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Inhibin B and anti-Müllerian hormone, but not testosterone levels, are normal in infants with nonmosaic Klinefelter syndrome.

Klinefelter syndrome is a major cause of infertility in the male. Nevertheless, pregnancies were recently obtained by intracytoplasmic injection of sperm retrieved by surgery or ejaculation, underscoring the need to understand the role of Sertoli and Leydig cell secretions during development. In 18 infants with prenatally diagnosed homogenous 47,XXY karyotype, blood samples were taken from birth to 3 yr of age. Inhibin B (INHB), anti-Müllerian hormone (AMH), testosterone, FSH, and LH levels were compared with those in six adolescents with XXY karyotype and reference values established in 215 control infants. In XXY infants FSH, LH, INHB, and AMH did not differ from controls. Testosterone levels during the first trimester exhibited a physiological increase but were lower than in controls (P = 0.0001). Significant correlations were found between testosterone and LH (P < 0001), between INHB and FSH (P = 0.0011), and between AMH and INHB (P = 0.025). In XXY adolescents, AMH and INHB were undetectable. Our findings demonstrate that testosterone secretion is impaired in infants with Klinefelter syndrome. By contrast, INHB and AMH secretions were not altered, which raises the question of the mechanism(s) governing the decline of Sertoli cell function after puberty.

Adolescent↗

Retrograde ejaculation and male infertility.

Incompetence of the internal urethral sphincter causes semen to pass into the bladder. Infertility can be successfully treated by restoring normal ejaculation or by sperm retrieval techniques.

Ejaculation↗

Focal testicular lesion after sperm extraction or aspiration: sonographic appearance simulating testicular tumor.

OBJECTIVE. We describe the sonographic features of focal intratesticular lesions seen in men who underwent sperm retrieval procedures. CONCLUSION. Although many urologists believe that solid intratesticular masses are malignant until proven otherwise, a growing number of benign focal testicular lesions have been described. Awareness of the cause and sonographic appearance of focal abnormalities in men who have undergone testicular aspiration or extraction should help radiologists suggest the correct diagnosis and advise a conservative approach on the basis of close surveillance by serial physical, laboratory, and imaging studies.

Adult↗

Y chromosome and male infertility: update, 2006.

Male factor infertility accounts for about half the cases of couple infertility and in around 50% of cases its etiology remains unknown. Molecular genetic techniques have unveiled a number of etiopathogenetic factors, including microdeletions of the Yq. Y chromosome microdeletions removing the AZoospermia Factor (AZF) regions are the most frequent molecular genetic causes of oligo/azoospermia. The intense effort of many laboratories contributed to a better understanding of the clinical significance of this genetic anomaly and to the identification of fertility candidate genes in the AZF regions. Important progress has been made on the structure of the Y chromosome and the mechanism of deletion. Studies aimed to define a predisposing genetic background for Yq deletions were not successful, perhaps due to the low number of patients analyzed so far. The screening for Yq deletions became a routine diagnostic test that provides an etiology for spermatogenic disturbances, and assess in the prognosis for testicular sperm retrieval according to the type of deletion. Assisted reproductive techniques represent an efficient symptomatic therapy for men bearing Y microdeletions, however, this genetic defect is transmitted to the male offsprings, affecting their fertility. Future studies should focus on understanding the biological function of AZF genes which is an essential step for the development of more appropriate and knowledge-based therapies.

Chromosome Deletion↗

Y chromosome and male infertility.

Male factor infertility accounts for about half the cases of couple infertility. In more than 60% of cases the origin of reduced testicular function is unknown but they may have an unidentified genetic anomaly. Microdeletions of the long arm of the human Y chromosome are associated with spermatogenic failure and have been used to define three regions of Yq (AZFa, AZFb and AZFc) that are recurrently deleted in infertile males. Several genes have been identified within this region and have been proposed as candidates for infertility. Many of these genes encode proteins involved in post-transcriptional gene expression and therefore could participate in the sperm maturation process. About 10-15% of azoospermic and about 5-10% of severely oligozoospermic men have Yq microdeletions. The deletions are associated with a wide range of histological pictures ranging from Sertoli Cell Only Syndrome (SCOS) to spermatogenic arrest and severe hypospermatogenesis. Assisted reproduction techniques such as in vitro fertilization (IVF) and Intra Cytoplasmic Sperm Injection (ICSI) alone, or in association with testicular sperm retrieval, represent an efficient therapy for these patients. However the potential of these techniques to transmit genetic defects causing male infertility raises the need for a systematic genetic screening and genetic counselling of these patients.

