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Can IVF cause twins?

The million dollar question! Can IVF cause twins? The truth is, there is a possibility that twins could be conceived, but it depends on the number of embryos transferred. If multiple embryos are transferred, each one has the possibility of developing into an embryo. The greater the number of embryos transferred, the greater the chances of having more and more embryos successfully develop. These twins, triplets, etc. would be fraternal-meaning they did not originate from the same embryo and hence are not genetically identical. IVF has also been shown to increase the rate of monozygotic twinning by two- to twelvefold when compared with the spontaneous occurrence of 0.4% (Vitthala 2018; Blickstein 1999; Blickstein 2003)

Image by Society For Assisted Reproductive Technology

This image by the Society For Assisted Reproductive Technology says it all. Multiple births are on the decline, especially twin births. In 2017, only 13% of IVF births resulted in twins. If you were curious about the chances of conceiving twins, you must have also wondered about triplets, quadruplets and quintuplets! Their births through IVF are down to less than 1%.

That brings me to how genetically identical twins arise! When a single zygote splits into two separate ones, identical twins develop (one twin from each zygote). The chance of this split occurring is higher for those who have undergone IVF compared to those who have conceived the embryo naturally. 

Genetically identical twins

It is important to keep in mind that these days, only one embryo is often transferred into the patient. This is to avoid the chances of conceiving twins if the patient does not desire twins. Nevertheless, as we have seen, identical twins arise from a single zygote so it is still possible to have twins with one embryo transferred.  Additionally, it is to support the health of both the mother and the baby. Conceiving twins has its own risks and it is important for the parents to understand that prior to opting for IVF the chances of having twins isn’t exactly in their hands!

Is it possible to perform IVF and reduce the chances of having twins?

Yes, it is! As previously mentioned, these days single embryos are often transferred into the patient. Additionally, recent evidence shows that blastocyst transfer in fresh IVF cycles is associated with a significantly increased probability of monozygotic pregnancy in comparison to cleavage-state embryo transfers. (Mateizel 2016; Maheshwari 2016). Though the reason for increased risk of monozygotic twinning with IVF is debatable, there have been a handful of studies which have found other influencing factors including the oocyte age being < 35 years old, prolonging the embryo culture, micromanipulation of the zona pellucida after procedures such as intracytoplasmic sperm injection (ICSI) or assisted hatching (AH), and after fresh embryo transfer. (Tarlatzis 2002; Jian 2004; Knopman 2014; Kanter 2015).

Something interesting to note is that embryologists often try to perform the transfer at the blastocyst stage. This is for higher chances of a successful pregnancy and it is also to reduce the risk of having multiple embryos develop. However, this type of transfer has actually proven to increase monozygotic splitting (Kolibianakis 2002; Desolle 2010). Meaning that even if one blastocyst is transferred, it very well may split into two embryos. Blastocyst transfer has been shown in multiple studies to significantly increase the monozygotic twinning (MZT) rate, estimated at 1.7% which is 4.25 times higher than the natural pregnancy MZT rate of 0.4% (Nakasuji 2014). One of the reasons it is though this happens is because culturing the blastocyst  We have to keep in mind however, that an IVF cycle is very expensive! One cycle will be at least around $10,000. A couple might not want to risk having to have a failed cycle and go through another one. (Remember that IVF is not only expensive, but emotionally exhausting too). Hence, the couple themselves might want several embryos transferred knowing that more than one might successfully implant. 

Another key aspect to remember is the statistics regarding single embryo transfer (SET). The probability of multiple embryos developing is 1.6%. This was discovered in a study involving 937,848 SET cycles and was published in Human Reproduction.

Speaking of SET cycles, check out the image below to see the gradual increase in SET cycles through the years! Embryologists are aware of the risk of having twins and want to ensure that they can do everything in their power to help an IVF cycle go the way you want it to! The image was obtained from the Society For Assisted Reproductive Technology which states that SET cycles are more common in women under the age of 38. This is most likely because of the decline in fertility as one ages. 

Image by Society for Assissted Reproductive Technology

What might increase the odds of multiple embryos developing?

According to the same study, researchers found that there are some procedures that might actually increase the chances of zygote. Some of these include using frozen-thawed embryos, maturing the fertilized egg for approximately 5 days in the laboratory prior to SET and assisted hatching. Assisted hatching is where an opening is created in the zona pellucida of an embryo. This is the outer coating of proteins. By doing this, it assists the embryo in hatching and attaching to the wall of the uterus for implantation.

What are the risks of having twins?

Twin babies are just precious! Two little bundles of joy! But it is important to understand some of the difficulties that could be faced when pregnant with twins. One of them is premature birth. 60% of twins are born prematurely before the 35th week of pregnancy. Being born prematurely leads to its own complications. For example, low birthweight is one. More than 50% of twins are born at a weight lower than 5.5 pounds. However, if the weight of a baby is as low as below 3.5 pounds the baby is also born before 32 weeks, the possibility of developing health defects is even greater. Some of these are mental retardation, cerebral palsy and vision or hearing loss. 

Another risk is the need for a cesarean section. Most women want to give birth naturally or want to avoid surgery unless very necessary. Unfortunately, when a patient is carrying twins, there is the risk of requiring surgery and as with most surgeries, there is a hefty recovery period that is certainly longer compared to that after natural birth. Cesarean also poses the risk of hemorrhage after the delivery. 

