Abus et danger du traitement au citrate de clomiphène dans l’infertilité masculine

Obiective

To describe a case of seminoma occurring in a patient with a past history of cryptorchidism, infertility and clomiphene citrate (CC) treatment. To review the literature of seminoma in association with these risk factors.

Case report

A 33 year old man developed typical seminoma in the right testis. A bilateral cryptorchidism was lately diagnosed and treated by orchidopexy at the age of 17. Primary infertility due to oligoasthenospermia was diagnosed at the age of 29. Treatment was initiated with CC at the dose of 25 mG/day. Semen quality improved gradually. After failure of various assisted reproductive techniques, a spontaneous pregnancy was achieved and a healthy baby delivered. Shortly after delivery the seminoma was diagnosed, after a totla of three years of treatment. Six cases of testicular tumors have been reported in the literature in which patients had been pretreated with fertility drugs for various priods of time before tumors was diagnosed. Cryptorchidism is a well-known risk factor for testicular malignancy, as is the infertil state. Clomiphene citrate may promote malignant transformation by activation of estrogen receptors, by raising gonadotropin and/or testosterone concentrations, or by other mechanisms.

Conclusion

Clomiphene citrate may have a previously unappreciated malignancy-promoting effect in infertile men, especially those with other risk factors. Clinicians treating similar patients should take this into account and the literature monitored for other associated cases.     

Place de l’embolisation percutanée de la varicocèle dans le traitement de l’infertilité

Objectives

To describe percutaneous embolization of varicocele and to evaluate the effect on fertility disorders.

Materials and methods

One hundred nineteen patients, aged 11 to 48 years, underwent percutaneous embolization for varicocele indicated by a fertility disorder in 23% of cases. Correction of the varicocele and resolution of associated pain, improvement of testicular trophicity and the effect on fertility were studied and a review of the literature was performed.

Results

Percutaneous embolization was performed using neuroleptanalgesia on an outpatient basis. The technique combined venous sclerotherapy and placement of coils in the gonadal vein. The technique was successful in 95% of cases and one complication was observed. At 3 months, the varicocele and related pain had resolved in 98% of treated patients. According to previous reports in the literature, the relations between varicocele and fertility disorders are still unclear, but improvement of fertility (semen quality and conception rates) after varicocele repair has been established.

Conclusion

Although the consequences of varicocele on fertility have not been fully elucidated, treatment of varicocele appears to be beneficial. Percutaneous embolization of varicocele is a safe and effective alternative to surgery. This technique, based on a urological and radiological consensus, is the first-line treatment for varicocele in our institution.     

Intérêt de la ponction épididymaire et de la biopsie testiculaire systématique dans la prise en charge de l’azoospermie obstructive

Introduction

In obstructive azoospermia (OA), even if spermatozoa recovery rate are high, pregnancy rates could be lower as expected. When almost surgeons stop if they could find motile spermatozoa in the epididymis after microsurgical epididymal sperm aspiration (MESA), in our center, we add systematically a testicular biopsy with testicular sperm extraction (TESE). What are our sperm extraction rates in MESA or TESE? Are pregnancy and miscarriage rates different regarding the sperm origin?

Material and methods

A retrospective study including 48 infertile couples with ICSI because of OA. Between 2003 and 2011, each patient had a complete aetiological exploration and a surgery with the association of MESA and TESE. ICSI were asynchronous. Each time it was possible, ICSI was realized first with epididymal spermatozoa.

Results

For 48 couples, 99 ICSI were realized. Fifteen couples had 24 ICSI-TESE because no spermatozoon was found in MESA. Eleven couples had 20 ICSI-TESE because of bad quality of sperm recovered with MESA. Twenty-two couples had 22 ICSI-MESA in first intention. If failed, 11 couples had continued with 12 ICSI-MESA and 10 with 20 ICSI-TESE. Although the number of injected oocytes (7,1±4,1 vs 6,9 ±3,6 P: 0,8) and embryos (4,5±3,0 vs 4,7±2,7; P: 0,7) were not significantly different in the two ICSI groups, the number of top quality embryos (2,4±1,9 vs 3,6±2,0 P: 0,005) and frozen embryos (0,9±1,8 vs 1,7±1,9 P: 0,04) were higher in the ICSI-TESE group. Pregnancy rate per punction (58,5% vs 26,5%, P: 0,002) was higher when testicular spermatozoa were used.

