The goal of any infertility treatment is the delivery of a healthy baby. As more couples receive infertility therapy through assisted reproductive technologies, there has also been an increase in the number of multiple pregnancies (twins) and high-order multiple pregnancies (triplets and greater). This dramatic increase in the number of multiples delivered in the U.S. over the last few decades can be directly attributed to the increase in fertility treatments.

In vitro fertilization (IVF) produces the highest rate of pregnancy of all current infertility treatments.  However, IVF also leads to a high risk of multiple gestations. This is directly due to transferring more than one embryo into the uterus at the time of embryo transfer. The more embryos  transferred, the higher the rate of multiple gestations and high-order multiple gestations.

IVF can require an enormous investment of time, energy, emotions, and capital. With such a heavy investment, couples undergoing infertility treatment cannot afford an IVF failure. Thus, some patients may request that their physician increases their chances of pregnancy by increasing the number of embryos returned to the uterus. However, this also leads to a higher rate of multiple and high-order multiple pregnancies.

Many people who struggle with infertility welcome any healthy pregnancy, including twins. However, most of these couples do not realize that twins and high-order multiple gestations (triplets and higher) have an increased risk of both maternal and fetal complications.

The most common fetal complications associated with multiples are:

• Increased rate of miscarriage
• Increased rate of malformations
• Discordance (disparity) in growth
• Intrauterine growth restriction (IUGR)
• Twin to twin transfusion syndrome (TTTS)
• Increased preterm and/or premature rupture of membranes (PPROM)
• Increased rate of death in-utero or after birth
• Cerebral palsy
• Vanishing twin syndrome

The most common maternal complications associated with multiples are:

• Increased levels of nausea, heartburn, vomiting, fatigue

• Pre-term labor and pre-term delivery (leading to infants with problems of prematurity)
• Iron deficiency anemia
• Pre-eclampsia (high blood pressure)
• Gestational diabetes
• Heart problems, including heart attack
• Incompetent cervix
• Increased need for partial or complete bed rest, and limited physical activity
• Increased rate of cesarean section delivery
• Increased chance of post partum hemorrhage

Complications After Birth from a Multiple Gestation:

• Lower birth weight
• Increased risk of infant death
• Need for prolonged hospitalization of infant(s) due to prematurity
• Complications of prematurity, including breathing problems such as apnea (temporary absence of breathing) and bradycardia (abnormally slow heartbeat).
• Intraventricular hemorrhage (cranial bleed) ranging from mild to severe
• Necrotizing enterocolitis – a life threatening disease of the intestines.
• Retinopathy of prematurity – significant eye problems.
• Hearing problems such as full or partial deafness in one or both ears.
• Difficulty in breastfeeding
• Increased risk of developmental delays

The idea of multiple gestations such as twins may seem magical and appealing. However, the reality is that multiple gestations (especially high-order multiple gestations) can lead not only to medical complications for both the mother and infants but also to strains upon the family. Multiple gestations such as twins means twice the amount of diapers, formula, baby furniture, baby gear, etc… This can lead to a considerable financial strain. A family’s finances may be burdened even more if one or more of the babies has special medical or developmental needs. Twins also mean twice the  amount of child care, leaving little time for activities of daily living (like bathing and cleaning) and other household tasks. This can lead to a logistical strain upon the family. With twins leading to twice the amount of childcare, it also means double the amount of sleep deprivation. Even the hardiest of parents/families may eventually develop an emotional strain.

The best way to reduce the risks of fetal, maternal, infant and family complications associated with multiple gestations and high-order multiple gestations is to avoid increasing the risks for multiple pregnancies.  The best way to reduce the incidence of conceiving with multiples in an IVF cycle is to limit the number of embryos transferred at the time of the embryo transfer. Reducing the incidence of multiples in an IVF cycle through Responsible Embryo Transferring is important to avoid the associated risks to both the fetuses and mother.

