Normal Follicle-stimulating Hormone Research Articles

Challenges in differential diagnosis between obstructive and non‐obstructive azoospermia

AbstractBackgroundSome cases of non‐obstructive azoospermia (NOA) are characterized by normal clinical parameters, including testicular volume and levels of reproductive hormones, mimicking obstructive azoospermia (OA).MethodsWe performed a retrospective review of a consecutive series of 1417 patients undergoing primary surgical sperm retrieval between 2014 and 2023. Follicle‐stimulating hormone (FSH) level below 7.6 IU/l and normal testicular size with a long axis measurement >4.6 cm were used as criteria to suspect OA.ResultsFour hundred and eighteen patients with normal testicular volume and FSH levels had an initial diagnosis of OA. Among them, 243 (58.1%) had histological signs of spermatogenic dysfunction, and 175 (41.9%) had true OA. One hundred eleven patients had long‐standing obstruction (median: 16.5 years) with a median Bergmann–Kliesch score (BKS) of 5 (interquartile range [IQR]: 4–6) and 100% sperm retrieval rate (SRR), though some required microdissection testicular sperm extraction (microTESE). Fifty‐eight patients with a history of epididymo‐orchitis had a median BKS of 4 (IQR: 2–6) and 100% SRR. Twenty patients with a history of unjustified medical treatment for male infertility had a median BKS of 3 (IQR: 1–4) and 80% SRR. Fifty‐four patients had uniform maturation arrest with a 5.5% SRR on microTESE.ConclusionMen with normal testicular volume and FSH level may have evidence of spermatogenic failure on pathology. Patients with complicated seminal tract obstruction commonly have hypospermatogenesis, but true NOA caused by uniform maturation arrest may also be observed. Patient counseling for suspected OA should not be overly optimistic, and couples should be warned about possibility of conversion to microTESE and risks of negative sperm retrieval.

Premature Ovarian Insufficiency After Coronavirus Disease 2019 (COVID-19): Autoimmune Follicle-Stimulating Hormone (FSH) and FSH Receptor Blockade.

Since the onset of the coronavirus disease (COVID-19) pandemic, a variety of long-COVID-19 symptoms and autoimmune complications have been recognized. We report three cases of autoimmune premature poor ovarian response in patients aged 30-37 years after mild to asymptomatic COVID-19 before vaccination, with nucleotide antibody confirmation. Two patients failed to respond to maximum-dose gonadotropins for more than 4 weeks, despite a recent history of response before having COVID-19. After a month of prednisone 30 mg, these two patients had normal follicle-stimulating hormone (FSH) levels, high oocyte yield, and blastocyst formation in successful in vitro fertilization cycles. All three patients have above-average anti-müllerian hormone levels that persisted throughout their clinical ovarian insufficiency. Two patients had elevated FSH levels, perhaps resulting from FSH receptor blockade. One patient, with a history of high response to gonadotropins 75 international units per day and below-normal FSH levels, had no ovarian response to more than a month of gonadotropins (525 international units daily), suggesting autoimmune block of the FSH glycoprotein and possible FSH receptor blockade. Auto-antibody production in response to COVID-19 before vaccination may be a rare cause of autoimmune poor ovarian response. Although vaccination is likely protective, further study will be required to evaluate the effect of vaccination and duration of autoimmune FSH or FSH receptor blockade.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

FSH-producing pituitary neuroendocrine tumor as a cause of ovarian hyperstimulation syndrome.

Functioning gonadotroph tumors are rare neoplasms that can cause ovarian hyperstimulation syndrome (OHSS) in women of reproductive age. Here, we present a case of a follicle-stimulating hormone (FSH)-producing pituitary neuroendocrine tumor (PitNET) with irregular menstrual cycles and OHSS in a Japanese woman. A 34-year-old woman with bilateral multi-cystic ovarian mass was referred to our hospital for ovarian surgery. The imaging feature of magnetic resonance imaging (MRI) of the ovary and elevated estradiol levels with normal FSH and low luteinizing hormone (LH) levels led us to suspect the presence of a functioning gonadotroph PitNET. MRI revealed a 19-mm pituitary tumor, and increased tracer uptake was observed in the pituitary lesion on 111In-pentetreotide scintigraphy. Transsphenoidal tumor resection resulted in the resolution of the ovarian enlargement, normalization of her menstrual cycles, and spontaneous pregnancy. Immunohistochemistry (IHC) of the resected tumor for pituitary transcription factors, including steroidogenesis factor 1 (SF1) and estrogen receptor alpha, demonstrated positive immunoreactivity, whereas IHC for pituitary-specific positive transcription factor 1 was negative, suggesting that the tumor belonged to the SF1 lineage of PitNETs (gonadotroph tumor). The tumor cells showed positive expression of FSHβ, while LHβ was mostly negative. Consistent with the high pituitary tumor uptake observed on 111In-pentetreotide scintigraphy, the pituitary tumor showed positive expression of somatostatin receptor 2A. Detailed clinical and histological evaluations will provide useful information to understand these rare functioning gonadotroph tumors better. Functioning gonadotroph tumors are very rare neuroendocrine tumors of pituitary origin. Women of reproductive age presenting with bilateral multi-cystic ovarian enlargement, irregular menstrual cycles, and hyperestrogenemia under unsuppressed follicle-stimulating hormone (FSH) levels should be evaluated for FSH-producing tumor. Raising awareness of OHSS due to functioning gonadotroph tumors is crucial to prevent unnecessary ovarian surgery. Comprehensive histological analysis may provide useful information to better understand the characteristics of functioning gonadotroph tumors.