Conclusion

Our approach is original with the systematic association of MESA and TESE for each OA man, when others stop surgery when they can find spermatozoa with MESA. We found that more than the half of epididymal explorations were not useful because negative or of bad quality. Embryo quality and per punction pregnancy rate were better with testicular spermatozoa. Association of MESA and TESE could improve the management of these infertile men without exposing them to an over surgical risk.     

L’apport de l’imagerie hybride TEMP/TDM dans la prise en charge du cancer différencié de la thyroïde

IntroductionSingle photon emission computed tomography combined with a low dose computed tomography (SPECT/CT), is a hybrid imaging integrating functional and anatomical data. The purpose of our study was to evaluate the contribution of the SPECT/CT over traditional planar imaging of patients with differentiated thyroid carcinoma (DTC).MethodsPost-therapy iodine 131 (¹³¹I) whole-body scan followed by cervico-thoracic SPECT/CT, were performed in 100 patients with DTC.ResultsAmong these 100 patients followed for a predominantly papillary DTC, planar imaging and SPECT/CT, were perfectly concordant in 70% of patients and discordant in the remaining 30%. The use of fusion imaging SPECT/CT compared to conventional planar imaging allowed us to correct our therapeutic approach in 27% (27/100 patients), according to the protocols of therapeutic management of our institute.ConclusionSPECT/CT is a hybrid imaging modality which provides better identification and more correct anatomic localization of the foci of radioiodine uptake with impact on therapeutic management.     

Approches cognitivo-comportementales de groupe dans la prise en charge précoce de jeunes adultes schizophrènes

One hundred and fifty young psychotic adults are treated at the Montreal Sacré-c?ur hospital’s specialized clinic for the treatment of first psychotic episodes. The clinic’s principal objective is the early intervention in the development of the psychotic process to ultimately decrease the length of time the psychosis remains untreated and avoid the deterioration of the cognitive, relational and social functioning of these young adults. This objective is achieved through the establishment of an important and long lasting therapeutic relationship, the use of new-generation anti-psychotic drugs, family-oriented intervention and the participation in a group cognitive-behavioural psychotherapy program. This program is divided into five sub-programs according to a continuum of social and cognitive functioning, ranging from weak to strong. The therapeutic activities of every subprogram are developed stepwise, and their sequence is determined by the resolution of the first psychotic episode as well as by the social integration of the participants. In this article, the authors present the structure and the functioning of the clinic. They also present the organization, and the general objectives, of the program as well as the different cognitive and behavioural strategies aimed at resolving the principal problems encountered by young adults at the time of their first psychotic episodes.     

Place des troubles de la spermatogenèse dans l’hypofertilité masculine

According to Thonneauet al., (1991), 14% of couples are subfertile. In at least 59% of the cases, a male factor was involved. This indicates that 8% (14% × 59%) of men are hypofertile. Since several causes can induce male infertility and because of the heterogeneous criteria and classifications used in the literature, the percentage of each etiologic factor has not been very precisely established. In a population of 2072 consecutive patients we identified an alteration of spermatogenesis in 52% of the cases. This indicates that about 4% of men might have a spermatogenic problem. The spermatogenic insufficiency was isolated in 43% of the cases (i.e. 23% of the total population) or associated with post-testicular causes of male infertility (infectious/inflammatory; autoimmune; obstructive) in 57% of the cases (i.e. 30% of the total population studied). An etiologic factor is clinically identified for 64% of the patients presenting with a spermatogenic insufficiency. The most relevant risk factors linked to spermatogenic alteration were history of mumps orchitis (OR [IC95%]=14,6 [3,4–62,3]), history of radiotherapy-chemotherapy (OR=14,7 [3,4–63,2]). These situations were found with a low frequency (1,4% and 1,3% of the cases respectively) but provoked a spermatogenic alteration in a large majority of cases (92,9% and 92,3% respectively). On the other hand, varicoceles (OR=3,7 [2,9–4,8]) and troubles in testicular descend (OR=2,9 [2,3–3,7]), were more frequent (20,6% and 20,1% of the cases respectively), but less frequently associated with spermatogenic insufficiency (in 73,7 and 69,6% of the cases).     

