation in (pre)pubertal boys. Regular follow-up, including the use of questionnaires, is essential to provide guidance for fertility preservation programmes and information on fertility restoration options and to address the psychosocial aspects of fertility preservation.

Polystyrene microplastics trigger testosterone decline via GPX1

As an emerging environmental endocrine disruptor, polystyrene microplastics (PS-MPs) are considered to have the anti-androgenic feature and impair male reproductive function. To explore the adverse effects of PS-MPs on testosterone synthesis and male reproduction and further elucidate underlying mechanisms, BALB/c mice and Leydig cells were employed in the present work. The results indicated that 50 μm PS-MPs accumulated in mouse testes and were internalized into the cytoplasm. This not only damaged the testicular histomorphology and ultrastructure, but also reduced the viability of Leydig cells and the serum level of GnRH, FSH, LH, and testosterone. After PS-MPs exposure, the ubiquitination degradation and miR-425-3p-targeted modulation synergistically contributed to the suppression of GPX1, which induced oxidative stress and subsequently activated the PERK-EIF2α-ATF4-CHOP pathway of endoplasmic reticulum (ER) stress. The transcription factor CHOP positively regulated the expression of SRD5A2 by directly binding to its promoter region, thereby accelerating testosterone metabolism and ultimately lowing testosterone levels. Besides, PS-MPs compromised testosterone homeostasis via interfering with the hypothalamic-pituitary-testis (HPT) axis. Taken together, PS-MPs possess an anti-androgenic characteristic and exert male reproductive damage effects. The antioxidant enzyme GPX1 plays a crucial role in the PS-MPs-mediated testosterone decline.

Effect of altrenogest treatment before weaning on reproductive performance and production efficiency in primiparous and multiparous sows

BackgroundMost sows will experience negative energy balance during lactation resulting in impaired follicular development. This study aimed to treat 28-day lactating sows with altrenogest (ALT) to suppress follicle enlargement during lactation, and to assess the estrus and reproductive performance post-weaning.MethodsIn this study, we conducted two trials. In trial 1, we monitored the follicular development of lactating sows including 10 primiparous sows and 10 multiparous sows during the whole lactation to confirm the ALT administration time. In trial 2, a total of 42 primiparous and 111 multiparous sows were allocated to three treatments: Ctrl (control group, n = 51): no treatment; TAI (timed artificial insemination group, n = 51): sows were injected with equine chorionic gonadotropin (eCG) after weaning 24 h and gonadotropin-releasing hormone (GnRH) when they expressed estrus; and AT-TAI (ALT treatment-timed artificial insemination group, n = 51): base on the process of TAI group, the sows were fed with 20 mg ALT per day before weaning 10 days. All sows were artificially inseminated twice at 12 h and 36 h after estrus. The follicle size changes and serum hormone levels were explored in this process.ResultsAlthough the follicle size of multiparous sows was larger than primiparous sows during the whole lactation (P < 0.05), similar change trends of follicle size were observed in primiparous and multiparous sows. Meanwhile, the FSH, LH and E2 levels of multiparous sows were higher than primiparous sows. The ALT treatment significantly inhibits the increase in follicle size (P < 0.05) and reduces the serum levels of FSH, LH and E2 (P > 0.05). Additionally, ALT treatment increases estrus concentration and the preovulatory follicle size (P < 0.05), meanwhile, it delays the weaning-to-estrus interval (WEI, P < 0.001). However, the estrus rate, pregnancy rate, total pigs born and born alive did not differ between treatments (P > 0.05).ConclusionsThere were significant differences in the size of follicles in the lactation between primiparous and multiparous sows. ALT treatment during the last ten days of lactation concentrated estrus expression leading to higher work efficiency of breeder in batch production, however, with no improvement in reproductive performance.

