Pregnancy after intracytoplasmic sperm injection following extended sperm preparation and hormone therapy in an azoospermic man with maturation arrest and microlithiasis: a case report and literature review.

In the management of azoospermia, a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI) is usually the most successful option for fatherhood. However, an outstanding question remains: How can at least a few spermatozoa be obtained from the ejaculate, thus avoiding the need for a surgical procedure? A 36-year-old man presented to Assisted Reproduction Unit with his 26-year-old wife. The ultrasound assessment revealed bilateral microlithiasis. Two spermograms revealed absolute azoospermia. Levels of follicle-stimulating hormone (FSH) and luteinising hormone were normal-low. The patient underwent 10 months of treatment with clomiphene citrate. A bilateral testicular sperm extraction failed to retrieve spermatozoa and revealed a maturation arrest at spermatocyte/spermatid stages depending on the tubules. Clomiphene citrate was replaced with recombinant FSH (rFSH). After 9-month treatment with rFSH, motile spermatozoa from droplets of ejaculate pellet were cryopreserved as a single straw. Ovarian stimulation was provided using classic antagonist protocol, and five mature oocytes were collected. Two consecutive fresh semen samples on the day of ICSI yielded seven motile spermatozoa, and fertilisation was achieved in all five oocytes. On day 3, two embryos were transferred, yielding positive beta-human chorionic gonadotropin and a healthy delivery of a boy and a girl.

Light microscopy morphological characteristics of the sperm flagellum may be related to axonemal abnormalities.

Although electron microscopy provides a detailed analysis of ultrastructural abnormalities, this technique is not available in all laboratories. We sought to determine whether certain characteristics of the flagellum as assessed by light microscopy were related to axonemal abnormalities. Forty-one patients with an absence of outer dynein arms (type I), a lack of a central complex (type III) and an absence of peripheral doublets (type IV) were studied. Sperm morphology was scored according to David's modified classification. Flagella with an irregular thickness were classified as being of normal length, short or broken. There were correlations between missing outer dynein arms and abnormal, short or coiled flagellum. Type III patients showed the highest flagellar defects (a short (P = 0.0027) or an absent flagellum (P = 0.011)). Just over 68% of the irregular flagella were short in Type III patients, whereas this value was only 34.5% in type I and 26.4% in type IV (P = 0.002). There was a negative correlation between misassembly and spermatozoa of irregular flagella (r = -0.79; P = 0.019). It is concluded that light microscopy analysis of flagellum abnormalities may help provide a correct diagnosis, identify sperm abnormalities with fertility potentials and outcomes in assisted reproduction technologies and assess the genetic risk.

[Testicular nodules of infertile men and contrast enhanced ultrasonography: preliminary study]. / Nodules testiculaires de l'homme infertile et échographie de contraste: étude préliminaire.

INTRODUCTION: The incidence of testicular nodules discovered during infertility evaluation is increasing. These nodules are suspicious of malignancy. There is no paraclinical examination which allows histological orientation to these nodules. The recommendations propose priority treatment by total orchidectomy. PATIENTS AND METHODS: Through a retrospective cohort study of infertile patients, our goal is to study the enhancement of testicular nodules after injection of ultrasound contrast. The secondary objective is to determine whether CEUS may argue in favor of conservative treatment. From june 2010 to march 2013, 24 patients had underwent ultrasound contrast study of abnormal testicular parenchyma detected prior to infertility evaluation carried ultrasound. The characteristics of ultrasound enhancement were correlated with the pathological findings of surgical patients and proposed treatments (surgery or surveillance). RESULTS: Fifteen patients were followed up, 9 were operated (7 partial orchidectomies, 2 total orchidectomies). Histological analysis found four Leydig cell tumors, 2 Sertoli cell tumors and 3 seminomas. No adverse changes were noted during the follow-up. This study showed a typical semiology of early, intense and homogeneous enhancement with a phenomenon of wash in 100% of Leydig cell tumors. All Leydig cell tumors have been treated by partial orchidectomy. Seminomas have intense enhancement in 100% of cases. There was a phenomenon of wash in 2 out of 3 cases. When a wash in was described, it was always described as heterogeneous. All seminomas were finally treated by total orchidectomy. The sensitivity and positive predictive value of ultrasound intense enhancement for the diagnosis of testicular cancer was 89% (Se) and 80% (PPV). CONCLUSION: There is a semiology of ultrasound enhancement of testicular nodules with features that can guide in favor of a malignant tumor, seminoma or Leydig cell tumor. If a prospective study was undertaken, these arrangements could guide us to treatments promoting preservation of the testicular parenchyma.

