Single Embryo Transfer
By Karen Synesiou, CFO, Center for Surrogate Parenting, Inc.

Single Embryo Transfer – the time has come

Pros and Cons

After years of suffering from infertility, many couples turn to surrogacy as the only alternative to creating a biological child of their own. Unfortunately, failed IVF cycle after failed IVF cycle, or one miscarriage followed by another will have exhausted many couples before they begin the journey through surrogacy. In addition, the financial burden added to the emotional cost of repeated IVF cycles can rapidly drain a couple's resources. It is therefore easy to understand why so many couples hope for a twin surrogacy pregnancy. The toll of infertility results in many couples willing to accept the risk of multiples, but at what cost?

This article will look at the option of implanting a single embryo and the risks associated with a twin or other multiple pregnancy. It is easy to understand that the larger the number of embryos implanted the larger the risk of multiple embryos implanting and therefore the riskier the pregnancy is for the surrogate mother and the unborn babies. A single embryo transfer resulting in a single gestation is logically less risky than carrying sextuplets.

Typically an infertility doctor in the United States will implant 2-5 embryos back into a woman’s uterus. It is commonly believed that the larger the number of embryos implanted, the higher the chance of obtaining a pregnancy.

Now a growing body of research suggests that, ultimately, implanting one embryo is just as likely to lead to a pregnancy as implanting multiple embryos. In addition this research suggests that the likelihood of multiple births, premature birth and low birth weight increases with the number of embryos implanted during an IVF procedure.
(http://www.cbsnews.com/stories/2007/10/05/health/webmd/main3336719.shtml)
(The New England Journal of Medicine Volume 351:2392-2402 Dec 2, 2004 Number 23)

NOTE: Common to almost all the research is the criteria for patient selection for Single Embryo Transfer: All candidates in this group should only include women who are at the highest risk of multiples and the lowest risk of reduced pregnancy rates/miscarriages:
  • Eggs from a woman who is 35 years old or younger

  • Women who produce at least five embryos of good quality

  • Women with a high likelihood of implantation (this would include the category of surrogate mothers.)

  • Women with normal FSH levels, who easily become pregnant but experience frequent miscarriages and are now working with a surrogate mother.



In a recent survey of women being treated for infertility, 20 percent said they would prefer multiples to a single baby. Less than half were aware of the health problems associated with twins, including an increased risk of cerebral palsy and low birth weight. (www.seattlepi.nwsource.com)




Are multiple pregnancies riskier than single pregnancies?

While the great majority of multiple pregnancies result in healthy babies, any pregnancy with twins or more is considered high risk. The more babies being carried, the higher the risk of complications. Babies born before their time are usually not completely ready for the outside world. Their lungs, brain, and other organs may not be fully developed, their immune system may not be ready to fight off infections, and they may not be able to suck or swallow.

Due to limited size of the mother’s womb, multiple pregnancies are much less likely to carry to full term than singleton births. Twin pregnancies are generally delivered 3-4 weeks earlier than a singleton pregnancy. The earlier a baby is born, the greater the health consequences for the babies. Premature babies born between 34 and 37 weeks gestation generally do very well. Babies born before 28 weeks may survive, but they'll need intensive medical care and a lot of luck.

What are the most common complications associated with multiples?
  • Preterm Labor/Delivery

  • Low Birth weight

  • Intrauterine Growth Restriction (IUGR)

  • Preeclampsia

  • Gestational Diabetes

  • Placental Abruption

  • Fetal Demise/Loss

  • Cesarean

  • Bleeding after Delivery

  • Costs


Let's look at each one of these risks to fully understand them.

Preterm Labor/Delivery:

Traditionally a pregnancy is considered full term at 40 weeks from the first day of the last menstrual period. (On the assumption that women have 28 day cycles and that conception occurred 14 days after the start of the menstrual cycle.) Therefore, when a woman is 10 weeks pregnant, she actually conceived 8 weeks ago. Based on this type of calculation, a pregnancy will have the expected date of delivery at 40 completed weeks but a pregnancy that has completed 37 weeks is considered full term already.

Preterm labor refers to contractions that begin to open the cervix before week 37 of the pregnancy. Preterm delivery is defined as delivery before 37 completed weeks of pregnancy. As can be seen from the chart below, the length of gestation decreases with each additional baby carried:

Type of Pregnancy Average GestationRisk Factor
Single baby 39 weeks -
Twins 35 Weeks 50%
Triplets 32 weeks90%


Note: In 2005 11% of singleton babies were born prematurely in the US, 62% of twins were delivered preterm, while 90% of triplets were preterm. Higher order pregnancies are almost always preterm. (www.marchofdimes.com/peristats - this is a very interesting site and I encourage you to visit it.)