Chromosome Deletion↗

Post-mortem human reproduction: legal and other regulatory issues.

Increasingly women are seeking to establish pregnancies using sperm retrieved from their dead or dying partners. This raises a number of issues of a broad nature, but is also of significance in terms of the relationship between regulatory mechanisms and private choices. This article reviews this relationship with specific reference to the United Kingdom position, but also taking account of case law and regulation in Australia, particularly in the State of Victoria.

Attitude to Death↗

Spinal cord injury and male infertility.

Spinal cord injury (SCI) commonly affects males in their reproductive years. After spinal cord injury, most men experience fertility related problems including erectile and ejaculatory dysfunction, impaired spermatogenesis, abnormal sperm viability, motility, and morphology, genitourinary infection and endocrine abnormalities. In this article we will review the pathophysiology, evaluation and management of infertility in spinal cord injury. The impact of spinal cord injury on seminal plasma and the contribution of seminal oxidative stress to the poor sperm quality of men with spinal cord injury will be presented. Success with sperm retrieval techniques and assisted reproductive technology in SCI men with spinal cord injury will be discussed.

Ejaculation↗

Pregnancy by insemination of cryopreserved spermatozoa from a man with retrograde ejaculation: a case report.

BACKGROUND: Owing to the prevalence of diabetes mellitus, spinal injuries and aggressive surgical treatment of cancer, the number of younger patients with retrograde ejaculation is increasing. Since medical treatment to restore antegrade ejaculation often fails, several options for accomplishing insemination by these patients, including the use of sperm-rich urine obtained after masturbation and in vitro fertilization with sperm retrieved from the seminal tract, have been reported. We used the least invasive and most inexpensive procedure in a patient/couple with this condition. CASE: A 23-year-old man suffered from retrograde ejaculation after a spinal injury. He could achieve erection and engage in sexual intercourse but seldom had an orgasm or the sensation of ejaculation. We obtained spermatozoa from urine produced after masturbation at home and froze them. We used these frozen-thawed spermatozoa for intrauterine insemination, leading to the term birth of a healthy infant. CONCLUSION: In selected patient/couples, frozen spermatozoa obtained from postmasturbation urine can be used successfully for intrauterine insemination. This minimally invasive and most inexpensive procedure should be tried before planning in vitro fertilization.

Adult↗

Assisted reproductive technology in the management of azoospermic men--the Austrian experience.

Experience with intracytoplasmic injection of epididymal (MESA) and testicular spermatozoa (TESE) in Austria is summarized. Data from recent publications in scientific journals and results presented at different meetings were stratified for male factors, sperm retrieval methods, assisted reproductive techniques and conceptions. Four cooperative groups of andrologists and gynaecologists reported on MESA and TESE in Austria. They achieved five deliveries (one twin) and two ongoing pregnancies in 40 couples.

Austria↗

Biochemical findings in the ejaculate of men with non-obstructive azoospermia.

In men with non-obstructive azoospermia, testicle biopsy can provide isolated sperm which can be used for fertilization of an oocyte. The male seminal plasma was examined for adequate biochemical parameters and then tested as potential diagnostic parameters for prediction of sperm presence in non-obstructive azoospermia. Sperm was obtained by preparation of the testicular tissue. Biochemical parameters in men with found sperm were compared to findings obtained from men without sperm in the testicular tissue. The following parameters were analysed: fructose, lactate dehydrogenase, total acid phosphatase, Zn, K, Na, Cl, pH. No statistically significant differences were found in both groups under study. Biochemical examination of the ejaculate cannot provide any prediction of sperm retrieval in non-obstructive azoospermia.

Humans↗

[Therapeutic strategies in azoospermia: management].

ICSI allows use of epididymal or testicular sperm in case of azoospermia. The aim of this study is to propose an algorithm for the management of the different situations of azoospermia according to our personal experience and according to data of literature. The following points are discussed: epididymal or testicular origin of sperm, retrieval technique, contribution of freezing, interest of in vitro culture, side effects and need of a preliminary biopsy. So a therapeutic strategy adapted to both types of azoospermia obstructive and non obstructive can be proposed.

Biopsy↗

Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study.

