Assisted reproduction by intracytoplasmic sperm injection: a survey on the clinical experience in 1994 and the children born after ICSI, carried out until 31 December 1993. ESHRE Task Force on Intracytoplasmic Sperm Injection. European Society for Human Reproduction and Embryology

The second report of the ESHRE Task Force on ICSI describes the outcome of 13,666 ICSI cycles carried out in 1994 by 90 centres in 24 countries. Most cycles used ejaculated spermatozoa (94.4%) while epididymal and testicular spermatozoa were used in 4.1% and 1.5% of the cycles. Outcome measures in the three types of spermatozoa included the number of: (i) intact oocytes after ICSI; (ii) normally fertilized oocytes; (iii) transferred and frozen embryos; (iv) embryo transfers and (v) cycles with positive serum HCG. The evolution of the pregnancies was analysed in terms of pregnancy losses and clinical pregnancies. The results of ICSI with spermatozoa from the ejaculate was analysed according to the year that ICSI started in the different centres. The survey also reports the follow-up of children born after ICSI carried out until 31 December 1993. A total of 455 pre- and postnatal karyotypes revealed the presence of nine abnormal karyotypes. Twenty-four centres reported on 807 ICSI children: 763 using ejaculated spermatozoa, 36 using epididymal spermatozoa and eight using testicular spermatozoa. Sixteen major congenital malformations were reported.      

Different fertilization rates between immotile testicular spermatozoa and immotile ejaculated spermatozoa for ICSI in men with Kartagener's syndrome: case reports

We report two cases of infertility treatment in couples where males suffered from Kartagener's syndrome (KS) and a total absence of motile sperm in the ejaculate. A total of three ICSI cycles was carried out. In all cycles, viable ejaculated or testicular spermatozoa were selected using the hypo-osmotic swelling (HOS) test. Case 1: In the first ICSI cycle total fertilization failure occurred after using ejaculated spermatozoa. In the following cycle testicular spermatozoa were used for ICSI, resulting in 75% fertilized oocytes and a pregnancy. Case 2: In the same ICSI cycle 50% of the oocytes were injected with ejaculated and 50% with testicular spermatozoa. The fertilization rates were 44 and 56% respectively and high quality embryos were achieved in both groups. One single embryo derived from testicular sperm was transferred with a resulting singleton pregnancy. In conclusion, testicular sperm for ICSI seem to have reliable fertilization capacity in men with KS, while ejaculated sperm, even if tested viable, seem more unpredictable. HOS test for selection of viable sperm for ICSI is recommended when ejaculated as well as testicular sperm are used for ICSI.     

Testicular needle biopsy, open biopsy, epididymal aspiration and intracytoplasmic sperm injection in obstructive azoospermia

Testicular or epididymal spermatozoa were obtained for in-vitrofertilization and intracytoplasmic sperm injection ICSI) in27 cycles out of 33 (in six men the azoospermia proved to havetesticular causes). Testicular needle biopsy carried out inaddition to surgical open biopsy proved to be an effective methodto obtain spermatozoa for ICSI from patients with obstructiveazoospermia. Thus it might be possible to replace scrotal operationsby simple needle biopsies. Embryos resulting from ICSI withtesticular spermatozoa were used in 19 transfers that resultedin six pregnancies. One pregnancy resulted from six embryo transfersfrom ICSI after microsurgical-epididymal sperm aspiration (MESA).The normal fertilization rates with testicular (37.3%) and MESAspermatozoa (53.7%) did not differ significantly from each other,but with testicular spermatozoa the rate was significantly lowerthan that obtained with ejaculated spermatozoa and ICSI (59.7%)in the matched couples. The abnormal fertilization of oocyteswith one pronucleus was significantly higher with testicularspermatozoa than with ejaculated spermatozoa in the controlcouples.     

Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm

BACKGROUND: Follow-up studies of children conceived after ICSI using epididymal or testicular sperm are important due to a still more extensive use of immature male germ cells for ICSI. It is, however, difficult to evaluate the potential risks of malformations of children born after ICSI, overcoming the natural fertilization processes, due to methodological limitations. METHODS: Follow-up study including all children born in Denmark and Norway following ICSI in Denmark, using epididymal or testicular sperm, was done. A questionnaire was sent to the parents between 3 months and 7 years after delivery. RESULTS: Of 341 couples, 329 returned the questionnaire giving a response rate of 96.5%. The study included 412 children, 225 girls and 187 boys, giving a sex ratio (males/males + females) of 45.4% compared with 53.1% in Danish children conceived after conventional IVF without ICSI (P < 0.005). Among a total of 14 (3.4%; 95% confidence interval (CI): 1.9%-5.7%) major malformations, three boys with hypospadias were the most remarkable finding (1.6%; 95% CI: 0.33-4.7%). CONCLUSIONS: An increased frequency of hypospadias in the male offsprings was seen compared with the general population. Apart from this, no increased major malformation rate was detected in ICSI children conceived with epididymal or testicular sperm when compared with malformation rates for IVF or spontaneously conceived children reported in the literature. The sex ratio was significantly lower for ICSI children conceived with epididymal or testicular sperm when compared with children conceived with conventional IVF.     

Andrology: Micromanipulation improves in-vitro fertilization results after epididymal or testicular sperm aspiration in patients with congenital absence of the vas deferens

In all, 58 couples suffering from infertility because of congenitalbilateral absence of the vas deferens underwent a total of 67combined microsurgical epididymal aspiration or testicular spermextraction (TESE) and in-vitro fertilization (TVT) treatments.The oocytes recovered were inseminated by either the microdropletIVF technique (n=20), subzonal insemination (SUZI; n= 10) orintracyto-plasmic sperm injection (ICSI; n= 37). Of the ICSIcycles, 12 were performed using spermatozoa obtained by TESE.Fertilization rates for epididymal spermatozoa were significantlyhigher for SUZI (17.9%, 17/95) and ICSI (34.4%, 137/398) thanfor microdroplet IVF (5.2%, 18/343) cycles. The proportion ofcycles in which fertilization was achieved was higher in theSUZI (80%) and ICSI (95%) cycles than in the IVF cycles (45%).Delivery or an ongoing pregnancy was achieved in one (5%) IVFcycle, two (20%) SUZI cycles and seven (18.9%) ICSI cycles.SUZI or ICSI using epididymal or testicular spermatozoa significantlyimproved the oocyte fertility rate. The ICSI procedure was especiallyadvantageous in patients for whom spermatozoa were obtainedfrom a testicular biopsy.     

Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa

BACKGROUND: Sperm DNA damage (fragmentation) is a recently discovered cause of male infertility for which no efficient treatment has yet been found. Previous findings have suggested that clinically relevant sperm DNA damage may occur at the post-testicular level. This study was undertaken to assess the clinical usefulness of ICSI with testicular spermatozoa in this indication. METHODS: The percentage of spermatozoa with fragmented DNA, assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling assay, and ICSI outcomes were compared in two sequential attempts performed, respectively, with ejaculated and testicular spermatozoa in 18 men with increased sperm DNA fragmentation. RESULTS: The incidence of DNA fragmentation was markedly lower in testicular spermatozoa as compared with ejaculated spermatozoa. No differences in fertilization and cleavage rates and in embryo morphological grade were found between the ICSI attempts performed with ejaculated and with testicular spermatozoa. However, eight ongoing clinical pregnancies (four singleton and four twin) were achieved by ICSI with testicular spermatozoa (44.4% pregnancy rate; 20.7% implantation rate), whereas ICSI with ejaculated spermatozoa led to only one pregnancy which was spontaneously aborted. CONCLUSIONS: These data show that ICSI with testicular spermatozoa provides the first efficient assisted reproduction treatment option for men with high levels of sperm DNA damage.     

A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994-1997.

This national cohort study included all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) registered in Denmark between January 1994 and July 1997 at five public and eight private fertility clinics. Laboratory and clinical data were obtained from the fertility clinics. The couples answered a questionnaire regarding the pregnancy and the health of the child (response rate 94%). Data validation was carried out through discharge charts. The mean age of the women was 32.1 years. In 84.2% of couples, male factor was the main reason for performing ICSI, and in 4.8% epididymal spermatozoa were used. The mean number of embryos replaced was 2.3 (range 1-3) and in 95% of cases fresh embryos were transferred. Only 183 women (28.5%) underwent prenatal diagnosis, resulting in 209 karyotypes with seven (3.3%) chromosome aberrations. Six major chromosomal abnormalities (2.9%) and one inherited structural chromosome aberration (0.5%) were found, but no sex chromosome aberrations. The frequency of multiple birth, Caesarean section rate, gestational age, preterm birth, and birth weight were comparable with previous studies. The perinatal mortality rate was 13.7 per 1000 children born with a gestational age of 24 weeks or more. In 2.2% (n = 16) of the liveborn infants, and in 2.7% (n = 20) of all infants, major birth defects were reported by the parents. Minor birth defects were found in nine liveborn infants (1.2%). In conclusion, the results of this study on outcome of ICSI pregnancies are in line with earlier reports, except that no sex chromosome abnormalities were found.     

