Normal Follicle-stimulating Hormone Levels 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.

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.

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).

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

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

Functions of Lysosomes in Mammalian Female Reproductive System

The lysosome is the most acidic membrane-bound intracellular organelle. Lysosomal acidity is primarily maintained by vacuolar H+-ATPase (V-ATPase) and counter ion channels. There are >60 hydrolytic enzymes in the lysosome for its fundamental digestive role. Lysosomes also play important roles in endocytosis, exocytosis, autophagy, and cell death. Studies that have implicated roles of lysosomes in the female reproductive system are reviewed here. In the ovary, lysosomes are implicated in the preparation of free cholesterol for steroidogenesis and degradation of regulators of steroidogenesis, regulation of follicular atresia, follicle rupture during ovulation, luteal cell survival, and luteal regression. In the oviduct, lysosomes are involved in endocytosis of both serum and oviductal luminal components. In the uterus during the menstrual/estrous cycle, lysosomes are associated with endometrial secretion, apoptosis, and menstruation. In the uterus during early pregnancy, lysosomes are involved in the temporal and directional changes of endocytosis, uterine epithelial acidification upon embryo implantation initiation, and embryo-maternal mutual communications via extracellular vesicles. In the placenta, lysosomes are implicated in nutrient transport and placental separation from the uterus for parturition. In the mammary gland, lysosomes are important for mammary gland development and involution. These findings suggest/demonstrate functions of lysosomes in multiple processes of female reproduction, from ovulation to ovarian steroidogenesis for pregnancy maintenance, and from essential in utero nurturing of developing embryos/fetuses via embryo/fetal-maternal communications, to optional postpartum nurturing of newborns via lactation. Future studies using genetically or modified animal models and pharmacological approaches will provide novel insights into the functions and mechanisms of lysosomes in the mammalian female reproductive system.

37-Year-Old Man With Fatigue and Erectile Dysfunction

37-Year-Old Man With Fatigue and Erectile Dysfunction

Epigenetic Aberration of FMR1 Gene in Infertile Women with Diminished Ovarian Reserve.

Objective The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of the FMR1 gene in blood and granulosa cells of 20 infertile women. Materials and Methods In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1 gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples. Results Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups. ConclusionOur data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

AZF micro-deletion in azoospermia and severe oligospermia: Molecular &amp; histopathological study in Duhok Province

Y chromosome micro-deletion (YCM) is a group of genetic diseases caused by missing gene (s) in specific regions of the Y chromosome. Many individuals with YCM show no manifestations and lead normal life. On the other hand, YCM is known to exist in a significant number of infertile males. Forty adult patients suffering from severe oligospermia and azoospermia were enrolled in the present study. Seminal fluid analyses were performed, and a blood sample was obtained for hormonal analysis and DNA extraction. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) profiles were measured and those who are azoospermic with normal FSH levels were subjected to testicular biopsy. The results revealed that 23 patients were azoospermic while 17 patients were severe oligospermic. It is also shown that ten azoospermic patients had normal serum gonadotrophin levels thus they were directed for testicular biopsy. Histopathological examination of testicular biopsy showed that four patients had obstructive azoospermia while the remaining six suffered maturation arrest. DNA was extracted according to the standard proteinase K/phenol-chloroform method in the medical biotechnology laboratory/Scientific Research Center/University of Duhok. Multiplex PCR was performed for genes located in the azoospermia factor (AZF) regions (AZFa, AZFb, and AZFc) to detect any possible micro-deletions. Y chromosome micro-deletions were determined in 26 patients out of a total of 40 patients. Micro-deletions in the AZFc sub-region appeared in 16 out of 26 patients (61.5 %), and 10 (38.5 %) sample showed AZFb, however, AZFa micro-deletion was not detected in any of the patients. In conclusion, it has been found that Y chromosome micro-deletions in the AZF region can be a determining factor for male infertility and the resultant manifestations.