Predictive role of 17α-hydroxy-progesterone serum levels of response to follicle-stimulating hormone in patients with abnormal sperm parameters

To study the possible role of serum 17α-hydroxy-progesterone (17αOH-P) levels in predicting favorable responses to follicle-stimulating hormone (FSH) administration in patients with normal serum FSH levels and idiopathic abnormal sperm parameters. Prospective cohort study. University-affiliated fertility center. Fifty patients with oligozoospermia, asthenozoospermia, and/or teratozoospermia and normal serum levels of gonadotropins and total testosterone (TT). Treatment with exogenous FSH is administered subcutaneously at a dose of 150 IU 3 times a week for 3 consecutive months. Luteinizing hormone levels, FSH levels, TT levels, 17αOH-P levels, testicular volume, conventional sperm parameters, and seminal spermatid concentration were evaluated before and after therapy. To evaluate the predictive role of pretreatment serum 17αOH-P levels on FSH responsiveness, the doubling of sperm concentration at the end of the FSH administration was considered a positive outcome. After therapy, patients showed a significant increase in sperm concentration, total sperm count (TSC), progressive motility, percentage of normal forms, FSH levels, TT levels, and testicular volume. There was a negative correlation between pretreatment 17αOH-P levels and the posttreatment increase in sperm concentration, TSC, progressive motility, and normal morphology, and a positive correlation with the posttreatment increase in spermatids. Predictive analysis showed that 17αOH-P levels (<1.18 ng/mL) foretold a doubling of sperm concentration with a sensitivity of 90.0% and a specificity of 73.3%, and of TSC with a sensitivity of 91.3% and a specificity of 81.48%. The results of this study suggest that pretreatment serum levels of 17αOH-P, a marker of steroidogenic function, appear to be able to predict the success of subcutaneous administration of exogenous FSH in terms of spermatogenesis improvement. Receiver operating characteristic curves indicated that 17αOH-P levels (<1.18 ng/mL) predict a doubling of sperm concentration and TSC after exogenous FSH administration to patients with idiopathic abnormal sperm parameters and normal gonadotropin levels.

Follicle Stimulating Hormone (FSH) as a Predictor of Decreased Oocyte Yield in Patients with Normal Anti-Müllerian Hormone (AMH) and Antral Follicle Count (AFC).

The purpose of the current study was to determine the utility of early follicular phase follicle-stimulating hormone (FSH) testing in patients undergoing in vitro fertilization (IVF). This was a retrospective review of patients from 2012 to 2015 at Mayo Clinic in Rochester, Minnesota, USA. Included subjects had a normal anti-Müllerian hormone (AMH) of 1 to 9 ng/ml and antral follicle count (AFC) of 10 to 29. Patients were stratified by FSH level when associated estradiol was less than 50 ng/ml. In total, 225 patients were categorized into three groups: high FSH (FSH ≥10 IU/L; n= 36), normal FSH (>5 IU/L and <10 IU/L; n=170), and low FSH (FSH ≤5 IU/L; n= 19). ANOVA and multiple logistic regression were used for statistical comparisons and for evaluation of the relationships between variables; significance level was set at <0.05. There were no significant differences in demographics, IVF cycle type, or peak estradiol level between the groups. Patients with a high basal FSH level had a similar clinical pregnancy rate and live birth rate compared to controls and patients with low FSH. High FSH level was associated with decreased follicular development (17 versus 22; p<0.01), oocyte yield (15 versus 18; p=0.02), and embryo yield (8 versus 10; p=0.04) despite higher total doses of gonadotropins. Patients with normal AMH and AFC levels could be further stratified into lower responders and starting doses of medications can be adjusted based on high basal FSH levels. Therefore, it is suggested to counsel patients on pregnancy outcomes which seem to be quite similar regardless of the FSH level.