Mutations du gène de la polymérase gamma de l’ADN mitochondrial (POLG) associées à l’infertilité masculine?

The single DNA polymerase gene of mitochondrial DNA (POLG) contains a polymorphic CAG repeat in the first coding exon. The promising results of a first study by Rovio et al. showing that several cases of male infertility were related to a “homozygous mutant” genotype with a number of CAG repeats differing from 10, prompted us to conduct a large study on 503 infertile and 90 fertile men. Our results do not confirm any significant relationship between the polymorphic CAG repeat in thePOLG gene and male infertility.     

Place de l’annonce dans la prise en charge des patients souffrant de cancer

Cancer is the leading cause of death in developed countries. About 365,500 new cases have been diagnosed in France in 2012 according to French National Cancer Institute. To break the cancer constitutes a traumatism for the patient. For the clinical oncologist, this is a well-known cause of professional burnout syndrome. Nuclear physicians seem to be often asked for results after an exam by the patient. The delivery of cancer diagnosis will be presented form the perspective of the patient, the clinical oncologist and the nuclear physician.     

Indications de l’imagerie dans l’infertilité masculine (bourses,testicules)

Imaging modalities in the work up of male infertility are almost resumed to Ultrasound with Color Doppler which is quite performant if its indications are well-balanced:

-To look for abnormalities of the seminal tract.

-To evaluate clinical varicoceles (Testis, associated abnormalities).

-To screen the neoscrotal pouchs of ectopic operatively corrected Testis (occult tumor, epididymal abnormalities).

     

Impact de l’imagerie hybride TEMP/TDM dans le diagnostic et la prise en charge de l’ostéome ostéoïde

IntroductionThe osteoid osteoma is a major bone benign tumors in children. It is more common in boys. The femoral and tibial locations account for 50% of cases. Clinically, it is revealed by nocturnal pain relieved by aspirin. The pain may precede by several months the radiographic abnormality. The purpose of our work is to elucidate the contribution of SPECT/CT in addition to the planar bone scintigraphy in the diagnosis and treatment of osteoid osteoma about two cases.Case reportClinical case No. 1: a 10-year-old child who presented a limp nocturnal pain in the left hip evolving for 4 months. The radiograph of the pelvis showed bone condensation subtrochanteric left femur. SPECT/CT showed an image for an osteoid osteoma. Surgical resection of the home revealed in the histological study an osteoid osteoma of the left femoral neck. The evolution was marked by an immediate pain relief and full recovery of the left lower limb mobility. Clinical case No. 2: an 11-year-old child who had a limp nocturnal pain at the upper end of the left femur evolving for 2 months. The pain was paroxysmal, relieved by salicylates. The X-ray of the pelvis showed a metaphyseal image with peripheral condensation and thickening of the cortex. SPECT/CT showed an image for an osteoid osteoma. The intervention was a tumor excision resection. Histopathological examination revealed a small nidus consistent with an osteoid osteoma. The evolution was marked by an immediate pain relief and normalization of the mobility of the left lower limb.DiscussionThe SPECT/CT can increase the sensitivity and specificity of planar bone scintigraphy. It confirms the location of osteoid osteoma and defines its anatomical relationships in order to optimize surgical management.ConclusionThe SPECT/CT contributes significantly to the diagnosis of osteoid osteoma when radiological images are atypical or unusual clinical expression.     

Indications d’une étude méiotique dans l’infertilité masculine

Meiotic investigation is rare in male infertility. Now, some mutations affecting spermatogenesis exhibit characteristic cytogenetic figures, whereas testicular histology does not show specific aspects of this pathology. In male infertility with abnormal somatic caryotype, the aim of meiotic survey is to find the mechanisms inducing spermatogenic failure, and thus to lead to a better understanding of normal spermatogenesis. In addition to cytogenetic techniques, meiosis is also investigated by electron microscopy and molecular biology. Also, we think that a larger place must be grant to meiotic study in male infertility evaluation when the indication of testicular histopathology was settled.     