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.     

Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983-1999)

BACKGROUND: To evaluate the safety of ICSI, this study compared data of IVF and ICSI children by collecting data on neonatal outcome and congenital malformations during pregnancy and at birth. METHODS: The follow-up study included agreement to genetic counselling and eventual prenatal diagnosis, followed by a physical examination of the children after 2 months, after 1 year and after 2 years. 2840 ICSI children (1991-1999) and 2955 IVF children (1983-1999) were liveborn after replacement of fresh embryos. ICSI was carried out using ejaculated, epididymal or testicular sperm. RESULTS: In the two cohorts, similar rates of multiple pregnancies were observed. ICSI and IVF maternal characteristics were comparable for medication taken during pregnancy, pregnancy duration and maternal educational level, whereas maternal age was higher in ICSI and a higher percentage of first pregnancies and first children born was observed in the ICSI mothers. Birthweight, number of neonatal complications, low birthweight, stillbirth rate and perinatal death rate were compared between the ICSI and the IVF groups and were similar for ICSI and IVF. Prematurity was slightly higher in the ICSI children (31.8%) than in the IVF children (29.3%). Very low birthweight was higher in the IVF pregnancies (5.7%) compared with ICSI pregnancies (4.4%). Major malformations (defined as those causing functional impairment or requiring surgical correction), were observed at birth in 3.4% of the ICSI liveborn children and in 3.8% of the IVF children (P = 0.538). Malformation rate in ICSI was not related to sperm origin or sperm quality. The number of stillbirths (born > or =20 weeks of pregnancy) was 1.69% in the ICSI group and 1.31% in the IVF group. Total malformation rate taking into account major malformations in stillborns, in terminations and in liveborns was 4.2% in ICSI and 4.6% in IVF (P = 0.482). CONCLUSIONS: The comparison of ICSI and IVF children taking part in an identical follow-up study did not show any increased risk of major malformations and neonatal complications in the ICSI group.     

Patients with absolutely immotile spermatozoa and intracytoplasmic sperm injection

The microinjection of completely immotile spermatozoa may impair the outcome of intracytoplasmic sperm injection (ICSI). Eleven couples underwent an initial ICSI cycle with 100% immotile freshly ejaculated spermatozoa. Two-pronuclear fertilization ensued in 18 of 145 (12.4%) successfully injected oocytes. None of these cycles resulted in a pregnancy. Nine couples underwent ICSI in subsequent cycles (n = 16). Ejaculated spermatozoa were injected in 15 cycles and testicular spermatozoa in one cycle. In 10 of the 15 cycles, motile spermatozoa were available at the time of injection. Motile testicular spermatozoa could also be injected. In the subsequent cycles, 91 of 176 (51.7%) successfully injected oocytes fertilized normally and four patients became pregnant. In the subsequent cycles where again immotile spermatozoa had to be injected no pregnancies occurred. In four subsequent cycles embryo cryopreservation was carried out. After replacement of two frozen-thawed embryos one additional pregnancy was obtained. In all, five healthy infants were born. It has been ascertained that motile spermatozoa can be detected either in repeated ejaculates or after testicular biopsy. The causes of total asthenozoospermia are variable and the problem is a sporadic rather than a permanent condition.      

