Manuel Gil-Salom

Testicular sperm extraction (TESE) and ICSI in patients with permanent azoospermia after chemotherapy

BACKGROUND Patients persistently azoospermic after chemotherapy have been considered traditionally as sterile unless sperm was frozen before therapy. Recent advances during the last decade combining testicular sperm extraction (TESE) and ICSI in patients with non-obstructive azoospermia allow these males to father their own genetic offspring. METHODS A retrospective study was conducted of 12 patients with non-obstructive azoospermia after chemotherapy undergoing TESE between 1995 and 2002. Cancer type and anti-neoplastic treatments were recorded, together with maximum testicular volume, serum FSH levels and testicular histopathology. When TESE was successful, spermatozoa were cryopreserved for performing ICSI later. RESULTS In five patients (41.6%) motile spermatozoa for cryopreservation and ICSI were retrieved. Four of them had received chemotherapy for testicular cancer, and one had been treated by chemotherapy/radiotherapy for Hodgkins disease. Clinical and histological parameters were unable to predict with certainty TESE outcome in an individual patient. Eight ICSI cycles were performed on five couples and one pregnancy was obtained which resulted in the delivery of a healthy girl. CONCLUSION Some patients with permanent azoospermia after chemotherapy can be successfully treated by TESE-ICSI. This procedure, however, may have potential genetic risks. Therefore, freezing semen before starting gonadotoxic therapy is the strategy of choice, and patients should be counselled accordingly.

Prognostic Factors for Response to Sildenafil in Patients with Erectile Dysfunction

Objective: To assess the clinical efficacy of sildenafil as treatment for erectile dysfunction (ED) the factors associated with treatment failure were investigated. Methods: Open, prospective study including 244 patients suffering from ED who were evaluated by anamnesis, physical exploration, blood test, dynamic penile color duplex ultrasonography and Sexual Health Inventory for Male (SHIM). The efficacy of sildenafil was assessed by repeating the SHIM 2 months after therapy, independent of the final dose used. Side effects were also recorded. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. Results: Overall, sildenafil was effective in 56.8% of 213 eligible patients. When the etiologic diagnosis was not included in the multivariate analysis, antecedents of diabetes mellitus, non–nerve–sparing radical prostatectomy and SHIM basal score were selected as predictors of a poor response. In a second analysis including etiologic diagnosis, only SHIM basal score and etiological diagnosis proved to be of prognostic value. Side effects were noticed by 24.4% of patients, none of them being severe. Conclusions: Sildenafil is a rather effective and well–tolerated treatment for ED. The basal severity of ED and etiological diagnosis are the prognostic factors most significantly associated with treatment outcome.

TESTICULAR SPERM EXTRACTION AND INTRACYTOPLASMIC SPERM INJECTION: A CHANCE OF FERTILITY IN NONOBSTRUCTIVE AZOOSPERMIA

PURPOSE We evaluate the efficacy of testicular sperm extraction and results of intracytoplasmic sperm injection in cases of nonobstructive azoospermia. In addition, we define predictive parameters for successful testicular sperm extraction in these patients. MATERIALS AND METHODS A total of 154 patients with nonobstructive azoospermia underwent multiple testicular biopsies to obtain testicular spermatozoa and for histopathological diagnosis. Results of testicular sperm extraction were related to suspected etiology of azoospermia, patient age, maximal testicular volume, serum follicle-stimulating hormone and histopathology. When testicular sperm extraction was successful, intracytoplasmic sperm injection was performed. RESULTS Spermatozoa were obtained from 63 patients (41%). No potential predictive parameters precluded successful testicular sperm retrieval. Fertilization was achieved in 74 of 76 intracytoplasmic sperm injection cycles. Normal 2 pronuclear fertilization was observed in 55% of the intact oocytes after microinjection. Clinical pregnancies were achieved in 21 cases for a pregnancy rate of 28% per started cycle. There were 4 miscarriages and 11 live births from 9 deliveries. In addition, a set of twins died after birth because of prematurity. Seven pregnancies were ongoing. CONCLUSIONS Men with nonobstructive azoospermia may have areas of preserved spermatogenesis in the testicles, and these spermatozoa can be retrieved for intracytoplasmic sperm injection. Although some clinical and histopathological parameters are associated with significantly different sperm recovery rates, it is not possible to predict with certainty the outcome of testicular sperm extraction in an individual patient. If testicular sperm extraction is successful, intracytoplasmic sperm injection offers the chance of pregnancy to these otherwise intractably infertile couples.

