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Partners of men with Klinefelter syndrome can benefit from assisted reproductive technologies.

OBJECTIVE: To report the birth of a healthy female infant from a father with nonmosaic Klinefelter syndrome (KS) and document the experience of men with KS undergoing assisted conception. DESIGN: Retrospective. SETTING: Private IVF center. PATIENT(S): Twelve couples with male factor infertility due to Klinefelter syndrome undergoing assisted reproduction treatment. INTERVENTION(S): Controlled ovarian hyperstimulation, testicular sperm extraction, intracytoplasmic sperm injection (ICSI), round spermatid injection (ROSI), and preimplantation genetic diagnosis. MAIN OUTCOME MEASURE(S): Testicular sperm retrieval rate, fertilization rate, and pregnancy outcome. RESULT(S): There was a sufficient amount of motile sperm for injection into mature oocytes in 6 of the 11 testicular biopsies (54.5%). Fertilization rates for ICSI and ROSI cases were 54.2% and 41.6%, respectively. The pregnancy rate per ET was 27.2%. None of the ROSI cases resulted in pregnancy. Two patients had spontaneous abortions at 8 and 18 weeks of gestation, respectively. Only one patient delivered a healthy female baby after 36 weeks of an uneventful pregnancy. CONCLUSION(S): Men with KS can benefit from assisted reproductive technologies, and the testicular sperm retrieval rate among them is promising. Although sex chromosome aberrations among the embryos from men with KS are not common, couples can be offered preimplantation genetic diagnosis before ET.

Abortion, Spontaneous↗

How successful is repeat testicular sperm extraction in patients with azoospermia?

BACKGROUND: Little is known about the extraction rate in repeated sperm retrieval procedures in azoospermic patients. This study aimed to assess the feasibility of repeated sperm recovery in these patients. METHODS: A total of 1066 azoospermic men had their first sperm recovery between 1 January 1995 and 31 December 2003. A total of 381 men had obstructive azoospermia (OA), 628 nonobstructive azoospermia (NOA) and 57 showed hypospermatogenesis. RESULTS: Overall, sperm could be retrieved in all procedures in the 598 cycles performed in OA men (100%). A total of 117, 57, 24, 11, 7 and 1 men underwent, respectively, two, three, four, five, six and seven sperm retrievals; all were successful. Of the 784 procedures performed on the 628 men with NOA, sperm could be retrieved in 384 procedures (49%). During the first testicular sperm extraction (TESE) procedure, sperm could be extracted in 261 men with NOA (41.6%). A total of 103 men had a second attempt, 34 had a third attempt, 11 had a fourth attempt, 6 had a fifth attempt and 2 had a sixth attempt. In these cycles, sperm could be extracted in, respectively, 77 (74.7%), 28 (82.3%), 11 (100%), 5 (83.3%) and 2 (100%) men. CONCLUSION: Repeated TESE ensures a high sperm recovery rate even in patients with NOA. In NOA patients, studies reporting on TESE may therefore overestimate the retrieval rate by reallocating successful patients. These data also show that when no spermatozoa can be obtained after thawing cryopreserved testicular sperm for ICSI in NOA patients, a repeat TESE procedure can be planned.

Humans↗

Application of 2 vibrators salvages ejaculatory failures to 1 vibrator during penile vibratory stimulation in men with spinal cord injuries.

PURPOSE: Penile vibratory stimulation is the treatment of first choice for anejaculation in men with spinal cord injury. Nonresponders to penile vibratory stimulation are usually referred for electroejaculation or surgical sperm retrieval. Compared to penile vibratory stimulation these methods are invasive and usually yield lower total motile sperm, potentially limiting options for assisted reproductive technologies. To avoid these less than ideal options a simple method to salvage penile vibratory stimulation failures would be of benefit to spinal cord injured patients. We investigated the recovery rate when 2 vibrators were used to salvage ejaculatory failures to 1 vibrator in men with spinal cord injury. MATERIALS AND METHODS: A retrospective chart review was performed in 297 spinal cord injured men who underwent a total of 965 trials of penile vibratory stimulation at our center between 1991 and 2006. Only trials with high amplitude vibrators were examined. All men underwent 2 or more penile vibratory stimulation trials using 1 vibrator applied to the dorsum or frenulum of the glans penis. Men failing to ejaculate with 1 vibrator received 1 or more trials in which the glans penis was then sandwiched between 2 vibrators. RESULTS: Of all men 49% and 57% of those whose level of injury was T10 or above responded to penile vibratory stimulation with 1 vibrator. Of failures with 1 vibrator 22% responded to penile vibratory stimulation with 2 vibrators. CONCLUSIONS: Application of 2 vibrators salvaged ejaculatory failures to 1 vibrator during penile vibratory stimulation procedures in men with spinal cord injury. This simple penile vibratory stimulation sandwich method is recommended before referring patients for electroejaculation or surgical sperm retrieval.

