Tyl H Taylor and Ilana Glassner
16 September 2007
Singleton pregnancy should be considered as the ideal goal of in-vitro fertilization (IVF) treatment. Clinicians often times have to resort to transferring multiple embryos in order to achieve this goal. However, transferring multiple embryos into the uterus increases the likelihood of multiple pregnancies. Recently, techniques that have existed within IVF have been suggested to decrease the chances of multiple pregnancies but still maintain the all-important clinical pregnancy rate.
Often the patient has been trying to get pregnant for many months if not years. Patient’s often opt for the less conservative approach of transferring more than enough embryos to maximize their chances of having a child, while the clinician gets stuck in the middle between trying to limit the chances of multiple pregnancies whilst still maintaining a reasonable chance of a singleton pregnancy.
Multiple pregnancies prove to be a risk not only to the mother but also the developing fetus. A mother carrying multiples has an increased risk of miscarriage, haemorrhaging, high blood pressure, diabetes, and pre-eclampsia. Furthermore, a caesarean section is often needed for delivery. With this procedure, comes an increase in the length of stay at the hospital, which in turn means a higher medical cost. Complications from a caesarean section include increase in blood loss, possible damage to the uterus and pelvic region, known as adhesions, which can complicate future pregnancies, and negative side effects from the anaesthesia. Also, multiple pregnancies have a financial, emotional, and physical toll on the parents.
Fetal complications for multiple gestations are much more life threatening. Preterm delivery and in turn, low birth weights tend to be the most talked about problem for multiples, but far from the worse. With preterm deliveries, the fetus can expect to have a higher chance of disabilities such as cerebral palsy, mental retardation, and an increase necessity for intensive care.
Finally, the multiple births and the maintenance of multiple children have a devastating emotional, physical, and financial effect on the parents. Due to these complications it is no wonder why multiple pregnancies should be avoided.
Pre-existing techniques have been used to diminish the possibility of multiple pregnancies within IVF without compromising on pregnancy outcome. These include extended culture, preimplantation genetic diagnosis for aneuploidy screening (PGD-AS), and single embryo transfer.
Extended culture, or blastocysts culture, is simply the culturing of embryos to day 5 to select the embryos that have progressed to the highest quality. Recent research indicates that a single blastocyst transfer can maintain a reasonable pregnancy rate while reducing the chances of multiple pregnancies (Styer et al., 2007). Blastocyst culture, however, does have its flaws. During extended culture, embryos that were suitable for freezing or transfer on day 3 may not develop to day 5 due to a multitude of factors, especially if the culture conditions are not optimal. Simply put, if the patient’s embryos are cultured to day 5, the patient will probably have fewer embryos for freezing or transfer than if the patient had a transfer on day 3. It is believed that fewer embryos are needed for transfer on day 5 to achieve pregnancy rates comparable to day 3.
Preimplantation genetic diagnosis was introduced in the early 1990’s and is gaining popularity amongst IVF clinic’s, not only for its ability to detect chromosomal defects in the embryo, but also for its ability to select those embryos which are chromosomally normal. It is possible for an embryo to appear physically normal but to contain chromosomally abnormalities that will cause the embryo’s demise later on in development. The goal is to replace embryos that are known to be chromosomally normal into the uterus, thereby increasing the likelihood of implantation and reducing the total number of embryos needed for transfer. Research indicates that this procedure can also maintain a high pregnancy rate while effectively reducing multiple pregnancies (Donoso et al., 2007). However a recent study conducted by Mastenbroek et al. (2007) found that PGD-AS actually lowered live birth rates in women of advanced maternal age.
Single embryo transfer (SET) has always been an option within IVF. SET is exactly what it implies. Instead of transferring of multiple embryos into the uterus, a single embryo is transferred. This does not eliminate the chances of a multiple pregnancy, as monozygotic twinning can still occur, but it does significantly lower the chances of multiples. However, it can also lower the overall chance of pregnancy. The American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology have implemented guidelines, not laws, in order to help clinics minimize multiple pregnancies. These guidelines take into account factors such as the age of the women and embryo quality. Clinics are encouraged to look at their specific patient population and determine which methods would be suitable for their patient base. Nonetheless, SET is being enforced in Belgium and is imposed on women under 36 years of age undergoing their first IVF cycle.
Perhaps a combination of all three techniques can be implemented to help reduce the risk of multiple pregnancies. However, as of yet, there seems to be no “magic formula” that tells embryologists and clinicians which embryos will implant and which ones will not. Hopefully research will continue to progress towards IVF’s ultimate goal of a healthy singleton pregnancy for all.
Further Reading:
Donoso P, Verpoest W, Papanikolaou EG, Liebaers I, Fatemi HM, Sermon K, Staessen C, Van der Elst J, Devroey P. Single embryo transfer in preimplantation genetic diagnosis cycles for women <36 years does not reduce delivery rate. Hum Repro. 2007;22(4):1021-5.
Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, Vogel NE, Arts EG, de Vries JW, Bossuyt PM, Buys CH, Heineman MJ, Repping S, van der Veen F. In Vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:61-3.
Styer AK, Wright DL, Wolkovich AM, Veiga C, Toth TL. Single-blastocyst transfer decreases twin gestation without affecting pregnancy outcome. Fertil Steril. 2007. Jul 17.
For more information please visit:
http://www.asrm.org/Patients/multiple_pregnancy_and_birth.pdf
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4.75 (out of 5)