(416) Clinical Characteristics of Men with Sexual Dysfunction Visiting an Andrology Clinic: A Single-Center Study in Saudi Arabia

Abstract Introduction Previous studies that investigated the clinical characteristics of sexual dysfunction in men in Saudi Arabia are limited. This study aimed to explore the clinical characteristics of sexual dysfunction in men visiting an andrology clinic in Saudi Arabia. Objective This study aimed to explore the clinical characteristics of sexual dysfunction in men visiting an andrology clinic in Saudi Arabia. Methods This study is a retrospective single-center cross-sectional study. A random sampling method was used to recruit participants between March and September 2019. Descriptive statistics were used to describe patients’ characteristics. Continuous data were reported as mean ± SD. Chi-squared and multiple logistic regression were used to find the associations between patient's age (older and younger than 50 years) and clinical characteristics of the participants. Results In total, 21.3% participants had diabetes and 9.5% had hypertension. More younger males suffered from sexual problems (69.8%) compared to older males (30.2%). Also, 37.5% participants were overweight, while 25.3% had class I obesity. Most participants had normal follicle stimulating hormone, prolactin, testosterone, luteinizing hormone, and prostate specific antigen levels. Approximately 69.5% had vitamin D insufficiency. Among those older than 50 years, 80.2% had diabetes (P &amp;lt; 0.05). Younger smokers accounted for 79% of the population, with a significant association between patient's age and smoking status (P &amp;lt; 0.05). Patients younger than 50 years with normal A1C levels had a 2.5 times higher risk of having sexual problems (P &amp;lt; 0.00, confidence interval 1.63–3.91). Conclusions MSD may be considered to be caused by other nonorganic problems. There is a significant need to increase Saudi men's awareness of sexual medicine. Disclosure No

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment.

Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited. This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols. Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0-13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p=.0278) and low INHB serum levels (p=.0130) were recorded after CT-HSCT, especially after myeloablative conditioning. The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.

Effect of CoQ10 Supplement on Spermogram Parameters and Sexual Function of Infertile Men Referred to The Infertility Center of Fatemieh Hospital, Hamadan, Iran, 2019: A Randomized Controlled Trial Study.

The aim of this study was to investigate the effects of the antioxidant supplement of CoQ10 and placebo in the male infertility treatment. The randomized controlled trial study was designed as a clinical trial. Samples in each group consisted of 30 members. The first group received 1 daily dose of 100 mg coenzyme Q10 capsules and the second group received a placebo treatment. Treatment in both groups lasted 12 weeks. Before and after the intervention of semen analysis, hormonal measurement of testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid stimulating hormone (TSH) were done. Sexual function was assessed before and after the intervention by using the International Index of Erectile Dysfunction questionnare. The mean age of participants was 34.07 (5.26) years in the CoQ10 group and 34.83 (6.22) in the placebo one. Normal volume of semen (P=0.10), viscosity (P=0.55), sperm count (P=0.28), and sperm motility (P=0.33) in the CoQ10 group increased without statistically significant differences. But the normal sperm morphology increased with statistically significant differences in the CoQ10 group (P=0.01). There was an increase in normal FSH levels and testosterone levels in the CoQ10 group compared with the placebo patients, but these differences were not statistically significant (respectively P=0.58, P=0.61). The results also revealed that the scores of erectile function (P=0.95), orgasm (P=0.86), satisfaction with sexual intercourse (P=0.61), overall satisfaction (P=0.69) and the score of the International Index of Erectile Function (IIEF, P=0.82) were greater after the intervention in the CoQ10 group than in the placebo group although the difference was not statistically significant. The use of CoQ10 supplement can improve sperm morphology; however, in other sperm parameters and also in some hormones increased after the intervention, this was not statistically significant and therefore the result is not conclusive (registration number: IRCT20120215009014N322).

Compensated Hypospermatogenesis: Elevated Follicle-stimulating Hormone Predicts Decline in Semen Parameters Among Men With Normal Index Semen Analysis

ObjectiveTo determine whether men with elevated follicle-stimulating hormone (FSH) and normal semen analysis (SA) are more likely to experience a decline in semen parameters over time compared to men with normal FSH. MethodsMen presenting for fertility evaluation between 2002 and 2020 with normal initial SA were dichotomized according to baseline FSH as normal (<7.6 IU/mL) vs elevated (≥7.6 IU/mL). Primary outcomes included the development of abnormal sperm concentration (<15 million/mL) and total motile sperm count <9 million. Secondary outcomes included abnormal sperm motility (<40%), morphology (<4%), and total number of SA abnormalities. ResultsThe final sample consisted of 858 men; 776 had normal FSH, and 82 had elevated FSH at presentation. Compared to men with normal FSH, men with elevated FSH had lower total motile sperm count (64.1 vs 107.3, P < .001) and higher testosterone levels (339 ng/dL vs 309 ng/dL, P = .03). At each follow-up timepoint, more men with elevated FSH had oligospermia compared to men with normal FSH. Men with elevated FSH were more likely to experience a decline in total motile sperm count below the intrauterine insemination threshold of 9 million and more likely to develop SA abnormalities over time. ConclusionIn men presenting for fertility evaluation with normal index SA, elevated FSH was associated with subsequent decline in semen parameters over time. Men with elevated FSH and normal SA, a condition we have termed compensated hypospermatogenesis, represent an at-risk population for whom close follow-up is warranted.