Adolescent↗

Abdominal electrical stimulation rescues failures to penile vibratory stimulation in men with spinal cord injury: a report of two cases.

Most men with spinal cord injury are anejaculatory. To retrieve their semen for insemination, the procedure of penile vibratory stimulation is recommended over electroejaculation. Some men with spinal cord injury, however, cannot ejaculate with penile vibratory stimulation. We present 2 cases in which a simple, over-the-counter abdominal muscle stimulator rescued failures to penile vibratory stimulation. Use of this safe, easy, and inexpensive method may prevent some patients from undergoing more expensive, more invasive sperm retrieval methods such as electroejaculation or surgical sperm retrieval from the testis or epididymis.

Adult↗

Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI.

BACKGROUND: Although ICSI provides a way of treating azoospermic men, concern has been raised about the potential risk for transmission of genetic abnormalities to the offspring. We quantified the incidence of chromosomal abnormalities in epididymal and testicular sperm retrieved from azoospermic patients undergoing ICSI. METHODS: Individual testicular sperm were collected from testicular biopsies with an ICSI pipette, and epididymal sperm were retrieved by microsurgical epididymal sperm aspiration. Samples were processed by fluorescent in-situ hybridization (FISH) for chromosomes 18, 21, X and Y and the results compared with those from normal ejaculated samples. RESULTS: The overall aneuploidy rate of 11.4% in men with non-obstructive azoospermia was significantly higher (P = 0.0001) than the 1.8% detected in epididymal sperm from men with obstructive azoospermia and also the 1.5% found in ejaculated sperm. No significant difference was found between the epididymal and ejaculated samples. When the chromosomal abnormalities were analysed, gonosomal disomy was the most recurrent abnormality in both obstructive and non-obstructive azoospermic patients, while autosomal disomy was the most frequent in ejaculated sperm. CONCLUSIONS: Sperm of non-obstructive azoospermic men had a higher incidence of chromosomal abnormalities, of which sex chromosome aneuploidy was the most predominant. Genetic counselling should be offered to all couples considering infertility treatment by ICSI with testicular sperm.

Adult↗

Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions.

BACKGROUND: Y chromosome microdeletions are associated with severe male factor infertility. In this study, the success rate of testicular sperm retrieval was determined for men with deletions of AZF regions a, b or c. METHODS: AZF deletions were detected by PCR of 30 sequence-tagged sites within Yq emphasizing the AZFa, b and c regions. Semen analysis and diagnostic testis biopsy or testicular sperm extraction (TESE) findings were correlated with the specific AZF region deleted. RESULTS: A total of 78 men with AZF deletions included three with AZFa deletion, 11 with AZFb, 42 with AZFc, 16 with AZFb+c and six with Yq (AZFa+b+c). All men with AZFa, AZFb, AZFb+c and Yq deletions were azoospermic and no sperm were found with TESE or biopsy. Of men with isolated AZFc deletion, sperm were found in 75% (9/12) by TESE and 45% (9/20) on biopsy (56% overall); 62% (26/42) were azoospermic and 38% (16/42) severely oligozoospermic. A total of 7 patients with deletion patterns that included the complete AZFa region and 23 that included the complete AZFb region who underwent TESE or biopsy did not have sperm detected by these surgical measures. CONCLUSIONS: Microdeletion of the entire AZFa or AZFb regions of the Y chromosome portends an exceptionally poor prognosis for sperm retrieval, whereas the majority of men with AZFc deletion have sperm within the semen or testes available for use in IVF/ICSI.

Adult↗

Exploring male fertility options after spinal cord injury: the role of the nurse clinician.

