Conception With ART Linked to Childhood Cancers


Taiwanese study finds increased risk mainly due to leukemia and hepatic cancers

A microscopy of in vitro fertilization.

Children conceived via assisted reproductive technology (ART) may have a higher risk of developing childhood cancers, a Taiwanese population-based cohort study suggested.

Over 14.9 million person-years of follow-up, ART conception was associated with an increased risk of any type of childhood cancer compared with natural conception (HR 1.58, 95% CI 1.17-2.12), and subfertility with non-ART conception (HR 1.42, 95% CI 1.04-1.95), reported Li-Yin Chien, ScD, of the National Yang Ming Chiao Tung University in Taipei City, and colleagues.

The increased cancer risk for children conceived with ART was mainly due to leukemias and hepatic tumors, with associated increased risk for leukemias (HR 2.10, 95% CI 1.20-3.70), and hepatic tumors (HR 2.71, 95% CI 1.28-5.73) compared with natural conception after adjusting for confounders. ART was also associated with higher risks for these cancers when compared with subfertility and non-ART (leukemias: HR 1.88, 95% CI 1.03-3.43; hepatic tumors: HR 2.41 95% CI 1.05-5.52), they noted in JAMA Network Open.

“Our findings suggest that couples seeking ART treatment need to be informed of the low but significantly increased risk of childhood cancers,” Chien and team wrote. “Healthcare workers should collect information on the mode of conception and screen children conceived through ART for early detection of childhood cancers.”

In an accompanying commentary, Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, noted that other studies have also reported associations with other cancers, such as neuroblastomas, central nervous system tumors, sarcomas, and retinoblastomas.

“Consistency in the findings for childhood cancer types would strengthen the evidence for an association of ART with the development of cancer in children, because different cancer types likely have different etiologies,” she wrote. “However, investigating different childhood cancer types is made difficult by their rarity, calling for large or collaborative studies.”

Furthermore, given that there is an association between ART and childhood cancers, “what part of ART conveys the risk?” Hargreave continued. “Whether the increased risk is associated with specific ART procedures, certain fertility drugs, or the underlying infertility of the parents remains to be investigated and will be important for furthering the understanding and possible prevention of cancer in children.”

In a stratified analysis, the association between mode of conception and childhood cancer did not differ significantly by source of infertility and child sex. However, while the use of frozen embryos was not associated with cancer risk, the use of fresh embryos was associated with increased cancer risk.

“Sensitivity analyses of unmeasured confounders for those associations indicated that fairly substantial confounding would be required to explain the associations,” Chien and team wrote.

Additionally, “although preterm birth and low birth weight seem to be plausible mechanisms, the findings of this study suggest that these variables did not mediate the association between ART conception and childhood cancers,” they added, though they found that the “other decomposed associations were not significant either, suggesting that the limited number of cases may have influenced the results.”

For this study, Chien and colleagues used registry data on 2,308,016 eligible parents-child triads in Taiwan from January 2004 through December 2017. Mean paternal and maternal ages were 33.3 and 30.8. Of the children, 52.1% were boys, 8.2% were born preterm, and 7.4% had low birth weight.

A total of 1,880 children with incident childhood cancer were identified.

The incidence rates of childhood cancers per million person-years were the highest for the ART group (203.1), followed by subfertility and non-ART (137.6), and lowest for natural conception (121.4). Incidence rates per million person-years for leukemias were 56.2 for ART, 34.4 for non-ART, and 29.8 for natural conception, while these rates for hepatic tumors were 34.6, 9.9, and 8.2, respectively.

Are IVF pregnancies more ‘precious’?


Two pregnant women

Do women with IVF pregnancies need special attention?

  • Women who have gone through fertility treatment often say it had a huge emotional and psychological impact on them and their partners.

In many cases, couples have spent years trying to conceive before going through several cycles of IVF, which can be expensive and traumatic, with no guarantee of success.

So are pregnancies achieved through assisted fertility treatments viewed as inherently more precious to everyone involved?