Gonadal Hormone Production after Hematopoietic Cell Transplant (HCT) in Patients with Sickle Cell Disease (SCD): A Stellar Study

Introduction HCT is the only therapy for SCD with curative intent, but the alkylator chemotherapies used in preparative regimens place patients at high risk for gonadal dysfunction. Adequate ovarian and testicular hormone production post-HCT is important for optimal health. Methods We enrolled children and adults with SCD ≥ 1-year post-HCT ("HCT") in the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) and a control group of patients with SCD not treated with HCT ("non-HCT"). We obtained annual surveys of gonadal health using a web-based platform. Surveys were completed by proxies for individuals <18 years and were self-report for individuals ≥18 years. Markers of ovarian reserve or testicular function were measured, including follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) in females and FSH and testosterone in males. The most recent survey was used for analysis when multiple surveys were available. The upper limit of normal (ULN) for age of pubertal onset was defined as 13 years in females and 14 in males, and the ULN for menarche was 15 years. Only females >13 years and males >14 years (ULN for activation of the hypothalamic pituitary gonadal axis) were included in the FSH analysis. Descriptive statistics were reported as median (Interquartile range [IQR]: 3rd quartile - 1st quartile), mean (min, max) or count (%). Statistical procedures involved a chi-squared test. The effect size was calculated using standard mean difference (SMD). Results Surveys were completed by 48 SCD HCT patients (30 females, 18 males) and 12 SCD control patients (8 females, 4 males). Median age (IQR) at survey completion was 14.8 years (11.8) for female HCT, 16.0 (10.4) for male HCT, 14.5 (11.6) for female non-HCT, and 21.0 (22.8) for male non-HCT. Median age (IQR) at HCT was 8.8 years (6.1) for females and 9.1 years (5.2) for males. Most patients underwent HCT in 2010-2020 (86.7% of females, 78.8% of males). Donor was predominantly matched related (90.0% of females, 94.4% of males) with bone marrow stem cell source (90.0% of females, 94.4% of males). Most patients received myeloablative conditioning (86.7% of females, 94.4% of males). Only female HCT patients (n=8, 32%) reported being told they might need hormones to enter puberty. In females who were ≥15 years, menarche was reported in 11 (78.6%) HCT and all of the non-HCT patients. Current menstruation was reported in 9 (64.3%) HCT and 3 (75.0%) of non-HCT patients, and 10 (71.4%) HCT and 1 (25%) non-HCT females reported ever having taken hormones, including birth control. P-values and SMD can be seen in Table 1. Hormone levels were measured in 68 HCT patients (41 female, 27 male). Most patients underwent HCT from 2010-2020 (82.9% of females; 74.1% of males) using matched related donor (90.2% of females, 92.6% of males) bone marrow (87.8% of females, 85.2% of males) following myeloablative conditioning (87.8% of females, 88.9% of males). For females, the median age at the time of AMH testing was 16.5 years (IQR 9.1) with a mean of 6.8 years (IQR 4.8) post-HCT. Based on the age and assay normal values, AMH levels were normal in 3 (7.3%), low but detectable in 7 (17.1%), and undetectable in 31 (75.6%) of patients. FSH was measured in 12 females who were >13 years and not on hormone therapy (Table 2). The median age at FSH testing was 18.0 years (IQR 5.1), with a mean of 8.7 years (IQR 3.5) post-HCT. FSH levels were normal in 7 (58.3%) and above the ULN in 5 (41.7%), 3 of which were menopausal (>30mIU/mL). Testosterone values were obtained in 15 males who were >14 years with a median age 18.9 years (IQR 5.9) and a mean of 6.9 years (IQR 5.1) post-HCT. The mean testosterone level was 365.8 ng/dl (range 152-592), 13 (86.7%) of which were in the normal range and 2 (13.3%) being low. FSH values in males >14 years were high in 4 (26.7%). Conclusions Nearly all females had diminished ovarian reserve post-HCT, with >75% having undetectable AMH levels. In addition, close to half of the females had elevated FSH levels, some in the menopausal range. However, females with normal FSH and normal or low AMH can consider post-HCT mature oocyte cryopreservation. Most males had normal testosterone levels, but >25% had elevated FSH levels which could be a signal of impaired spermatogenesis. These findings highlight the importance of studying the impact of HCT on gonadal function and the consideration of these outcomes when developing protocols for curative therapy in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The positive predictive value of using fsh and Inhibin-B serum levels to diagnose gonadotropin insufficiency in bilateral cryptorchid boys is high