Male sexual function and fertility are important areas that need to be addressed for men undergoing spinal cord injury (SCI) rehabilitation. Rehabilitation nurses need to understand what fertility after SCI involves. Significant advances in the areas of sperm retrieval and advanced reproductive technologies have made biological parenthood for many men with SCI a viable option. This article reviews the various sperm retrieval techniques and advanced reproductive technologies available today. It also describes the unique role of a nurse clinician working in a fertility clinic designed specifically to address the fertility concerns of men and their partners after SCI.

Critical Pathways↗

Increased current delivery and sperm collection using nifedipine during electroejaculation in men with high spinal cord injuries.

Elevated blood pressure associated with autonomic hyperreflexia during electroejaculation in persons with high spinal cord injuries often prevents successful sperm retrieval. The ability of the calcium channel blocker nifedipine to reduce the effects of autonomic hyperreflexia, to facilitate greater current delivery, and to increase sperm collection was evaluated in six persons with spinal cord injuries. Ten milligrams of nifedipine given sublingually ten to 15 minutes before electroejaculation attempts helped to moderate autonomic hyperreflexia and the associated blood pressure elevations. These effects of nifedipine allowed greater current delivery and ultimately increased the chances of successful sperm retrieval in the six men. No adverse drug effects were observed.

Adult↗

Predictive factors of successful testicular sperm recovery in non-obstructive azoospermia patients.

Recovery of testicular spermatozoa from non-obstructive azoospermic patients for intracytoplasmic sperm injection (ICSI) is a recent advance in the treatment of male infertility. The purpose of this study is to identify predictive factors for sperm recovery in non-obstructive azoospermic patients. A total of 178 men with non-obstructive azoospermia had multiple testicular sperm extraction (TESE) procedures to recover spermatozoa for intracytoplasmic sperm injection (ICSI) from June 1996 to February 1999. Testicular volume, serum follicle stimulating hormone (FSH) level and testicular histology were examined as positive predictive factors for sperm recovery. Testis biopsies were categorized as severe hypospermatogenesis, maturation arrest and Sertoli cell-only syndrome based on the most advanced pattern of spermatogenesis seen on histology. Sperm retrieval success rates for the patients in three histopathological categories were compared. Spermatozoa were successfully recovered in 94 of 178 (52.8%) men. Sperm were retrieved in 13 of 80 (16.3%) with Sertoli cell-only syndrome, 15 of 24 (62.5%) with maturation arrest, and 66 out of 74 (89.2%) with severe hypospermatogenesis. Spermatozoa recovery has no correlation with testicular volume or serum FSH level. When compared against Sertoli cell-only syndrome, the odds of sperm retrieval success rate was 44.3 times higher in severe hypospermatogenesis and 8.4 times in maturation arrest. These results demonstrate meaningful correlation between successful testicular sperm recovery and testis histopathology. Only testicular histopathology can be used as a predictor of successful sperm recovery.

Adult↗

The efficacy of repeat percutaneous epididymal sperm aspiration procedures.

PURPOSE: The development of intracytoplasmic sperm injection spawned new methods of sperm retrieval for men with obstructive azoospermia who did not want to undergo reconstruction of the seminal tract. There is a wide array of different procedures that may be performed in these cases, for instance percutaneous epididymal sperm aspiration (PESA) and microepididymal sperm aspiration. However, concerns regarding the presence of sperm in a second PESA attempt due to possible fibrosis have been suggested by many authors. We evaluate if it is worthwhile to repeat percutaneous epididymal sperm aspiration. MATERIALS AND METHODS: The records of 20 patients (23 attempts) who underwent repeat PESA from January 1996 to September 2000 for assisted reproductive technique purposes were reviewed. In all patients the repeat procedure was performed on the same side as the previous PESA. Data were collected on patient age, presence of motile sperm during PESA, epididymal side, pregnancies and abortion rates. RESULTS: Mean patient age +/- SD was 32.4 +/- 5.6 years. One patient was excluded from our analysis due to lack of information on the chart regarding the side of the procedure. Repeat PESA was performed in the right epididymis in 12 attempts and in the left in 10. Of the remaining 19 patients 14 (73.68%) did not and 5 (26.3%) have sperm in the epididymal fluid. In these 5 patients 8 repeat PESA procedures were performed (3 procedures in 1 and motile sperm was always found (8 of 22 attempts, 36.4%). Three patients achieved pregnancy with the motile sperm retrieved from the repeat PESA (3 of 8 repeat attempts, 37.5%). No abortions were detected. CONCLUSIONS: More than a third of repeat PESA attempts resulted in the presence of motile sperm. Before performing testicular sperm aspiration or extraction in patients who have undergone previous PESA without achieving pregnancy, repeat PESA may be done. Further attempts should be added in the future to confirm these results.