Intracerebroventricular injection of spexin stimulates the hypothalamic-pituitary-testicular axis and increases the secretion of male reproductive hormones in rats

BackgroundMale reproductive functions are regulated in the hypothalamic-pituitary-gonadal (HPG) axis. Any problem in this axis would lead to the deterioration of reproductive functions. The present study aimed to investigate the effects of intracerebroventricular (icv) Spexin (SPX) infusion on the HPG axis in detail. Methods40 Wistar albino rats were divided into four groups: control, sham, SPX 30 nmol and SPX 100 nmol (n=10). 30 nmol/1 µl/hour SPX was administered icv to the rats in the SPX 30 nmol group for 7 days, while rats in the SPX 100 nmol group were administered 100 nmol/1 µl/hour SPX. On the 7th day, the rats were decapitated, blood and tissue samples were collected. Serum LH, FSH and testosterone levels were determined with the ELISA method, GnRH mRNA expression level was determined in hypothalamus with the RT-PCR method. Seminiferous tubule diameter and epithelial thickness were determined with the hematoxylin-eosin staining method. ResultsSPX infusion was increased GnRH mRNA expression in the hypothalamus tissue independent of the dose (p<0.05). Serum LH, FSH and testosterone levels in the SPX groups were increased when compared to the control and sham groups independent of the dose (p <0.05). Histological analysis revealed that SPX infusion did not lead to any changes in seminiferous epithelial thickness, while the tubule diameter increased in the SPX groups (p<0.05). ConclusionThe study findings demonstrated that icv SPX infusion stimulated the HPG axis and increased the secretion of male reproductive hormones.

P-598 Novel inactivating homozygous mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) and first live birth after in vitro maturation (IVM): a breakthrough

Abstract Study question How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation? Summary answer We report the first live birth after IVM in a patient with a novel homozygous inactivating LHCGR mutation (exon 6,c.470A&amp;gt;G). What is known already LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells. Inactivating mutations of the LHCG receptor lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purpose. Until now, egg donation represented the only option to treat their infertility. Study design, size, duration A case report. Participants/materials, setting, methods A 35 year-old nulliparous patient was referred to our university hospital for primary infertility. Main results and the role of chance The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia. Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger. We identified by genetic analysis a novel homozygous inactivating LHCGR mutation (exon 6, c.470A&amp;gt;G) that had never been described previously. IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen. Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy. The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain. Limitations, reasons for caution By definition, a case-report requires further studies to confirm our findings. Wider implications of the findings We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this live birth successfully obtained places IVM as the only reliable option for these patients to conceive with their own eggs. Trial registration number not applicable

O-258 Clinical factors associated with sperm retrieval success in hypogonadal nonobstructive azoospermic males undergoing microdissection testicular sperm extraction

