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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Dec 5, 2013

 

More than a third of twin births and more than three-quarters of triplets or higher-order
births in the United States in 2011 were the result of fertility treatments.







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IVF fertility treatments keep multiple births high

Non-IVF treatments are biggeat contributor with ovarian stimulation and ovulation induction. But, fertility technology in the United States has a huge influence on the frequency of twins, triplets, and other multiple births.

New estimates of fertility technology are published Dec. 5 in the New England Journal of Medicine. Dr. Eli Y. Adashi, professor of obstetrics and gynecology at Brown University, and his colleagues calculated that more than a third of twin births and more than three-quarters of triplets or higher-order births in the United States in 2011 were the result of fertility treatments.


The proportion of triplets or more related to medical assistance has actually dropped from a peak of 84 percent in 1998 after in vitro fertilization (IVF) guidelines discouraging implantation of three or more embryos took effect that year, the study reports.

IVF has also improved enough that single embryo transfers now often succeed in producing healthy pregnancies.

But in the meantime, non-IVF fertility treatments such as ovarian stimulation and ovulation induction — for instance, with the drug clomiphene citrate — have increased to become the predominant source of medically assisted multiple births in the country while IVF is increasingly producing twins.


Some mothers and couples may hope for twins through fertility treatments, Adashi said, but more often multiple births are not desired. In those cases, he said, the new parents and children incur unwarranted medical risk and long-term financial costs that doctors should strive to prevent.

"We do have a real problem with way too many multiple births in the United States with consequences to both mothers and babies," said Adashi, the study's senior author and former dean of the Warren Alpert Medical School of Brown University. "It's an unintended consequence of otherwise well intentioned and remarkable technology."

To arrive at their estimates, the team, including lead author Aniket Kulkarni of the U.S. Centers for Disease Control and Prevention, gathered data on multiple births from 1962 to 1966 (before any medical fertility treatments were available) and from 1971 through 2011.


Data on IVF procedures has been available since 1997, but no data is available that directly reflects the contribution of non-IVF procedures to rates of multiple births.


The team therefore estimated the role of non-IVF technologies by subtracting the multiple births arising from IVF from the overall number of multiple births, while also accounting for the impact of maternal age on birth plurality. The data from the 1960s, meanwhile, provided a statistical baseline for natural multiple birth rates without medical intervention that the team also used in their estimates.

Multiples multiply

The contribution of fertility treatments over the last 40 years is unmistakable: Between 1971 and 2011, the percent of U.S. births that were multiples doubled to 3.5 percent from 1.8 percent. Even after adjusting for maternal age, the rate of twin births rose 1.6 times between 1971 and 2009, the authors reported.

And while triplets or more due to IVF have dropped to 32 percent of cases from 48 percent between 1998 and 2011, the percent of triplets or more due to non-IVF procedures rose to 45 percent of cases from 36 percent during that same time.

"IVF is moving, in a sense, in the right direction and cleaning up its act, whereas the non-IVF technologies are at a minimum holding their own and possibly getting worse," Adashi said. "From a policy point of view what that means is that [we] need to focus on the non-IVF technologies, which really hasn't been done in a concerted way because they weren't considered all that relevant to this mix."


Ultimately, Adashi said, it may be harder to curb multiple births from non-IVF treatments than from IVF.

While multiple births from IVF are a direct result of the number of embryos that are fertilized and intentionally implanted, non-IVF therapies involve medications that stimulate ovulation and follicle growth in ways that cannot be precisely predicted or controlled.


The new estimates will at least focus more attention on the major contribution non-IVF treatments make on multiple births, the authors wrote. That may spur improved data gathering, such as creation of a registry of non-IVF treatments and outcomes, and ultimately more careful practice regimens.

"Increased awareness of multiple births resulting from non-IVF fertility treatments may lead to improved medical practice patterns and a decrease in the rate of multiple births," the paper concludes.

Abstract
BACKGROUND
The advent of fertility treatments has led to an increase in the rate of multiple births in the United States. However, the trends in and magnitude of the contribution of fertility treatments to the increase are uncertain.

METHODS
We derived the rates of multiple births after natural conception from data on distributions of all births from 1962 through 1966 (before fertility treatments were available). Publicly available data on births from 1971 through 2011 were used to determine national multiple birth rates, and data on in vitro fertilization (IVF) from 1997 through 2011 were used to estimate the annual proportion of multiple births that were attributable to IVF and to non-IVF fertility treatments, after adjustment for maternal age. Trends in multiple births were examined starting from 1998, the year when clinical practice guidelines for IVF were developed with an aim toward reducing the incidence of multiple births.

RESULTS
We estimated that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from 1998 to 2011. This decrease coincided with a 70% reduction in the transfer of three or more embryos during IVF (P<0.001) and a 33% decrease in the proportion of triplet and higher-order births attributable to IVF (P<0.001).

CONCLUSIONS
Over the past four decades, the increased use of fertility treatments in the United States has been associated with a substantial rise in the rate of multiple births. The rate of triplet and higher-order births has declined over the past decade in the context of a reduction in the transfer of three or more embryos during IVF. (Funded by the Centers for Disease Control and Prevention.)

In addition to Adashi and Kulkarni, other authors on the paper are Dr. Denise Jamieson, Dr. Dmitry Kissin, and Maria Gallo of the CDC; Dr. Howard Jones of Johns Hopkins School of Medicine; and Dr. Maurizio Macaluso of Cincinnati Children's Hospital Medical Center.