Despite early surgery, many boys with bilateral cryptorchidism at surgery have a reduced number of germ cells per tubular cross-section (G/T) in testicular biopsies and/or low inhibin-B with no elevated follicle-stimulating hormone (FSH) as expected based on a normal gonadotropin feed-back mechanism. Such boys have a high risk of later infertility because of insufficient gonadotropin stimulation and may benefit from adjuvant hormonal treatment. Testicular biopsies are not always wanted or accepted. The study aim was to investigate the value of a low inhibin-B and normal FSH to identify patients that might benefit from adjuvant hormonal treatment avoiding the need for testicular biopsy. A series of boys with cryptorchidism were evaluated with serum levels of inhibin-B and FSH in relation to G/T in testicular biopsies, which were compared to previously published age-matched normal control values. A total of 365 boys who underwent bilateral orchidopexy between 0.4 and 7.8 (median: 2) years of age were included. Twenty-seven (7%) patients had increased FSH and low G/T, whereas 11 of these also had low inhibin-B indicating hypergonadotropic hypogonadism. Moreover, 85 (23%) patients between 0.75 and 7.5 (median: 2) years of age had both low G/T (median: 0.3) and low inhibin-B (median: 56pg/ml) but normal FSH (median: 0.6 U/l) indicating a gonadotropin insufficiency. Three patients with normal FSH and low inhibin B had normal G/T. Our study shows that if surgeons prefer to avoid testicular biopsies and only wish to rely on hormonal parameters (low inhibin-B and normal FSH) in order to diagnose a gonadotropin insufficiency as the cause of hypogonadism, they will identify only about 30% of such cases and overlook about 70% of patients sharing the same endocrinopathy. In addition, if surgeons treat patients for gonadotropin insufficiency only based on low inhibin-B and normal FSH they will solely treat patients with gonadotropin insufficiency and would not overtreat patients. Adjuvant hormonal treatment was indicated by a gonadotropin insufficiency discerned in 23% of boys with bilateral cryptorchidism. Without histology, the clinicians are left with more difficult clinical judgments to identify patients for adjuvant hormonal treatment. The positive predictive value of low inhibin-B and normal FSH corroborated by low G/T was 0.97 (85/85+3), but the sensitivity was low (0.30).

The use of vinylcyclohexene diepoxide to create diminish ovarian reserve model on rats

Background: Infertility remains a significant issue in the world of health. Now Assisted Reproductive Technology (ART) is widely used to help couples with infertility. In ART diminish ovarian reserve patients have a very low success rate of pregnancy. To help patients with Diminished Ovarian Reserve (DOR), research is conducted using an animal model. vinylcychlohexene diepoxide (VCD) has ovotoxic effects. This study looked at the use of VCD in inducing targeted DOR conditions in animals (rats), create a model that could be used for future animal studies in infertility. Methods: Adult female Rattus norvegicus were used in this study. All were given VCD injections at 80 mg/kg intraperitoneally for 15 days. An examination of Follicle Stimulating Hormone (FSH) levels will be carried out on days 0,3,5,7, and 15. To mimic IVF process, all rats got an injection of 10 IU of Pregnant Mare Serum Gonadotropin (PMSG) and 10 IU human Chorionic Gonadotropin (hCG) to confirm DOR. Ovarectomy was performed, dominant follicles were taken, denudation was carried out, and the oocytes were cultured for 12 hours. Then, oocytes were assessed through a microscope. Results: Starting from day 5 post VCD induction, there was a significant increase in the FSH level in the group of rats that were induced with the administered VCD dose compared to the control group that experienced normal FSH fluctuations. The FSH concentration reached &gt;50%. It was found that the number of degenerated oocytes had an average of 1.11. Oocytes that were in Germinal-Vesicle (GV) stage had an average of 1.89, while in the Metaphase I (M1) stage the average is 2.882. Lastly, the number of oocytes in the Metaphase (MII) stage which is fully matured had an average of 1.117. Conclusions: VCD can become an important tool for future studies that needs an animal model with DOR.

