1 Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Göteborg and 2 Fertility Center Scandinavia, Carlanderska Hospital, Göteborg, Sweden
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Abstract |
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Key words: epididymal spermatozoa/ICSI/pregnancy outcome/sperm parameters/testicular spermatozoa
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Introduction |
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In order to provide a reliable answer to the concerns expressed about the safety of ICSI, special effort must be made to follow up the pregnancies and the short-term and long-term health of children born after ICSI. It is also important to analyse the effects of sperm quality and origin on this outcome. There is some evidence that the use of severely defective spermatozoa in ICSI is an additional risk factor for an adverse perinatal outcome (Aytoz et al., 1998); however, this has yet to be confirmed in further studies.
In this study, we report the outcome of a 5 year cohort of pregnancies obtained after ICSI, classified according to sperm origin and quality. The main endpoint was delivery outcome and the secondary endpoint was early pregnancy loss.
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Material and methods |
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The reasons for this particular group division were the following: group 1 included patients with mild/moderate oligozoospermia as the sole known infertility factor but could have included women with oocyte factors; group 2 resembled group 1 when it came to male factors but included cases with known female factors as well; group 3 included couples with severe oligozoospermia. The values of <15x106 or <5x106/ml spermatozoa are the lower limits for severe oligozoospermia, accepted internationally and by WHO (World Health Organization,1992). An increased incidence of chromosomal aberrations has been detected in men with severe oligozoospermia and non-obstructive azoospermia (Assche et al., 1996).
Standard oocyte retrieval, embryo culture and transfer procedures have been described previously (Wikland et al., 1983, 1994
). The sperm preparation and micro-insemination procedures utilized by us have also been reported earlier (Hamberger et al., 1995
). Epididymal spermatozoa were obtained by microsurgical epididymal sperm aspiration (MESA) (Temple Smith et al., 1985
; Silber et al., 1994
) or percutaneous sperm aspiration (PESA) (Craft and Shrivastav, 1994
; Shrivastav et al., 1994
; Westlander et al., 1999
). Testicular spermatozoa were obtained by testicular sperm extraction (TESE) (Schoysman et al., 1993
) or by fine-needle testicular sperm aspiration (TESA) (Tsirigotis and Craft, 1995
).
For cryopreservation, we used the technique previously described (Lassalle et al., 1985), with embryos frozen at the 24-cell stage, corresponding to day 2 after oocyte retrieval.
In the epididymal sperm group (group 4), frozenthawed spermatozoa were used in 16 pregnancies but due to the small number, this group was analysed together with pregnancies achieved with fresh epididymal spermatozoa having first established that there was no detectable difference between them. Only fresh spermatozoa were used in the other groups.
Details of treatment and fertility history were collected from the clinics' medical records and obstetric and perinatal histories were obtained from records at the obstetric departments where the patients were treated and/or gave birth. Data were obtained by telephone interview in 10 cases. The study was approved at the outset by the Ethics Committee in Göteborg.
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Definitions |
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A pregnancy was defined as clinical if a gestational sac(s) was visualized by ultrasonography in the seventh week of gestation. The diagnosis of an ectopic pregnancy was confirmed by laparoscopy. Early spontaneous abortion: pregnancy loss before 12 completed weeks of gestation. Late spontaneous abortion: pregnancy loss after 12 weeks and before 28 weeks of gestation. Stillborn: intrauterine death after 28 weeks of gestation. Delivery: the birth of a liveborn or stillborn infant. Early neonatal death: the death of a liveborn infant during the first 7 days after birth. Perinatal mortality: the sum of stillborn and early neonatal deaths per 1000 infants born. Preterm birth: delivery before 37 weeks of gestation. Very preterm birth: delivery before 32 weeks of gestation. Low birthweight (LBW): a liveborn or stillborn infant weighing <2500 g at birth. Very low birthweight (VLBW): a liveborn or stillborn infant weighing <1500 g at birth. Small for gestational age (SGA): birthweight <2 SD, according to the Swedish reference tables for birthweight (Marsál et al., 1996). Malformation: any congenital malformation defined in the International Classification of Diseases (ICD, 1977, 1992; Chapter 14 in ICD-9 and Chapter 17 in ICD-10).
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Statistical methods |
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Results |
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Discussion |
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Analysis of the malformation and chromosomal aberration rates after different kinds of assisted reproduction technologies is, no doubt, crucial. Concerns have been raised regarding the possibility of an increased rate of malformations and chromosomal aberrations after ICSI, based on the fact that the ICSI technique itself is invasive and makes it possible for spermatozoa of inferior quality to fertilize oocytes. In addition, it is well known that men with severe oligozoospermia and non-obstructive azoospermia carry a higher rate of chromosomal aberrations that might be transmitted to the offspring (Lundin et al., 1998). In the present study, a total of 87/1192 infants (7.3%) with malformations were recorded, of which 40/1192 (3.4%) were classified as minor and 47/1192 (3.9%) as relatively serious malformations. The malformations were distributed evenly, with no accumulation in any particular subgroup.