[Azoospermia and a history of inguinal hernia repair in adult]. / Azoospermie et antécédent de cure de hernie inguinale chez l'adulte.

BACKGROUND: Inguinal hernia repair is one of the most performed surgeries in the world. It is recognized that any surgery of the pelvic floor may represent a risk factor of male infertility. METHOD: Retrospective study of patients with azoospermia and a history of adult inguinal hernia repair surgery and referred to our center between January 1990 and January 2011 for infertility. RESULTS: Among 69 azoospermia patients with history of adult inguinal hernia repair surgery, 60 patients underwent surgical extraction of sperm that was successful in 75% (45/60). Positive extraction rate decreases in the subgroup of patients with risk factors for infertility (61.4%) as well as in the group with bilateral inguinal hernia (67.9%). There was no statistically significant difference in the positive rate of sperm retrieval according to surgical technique or according to the use of polypropylene mesh (P>0.05). CONCLUSION: The obstruction of the vas deferens due to an inguinal hernia repair was a potential iatrogenic cause of male infertility that was rare and underestimated. The influence of using a polypropylene mesh was not clearly demonstrated. The management of these patients is based on prevention in order to identify patients with risk factors of infertility in order to propose a presurgery cryopreservation of sperm. LEVEL OF EVIDENCE: 5.

[Clinical and paraclinical features of Klinefelter syndrome consulting for male infertility]. / Aspects cliniques et paracliniques des syndromes de Klinefelter consultant pour infertilité masculine.

PURPOSE: To attract urologists' attention on screening of Klinefelter syndrome consulting for infertility, describing its usual phenotype, in order to propose a possible reproductive technique, to prevent and to treat associated comorbidities and to manage the frequent discovery of ultrasonographic testicular lesions. PATIENTS AND METHODS: Retrospective analysis over 10 years of clinical and paraclinical features of the patients who consulted for infertility and had a 47,XX7 regular or mosaic karyotype. RESULTS: One hundred and forty-nine patients, 31.7 year-old on average [20.7-42.7], all had a severe bilateral testicular hypotrophy, subsequently confirmed by ultrasonography (mean total testicular volume: 3.7 mL [-0.20-7.64]). One hundred and twenty-two (81.9%) had normal secondary sexual characteristics, only 4 of them (2.7%) already knew their diagnosis. Their mean total testosterone levels were low (3.12 ng/mL [0.39-5.86]) but remain normal. A total of 34.2% of patients had subclinical testicular nodules discovered by ultrasonography. Excision was performed in 12 cases, confirming Leydig cell tumors. CONCLUSION: Klinefelter syndrome diagnosis can be made during a first consultation with a bilateral testicular hypotrophy as "pathognomonic" point of call in an often poor clinical observation. It is completed by an azoospermia or severe oligozoospermia. If they want to, this allows to quickly guide patients to suitable medical reproductive technique but, especially, to prevent and quickly treat comorbidities associated to this diagnosis, and also to reassure patients about the frequent discovery of subclinical testicular lesions.

[Andrological description of a population of azoospermic men with agenesis of the vas deferens]. / Description andrologique d'une population azoosperme avec une agénésie des canaux déférents consultant pour infertilité.