Something else to look out for is Twin-Twin Syndrome (TTS). This happens when a set of identical twins share a placenta. Because the placenta manages the blood flow into the fetuses and the exchange of materials from the mother to the baby, there is a risk of one baby obtaining more blood flow compared to its sibling. 

Pre-eclampsia is another risk. You might have heard about pre-eclampsia and pregnancy but do not know what exactly it is. It often occurs around 20 weeks into the pregnancy and is characterized by high blood pressure and damage to the liver and kidneys. When doctors diagnose pre-eclampsia, the most effective cure is to deliver the baby as it poses very high risks to the mother and baby. However, if the diagnosis is made very early on in the pregnancy, it becomes a little tricky because the baby requires more time to develop and grow inside the womb but also must be monitored very closely because of the pre-eclampsia. 

Conclusion

From the studies included in this blog post, it does seem that IVF may increase the likelihood of monozygotic splitting. Hence, when opting for IVF it is better to be ready for the possible situation of conceiving twins. As we’ve mentioned before, twins or no twins, every newborn is precious and absolutely perfect. The preparedness is rather for embracing some of the differences that may appear in finances and the health problems that occur in twin newborns and their mothers. However, as we have seen, it is not all black and white. Every IVF cycle does not have high chances of producing twins. Influencing factors include the oocyte age being < 35 years old, prolonging the embryo culture, micromanipulation of the zona pellucida after procedures such as intracytoplasmic sperm injection (ICSI) or assisted hatching (AH), and after fresh embryo transfer. (Tarlatzis 2002; Jian 2004; Knopman 2014; Kanter 2015). I would suggest reading some of the studies we have referenced in this blog post to learn more. And more importantly, talk to your physician if you have any questions about the possibility of having twins and more information on how to reduce the chances of that happening if that is your desire. IVF was introduced around 42 years ago so there is still a lot we can learn and develop! ART is beautiful in that it makes the dreams of soon-to-be parents come true. The science behind it however, is nearly equally and stunning and 

References:

  1. Sundaram, Viji et al. “Multi-chorionic pregnancies following single embryo transfer at the blastocyst stage: a case series and review of the literature.” Journal of assisted reproduction and genetics vol. 35,12 (2018): 2109-2117. doi:10.1007/s10815-018-1329-8
  2. Vitthala S, Gelbaya TA, Brison DR, Fitzgerald CT, Nardo LG. The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis. Hum Reprod Update. 2009;15(1):45–55. doi: 10.1093/humupd/dmn045. 7. 
  3. Blickstein I, Verhoeven HC, Keith LG. Zygotic splitting after assisted reproduction. N Engl J Med. 1999;340(9):738–739. doi: 10.1056/NEJM199903043400916. 
  4. Blickstein I, Jones C, Keith LG. Zygotic-splitting rates after single-embryo transfers in in vitro fertilization. N Engl J Med. 2003;348(23):2366–2367. doi: 10.1056/NEJMc026724. 
  5. Mateizel I, Santos-Ribeiro S, Done E, Van Landuyt L, Van de Velde H, Tournaye H, Verheyen G Hum Reprod. 2016 Nov; 31(11):2435-2441.
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  7. Tarlatzis BC, Qublan HS, Sanopoulou T, Zepiridis L, Grimbizis G, Bontis J. Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer. Fertil Steril. 2002;77(1):196–198. doi: 10.1016/S0015-0282(01)02958-2. 
  8. 12. Jain JK, Boostanfar R, Slater CC, Francis MM, Paulson RJ. Monozygotic twins and triplets in association with blastocyst transfer. J Assist Reprod Genet. 2004;21(4):103–107. doi: 10.1023/B:JARG.0000029493.54929.be. 
  9. Knopman JM, Krey LC, Oh C, Lee J, McCaffrey C, Noyes N. What makes them split? Identifying risk factors that lead to monozygotic twins after in vitro fertilization. Fertil Steril. 2014;102(1):82–89. doi: 10.1016/j.fertnstert.2014.03.039. 
  10. Kanter JR, Boulet SL, Kawwass JF, Jamieson DJ, Kissin DM. Trends and correlates of monozygotic twinning after single embryo transfer. Obstet Gynecol. 2015;125(1):111–117. doi: 10.1097/AOG.0000000000000579. 
  11. Nakasuji T, Saito H, Araki R, Nakaza A, Nakashima A, Kuwahara A, Ishihara O, Irahara M, Kubota T, Yoshimura Y, Sakumoto T J Assist Reprod Genet. 2014 Jul; 31(7):803-7.
  12. Kolibianakis EM, Devroey P. Blastocyst culture: facts and fiction. Reprod BioMed Online. 2002;5(3):285–293. doi: 10.1016/S1472-6483(10)61834-2. 
  13. Dessolle L, Allaoua D, Fréour T, le Vaillant C, Philippe HJ, Jean M, Barrière P. Monozygotic triplet pregnancies after single blastocyst transfer: two cases and literature review. Reprod BioMed Online. 2010;21(3):283–289. doi: 10.1016/j.rbmo.2010.04.011. 

Pooja is the content manager at ART Compass and works on the blog and social media content. She is an undergraduate student at Drew University pursuing a major in Biochemistry and Molecular Biology and minors in Business and Sociology. She has undertaken a literary research project on stem cell treatments for multiple sclerosis and wishes to continue stem cell research during her time at Drew. She is an associate member of the Tri-Beta Biology Honors Society and volunteers on an EMS squad and at the Red Cross. She hopes to attend medical school in the future.

Pooja Kasarapu
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