Multiple births The major complication of<unk>  is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. Britain, Belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed<unk>  pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of less than . There is some evidence that making a double embryo transfer during one cycle achieves a higher live birth rate than a single embryo transfer; but making two single embryo transfers in two cycles has the same live birth rate and would avoid multiple pregnancies. Sex ratio distortions Certain kinds of<unk> , in particular ICSI (first applied in 1991) and blastocyst transfer (first applied in 1984) have been shown to lead to distortions in the sex ratio at birth. ICSI leads to slightly more female births (51.3% female) while blastocyst transfer leads to significantly more boys (56.1% male) being born. Standard<unk>  done at the second or third day leads to a normal sex ratio. Epigenetic modifications caused by extended culture leading to the death of more female embryos has been theorised as the reason why blastocyst transfer leads to a higher male sex ratio, however adding retinoic acid to the culture can bring this ratio back to normal. Spread of infectious disease By sperm washing, the risk that a chronic disease in the individual providing the sperm would infect the female or offspring can be brought to negligible levels. In males with hepatitis B, The Practice Committee of the American Society for Reproductive Medicine advises that sperm washing is not necessary in<unk>  to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of vertical transmission during<unk>  is no different from the risk in spontaneous conception. However, there is not enough evidence to say that ICSI procedures are safe in females with hepatitis B in regard to vertical transmission to the offspring. Regarding potential spread of HIV/AIDS, Japan's government prohibited the use of<unk>  procedures for couples in which both partners are infected with HIV. Despite the fact that the ethics committees previously allowed the Ogikubo, Tokyo Hospital, located in Tokyo, to use<unk>  for couples with HIV, the Ministry of Health, Labour and Welfare of Japan decided to block the practice. Hideji Hanabusa, the vice president of the Ogikubo Hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove HIV from sperm. Other risks to the egg provider/retriever A risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome, particularly if hCG is used for inducing final oocyte maturation. This results in swollen, painful ovaries. It occurs in 30% of patients. Mild cases can be treated with over the counter medications and cases can be resolved in the absence of pregnancy. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. In severe cases patients have sudden excess abdominal pain, nausea, vomiting and will result in hospitalisation. During egg retrieval, there exists a small chance of bleeding, infection, and damage to surrounding structures such as bowel and bladder (transvaginal ultrasound aspiration) as well as difficulty in breathing, chest infection, allergic reactions to medication, or nerve damage (laparoscopy). Ectopic pregnancy may also occur if a fertilised egg develops outside the uterus, usually in the fallopian tubes and requires immediate destruction of the fetus.<unk>  does not seem to be associated with an elevated risk of cervical cancer, nor with ovarian cancer or endometrial cancer when neutralising the confounder of infertility itself. Nor does it seem to impart any increased risk for breast cancer. Regardless of pregnancy result,<unk>  treatment is usually stressful for patients. Neuroticism and the use of escapist coping strategies are associated with a higher degree of distress, while the presence of social support has a relieving effect. A negative pregnancy test after<unk>  is associated with an increased risk for depression in women, but not with any increased risk of developing anxiety disorders. Pregnancy test results do not seem to be a risk factor for depression or anxiety among men. Studies show that there is an increased risk of venous thrombosis or pulmonary embolism during the first trimester of<unk> . When looking at long-term studies comparing women who received or did not receive<unk> , there seems to be no correlation with increased risk of cardiac events. There are more ongoing studies to solidify this. Spontaneous pregnancy has occurred after successful and unsuccessful<unk>  treatments. Within 2 years of delivering an infant conceived through<unk> , subfertile couples had a conception rate of 18%. Birth defects A review in 2013 came to the result that infants resulting from<unk>  (with or without ICSI) have a relative risk of birth defects of 1.32 (95% confidence interval 1.24–1.42) compared to naturally conceived infants. In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through<unk> , notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia; the mechanism of causality is unclear. However, in a population-wide cohort study of 308,974 births (with 6,163 using assisted reproductive technology and following children from birth to age five) researchers found: "The increased risk of birth defects associated with<unk>  was no longer significant after adjustment for parental factors." Parental factors included known independent risks for birth defects such as maternal age, smoking status, etc. Multivariate correction did not remove the significance of the association of birth defects and ICSI (corrected odds ratio 1.57), although the authors speculate that underlying male infertility factors (which would be associated with the use of ICSI) may contribute to this observation and were not able to correct for these confounders. The authors also found that a history of infertility elevated risk itself in the absence of any treatment (odds ratio 1.29), consistent with a Danish national registry study and "implicates patient factors in this increased risk." The authors of the Danish national registry study speculate: "our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants." + Risk in singleton pregnancies resulting from<unk>  (with or without ICSI) Condition Relative risk 95% confidence interval Beckwith–Wiedemann syndrome 3-4 congenital anomalies 1.67 1.33–2.09 ante-partum haemorrhage 2.49 2.30–2.69 hypertensive disorders of pregnancy 1.49 1.39–1.59 preterm rupture of membranes 1.16 1.07–1.26 Caesarean section 1.56 1.51–1.60 gestational diabetes 1.48 1.33–1.66 induction of labour 1.18 1.10–1.28 small for gestational age 1.39 1.27–1.53 preterm birth 1.54 1.47–1.62 low birthweight 1.65 1.56–1.75 perinatal mortality 1.87 1.48–2.37 Other risks to the offspring If the underlying infertility is related to abnormalities in spermatogenesis, it is plausible, but too early to examine that male offspring are at higher risk for sperm abnormalities.<unk>  does not seem to confer any risks regarding cognitive development, school performance, social functioning, and behaviour. Also,<unk>  infants are known to be as securely attached to their parents as those who were naturally conceived, and<unk>  adolescents are as well-adjusted as those who have been naturally conceived. Limited long-term follow-up data suggest that<unk>  may be associated with an increased incidence of hypertension, impaired fasting glucose, increase in total body fat composition, advancement of bone age, subclinical thyroid disorder, early adulthood clinical depression and binge drinking in the offspring. It is not known, however, whether these potential associations are caused by the<unk>  procedure in itself, by adverse obstetric outcomes associated with<unk> , by the genetic origin of the children or by yet unknown<unk> -associated causes. Increases in embryo manipulation during<unk>  result in more deviant fetal growth curves, but birth weight does not seem to be a reliable marker of fetal stress.<unk> , including ICSI, is associated with an increased risk of imprinting disorders (including Prader-Willi syndrome and Angelman syndrome), with an odds ratio of 3.7 (95% confidence interval 1.4 to 9.7). An<unk> -associated incidence of cerebral palsy and neurodevelopmental delay are believed to be related to the confounders of prematurity and low birthweight. Similarly, an<unk> -associated incidence of autism and attention-deficit disorder are believed to be related to confounders of maternal and obstetric factors. Overall,<unk>  does not cause an increased risk of childhood cancer. Studies have shown a decrease in the risk
In vitro fertilisation
Egg donation
Embryo transfer
Fetal surgery
Intracytoplasmic morphologically selected sperm injection
Assisted reproductive technology
Artificial insemination
Partner-assisted reproduction