CONTEXT: In the 1990's, congenital agenesis of the vas deferens was identified as a minor form of cystic fibrosis in relation to the frequency of mutations of the CFTR gene associated. It is responsible for masculine infertility by obstructive azoospermia; which is not accessible to a surgical treatment. However, surgical sperm retrieval and injection de spermatozoïde en intracytopasmique (ICSI) allow fatherhood for these patients. PATIENTS AND METHODS: A retrospective analysis of 104 consecutive patients from 1996 to 2006. A comprehensive clinical, spermiologic, hormonal, imaging and genetic workup was carried on. The data from the surgical extractions and the attempts of ICSI were collected. RESULTS: Seventy-five percent of the patients had a mutation of the CFTR gene; ultrasound imaging revealed a renal or a seminal vesicle abnormality in 20% and 84.5% of the patients, respectively. The association of a semen volume less than 2 mL with a pH less than 7.2, a fructose less than 2 and mean sudoral chlore greater than 60 mmol/L enabled an immediate identification of 30% of patients carrier of the mutation and without renal abnormality. The sperm extraction rate was 98%. CONCLUSION: A search for the CFTR gene mutations and an ultrasound imaging of the genito-urinary system are essential to the workup of these patients. The association of a semen volume less than 2 mL, a semen pH less than 7.2 and a fructose less than 2 must point towards a minor form of cystic fibrosis and prompt the workup of genetic abnormalities and sudoral chlore testing. The results of the sperm extraction combined to the technical advances of IVF/ICSI allow excellent pregnancy rates of 66% for the companions of these patients.

[Ejaculatory disorders except premature ejaculation, orgasmic disorders]. / Troubles de l'éjaculation à l'exception de l'éjaculation prématurée, troubles de l'orgasme.

INTRODUCTION: Disorders of ejaculation and orgasm apart from premature ejaculation are pretty uncommon. METHODS: Medical literature was reviewed and combined with expert opinion of the authors. RESULTS: The semiology of these disorders is essential: aspermia, hypospermia, retrograde ejaculation, delayed or absent ejaculation with or without orgasm. Whether this is a lifelong or acquired condition, it is essential to assess the side-effects of medications i.e. psychotropic drugs, including antidepressant, neuroleptics, tramadol, alphablockers: tamsulosin and silodosin must always be surveyed. CONCLUSION: The management is often difficult, especially with a parenthood perspective. The management of lifelong disorders must rely on psychosexual therapies.

[Drugs for sexual medicine]. / Les médicaments de la médecine sexuelle.

AIM: To describe drugs used in sexual medicine. METHOD: Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). RESULTS: 5PDIs and intracavernous injection of alprostadil are first- and second-line therapies of erectile dysfunction. Dapoxetine is the first specific and approved treatment of premature ejaculation. Androgene supplementation improves sexual desire among patient with hypogonadism as much as initial serum testosterone levels are low. Female sexual dysfunctions pharmacology is to date less developed, although candidate drugs reach phase III clinical studies. CONCLUSION: Pharmacology is one but not the only therapeutic avenue in sexual medicine. Despite real breakthrough such as 5PDIs for erectile dysfunction, incomplete knowledge and understanding of physiology, pathophysiology and pharmacology of human sexual function reduces its development particularly for women.

[Management of testicular lesions in a population of infertile patients]. / Prise en charge des nodules testiculaires dans une population de patients infertiles.

INTRODUCTION: Testicular parenchyma abnormalities and testis cancers are more frequent in infertile men, hence the guidelines recommending a systematic scrotal ultrasound. METHODS: A retrospective review of all patients treated with total or partial orchidectomy, from January, 2000 to July, 2010, for a testicular lesion discovered during an infertility evaluation work-up. Physical, examination data, type of surgery and pathological results were reported. RESULTS: Forty-five patients were treated. The majority of tumors (80%) were non palpable, and incidentally discovered with scrotal ultrasonography. Eight cases were partial orchidectomies, and 37 cases were radical orchidectomies. A frozen section examination was performed in 13 cases, and led to two radical orchidectomies. Standard histological examination revealed 33 (73.3%) benign lesions (11 Leydig cell hyperplasias, 17 Leydig cell tumors, five Sertoli cell tumors) and 10 (22.2%) malignant lesions (nine seminomas and one teratoma). Ten patients had a Klinefelter syndrome, for whom all the lesions were benign. CONCLUSION: The majority of non-palpable testicular lesions, discovered by ultrasonography in a population of infertile men were benign tumors. Conservative management in this context appears to be an option, to preserve the endocrine function and the fertility of these patients, while being ontologically safe.