The rate of malformations might appear slightly higher than registry data from the general population, in which the reported rate is often 34% (Bergh et al., 1999). However, it must be emphasized that the data in this study have been analysed by scrutinizing almost all individual records for the 1192 infants. In fact, in a recent report (Wennerholm et al., 2000
) it was found that 4/47 (8.5%) serious malformations were not reported to the Medical Birth Registry or the Registry of Congenital Malformations in Sweden. Therefore, for proper comparison, data have to be collected in the same way and strictly identified control groups are preferable. Even if the malformation rate seems reassuring, one has to remember that the power to detect an increase in malformations in this study is rather low. With 80% power and a significance level of 5%, it would only be possible to detect an almost doubled malformation rate, i.e. an increase from 3.5 to 6.0%, in the total ICSI population of 1192 infants. In the severe oligozoospermia subgroup (220 infants), the power to detect a doubled rate, i.e. an increase from 3 to 6%, is only 33%. In previous studies, available data on major birth defects in children born after ICSI, using mainly ejaculated spermatozoa, has shown that there are no differences between these children and children born after conventional IVF or spontaneous conception (Bonduelle et al., 1995
; Govaerts et al., 1998
; Tarlatzis and Bili, 1998
). Recently, however, data from the French national registry (FIVNAT) were reported showing a significant increase in the malformation rate (including chromosomal anomalies) compared with conventional IVF (Rossin-Amar et al., 1999
).
Chromosomal aberrations were found in four of 149 prenatal karyotypes and in two postnatal karyotypes in this study. No sex chromosome aberrations were detected. This might be of interest since earlier studies have indicated a possible increased rate of sex chromosome anomalies in children born after ICSI (In't Veld et al., 1995; Bonduelle et al., 1998).
In summary, the results from this study concerning the obstetric outcome of children born after ICSI, classified according to sperm origin and quality, showed that the outcome was similar to other published series for ICSI and conventional IVF. The major problem seems to be the high rate of twin pregnancies and neither the ICSI technique per se nor sperm origin or quality seemed to cause a substantial increase in adverse outcome.
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Acknowledgments |
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Notes |
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References |
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Aytoz, A., Camus, M., Tournaye, H. et al. (1998) Outcome of pregnancies after intracytoplasmic sperm injection and the effect of sperm origin and quality on this outcome. Fertil. Steril., 70, 500505.[ISI][Medline]
Bergh, T., Ericson, A., Hillensjö, T. et al. (1999) Deliveries and children born after in-vitro fertilisation in Sweden 198295: a retrospective cohort study. Lancet, 354, 15791585.[ISI][Medline]
Bonduelle, M., Legein, J., Derde, M. et al. (1995) Comparative follow-up study of 130 children born after intracytoplasmic sperm injection and 130 children born after in-vitro fertilisation. Hum. Reprod., 10, 33273331.[Abstract]
Bonduelle, M., Buysse, A., Van Assche, E. et al. (1996) Prospective follow-up study of 877 children born after intracytoplasmic sperm injection (ICSI) with ejaculated, epididymal and testicular spermatozoa and after replacement of cryopreserved embryos obtained after ICSI. Hum. Reprod., 11 (Suppl. 4), 131155.[ISI][Medline]
Bonduelle, M., Aytoz, A., Van Assche, E. et al. (1998) Incidence of chromosomal aberrations in children born after assisted reproduction through intracytoplasmic sperm injection. Hum. Reprod., 13, 781782.
Craft, I. and Shrivastav, P. (1994) Treatment of male infertility. Lancet, 344, 191192.[ISI][Medline]
Girardi, S., Mielnik, A. and Schlegel, P. (1997) Submicroscopic deletions in the Y chromosome of infertile men. Hum. Reprod., 12, 16351641.[Abstract]
Govaerts, I., Devreker, F., Koenig, I. et al. (1998) Comparison of pregnancy outcome after intracytoplasmic sperm injection and in-vitro fertilisation. Hum. Reprod., 13, 15141518.[Abstract]
Hamberger, L., Sjögren, A., Lundin, K. et al. (1995) Microfertilisation techniques the Swedish experience. Reprod. Fertil. Dev., 7, 263268.[ISI][Medline]
ICD 9 (1977) Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death. Based on the Recommendations of the Ninth Revision Conference, 1975, and adopted by the Twenty-ninth World Health Assembly. World Health Organization, Geneva, Vol. 1, Chap. XIV.
ICD 10 (1992) International Statistical Classification of Diseases and Related Health Problems, 10th revision. World Health Organization, Geneva, Vol. 1, Chap. XVII.
In't Veld, P., Brandenburg, H., Verhoeff, A. et al. (1995) Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet, 346, 773.[ISI][Medline]
Kjessler, B. (1966) Karyotype, meiosis and spermatogenesis in a sample of men attending an infertility clinic. In Monographs in Human Genetics. Kärger, Basel, Vol. 2, pp. 174.