Abstract Study question What factors are associated with sperm retrieval (SR) success through microdissection testicular sperm extraction (micro-TESE) in nonobstructive azoospermic (NOA) males with biochemical hypogonadism? Summary answer The SR success in hypogonadal NOA males is associated with FSH levels, pre-micro-TESE hormonal stimulation, presence of clinical varicocele, varicocelectomy history, and testicular histopathology results. What is known already Previous studies have investigated clinical predictors for SR success in NOA males, such as testicular volume, genetic status, and testicular histopathology, but these factors cannot be modified before SR. On the other hand, pre-SR hormonal stimulation and varicocele repair have shown potential for improving SR rates, although the evidence is inconclusive due to heterogeneity in patients and treatments. This lack of information makes it difficult for clinicians to determine whether medical or surgical interventions should be used before SR in NOA patients. Study design, size, duration This observational cohort study involved 616 hypogonadal NOA patients with primary spermatogenic failure who underwent micro-TESE at a University-affiliated center for male reproductive health between 2014 and 2021. Biochemical hypogonadism was defined as total testosterone (T) levels &amp;lt;350 ng/dL, measured from morning venous samples. All patients were naïve concerning previous SR attempts and were categorized into two groups based on whether they received pre-SR hormonal stimulation with recombinant gonadotropins (hCG alone or combined with FSH). Participants/materials, setting, methods Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological evaluations for NOA. Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success. Adjusted risk ratio (aRR) assessed the relationship between SR success and relevant predictors. SR rates were compared between patients receiving hormonal stimulation and those who did not. Logistic regression analysis evaluated the effect of baseline FSH levels, stratified by normogonadotropic (&amp;lt;12 IU/L) and hypergonadotropic (≥12 IU/L) classes, on SR success. Main results and the role of chance The overall micro-TESE success rate was 56.6%. Independent predictors of SR success included baseline FSH levels (aRR 0.98, 95% CI 0.96-0.99, p = 0.04), pre-SR hormonal stimulation (aRR 1.52, 1.28-1.73, p = 0.0002), the presence of clinical varicocele (aRR 0.09, 0.01-0.66, p = 0.04), history of previous varicocelectomy (aRR 1.53, 1.14-1.84, p = 0.01), and testicular histopathology results (p &amp;lt; 0.05). Patients who received hormonal stimulation achieved higher SR success rates than untreated patients (62.5% [182/291] vs. 51.4% [167/325], p = 0.006; aRR 1.52, 95% CI 1.28-1.73). Among patients receiving hCG-based hormonal stimulation, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p &amp;lt; 0.0001). A pre-micro-TESE T level of 418.5 ng/dL (AUC: 0.78) and a Delta T of 258 ng/dL (AUC: 0.76) distinguished treated patients with positive and negative SR outcomes. Subgroup analysis by baseline FSH levels showed that normogonadotropic individuals (aRR 1.41, 1.16-1.58, p = 0.002) benefited from hormonal stimulation, whereas hypergonadotropic subjects did not (aRR 1.20, 0.86-1.50, p = 0.23). The frequency of patients showing biochemical hypogonadism after hCG stimulation was reduced to 22.3% (65/291). The micro-TESE postoperative complication rate was 2.3% (14/616), while the frequency of patients exhibiting adverse effects presumably attributed to hormonal stimulation was 10.3% (30/291). Limitations, reasons for caution Limitations of the study include its observational nature and the absence of pregnancy data. The study focused on micro-TESE as the SR method and hormonal stimulation solely based on hCG (as monotherapy or associated with FSH), so results may differ with other treatments. Wider implications of the findings Our study underscores the complexity of counseling hypogonadal men with NOA, stressing the significance of assessing various factors. While our findings suggest potential benefits from pre-SR interventions, particularly hormonal stimulation and varicocele repair, none of the identified predictors can definitively determine the likelihood of successful SR. Trial registration number NCT05110391

P-062 The impact of isolated teratozoospermia on cumulative live birth rates in IVF and ICSI treatment: a retrospective analysis of 5254 completed cycles

