5 million babies have been born by ART methods since the birth of the first IVF baby Louise Brown in 1978 (ICMART 2012). IVF newborns accounted for over 1.5% of the United States total of 3.9 million. Unfortunately, not all IVF procedures that result in a pregnancy lead to a live birth. Approximately 15-20% of IVF pregnancies do not result in a live birth. IVF pregnancies are at increased risk of adverse perinatal outcome. However, the majority of the children conceived by IVF will have a good outcome.
A remarkable decline in the risk of preterm or very preterm delivery and stillbirth rates has been observed over the past twenty years. The improvement is primarily due to new regulations which limit the number of embryos, which can be transferred into the woman to avoid risky multiple births and also improved techniques (Human Reproduction 2015). The table below summarizes the overall outcome of IVF pregnancies compared to natural conception.
Pregnancy after IVF
|IVF pregnancy||Natural conception||Comments|
|Miscarriage||14-30%||15-20%||Slight increase, due to older age.|
|Ectopic pregnancy||1-11%||0.2-1.4%||Increase due to many factors.|
|Preterm delivery||24-30%||6-7%||Four-fold increase.|
|Small birth weight||27-32%||5-7%||Five-fold increase.|
|Stillbirth rate||1.2%||0.6%||Two-fold increase.|
|Perinatal death||2.7%||1.0%||Two-fold to four-fold increased risk.|
|Congenital abnormalities||1.0-5.4%||0.8-4.5%||30-40% increase. However, the absolute risk is nevertheless low.The increase is partly attributable to the underlying infertility as couples who take longer than 12 months to conceive also have an increased risk of abnormalities.|
|Caesarean section||33-58%||10-25%||Increase mainly because of multiple pregnancy and woman's age.|
|twins||24-31%||1.2-4.5%||Increase due to higher number of embryos transferred.|
Pulmonary embolism and venous thromboembolism
The risk of pulmonary embolism (blockage of the main artery of the lung)) and venous thromboembolism (blood clot in the veins) Is increased during normal pregnancy, compared with non pregnant women. Pulmonary embolism and venous thromboembolism are potentially serious conditions and is a leading cause of maternal death
Swedish study (published in the BMJ 2013) reported that IVF is associated with an increased risk of pulmonary embolism and venous thrombosis in the first trimester of pregnancy compare with pregnant women who conceived naturally (4.2 in 1000 compared to 2.5 in 1000) and 0.08% compared with 0.05% for pulmonary embolism.
Outcome of children born following IVF treatment
Follow-up of children born as a result of IVF, ICSI and other forms of assisted conception is needed to study issues such as genetic risk, congenital malformation, psychological, physical development, and educational development, fertility, and risk of cancer. Some studies demonstrated no significant differences in the incidence of congenital and chromosomal abnormalities in children conceived after IVF compared to children conceived naturally. Furthermore, children appear to develop normally both from fresh and frozen embryo transfer. However, a recent major US study showed that babies born using assisted reproductive techniques like IVF are twice as likely to suffer from some heart problems and cleft lip and have four times the risk of certain gastrointestinal conditions.
Why some studies find birth defects more common among IVF-conceived babies, remaines to be answered. It is possible that the same reasons people have trouble conceiving and seek out fertility treatment could influence their increased risk of having a baby with a birth defect. There are evidences that couples who took longer than 12 months to conceive have an increased risk of structural chromosomal abnormalities. The IVF techniques themselves could be involved. Another possible cause is that babies conceived through fertility treatments are monitored more closely than other babies.
The confidentiality affected by Human Fertilization and Embryology Act in the United Kingdom to the parents and children resulted from ART has meant that follow up of these children has not been possible.
No association has been found in the short to medium term related to cancer in children born from ovulation induction and IVF. Long-term health outcomes in women and children after IVF is still awaited
Autism and mental disability
The overall risk of an IVF baby beeing affected by Autism (neuro-developmental disorder characterised by poor communication skills) and mental disability is very small. Avi Reichenberg and colleagues (JAMA 2013) reported a higher risk of autism and disability in ICSI babies compared with standard babies and IVF babies have a slighly higher risk than babies conceived naturally (0.136% , 0.093%, and 0.029%. Babies born by surgical sperm retrieval and ICSI have the highest risk. The exact mechanism for the higher incidence is unclear
Frozen vs fresh embryo
A recent study from Denmark, Norway and Sweden compared the outcome babies born after fresh and frozen embryo transfers (FER) and in general population. The researchers found children born after FER had higher rates of pre-term birth (PTB), very pre-term birth (VLTB), low birth weight (LBW), very low birth weight (VLB), large for gestation age (LGA) compared to spontaneous conceptions. However, when compared to fresh IVF births, children born after FER fared better, having lower rates of PTB, LBW, and SGA (small for gestational age). But they also found children born after FER to have higher rates of LGA than those born from fresh IVF (The Society for Maternal-Fetal Medicine. San Francisco, California, 2013)
Recently,researchers from the USA reported that extremely high estrogen levels at the time of embryo transfer may increase the risk that infants will be born small for their gestational age and the risk of pre-eclampsia and proposed freezing embryos of women who have excessively elevated estrogen at the time of egg collection, followed by embryo transfer in a later cycle when hormonal levels were closer to those of a natural cycle
Thatcher and colleagues (Lancer 1989) reported a higher proportion of male birth after IVF (64%) and Ghazzawi and colleagues (I journal Gynecol Obstet 2000). reported a higher proportion of female birth after ICSI (61.7%) More recently, Dean and colleagues (BJOG 2010) retrospectively analysed the sex of the babies at birth following a single embryo transfers in Australia and New Zealand. There were 13,165 babies born by 13,165 women who had a single embryo transfer (SET) between 2002 and 2006. They reported that ICSI was associated with more females than males and IVF was associated with more males than females. Furthermore, they found that Blastocyst transfer was associated with more male than female. They quoted the following sex birth: IVF with a single Blastocyst: 56.1% males, IVF with a single cleaved embryo: 51.6 males, ICSI with single Blastocyst: 52.5% males and ICSI with single cleaved embryo: 48.7% males.
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