A Follow Up on IVF Children

Källén B, Finnström O, Nygren KG, Otterblad Olausson P., Wennerholm. U.-B. (2005). In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity, and mortality. BJOG, 112, 1529-35.

I have been very fortunate to work with Dr. Nygren on the international ACT initiative, which aims to provide people with information and guidance about the simple and effective approaches, including treatments, that can be taken to help them achieve a pregnancy. Dr. Nygren is deeply committed to his work and is world renowned for his international Assisted Reproduction Technology work, particularly with children and relating to data collection and assessment.

 

Naturally, I am very interested to hear about the IVF children and their well-being. We can now present a summary of Dr. Nygren’s report on 16,280 of these children. Dr. Nygren’s formal qualifications are as follows: Karl Nygren, MD, PhD is a clinician in the OBGYN Department of the Infertility IVF clinic at Sophiahemmet Hospital in Stockholm, Sweden. He started the first private IVF clinic in the Nordic countries, in Stockholm in 1984. He is senior adviser to the Swedish Board of Health & Welfare, Chairman of the EIMs Consortium in ESHRE, Honorary member of ESHRE and Chairman of the International Committee on the Monitory of ART. He is a member of the Assisted Conception Taskforce (ACT).

 

 

 

Karl G. Nygren, MD, PhD

 

 

 

In Sweden, unique circumstances make it possible to conduct retrospective register studies to follow up on the health of its citizens.

 

For many years, population-based health registers have collected different kinds of health data on their Swedish citizens. These registers are managed and controlled by the Swedish Board of Health and Welfare and its Centre for Epidemiology.

 

A unique and personal identification number, or PIN code, is assigned to each and every person in the country. Through cross-referencing, it is possible to collect data on certain individuals or subgroups of individuals whose names appear in several of these registers. The PIN codes are used extensively in community services and in all areas of health care.

 

 

The study ran from the birth of the first IVF child, born in 1982, until the end of 2001. The PIN codes from all 16,280 IVF children were cross-linked to five different health registers. These were The Cancer Register, The Malformation Register, The Birth Register, The Causes of Death Register and The Hospital Discharge Register.

 

Data from all 16,280 children born in 13,261 deliveries and their 12,186 mothers was compared to all other 2,039,943 children born in the country during these years, and their mothers. This is the largest database of its kind in the world and results from this study have recently been published in international scientific journals [1]. I am pleased to provide a summary of the results below.

 

During the 20 years since the first IVF child was born in Sweden, clinical policy changed to reflect increasing understanding of the health risks associated with multiple births. Not only in Sweden, but around the world, there has been an effort to begin to reduce the number of embryos transferred. This transition has been slow in most countries so far, but more evident in the Nordic countries. In Sweden, multiple pregnancies and deliveries declined markedly during this time period. Twins decreased from 29% during 1994 to 18.5% of all IVF deliveries in 2001, and this trend has continued until today: in 2008, the proportion of IVF twins is now as low as 5% (compared to 2% in the general population)!

 

Triplet births also decreased from 3% to 0.5%. As a consequence, preterm births (which are strongly associated with multiple gestations) decreased from 25% to 10% (compared to 5% in the general population). Both neonatal morbidity and neonatal mortality decreased by approximately 50%.

 

 

Major congenital malformations were reported in 5% of IVF and ICSI singletons, compared to 3% in children in the general population. A few specific diagnoses were found to have increased for singletons only, and not when comparing IVF-twins to other twins. This unexpected finding seems, to a certain extent, to be due to the fact that IVF twins are almost always dizygotic (fraternal) whereas other twins are monozygotic (identical). The malformation risk is lower for dizygotic twins.

 

In singletons, neural tube defects such as spina bifida, (0.3% in ICSI/IVF children compared to 0.03% in the general population) and atresias—missing or blocked passages of the gastrointestinal tract—(0.34% vs 0.18%) were seen more frequently. There was also an increased incidence of hypospadias (wrongly positioned opening on the penis, 0.46% vs 0.28%) but this was only observed after ICSI, not after IVF.