Abstract Study question To assess fecundity using cumulative live birth rate (CLBR) per egg collection to determine if IVF and ICSI outcomes are significantly influenced by sperm morphology. Summary answer The presence of isolated teratozoospermia does not have a significant impact on the CLBR of IVF treatment. What is known already There is ongoing debate regarding the clinical significance. Some studies indicate a pivotal role of sperm morphology in successful pregnancies, others cast doubt on its reliability as a predictive factor. Despite the application of stringent grading criteria, concerns remain about the subjective nature of assessing sperm morphology. Discrepancies in success rates between normozoospermic and isolated teratozoospermic groups shown by previous research findings underscore the uncertainty surrounding this matter. Inconsistent findings in previous research may be explained by limited sample sizes and a focus on immediate successes, neglecting subsequent frozen cycles. This study seeks to address the overlooked aspects of teratozoospermia. Study design, size, duration A retrospective study was conducted at Waterstone Clinic, involving 5254 IVF/ICSI autologous cycles completed between 2009-2022 cycles (completed meaning all embryos were either transferred or disposed of). Cycles were categorised according to sperm morphology and divided into two groups: the isolated teratospermic (ITS) group (1218 cycles) defined as having less than 4% normal morphologic forms with all other semen parameters being normal, and the normal sperm (NS) group (4036 cycles). Participants/materials, setting, methods The primary outcome measures, included fertilisation rate, number of cryopreserved embryos per egg collection, and CLBR. Employing multivariate statistics, the analysis explored the impact of interferons on CLBR in relation to variables such as sperm morphology, female age, egg number, and aetiology. Main results and the role of chance The female base characteristics were similar between the two groups in terms of age (37.1 vs 37.1 y/o), oocyte number (9.4 vs. 9.7) and FSH level (7.6 vs. 7.6 IU/L). Statistically significant differences were observed in fertilisation rates (61.7% vs. 65.8%, p &amp;lt; 0.001) and fertilisation failure (5.9% vs. 3.3%, p &amp;lt; 0.001) from IVF treatments when comparing the ITS and the NS groups. However, there was not any significant difference in the number of cryopreserved embryos between the two groups. Additionally, the CLBR did not show any significant difference between the two groups for IVF (35.8% vs. 37.8%, p &amp;gt; 0.05) or ICSI treatments (38.1% vs. 33.2%, p &amp;gt; 0.05). ICSI did not confer any benefit in improving the CLBR outcome when compared to conventional IVF, when adjusted for female age, number of oocytes collected, and aetiology. Limitations, reasons for caution While this study is retrospective it encompasses a substantial cohort. A potential for bias due to the selection criteria for IVF and ICSI exists. The intrinsic subjectivity in sperm morphology assessment introduces additional potential bias. Wider implications of the findings Despite the lack of support from CLBR to advocate for choosing ICSI in patients with ITS, this study suggests that couples with ITS experience lower fertilisation and higher fertilisation failure rates with IVF. This observation can serve as a valuable indicator for investigating the occurrence of fertilisation failure. Trial registration number not applicable

P-665 High FSH level impairs VEGF secretion by thawed human ovarian tissue

Abstract Study question How does a high FSH level as related to POI (premature ovarian insufficiency) affect VEGF secretion by thawed human ovarian tissue? Summary answer After thawing, the high FSH concentration of 175mIU/mL (10ng/mL) significantly decreased VEGF secretion by human ovarian tissue by 25.6%. 17.5mIU/mL did not change VEGF secretion. What is known already Cryopreservation of ovarian cortical tissue has become an important method in fertility preservation. However, 70% of the follicles do not survive the reimplantation process due to an insufficient blood supply and oxidative stress. Human ovarian tissue secretes angiogenic factors, including VEGF, spontaneously. Its regulation by FSH is not known although 50% of the reimplantation patients show increased FSH levels (&amp;gt;25mIU/mL) due to POI. Study design, size, duration Provided a signed consent, biopsy punches of ovarian cortical tissue from 8 patients undergoing fertility preservation were studied. Slow freezing and thawing was applied as in the intern routine instructions. Participants/materials, setting, methods Human ovarian cortical tissue was cultured in full medium at 37 °C for 48h after thawing in presence or absence of 17.5mIU/mL (1ng/mL) or 175mIU/mL (10ng/mL) recombinant human FSH. VEGF-A secretion was measured by ELISA. The expression of VEGF-A, HIF-1α and FSHR was assessed by immunohistofluorescence per follicle. The effect of FSH was assessed by one-way-ANOVA with Tukey’s post test. The effect of culture or follicular maturation stage was analyzed by t test. Main results and the role of chance After thawing, VEGF secretion recovers and rises over time. The addition of 175mIU/mL FSH significantly impaired VEGF-A expression compared to untreated ovarian tissue (p = 0.016). The analysis of 481 follicles showed similar results of FSH affecting VEGF-A expression by immunostaining. In particular, primordial follicles expressed significantly less VEGF-A compared to growing follicles (primary+secondary; p &amp;lt; 0.0001). 48h tissue culture significantly increased VEGF-A expression in primordial follicles (p = 0.0041). The addition of the high FSH level significantly decreased VEGF-A expression in growing follicles (p = 0.0005). Limitations, reasons for caution Although VEGF-A is a key factor in angiogenesis, more factors are known to affect angiogenesis. The direct effect on angiogenesis should be evaluated. Moreover, the conditions in tissue culture may not represent those after reimplantation. Wider implications of the findings High FSH levels, as seen in patients with POI, might impair ovarian VEGF expression and angiogenesis. Hormone replacement therapy (HRT) might be endorsed before and during ovarian tissue reimplantation. More clinical and biological data are required to understand the regulators of angiogenesis after ovarian tissue reimplantation adequately. Trial registration number not applicable