Many times premature labor is a result of preterm premature rupture of the membranes (PROM), i.e. water breaking prior to 37 weeks of gestation. Usually a baby will be born within one week of the membrane rupture. Being pregnant with twins or triplets can cause PROM because the uterus becomes very big. (www.aafp.org/afp/20060215/665ph.html)

Complications of preterm birth include low birth weight, breathing and digestive difficulties, underdeveloped organs, learning disabilities and developmental problems.

Low Birth Weight:

Twins and triplets often do not have a chance to reach a healthy weight before they are born:

Type of Pregnancy Average Weight
Single baby 7 lbs
Twins 5.5 lbs
Triplets 4 lbs each


Babies born at under 5.5 pounds are considered to have a low birth weight. Only 6.4% of singleton (one baby) babies born in 2005 had a low birth weight whereas almost 60% of multiple births had a low birth weight. (www.marchofdimes.com/peristats)

Babies born before 32 weeks and weighing less than 3 pounds (1,500 grams) have an increased risk of developing complications as newborns as well as having long-term problems such as mental retardation, cerebral palsy, vision loss, and hearing loss.

Intrauterine Growth Restriction (IUGR):

Multiple gestations grow at approximately the same rate as a single pregnancy up to a certain point. The growth rate of twin pregnancies begins to slow at 30 to 32 weeks. Triplet pregnancies begin slowing at 27 to 28 weeks. Intrauterine growth restriction seems to occur because the placenta cannot handle any more growth and because the babies are competing for nutrients.

Preeclampsia:

Preeclampsia, Pregnancy Induced Hypertension (PIH), Toxemia, and high blood pressure are all synonymous terms. Preeclampsia is a disorder characterized by high blood pressure and protein in the urine. Preeclampsia reduces blood flow to the uterus, thus this condition may deprive the babies of oxygen and nutrients.

Type of Pregnancy Risk Factor
Single baby 5%
Twins 10-15%
Triplets 50%


This condition tends to develop earlier in twin pregnancies, and once it starts it can be especially severe. When preeclampsia is severe it can affect a woman’s organs and cause serious or even life-threatening problems.

Mothers who are pregnant with multiples are at extremely high risk for preeclampsia, also known as Toxemia or Pregnancy Induced Hypertension (PIH). In fact women expecting twins are more than twice as likely to develop this complication. (www.marchofdimes.com/professionals/14332_4545.asp). It typically occurs in the second half of pregnancy. Symptoms usually develop after the twentieth week of pregnancy and are typically detected during a routine checkup. They include water retention, puffiness in the hands or feet, elevated blood pressure, protein in the urine or a weekly weight gain of more than 2 pounds. More severe symptoms include: agitation or confusion, changes in the mother's mental state, nausea or vomiting, headaches, fatigue, abdominal pain, or shortness of breath.

What is the treatment?

Ultimately, the only way to "cure" preeclampsia is to deliver the babies. Doctors have to weigh the impact on the mother's health against the condition of the twins, or other multiples. In some cases, the condition can be controlled by moderating the mother's behavior: increasing her water intake, reducing her salt intake, or instituting a routine of bed rest while lying on her left side to limit pressure on major blood vessels. Her caretakers will also likely require more frequent office visits in order to monitor her blood pressure and urine protein levels.

In more severe cases, hospitalization may be required to ensure complete bed rest. Medications such as magnesium sulfate or hydralazine may be administered, although the side effects of these drugs can cause further medical issues. In the most severe cases, labor will be induced or a c-section will be performed.

What are the health effects on the mother?

Once the babies are delivered, the symptoms should subside and the mother's health would no longer be at risk. However, women are at risk for developing eclampsia up to six weeks after delivery of their babies; their doctors will continue to monitor their blood pressure during that postpartum period. If left unchecked, preeclampsia can damage the mother's kidneys, liver and brain.

What is the impact on the babies?

Because the "cure" for preeclampsia is delivery of the babies, they are at an increased risk for premature birth. While the impact of prematurity presents a variety of complications, remaining in utero presents its own set of risks. When blood flow to the placenta is restricted, the fetuses receive reduced oxygen and nutrients. This may produced babies with IUGR (Intrauterine Growth Retardation), low-birth weights or even stillbirths.

