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.

The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.

OBJECTIVE: To determine an optimal insemination technique in patients undergoing IVF after failed IUI and the role of intracytoplasmic sperm injection (ICSI) in such cases. DESIGN: Prospective, randomized study in couples with unexplained infertility (n = 63) and mild endometriosis (n = 7) undergoing IVF after four IUI cycles. Sibling oocytes were randomized into standard IVF or ICSI insemination according to the order of retrieval. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Italy. PATIENT(S): Seventy couples with unexplained infertility undergoing IVF after failing to conceive with controlled ovarian stimulation and IUI. INTERVENTION(S): In vitro fertilization and ICSI. MAIN OUTCOME MEASURE(S): Fertilization, cleavage, and embryo quality were compared in IVF- and ICSI-inseminated oocytes. RESULT(S): There was no significant difference in fertilization rates between ICSI (60.4%) and conventional IVF (54.0%). Similarly, there was no difference in embryo quality between both groups. There was no total fertilization failure in ICSI-inseminated oocytes, whereas 8 (11.4%) of 70 cases showed absence of fertilization when conventional IVF was used. CONCLUSION(S): Couples with unexplained infertility and mild endometriosis failing to conceive with IUI and undergoing IVF have an 11.4% chance of fertilization failure that can be overcome easily by using ICSI in at least some oocytes. ICSI, however, is not superior to IVF as an insemination technique in most cases. These data should be used in counseling patients.

Fertilization after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa.

OBJECTIVE: To assess the possibility of cryopreserving testicular tissue extracted sperm for intracytoplasmic sperm injection (ICSI). DESIGN: A report of two cases. Our study was approved by the Ethical Committee at the Instituto Valenciano de Infertilidad. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad. PATIENTS: Two azoospermic patients with severe spermatogenic failure but with focal spermatogenesis on testicular biopsies. In both cases, a first ICSI attempt with fresh testicular biopsy extracted sperm was unsuccessful. INTERVENTIONS: Cryopreservation of testicular spermatozoa in 100-micro L "pills." Intracytoplasmic sperm injection with thawed testicular spermatozoa. MAIN OUTCOME MEASUREMENTS: Fertilization rate, cleavage rate, embryo quality, clinical pregnancy. RESULTS: Fertilization rates were 36 percent and 100 percent after ICSI with fresh testicular spermatozoa, and 63 percent and 57 percent after ICSI with cryopreserved testicular sperm. In both cases, cleavage rates and embryo quality were similar when using fresh and cryopreserved testicular spermatozoa. No clinical pregnancies were achieved. CONCLUSION: High fertilization rates can be obtained after ICSI with frozen-thawed testicular tissue extracted spermatozoa. Cryopreservation of testicular sperm may avoid repetition of testicular biopsies in azoospermic patients in whom the only source of spermatozoa is the testicle.

In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage: an analysis of chromosome abnormalities in human preimplantation embryos.

OBJECTIVE: To analyze the incidence of numeric chromosomal abnormalities in preimplantation embryos from women with unexplained recurrent miscarriage (RM) so as to seek an etiology and to determine whether the use of IVF may be indicated to treat these cases. DESIGN: Prospective controlled study. SETTING: University laboratory of reproductive genetics and a tertiary referral center for infertility. PATIENT(S): Nine women with a mean (+/-SD) of 3.9 +/- 0.6 RMs who were undergoing IVF and preimplantation genetic diagnosis, and a control group of young (n = 10) and older (n = 6) patients who were undergoing preimplantation genetic diagnosis because of sex-linked diseases. INTERVENTION(S): In vitro fertilization, embryo culture for 72 hours, blastomere biopsy, and analysis of chromosomes 13, 16, 18, 21, 22, X, and Y with the use of fluorescent in situ hybridization. Transfer of chromosomally normal embryos into the uterus. MAIN OUTCOME MEASURE(S): Numeric chromosomal abnormalities in human embryos. RESULT(S): Sixty-six embryos from patients with RM were compared with 62 embryos from young patients and 41 embryos from older patients. There was a significant increase in the rate of abnormal embryos in the patients with RM and the older patients compared with the controls. Abnormalities in most of the chromosomes studied were higher in the RM group than in the control group, especially those affecting chromosome 13. CONCLUSION(S): There was an increase in numeric chromosomal abnormalities in preimplantation embryos from women with RM that could be the cause of infertility in many couples with unexplained RM. The use of IVF in such circumstances may be indicated if successful preimplantation genetic diagnosis is added to the procedure.