A predictive score for testicular sperm extraction quality and surgical ICSI outcome in non-obstructive azoospermia: a retrospective study.

BACKGROUND: In non-obstructive azoospermia (NOA), testicular sperm extraction (TESE) is successful in ≈ 50% of cases. A parameter for predicting TESE quality and pregnancy rates after ICSI of testicular spermatozoa is still lacking. METHODS: We retrospectively evaluated the total testicular volume (TTV), hormone levels and TESE quality in 280 patients with NOA. After successful TESE, the characteristics of the ICSI cycles and the take-home baby rates were evaluated. RESULTS: TESE was successful in 149 patients (53.2%). In a multivariate logistic regression analysis, only TTV, FSH and inhibin B were correlated with the TESE outcome. A score including these three parameters was the best predictor of successful TESE (positive likelihood ratio: +3.01). When the score was <18.5, TESE was successful in 77.4% of cases and 'sperm rich' (i.e. yielding >100 spermatozoa) in 91.1% of cases; 42.8% of couples took a baby home. The take-home baby rate did not depend on whether the score was <18.5 or between 18.5 and 3700. If the score was >3700, TESE was successful in 37.8% of cases and 'sperm rich' in 14.3% of cases; only one couple took a baby home (a rate of 7.7 versus 42.8% when the score was <18.5; P< 0.001). Owing to low sperm retrieval on the day of oocyte retrieval, fewer oocytes were injected when the score was >3700 than when <3700. CONCLUSIONS: Thanks to better knowledge of TESE quality, the present score could help to improve care and pre-ICSI counseling for patients with NOA.

Correlation between testicular sperm extraction outcomes and clinical, endocrine and testicular histology parameters in 120 azoospermic men with normal serum FSH levels.

We retrospectively evaluated the clinical and hormonal profiles, sperm extraction outcomes and testicular histology parameters in 120 azoospermic men with normal serum follicle-stimulating hormone (FSH) level. Microsurgical epididymal sperm aspiration (MESA) and testicular sperm extraction (TESE) were performed in 33 and 87 cases, respectively. Sperm were successfully retrieved in all the MESA procedures and in 65 of the TESE procedures. The mean serum FSH and inhibin B levels and the testicular volume differed significantly according to whether or not sperm were retrieved. The threshold serum inhibin B value for predicting successful TESE was 123.5pg/mL (sensitivity: 69.7%; specificity: 66.7%). The 13 patients with Sertoli cell only syndrome (SCOS) had a higher mean serum FSH level and a lower mean serum inhibin B level than the other phenotypes. TESE was negative for 11 of the 13 SCOS men. The mean±SD inhibin B level was significantly lower in patients with 5-10IU/L of FSH than those with 2-5IU/L of FSH (108.30±53.86 vs. 175.23±70.17pg/mL, respectively). The sperm retrieval rates were 71.42% for the group with 5-10IU/L of FSH and 87.32% for the group with 2-5IU/L of FSH. Ten of the 13 SCOS men had a FSH level between 5 and 10IU/L. The clinical pregnancy rate was significantly lower (p=0.04) in the group with 5-10IU/L (50%) of FSH than in the group with 2-5IU/L (77.5%) of FSH. In conclusion, there is no FSH value below which spermatogenesis is always found. Inhibin B assays and clinical assessments are thus of particular value in men with normal serum FSH levels.

[Why and how to assess hypospermia?]. / Pourquoi et comment réaliser un bilan d'hypospermie ?

Hypospermia is a semen volume lower than 2 mL on at least two semen analyses. The etiologies of hypospermia are many and may be divided into two pathophysiologic sub-groups: disturbances of ejaculation reflex leading to partial retrograde ejaculation and seminal glands and ducts anatomic and functional anomalies. In this last pathologic mechanism, the mutations of CFTR gene, involved in many different forms of cystic fibrosis, represent a possible cause of hypospermia. The molecular anomaly of CFTR gene's screening is very important for the potential descendents and for the patient himself. It must be considered any time clinic and/or paraclinic context is evocative.