MP89-03 NORMAL PREOPERATIVE FOLLICLE-STIMULATING HORMONE LEVEL IS ASSOCIATED WITH IMPROVEMENT IN SEMEN PARAMETERS FOLLOWING MICROSURGICAL VARICOCELECTOMY

You have accessJournal of UrologyInfertility: Therapy I1 Apr 2017MP89-03 NORMAL PREOPERATIVE FOLLICLE-STIMULATING HORMONE LEVEL IS ASSOCIATED WITH IMPROVEMENT IN SEMEN PARAMETERS FOLLOWING MICROSURGICAL VARICOCELECTOMY Lunan Ji, Samuel A. Shabtaie, Nachiketh Soodana Prakash, and Ranjith Ramasamy Lunan JiLunan Ji More articles by this author , Samuel A. ShabtaieSamuel A. Shabtaie More articles by this author , Nachiketh Soodana PrakashNachiketh Soodana Prakash More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2801AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We investigated whether preoperative follicle-stimulating hormone (FSH) level is associated with changes in postoperative semen parameters following microsurgical varicocelectomy. METHODS We identified 37 men who had undergone microsurgical varicocelectomy between August 2015 and June 2016. We compared semen parameters in men based on their preoperative FSH level, defined as normal <10 mIU/ml (n=25) and abnormal =>10 mIU/ml (n=12). We compared varicocele grade, testis volume, prevalence of bilateral disease, preoperative, and postoperative semen parameters (at 3 months) between men with normal and abnormal FSH. RESULTS The age, varicocele grade, preoperative testosterone levels were similar between men who underwent microsurgical varicocelectomy with normal and high FSH. Men with higher FSH had higher rates of bilateral disease. In a univariate analysis, men with FSH <10 mIU/mL had higher increases in absolute total sperm count (20.4M vs. 0.8M, p=0.002), sperm concentration (5.2M/mL vs. 1.4M/mL, p=0.05), and total motile count (5.1M vs. 1.4M, p=0.02) postoperatively compared to those with abnormal FSH. As expected, testis volume was smaller in the men with high FSH (12 cc vs. 14 cc, p=0.004). Change in motility was not significantly different between men with abnormal and normal FSH. CONCLUSIONS Our study suggested an association between men with normal FSH levels (<10 mIU/ml) and significant improvements in total sperm count, sperm concentration, and total motile count among those who underwent microscopic varicocelectomy. Normal FSH levels can suggest preserved spermatogenesis and greater improvement in semen parameters following varicocele repair. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1203 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Lunan Ji More articles by this author Samuel A. Shabtaie More articles by this author Nachiketh Soodana Prakash More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Antral Follicles Count and Anti-Müllerian Hormone Levels after Gonadotoxic Chemotherapy in Patients with Breast Cancer: Cohort Study.

Aim To assess ovarian reserve (OVR) by means of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) measurement in eumenorrheic women with breast cancer, exposed to gonadotoxic chemotherapy. Method Fifty-two women (35.3 ± 3.8 years old) with breast cancer and undergoing cyclophosphamide-containing chemotherapy were enrolled. The assessment was performed before chemotherapy (T1) and after 2 (T2) and 6 months (T3). Results Six months after chemotherapy, the prevalence of regular cycles was 60%. Anti-Müllerian hormone decreased down to undetectable levels at T2 and T3 (T1: 2.53 [1.00-5.31]; T2 < 0.08; T3: < 0.08 [< 0.08-1.07] ng/mL), (p < 0.0001). Antral follicle count was 11 [8.0-13.5] follicles at T1 and lower at T2 (5.50 [3.75-8.0] and T3 (5.0 [2.5-7.0]) (p < 0.0001). In patients who remained with regular cycles during chemotherapy or resumed normal menses, FSH and estradiol levels remained unchanged. Conclusion Anti-Müllerian hormone and AFC are useful as markers of OVR decline in women exposed to chemotherapy. Follicle-stimulating hormone is only adequate in women who become amenorrheic.