Clomiphene citrate is a well-established agent that has been empirically used in cases of idiopathic oligospermia. Clomiphene increases endogenous gonadotropin-releasing hormone secretion from the hypothalamus and gonadotropin hormone secretion directly from the pituitary and, thus, increases intratesticular testosterone concentration. Using intracytoplasmic sperm injection (ICSI), very few sperm may be required for fertilization. The objective of this study was to determine if the application of clomiphene citrate in males with nonobstructive azoospermia might produce sufficient sperm for ICSI, either by resulting in sperm identified in the ejaculate or by potentially improving outcomes of surgical testicular sperm extraction. Forty-two patients with nonobstructive azoospermia (age range, 25-39 years) from 3 international centers were evaluated with routine history, physical examination, and hormonal assessment. Initial testicular biopsy demonstrated maturation arrest in 42.9% and hypospermatogenesis in 57.1% of patients. Clomiphene citrate was administered, with the dose titrated to achieve serum testosterone levels between 600 ng/dL and 800 ng/dL, and semen analyses were performed at periodic intervals. In patients remaining azoospermic on semen analysis, surgical testicular biopsy and sperm extraction were performed. After clomiphene citrate therapy, 64.3% of the patients demonstrated sperm in their semen analyses ranging from 1 to 16 million sperm/mL, with a mean sperm density of 3.8 million/mL. Sufficient sperm for ICSI was retrieved by testicular sperm extraction in all patients, even though 35.7% remained azoospermic. Additionally, clomiphene citrate administration resulted in a statistically significant increase in testis biopsy patterns associated with greater likelihood of sperm obtained by surgical extraction (P < .05). We conclude that clomiphene citrate administration may result in sperm in the ejaculate of patients with nonobstructive azoospermia or the simplification of testis sperm retrieval. Surgeons may consider a course of clomiphene citrate administration prior to surgical sperm retrieval in patients with nonobstructive azoospermia.

Adult↗

Percutaneous testicular sperm aspiration and intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia: an easy alternative to TESE and MESA.

OBJECTIVE: To evaluate the recovery rate of sperm from the testis using percutaneous testicular aspiration with a 22-gauge hypodermic needle followed by evaluation of the fertilization rate and pregnancy rate after intracytoplasmic sperm injection. MATERIALS AND METHODS: This is a prospective observational study performed in a private in vitro fertilization setting in Kuwait. Fifteen patients with obstructive and non-obstructive azoospermia were included in the study. Thirteen of them had previous microepididymal sperm aspiration, percutaneous epididymal sperm aspiration or testicular sperm extraction. The sperm were retrieved using percutaneous testicular aspiration under local analgesia. This was followed by intracytoplasmic sperm injection. A total of 146 eggs were collected and 112 were injected. RESULTS: Normal fertilization occurred in 91 oocytes (87.5%) and the total number of embryos cleaved was 83 (91%). Embryo transfer was performed in 13 with pregnancy rate of 33.3 per treatment cycle and 38.5 per embryo transfer. Failure to retrieve sperm was encountered in 2 cases both in the hypospermatogenesis group. CONCLUSIONS: Percutaneous testicular sperm aspiration using hypodermic needles under local analgesic is an easy and cheap method with high patient acceptability, minimal complications and no need of special training. In this small group, it seems to have an acceptable success rate in terms of sperm retrieval and pregnancy in the obstructive type as well as hypospermatogenesis, but to lesser extent.

Embryo Transfer↗

Vigorous prostatic massage: a simple method to retrieve spermatozoa for intracytoplasmic sperm injection in psychogenic anejaculation: case report.

A simple, non-invasive method to retrieve spermatozoa from patients with anejaculation is described. Three patients with psychogenic primary anejaculation were referred for intracytoplasmic sperm injection (ICSI). On the day of oocyte retrieval, vigorous prostatic massage was done. Examination of the expressed prostatic secretion revealed a sufficient number of motile spermatozoa in cases 1 and 3. In case 1, only one poor quality oocyte was obtained and ICSI was unsuccessful. Spermatozoa were cryopreserved for future use. In case 2, no spermatozoa were retrieved by prostatic massage. A testicular biopsy was performed to retrieve spermatozoa for ICSI. Unfortunately no pregnancy resulted. In case 3, retrieved spermatozoa were successfully used for ICSI, and 19 ova were injected. Fertilization occurred in 10 of these; seven were cryopreserved and three embryos were transferred. Ultrasound scan has confirmed a singleton pregnancy, which is ongoing. We conclude that vigorous prostatic massage could be an effective method of sperm retrieval for assisted conception in selected patients with anejaculation.

Adult↗

Cryopreservation of epididymal sperm.