Sperm DNA fragmentation levels in testicular sperm samples from azoospermic males as assessed by the sperm chromatin dispersion (SCD) test

OBJECTIVE To analyze sperm DNA fragmentation (SDF) in testicular sperm samples from patients with azoospermia either from spermatogenic failure or from duct obstruction. Several technologies can be applied in the evaluation of SDF, but given the ease and low costs, the sperm chromatin dispersion test (SCD) has emerged as a promising standard. DESIGN Prospective blind observational cohort study. SETTING University-affiliated private IVF setting. PATIENT(S) Azoospermic patients from couples undergoing intracytoplasmic sperm injection cycles. INTERVENTION(S) Testicular sperm extraction (TESE). MAIN OUTCOME MEASUREMENT(S) We determined testicular SDF, and a basic comparison between nonobstructive (n = 22) and obstructive azoospermia (n = 40) was performed. We also correlated SDF with embryo quality and pregnancy outcome. RESULT(S) SDF in the testicular sperm of patients with nonobstructive azoospermia was significantly higher, 46.92% (SEM = 4.47), than that of patients with obstructive azoospermia, 35.96% (SEM = 2.63). A moderate relationship between embryo morphology and testicular SDF was detected. Logistic regression analysis of the effect of testicular SDF on pregnancy outcome revealed no significant effect (odds ratio = 1.015). CONCLUSION(S) Ours is the first report of SDF analysis in testicular sperm by using SCD in azoospermia. This result suggests that spermatogenesis failure may result in a severe affectation of sperm DNA integrity. The degree of DNA fragmentation using the SCD test is not reflected in pregnancy chances, and the explanation could be that embryos have been selected.

Pregnancy in an azoospermic patient with markedly elevated serum follicle-stimulating hormone levels

OBJECTIVE To assess the possibility of achieving a pregnancy in an azoospermic patient with markedly elevated serum FSH level. DESIGN A case report. SETTING In vitro fertilization program at the Instituto Valenciano de Infertilidad. PATIENT An azoospermic patient with small testes and serum FSH level (38.7 mIU/mL) higher than three times normal. Testicular biopsy revealed Sertoli cell-only syndrome with focal spermatogenesis. INTERVENTIONS Intracytoplasmic microinjection of testicular tissue-extracted spermatozoa. MAIN OUTCOME MEASUREMENTS Fertilization rate, cleavage rate, clinical pregnancy. RESULTS Eight of 11 (73%) intact oocytes showed two pronuclei. All of them cleaved normally. Four embryos were replaced into the uterine cavity and the other four were cryopreserved. A twin clinical pregnancy was achieved. CONCLUSION Spermatozoa may be present in testicular biopsy specimens of azoospermic patients with severe spermatogenic failure despite markedly elevated serum FSH level. These patients can be fertile after intracytoplasmic testicular sperm microinjection.

Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos

OBJECTIVE To evaluate the effect of sperm chromosome abnormalities--disomy for sex chromosomes and diploidy--in the chromosomal constitution of preimplantation embryos. DESIGN Retrospective cohort study. SETTING Infertility clinic. PATIENT(S) Three groups: 46,XY infertile men with increased incidence of sex chromosome disomy in sperm; 46,XY infertile men with increased diploidy rates in sperm; 47,XYY infertile men with increased sex chromosome disomy and diploidy rates in sperm. INTERVENTION(S) Sperm collection for fluorescence in situ hybridization analysis. Embryo biopsy for preimplantation genetic screening. MAIN OUTCOME MEASURE(S) Frequencies of numerical abnormalities in sperm for chromosomes 13, 18, 21, X, and Y, and in embryos for chromosomes 13, 16, 18, 21, 22, X, and Y. RESULT(S) A significant increase of chromosomally abnormal and mosaic embryos was observed in the three study groups compared with controls. Those sperm samples with increased sex chromosome disomy rates produced significantly higher percentages of aneuploid embryos, with a threefold increase for sex chromosomes. Sperm samples with increased diploidy rates were mainly associated to the production of triploid embryos. CONCLUSION(S) A strong correlation between sperm and embryo chromosomal constitution has been shown in infertile men with 46,XY and 47,XYY karyotypes.