Gestational Diabetes:

The increased risk for gestational diabetes in a multiple pregnancy appears to be a result of the two placentas increasing the resistance to insulin, increased placental size, and an elevation in placental hormones.

Placental Abruption & Previa:

Placental abruption is when the placenta detaches from the uterine wall before delivery. It is three times more likely to occur in a multiple pregnancy. This may be linked to the fact that there is an increased risk of developing preeclampsia. Placenta abruption usually happens in the second half of the pregnancy and can lead to growth problems, preterm delivery or stillbirth.

In multiple pregnancies abruption is especially common just after the first baby has been delivered vaginally. Once abruption has occurred, the other baby will most likely be delivered via cesarean section.

With placenta previa, the placenta can implant low in the uterus, partially or completely covering the cervix. Placenta previa presents as painless bleeding and because the placenta is covering the cervix, a c-section may be necessary. This situation is more common in multiple pregnancies owing to the increased number and/or size of placentas present.

Iron-deficiency Anemia

The majority of women pregnant with multiples eventually develop iron-deficiency anemia, a condition characterized by low levels or iron in the red blood cells which carry oxygen to the tissues. The risk increases with each additional baby that is carried, particularly if you had low or borderline iron reserves before becoming pregnant. Symptoms include fatigue, light-headedness, pallor and shortness of breath. If untreated, anemia can adversely affect the babies' growth, as well as increase your own risk for complications both during the pregnancy and after the birth. This condition can be controlled by diet and taking iron supplements.

Fetal Demise or Loss:

In a twin pregnancy, one twin might miscarry early in the pregnancy while the other stays in place. This situation – vanishing twin syndrome – occurs in about 20% of all twin pregnancies.

Stillbirths — the loss of a baby after 20 weeks — are slightly more common in multiple pregnancies, but they are still rare. Only about 1 to 2 percent of twins or triplets are stillborn, compared with about 0.5 percent of singletons.

No special medical care usually necessary if the vanishing twin occurs in the first trimester. If the fetal death is in the second trimester then the pregnancy will most likely be treated as high-risk. Cerebral palsy may result in the surviving twin. (www.americanpregnancy.org/multiples/vanishingtwin.html)

Cesarean:

If you are pregnant with multiples it does not necessarily mean that there will be a cesarean birth. About 72% of women carrying twins deliver their babies by c-section versus 28% of singleton deliveries. (www.marchofdimes.com/peristats)

A more recent study suggests that cesarean delivery alone may be a risk factor for emergent peripartum hysterectomy (Excessive bleeding after delivery that cannot be controlled by conservative methods and is often a last resort to save the life of the woman). When compared to singletons, higher-order multiple gestations had a nearly 24-fold increased risk of emergent peripartum hysterectomy. (www.ncbi.nlm.nih.gov/pubmed/15932831?dopt=AbstractPlus).

Bleeding after Delivery

The risk of excessive bleeding after delivery increases with a multiple pregnancy due to the larger placental area, (usually two placentas) and due to the over distended uterus.

Costs

A 1994 study at the Brigham and Women's Hospital, Boston, analyzed the costs of over 14,000 births. They concluded that the charge for a singleton birth was $9,845, twins were $37,947 and triplets at $109,765. They concluded that multiple gestation pregnancies dramatically increased hospital charges and that the risks and costs associated with multiple gestation pregnancies cannot be ignored. (https://content.nejm.org/cgi/content/full/331/4/244?ck=nck)




Below is a brief outline of some recent research projects regarding implanting a single embryo versus implanting two embryos.

1. A six year study undertaken in Copenhagen:
(http://www.medpagetoday.com/OBGYN/Infertility/tb1/1228?pfc=101&spc=235)


This study found that the practice of implanting multiple-embryos led to a higher rate of multiple pregnancies. After studying pregnancies conceived through IVF, the researchers noted there was an increase risk in conceiving a multiple pregnancy as opposed to pregnancies conceived naturally. It was further noted that these pregnancies often resulted in higher risks of lower birth weights.

Clinicians in Copenhagen began a search into options to reduce the risk of multiples and the lower birth rates resulting from multiple gestations.

Results:

Spontaneous/NaturalSingle Embryo Transfer
Conception rates/cycle25% 46.4%
Birth weight(pounds) 7.34 7.32
Weeks of gestation 38.938.7
Chances of low birth weight 4.3%5.3%


Conclusion: The researchers compared the statistics of babies conceived naturally with babies born as a result of a single embryo transfer. The study found that infants born from single embryo transfers have a similar gestational age and birth weight compared with infants born from spontaneous/natural conception. Thus the fact that a baby was conceived through IVF was negligible with regards to causing birth risks.

