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Assisted reproduction: a reassuring picture

Gabor T Kovacs
Med J Aust 1996; 164 (10): 628-630.
Published online: 9 September 1999
Medicine and the Community

Assisted reproduction: a reassuring picture

Many couples seek solutions to problems of infertility by using assisted reproduction techniques. Despite very different beginnings, children conceived after donor insemination, ovum donation, in-vitro fertilisation or gamete intrafallopian transfer show no adverse long term effects, either physically or psychosocially.

Gabor T Kovacs

MJA 1996; 164: 628-630

Introduction - Donor insemination - Ovum donation - Issues of genetic identity - In-vitro fertilisation - Intracytoplasmic sperm injection (ICSI) - Reproductive technology and the risk of cancer - Conclusions - References - Authors' details
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Introduction A 1995 report on assisted conception from the Australian Institute of Health and Welfare showed that there were over 2300 births after conception by in-vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) in 1993, and that about 1% of all births in Australia are a result of these techniques.1 Between 1980 and 1993, more than 15 000 babies were born in Australia after conception by IVF and GIFT.1 Since the mid-1970s, several hundred more have been born each year after artificial insemination with donor sperm. As more families are using assisted reproduction techniques, the long term outcome of these children and their families has become an important issue.



Donor insemination
The first investigation of long term outcomes after assisted reproduction was performed on 54 children born after conception by donor sperm in Tokyo in 1968.2 These children, aged up to 11 years, were not inferior in measures of body weight and length or in intelligence and development quotients when compared with a control group of children conceived naturally. Over the next decade, the same conclusions were reached when the study was expanded to include 133 children.3

Similar results for psychomotor development and psychological adjustment in children born through donor insemination programs were found in two early 1980s retrospective French studies of 30 and 75 families,4,5 and in a 1990 American study of 362 families.6

The first assessment of families who had had children by donor insemination in Australia was a retrospective study in 1982 that showed no major obstetric, paediatric or emotional problems in 50 children aged between one and three years.7 Researchers at the Prince Henry Institute in Melbourne in 1993 did the first controlled study of the psychosocial development of children conceived by donor insemination.8 Twenty-two children conceived by this technique and aged from six to eight years were compared with matched controls (20 children conceived naturally and 10 adopted children). Psychomotor scores derived from the Achenbach Child Behaviour Checklist showed no significant difference between the three groups of children.8

In a Sydney study by Durna et al., 76% of 276 couples thought that having had a child by donor insemination had a positive personal effect and less than 1% had regrets.9 Forty-seven per cent felt their marriage had improved, which is similar to the 54% seen in an American study.6 Marriage breakdown was reported at 3.6%, which is less than the rate for the general population. Durna et al. concluded that prospective couples could be reassured that having a child by donor insemination can have positive psychosocial effects on their relationships.

The most detailed study of families with a child conceived by assisted reproductive technology was by Golombok et al., who studied 45 families with a child by donor insemination, 41 families with a child by IVF, 55 families with an adopted child and 43 control families.10 Assessments involving interviews and questionnaires were carried out on children aged from four to eight and their parents to determine the children's emotions, behaviour and relationships, and the parents' psychological state and quality of parenting. The quality of parenting for children conceived by assisted reproductive technology appeared superior to that of naturally conceived children. There were no significant differences between children conceived by donor insemination and children conceived by IVF.


Ovum donation
A survey of donor oocyte clinics worldwide in 1991 identified just over 200 such pregnancies.11 Thirty-six couples who conceived children using donor oocytes in Melbourne between 1983 and 1991 unanimously agreed that they would recommend ovum donation.12 However, as the technique of ovum donation is a more recent development, the number of studies are limited and further studies are needed to assess long term outcome.



Issues of genetic identity
Of increasing concern is the issue of genetic identity. What are the psychosocial effects on a child conceived from donated gametes who knows about his or her true biological origins? The issue may not be resolved for several years as open discussion about donor insemination has only recently become acceptable. In the study by Durna et al., 21% of couples were concerned about telling their child about donor insemination.9A 1995 study by Daniels et al. found considerable disagreement and debate about whether to tell their child among 58 couples who had conceived a child through donor insemination at the Dunedin Infertility Clinic (New Zealand).13 Controlled studies are required to compare children who know their biological origins with children who do not.



