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DATA

How likely is it that IVF will result in multiple births and how can we tell?

B.A. Malizia, L.E. Dodge, A.S. Penzias, M.R. Hacker

July 12, 2016
Emma Holt

Multiple Births after in vitro Fertilization (IVF)

Multiple pregnancies are a well-known significant effect of IVF.  But is it possible to calculate the probability of liveborn multiples after IVF?  A team of medical professionals and one science doctor estimated the cumulative probability of liveborn multiples after IVF and hope this knowledge will improve counseling of IVF patients by healthcare providers.

The Research

In February 2013, a scientific study entitled “The cumulative probability of liveborn multiples after in vitro fertilization: a cohort study of more than 10,000 women” was published in the journal Fertility and Sterility.  The four researchers and authors of this study set the objective of estimating cumulative probability of liveborn multiples after IVF with the goal of improving patient counseling.  Put simply, a liveborn multiple pregnancy is any pregnancy that results in the birth of more than one baby.  Liveborn multiples include twins, triplets, or higher-order multiples (quadruplets, quintuplets, etc.).  The number of multiple-gestation pregnancies and liveborn multiples from assisted reproductive technology (ART), such as IVF, has been on the decline since 1997, but a significant number of pregnancies occurring after ART still involve liveborn multiples.  Liveborn multiples are conflictingly viewed as a joyful occurrence (or perhaps surprise) and a strain on parents, physicians, and the health system.  The authors continue to state that liveborn multiples are often sensationalized by the media (i.e. Octomom), which leads people to view these types of births as rarer than they actually are following ART.  Even with this sensationalism of liveborn multiples after ART, patients still rarely understand its importance before IVF and other ART treatments. 

Who did the researchers study?

To better inform patients about the possibility of liveborn multiples, the authors of this study sought to report the cumulative probability of liveborn multiples within a large cohort of 10,169 women throughout their entire course of treatment.  This study was a retrospective cohort study.  This means that rather than assign individual women to different groups to receive different treatments, the researchers formed and studied a retrospective cohort by observing all women who had already elected to undergo their first, fresh nondonor IVF cycle.  All women at Boston IVF from January 1, 2000 to June 30, 2010 who were undergoing the stated treatment were followed for at least one year after their first IVF cycle.  The observation continued until treatment was discontinued or a live infant was delivered; whichever incident occurred first marked the stopping point for the observation.

Standard IVF procedures were utilized at the medical center.  The first treatment cycle was fresh embryo transfer, but the following cycles (if a patient continued treatment) could contain frozen embryo transfer cycles.  The researchers collected data on patient characteristics, details of each IVF cycle, and pregnancy outcomes from the patients’ medical records.  Levels of β-hCG was used to mark pregnancy.  Number of gestational sacs and fetal heartbeats were used to indicate number of gestational embryos.

What did the researchers find?

The researchers found the total cumulative live birth rate of the 10,169 women (who underwent up to six IVF cycles) to be 73.8%.  When the authors stratified this number by number of liveborn infants, they found that the cumulative live birth rate for singleton births was 52.7%, for twins was 19.8%, and for triplets was 1.3% (no woman was observed to have more than 4 fetal heartbeats on any ultrasounds).  The authors further note that the twin cumulative live birth rate doubled in cycles one to three; this rate of increase slowed for the rest of the cycles (cycles 3 to 6).  In contrast, the triplet cumulative live birth rate doubled from cycles 1 through 3 only to double again in the remaining cycles 3 through 6.  No births of more than three infants occurred in this study, although births of more than three infants following IVF have been documented prior (again, i.e. Octomom). 

Researchers found that the number of fetal heartbeats does not guarantee the number of liveborn multiples a woman will have.  For example, twelve women in the study had more than three fetal heartbeats at the first ultrasound, and 66.7% of these women were found to deliver twins.  The authors do state that they did not allow for an investigation as to how this reduction from fetal heartbeats to liveborn multiples occurred, so it was not possible to tell if these reductions had been performed medically at the patients’ requests or if they occurred spontaneously.  As stated by the authors, medical reductions pose ethical, legal, and/or personal concerns for some couples, and an ability to estimate the likelihood of liveborn multiples could help circumvent this issue.

For women who employed their own oocytes (eggs) for IVF, it was found that overall cumulative live birth rate decreased as the women’s age increased.  Put simply, women who used their own oocytes for IVF treatment and who were older had a lower cumulative live birth rate than younger women.  This pattern remained true for liveborn multiples as well.  Women under the age of 35 were deemed to have the highest absolute risk of liveborn multiples, but this cumulative rate of liveborn multiples was found to be only 20.6% after three IVF cycles and 26.8% after six IVF cycles.  Women aged 40 or higher had the lowest absolute risk of liveborn multiples, and this cumulative rate of liveborn multiples was found to be 5.2% after three IVF cycles and 9.5% after six cycles of IVF treatment. 

Reflection

It is of great value to note the author’s caveat that the cumulative live birth rates reported in this study may not be applicable on a national or global scale, for Massachusetts (the study location) had lower per cycle rates for pregnancy, live birth, and multiple live birth than that reported in national summary data in 2009.  Additionally, the authors state that the statistical analyses used in the study could have led to overestimates of cumulative live birth rates.  The large number of women studied and the use of both fresh and frozen embryo transfer data lend strength to this data, but the study’s possible limitations must not be overlooked.  Scientific research is a continuous endeavor that shifts and changes as new knowledge is acquired, so it is possible that even more accurate estimates of cumulative probabilities of liveborn multiples may exist in the scientific literature today.  Your doctor may be aware of such probabilities, and you should always address any questions, concerns, or relevant information you find regarding your treatment plan with your doctor.  Perhaps even mention this specific article and ask for your doctor’s opinions at your next visit.

You may choose to use this information to discuss your treatment plan with your doctor, for the information provided here is meant to empower you and inform you about the research conducted regarding fertility.  This information is provided in the hope that you can have discussions with your doctor and advocate for yourself, but it is not meant to serve as a medical recommendation.  Please always consult your doctor prior to deciding on a treatment plan that is the best option for you and your body. 

Stay informed, stay empowered, and good luck on your journey.

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