[Optimal evaluation of the infertile male. 2007 French urological association guidelines]. / Evaluation de l'homme infertile: recommandations AFU 2007.

An infertility evaluation should be performed if a couple has not achieved conception after one year of unprotected intercourse. An evaluation should be performed earlier if male or female infertility risk factors exist and if the couple questions its fertility potential. The initial screening of the male should include a reproductive history and a physical examination performed by a urologist or a specialist in male fertility and two semen analyses. Additional procedures and testing may be used to elucidate problems discovered during the full evaluation. The minimal initial endocrine evaluation should include serum total testosterone and serum follicle-stimulating hormone levels. An endocrine evaluation should be performed if sperm concentration is abnormally low, sexual function is impaired, and when other clinical findings suggest a specific endocrinopathy. A postejaculatory urinalysis should be performed if ejaculate volume is less than 1 mL, except in patients with bilateral vasal agenesis or possible hypogonadism. With a diagnosis of retrograde ejaculation, specific management should be considered before advising assisted reproductive technology. Scrotal ultrasonography is indicated when physical examination of the scrotum is difficult or inadequate, or when a testicular mass is suspected. Transrectal ultrasonography (TRUS) is indicated in patients who are azoospermic or have a low ejaculate volume. Specialized testing of semen is not required for routine diagnosis of male infertility. However, some tests may be useful for a few patients to identify a male factor contributing to unexplained infertility, or to select therapy (e.g., assisted reproductive technology). Before performing intracytoplasmic sperm injection, karyotyping and Y-chromosome analysis should be offered to men who have nonobstructive azoospermia and severe oligospermia. Genetic testing for gene mutations of the ABCC7 (ex-CFTR) gene should be offered to male and female partners before proceeding with treatments that use the sperm of men with congenital bilateral absence of the vasa deferentia or congenital unilateral abnormality of the seminal tract. Genetic counseling may be offered when a genetic abnormality is suspected in the male or female partner, and it should be provided when a genetic abnormality is detected. Genetic testing in the female partner, when non symptomatic, should only be advised by a physician from a multidisciplinary team registered by the ministry of health. Evaluation by testis biopsy and deferentography should be performed by a urologist or an andrologist registered for sperm retrieval.

[Results of surgical testicular sperm extractions (TESE) in a population of azoospermic patients with a history of cryptorchidism based on a 10-year experience of 142 patients]. / Résultats des extractions chirurgicales testiculaires de spermatozoïdes (TESE) dans une population de patients azoospermiques avec antécédent de cryptorchidie : à propos d'une expérience sur dix ans auprès de 142 patients.

INTRODUCTION: Cryptorchidism is a common and possible etiology of male infertility. OBJECTIVES: This is a retrospective study of 142 azoospermic men with history of cryptorchidism. A testicular sperm extraction (TESE) was performed for each of them, between 1995 and 2005, to realize in vitro fecundation with intracytoplasmic sperm injection (ICSI). MATERIAL AND METHODS: We studied the clinical pattern (age at the treatment, unilateral or bilateral cryptorchidism), hormonal levels (total testosterone and FSH) and ultrasound examinations in this population. Then, we studied the rates of successful TESE according to these various characteristics. RESULTS: The main origin of azoospermia is non obstructive (secretory). A great majority of the patients (71.8%) has benefited of an orchidopexy before the age of 10 years which does not seem to represent a factor of better forecast of surgical extraction of sperm cells. In the subgroup of the bilateral cryptorchidy, the rate of extraction was 63% (55/87). In the subgroup of the one-sided cryptorchidy, it was 61.9% (36/42). CONCLUSION: For us, history of cryptorchidism is an etiology of good prognosis for azoospermia, since the rate of TESE with positive sperm retrieval is 65%. In our population, the subgroups of patients whose FSH is normal and/or whose testicular volume is higher than 10 cm3 are those whose forecast is still better, because the rate of TESE with positive sperm retrieval is 75%.