Adult↗

Enzymatic digestion of testicular tissue may rescue the intracytoplasmic sperm injection cycle in some patients with non-obstructive azoospermia.

Recovery of testicular spermatozoa from azoospermic patients with testicular failure, followed by intracytoplasmic sperm injection (ICSI) is a recent advance in the treatment of male infertility. In most cases, free spermatozoa are recovered from testicular tissue after mechanical mincing of multiple biopsies. Testicular sperm retrieval, however, remains unsuccessful in 30-50% of male patients suffering from Sertoli cell-only syndrome and maturation arrest. In this study, a strategy was developed in order to maximize the chance of sperm retrieval in difficult cases of testicular failure. The ultimate step was the use of enzymatic procedures (collagenase type IV) to dissociate the testicular tissue completely. Testicular tissue of 41 patients for whom no spermatozoa were found after mechanical mincing of the testicular tissue was investigated. In 14 out of the 41 cases (34%), enough spermatozoa for ICSI were found after fine mincing of multiple biopsies and several hours' search in the cell suspension treated with the erythrocyte-lysing buffer (ELB). In 27 out of the 41 patients, no spermatozoa were found even after the use of ELB. In seven out of these 27 failures (26%), spermatozoa for ICSI were retrieved after enzymatic dissociation of the residual minced tissue pieces, thus making ICSI possible despite failure to find spermatozoa with conventional mincing. From this study, we may conclude that enzymatic digestion of testicular tissue is easy to perform, is not time-consuming and constitutes a successful method in reducing the sperm recovery failures in patients with non-obstructive azoospermia.

Adult↗

Postmortem sperm procurement: a legal perspective.

PURPOSE: Postmortem sperm procurement with subsequent artificial insemination has become a technically feasible method for posthumous conception. A variety of legal questions exist involving the rights and relationships of the deceased, his family and his issue. We addressed these questions and designed a workable protocol for postmortem sperm procurement. MATERIALS AND METHODS: MEDLINE, WESTLAW and LEXIS medical literature, and case law searches were conducted. United States and international case law, United States (federal and state) statutes, Uniform Law Commissions Acts, and law review commentaries and articles were reviewed. RESULTS: While postmortem sperm procurement is being requested throughout the United States, no standard protocol or procedural guidelines have been established by federal or state statute. Furthermore, the courts have not yet addressed this specific scenario in reported case law. Statutes and case law do address related factual scenarios and issues, including property rights in human bodies, rules governing transplantation of human organs/body parts, rights of parties in in vivo sperm bank donations and responsibilities of parents to the conceptus of artificial insemination. CONCLUSIONS: A workable protocol can be established by analyzing case law and statutes addressing factually similar scenarios. Urologists must focus on the express intent of the decedent and limit any postmortem sperm retrieval to the specific requests made by the decedent. Decedent requests should be documented in writing. The decedent must be competent and of majority age. In the absence of decedent expressed affirmative directive calling for sperm retrieval, no other relative or guardian may authorize this retrieval. Issues regarding the legitimacy and inheritance rights of the conceptus will most consistently be addressed when explicitly provided for in the will of the decedent.

Cadaver↗

Structural and functional changes to the testis after conventional versus microdissection testicular sperm extraction.