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.

The impact of endometriosis in couples undergoing intracytoplasmic sperm injection because of male infertility.

To assess the impact of endometriosis on intracytoplasmic sperm injection (ICSI) outcome, we have retrospectively evaluated 980 ICSI cycles, comparing the results of women with and without endometriosis. A total of 101 cycles was identified in which various degrees of endometriosis were involved, and in the remaining 879 cycles, male infertility was the only cause of infertility. Ejaculated spermatozoa were microinjected in all cycles. There was a significant reduction (P = 0.004) in the number of oocytes retrieved from women with endometriosis as compared to those without endometriosis. However, there were no significant differences in either fertilization or pregnancy and implantation rates between women with or without endometriosis. We conclude that the presence of endometriosis in patients undergoing ICSI because of severe male infertility does not affect fertilization, pregnancy and implantation rates, although significantly fewer oocytes are retrieved from patients with endometriosis.

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.

Intracytoplasmic sperm injection: a treatment for extreme oligospermia.

PURPOSE: We evaluated the efficacy of intracytoplasmic sperm injection in patients with extreme oligospermia. MATERIALS AND METHODS: A total of 67 intracytoplasmic sperm injection cycles was attempted in 58 infertile couples in which the husbands had extreme oligospermia (less than 100,000 spermatozoa per ml. ejaculate). RESULTS: Fertilization was achieved in 65 of 67 cycles. Mean fertilization rate per cycle was 66.4%. A total of 18 clinical pregnancies was obtained, for a pregnancy rate of 26.8% per started cycle. There were 4 miscarriages and 8 live births from 5 deliveries. Nine pregnancies are ongoing. CONCLUSIONS: Intracytoplasmic sperm injection in patients with extreme oligospermia is associated with high fertilization rates and offers the chance of pregnancy to these otherwise intractably infertile couples.

Is there a place for preimplantation genetic diagnosis screening in recurrent miscarriage patients?

Chromosomal abnormalities are one of the factors known to interfere with normal embryo development; thus preimplantation genetic diagnosis (PGD) for chromosome anomalies may be a new tool for improving the pregnancy rate in selected groups of patients. Embryos from three groups of patients (control, aged and recurrent miscarriage patients) were screened by PGD using specific DNA probes for chromosomes 13, 16, 18, 21, 22, X and Y. The control and aged groups were included in the PGD study because the women carried sex-linked genetic disease. The frequencies of chromosome anomalies observed in older women (46.3%) and in recurrent miscarriage patients (53%) were significantly higher (P < 0.05) than the frequency in the control group (19.3%). After PGD screening and transfer of normal embryos, pregnancies were obtained in women who had undergone repeated abortions (approximate 25% pregnancy rate per transfer) but not in older women. On the basis of these data, it seems that PGD screening of embryos can help some women undergoing repeated abortions, as these techniques allow successful pregnancies to be obtained or, if no pregnancy can be obtained, the results may help the couple to decide whether to enter an embryo or gamete donation programme.

Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome.

BACKGROUND: An increased incidence of chromosome abnormalities has been reported in sperm samples of many infertile men by fluorescence in-situ hybridization (FISH). METHODS: Sperm aneuploidy and diploidy rates for chromosomes 13, 18, 21, X and Y were evaluated in 63 patients with normal karyotypes using dual and triple-colour FISH techniques. Indications for sperm FISH analysis were: recurrent miscarriages of unknown aetiology (RM, n = 40), repeated implantation failure after intracytoplasmic sperm injection (ICSI) (IF, n = 19), previous Down's syndrome pregnancies (n = 3), and meiotic abnormalities (MA, n = 1). Nine healthy normozoospermic donors were also evaluated as a control group. RESULTS: A significant increase in the incidence of sex chromosome disomies was found in the RM, IF and MA groups. Oligoasthenoteratozoospermic patients (n = 21) showed significantly higher rates of diploidy and disomies for sex chromosomes and chromosomes 18 and 21 than normozoospermic patients (n = 14). Thirty-one patients with normal and seven with abnormal FISH results had undergone several ICSI treatments (108 and 23 cycles respectively). Couples with abnormal sperm FISH results showed decreased pregnancy and implantation rates and increased miscarriage rates. CONCLUSIONS: Patients with a clinical background of recurrent miscarriages of unknown aetiology or implantation failure after ICSI are at risk of showing sperm chromosomal abnormalities, the incidence of which is higher in oligoasthenoteratozoospermic patients.

