A study was done in 2009 to determine whether a policy of elective single-embryo transfer (e-SET) in IVF lowers the rate of multiple births (twins, etc.) without compromising the live birth rate. Elective single-embryo transfer (e-SET) is the transfer of one embryo into the uterus during IVF as compared to two.

Risks of multiple births:

Double embryo transfer (DET) in IVF increases the chance for multiple births. With this increased chance come increased risks for the children and the mother.

• higher prematurity risk
• low birth weight
• neurological disorders
• birth defects
• long-term medical problems

• pregnancy induced hypertension / pre-eclampsia
• gestational diabetes
• anemia
• caesarean section
• Blood loss during delivery

Sadly, twin babies are seven times more likely to die in the neonatal period (from birth until 28 days) compared with single born children. As one would expect, with an increase in the size of the multiple birth (triplets, etc.) comes an increase in these risks.

IVF Study Findings

The number of IVF attempts needed to achieve the same live birth rates is higher in women who have only one embryo transferred. In other words, the chance for an IVF pregnancy is lower when only one embryo is placed into the uterus. On the other hand, there was a marked decrease in chance for a twin pregnancy.

In the U.S., the Society for Assisted Reproductive Technologies (SART) has guidelines for the correct number of embryos to be transferred in IVF cycles. Increased adherence to these guideline resulted in IVF twin rates decreasing from 24.3% in 2004 to 20.3%in 2006.

Moreover, the increasing use of the less costly, milder treatment protocols allows for more IVF cycles to be performed during the same period of time. This achieves a similar cumulative live birth rate compared with double embryo transfer (DET).

Materials and Methods

This particular analysis study searched databases for IVF studies published between January 1974 and September 2008. The data from the studies they found were combined into one large database. This is called a meta-analysis.

All studies that evaluated the effects of e-SET vs. double embryo transfer on pregnancy rate or live birth rate and multiple birth rate in IVF were looked at. The authors excluded nonrandomized studies and others that did not meet their particular criteria.

Outcomes Measured

• IVF live birth rate per patient
• IVF multiple birth rates per total number of live births

• Implantation rate: number of gestational sacs with fetal heart beat seen on ultrasound divided by the total number of embryos transferred.
• Pregnancy: a positive urine test (b-hCG level) 14 days after embryo transfer.
• Clinical pregnancy: visualization by ultrasound of a gestational sac with a fetus and fetal heart movements at 6 weeks gestation.
• Ongoing pregnancy: at least one gestational sac with a visible fetal heart beat beyond 12 weeks gestation
• Miscarriage and ectopic pregnancy: a pregnancy that is lost or found to be growing outside of the uterus and is therefore nonviable
• Preterm Delivery: less than 37 weeks of gestation per live birth
• Studies were conducted 1999-2008
• Mean number of participants =225
• Embryos were implanted on day 2 to 3 after the egg retrieval
• The age range of the subfertile women was 30-36
• Implantation rate: no difference between e-SET and DET
• Pregnancy Rate/patient: 2/3 of the studies that reported on it showed a reduction in the chance for pregnancy with e-SET compared with DET
• Miscarriage and ectopic pregnancy rate: no difference between e-SET an DET

Results

7160 available publications were found after the searching of the data bases. The titles of these were examined to exclude irrelevant papers resulting in 39 potentially eligible studies. Seven Randomized control trials (RCTs) were included in the systematic review. An RCT is a type of study in which the patients are assigned to the different treatment groups at random. This helps reduce the chance for the results to be biased. Of these ONLY 6 were included in the meta-analysis.

Statistics Found

• Live birth rate per patient:(documented in all except one trial) ranged from 20.7% to 30.0% in the e-SET group and between 31.7% and 47.4% in the DET group.
• Multiple birth rate per total number of live births: was assessed in all 6 studies and ranged between 0 and 4.5% in the e-SET group and between 16.4% and 39.3% in the DET group.

The investigators in the two larger trials observed a statistically significant reduction in the likelihood of live birth after e-SET compared with DET.

Other Outcomes

• Implantation rate: no difference between e-SET and DET
• Pregnancy Rate/patient: 2/3 of the studies that reported on it showed a reduction in the chance for pregnancy with e-SET compared with DET
• Miscarriage and ectopic pregnancy rate: no difference between e-SET an DET

Discussion

Bottom Line

This meta-analysis demonstrates that, in women younger than 36 years, e-SET of cleavage stage embryos reduces the likelihood of live birth by 1.5 times and multiple birth by 17 times as compared with DET.

Financial Burdens to Consider

Most couples welcome twins regardless of the risks especially if they are only entitled to one round of IVF treatments. Knowing that choosing DET over e-SET increases the probability of live birth discourages couples from having e-SET.

The problem lies in the fact that the costs of antenatal and neonatal care for multiple pregnancies are a financial burden on the government and on society as a whole. Not to mention, the risks are far greater.

It has been noted that couples who get their treatments paid for are two times more likely to go through e-SET than those who self-fund their own treatments.

Conclusion

The transfer of a single, good quality embryo selected using objective methods will be a central part of IVF treatment in the years to come. In contrast to many areas of reproductive medicine and infertility where additional evidence is often sought and further trials are warranted, we believe there now is sufficient information to offer e-SET practice in selected, good-prognosis women who are undergoing IVF treatment. Patients must be counseled that the chance for pregnancy is lower and more attempts may be required to achieve pregnancy.

In the future, we hope that new technologies will enable better selection of embryos and thus improve the chances for IVF pregnancy with a single embryo.