OBJECTIVES: To compare, in a retrospective study, the ultrasound findings and hormonal changes after testicular sperm extraction (TESE) using the conventional multiple biopsy approach and the more recent microdissection technique. TESE has been performed using the conventional multiple biopsy approach and the more recent microdissection technique. METHODS: A total of 435 men with nonobstructive azoospermia who had undergone 543 TESE attempts were included in the study. The initial 83 attempts were done using the conventional open technique and the remaining 460 attempts were performed by microdissection. The sperm retrieval rates were compared, as were the complication rates as assessed by ultrasound and endocrinologic evaluations between the two groups. RESULTS: The retrieval rate by the conventional technique was 32% and by microdissection was 57% (P = 0.0002). In patients with hypospermatogenesis, the retrieval rate differed between the two approaches (P = 0.03). Ultrasound findings demonstrated fewer acute and chronic changes in the microdissection group than in the conventional group (P < 0.05). At 3 to 6 months after surgery, the testosterone levels had dropped to 80% of their pre-TESE levels in both groups (P < 0.01). The levels rose back to 85% after 12 months and to 95% after 18 months. The mean follicle-stimulating hormone levels increased from 22 +/- 2 to 30 +/- 3 IU/L (P = 0.02), and the luteinizing hormone levels increased from 12 +/- 2 to 16 +/- 2 IU/L (P = 0.2). CONCLUSIONS: TESE has effects on testicular function, but the microdissection procedure is relatively safer than the conventional technique and improves the sperm retrieval rate significantly in patients with nonobstructive azoospermia.

Adult↗

The use of enzymatic procedures to recover testicular germ cells.

Intracytoplasmic sperm injection (ICSI) with testicular spermatozoa and ejaculated spermatids has been applied successfully to treat infertility because of azoospermia due to obstruction or testicular failure. In most cases, free spermatozoa are recovered from testicular tissue after mechanical mincing of multiple biopsies. Testicular sperm retrieval, however, remains unsuccessful in a high proportion of male patients suffering from testicular failure. In the present study, four media for enzymatic collagen digestion of testicular tissue were compared on 15 testis biopsies obtained from azoospermic patients following an ICSI treatment and on five biopsies from orchiectomy patients. To dissociate the testicular tissue, collagenase type IA, collagenase type IV, collagenase type IA supplemented with elastase and collagenase type IV supplemented with elastase were used. The preparations with only collagenase type IV provided the best dissolution of the cells from their tissue, with a higher yield of free vital testicular spermatozoa and single round germ cells. Enzymatic digestion of testicular tissue has the advantage, especially in cases of testicular failure, that several biopsies can be concentrated into one pellet of single cells. In this way, the sperm retrieval in cases of testicular failure might be optimized to yield the maximal numbers of spermatids and/or spermatozoa.

Adult↗

Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision.

Testicular sperm extraction (TESE) is often an effective method for sperm retrieval from men with non-obstructive azoospermia. However, TESE has been a blind procedure that does not identify the focal sperm-producing areas of the testicle until after tissue has been excised from the patient. Experience with a new technique of microdissection of testicular tubules is presented here that identifies sperm-containing regions before their removal. Identification of spermatogenically active regions of the testicle is possible by direct examination of the individual seminiferous tubules. The underlying concept for this technique is simple: seminiferous tubules containing many developing germ cells, rather than Sertoli cells alone, are likely to be larger and more opaque than tubules without sperm production. In a sequential series of TESE cases for men with non-obstructive azoospermia, the ability to find spermatozoa increased from 45% (10/22) to 63% (17/27) after introduction of the microdissection technique. Microdissected samples yielded an average of 160,000 spermatozoa per sample in only 9.4 mg of tissue, whereas only 64,000 spermatozoa were found in standard biopsy samples that averaged 720 mg in weight (P < 0.05 for all comparisons). For men where microdissection was attempted, successful identification of enlarged tubules was possible in 56% (15/27) of cases. However, spermatozoa were retrieved with microdissection TESE for six men in whom sperm retrieval was unsuccessful with standard TESE approaches (35% of all men with spermatozoa retrieved). These findings suggest that microdissection TESE can improve sperm retrieval for men with non-obstructive azoospermia over that achieved with previously described biopsy techniques.

Dissection↗

Semen production in adolescent cancer patients.

