August 2012 eNews
Breaking It Down: The Truth about IVF and Birth Defects
By Harvey J. Stern MD, PhD
On May 5th of this year an article entitled "Reproductive Technologies and the Risk of Birth Defects" was published in the New England Journal of Medicine by Dr. Michael Davies and colleagues from the University of Adelaide in South Australia. Release of this report was carefully orchestrated to receive maximal media attention and headlines proclaimed that "fertility treatments caused an increase in birth defects in the resulting children." Naturally, couples currently engaged in in-vitro fertilization (IVF) cycles as well as those considering IVF with or without intracytoplasmic sperm injection (ICSI), or other assisted reproductive technologies (ART) were very concerned by the reports on the news and in the press. It is important, however, to look past the media "sound-bites" and look critically at what the studies are actually saying. I am reassured by this and another recent study (see below) that ART procedures are safe and do not in themselves produce an increase in birth defects in children.
Before looking at the studies, it will be helpful to define a few terms frequently used in medical epidemiology studies such as these. When one is comparing a specific outcome, such as a birth defect, in two populations of patients (for example, IVF versus natural conception), one will describe a relative risk, (RR) or the risk in one population compared to another. Again using birth defects and IVF, one would calculate the risk in IVF children divided by the risk in naturally conceived infants. If the risks are equal, the RR is 1. If a risk is twice as high in IVF pregnancies versus natural conception, the relative risk (RR) is 2. A RR of 1.2 would indicate a risk that is 20% higher. The importance of RR is related to the actual occurrence of the outcome in the population. Birth defects are seen in approximately 3% of newborns, a relatively rare event. A 20% increase in this risk (3.6%) will still result in a rare event. For this reason, clinicians are most interested in findings that indicate a 4 to 10-fold increase in risk (RR of 4-10) when considering rare events. A second factor in understanding RR is related to adjustments that are made to collected information to account for differences between the groups being compared such as smoking, hypertension, history of premature delivery, diet, BMI, toxic exposures etc. The result of the analysis is called the multivariate-adjusted RR and generally is the most accurate representation of the collected information. OK, enough technical stuff!!
The study in the New England Journal of Medicine compared the observed rates of birth defects in children (followed from newborn to 5 years) and terminations of pregnancy in patients in South Australia undergoing IVF (with or without ICSI) versus that in children conceived spontaneously. The total population included 309,000 births with approximately 6,200 (2%) resulting from assisted reproduction. Detailed records of all IVF cycles as well as records of birth defects in all liveborns and fetuses are kept in a South Australia Health Department database and were available for review. Among the total IVF cases (+/-ICSI), birth defects were seen in 8.3% of pregnancies compared with 5.8% in spontaneously conceived children (RR 1.43). The adjusted RR was 1.28. When further analyzed, the adjusted RR for IVF was 1.07 and for ICSI/IVF was 1.57. The authors concluded that there is an increased risk of birth defects among births achieved with assisted reproduction as compared to births resulting from natural conception. After adjustment for confounding factors, however, the difference between natural conception and IVF conception was no longer significant, however the birth defect rate when ICSI was used remained significantly above that of spontaneously conceived children.
First of all, is this information new? Actually, no. For many years it has been known that there is a slight increase in the incidence of birth defects after ART. In 2002, Hansen and colleagues published a study (again in the New England Journal of Medicine, and again with much media attention) entitled "The Risk of Major Birth Defects after ICSI and IVF." Their study from Western Australia (I guess it's a big country) was similar, but much smaller with about 5,100 infants of which about 1,100 were conceived by ART. Their results showed the adjusted RR for birth defects in IVF or IVF with ICSI was 2. In contrast to the 2012 study, there was no difference in risk for IVF with or without ICSI.
The major question that was raised at the time was whether the increase in birth defects was caused by the ART procedures themselves versus genetic factors intrinsic to the couple and likely responsible for their infertility. The 2012 article gives us a hint. As part of their data collection, the group was able to collect information on the reproductive outcomes of former successful IVF patients who subsequently conceived spontaneously, as well as couples given a diagnosis of infertility but who did not receive any ART treatment prior to spontaneously conceiving. In both cases, the adjusted RR for birth defects compared to a group with spontaneous conception without an infertility history was 1.2-1.3. This indicated that just having a diagnosis of infertility was associated with an increased risk of birth defects in children even in pregnancies where ART was not used. The factors that cause infertility in couples, not the ART procedures themselves, are responsible for the increased risk of birth defects. This is consistent with what most clinicians in reproductive medicine currently believe.