The advent of ICSI and the perfecting of freezing protocols for sperm samples that in the pre-ICSI era would not have been frozen, allows now routine cryopreservation of epididymal sperm regardless of their quality and quantity. There are two methods to retrieve epididymal sperm: microsurgical epididymal sperm aspiration (MESA) and percutaneous epididymal sperm aspiration (PESA). The majority of the literature has focused on the technique of MESA to obtain sperm on the claim that the amount of sperm retrieved with PESA might not be sufficient to allow cryopreservation. However, there are no data on cryopreservation and ICSI with epididymal sperm collected with PESA technique. In this study, a total of 68 consecutive cycles of PESA, of which 46 were performed with fresh epididymal sperm and 22 with frozen/thawed specimens were retrospectively analyzed. In the fresh epididymal group (n = 46), 446 eggs were injected and 207 cleaving embryos were obtained (fertilization rate of 46%). In the cryopreserved epididymal sperm group (n = 22), 216 eggs were injected and 115 cleaving embryos were obtained (fertilization rate of 53%, P = NS). There were 18 pregnancies (39%) with 17 (37%) delivered/ongoing in the fresh group, while there were 11 (50%) with 9 (41%) delivered/ongoing in the frozen group (P = NS). Epididymal sperm for cryopreservation was available in 44 of the 46 PESA cycles. Additionally, in the fresh group, 19 couples had excess embryos for cryopreservation while in the frozen group, ten couples had excess embryos for cryopreservation. A total of 17 frozen embryo transfer with epididymal sperm from PESA were analyzed. Of these, 12 FET were from embryos from the fresh epididymal group and three pregnancies with livebirths (25%) were recorded. Five FET were performed with extra embryos from frozen epididymal sperm and two (40%) pregnancies with livebirths were obtained. In summary, these data show that epididymal sperm obtained by PESA can be successfully cryopreserved in order to avoid future retrievals procedures and fertilization and pregnancy rates are similar between fresh and cryopreserved epididymal sperm. It is also reported for the first time that the transfer of frozen embryos obtained with either fresh or frozen thawed epididymal sperm leads to the same pregnancy'and delivery rate.

Cryopreservation↗

Results of assisted reproductive technique in men with cystic fibrosis.

BACKGROUND: Sterility in men with cystic fibrosis (CF) raises the question of the use of assisted reproductive techniques (ART). A multidisciplinary network including adult CF centre and reproductive medicine units was set up to answer requests for ART. METHODS: This retrospective study included 25 men with CF between 1994 and 2004. Clinical status, semen analysis, CF mutations analysis and artificial insemination by donor (AID) or ICSI after surgical retrieval of sperm were monitored. RESULTS: All CF men had azoospermia. Two chose AID first (one delivery); 23 chose ICSI. Sperm were surgically retrieved in 21 cases, and ICSI was performed in 19. Pregnancies occurred in 12 of these 19 couples (63%) (two ectopic pregnancies, two spontaneous abortions, one termination of pregnancy for polymalformed twins and 11 single deliveries in nine couples). Two couples tried AID after ICSI failed; one had twins. Another adopted a child, and two had a spontaneous pregnancy. After a follow-up of 4.1+/-2.3 years, two patients died, two underwent lung transplantation and 21 remained stable. CONCLUSION: ART can help men with CF to become a father, but their health status and short survival need careful counselling and multidisciplinary medical care.

Cystic Fibrosis↗

Cytogenetic and molecular study of a premature male infant with 46,XX derived from ICSI: case report.

We investigated the aetiology of the male phenotype in a premature infant derived from ICSI with a 46,XX karyotype. A karyotypically normal couple underwent ICSI because of obstructive azoospermia in the male partner. Sperm were retrieved by testicular sperm extraction (TESE), cryopreserved, and later used for ICSI. The pregnancy after ICSI ended at 20 weeks. A normal-appearing male was delivered but he did not survive. Umbilical cord blood and placenta were sampled and used for molecular and cytogenetic investigation. The 46,XX karyotype from G-banding in this male infant correlated to a balanced female comparative genomic hybridization (CGH) profile in placental tissue. No PCR amplification of SRY on the p arm of the Y chromosome was observed while fluorescence in-situ hybridization (FISH) with the SRY probe also could not detect the gene in cord blood or placental tissues. CGH and FISH, with X and Y centromeric probes, failed to detect mosaicism in the trophoblast, stroma and amnion. Skewed X-chromosome inactivation (81%) was found in the chorionic villi. The molecular and cytogenetic studies indicated a 46,XX male infant without the SRY gene or 46,XX/XY mosaicism. The possible mechanism in this SRY-negative XX male by ICSI is discussed.

Adult↗