Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation

An ever increasing number of American women first seek IVF treatment in their late 30’s or early 40’s.This trend is in large part due to the fact that more and more women are choosing to defer childbearing until they have fulfilled their career aspirations. While such deliberate deferment is understandable, it nevertheless poses significant problems, because women in their late 30’s and early 40’s have about one half the chance of having a baby following IVF than do women in their early to mid-30’s. There are two primary reasons for this:

First is the fact that advancing age beyond 35 years is accompanied by an inevitable and progressive increase in numerical chromosomal egg abnormalities (aneuploidy) that lead to “incompetent” embryos that cannot propagate viable pregnancies. That is why we see a profound and steady decline in IVF success rates as well as an increase in chromosomal miscarriages and birth defects such as Down’s syndrome with advancing maternal age.

Second, as women get older, there occurs a progressive decline in their ovarian egg supply, referred to a diminished ovarian reserve (DOR) which manifests with a declining response to fertility drugs, an elevated basal blood FSH level and a falling blood AMH concentration” When it comes to IVF, DOR results in less eggs being accessible at egg retrieval and consequentially, fewer “competent” embryos available for transfer to the uterus.

Most women/couples would like to have more than one child. This desire is no less prevalent in older women. However, by the time the older woman decides to do IVF, goes through the process successfully, has a baby, completes breastfeeding, and thereupon re-establishes regular menstruation in order to try for another IVF baby, a period of 2-3 years will have elapsed. While such a hiatus would usually be of little consequence to a young woman, for an older woman such a delay could seriously impact her “biological clock” so as to drastically reduce her chance of having another baby with her own eggs.

The concept of Embryo Banking/Stockpiling: Embryo Banking offers a potential alternative to IVF with egg donation,  for older women and those with DOR who wish to minimize the relentless effect of the “biological clock”. The process involves undergoing several IVF stimulation/egg retrieval procedures in relatively quick succession, biopsying them for preimplantation genetic sampling (PGS) and then freezing/banking all those that survive to the blastocyst stage (day 5-6 post-fertilization) embryos for future dispensation, rather than having them transferred to the uterus immediately .Once enough biopsied embryos (usually 4-8) have been stockpiled, all biopsied material derived from those embryos that reached the blastocyst stage are dispatched for PGS testing by  generation gene sequencing-(NGS) . Those embryos found to have a normal number of chromosomes (euploid) are held for subsequent transfer to the uterus in a later FET cycle (i.e. “staggered” embryo transfer). ”Such embryo banking/stockpiling” literally stops the biological clock in its tracks, allowing for the subsequent elective thawing of one or two frozen embryos at a time in future frozen embryo transfer (FET) cycles. This process would avert the risk of progressive declining egg/embryo “competency” over time.

Embryo banking/stockpiling would not have been feasible a decade ago since it was not until quite recently that we became able to reliably identify chromosomally normal (“competent”) embryos for selective banking. Embryo freezing technology has also evolved dramatically over that time. Just a few years ago, the freezing process took a serious toll on embryos, severely damaging up to 50% of them in the freeze/thaw process. But that was then…Today, through embryo karyotyping with NGS for the selection of euploid embryos we are able to much better identify “competent” embryos for banking and stockpiling. In addition, the recent introduction of much improved egg/embryo freezing through ultra-rapid cryopreservation (or possibly even improved) eliminates most of the potential damage incurred to “competent” embryos during the freezing and thawing process. In fact, in IVF centers of excellence, the frozen embryo transfer (FET) process using vitrified/thawed embryos now yields at least the same IVF success rate as when fresh embryos are transferred!
These innovations (PGS and blastocyst Vitrification) have not only made embryo banking/stockpiling feasible, but have rendered the approach a most appealing option for older women and women with DOR who seek to undergo IVF using their own eggs.

This having been said, PGS is not an indispensable part of embryo banking. The process can be done without it. But, given the inevitability of an age-related increase in the incidence of chromosomal abnormalities in the egg/embryo, it would be impossible for patients to know whether they have stored the most “competent” embryos and thus which ones to transfer to the uterus for the best chance of success when the time comes.