[Unilateral partial deferential agenesia and CFTR gene composite heterozygoty (deltaF508/V938G)]. / Agénésie déférentielle partielle unilatérale et hétérozygotie composite du gène CFTR (DeltaF508/V938G).

This is a case report of a thirty-year-old-man consulting for a primary infertility that was diagnosed four years ago. Andrologic exam was normal. Two spermograms found normal spermatic parameters. An uro-genital echography with a RMI showed that a unilateral agenesia of the left vas deferens in the pelvic portion. Then, a composite heterozygoty of the CFTR gene (DeltaF508/V938G) was found. This is the first time that the association of these two mutations has been described. This case also makes it possible to wonder about the need for realizing, or not, a systematic basis imagery (ultrasound examination in first), in the event of infertility of the couple. In this context, the discovery of an echographic anomaly made it possible to identify CFTR mutations, whose physiopathological implication in the infertility can be discussed (CFTR related disorders)...

[Effects of father's age on fertility, results of ART and health of children]. / Conséquences de l'âge du père sur la fertilité, les résultats de l'AMP et la santé des enfants.

Many studies exist on the impact of female age on fertility, success of assisted reproductive technologies and on obstetric, fetal and neonatal adverse outcomes. Late paternity seems commonplace especially in the media… But there are reliable scientific data which confirm decline of fertility related to male age but also an increased risk of genetic diseases for the offspring. The objective of this article is to make a synthesis of the literature on this subject.

[Necrozoospermia: From etiologic diagnosis to therapeutic management]. / La necrozoospermie : du diagnostic étiologique à la prise en charge thérapeutique.

This review describes necrospermia, its diagnosis, causes and management. Sperm vitality is commonly assessed in the laboratory of reproductive biology, with the eosin test or with the hypo-osmotic swelling test. Necrospermia is defined by a percentage of living spermatozoa inferior to 58%, and can be related to male infertility. Several pathological mechanisms may be involved and can be classified either in testicular causes (hyperthyroidism, local hyperthermia, varicocele), or post-testicular causes (epididymal necrospermia, dysregulation of seminal plasma, adult polycystic kidney disease, vasectomy reversal, anti-sperm antibodies) or both (infection, toxic, age, spinal cord injury). The first treatment is to correct the underlying cause, if possible. Repetitive ejaculation has demonstrated to be effective as well. Many drugs would also improve the sperm vitality (antioxidants, non-and-steroidal anti-inflammatory drugs) but there is currently no guideline to recommend their use. With necrospermia, fertilization rates are lower but in vitro fertilization (IVF) with Intracytoplasmic sperm injection (ICSI) improves the chances of conception.

Extreme spermatogenesis failure: andrological phenotype and intracytoplasmic sperm injection outcomes.

Patients with very low sperm count through direct sperm examination can exhibit extreme oligozoospermia or cryptozoospermia (after centrifugation). The management of these patients is a real challenge for both clinicians and biologists. In this retrospective and comparative cohort study, we compared the andrological phenotype of patients with extreme alterations of spermatogenesis and assessed whether the origin of spermatozoa (testicular or ejaculate) had any influence on intracytoplasmic sperm injection (ICSI) outcomes. A total of 161 ICSI cycles were performed using ejaculated spermatozoa from 75 patients with extreme oligozoospermia (EOS) or cryptozoospermia (CS) and 150 ICSI cycles using extracted testicular spermatozoa from 74 patients with non-obstructive azoospermia (NOA). Physical, hormonal, ultrasound assessments, and ICSI outcomes were performed in each group. Cryptorchidism was significantly more frequent in the NOA group (60.8% vs. 22.6%, p = 0.001). FSH levels were significantly higher [18.9 IU/L (5.9-27.0) vs. 15.3 IU/L (9.0-46.5), p = 0.001] and the majority of inhibin B levels measured were found mostly undetectable in the NOA group as compared to EOS/CS group (31.1% vs. 10.7%, p = 0.0004). Moreover, we found no significant differences in the respect to the fertilization rates (48.9% and 43.3%, p = 0.43), implantation rates (17.4% and 15.9%, p = 0.77), and percentage of top quality embryo (22.4% and 20.4%, p = 0.73) between the two groups. The clinical pregnancy rates per embryo transferred were comparable in both groups (28.3% and 27.4%, p = 0.89). In this study, we showed for the first time a different andrological phenotype between EOS/CS and NOA groups. Indeed, cryptorchidism was significantly more frequent with more severe endocrine parameters found in the NOA group. These results reflect a more profound alteration in spermatogenesis in NOA patients. However, there was no difference in ICSI outcomes between NOA and EOS/CS groups.