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“Until you go home with your baby in your arms, that anxiety is always there.”

Susan SeenanInfertility Network UK

A study from Plymouth University published last month suggests they are. Dr Yaniv Hanoch asked 160 Israeli obstetricians and gynaecologists whether they would recommend a test for a serious medical condition during pregnancy.

He found that doctors were three times more likely to recommend the test, which carried a small risk, for a natural pregnancy than for an IVF pregnancy.

Dr Hanoch, associate professor in psychology, said: “When considering a procedure that may endanger a pregnancy, the value ascribed to loss of that pregnancy may seem greater if the pregnancy was achieved by tremendous effort.”

In 2005, Minkoff and Berkowitz published a study in the American journal, Obstetrics and Gynecology entitled ‘The Myth of the Precious Baby’.

It said that because increasing numbers of pregnant women were aged over 40 and more were pregnant thanks to assisted reproductive technologies, this had resulted in more ceasarean deliveries, reinforcing the idea among obstetricians that they were dealing with ‘precious babies’.

Ante-natal check up
IVF women often want reassurance on aches and pains during pregnancy

On the ground, there is less evidence of sensitivity and understanding from health professionals towards women with IVF pregnancies.

Susan Seenan, from the Infertility Network UK, says the system lets these women down.

“When these women finally go to their GP and say they are pregnant, they are referred for ante-natal care and that’s it.

“Even when they make it known they have had IVF, they are seen as just another pregnant lady.”

She says sometimes even when women reveal they have suffered miscarriages or have had fertility issues, there is a lack of sympathy.

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Some women like to feel they have access to extra information as required, even if it’s just a phone number to speak to a midwife about any aches or pains.”

Mr Tim ChildOxford Fertility Unit

She says fertility treatment is widely recognised to be a physically, psychologically and financially demanding process – and it can leave women feeling they have been on an ’emotional rollercoaster’.

“A lot of women feel very anxious, because they have been through so much, and many women really do worry that everything will be OK.

“Until you go home with your baby in your arms, that anxiety is always there. People need to understand why they are feeling vulnerable and anxious.

“If they have been through the IVF system they will have had a lot of attention, appointments, blood tests and scans – and they expect that attention to continue.”

Instead, many women are left feeling isolated when they are most in need of reassurance.

Seenan says this could be remedied by providing support in the form of a phoneline to call in times of anxiety or information leaflets to read.

Research does seem to confirm higher levels of anxiety in women with IVF pregnancies, says Julie Jomeen, professor of midwifery at Hull University, who adds that their feelings can mean they want a more medicalised approach to their pregnancy.

Older mums-to-be may request a caesarean section delivery, believing that it is safer, for example.

An obstetrician discussing options with a pregnant womanSome women choose not reveal they had fertility treatment

Or a woman who is scared of losing her baby throughout pregnancy, may need reassurance that normal symptoms of pregnancy, such as backache, are not something more serious.

Mr Tim Child, medical director at the Oxford Fertility Unit at the University of Oxford, acknowledges that women who have conceived naturally can have anxieties too, but he says it would be understandable if IVF women felt they needed more support.

“Some women like to feel they have access to extra information as required, even if it’s just a phone number to speak to a midwife about any aches or pains.”

He says not all women want to disclose that they have been through IVF because there is still some stigma attached to it. Others may want to be treated the same as every other woman, so their IVF history may not always appear on their personal notes.

Medically, there are slightly higher risks of complications in IVF pregnancies, particularly if the woman is older, has underlying health problems or is having twins, so Mr Child says consultants should be vigilant.

A study is currently underway at Oxford into how midwives care for women have had fertility treatment.

When women with IVF pregnancies are open about their anxieties, what they are looking for is not special treatment in the belief that their baby is more precious than anyone else’s, but reassurance and support during the final stages of a long and emotional journey.

Even when the baby is born, it doesn’t end, Susan Seenan says.