BACKGROUND: The influence of an accompanying person (parent, guardian or nurse) on the ability of an adolescent (post-pubescent, <20 years of age) to produce a semen sample for cryopreservation, is undetermined, as is the potential for use of urine samples to retrieve sperm in those adolescents that are unable to produce a semen sample. METHODS: The records from 1991-2000 inclusive were reviewed to derive those adolescent patients who were unable to produce semen for cryopreservation prior to undergoing treatment for a malignant condition. RESULTS: During the study period 238 adolescents attended our unit of whom 205 (86.1%) banked semen ('producers'). The remaining 33 adolescents (13.9%) were initially unable to produce a sample ('non-producers'), four of these provided a urine specimen for analysis (12.1%) and of these one had sufficient sperm for cryopreservation. Of the 'accompanied' patients 29.7% (19/64) were non-producers while in the 'unaccompanied' patients only 8.0% (14/174) were non-producers (chi(2) = 16.58, P < 0.001). The relative risk (RR) of not producing a semen sample for the accompanied group of patients was greater than that for the unaccompanied group (RR = 3.689, 95% confidence interval: 2.0-6.9). One patient returning alone successfully provided a semen sample for storage. CONCLUSION: Units should consider the effect of the presence of an accompanying person when an adolescent is unable to produce a semen sample and should consider requesting urine to retrieve sperm.

Adolescent↗

Intracytoplasmic injection of fresh and cryopreserved testicular spermatozoa in patients with nonobstructive azoospermia--a comparative study.

OBJECTIVE: To compare the outcome of intracytoplasmic sperm injection (ICSI) with fresh and frozen-thawed testicular spermatozoa in patients with nonobstructive azoospermia. DESIGN: Retrospective analysis of consecutive ICSI cycles. SETTING: In Vitro Fertilization Unit, Assaf Harofeh Medical Center. PATIENT(S): Eighteen with nonobstructive azoospermia in whom testicular sperm was found after testicular sperm extraction. INTERVENTION(S): Testicular sperm retrieval, cryopreservation, and ICSI with fresh or frozen-thawed testicular spermatozoa. MAIN OUTCOME MEASURE(S): Two-pronuclear fertilization; embryo cleavage rates, mean number of embryos transferred per cycle, and their relative quality, embryo implantation, clinical pregnancy, and ongoing pregnancy rates (PRs) per ET. RESULT(S): No statistically significant differences were noted in all parameters examined between ICSI cycles with fresh or cryopreserved testicular spermatozoa from the same nine patients and comparing all ICSI cycles performed; with fresh (25 cycles) and thawed (14 cycles) testicular spermatozoa, respectively: two-pronuclear fertilization, 47% versus 44%; embryo cleavage rates, 94% versus 89%; implantation rates, 9% versus 11%; and clinical PR, 26% versus 27%. The delivery or ongoing PR using fresh sperm was better (21% versus 9%), but the difference did not reach statistical significance. The cumulative clinical PRs and ongoing PRs per testicular sperm extraction procedure were 36% and 24%, respectively. CONCLUSION(S): Testicular sperm cryopreservation using a simple freezing protocol is promising in patients with nonobstructive azoospermia augmenting the overall success achieved after surgical sperm retrieval.

Adult↗

Conventional multiple or microdissection testicular sperm extraction: a comparative study.

BACKGROUND: Testicular sperm extraction (TESE) with ICSI is becoming the first-line treatment for non-obstructive azoospermia (NOA). Recently, the sperm retrieval rate (SRR) by microdissection TESE was reported to be higher than by conventional TESE. However, a comprehensive comparison between multiple and microdissection TESE patients including histological findings has not been reported. METHODS: Patients with NOA who underwent microdissection TESE (n = 56) or multiple TESE (n = 37) were compared. Pre-operative characteristics were similar between groups. In addition, microscopic findings during microdissection TESE also were investigated. RESULTS: Operative time was significantly longer for microdissection TESE than for multiple TESE. Histological examination suggested that spermatogenesis was relatively more impaired in the microdissection TESE group than in the multiple TESE group. Despite this, SRR by microdissection TESE (42.9%) appeared higher than by conventional TESE (35.1%) although this observation failed to reach statistical significance. Seventeen of 26 patients (65.4%) with heterogeneous tubule were successful for sperm retrieval. No severe operative complications occurred in any patient in either group, and no patient required post-operative hormone replacement to treat hypogonadism. CONCLUSIONS: Microsurgical technique is safe and may improve SRR for TESE in a variety of patients with NOA, especially patients with heterogeneous testicular tubules.

Adult↗