Testosterone levels in men with erectile dysfunction

To investigate the frequency of hypogonadism in men with erectile dysfunction (ED) and to assess which factors are related with low testosterone levels.

Testicular sperm from patients with obstructive and nonobstructive azoospermia: aneuploidy risk and reproductive prognosis using testicular sperm from fertile donors as control samples

OBJECTIVE To establish a baseline incidence of chromosomal abnormalities in testicular sperm of fertile men and to determine the best control sample for comparisons with azoospermic males to estimate their reproductive prognosis. DESIGN Prospective study. SETTING Infertility clinic. PATIENT(S) Sixteen obstructive azoospermic (OA) and 19 nonobstructive azoospermic patients (NOA). Control samples were ejaculated sperm from ten fertile donors and testicular sperm from ten other fertile donors. INTERVENTION(S) Fluorescence in situ hybridization (FISH) in sperm. MAIN OUTCOME MEASURE(S) Sperm numerical abnormalities for chromosomes 13, 18, 21, X, and Y; ongoing implantation and pregnancy rates in intracytoplasmic sperm injection (ICSI) cycles. RESULT(S) In control samples, testicular sperm showed higher incidences of diploidy (0.27% vs. 0.10%) and disomy for chromosomes 13 (0.16% vs. 0.07%), 21 (0.25% vs. 0.12%), and sex chromosomes (0.34% vs. 0.21%) than ejaculated sperm. Comparisons with ejaculated control samples showed 12.5% OA and 68.4% NOA patients having significantly higher incidence of sperm chromosomal abnormalities. Compared with testicular control subjects, fewer OA (6.3%) and NOA (42.1%) patients had chromosomally abnormal sperm. NOA patients had lower ongoing implantation and pregnancy rates than OA patients, particularly those with abnormal FISH compared with testicular control samples. CONCLUSION(S) Sperm FISH analysis using testicular sperm control samples better identifies NOA patients with a lower likelihood of reproductive success.

Intracytoplasmic Testicular Sperm Injection: An Effective Treatment for Otherwise Intractable Obstructive Azoospermia

PURPOSE We evaluated the efficacy of intracytoplasmic sperm injection with testicular spermatozoa. MATERIALS AND METHODS Intracytoplasmic sperm injection was performed with spermatozoa obtained from testicular biopsy specimens in 15 patients with obstructive azoospermia, in whom standard microsurgical procedures were not feasible or had previously failed. RESULTS Fertilization was achieved in 14 of 15 cycles. Mean fertilization rate per cycle was 63.6%. Four clinical pregnancies occurred, for a pregnancy rate of 26.7% per started cycle and 28.6% per transfer. CONCLUSIONS Intracytoplasmic testicular sperm injection is followed by high fertilization rates, and offers the chance of a pregnancy to otherwise intractably infertile couples with obstructive azoospermia.

Aneuploidies in embryos and spermatozoa from patients with Y chromosome microdeletions

In patients with Y chromosome microdeletions and high percentage of numeric chromosome abnormalities detected by fluorescence in situ hybridization on sperm, a high percentage of abnormal embryos was observed compared with oligozoospermic patients without Y chromosome microdeletions, with a significant increase in the percentage of embryos with monosomy X. Differences in fertilization rates between the different patient groups were not observed; however, blastocyst rates were significantly impaired in patients with Y chromosome microdeletions.