Lassalle, B., Testart, J. and Renard, J.P. (1985) Human embryo features that influence the success of preservation with the use of 1,2 propanediol. Fertil. Steril., 44, 645651.[ISI][Medline]
Lissens, W., Mercier, B., Tournaye, H. et al. (1996) Cystic fibrosis and infertility caused by congenital bilateral absence of the vas deferens and related clinical entities. Hum. Reprod., 11 (Suppl. 4), 5578.[Abstract]
Loft, A., Petersen, K., Erb, K. et al. (1999) A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 19941997. Hum. Reprod., 14, 21432148.
Lundin, K., Hanson, C. and Hamberger, L. (1998) Are the new microfertilisation techniques associated with an increased genetic risk to the offspring? Acta Obstet. Gynecol. Scand., 77, 792798.[ISI][Medline]
Marsál, K., Persson, P., Larsen, T. et al. (1996) Intrauterine growth curves based on ultrasonically estimated fetal weights. Acta Paediat., 85, 843848.[ISI][Medline]
Nagy, Z., Liu, J., Cecile, J. et al. (1995) Using ejaculated, fresh and frozenthawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection. Fertil. Steril., 63, 808815.[ISI][Medline]
Palermo, G., Colombero, L., Schattman, G. et al. (1996) Evolution of pregnancies and initial follow-up of newborns delivered after intracytoplasmic sperm injection. J. Am. Med. Assoc., 276, 18931897.[Abstract]
Rossin-Amar, B., Safi, A., Pouly, J.L. et al. (1999) Analysis of babies conceived by ICSI. Comparison with babies born after conventional in-vitro fertilization or natural conception. Hum. Reprod. 14 (Abstract Bk. 1), p79.
Schoysman, R., Vanderzwalmen, P., Nijs, M. et al. (1993) Pregnancy after fertilisation of human testicular sperm. Lancet, 342, 1237.
Shrivastav, P., Nadkarni, P., Wensvoort, S. et al. (1994) Percutaneous epididymal sperm aspiration for obstructive azoospermia. Hum. Reprod., 9, 20582061.[Abstract]
Silber, S.J., Devroey, P. and Van Steirteghem, A.C. (1994) Conventional in-vitro fertilization versus intracytoplasmic sperm injection for patients requiring microsurgical sperm aspiration. Hum. Reprod., 9, 19051909.
Tarlatzis, B. and Bili, H. (1998) Survey on intracytoplasmic sperm injection: report from the ESHRE ICSI Task Force. Hum. Reprod., 13, 165177.[Abstract]
Temple Smith, P.D., Southwick, G.J. and Yates, C.A. (1985) Human pregnancy by in vitro fertilisation (IVF) using sperm aspirated from the epididymis. J. In Vitro Fertil. Embryo Transfer, 2, 119122.[Medline]
Tournaye, H., Devroey, P., Camus, M. et al. (1992) Comparisons of in vitro fertilisation in male and tubal infertility. Hum. Reprod., 7, 218222.[Abstract]
Tournaye, H., Liu, J. and Nagy, Z. (1995) Intracytoplasmic sperm injection (ICSI): the Brussels experience. Reprod. Fertil. Dev. 7, 269279.[ISI][Medline]
Tsirigotis, M. and Craft, I. (1995) Sperm retrieval methods and ICSI for obstructive azoospermia. Hum. Reprod., 10, 758760.[ISI][Medline]
Wennerholm, U-B., Bergh, C., Hamberger, L. et al. (1996) Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection. Hum. Reprod., 11, 11131119.[Abstract]
Wennerholm, U-B., Hamberger, L., Nilsson, L. et al. (1997) Obstetric and perinatal outcome of children conceived from cryopreserved embryos. Hum. Reprod., 12, 18191825.[Abstract]
Wennerholm, U.-B., Bergh, C., Hamberger, L. et al. (2000) Incidence of congenital malformations in children born after ICSI. Hum. Reprod., 15, 944948.
Westlander, G., Hamberger, L., Hanson, L. et al. (1999) Diagnostic epididymal and testicular sperm recovery and genetic aspects in azoospermic men. Hum. Reprod., 14, 118122
World Health Organization (1992) WHO Laboratory Manual for the Examination of Human Semen and SemenCervical Mucus Interaction. 3rd edn, Cambridge University Press, Cambridge.
Wikland, M., Nilsson, L., Hansson, R. et al. (1983) Collection of human oocytes by the use of sonography. Fertil. Steril., 39, 603606.[ISI][Medline]
Wikland, M., Borg, K., Hamberger, L. et al. (1994) Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction. Hum. Reprod., 9, 14301436.[Abstract]
Wisanto, A., Bonduelle, M., Camus, M. et al. (1996) Obstetric outcome of 904 pregnancies after intracytoplasmic sperm injection. Hum. Reprod., 11 (Suppl.), 121129.[Abstract]
Submitted on November 11, 1999; accepted on February 14, 2000.