AB068. Practical diagnosis and treatment algorithm for azoospermia

A male factor is solely responsible in approximately 20% of cases of infertility and contributory in another 30-40%. Azoospermia is present in 15-20% of infertile males. Although the main goal of the evaluation of the infertile men is to identify the reversible conditions, to identify the irreversible causes that can or cannot be managed by assisted reproductive techniques (ART) is also important. Etiologies for azoospermia can be categorized as pre-testicular, testicular and post-testicular. Azoospermia is defined as the absence of sperm from at least two centrifuged semen samples. The initial evaluation of the azoospermia men includes a thorough history, physical examination, and hormonal tests. Physical examination should focus on testis size and presence of vas deferens and varicocele. Hormonal evaluation should include measurement of serum testosterone and follicle stimulating hormone (FSH) levels. When the vasa are palpable, testis size, semen volume and serum FSH are key factors in determining the etiology of the azoospermia. If the semen volume is reduced and this is not an artifact, the first laboratory test is post-ejaculatory urinalysis to exclude a retrograde ejaculation. After exclusion of retrograde ejaculation, transrectal ultrasonography (TRUS) should be considered to identify ejaculatory duct obstruction (EDO). Dilation of the seminal vesicles serves as a sign of EDO. Seminal vesicle aspiration to identify sperm at the time of TRUS can increase the diagnostic accuracy. In our center, TRUS-guided opacification of the seminal tracts with a mixture of contrast media and dye is performed to facilitate effective transurethral resection (TUR) of ejaculatory duct. Based on our experiences, patients with midline cysts who are treated by TUR are expected to have the best outcome. Testis size and level of serum FSH in azoospermic males with normal semen volume are critical factors in determining diagnostic strategies. Men with elevated FSH and bilateral small testis have non-obstructive azoospermia (NOA). Diagnostic testicular biopsy is not required in cases of NOA. Elevated FSH is indicative of a significant problem with spermatogenesis whereas a normal serum FSH does not guarantee intact spermatogenesis. Therefore, patients with normal testis size and FSH level should undergo a testicular biopsy to provide a definitive diagnosis. If the testicular biopsy is normal, most men have bilateral epididymal obstruction. Epididymal obstruction can be identified only by surgical exploration. Vasography is performed at the time of reconstructive surgery. Once sperm are found from the epididymal tubule, vasoepididymostomy is performed. The best results can be achieved by surgeons with training and on-going experience in microsurgery. There is some evidence that a small percentage of men with NOA may benefit from treatment of a clinical varicocele. Therefore, it is reasonable to offer men with NOA and clinical varicoceles a varicocelectomy. However, the most men will still need to use intracytoplasmic sperm injection (ICSI) to conceive. Testicular sperm extraction (TESE) should be offered to all men with NOA. Microsurgical TESE increases retrieval rates, and should be preferred in severe cases of NOA.

PP.24.04

Objective: To study the relationship between changes in the content of estradiol and follicle-stimulating hormone (FSH), the restructuring process of the cardiovascular system in women with hypertension. Design and method: 64 women in the late reproductive age with hypertension not taking antihypertensive therapy. All determined by the level of estradiol and FSH. Depending on the degree of estradiol and FSH patients with hypertension were divided into groups. In group 1 (gr.) Included 34 hypertensive age 39,11 ± 4,3 years with the menstrual cycle and estrogen deficiency. In the 2nd c. - 30 with hypertension, age 39,14 ± 2,23 years, with the menstrual cycle and normal levels of estradiol and FSH. A comparison group of 20 healthy women, 38,45 ± 4,12 years with normal levels of estradiol and FSH without hypertension. Performed duplex scanning of the common carotid artery (CCA). Results: Observed expansion of the mean diameter of CCA in patients with hypertension and estrogen deficiency. Blood flow velocity in the CCA significantly lower in comparison with the control in patients with hypertension and gipoestrogeniya. Resistance index was higher in patients with hypertension 1 gr. in comparison with the control and patient 2 gr. The elastic properties of the wall of the carotid artery decreased: from 41,3 ± 10,8 x ∼ 3 / kPa in patients with hypertension and normal levels of estradiol to 36,4 ± 10,8 x Yu- 3 / kPa p = 0.034 for patients with hypertension with decreased levels of estradiol. The index of stiffness was higher in comparison with the control as in patients with hypertension estrogenodefitsitom, and without it. Conclusions: Duplex scanning of carotid arteries in women with hypertension shows expansion of the lumen of the CCA, reducing blood flow velocity, expressed against the backdrop of estrogen deficiency, indicating that the more significant changes in the vascular wall in hypertensive patients compared with having normal levels of estradiol.

Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation.

To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation. In a prospective study, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and prolactin (PRL) of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD). male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p < 0.05), whereas E2 and PRL normalized (p < 0.05). The MELD score did not influence changes in FSH, PRL and LH, however, the more severe the cirrhosis was, the more significant was the normalization of E2 (p = 0.01). Patients with cirrhosis and male hypogonadism have inappropriately normal levels of FSH and LH, associated with an increase in E2 and LRP. After liver transplantation, FSH and LH increased, while E2 and PRL returned to normal. Changes in E2 levels were most pronounced in patients with MELD > 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

Follicle-stimulating hormone/luteinizing hormone ratio as an independent predictor of response to controlled ovarian stimulation.