The focus of Responsible Embryo Transferring is to promote simple communication between the patient and IVF doctor to discuss all of the risks associated with transferring multiple embryos when deciding how many embryos to transfer. The goal of Responsible Embryo Transferring is to be able to maintain high pregnancy rates while limiting the number of embryos transferred. Elective single embryo transfers (eSET) are now commonly offered to good candidate patients who have high quality embryos.

A recent analysis report reviewing the pregnancy rates between single embryo transfer IVF cycles and two embryo transfer cycles revealed that the chance of pregnancy from a single embryo transfer is approximately 61% as compared to a pregnancy rate of 68.1% from a two embryo transfer. This report also stated that the rate of multiple gestations is approximately 23% from a single embryo transfer as compared to 52.1% from two embryo transfers.  Hence, a single embryo transfer is able to maintain a high success rate while significantly reducing the chance of multiples.

The American Society for Reproductive Medicine (ASRM), and the Society for Assisted Reproductive Technology (SART), the two leading infertility societies in the United States have jointly published guidelines on the number of embryos that should be transferred back into the woman at the time of uterine embryo transfer. These guidelines are based upon strict criteria such as the age of the woman and the health of the embryos.

Here are the ASRM/SART guidelines in regards to the number of embryos that should be transferred:

A. For patients under the age of 35 who have a more favorable prognosis, consideration should be given to transferring only a single embryo. No more than two embryos (cleavage stage or blastocyst) should be transferred.

B. For patients between 35 and 37 years of age who have a more favorable prognosis, no more than two cleavage-stage embryos should be transferred. All others in this age group should have no more than three cleavage-stage embryos transferred. If extended culture is performed, no more than two blastocysts should be transferred to women in this age group.

C. For patients between 38 and 40 years of age who have a more favorable prognosis, no more than three cleavage-stage embryos or two blastocysts should be transferred. All others in this age group should have no more than four cleavage-stage embryos or three blastocysts transferred.  D. For patients 41–42 years of age, no more than five cleavage-stage embryos or three blastocyts should be transferred.

E. In each of the above age groups, for patients with two or more previous failed fresh IVF cycles or a less favorable prognosis, one additional embryo may be transferred according to individual circumstances.  The patient must be counseled regarding the risks of multifetal pregnancy. Both the counseling and the justification for exceeding the recommended limits must be documented in the patient’s permanent medical record.

F. In women >43 years of age, there are insufficient data to recommend a limit on the number of embryos to transfer.

G. In donor egg cycles, the age of the donor should be used to determine the appropriate number of embryos to transfer.

H. In frozen embryo transfer cycles, the number of good-quality thawed embryos transferred should not exceed the recommended limit on the number of fresh embryos transferred for each age group.

The guidelines were revised in 2009 to clarify that while exceptions may be allowable for patients with a less favorable prognosis, those exceptions are quite limited. Additionally, regardless of prognosis, only one more embryo than called for in the guidelines should be transferred.

Ultimately, deciding on the appropriate number of embryos to transfer should be a team effort. The couple, embryologists, and physician should all discuss the guidelines and what may be the best number of embryos to transfer to increase the chance of success but decrease the chance of multiple gestations. Ask your doctor if the number of embryos recommended to be transferred is the responsible number for you.

Sources:
1. Fliser E., Licciardi F. “One at a time.” Fertility and Sterility 2006;85:555– 8.
2. Speroff and Fritz. “Clinical Gynecologic Endocrinology and Infertility”, 8th
edition, 2011.
3. The American Fertility Association Library. “How Many is Too Many?
Responsible Embryo Transfer”, 2011.
4. The Practice Committee of the Society for Assisted Reproductive
Technology and the Practice Committee of the American Society for
Reproductive Medicine. “Guidelines on number of embryos transferred.”
Fertility and Sterility 2006;86(Suppl 4):S51–52.
5. Williams Obstetrics. 23rd edition, 2009.