The IGF1/FSH Ratio Correlates with Sperm Count and Testicular Volume

BACKGROUND. Several studies have already investigated the relationship between IGF1 and semen parameters. However, clinical studies rarely concluded on the existence of a relationship between IGF1 and the sperm number, and whether the IGF1 serum levels have a practical value in the diagnostic work-up of patients with oligozoospermia is still unclear. OBJECTIVE. Molecular evidence reported that IGF1 and FSH belongs to the same molecular pathway. The aim of this study is to assess whether insulin-like growth factor-1 (IGF1)/follicle-stimulating hormone (FSH) ratio has an impact on testicular function and, specifically, on sperm number and testicular volume in a cohort of unselected men. METHODS. This is a cross-sectional study on 59 patients who attended the Seminology laboratory of the Division of Endocrinology of the University of Catania (Catania, Italy) for semen analysis. Data were analyzed to evaluate the relationships between IGF1 or IGF1/FSH ratio and sperm concentration, total sperm count (TSC), and testicular volume (TV). We also evaluated the occurrence of any difference in IGF1 and FSH serum levels and the IGF1/FSH ratio in patients with oligozoospermia and those with a TSC &gt; 39 million/ejaculate. MAIN RESULTS AND ROLE OF CHANGE. Patients had a mean age of 31.0 ± 8.5 years. The mean FSH and IGF1 levels were 3.95 ± 2.55 mIU/mL and 232.59 ± 65.13 ng/mL, respectively. IGF1 serum levels did not correlate with sperm concentration, TSC, and TV. The IGF1/FSH ratio showed a positive correlation with sperm concentration (r = 0.408; p = 0.004), TSC (r = 0.468; p = 0.001), and TV (0.463; p = 0.002). Patients with oligozoospermia (Group 1, 23.7%, n = 14) had a significant lower IGF1/FSH ratio (57.9 ± 9.5 vs. 94.1 ± 8.7; p = 0.03) compared to those with TSC &gt; 39 million/ejaculate (Group 2, 76.3%, n = 45). They did not differ significantly for neither IGF1 nor FSH serum levels. CONCLUSION. We found a positive correlation between the IGF1/FSH ratio and sperm concentration, TSC and TV. Furthermore, patients with oligozoospermia showed a significantly lower ratio compared to those with a normal TSC, while neither IGF1 nor FSH differed significantly in the two groups. Our results may reflect the existence of a molecular pathway to which IGF1 and FSH belongs. However, further studies are needed.

FSH can improve semen parameters in patients with idiopathic oligoasthenoteratozoospermia: A systematic review and meta-analysis.

Follicle-stimulating hormone (FSH) is commonly used in assisted reproductive technology to promote the development and maturation of follicles in female patients. However, there is no consensus on treating FSH in males with idiopathic oligoasthenoteratozoospermia (iOAT), especially in patients with normal serum FSH levels. To determine the role of FSH in improving semen quality in patients with iOAT, we conducted a detailed search in the commonly used database to find all studies on FSH in the treatment of iOAT. We compared the results, including semen volume, sperm count, sperm concentration, percentage of forward sperm motility, percentage of total sperm motility, percentage of normal forms and DNA fragmentation index (DFI) between the two groups treated with FSH or not. A total of 12 randomized controlled trials and one retrospective case-control study, including 924 people, were included in our meta-analysis. We found that sperm counts (MD 17.75; 95% CI 11.53-23.98 and p < 0.00001) were significantly increased in patients treated with FSH, along with improvements in sperm concentration (MD 4.52; 95% CI 1.46-7.58 and p=0.004), percentage of normal forms (MD 2.87; 95% CI 0.19-5.56 and p=0.04) and DFI (MD -12.62; 95% CI -19.27-5.97 and p=0.002). However, we found no significant differences in the two groups' changes in other semen parameters. The use of FSH can improve some semen parameters in patients with iOAT, such as sperm count, percentage of normal forms, sperm concentration and DFI.

P-451 Gonadal development and function after high-risk gonadotoxic treatment and immature testicular tissue banking

Abstract Study question What is the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function of pre- and pubertal boys? Summary answer There is a risk for impaired reproductive hormone levels after high-risk gonadotoxic treatment protocols, especially after conditioning therapy before hematopoietic stem cell transplantation. What is known already Experimental fertility preservation programs have been started to safeguard the future fertility of pre- and pubertal boys requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies on their gonadal development and function are rather limited. Study design, size, duration A two-center follow-up study, conducted between 2002 and 2020, evaluated the gonadal development and function of pre- and pubertal boys who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of a high-risk gonadotoxic treatment and the testicular biopsy procedure. Participants/materials, setting, methods A cohort of 60 pre- and pubertal boys without ongoing spermatogenesis and requiring HR-C/R or CT-HSCT were included. Exclusion criteria were testicular cancer diagnosis and hormonal substitution treatment. Testicular growth measured with a Prader orchidometer and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and inhibin B (INHB) were analyzed after treatment completion and compared between HR-C/R and CT-HSCT treatment protocols as well as between boys accepting TTB and those refusing TTB. Main results and the role of chance Of the 60 pre- and pubertal boys included, 26 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted by 39 boys and refused by 21 boys. Most boys were prepubertal at diagnosis (87%), at treatment completion (78%) and at TTB (79%). After 5.0 (1.0-11.0) years post-treatment, most patients had normal testicular volumes (86%) and normal LH (81%), FSH (81%), testosterone (70%) and INHB (65%) serum levels. Testicular growth (P = 0.3773), LH (P = 0.4844), FSH (P = 0.1613) and INHB (P = 0.2553) were not significantly different between the treatment groups, but significantly more abnormal testosterone serum levels (P = 0.0138) were recorded after CT-HSCT (43%) compared to HR-C/R (10%). TTB had no effect on testicular growth (P &amp;gt; 0.9999), LH (P = 0.7186), FSH (P &amp;gt; 0.9999) and INHB (P = 0.7074). A significant difference for testosterone was observed between the TTB groups (P = 0.0210), but no significant difference for testosterone or the other hormones was observed when comparing the effect of the biopsy procedure within each treatment group separately. The Spearman’s correlation test reveals a significant positive correlation between patients treated by CT-HSCT and patients having chosen for TTB (P &amp;lt; 0.001). In boys who underwent a hemi-orchiectomy or small biopsy, the volumes of the biopsied and contralateral non-biopsied testes were not significantly different (P &amp;gt; 0.9999). Limitations, reasons for caution This clinical follow-up study included a low patient number and the follow-up period was rather limited. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings. Wider implications of the findings A more accurate understanding of the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function will allow better counseling of patients interested in fertility preservation and optimize selection of patients eligible for fertility preservation. Trial registration number not applicable

