Embryo Splitting To Increase the Availability of “Competent” Embryos For IVF

I recently received several inquiries from visitors to our SIRM discussion boards (http://forums.haveababy.com/index.php?showforum=1 ) on the subject of “embryo splitting” to try and improve the opportunities to conceive through IVF. Here is one example of such an inquiry that recently appeared on the SIRM-Las Vegas regional discussion board:

“I've been reading on embryo splitting (for readers: manually splitting embryos in the lab …..in order to increase the number of embryos to transfer/freeze). The AMA seems to not have an issue with it and understands that it could help infertile couples increase their chances: (www.amassn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion2145.shtml)”

Against this background, I wish to share the article below with those of you that may be interested in this topic.

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"Spontaneous embryo splitting resulting in monozygotic ("identical") twinning is a well established peculiarity of nature".

There exists a period during early mammalian embryo development when embryos can be separated purposely into halves or even quarters without drastically reducing the probability that each portion of an embryo is able to develop into a fetus. The usefulness of embryo sectioning is realized any time that the number of embryos suitable for transfer is limited.

When mammalian embryos are surgically split (sectioned) prior to converting into a blastocyst, the number of cells and the size of the resulting blastocysts seem to be unaffected. The developmental time clock also remains relatively unaffected. While bisected embryos develop into blastocysts with slightly less than half the number of inner cell mass cells, and slightly more than half the number of cells forming the trophoblast, these alterations do not seem affect the implantation rate of mammalian, non-human embryos. It remains to be discovered whether the same would apply in the case of human embryos.

Several concerns have been raised regarding the production of abnormal offspring and other potential complications that might result from surgically inducing monozygotic twinning through microsurgical embryo splitting (MES). However, it is a fact that in the cattle industry, where MES has been performed successfully for many years, there has to date been not s single report of abnormalities in the offspring.

Microsurgical Embryo Splitting (MES) might ideally be combined with full karyotyping (chromosomal recognition) using comparative genomic hybridization (CGH) on 6-9 cells, day 3 embryo(s) to identify “competent” embryos. This would be followed by MES on day 3 (the cleaved embryo stage of development), or on day 4 (the morula stage). The resulting hemi-embryos so produced would thereupon be cultured for a few days longer to the blastocyst stage when they would either be transferred fresh to the uterus or be vitrified (frozen) and banked for subsequent dispensation. In this manner MES might serve as a means to increase the number of available embryos per woman.

Potential complications such as twin-to-twin transfusion, umbilical cord entanglement and obstructed birth, which often occur with natural spontaneous monozygotic twinning, are not encountered in MES-induced twinning. The explanation lies in the fact that unlike natural monozygotic twins that often occupy a single, common gestational sac and frequently share a common blood supply derived from a single placenta, MES-induced monozygotic twins invariably have their own placentas and reside in separate gestational sacs.

MES, should it become a feasible, acceptable and practicable clinical option in ART could by increasing the number of available viable embryos offer hope for thousands of women who because of advanced reproductive age and/or diminished ovarian reserve are only capable of producing very few "competent" eggs/embryos at a time. It might also prove to be of benefit in cases where (out of personal choice) IVF is performed without the use of fertility drugs (Natural Cycle IVF) and where accordingly only one or two eggs/embryos are generated. ----------------------------------------------------------------------
Addendum: SIRM-Las Vegas is soon to launch a limited study to evaluate the efficacy of MES. Criteria for consideration of inclusion in this study will be as follows:

• Age less than 36 years • Regular menstruation/ovulation

• Normal endometrial cavity

• Absence of alloimmune implantation dysfunction

• Absence of a significant male factor infertility.

We intend, provisionally to focus this study on young couples considering Natural Cycle IVF.
Please email Tom Anderson (toma@sherinstitute.com) if you would like to be considered for inclusion in this proposed study.