P-664 Insulin-like peptide 3 as a potential biomarker in predicting IVF success and ovarian reserve in women with unexplained infertility and diminishing ovarian reserve

Abstract Study question Could insulin-like peptide 3 (INSL3) predict ovarian reserve and in vitro fertilization (IVF) success in women with unexplained infertility (UI) and diminishing ovarian reserve (DOR)? Summary answer In women with DOR, reduced intrafollicular and serum INSL3 levels correspond with low AMH and high FSH levels, similar to established ovarian reserve markers. What is known already INSL3, belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Study design, size, duration This research was carried out at the IVF centers of two tertiary university hospitals, assessing 49 infertile women with either UI (n = 24) or DOR (n = 25) during IVF treatment. A control group (n = 26) comprised women with normal ovarian reserve undergoing IVF due to male or tubal factors. Outcome parameters are ovarian reserve markers (serum FSH, estradiol, AMH, INSL3 concentration and antral follicle count [AFC]), positive pregnancy rate and live birth rate (LBR) (gestational age ≥28 weeks). Participants/materials, setting, methods Women aged between 20-40 with a body mass index (BMI)&amp;lt;30 kg/m² were included. Serum FSH, estradiol, AMH, INSL3 levels and AFC were evaluated on menstrual cycle days 2 or 3, and INSL3 in follicular fluid from dominant follicles (&amp;gt;14 mm) were evaluated during oocyte retrieval. Exclusions included endocrine abnormalities (e.g., polycystic ovary syndrome, hyperprolactinemia, hypo and hyperthyroidism) cycle cancellation due to lack of a viable embryo, uncorrected Mullerian anomalies, recurrent miscarriage history and hydrosalpinx presence. Main results and the role of chance The mean age in the study groups was 28.41±3.5 (UI), 32.40±4.21 (DOR), and 29.65±3.91 (control). In the DOR group, female age (p = 0.001), BMI (p = 0.049), duration of infertility (p = 0.006), previous IVF attempts (p &amp;lt; 0.001), basal FSH (p &amp;lt; 0.001), and basal estradiol (p &amp;lt; 0.001) were higher, while AMH (p &amp;lt; 0.001), AFC (p &amp;lt; 0.001), and follicular fluid INSL3 (p &amp;lt; 0.001) were lower. Serum INSL3 in DOR was lower but not statistically significant. No correlation was found between serum INLS, follicular fluid INSL3, ovarian reserve markers, positive pregnancy rates, miscarriage, and LBR. DOR group had longer stimulation durations (p = 0.017), but lower max estradiol (p &amp;lt; 0.001), fewer oocytes (p &amp;lt; 0.001), mature follicles (p &amp;lt; 0.001), and PN (p &amp;lt; 0.001). Pregnancy rates were 54.1% (UI), 24% (DOR), and 53.84% (control); LBRs were 54.1% (UI), 20% (DOR), and 42.3% (control), with significant differences in pregnancy tests (p = 0.04) and LBR (p = 0.03), both lower in DOR. Univariate analysis identified duration of infertility (p = 0.019) and basal FSH (p = 0.009) as significant LBR predictors. Multivariable analysis confirmed basal FSH (p = 0.033) as significant, with increased duration of infertility and basal FSH level reducing LBR probability. Limitations, reasons for caution The limited sample size of our study potentially undermines the robustness of circulating INSL3 as a predictive biomarker for DOR, evidenced by the non-significant decrease in serum INSL3 levels in the DOR group. Moreover, the lack of INSL3 level assessment during oocyte retrieval further constrains our findings. Wider implications of the findings Our research explored INSL3 as a viable biomarker for predicting ovarian reserve and IVF success in UI and DOR cases. Reduced INSL3 levels in circulation and follicular fluid in DOR patients could be beneficial in clinical practice. Trial registration number not applicable

