The development of intracytoplasmic sperm injection.
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Cytoplasm↗
Biomedical subjects
H Tournaye
Publications and source records attributed to H Tournaye.
Correlation between testicular histology and outcome after intracytoplasmic sperm injection using testicular spermatozoa.
A comprehensive study is presented of a series of 124 infertile men undergoing testicular sperm retrieval for intracytoplasmic sperm injection (ICSI). In this study we correlated the histological changes observed in the testicular tissue with the results of the wet preparation and the outcome after ICSI using testicular spermatozoa. In all patients with normal spermatogenesis and hypospermatogenesis spermatozoa were recovered from the wet preparation. The sperm recovery rate as 84% in patients with incomplete germ-cell-aplasia and maturation arrest, while in patients with complete germ-cell aplasia or maturation arrest this figure was 76%. In these patients more specimens were sampled and fewer spermatozoa were recovered. Since no spermatozoa were recovered in only 10 patients, ICSI with testicular sperm was performed in the remaining 114 couples (91.9%). The normal fertilization rate was 57. 8%. The fertilization rate was significantly lower in couples among whom the husband showed germ-cell aplasia and maturation arrest. Overall, 55.2% of normally fertilized oocytes developed into embryos showing <=50% of anucleate fragments. There were no major differences between the different histological categories in terms of embryonic development in vitro. The overall pregnancy rates per testicular sperm extraction (TESE) procedure, per ICSI procedure and per transfer were respectively 36.3, 39.5 and 43.7%. The overall implantation rate per embryo (sacs/embryos replaced) was 20.3%. A lower implantation rate was observed in couples among whom the husband had maturation arrest (not statistically significant). The above data show that testicular biopsies may have an important therapeutic role in the management of infertility in azoospermic patients.
Adult↗
Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia.
From 1 August 1993 until 30 September 1994, 69 couples suffering from azoospermia underwent testicular sperm extraction and intracytoplasmic sperm injection. In 50 couples with obstructive azoospermia a total of 631 metaphase-II oocytes were injected after testicular sperm extraction yielding a 2-PN fertilization rate of 57%. In female patients <40 years of age an ongoing pregnancy rate per transfer of 42% (14/33) was obtained. So far, eight healthy babies have been born, including two singletons and three twin gestations. In 19 couples with non-obstructive azoospermia a total of 264 metaphase-II oocytes were injected after testicular sperm extraction, yielding a 2-PN fertilization rate of 58%. An ongoing pregnancy rate per transfer of 31% (5/16) was established. So far, six healthy babies have been born including one singleton, one twin and one triplet gestation.
Adult↗
Female age predicts embryonic implantation after ICSI: a case-controlled study.
From 1 October 1991 until 31 December 1993, 1270 cycles for intracytoplasmic sperm injection were performed. Of these, 71 (5.6%) were carried out in women >/=40 years of age. The semen characteristics in couples >/=40 years of age or <40 years were similar. The mean male age for the older group of women was 47.1 years (range 34-67) versus 35 years (25-71) for the younger group of women (P < 0.001). The mean female age was 41.9 years (range 40-47) and 31.8 years (range 23-39). The numbers of cumulus-oocyte complexes and metaphase-II oocytes were significantly lower in women >/=40 years of age (P < 0.001). The mean numbers of replaced embryos were respectively 2.3 (133/59) in women >/=40 years of age and 2.5 (160/63) in women <40 years of age. The delivery rate per retrieval and per transfer was significantly lower in women >/=40 years of age (P < 0.05). The delivery rates per retrieval and per transfer were respectively 7% (5/71) and 8.5% (5/59) in the older group of women versus 22.5% (16/71) and 25.4% (16/63) in the younger group. Female age is the predictive factor for embryonic implantation.
Adult↗
Testicular sperm recovery in nine 47,XXY Klinefelter patients.