Efficacy of intracytoplasmic sperm injection using testicular spermatozoa.

In patients with obstructive azoospermia in whom standard microsurgical procedures fail or are unfeasible, the only source of spermatozoa is the testicle. In addition, in some azoospermic patients with severe spermatogenic failure, a few spermatozoa may be present in testicular biopsy specimens despite high serum follicle stimulating hormone concentrations. In all these cases, intracytoplasmic sperm injection (ICSI) with testicular biopsy-extracted spermatozoa may offer the chance of pregnancy. To assess the efficacy of this procedure, we compared the results of two series of ICSI cycles performed during the same time period: 21 cycles using testicular biopsy-extracted spermatozoa and 83 cycles using ejaculated spermatozoa. Mean fertilization rates (59% with testicular and 68% with ejaculated spermatozoa), mean cleavage rates (93% with testicular and 90% with ejaculated spermatozoa), embryo quality (77% good quality embryos in the testicular sperm group and 77% in the ejaculated sperm group) and clinical pregnancy rates (36.8% in the testicular sperm group and 28% in the ejaculated sperm group) were not significantly different in both groups. We conclude that high fertilization, cleavage and pregnancy rates can be achieved with intracytoplasmic testicular sperm injection, reaching levels comparable with those of ICSI using ejaculated spermatozoa.

Pregnancies after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa.

In 25 patients (14 suffering from obstructive azoospermia, six from non-obstructive azoospermia, three from asthenoazoospermia and two from absence of ejaculation) spermatozoa were extracted from testicular biopsies. Intracytoplasmic sperm injection (ICSI) with fresh testicular spermatozoa was performed in 18 cases; spermatozoa in excess were cryopreserved in pills. No pregnancies were achieved. In the remaining seven patients, testicular spermatozoa were retrieved and cryopreserved during a diagnostic testicular biopsy. After thawing, sperm motility was assessed in 17 cases (68%), and 18 ICSI with cryopreserved testicular spermatozoa were performed. The mean two-pronuclear (2PN) fertilization rate was 59%, the mean cleavage rate was 92%, and six clinical pregnancies were achieved, all of them still ongoing (pregnancy rate 33%). A comparison of the results of ICSI carried out with fresh or cryopreserved testicular spermatozoa showed that the mean 2PN fertilization rates per cycle (53 compared with 55%), mean cleavage rates per cycle (99 compared with 96%) and embryo quality were not significantly different. In conclusion, cryopreservation of testicular spermatozoa is feasible, even in patients with non-obstructive azoospermia, and the results of ICSI with frozen-thawed testicular spermatozoa are similar to those obtained using fresh testicular spermatozoa. Cryopreservation of testicular spermatozoa may avoid repetition of testicular biopsies to retrieve spermatozoa for successive ICSI cycles in patients in whom the only source of motile spermatozoa is the testicle.

Implications of sperm chromosome abnormalities in recurrent miscarriage.

PURPOSE: Our purpose was to assess the existence of sperm chromosome abnormalities in recurrent pregnancy loss in an assisted reproduction program. METHODS: In this prospective study, 12 sperm samples from couples undergoing in vitro fertilization with two or more first-trimester spontaneous abortions were analyzed. Diploidy and disomy in decondensed sperm nuclei were assessed for chromosomes 13, 18, 21, X, and Y using two- and three-color fluorescence in situ hybridization. RESULTS: Sex chromosome disomy in sperm samples from recurrent abortion couples was significantly increased compared to that from internal controls (0.84% vs 0.37%). In a subpopulation of seven couples who underwent oocyte donation, mean frequencies for sex chromosome disomy (1%) were even higher and diploidy (0.43%) was also significantly increased. CONCLUSIONS: These results suggest an implication of sperm chromosome abnormalities in some cases of recurrent pregnancy loss.