PGD in 47,XXY Klinefelter's syndrome patients

The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis, may benefit from the ICSI technique in order to father a child. As ICSI use has become more common, centres have introduced infertility treatment for Klinefelter patients. To date, 34 healthy children have been born using ICSI without PGD, and the conception of one 47,XXY fetus has been reported. In view of the possible risk of an increased gonosome number in the spermatozoa of Klinefelter patients, a safer approach--offering these couples ICSI combined with PGD--has been used, and has resulted in the birth of three healthy children. Couples in which the male suffered from Klinefelter's syndrome were first treated in 1995; these patients were offered ICSI + PGD using FISH technology, notably to enumerate the X and Y chromosomes. ICSI + PGD was performed in 32 cycles of 20 couples with spermatozoa originating from a fresh ejaculate (n = 1), testicular biopsy (n = 21) or frozen-thawed testicular biopsy (n = 10). Normal fertilization occurred in 56.0 +/- 22.4% of the successfully injected oocytes. On day 3 of development, 119 embryos from 29 cycles were of sufficient quality to undergo biopsy and subsequent PGD; a positive result was obtained in 113 embryos. Embryos were available for transfer in 26 cycles, with a mean of 1.6 +/- 0.6 embryos per transfer. Eight pregnancies were obtained, and five resulted in a delivery. A total of 113 embryos from couples with Klinefelter's syndrome was compared with 578 embryos from control couples with X-linked disease where PGD was used to determine gender. A significant fall occurred in the rate of normal embryos for couples with Klinefelter's syndrome (54.0%) compared with controls (77.2%). Moreover, a significantly increased risk of abnormalities was observed for sex chromosomes and autosomes; for each autosome separately, this reached significance level for chromosomes 18 and 21 only. Hence, a cautious approach is warranted in advising couples with non-mosaic Klinefelter's syndrome. Moreover, the use of ICSI + PGD or prenatal diagnosis should be carefully considered.     

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.      

A review of ten years experience of ICSI

This review summarizes the introduction of ICSI in the early 1990s as an assisted fertilization procedure in couples with severe male factor infertility, who could not be helped by conventional IVF. As for current practice, the indications for ICSI using fresh or frozen-thawed ejaculated, epididymal or testicular sperm are reviewed as well as some reports on the use of ICSI in non-male infertility. The main steps in an ICSI cycle are well standardized by now; it is rare that ICSI cannot be carried out and the results in terms of fertilization, embryo transfer and clinical pregnancy rate have been consistent for many years, indicating that a substantial number of couples can now have their own genetic child instead of having to use artificial insemination with donor sperm. This review also emphasizes the importance of assessing the risk of ICSI for the children: there is a slight increase in de novo chromosomal abnormalities, the major congenital malformation rate is similar for IVF and ICSI (between 3 and 4%), and at approximately 2 years of age the developmental outcome as assessed by the Bayley scale is similar for IVF and ICSI. Recent publications mention that a few children are affected by diseases caused by imprinting disorders. Future studies are needed to assess the association between assisted reproductive technologies and imprinting disorders. ICSI is frequently used in couples undergoing preimplantation genetic diagnosis. PGD stricto sensu as well as PGD for aneuploidy screening and for Klinefelter patients are reviewed using the ESHRE PGD Consortium data.     

Prospective follow-up study of 423 children born after intracytoplasmic sperm injection

In order to evaluate the safety of the intracytoplasmic sperminjection (ICSI) procedure, a prospective follow-up study of423 children born after ICSI was carried out. The aim of thisstudy was to compile data on karyotypes, congenital malformations,growth parameters and developmental milestones. Before startingthe infertility treatment, couples were asked to participatein a follow-up study including genetic counselling and prenataldiagnosis. The follow-up study of the child was based on a visitto the paediatrician-geneticist at birth or at 2 months of age,at 1 year and at 2 years of age when a physical examinationfor major and minor malformations and a psychomotoric evaluationwere done. Between April 1991 and September 1994, 320 pregnanciesobtained after ICSI led to the birth of 423 children (222 singletons,186 twins and 15 triplets). Prenatal diagnosis determined atotal of 293 karyotypes, one of which was abnormal (0.3%), andfour were benign familial structural aberrations, all inheritedfrom the paternal side. A total of 14 (3.3%) major malformationswere observed, defined as those causing functional impairmentor requiring surgical correction. Neurological or developmentalproblems at the age of 2 months were found in 14 children, fourof whom were multiples. Compared to most registers of childrenborn after assisted reproduction and to registers of malformationsin the general population, the figure of 3.3% major malformationsis within the expected range. Before drawing any firm conclusion,further careful evaluations of the available data are necessary.     