Klinefelter's syndrome is generally characterized by hypergonadotrophic hypogonadism and azoospermia. The clinical features, however, are variable, and occasionally severe oligozoospermia may be present. Usually in these cases a 46,XY/47,XXY mosaic karyotype is involved. However, focal spermatogenesis and severe oligozoospermia have been reported in 47,XXY individuals too. In the present study we investigated whether testicular spermatozoa can be recovered in 47,XXY patients with a view to intracytoplasmic sperm injection (ICSI). In four out of nine apparently non-mosaic 47,XXY patients, spermatozoa were recovered from the wet preparations of testicular tissue and ICSI was performed in three couples. In one patient in whom spermatozoa were successfully recovered and used for ICSI, no spermatozoa were retrieved at a second trial. Although these results show that in some 47,XXY individuals testicular spermatozoa can be successfully recovered and even used for ICSI, at present this approach should be considered experimental. There may indeed be some concern about the chromosomal normality of the embryos generated through this infertility treatment. Patients with Klinefelter's syndrome should therefore be counselled about the complexity of this treatment, which involves multiple testicular biopsies from hypogonadal testes, ICSI and preimplantation diagnosis by fluorescence-in-situ hybridization.
Adult↗
Preimplantation diagnosis for X and Y normality in embryos from three Klinefelter patients.
In some 47,XXY Klinefelter patients without evidence of mosaicism, testicular spermatozoa can be successfully recovered and used for intracytoplasmic sperm injection (ICSI). To ensure the replacement of embryos with a normal X and Y chromosome pattern, preimplantation diagnosis can be performed. This paper reports on three 47,XXY Klinefelter patients from whom it was possible to retrieve testicular spermatozoa in order to perform ICSI. From their healthy wives a total of 27 oocyte-cumulus complexes were retrieved from which 22 metaphase-II oocytes were obtained and injected; 19 of these were intact after injection. Two distinct pronuclei were observed in eight oocytes (42.1%) 18 h after injection. On day 3 of development, five embryos (62.5%) had reached at least the 6-cell stage and were of sufficient quality to undergo biopsy and subsequent preimplantation diagnosis for sex chromosome analysis by fluorescent in-situ hybridization. The four embryos diagnosed as normal were transferred to three respective patients, resulting in one biochemical pregnancy. The remaining cells of the fifth embryo were analysed afterwards, revealing a normal X and Y chromosome constitution. So far, in the five embryos diagnosed, a normal sex chromosome pattern has been observed.
Embryo, Mammalian↗
Tubal transfer: a forgotten ART? Is there still an important role for tubal transfer procedures?
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Embryo Transfer↗
Results of microsurgical epididymal sperm aspiration (MESA) ans testicular sperm extraction (TESE) in azoospermic men using intracytoplasmic sperm injection (ICSI).
The rationale and results of using epididymal and testicular spermatozoa with intracytoplasmic sperm injection (ICSI) for zoospermic patients are reviewed. A total of 128 consecutive ICSI/MESA cycles and a total of 120 consecutive ICSI/TESE cycles were performed up to December 1994. The two-pronuclei fertilization rate per intact oocyte (observed after the injection) was 58% and 60%, respectively, when epididymal and testicular spermatozoa were used. The embryo transfer rate was similar for the two procedures (91% after ICSI/MESA and 90% after ICSI/TESE). Fifty women became pregnant (positive HCG) when epididymal spermatozoa were used (39% per cycle and 40% per embryo transfer). These results are comparable to those obtained when ejaculated spermatozoa are used.
Cell Separation↗
Intracytoplasmic sperm injection (ICSI): the Brussels experience.