P-353 Perfluorooctanoic acid (PFOA) impacts murine ovarian follicle development through apoptotic signaling pathways and exhibits transgenerational effects

Abstract Study question How does Perfluorooctanoic Acid (PFOA) exposure impact ovarian function and the physiological and reproductive health of subsequent offspring? Summary answer PFOA exposure leads to ovarian dysfunction, characterized by follicular depletion and hormonal imbalances, and adversely affects the reproductive health of offspring. What is known already Mass spectrometry reveals higher perfluorinated compound levels in premature ovarian failure patients compared to healthy individuals. PFOA, an environmental contaminant, is known for its endocrine-disrupting effects, but its specific impact on ovarian function and transgenerational health remains less explored. This study addresses the gap by examining PFOA’s direct ovarian effects and its consequential impacts on offspring, using both in vivo and in vitro models. Study design, size, duration This study employs mouse models and ovarian granulosa cells to assess PFOA’s impact. Mice were administered PFOA (50mg/Kg) and evaluated for ovarian function and offspring health. Ovarian tissue underwent histological analysis and hormone assays. RNA transcriptome sequencing identified activated apoptotic pathways post-PFOA exposure. Offspring physiological and reproductive parameters were also examined. Parallel in vitro experiments with ovarian granulosa cells at 50uM PFOA concentration provided insights into cellular apoptosis. Participants/materials, setting, methods Clinically, we collected serum samples from approximately 100 Premature Ovarian Insufficiency (POI) patients and 100 healthy individuals, analyzed using mass spectrometry. In murine experiments, we simulated human environmental exposure to PFOA (particularly in high-exposure professions) using a 50mg/Kg dose administered via gavage. Transcriptome sequencing analyzed potential signaling pathways in both experimental and control mice. Offspring underwent physiological metabolic assessments and fertility evaluations, including fertilization and blastocyst rates. Main results and the role of chance Mass spectrometry results from human samples revealed significantly higher levels of perfluorinated compounds in POI patients compared to healthy controls, suggesting a potential link between PFOA exposure and ovarian dysfunction. In murine models, PFOA administration at 50mg/Kg resulted in notable ovarian changes. Histological analysis showed a reduction in follicle counts and abnormalities in AMH and FSH levels, indicative of premature ovarian failure. Transcriptome sequencing of these mice highlighted the activation of apoptotic pathways, especially the PI3K/Akt/mTOR signaling, post-PFOA exposure. This suggests a mechanistic pathway through which PFOA may induce ovarian dysfunction. Furthermore, offspring of PFOA-exposed mice displayed significant reproductive health challenges. They exhibited irregularities in estrous cycles and a decrease in oocyte fertilization rates, pointing to potential transgenerational effects of PFOA exposure. These findings in murine models align with the elevated perfluorinated compound levels observed in human POI patients, reinforcing the hypothesis of PFOA’s detrimental impact on ovarian health and subsequent generational fertility. The consistency of results across human clinical data and animal models strengthens the argument for a causal relationship between PFOA exposure and reproductive health risks. Limitations, reasons for caution While these findings highlight PFOA’s detrimental effects on ovarian function and offspring health, translating results from animal models to humans necessitates caution. The specific mechanisms and potential variability in human response to environmental PFOA exposure require further investigation. Wider implications of the findings This research underscores the far-reaching impacts of environmental contaminants like PFOA on reproductive health. It emphasizes the need for stringent regulation of such pollutants and further studies to understand their long-term effects on human health, particularly regarding fertility and intergenerational wellbeing. Trial registration number not applicable

P-007 Surgical sperm retrieval rate in men with Klinefelter syndrome is associated with testicular volume - but not with body constitution or Sertoli cell markers