Shortly after the Davies study was released, another study was published in the journal Fertility and Sterility by Wen and colleagues from Nanjing University in China. The authors reviewed all medical literature published on IVF and birth defects through September 2011 and for those reports meeting certain criteria, the data was pooled into what is called a meta-analysis. In this case, data from 46 different studies including 140,500 infants conceived with ART were compared to spontaneously conceived children. The total adjusted RR for ART procedures versus spontaneous conception was 1.36 which is similar to that of the Davies study (1.28). When comparing IVF versus IVF with ICSI, however, there was no difference in risk (RR 1.05).
The take-home message is that couples who need assisted reproduction to conceive have a slightly higher risk of having children with birth defects than couples able to conceive on their own. However, the actual risk remains relatively small. The increase in risk attributed to ICSI in the Davies study was not confirmed in the larger meta-analysis of Wen. It's important to remember that having children whether spontaneous or assisted always involves some risk. Overall, couples who need to rely on ART for building their family should feel no hesitation about their medical treatment.
Dr. Harvey J. Stern is the Director of Reproductive Genetics at the Genetics & IVF Institute.
What's New at GIVF
GIVF a Leader in a Quickly Emerging Field
Using an Egg Donor to Conceive Has Nearly Doubled Across the U.S.
Couples looking to conceive are relying more on egg donors to help build their family. The CDC recently announced that the use of donor eggs has nearly doubled since 2000, increasing 80.5%. GIVF is a specialist in Donor Egg IVF for many reasons. One indicator is that we have the highest percentage of Donor Egg IVF cycles to total cycles in the top 50 fertility clinics. In other words, we do more Donor Egg IVF cycles inside our doors than anything else, which makes our doctors, nurses, and egg donor coordinators extremely knowledgeable and efficient.
We are also among the highest in the U.S. when it comes to success rates for donor egg, have a large group of high quality donors available immediately, and offer the options to do a fresh transfer or use frozen eggs through our in-house Fairfax Egg Bank®. GIVF was the first clinic in the Mid Atlantic region to offer an egg bank for frozen eggs. Not to mention that we have some tremendous donor egg coordinators who offer personal attention for both the donor and the recipient. We are proud to offer the best Donor Egg IVF program in the nation.
Finding Cancer Early and Saving Lives in Sierra Leone
GIVF is proud to support this mother’s and children's health initiative.
Medical care for women in Sierra Leone is scarce. In fact, one mammography machine serves the entire country. Cervical cancer, which is generally curable if caught early, kills nearly 70% of the women who are diagnosed. In sharp contrast, almost the same percentage, 69% of women in the U.S. diagnosed with cervical cancer will live. The importance of screening and early detection is staggering.
Helping Children Worldwide and a medical team led by four Northern Virginia physicians are working to change that. With support from the Genetics & IVF Institute and other donors, they have launched a breast and cervical cancer screening program in Sierra Leone.
Cancer diagnosis and treatment are becoming priorities for the Ministry of Health in Sierra Leone, but resources are limited and medical personnel often lack adequate training. To train local medical personnel and provide lifesaving services for women, volunteer physicians traveled to Sierra Leone's second largest city, Bo, with $45,000 of donated supplies and equipment. Dr. Mary Beth Cantwell, anesthesiologist at Fairfax Anesthesiology Associates, Dr. Cynthia Horner, Family Medical Director at Herndon Family Medicine, Dr. Carol McIntosh, OB/GYN at Inova Fairfax Hospital, which is a founding shareholder of GIVF, and Dr. Kirsten Edmiston, medical director of Inova Cancer Services and a specialist in breast and cervical cancer, and four other medical workers are committed to saving lives in Sierra Leone.
Working with local medical staff and government representatives at Mercy Hospital in Bo, which was built by Helping Children Worldwide, the visiting medical team taught women how to do breast self exams and performed PAP smears, breast surgeries, and cervical cauterizations. They brought biopsies and PAP smears back to Virginia for testing. The doctors are continuing to provide support for medical staff in Bo by communicating via telemedicine to help make diagnoses and advise on treatment. The team is also working to help design a new surgery center at the hospital in Bo.
For Dr. Edmiston and others, the work has just begun. Dr. Edmiston says, "When I went there, I saw that this is an area with tremendous need where we can really make a difference and improve people's lives. With help from donors like GIVF and others who support the work, we can continue to help." She says that the team plans to return to Bo next year to continue to train personnel and treat patients.
GIVF President David Wise, says, "We applaud both Helping Children Worldwide and the wonderful volunteer medical team for their exceptional work and are proud to support them. GIVF is dedicated to improving women's health in the U.S. and abroad."
To learn more about Helping Children Worldwide, please visit www.helpingchildrenworldwide.org. You can also check out their August newsletter here.
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