The present report covers the results of a 26-month period in which 1275 consecutive treatment cycles by intracytoplasmic sperm injection (ICSI) were performed in 919 couples. These couples were afflicted with male factor infertility and had had at least one previous failed conventional in vitro fertilization (IVF) treatment cycle. In other couples, the husband had semen parameters incompatible with conventional IVF or suffered from excretory azoospermia which required microsurgical epididymal sperm aspiration or testicular sperm retrieval. Overall, the 2 pronuclear (PN) fertilization rate was 47.7% per retrieved oocyte-cumulus complex and 66.4% per successfully injected metaphase II oocyte. Embryo transfer was performed in 90.8% of started cycles and 362 clinical pregnancies were recorded, giving a clinical pregnancy rate of 28.4% per started cycle or 31.3% per transfer. In addition, updated results on the outcome of pregnancies after microassisted fertilization are presented. As of 30 August 1994, 416 children have been born. Although 16 major congenital malformations have been observed (3.9%), there appears to be no reason for serious concern as regards the occurrence of major congenital anomalies after ICSI.
Belgium↗
Fertilizing capacity of epididymal and testicular sperm using intracytoplasmic sperm injection (ICSI).
For men with uncorrectable obstructive azoospermia, their only hope of fathering a child is microsurgical epididymal sperm aspiration (MESA) combined with in vitro fertilization (IVF). In 1988, proximal epididymal sperm were demonstrated to have better motility than senescent sperm in the distal epididymis, and it was thought that retrieval of motile sperm from the proximal epididymis would yield reliable fertilization and pregnancy rates after conventional IVF. However, the results to date have been poor, and although a minority of patients achieved good fertilization rates with IVF, the vast majority (81%) had consistently poor or no fertilization and the pregnancy rate averaged only 9%. Recently, intracytoplasmic sperm injection (ICSI) has been successfully used to achieve fertilization and pregnancies for patients with extreme oligoasthenozoospermia. ICSI has therefore been applied to cases of obstructive azoospermia and, in this report, 67 MESA-IVF cases are compared with 72 MESA-ICSI cases. The principle that motile sperm from the proximal segments of the epididymis should be used for ICSI was followed, although in the most severe cases in which there was an absence of the epididymis (or absence of sperm in the epididymis), testicular sperm were obtained from macerated testicular biopsies. These sperm only exhibited a weak, twitching motion. In 72 consecutive MESA cases, ICSI resulted in fertilization and normal embryos for transfer in 90% of the cases, with an overall fertilization rate of 46%, a cleavage rate of 68%, and ongoing or delivered pregnancy rates of 46% per transfer and 42% per cycle. The pregnancy and take-home baby rates increased from 9% and 4.5% with IVF to 53% and 42% with ICSI. There were no differences between the results for fresh epididymal, frozen epididymal or testicular sperm, and the number of eggs collected did not affect the outcome. The results were also unaffected by the aetiology of the obstruction such as congenital absence of the vas deferens or failed vasoepididymostomy. The only significant factor which affected the pregnancy rate was female age. It is concluded that although complex mechanisms involving epididymal transport may be beneficial for conventional fertilization of human oocytes (in vivo or in vitro), none of these mechanisms are required for fertilization after ICSI. Given the excellent results with epididymal and testicular sperm, ICSI is obligatory for all future MESA patients. Finally, the use of ICSI with testicular sperm from men with non-obstructive azoospermia is also discussed.
Cytoplasm↗
High fertilization and pregnancy rate after intracytoplasmic sperm injection with spermatozoa obtained from testicle biopsy.
In cases requiring microsurgical epididymal sperm aspiration (MESA) for congenital absence of the vas deferens (CAVD) or irreparable obstructive azoospermia, often no spermatozoa can be retrieved from the epididymis, or there may even be no epididymis present. We wished to see whether testicular biopsy with testicular sperm extraction (TESE) in such cases could yield spermatozoa that would result in successful fertilization and pregnancy (despite the absence of epididymal spermatozoa) using intracytoplasmic sperm injection (ICSI). In the same setting during the same 2-week period, 28 patients with CAVD or irreparable obstruction were treated; 16 consecutive fresh MESA-ICSI cycles and 12 cycles which required testicular biopsy with testicular sperm extraction (TESE-ICSI) were performed. Normal two-pronuclear fertilization rates were similar in both groups: 45% for epididymal spermatozoa and 46% for testicular biopsy-extracted spermatozoa. Cleavage rates were also similar (68% for epididymal and 65% for testicular spermatozoa). The ongoing pregnancy rates in this series were 50 and 43% respectively. We conclude that epididymal spermatozoa and testicular spermatozoa yield similar fertilization, cleavage and ongoing pregnancy rates using ICSI. When epididymal spermatozoa cannot be retrieved, a testicular biopsy can be performed and the few barely motile spermatozoa thus obtained can be used for ICSI. It appears that all cases of obstructive azoospermia can now be successfully treated.