Abstract Study question Do sperm retrieval and pregnancy rates in men with Klinefelter syndrome (KS) depend upon sperm retrieval method, age, testicular volume, body weight, and hormone concentrations? Summary answer Successful sperm retrieval was significantly associated with total testicular volume but not with sperm retrieval method, age, body weight, BMI, FSH, inhibin-B or AMH. What is known already Testicular sperm can be retrieved from approximately 40% of men with KS, resulting in an average pregnancy rate of 16%. The sperm retrieval rate seems to be unrelated to the age of the man and to preoperative FSH-levels. A decrease in testosterone concentration is usually observed 3 months after surgery. Possible negative effects of testosterone substitution therapy prior to surgery and the predictive value of body constitution, testicular volume and the Sertoli cell markers, AMH and inhibin-B, for sperm retrieval success in KS men are only partly known. Study design, size, duration A total of 14 KS patients underwent subcapsular orchiectomy and 34 KS patients underwent m-TESE at Centre of Andrology &amp; Fertility Clinic, Odense University Hospital. Pre-surgery examination included ultrasonography of the testicles, genetic analyses (standard chromosome analysis and screening for Y microdeletions and CFTR variants) and hormone analyses (including FSH, LH, testosterone, estradiol, prolactin, TSH, AMH, inhibin-B). Testosterone, LH, and FSH were also measured 3 months after surgery. Participants/materials, setting, methods Forty-three men had a 47,XXY karyotype, while 5 (2 from the subcapsular group and 3 from the m-TESE group) had a mosaic karyotype including 47,XXY. Subcapsular orchiectomy was performed unilaterally, while m-TESE was usually performed bilaterally. To avoid freezing the sperm retrieved, oocytes from the female partner was aspirated and vitrified after FSH-stimulation according to our usual IVF protocols. Oocytes were thawed on the day of sperm retrieval and embryos transferred in estrogen-progesterone stimulated cycles. Main results and the role of chance Sperm were obtained in 19 (40%) of the 48 men with KS. In 10 couples (21%) pregnancy was obtained and 7 women (15%) gave birth to at least one child resulting in ten children (6 girls and 4 boys), while one pregnancy is still ongoing. In the group who had a subcapsular orchiectomy, 5 (36%) had sperm retrieved, and pregnancy was obtained in 3 (20%) cases. Two gave birth to a child, while the third woman have had several abortions, most likely due to large fibromyomas of the uterus. In the m-TESE group 14 (41%) had sperm retrieved, and pregnancy was obtained in 7 (21%) cases. Five women (15%) gave birth to 8 children, while 1 pregnancy is still ongoing and the seventh experienced an early pregnancy loss. Furthermore, 3 couples have still not embryos transferred. Sperm were found in 3 men (60%) with mosaic karyotype. Sperm retrieval success was significantly associated with testicular volume (mean total testicular volumes of 3.4 mL vs. 2.3 mL; p &amp;lt; 0.01) but not with age, height, body weight, BMI or preoperative FSH, inhibin-B or AMH levels. Testosterone levels measured 3 months after the surgery, did not differ between men irrespective of surgical method. Limitations, reasons for caution The numbers of patients are limited and randomized studies with sufficient power are difficult to perform. AMH and inhibin-B, were only measured in the m-TESE group. Wider implications of the findings In KS patients, sperm retrieval and pregnancy rates were similar irrespective of the sperm retrieval method. Also serum testosterone 3 months postoperatively and cosmetic results experienced by patients were similar. Multicenter studies and larger studies are needed to provide more detailed information of the potential predictors for successful sperm retrieval. Trial registration number Not applicable

O-304 Is there any association between thyroid-stimulating hormone (TSH) levels and semen parameters? A retrospective study in a European fertility clinic