Etablissement de l’empreinte parentale dans la lignée germinale. Conséquences pour la prise en charge en AMP

Genomic imprinting is an epigenetic phenomenon in eutherian mammals that results in the differential expression of the paternally and maternally inherited alleles of a gene. Imprinted genes are necessary for normal mammalian development. Parental specific epigenetic modifications are imprinted on a subset of genes in the mammalian genome during germ cell maturation. Imprinting involves both cytosine methylation within CpG islands and changes in chromatin structure. All such epigenetic modifications are potentially reversible and can be erased. After the erasure step, new parental imprints are initiated, resulting in reintroduction of sex-specific imprints in the male and female germ line. Although the function of genomic imprinting is not clear, it has been proposed that it evolved in mammals to regulate intrauterine growth and mammalian development. If the epigenotype of individual gametes is directly correlated with their later developmental capacities, genomic imprinting would have important practical implications in reproductive medicine for the use of embryos derived from assisted reproduction.     

Gène CFTR et infertilité masculine en 2001 Conseil génétique, diagnostic prénatal, diagnostic pré-implantatoire

As the vas deferens is also absent in the majority of CF (cystic fibrosis) males, it has been proposed that CBAVD (Congenital Bilateral Absence of Vas Deferens) males may present an incomplete or mild form of CF. Many studies using more extensive mutation analysis have confirmed the role of CFTR gene defects: 80% of CBAVD patients carry one or two mutations. Each patient with a diagnosis of CBAVD should also be examined for pulmonary and pancreatic signs, and sweat tests should be performed. In couples with CBAVD linked to CFTR mutations, the risk of having children with CF or infertility is increased if the female is also a carrier. The woman should be screened for the most frequent CFTR mutations according to her ethnic background. After screening for 80% of the mutations responsible for CF, the residual risk of being a carrier with negative screening is: Z=h(1?a)/(1?ah)=1/120 considering a carrier frequency of 1/25 in the general population. In the case of positive screening, antenatal diagnosis by chorionic villus sampling may be proposed. However, in some situations it is difficult to predict the phenotypic consequences for the child, particularly when a severe transmutation of a variable allele is identified. As these couples require medically-assisted reproduction techniques, pre-implantation genetic diagnosis appears to be more appropriate than antenatal diagnosis. Only embryos that inherit the non-mutated maternal CFTR allele are replaced in the uterus. Examination of childre born to couples with CBAVD is mandatory: immunoreactive trypsinogen assay at 3 days of age, sweat test at 3 months and clinical examination, especially looking for signs of CF. Identification of CFTR mutations in a CBAVD patient has important consequences for his family. Each sibling has a 50% risk of being a carrier and a 25% risk of inheriting the same genotype. The genetic counsellor must inform these siblings about the possible risk of having CF children if they carry CFTR mutations and if their partner is also a carrier.     

Blessures dans la filiation et infertilité masculine : étude comparative et psychodynamique

The family history of a set of infertile men was the aim of the present study, through a filiation events grid based on a psychoanalytical approach. During the genetic counselling before ICIS procedure, the family chart was established and the filiation grid applied to a group of 30 infertile men requiring assisted reproductive procedures, as well as to a control group of 30 fertile men recruited in a maternity hospital after birth of their child. The filiation events differed significantly between two groups. It can be therefore assumed that difficulties in the past generation may play a part in some cases of infertility. A psychodynamic approach is then developed to highlight the hypothesis of a link between the traumatic impact of these filiation events on these men and its translation as a somatic expression.     

Incidences de la restriction calorique et du Nickel sur l’aromatase testiculaire du rat

This study was designed to determine whether intermittent fasting induces malnutrition that, according to many authors, accentuates the cytotoxic effects of environmental pollutants, or caloric restriction that reduces these effects. Ninety six male Wistar rats (180g) were divided into two groups: one group was fed daily (N) and the other group was fed every second day (J) for one month. At the end of one month, each group was then divided into two subgroups, one subgroup received an injection of 0.9% NaCI (groups NO and JO), the other subgroup received an injection of 4 mg/kg NiCI^b2 (groups NNi and JNi). Intermittent fasting was continued in parallel to treatment for 1, 3, 5 and 10 days. Under these experimental conditions, nickel increased testicular aromatase activity and altered total RNA, while no alteration of these biomarkers was observed with intermittent fasting. The combination of these two factors, nickel and intermittent fasting, did not amplify these effects. In contrast, protection of RNA by intermittent fasting was observed, especially overexpression of aromatase mRNA.