Double Embryo Transfer after IVF vs. TWO-Single Embryo Transfers: time to refine our definition of treatment success

Fertility treatment in the USA has always been different from most of the rest of the world. Although the first IVF pregnancy was conceived in England; the first IVF pregnancy involving ovarian stimulation  to produce more eggs occurred in Norfolk, VA in 1981. Thus began the modern trend of producing multiple embryos in order to boost the chance for a pregnancy. We’ve achieved that goal. As I wrote about several months back fertility treatments have become both safer and more successful. Yet pregnancy following IVF still has higher risks than naturally conceived pregnancies. New data now supports that lowering the number of embryos transferred per cycle may be the key to both higher pregnancy rates and lower risks. Here’s what we now know.

Multiple pregnancies—twins in particular—remain fairly common after IVF. In 2013, (the most recent year that we have outcome data available for ) most embryo transfers involved two embryos or dual embryo transfer (DET). Not surprisingly, the incidence of twins or higher order multiples nearly reached 30% of those that became pregnant. By comparison the natural incidence of twins is about 2%. One of the major factors that appear to drive this continued trend for twins over singletons is that most patients don’t have enough information available to them to make a fully informed decision of one vs. two embryos.  In fact as one recent editorial stated “it is not the fear of multiples that drives decisions about the number of embryos to transfer…but rather the fear of not conceiving at all .”

Many of the most successful programs have been urging their patients to consider single embryo transfer based upon their clinic-specific success rates. Some have even demonstrated that imposing a mandatory policy of single embryo transfer (SET) is well supported by patients in these settings . But now we have new data suggesting that patients at the typical center should also be considering SET.

A just published study  using the national database for IVF centers’ information gathered from 2006 to 2012 has provided new insights into live birth rates (LBR) from elective SET vs. DET. They demonstrated that LBR is as good as or better with two SET cycles than with one DET cycle. In fact, in some patients the LBR was up to 20% higher with an incidence of twins of around 1 to 3% (due to a single embryo splitting and forming identical twins). Other studies have also demonstrated that when two or more embryos are transferred, the excess embryos have a negative effect on the one remaining. This impact may manifest as a low birth weight, a higher risk of preterm labor or an elevated risk of miscarriage. It can even contribute as adverse neurologic effects on the embryo that survives to term; resulting in a child with cognitive or developmental impairment. The studies’ authors concluded that “success for modern IVF should be defined as a singleton pregnancy that results in a healthy singleton infant who is born at term.”

The greatest challenge toward achieving that goal remains the cost and availability of fertility services. Currently, only about a quarter of the states require insurance companies provide any coverage for fertility treatments. However, databases  demonstrate that in states where IVF is covered by insurance; fewer embryos are transferred per cycle and lower multiple gestations occur. This actually lowers the cost to insurance companies since there is universal coverage mandated for pregnancies and singleton pregnancies cost less. Therefore, the burden for the cost of multiple pregnancies tends to fall back upon the insurance companies that often opposed providing the fertility treatment as a covered benefit. Hopefully, as this information becomes more widely available we will see more patients choosing SET as the best outcome; instead of simply making a choice based upon personal financial pressures  which are becoming more a by-product of where they live .

[r1]Link to first IVF  http://www.fertstert.org/article/S0015-0282(07)02985-8/fulltext

[r2]Link to https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0

[r3]http://www.ajog.org/article/S0002-9378(15)00248-3/abstract

[r4]http://www.fertstert.org/article/S0015-0282(11)02256-4/fulltext

[r5]http://www.ajog.org/article/S0002-9378(15)00127-1/abstract

[r6] http://www.asrm.org/insurance.aspx

[r7]http://www.fertstert.org/article/S0015-0282(10)00983-0/abstract

[r8]http://familybuilding.resolve.org/fertility-scorecard

HORMONE HAPPENINGS—Greene Guide’s News Recap

It’s time to review the latest findings in Reproductive Medicine. This month there are new insights into why more boys are born in the US than girls as well as a new strategy for women undergoing fertility treatment to reduce the risk of having a child with autism. As always, I have included links to the studies for you check them out for yourself:

  • More Boys are Born than Girls; here’s why—about 51% of all of the babies born are male. This observation has been consistent for several hundred years.  A new study  has provided the most comprehensive data to explain why we don’t see an equal number of boys and girls in the delivery room. It turns out that the explanation is based upon what happens during pregnancy; not prior to fertilization as previously assumed. The researchers found that although a higher number of male are lost during the first trimester; female fetuses are more likely to miscarry later in pregnancy. The end result is that a slightly higher number of males survive until birth than females.
  • Supplementing Estrogen Does Not Improve Pregnancy Outcome—there has long been debate amongst fertility centers as to whether or not additional estrogen is beneficial to pregnancy rates. New data  shows that levels higher than the normal physiologic ones are not helpful. Other studies have suggested the extra estrogen may even boost the risk of blood pressure problems later in pregnancy. Combined these findings support the ongoing trend to create a hormonally balanced environment rather than simply adding more.
  • Genetic Testing improves Live Birth Rate in Women over 40—using pre-implantation genetic screening (PGS) to identify the healthiest embryos for transfer is an effective tool according to new information . They demonstrated a live birth rate that was three times higher using this technique then using standard IVF alone for women over 40. This means that identifying healthy embryos prior to transfer is a highly effective strategy to achieve a successful birth.
  • Single Embryo Transfer associated with Lower Risk of Autism—previous data has suggested that there may be a higher risk of Autism Spectrum Disorder (ASD) associated with advanced reproductive techniques (ART). Other studies have shown that this is more likely age related or that it might be due to the population of patients seeking fertility treatment. This new study  found that when only singleton pregnancies result following IVF; the observed risk disappears. This is another good reason to consider elective single embryo transfer (ESET).
  • Vitamin D Deficiency associated with Lower Pregnancy Rate in IVF—a comprehensive review  of 34 published trials has found that women with lower than normal vitamin D levels have less success when undergoing IVF treatment. There is not yet proof that supplementing with vitamin D reverses this trend. However, given the other health benefits and the low cost of this “sunshine hormone” it sure makes sense to consider vitamin D supplementation for women whose level is lower than normal.
  • Smoking during Pregnancy can have Lasting Effects Upon your Child—it has long been recognized that women that were smokers had lower fertility rates, higher miscarriage rates and earlier onset of menopause than nonsmokers. New information  now suggests that at least some of these negative reproductive effects can be passed on their children as well. Specifically, they found girls born to women that smoked had an earlier onset of puberty than those born to nonsmokers. Noted by the investigators was that early onset of puberty is also linked to a higher risk of certain types of cancer including breast cancer.

[r1]Link to http://www.pnas.org/content/early/2015/03/27/1416546112

[r2]Link to http://link.springer.com/article/10.1007/s10815-014-0402-1?wt_mc=alerts.TOCjournals

[r3]Link to http://link.springer.com/article/10.1007/s10815-014-0417-7?wt_mc=alerts.TOCjournals

[r4]Link to http://consumer.healthday.com/cognitive-health-information-26/autism-news-51/ivf-kids-have-higher-odds-of-autism-study-finds-697622.html

[r5]Link to http://link.springer.com/article/10.1007/s10815-014-0407-9?wt_mc=alerts.TOCjournals

[r6]Link to http://www.reuters.com/article/2015/03/19/us-womens-health-smoking-pregnancy-idUSKBN0MF29W20150319