[Stimulation of spermatogenesis: For whom? Why? How?]. / Stimulation de la spermatogenèse : pour qui ? Pourquoi ? Comment ?

The stimulation of spermatogenesis is the best treatment of infertility for male hypogonadotropic-hypogonadism. The results are very pleasing because a real improvement of semen is sometimes obtained with spontaneous pregnants describing in the literature but after a long duration of treatment, often many months. Sometimes, the treatment improves the technical conditions of ICSI for the embryologists. Stimulation of spermatogenesis by gonadotrophins rFSH and/or hCG is the most used but others treatments, like pulsatile GnRH therapy or clomifene citrate can be used. The purpose of this review is to described the different protocols of stimulation of spermatogenesis and explain their results and finally to see if others indications of stimulation of spermatogenesis are existing.

Leydig cell tumor of the testis with azoospermia and elevated delta4 androstenedione: case report.

BACKGROUND: Secreting interstitial cell (Leydig cell) tumors are rare. In adults, the clinical picture and steroid levels are variable. CASE PRESENTATION: This paper presents a case of left testicular tumor, showing azoospermia with normal serum level of total testosterone, collapsed FSH and LH, and high delta4 androstenedione. Histopathological investigation revealed a Leydig cell tumor. TESE allowed spermatozoa extraction and freezing. Testicular histology found hypospermatogenesis and germ-cell aplasia with interstitial fibrosis. Surgical resection of the tumor resulted in normalization of gonadotropins and fall in serum delta4 androstenedione to subnormal levels in the postoperative period confirming that the tumor was secreting delta4 androstenedione. It was hypothesized that high delta4 androstenedione resulted in intra tumoral 17 ß-HSD overtaken by delta4 androstenedione or that 17 ß-HSD activity in the tumor was different from that of normal Leydig cells. Three months after surgery sperm analysis found a complete recovery of spermatogenesis. A spontaneous pregnancy occurred 3 months after surgery and a girl was born. CONCLUSIONS: In this case, the diagnosis of testicular Leydig cell tumor secreting delta4 androstenedione was made in a context of azoospermia.

INTRODUCTION: Les tumeurs testiculaires interstitielles (ou tumeurs testiculaires à cellules de Leydig) à expression endocrine sont rares. Chez l'adulte le tableau clinique et le bilan hormonal sont variables. PRÉSENTATION DU CAS: Cet article présente le cas d'une tumeur testiculaire gauche dans un contexte d'azoospermie. Le bilan hormonal montre des gonadotrophines effondrées, une testostéronémie normale et une delta4 androstenedione augmentée. L'examen anatomopathologique a mis en évidence une tumeur à cellule de Leydig. La TESE a permis l'extraction et la congélation de spermatozoïdes. L'histologie a retrouvé un aspect mixte d'hypospermatogenèse diminuée incomplète et d'aplasie. Dans les suites de l'orchidectomie partielle gauche les taux de gonadotrophines se sont normalisés ainsi que le taux de delta4 androstenedione. L'hypothèse physiopathologique est que l'augmentation de la delta4 androstenedione résulte de la sursaturation de la 17 ß-HSD intra-tumoral ou que l'activité de la 17 ß-HSD intra-tumoral est différente de celle dans les cellules de Leydig normales. Trois mois après la chirurgie, le spermogramme a montré une normalisation des paramètres spermatiques et une grossesse spontanée est survenue permettant la naissance d'une petite fille. CONCLUSION: Dans ce cas clinique, le diagnostic de tumeur testiculaire à cellule de Leydig sécrétant de la delta4 androstenedione a été fait dans un contexte d'azoospermie.