 

 

The infant mortality rate for IFV/ICSI babies was found to be 1.2% versus 0.8% in the general population, with no difference when comparing standard IVF to ICSI. There was a small but significant increase of cerebral haemorrhage (times 2), convulsions (times 1.4), respiratory problems (times 2.5) and neonatal sepsis (times 1.5) after IVF/ICSI.

 

 

There was no increased risk of cancer among IVF/ICSI children. However, hospitalisations were found to be twice as frequent until 6 years of age for IVF/ICSI children compared to naturally conceived children. This was partly explained by the increase in preterm and multiple births and might also reflect different parental attitudes seen in IVF/ICSI parents towards medical care for their children.

 

 

IVF mothers were on average 3 years older, smoked less, more often had low or high body mass index (BMI), had more previous miscarriages, and used medications not used by mothers of naturally conceived children.

 

 

IVF mothers had a higher risk during pregnancy of ovarian torsion (times 10), early pregnancy bleeding (times 5), pre-eclampsia (times 1.6), blood loss at delivery (1.5), premature rupture of membranes (2.5) and caesarean section (1.4). We found no evidence that these increased medical risks were due to IVF or ICSI treatments. However, two main factors were identified as possible causes: the increased incidence of premature births (caused primarily by the increase in multiple gestations) and maternal factors, such as age and infertility problems that were not resolved by the IVF treatment.

 

There was a decrease in the risk of cancer in general, but reports suggested an increase in the risk of ovarian cancer in women who have had IVF/ICSI. However, it is important to understand that this risk was already present before undergoing IVF treatment, and was not increased after treatment.

 

There was no increase in maternal mortality between IVF/ICSI mothers compared to the general obstetric population.

 

 

IVF mothers differed markedly from other mothers, both pre-treatment and during pregnancy.

 

IVF/ICSI children had an increased risk of prematurity followed by increased risks for morbidity and mortality.

 

Infant malformations were somewhat increased compared to the general population.

 

There was no increase in the incidence of cancer among IVF/ICSI children.

 

Limiting the number of embryos transferred was effective. We observed a trend toward a declining proportion of multiple pregnancies and a resulting decline in health risks for both mother and child.

 

The vast majority of IVF/ICSI children were healthy and thriving.

 

 

We found no evidence that the increased medical risks were due to the IVF treatment itself, but rather related to multiple births and to maternal factors like age and infertility.

 

The medical risks related to multiple births have become more clearly understood over the last 20-25 years and IVF technology has advanced considerably. As a result, IVF clinics have begun transferring fewer embryos and achieving higher singleton pregnancy rates. Our unique opportunity in Sweden to follow the health status of both mothers and children in IVF/ICSI programs over a 20-year time period has provided further strong evidence for a shift in clinical policies worldwide towards single embryo transfer as the norm in IVF treatments.

 

Källén, B., Finnström, O., Nygren, K. and Olausson, P. (2005). In vitro fertilization (IVF) in Sweden: Risk for congenital malformations after different IVF methods. Birth Defects Research Part A: Clinical and Molecular Teratology 73 (3), 162-169.

 

Källén, B., Finnström, O., Nygren, K.G., Otterblad Olausson, P. (2005). Temporal trends in multiple births after in vitro fertilisation in Sweden, 1982-2001: a register study. BMJ 331, 382-3.

Källén B, Finnström O, Nygren KG, Otterblad Olausson P. (2005). In vitro fertilization (IVF) in Sweden: infant outcome after different IVF fertilization methods. Fertil Steril, 84 (3), 611-17.

 
Källén B, Finnström O, Nygren KG, Otterblad Olausson P. (2005). In vitro fertilization in Sweden: child morbidity including cancer risk. Fertil Steril, 84 (3), 605-10.

Källén B, Finnström O, Nygren KG, Otterblad Olausson P. (2005). In vitro fertilization in Sweden: maternal characteristics. Acta Obst Gynecol Scand, 84, 1185-91.