Staggered IVF: An Excellent Option When Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate

Dr. Geoffrey Sher - February 22, 2022
Staggered IVF: An Excellent Option When Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate

 

Many physicians treating infertile women over 40 years old who have patent fallopian tubes still opt to start with the least invasive strategy rather than going straight to IVF. This usually begins with the prescribing of oral and then injectable fertility drugs with or without artificial insemination/IUI. The rationale for this approach is that IVF is significantly more expensive than such alternatives.  While the cost of an IVF procedure is certainly more expensive, what is often ignored is that it is also far more likely to achieve the desired result of a live birth. When one considers that the real price (financial as well as emotional) resides in the cost of having a baby rather than the cost of a procedure, doing IVF often turns out to be less costly.

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It is well established that regardless of a woman’s age or the cause of her infertility, the chance of pregnancy following IVF is several-fold greater than with any other method of treatment including intrauterine insemination (with or without the use of fertility drugs) and that this difference becomes much more pronounced with advancing age. For example, the chance of an ovulating woman of under 35 who has patent Fallopian tubes and a fertile male partner, having a baby after a single attempt at IUI is <15%. For a woman in her mid-40s the chance is <3%. With IVF, the comparable chances of success would be about 40% and 15%, respectively.

This does not mean that all infertile women who have patent Fallopian tubes and fertile male partners should select IVF over less invasive and less expensive treatments. What it does suggest, however, is that women running out of time on the “biological clock” (i.e., women in their 40’s, and women who have diminished ovarian reserve -DOR), should probably go directly to IVF rather than waste precious time on less effective treatment options. It must also be recognized that the older the woman, the greater the risk of miscarriage and of having a chromosomally abnormal baby. For example: At age 30 the risk of miscarriage is about 15% and the chance of a woman giving birth to a chromosomally abnormal baby (e.g. Down syndrome) is <1:1000. Conversely, in the mid-40’s the comparable risk of miscarriage is >40%, and 1:60-80, respectively.

Making strong a case for Embryo banking with Staggered IVF and PGS embryo testing: Against this background, in an attempt to try and put the “biological clock” on hold and provide older infertile women and those with DOR with an alternative to IVF/egg donation, we recently introduced Embryo Banking with Staggered IVF and Preimplantation Genetic Sampling (PGS)/ Preimplantation Genetic Testing for Aneuploidy (PGT-A) of embryos. This approach usually requires  more than one IVF procedure, biopsy of all potentially viable embryos for PGS/PGT, holding all biopsied specimens until several (4-8) blastocysts have been cryobanked and then sending the biopsied DNA for NGS (Next Generation Gene Sequencing .

Once the PGS/PGT results are known, the woman returns in a subsequent cycle for the selective transfer of up to two PGS-normal embryos to her uterus. Staggered IVF refers to the process whereby embryos are transferred in a different cycle to the one where the eggs were harvested. The use of embryo banking with Staggered IVF and selectively transferring only PGS/PGT-normal embryos is an efficiency tool which significantly improves the baby rate per embryo transferred (to as high as 40-50%), reduces the miscarriage rate by a factor of 5-6 and minimizes the risk of the birth of a baby who has chromosomal birth defects (e.g. Down syndrome).

The “competency” (numerical chromosomal integrity) of a woman’s eggs declines rapidly with advancing age (about 1:2 are normal in her early 30’s as compared to 1:6 at 40Y and about 1:20 by 45Y). In addition, the older the woman gets, the more her total egg supply diminishes, ultimately resulting in DOR. For these reasons, advancing age and DOR reduce fertility, increase the risk of miscarriage and result in a rise of chromosomal birth defects (e.g. Down syndrome). IVF can markedly improve outcome by maximizing the number of eggs available for fertilization and making the resulting embryos available for genetic testing. The introduction by SFS of Staggered IVF, Embryo Banking and PGS/PGT with the selective transfer of only “chromosomally competent” embryos represents an excellent “efficiency tool” which markedly improves  pregnancy rate, reduces the chance of miscarriage an minimizes the risk of chromosomal birth defects. As such I strongly recommend this approach for older women and women who (regardless of age) and as such are running out of time on their “biological clocks.”

 


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