Andrology

In patients with obstructive azoospermia in whom standard microsurgicalprocedures fail or are unfeasible, the only source of spermatozoais the testicle. In addition, in some azoospermic patients withsevere spermatogenic failure, a few spermatozoa may be presentin testicular biopsyspecimens despite high serum follicle stimulatinghormone concentrations. In all these cases, intra cytoplasmicsperm injection (ICSI) with testicular biopsy-extracted spermatozoamayoffer the chance of pregnancy. To assess the efficacy of thisprocedure, we compared the results of twoseries of ICSI cyclesperformed during the same time period: 21 cycles using testicularbiopsy-extracted spermatozoa and 83 cycles using ejaculatedspermatozoa. Mean fertilization rates (59% with testicular and68% with ejaculated spermatozoa), mean cleavage rates (93% withtesticular and 90% with ejaculated spermatozoa), embryoquality(77% good quality embryos in the testicular sperm group and77% in the ejaculated sperm group) and clinical pregnancy rates(36.8% in the testicular sperm group and 28% in the ejaculatedsperm group) were not significantly different in both groups.We conclude that high fertilization, cleavage and pregnancyrates can be achieved with intra cytoplasmic testicular sperminjection, reaching levels comparable with those of ICSI usingejaculated spermatozoa.     

Pregnancies achieved with testicular and ejaculated spermatozoa in combination with intracytoplasmic sperm injection in men with totally or initially immotile spermatozoa in the ejaculate

The efficacy of intracytoplasmic sperm injection (ICSI) employingtesticular and ejaculated spermatozoa was assessed in 24 coupleswith totally or initially immotile spermatozoa. No criteriawere employed in selecting which patients would be treated withtesticular or ejaculated spermatozoa. The men were chosen atrandom. Testicular spermatozoa obtained by testicular spermextraction were used in 14 and ejaculated spermatozoa were usedin 10 of these couples. In all cases, asthenozoospermia wastotal in their basal semen sample. In 12 male partners, spermatozoawere totally immotile before and after Percoll gradient fractionation(totally immotile). In the remaining 12 men, spermatozoa initiallyshowed a total absence of motility; however, some of the spermatozoahad showed very poor motility (0.1%) after Percoll gradientfractionation and a 13–2.0 h incubation period (initiallyimmotile). Of these 24 total asthenozoospermic males, 14 alsohad total terato-zoospermia. The fertilization and cleavagerates in the testicular and ejaculated sperm groups were 533and 963 and 543 and 94.4% respectively. One cycle resulted incomplete fertilization failure, and in 23 embryo transfer cyclesa total of 10 pregnancies were obtained (41.6%). Eight pregnancieswere achieved in the testicular sperm group, while only twopregnancies were obtained in the ejaculated sperm group. Fourpregnancies, two from the ejaculated sperm group and two fromthe testicular sperm group, resulted in clinical abortions inthe first trimester. Of the remaining six pregnancies, two havealready resulted in healthy births and four pregnancies arenow in the second or third trimester in the testicular spermgroup. Using testicular spermatozoa in combination with ICSIcan be an alternative mode of treatment in cases with totallyor initially immotile spermatozoa in the ejaculate. Very lowpregnancy rates have been obtained and no ongoing pregnancyhas been achieved using ejaculated spermatozoa in these cases.     

A comparison of ICSI outcomes with fresh and cryopreserved epididymal spermatozoa from the same couples

The published experience with frozen-thawed epididymal spermatozoa and intracytoplasmic sperm injection (ICSI) suggests that fertilization and pregnancy success rates are comparable to those achieved with freshly retrieved spermatozoa. However, no study has exactly compared clinical outcomes between the two IVF/ICSI cycles in the same couples. To formally address this issue, we assessed ICSI outcomes in couples each of whom had had two IVF/ICSI cycles: one using fresh and the second using frozen-thawed epididymal spermatozoa obtained from a single aspiration procedure. From a pool of 101 consecutive patients undergoing IVF/ICSI with epididymal spermatozoa, 19 couples initially used fresh epididymal spermatozoa and subsequently underwent a second IVF/ICSI procedure with frozen-thawed spermatozoa from the same aspiration. Normal (2PN) oocyte fertilization rates, embryo quality and pregnancy rates were compared between the two IVF/ICSI cycles for each couple. In the fresh epididymal sperm group, 58.4% of the injected oocytes fertilized normally compared with 62.0% of the injected oocytes in the frozen-thawed epididymal sperm group, revealing no statistically significant difference. Graded embryo quality also did not differ significantly between the paired IVF/ICSI cycles. The clinical pregnancy rates were 31.6% (6/19) and 36.8% (7/19) in the first and second cycles respectively. All but one pregnancy were singletons. In summary, this study provides strong evidence to support the notion that motile, cryopreserved and thawed epididymal spermatozoa are equal to freshly retrieved spermatozoa for ICSI in couples with obstructive azoospermia.     