Biopsy↗
Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia.
In this study (May 1 until August 31, 1994) a total of 15 azoospermic patients suffering from testicular failure were treated with a combination of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). Spermatozoa were available for ICSI in 13 of the patients. Out of 182 metaphase II injected oocytes, two-pronuclear fertilization was observed in 87 (47.80%); 57 embryos (65.51%) were obtained for either transfer or cryopreservation. Three ongoing pregnancies out of 12 replacements (25%) were established, including one singleton, one twin and one triplet gestation. The ongoing implantation rate was 18% (six fetal hearts out of 32 embryos replaced).
Adult↗
Recent concepts in the management of infertility because of non-obstructive azoospermia.
Testicular biopsy has been widely used for the diagnosis of male infertility. Since the introduction of intracytoplasmic sperm injection (ICSI), spermatozoa recovered from a testicular biopsy specimen can be successfully used for establishing pregnancies. A few spermatozoa may be recovered from a wet preparation of a testicular biopsy, not only in obstructive azoospermic patients, but also in many patients with non-obstructive azoospermia. In 36 out of 38 non-obstructive azoospermic patients sperm cells were recovered from a testicular biopsy specimen. However in two patients, spermatozoa could not be found after further preparation of the biopsy specimens for ICSI. In the remaining 32 patients, a normal fertilization rate of 56.8% per successfully injected oocyte was obtained after ICSI of testicular spermatozoa. In 84% of patients, embryos were replaced with an overall pregnancy rate of 28.9% per testicular biopsy or 34.3% per embryo transfer. The results clearly indicate that at present an excisional testicular biopsy should be offered to all azoospermic patient, irrespective of concentration of follicle stimulating hormone, testicular size or medical history.
Biopsy↗
Use of pentoxifylline in assisted reproductive technology.
Methods for improving the fertilizing potential of the spermatozoa in human in-vitro fertilization (IVF) include the stimulation of sperm function in vitro. Metabolic stimulation in vitro has become a major issue in assisted reproductive technology (ART). Here, we review our research on the unselective use of pentoxifylline in IVF for male-factor infertility. Data from our controlled studies indicate that an indiscriminate use of 3.6 mM pentoxifylline, alone or in combination with 3.0 mM 2-deoxyadenosine, is not beneficial in enhancing fertilization rates in zero and poor in-vitro fertilizers or in the presence of antisperm antibodies. An assessment of the effects of pentoxifylline on sperm function prior to IVF may ensure a more rational use of these compounds in selected cases undergoing ART. At present, however, controlled studies in subgroups of patients selected by functional testing are still lacking.
Animals↗
Fertility after hysteroscopic myomectomy.
The available data concerning hysteroscopic myomectomy for submucous myomas has been reviewed with the aim of evaluating the safety and efficacy of this technique in infertile women who wish to preserve or to enhance their fertility potential. A total of 134 infertile patients undergoing hysteroscopic myomectomy by resectoscope or by Nd: YAG laser or by scissors have been collectively recorded. Of these, 79 (58.9%) patients conceived. This clinical outcome is similar to that occurring after laparotomic submucous myomectomy. Moreover, the hysteroscopic approach has several advantages over its abdominal counterpart, such as reduction of length of time of hospitalization, less morbidity and no hysterotomy. The operative risk of hysteroscopic myomectomy is < 3%. Uterine perforation, distension system hazard, infection and haemorrhage are the commonest complications. Hysteroscopic myomectomy is a safe, effective and relatively simple surgical procedure for the restoration of fertility.