Abstract Study question Is there any association between TSH levels and semen parameters considering age, body mass index (BMI), and life style? Summary answer In line with the results of logistic regression, normal TSH values increase the probability of having a higher sperm count. What is known already To date, association between TSH levels, semen parameters and other hormones have not been thoroughly investigated in European andrology labs. However, while andrology guidelines do not support a systematic evaluation of thyroid function, some studies reported that men in infertility clinics have higher risks of presenting thyroid disorders than in the general population. Study design, size, duration Both partners investigated for sterility are routinely checked for TSH in the work up of our clinic. We examined for 2021 – 2023 all 347 male patients (infertile/fertile) with complete records of demographic data, semen analysis and hormone analysis. Patients suffering from azoospermia, genital tract infections, hormonal supplementation or heavy medical treatments (radiotherapy, chemotherapy), as well as those receiving iodine supplements or drugs that could potentially affect testicular or thyroid physiology, were excluded. Participants/materials, setting, methods Age, BMI, smoking and detailed alcohol intake were recorded. A blood sample was taken from each patient in connection with the sperm collection to measure TSH, FSH, LH, prolactin and testosterone levels. Spearman’s correlation coefficients were used to determine correlations among hormones. Statistical analyses were performed using semen parameters as dichotomized using WHO reference values. Men above the reference values for count, concentration and motility were used as comparison subjects in multivariate logistic regression. Main results and the role of chance The analysis explored relationships between age, BMI, smoking, alcohol consumption and semen parameters with TSH hormone levels. The mean age of the participants was 35.8 ±7.43 years and BMI was 27.2 ±4.54 kgm-2. Of all participants, 37% reported being smokers, alcohol consumption was 3% regularly, 35% occasionally, 44% rarely, 18% none. Considering a TSH level (0.4-4 mIU/l) as normal, the prevalence of thyroid dysfunction in the cohort was 0.9% (TSH &amp;lt;0.4) and 1.1% (TSH &amp;gt;4) implying that most patients had normal TSH levels. In this cohort, TSH levels were not found to be significantly affected by age, BMI, smoking or alcohol consumption despite being known as putative confounding factors influencing TSH levels. Among the various hormones evaluated, only one significant positive correlation was found between TSH and Prolactin (r = 0.199, p = 0.0001), while a trend towards a negative correlation between TSH and LH (r=-0.101, p = 0.073) was suggested. Multivariate logistic regression analysis showed, not surprisingly, that age was a factor influencing sperm count, sperm concentration as well as total and progressive sperm motility. Logistic regression also showed that when TSH values were within the normal range, sperm counts were significantly higher (OR:1.302, P = 0.043; CI95%:1.009-1.681). Limitations, reasons for caution Sperm morphology and viability were not recorded. Evaluation of thyroxine (T4) and triiodothyronine (T3) levels could be useful. The crucial role of iodine and the complex relationship between iodine and selenium status (which depends on geographical location) in affecting thyroid function should be taken into account in future studies. Wider implications of the findings Male patients with abnormal TSH levels are not very common in this region. Normal TSH level is associated with a higher sperm count. TSH assessment in infertile couples should be routine in both partners, given the recorded worldwide increase in thyroid dysfunction and iodine deficiency. Trial registration number not applicable

The proliferation and differentiation of spermatogonial stem cells in the frist wave of spermatogenesis in rats with Trib3 gene knockout

This study explores the effects of Trib3 gene knockout on adult male rat spermatogenesis. Using CRISPR/Cas9, we knocked out the Trib3 gene in Wistar rats. Results indicate altered expression of PLZF, ID4, and c-KIT in knockout rats, suggesting impaired spermatogonial stem cell proliferation and differentiation. Histological analysis reveals reduced seminiferous tubule area and decreased spermatocyte numbers. Mating experiments demonstrate reduced offspring rates after the second self-mating in knockout rats. SYCP3, a meiosis marker, shows elevated expression in knockout rat testes at 14 days postpartum, suggesting an impact on reproductive processes. ELISA results indicate decreased testosterone, FSH, and FGF9 levels in knockout rat testicular tissues. In conclusion, Trib3 gene deletion may impede spermatogonial self-renewal and promote differentiation through the FSH-FGF9- c-KIT interaction and p38MAPK pathway, affecting reproductive capacity. These findings contribute to understanding the molecular mechanisms regulating spermatogenesis.