Genetics: The use of epididymal and testicular spermatozoa for intracytoplasmic sperm injection: the genetic implications for male infertility

The results and rationale of using testicular and epididymalspermatozoa with intracytoplasmic sperm injection (ICSI) forsevere cases of male infertility are reviewed. A total of 72consecutive microsurgical epididymal sperm aspiration (MESA)cases were performed for congenital absence of the vas (CAV)and for irreparable obstructive azoospermia. ICSI was used toobtain normal embryos for transfer and fertilization in 90%of the cases. The overall fertilization rate was 46% with anormal cleavage rate of 68%. The pregnancy and delivery ratesper transfer were 58 and 37% respectively. The delivery rateper cycle was 33%. In many cases, no epididymal spermatozoawere available and so testicular sperm extraction (TESE) wasused for sperm retrieval. The transfer rate was lower with TESE(84 versus 96%) and the spermatozoa could not be frozen andsaved for use in future cycles. However, there was little differencein pregnancy rates using epidiymal or testicular spermatozoa.The results were not affected by whether the obstruction wascaused by CAV or failed vasoepididymostomy. Both fresh and frozenspermatozoa gave similar results; the only significant factorappeared to be the age of the female. Because of the consistentlygood results obtained using epididymal sperm with ICSI whencompared with conventional IVF, and the similarly good resultswith testicular tissue spermatozoa, ICSI is mandatory for allfuture MESA patients. All CAV patients and their partners shouldbe offered genetic screening for cystic fibrosis; hence pre-implantationembryo diagnosis should be available in any full service MESAprogramme. It is now clear that even with non-obstructive azoospermia,e.g. Sertoli-cell only, or maturation arrest, there are usuallysome small foci of spermatogenesis which allow TESE with ICSIto be carried out. This means that even in men with azoospermiadue to absence of spermatogenesis or to a block in meiosis,there are usually a few spermatozoa available in the testesthat are adequate for successful ICSI. Finally, it is likelythat some forms of severe male factor infertility are geneticallytransmitted and although ICSI offspring have been shown to becompletely normal, it is possible that the sons of these infertilecouples will also require ICSI when they grow up and wish tohave a family.     

Cumulative delivery rates after intracytoplasmic sperm injection: 5 year follow-up of 498 patients.

The use of life-table analysis for infertility data has the advantages of clarity and ease of application. Success rates per cycle have been reported, but not cumulative delivery rates for intracytoplasmic sperm injection (ICSI). We selected retrospectively 498 Belgian patients <37 years old, who had their first ICSI cycle between July 1992 and December 1993. Follow-up was till the end of October 1997. Outcome measure was any delivery >25 weeks. These couples underwent 963 ICSI cycles using fresh ejaculated spermatozoa. The indications for ICSI were long-standing severe male infertility or fertilization failure after conventional in-vitro fertilization (IVF). Cumulative delivery rates were calculated by life-table analysis and compared according to age groups and sperm quality. There were 298 deliveries within a mean rate per cycle of 31%. The average number of cycles required for a delivery was 3.15 (CI 2.88; 3.43). Twenty-three (4.6%) spontaneous pregnancies occurred after the patients had finished therapy. There was no significant difference between the sperm quality groups but delivery rates decreased significantly with increasing female age. The real delivery rate after six cycles was 60%, while the expected cumulative delivery rate was 86%. This life-table analysis may provide a means by which to counsel couples on the likelihood of a delivery following ICSI.     

In-vitro fertilization and intracytoplasmic sperm injection in the treatment of infertility after testicular cancer

Treatment of testicular cancer (TC) may cause infertility due to reduced sperm quality with or without an ejaculation problem. In cases of anejaculation or retrograde ejaculation, spermatozoa can be obtained by transrectal electroejaculation (TE) or testicular sperm extraction (TESE) and used for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In this study, 15 out of 17 couples evaluated for infertility after TC, underwent a total of 21 treatment cycles, resulting in 18 embryo transfers. Spermatozoa were obtained by TE in 16 cycles, by masturbation in three cycles and by TESE in one. In one cycle no spermatozoa were found using TESE. Fertilization and cleavage was achieved by IVF in seven cycles and ICSI in 11 cycles; average fertilization rates of 57 and 55% respectively were observed. Twelve clinical pregnancies occurred, of which 11 have been delivered or are ongoing. The ongoing pregnancy rate was 57% per cycle. These results show that infertility after testicular cancer can be treated effectively with IVF and that ICSI even permits treatment of patients who have severe oligozoospermia.