PD09-06 ELEVATED FOLLICLE STIMULATING HORMONE (FSH) PREDICTS DECLINE IN SEMEN PARAMETERS AMONG MEN WITH NORMAL INDEX SEMEN ANALYSIS

You have accessJournal of UrologyCME1 May 2022PD09-06 ELEVATED FOLLICLE STIMULATING HORMONE (FSH) PREDICTS DECLINE IN SEMEN PARAMETERS AMONG MEN WITH NORMAL INDEX SEMEN ANALYSIS Richard Fantus, Minh Pham, Cecilia Chang, Justin Dubin, Robert Brannigan, and Joshua Halpern Richard FantusRichard Fantus More articles by this author , Minh PhamMinh Pham More articles by this author , Cecilia ChangCecilia Chang More articles by this author , Justin DubinJustin Dubin More articles by this author , Robert BranniganRobert Brannigan More articles by this author , and Joshua HalpernJoshua Halpern More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002535.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A significant proportion of men presenting for fertility evaluation have elevated follicle stimulating hormone (FSH) despite normal semen parameters. Since elevated FSH is presumed to be indicative of impaired spermatogenesis, the significance of this finding in men with normospermia remains unknown. We hypothesized that men with normospermia and elevated FSH were more likely to experience decline in semen parameters over time. METHODS: We performed a retrospective analysis of men with presenting for fertility evaluation throughout an integrated healthcare system. Men with all normal semen parameters according to the World Health Organization 5th edition were included. Men without at least one follow-up semen analysis (SA) after the index SA were excluded. Men were stratified according to baseline FSH as normal (<7.6 mIU/mL) vs elevated (≥7.6 mIU/mL). We examined the proportion of men who subsequently had an SA abnormality at the 2nd, 3rd, and 4th SA according to baseline FSH levels. Chi-squared test was used to compare the proportion of men with abnormal SA at each follow-up. RESULTS: Among 879 men with normal semen parameters at index SA, 82 (9.3%) had elevated FSH at the time of index SA. By the second SA, 10 (12.2%) of men with elevated FSH had declined to abnormal sperm concentration whereas just 44 (5.5%) of men with normal FSH had declined (p=.017). By the third SA, 34.6% (9/26) of men with elevated FSH had declined to oligospermia whereas just 7.2% (13/181) of men with normal FSH had declined (p <0.001). By the fourth SA, 60.0% (4/10) of men with elevated FSH had declined to oligospermia whereas just 10.3% (6/58) of men with normal FSH had declined (p=0.001). When considering aggregate semen parameters, a smaller proportion of men with elevated FSH had a normal SA (concentration, motility, and morphology) compared to men with normal FSH at the second, third, and fourth SA (p=0.005, p=0.012, and p=0.1095, respectively). CONCLUSIONS: Men with normal semen parameters and elevated FSH are more likely to experience serial decline in sperm concentration and overall semen parameters compared to men with normal FSH. Patients with elevated FSH should be counseled regarding potential decline and may consider short interval repeat semen analyses for the duration of attempts to conceive. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e179 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Richard Fantus More articles by this author Minh Pham More articles by this author Cecilia Chang More articles by this author Justin Dubin More articles by this author Robert Brannigan More articles by this author Joshua Halpern More articles by this author Expand All Advertisement PDF DownloadLoading ...