In-vitro fertilisation
There are no reports that have followed up children conceived by GIFT. The first cohort of IVF children were born in Australia. In an initial follow-up report from Melbourne in 1985, 52 children conceived by IVF were assessed developmentally at birth and at 10 months, and 33 had a psychosocial assessment between one and three years of age.14 The principal findings were the caesarean section rate was much higher (37%); the rate of premature births was four times the expected rate; and the number of very low birthweight children and twins were 10 times more than that expected for children conceived naturally. Scores on the Bayley Scales of Infant Development fell within normal range. Although this was an uncontrolled study and there was an increased rate of obstetric intervention, the authors concluded that these families did not have an increased rate of psychosocial or developmental problems. Similar results were found in a Perth study in 1986 in which 20 children conceived by IVF were reviewed a year after birth.15

In a controlled American study of 83 children conceived by IVF and 93 controls, physical examination, neurological and developmental examination, echocardiography, electrocardiography and abdominal and cranial ultrasound examination were performed on each child.16 There was no significant difference in mental or psychomotor development. However, in a small but controlled French study, there was a significant difference in the relationship between mothers and their children conceived through IVF compared with infertile women having ovulation induction and a control group of mothers who had conceived naturally.17

The largest controlled study on outcomes after IVF was based on 314 children conceived through IVF and 150 matched controls in Melbourne.18 Families were assessed when the children were two years of age and underwent tests such as the Short Temperament Questionnaire for Toddlers, Family Environment Scale, General Health Questionnaire, Dyadic Adjustment Scale, Interview Schedule for Social Interaction and the Monash Family Interview. The authors found that both the cognitive and motor development of children conceived through IVF fell within the normal range, and that there was no difference in parental concerns or child care patterns between the IVF parents and the control parents, and no difference in neonatal problems or physical outcomes (including disabilities or congenital malformations). However, there was a high caesarean section rate.



Intracytoplasmic sperm injection (ICSI)
In ICSI , a single sperm is injected into the cytoplasm of the ovum, under microscopic control. It is used in cases of severe male subfertility. A recent Dutch study reported five cases of sex chromosomal anomalies among 15 fetuses conceived after ICSI and tested by chorionic villus sampling.19 However, this sample size was too small to draw any clinically relevant conclusions. In contrast, the Brussels group who developed the ICSI technique in 1991 reported on 669 children born by mid-1995 who had been conceived by this method.20 Of the 491 who had had prenatal karyotyping, 479 (97.6%) had a normal karyotype and 12 (2.5%) had an abnormal karyotype (half of these were benign structural aberrations). Major congenital malformations were reported in 18 (2.7%) of the 669 children born following ICSI.

A review of Australian and New Zealand microinsemination data up to 1993 found nine major abnormalities among 220 fetuses but no chromosomal anomalies.1 The National Perinatal Statistics Unit is assessing a larger cohort by collecting data for all ICSI pregnancies in Australia in 1994 and 1995 (P Lancaster, Director, AIHW National Perinatal Statistics Unit, Sydney, NSW, personal communication).



Reproductive technology and the risk of cancer
A recent retrospective study found no increased incidence of breast or ovarian cancer in 5564 women who had had ovarian stimulation as part of their infertility treatment compared with 4794 infertile couples.21


Conclusions In 1992, the National Health and Medical Research Council of Australia established a Working Party to examine the long term health effects on families who have had a child by assisted conception.22 After reviewing the literature, this Working Party asked more questions than it answered and recommended the continuation of long term studies of these families. No deleterious long term effects of reproductive technology have been shown in either the offspring or their families. It appears that families with a child conceived by donor insemination, IVF or GIFT do not have an increased risk of psychosocial or developmental problems compared with children conceived naturally.