2. A Study in Sweden
(http://www.medscape.com/viewarticle/495167, http://www.swedish.org/110325.cfm)

This study focused on how to reduce the risk of premature birth and perinatal death (fetal demise after 22 weeks gestation) in IVF. Prior studies had concluded that pregnancies conceived from an IVF cycle involving transferring more than one embryo resulted in a higher than average incidence of multiple gestations, premature births and birth defects.

Results:
Single EmbryoTwin Embryos
Conception rates/cycle38.8 42.9
Rate of twins 0.8 33.1


Conclusions: In women under 36 years of age, transferring one fresh embryo reduces the rate of multiple births: 0.8% versus 33.1%. Furthermore, the pregnancies achieved after a single embryo transfer were substantially similar to the pregnancy rate that is achievable with a two-embryo transfer: 38.8% versus 42.9%. The rate of twins was high (33.1%) when two embryos were transferred as compared with the rate of twins after a single embryo transfer (0.8%). In other words the rate of conceiving twins was drastically higher if two embryos were implanted. However the rate of achieving a pregnancy was not drastically increased by implanting two embryos. Thus, implanting two embryos only very slightly increases the chance of achieving a pregnancy but results in a drastic increase in the twin rate.

3. A Study in Scandinavia
(http://www.medicalnewstoday.com/articles/10107.php)

Over 660 women patients took part in this study. All the women were under 36 years of age, undergoing a first or second IVF cycle, and had at least two good quality embryos available for transfer or freezing. They had either two embryos implanted, or one embryo implanted and one frozen for use in a second transfer.

Single EmbryoTwin Embryos
Conception rates/cycle39.7 43.5


Conclusion: You get a very similar conception rate from single embryo transfers, but you do not have the high rate of multiple births and the resulting risks associated with premature birth.

4. A Study in Australia
(http://www.eurekalert.org/pub_releases/2003-06/esfh-sas062403.php)

Women who chose to have two embryos transferred in one cycle had a higher chance of success first time round – their live birth rate was 50% as opposed to 36% among the women who chose to have a single embryo transferred. But when the previously frozen embryos were subsequently transferred to the women who had failed to become pregnant in the first cycle, the cumulative live birth rates for both groups of women was 60%. In other words, a success rate of 50% is achieved if you implant 2 embryos in one transfer. However if you implant two embryos by implanting one embryo per transfer (in other words do two transfers) the success rate is 60%.
The study group comprised of 382 women: 107 chose single embryo transfers and 275 chose two embryo transfers. From the one embryo transfer: 3 sets of twins were conceived and delivered. From the two embryo transfers: 90 sets of twins were conceived, 4 resulted in miscarriages of both babies and 18 resulted in the loss of one twin.

Single EmbryoDual Embryos
Live birth rates after 1 transfer3650
Cumulative live birth rate (fresh & frozen cycles)6060
Rate of twins2.8%32.5%


Conclusion: Under the conditions of this study, twin pregnancies can be reduced drastically without compromising a patient's chance of a successful pregnancy. This is the first study to show that when counting frozen as well as fresh embryos, a single embryo transfer does not reduce the chances of having a baby. Currently, all patients under 38 years old are offered single embryo transfers and approximately 70% accept. They have an ongoing pregnancy rate of 40%.

5. Study at Brigham & Womens, New England

Brigham & Womens has developed an algorithm designed to select the optimum number of embryos to transfer in order to maximize the likelihood of pregnancy yet minimize the risk of a multiple pregnancy. This algorithm is used to identify those women who are optimal candidates to receive a single embryo transfer. Using the algorithm has resulted in a 41% success rate per egg retrieval, accompanied by a decrease in multiple-gestation rates to 3%. The national average multiple-gestation rate for IVF patients is around 40%.

6. Success rates for one embryo transfer at Seattle Reproductive Medicine:
(http://seattlepi.nwsource.com/local/212389_hcenter17.html)

By selecting the best candidates and transferring more mature embryos – blastocysts – 76% of women undergoing a single embryo transfer got pregnant, compared with 78% of those who received two.

Conclusion: As a result of all six studies above, from countries around the world, it can be clearly concluded that for certain candidates, a single embryo transfer is as successful as a multiple embryo transfer and avoids a multiple gestation with associated risks.




AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE
PATIENT’S FACT SHEET


Complications of Multiple Gestation

The American Society for Reproductive Medicine grants permission to photocopy this fact sheet and distribute it to patients.
(http://www.asrm.org/Patients/FactSheets/complications-multi.pdf)

The objective of infertility treatment should be the birth of a single, healthy child. Many of the treatment options presented to infertile couples, however, are associated with high risks of multiple gestation. Moreover, many couples view multiple gestation as desirable and are unaware of the risks they pose to both mother and babies. Couples should understand these potential risks before starting treatment.

Complications of the Fetus and Newborn with Multiple Gestation
  • Preterm birth occurs in over 50% of twin pregnancies, 90% of triplet pregnancies, and virtually all quadruplet pregnancies.

  • Compared to singleton pregnancies, a twin is seven times more likely and a triplet is over 20 times more likely to die in the first month of life.

  • Prematurity is associated with an increased risk of respiratory distress syndrome (RDS), intra-cranial hemorrhage, cerebral palsy, blindness, low birth weight, and neonatal morbidity and mortality. RDS accounts for 50% of all neonatal deaths associated with premature birth.

  • Intrauterine growth restriction, intrauterine death of one or more fetuses, miscarriage, and congenital anomalies are all more common.

  • Lifelong disability is over 25% for babies weighing less than 1,000 grams (2 lbs., 3 oz.).


Maternal Complications Associated with Multiple Gestation
  • Preeclampsia, also called pregnancy-induced hypertension, occurs three to five times more frequently. Severe preeclampsia may be life threatening.

  • Premature labor requiring prolonged bed rest or hospitalization is common.

  • Placental abnormalities associated with maternal hemorrhage are more likely to occur.

  • Gestational diabetes, anemia, and polyhydramnios (excess amniotic fluid) occur more frequently.

  • Cesarean section is often needed for twin pregnancies and almost always required for triplets.


Other Considerations
  • Multiple gestation is associated with more nausea and vomiting, anemia, fatigue, weight gain, heartburn, lack of sleep, depression, and marital discord.

  • Multifetal reduction may be advised for the health of the mother and to improve survival of the pregnancy. However, it is unclear how effective it is in reducing the rate of many of the above problems. Couples contemplating this option should consider counseling.


Prevention of Multiple Gestation

  • Careful monitoring during treatments with fertility drugs

  • Limit the number of embryos transferred during in vitro fertilization (IVF). Transfer of multiple embryos may not improve delivery rates but clearly increases the risk of a multiple pregnancy.





The American Society for Reproductive Medicine grants permission to photocopy this fact sheet and distribute it to patients.

If the IVF doctor supports the idea of single embryo transfer, more than 90% of patients proceed with that recommendation.
(http://www.cbsnews.com/stories/2007/10/05/health/webmd/main3336719.shtml)




Conclusion:

If you fall within the category below, serious consideration should be given to implanting one embryo at a time.
  • Age of woman producing the eggs is younger than 36 years

  • Chance of implantation is high


Therefore this article applies mainly to Intended Parents under the age of 36 years, or where an egg donor is helping. It is fair to state that all surrogate mothers, once they have passed their medical screening, have a very high chance of getting pregnant.

For patients over the age of 36 years and participating in gestational surrogacy the choice of how many embryos to implant is more difficult. Things to consider:
  • If you produce at least 5 good blastocysts and do not have a history of miscarriages, it is reasonable to consider implanting one embryo.

  • If you produce fewer than 5 blastocysts it is reasonable to implant two embryos.

  • If you can get pregnant quickly and easily, but have a history of miscarriage and you produce at least 5 blastocysts, it is reasonable to consider implanting one embryo.

  • If the woman producing the eggs is over the age of 38 years old, it is reasonable to consider implanting two embryos.


Each case should be treated individually and consideration should be given to
  • the cause of infertility

  • age of the woman producing the eggs

  • previous childbirth and date of last pregnancy, if applicable.

  • Age of intended parents




The question each couple needs to ask themselves is:

Do you want a twin pregnancy or a healthy child?




In light of the information provided above, this appears to be a valid question for each couple to consider. In addition, the entire IVF field needs to change the way it defines success.

From the author: A lot of online reading went into this article and I have simply lost track of some of the articles read. It is easy to find information on this subject by going to Google and searching for single embryo transfer, multiple pregnancies, risk of twins, risk of multiples, etc. to find thousands of articles offering fabulous information.