To determine whether a follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratio over 3 in the setting of a normal FSH (<12 IU/l) is associated with a higher rate of failed controlled ovarian stimulation cycles. Retrospective cohort. A total of 676 patients were identified; 198 patients had a FSH/LH ratio >3 and 477 patients had a FSH/LH ratio <3. Exclusion criteria included: age >40 years; estradiol (E2) prime protocols; E2 at start >70 pg/ml; and FSH at start >12 IU/l. The main outcome measure was cycle cancellation. An elevated FSH/LH ratio >3 was more likely to result in the individual's cycle cancelled (15 vs 5.24%; p = 0.0001). The total gonadotropin dosage was greater in the higher ratio versus lower ratio group (2636 vs 2242 IU; significant). Peak E2 was significantly lower in the FSH/LH >3 group (peak E2: 1635 vs 1942 pg/ml). The value of the FSH/LH ratio in patients with normal FSH levels, may have a role in determining the appropriate stimulation protocol and predict cycle cancellations.

How Do I Recommend Extended Adjuvant Hormonal Therapy?

Estrogen-dependent growth of some breast cancers was a key observation, which led to the development of tamoxifen and aromatase inhibitors (AIs). Tamoxifen and AIs have different modes of action and side-effect profiles. Based on evidence, both in laboratory models and clinical trials, longer duration of hormone suppression therapy is beneficial. The most important factor deciding their use is "menopausal status." Sometimes, defining menopause might be challenging in clinical practice. Measuring serum follicle stimulating hormone (FSH) and estradiol levels are helpful when in doubt. Tamoxifen should be offered to those women with normal FSH and estradiol levels even with cessation of menstruation. Once menopause is defined, it is relatively clear to decide about the endocrine therapy. Premenopausal women should be treated with tamoxifen and postmenopausal women with AIs. Perimenopausal women should be treated with tamoxifen initially and later switched to AIs once they become postmenopausal. With current recent evidence, premenopausal women should be treated with 10 years of tamoxifen. Current evidence also supports 5 years of an AI alone or 5 years of tamoxifen followed by 5 years of an AI; studies evaluating longer duration of AI treatment are in progress (Figure 1). Compliance with long-term use of these adjuvant endocrine therapies depends on screening for and management of side effects. Patients taking tamoxifen should be clinically screened for thromboembolism and for endometrial cancer if abnormal bleeding occurs. Patients on AI should pay careful attention to management of other chronic health disorders. They also should be screened for optimal bone health. Management of vasomotor symptoms also helps with adherence to long-term treatment for both tamoxifen and AIs.

Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome

BackgroundLaminopathies, due to mutations in LMNA, encoding A type-lamins, can lead to premature ageing and/or lipodystrophic syndromes, showing that these diseases could have close physiopathological relationships. We show here that lipodystrophy and extreme insulin resistance can also reveal the adult progeria Werner syndrome linked to mutations in WRN, encoding a RecQ DNA helicase.MethodsWe analysed the clinical and biological features of two women, aged 32 and 36, referred for partial lipodystrophic syndrome which led to the molecular diagnosis of Werner syndrome. Cultured skin fibroblasts from one patient were studied.ResultsTwo normal-weighted women presented with a partial lipodystrophic syndrome with hypertriglyceridemia and liver steatosis. One of them had also diabetes. Both patients showed a peculiar, striking lipodystrophic phenotype with subcutaneous lipoatrophy of the four limbs contrasting with truncal and abdominal fat accumulation. Their oral glucose tolerance tests showed extremely high levels of insulinemia, revealing major insulin resistance. Low serum levels of sex-hormone binding globulin and adiponectin suggested a post-receptor insulin signalling defect. Other clinical features included bilateral cataracts, greying hair and distal skin atrophy. We observed biallelic WRN null mutations in both women (p.Q748X homozygous, and compound heterozygous p.Q1257X/p.M1329fs). Their fertility was decreased, with preserved menstrual cycles and normal follicle-stimulating hormone levels ruling out premature ovarian failure. However undetectable anti-müllerian hormone and inhibin B indicated diminished follicular ovarian reserve. Insulin-resistance linked ovarian hyperandrogenism could also contribute to decreased fertility, and the two patients became pregnant after initiation of insulin-sensitizers (metformin). Both pregnancies were complicated by severe cervical incompetence, leading to the preterm birth of a healthy newborn in one case, but to a second trimester-abortion in the other. WRN-mutated fibroblasts showed oxidative stress, increased lamin B1 expression, nuclear dysmorphies and premature senescence.ConclusionsWe show here for the first time that partial lipodystrophy with severe insulin resistance can reveal WRN-linked premature aging syndrome. Increased expression of lamin B1 with altered lamina architecture observed in WRN-mutated fibroblasts could contribute to premature cellular senescence. Primary alterations in DNA replication and/or repair should be considered as possible causes of lipodystrophic syndromes.