References
  1. Lancaster P, Shafir E, Huang J. Assisted conception in Australia and New Zealand 1992 and 1993. Australian Institute of Health and Welfare and the Fertility Society of Australia. Sydney: AIHW, 1995.
  2. Iizuka R, Sawada Y, Nishina OM. The physical and mental development of children born following artificial insemination. Int J Fertil 1968; 13: 24-32.
  3. Mochimaru F, Sato H, Kobayaski T, Iizuka R. Physical and mental development of children born through AID. In: David G, Price WS, editors. Human artificial insemination and semen preservation. New York: Plenum Press, 1980: 277-282.
  4. Semenov G, Mises R, Bissery J. Attempt at follow-up of children born through AID. In: David G, Price WS, editors. Human artificial insemination and semen preservation. New York: Plenum Press, 1980: 474-477.
  5. Manuel C, Czyba J. Follow-up study on children born through AID. In: David G, Price WS, editors. Human artificial insemination and semen preservation. New York: Plenum Press, 1980: 467-474.
  6. Amuzu B, Laxova R, Sander S. Pregnancy outcome, health of children, and family adjustment after donor insemination. Obstet Gynecol 1990; 75: 899-905.
  7. Clayton CE, Kovacs GT. AID offspring. Initial follow-up study of 50 couples. Med J Aust 1982; 1: 338-339.
  8. Kovacs GT, Mushin D, Kane H, Baker HWG. A controlled study of the psychosocial development of children conceived following insemination with donor semen. Hum Reprod 1993; 8: 788-790.
  9. Durna EM, Bebe J, Leader LR, et al. Donor insemination: effects on parents. Med J Aust 1995; 163: 248-251.
  10. Golombok S, Cook R, Bish A, Murray C. Families created by the new reproductive technologies: quality of parenting and social and emotional development of the children. Child Dev 1995; 64: 285-298.
  11. King CM, Kovacs GT. Oocyte donation: survey of results. In: Oocyte Donation. Reprod Fertil Dev 1992; 4: 119-124.
  12. Munro J, Leeton J, Horsfall T. Psychosocial follow-up of families from a donor oocyte programme: an exploratory study. In: Oocyte Donation. Reprod Fertil Dev 1992; 4: 125-130.
  13. Daniels KR, Lewis GM, Gillett W. Telling donor insemination offspring about their conception: the nature of couples decision making. Soc Sci Med 1995; 40: 1213-1220.
  14. Mushin DN, Spensley J, Barreda-Hanson M. Children of invitro fertilization. Clin Obstet Gynecol 1985; 12: 865-876.
  15. Yovich JL, Parry TS, French NP, Grauaug AA. Development assessment of twenty in vitro fertilization (IVF) infants at their first birthday. J InVitro Fertil Embryo Transfer 1986; 4: 253-257.
  16. Marin N, Wirth F, Johnson DH, et al. Congenital malformations and psychosocial development in children conceived by in vitro fertilization. J Pediatr 1989; 115: 222-227.
  17. Raoul-Duval A, Bertrand-Servais, Frydman R. Comparative prospective study of the psychological development of children born by in vitro fertilization and their mothers. J Psychosom Obstet Gynaecol 1993; 14: 117-126.
  18. Halasz G, Munro J, Saunders K, et al. The growth and development of children conceived by IVF. Report to the Commonwealth Department of Health, Housing, Local Government and Community Services; Research and Development Grants Advisory Committee (RADGAC); and Victorian Health Promotion Foundation. Melbourne, Monash University Department of Psychological Medicine, 1993.
  19. Veld P, Brandenburg H, Verhoeff A, et al. Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 1995; 346: 773.
  20. Liebaers I, Bonduelle M, Legein J, et al. Follow-up of children born after intracytoplasmic sperm injection. In: Hedon B, Bringer J, Mares P, editors. Fertility and sterility: a current overview. New York: Parthenon, 1985: 409-412.
  21. Venn A, Watson L, Lumley J, et al. Breast and ovarian cancer incidence after infertility and invitro fertilisation. Lancet 1995; 346: 995-1000.
  22. National Health and Medical Research Council. Long term effects on women from assisted conception. Consultation document. Canberra: NHMRC, 1995.

This article is based on a lecture presented at the 15th World Congress on Fertility and Sterility, Montpellier, France, 17-22 September 1995.


Authors' details Department of Obstetrics and Gynaecology, Monash Medical School, Box Hill Hospital, Box Hill, VIC.
Gabor T Kovacs, MD, FRACOG, Director. Chairman, IVF Directors Group, Fertility Society of Australia.

No reprints will be available from the author.





  • Gabor T Kovacs


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