Prediction of poor ovarian response during In vitro fertilization in Nigerian women: A comparison of basal antral follicle count and follicle-stimulating hormone

Background: Poor ovarian reserve has been shown to be associated with poor outcomes of in-vitro fertilization (IVF) treatment. Women who can be reliably identified as expected poor responders can be advised on chances of poor outcomes that may dissuade them from wasting resources on IVF using their own eggs; and offered donor eggs, especially in a resource-poor country like Nigeria. Many centres routinely perform basal follicle-stimulating hormone (FSH) assay before IVF; however, basal antral follicle count (AFC) has emerged as a more reliable test of ovarian reserve that can be provided at a reduced cost compared to FSH in an IVF clinic setting. The determined predictive values of basal AFC compared to FSH in Nigerian women can be used to predict poor ovarian response during IVF treatment; and also to influence local clinical practice in IVF by offering a more reliable and affordable test, thereby avoiding wastage due to duplicate and unnecessary investigations. Aim: The aim is to determine the diagnostic accuracy of basal AFC compared to basal FSH for the prediction of ovarian response during the IVF cycle in Nigerian women. Patients, Materials and Methods: This was a hospital-based prospective comparative study in two private fertility centres in Abuja. Consecutive 166 women that underwent IVF treatment cycles who met the inclusion criteria were recruited. On day 2 to day 4 of a normal cycle, FSH assay and AFC using the Broekmans’ systematic process were done. They had controlled ovarian hyperstimulation by antagonist or agonist and occasionally long protocols. The poor response was defined as <4 follicles of >17 mm on the day of human chorionic gonadotropin trigger or ≤3 oocytes retrieved. Receiver operating characteristics (ROC) analysis was done to determine the level of the area under the curve (AUC) and optimum cut-off values of FSH and AFC in predicting poor ovarian response. Results: Twenty-eight (16.9%) had poor responses. ROC analysis demonstrated that AFC had the largest (AUC = 0.707, P = 0.001) relative to FSH (AUC = 0.591, P = 0.128). The ROC analysis showed that the optimum cut-off value for the prediction of poor response for AFC was ≤10, which had a higher accuracy of 67.5%, while for FSH was ≥8.15 mIU/ml with a lower accuracy of 61.5%. They both had the same sensitivity of 60.7%; however, AFC had better specificity, negative and positive predictive value, and higher odds ratio for the prediction of poor ovarian response. The positive and negative likelihood ratios of both cut-off values suggest that they may not be useful as diagnostic tests. Conclusion: ROC analysis estimated that AFC more accurately predicts poor ovarian response by its larger and more significant AUC compared to FSH in our population of women.

Tamoxifen as Empirical Treatment in Males with Primary Infertility and Normal Gonadotropic Hormonal Levels: A Prospective Study

Background: One of the most commonly employed medical therapies for idiopathic male infertility are antiestrogens. Tamoxifen as estrogen receptor blockers have been used as empiric treatments for male infertility, acting through blocking estrogen receptor at the hypothalamus and pituitary levels and so preventing the important negative feedback of estrogens to the pituitary and hypothalamus as a result that leading to gonadotropin releasing hormone (GnRH) stimulation and pulsatile release of luteinizing hormone (LH)/follicle-stimulating hormone (FSH). Objective: To assess tamoxifen role in the treatment of men with primary infertility who are normogonadotropic. as it is widely prescribed drug for that purpose as well as to evaluate possible patient’s criteria for a better response to tamoxifen. Methods: One hundred twenty-three patients with idiopathic primary infertility and normal FSH, LH, and testosterone serum levels were enrolled in this prospective study. All patients received 20 mg tamoxifen daily as a single dose for at least 3 months, and semen analysis (total sperm concentration, total number of progressive motile sperms and percentage of normal sperm morphology) as well hormones levels were evaluated, with the values being compared with those before treatment. Results: Overall, there was no statistically-significant improvement in semen parameters 3 months after treatment (P&gt;0.05); however, patients with pretreatment lower normal FSH level of (1.7-6.85 mIU/ml) and those with pretreatment sperm concentration of (five to ten million per ml) showed statistically significant improvement in sperm concentration after tamoxifen therapy (p=0.044 and p=0.012 respectively). Conclusion: Tamoxifen is an acceptable treatment for idiopathic male infertility. A better response can be expected in patients with pretreatment lower normal FSH level of (1.7-6.85 miu/ml) and sperm concentration of 5-10 million per ml. It might be used as first line treatment to enhance sperm concentration, giving its availability and lower cost in comparison to other hormonal therapies. Keywords: Male Infertility, tamoxifen, empirical treatment Citation: Al-Anbary LA. Tamoxifen as empirical treatment in males with primary infertility and normal gonadotropic hormonal levels: A prospective study. Iraqi JMS. 2021; 19(2): 230-236. doi: 10.22578/IJMS.19.2.12

Addition of a carboxy-terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice.

Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G-protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.