“Because the baby has been wanted for so along, you put pressure on yourself to be a perfect parent. So you’re not allowed to complain when it cries at night or doesn’t feed well. But in the end, we are just parents like anyone else.”

Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study.


Abstract

Objective To assess the mental health of children born after fertility treatment by comparing their risk of mental disorders with that of spontaneously conceived children.

Design Prospective register based cohort study.

Setting Nationwide register based information from Danish National Health Registers cross linked by a unique personal identification number assigned to all citizens in Denmark.

Participants All children born in Denmark in 1995-2003 with follow-up in 2012 when the children were aged 8-17; 33 139 children were conceived after fertility treatment and 555 828 children were born after spontaneous conception.

Main outcome measures Absolute risks and hazard ratios for overall and specific mental disorders estimated with adjustment for potential confounding variables. Estimated association between the risk of mental disorders and subtypes of procedures, hormone treatments, gamete types, and cause of infertility.

Results The risk of mental disorders in children born after in vitro fertilisation or intracytoplasmic sperm injection was low, and was no higher than in spontaneously conceived children, except for a borderline significant increased risk of tic disorders (hazard ratio 1.40, 95% confidence interval 1.01 to 1.95; absolute risk 0.3%). In contrast, children born after ovulation induction with or without insemination had low but significantly increased risks of any mental disorder (1.20, 1.11 to 1.31; absolute risk 4.1%), autism spectrum disorders (1.20, 1.05 to 1.37; 1.5%), hyperkinetic disorders (1.23, 1.08 to 1.40; 1.7%), conduct, emotional, or social disorder (1.21, 1.02 to 1.45; 0.8%), and tic disorders (1.51, 1.16 to 1.96; 0.4%). There was no risk systematically related to any specific type of hormone drug treatment.

Conclusions There was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination. Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously.

Discussion

In this large long term follow-up of an unselected cohort of children conceived after fertility treatment, we found a systematically small increased risk of mental disorders in children born after induced ovulation/intrauterine insemination compared with spontaneously conceived children. When we considered the diagnoses in categories of mental disorders, there was a significant increased risk of autistic spectrum disorders, hyperkinetic disorders, tic disorders, and conduct, emotional, or social disorders. In contrast, beside a borderline significantly increased risk of tic disorders, we found no association between conception after IVF/ICSI and risk of mental disorders in childhood or adolescence. There were no systematic associations between cryopreserved embryos or gametes, types of hormones, or cause of infertility and risk of mental disorders.

What is known on this topic

  • Children born after fertility treatment have an increased risk of some perinatal outcomes such as low birth weight, shorter gestational age, and congenital malformations
  • The risk of malformations is related to the subfertility rather than the procedures or treatments
  • Long term development is sparsely investigated and few have studied children born after induced ovulation
  • The overall long term development of children born after IVF/ICSI is comparable with that of children conceived spontaneously
  • Children born after induced ovulation seem to have a small increased risk of autism, hyperkinetic disorders, conduct, emotional or social disorder, and tic disorders, but the absolute risks are low
  • Source: BMJ

What this study adds

 

Live-Birth Rates After Assisted Reproductive Technology Can Approach Natural Rates.


Live-birth rates after assisted reproductive technology can approach those seen after natural conception, according to a New England Journal of Medicine study.

Using registry data, researchers estimated cumulative live-birth rates for almost 250,000 women undergoing more than 470,000 assisted reproductive cycles from 2004 through 2009.

Among the findings:

  • Nearly 60% of women had a live birth.
  • When autologous oocytes were used, birth rates declined with increasing maternal age.
  • When donor oocytes were used, birth rates were over 60%, regardless of patient age.

In Journal Watch Women’s Health, Dr. Robert Rebar writes: “Although live-birth rates with assisted reproductive technology have improved impressively, procedures remain stressful and costly, and discontinuation rates are high.” Nonetheless, he adds, “this study confirms just how much these procedures have advanced; furthermore, the findings make a strong case for encouraging use of donor oocytes in infertile women who are 43 or older.”

Source:NEJM