Female↗
Obstetric outcome of 424 pregnancies after intracytoplasmic sperm injection.
An evaluation of the outcome of pregnancies resulting from intracytoplasmic sperm injection for severe male factor infertility was conducted by analysing the data obtained from the patients and/or their obstetrician/gynaecologist on standardized questionnaires. The data from 424 pregnancies between April 1991 and September 1994 were analysed. Early pregnancy loss before 16 weeks occurred in 99 cases (23.3%), including 48 clinical abortions (11.3%), 47 subclinical pregnancies (11.1%) and four ectopic pregnancies (0.9%). Vanishing twins and triplets, which could be regarded as early embryonic wastage, were found in 36 cases (8.5%). One pregnancy was interrupted at week 15 of gestation because of anhydramnios, and four pregnancies (0.9%) ended in spontaneous late abortions before 26 weeks. A total of 320 pregnancies (75.5%) resulted in the birth of at least one child; 222 of these (69.3%) were singletons, 93 were twins (29.1%) and five were triplets (1.6%). The problems of prematurity and low birthweight were especially related to the multiplicity of pregnancies. Furthermore, from among the total of 423 babies born, we have observed three cases of stillbirth and five cases of neonatal mortality. The perinatal mortality rate was therefore 18.9 per 1000 births. The results of this study show that the obstetric outcome of these pregnancies was similar to that obtained after conventional in-vitro fertilization and other assisted reproduction techniques.
Abortion, Spontaneous↗
Comparison of four mechanical methods to retrieve spermatozoa from testicular tissue.
To maximize the total number of spermatozoa which can be retrieved from a testicular biopsy, four mechanical methods for preparation were compared. In all, 17 biopsies were divided into four equal fractions, which were weighed individually and prepared by rough shredding (control), fine mincing, vortexing and crushing (electrical Potter). After resuspension in an erythrocyte-lysing buffer, removal of the remaining tissue pieces, washing and centrifugation, the following parameters were evaluated: number of spermatozoa per 100 mg tissue, percentage motility, percentage vitality and percentage normal morphology (strict Kruger criteria). After further purification by discontinuous Percoll centrifugation, the same parameters were assessed again. This procedure was efficient in obtaining only spermatozoa in the final fraction. Before Percoll centrifugation, only minor differences between methods were observed. Percoll centrifugation generally resulted in a pronounced loss of sperm cells, partly because of the abnormal dimensions of the eliminated cells. After Percoll centrifugation, treatment of the testicular tissue by fine mincing was the most effective method in terms of the total number of motile spermatozoa and percentage normal morphology.
Adult↗
Successful fertilization and establishment of pregnancies after intracytoplasmic sperm injection in patients with globozoospermia.
Globozoospermia or round-headed spermatozoa is a rare type of teratozoospermia where the acrosome is absent resulting in male infertility with no known therapy. A few studies have shown that round-headed spermatozoa cannot bind to or penetrate the zona pellucida, and no normal fertilization has been observed in in-vitro fertilization (IVF) after insemination of human oocytes with round-headed spermatozoa. In this study, the fertilization capacity of round-headed spermatozoa after intracytoplasmic sperm injection (ICSI) into human oocytes has been examined. In pre-clinical experiments, 45 oocytes were injected; 41 oocytes were intact after injection, 15 oocytes were fertilized normally, and 13 of these 15 oocytes developed further in vitro. ICSI was carried out in 11 treatment cycles of seven infertile couples with globozoospermia. Normal fertilization and embryo transfer occurred in four cycles (three patients). Positive serum human chorionic gonadotrophin was observed in three cycles (two patients); one patient had a pre-clinical abortion and the other patient became pregnant twice; the first pregnancy was ectopic and the second pregnancy is a twin pregnancy which is currently at 16 weeks of gestation.
Acrosome↗