I want to emphasize that PGS does not improve embryo quality. It is merely an efficiency tool that allows us to select the most “competent” embryos for transfer and thereby significantly improve the baby rate per embryo transferred. It is also well to bear in mind that embryo aneuploidy not only reduces the chance of a successful pregnancy but it is also the commonest cause of miscarriages and certain birth defects (e.g. Down’s syndrome). Thus PGS embryo selection not only improves IVF success (per embryo transferred),reduces the risk of miscarriages and birth defects  but by identifying the most “competent” embryos  it also reduces the incentive to transfer multiple embryos at a time, thereby dramatically reducing  the occurrence of high-order multiple pregnancies (triplets or greater).

Proudly, Levent Keskintepe and I were the first to introduce PGS embryo selection into the clinical IVF arena. We initially used a PGS method known as comparative metaphase genomic hybridization (mCGH) but now have largely switched to NGS (an improved method).  Since introducing clinical PGS for IVF we have reported hundreds of successes using this approach, which has since gained wide acceptance in throughout the IVF field.  It is against this background that we now provide selective embryo banking/stockpiling to an ever increasing number of older women and women with DOR.

4 Comments

Amanda

Hi Dr Sher,

Firstly, thank you so much for providing such a wonderfully informative website to women all around the world. I’m so grateful for all that I have learnt (and continue to learn) from all of the articles on your blog.

I am 41 years (+ 10months) of age. I have DOR, high natural killer cells and my partner and I share a complete match of the DQ Alpha gene. Through my specialist (here in Australia), I am able to undertake LMIT / LIT and immune suppression therapy for the DQ Alpha gene / natural killer cell issues. My partner and I don’t have children as yet. Last month we completed our 1st freeze all cycle for embryo banking. We are currently awaiting the PGS results for the one blastocyst that developed.

Given our circumstances, how many competent embryos would you suggest we need to wait to have set aside to give us the best chances for achieving a successful second pregnancy? Once we have the recommended number for a second pregnancy we can then focus our attention on a first pregnancy.

For embryo banking, your article recommends undergoing several IVF stimulation / egg retrieval rounds in relatively quick succession. By “quick succession” are you suggesting that the cycles be completed back to back or with a month break in between cycles?

I recently read of a patient at a clinic who was embryo banking and who had completed nine back to back IVF cycles and egg yields increased over time. Would completing back to back cycles like this be something that you would recommend?

I have read about your recommended A/ACP which I will propose to our specialist for my next cycle.

Many thanks in advance for your feedback and advice.

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Dr. Geoffrey Sher

Hi Amanda,

Women who have a complete DQ alpha match with there partners and also have activated NK cells, are in my experience highly unlikely to attain a viable pregnancy, regardless of treatment (LIT/IVIG/IL + steroids). However, I would emphasize that it is NOT, NK cell concentration that matters. It is NK cell activation that counts and this required performance of a blood K-562-Target Cell Test or endometrial cytokine analysis. Moreover, a matching DQ alpha has no relevance in the absence of NK cell activation.

As for your diminished ovarian reserve, please consider the following:

Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, www. SherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview

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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

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reply
Amanda

Thank you very much for your reply Dr Sher.

Just a few queries remain unanswered that I’m hoping you can shed light on…

For embryo banking, your article recommends undergoing several IVF stimulation / egg retrieval rounds in relatively quick succession. By “quick succession” are you suggesting that the cycles be completed back to back or with a month break in between cycles?

I recently read of a patient at a clinic who was embryo banking and who had completed nine back to back IVF cycles and that her egg yields increased over time. Would completing back to back cycles like this be something that you would recommend?

My partner and I are in the process of embryo banking with one IVF cycle completed so far. Given our circumstances (outlined in my previous comment/query), how many competent embryos would you suggest we need to wait to have set aside to give us the best chances for achieving a successful second pregnancy? Once we have the recommended number for a second pregnancy we can then focus our attention on a first pregnancy.

Thanks again for your feedback and advice.

reply
Dr. Geoffrey Sher

Yes! I strongly advocate at least 1 resting cycle between each stimulation.

I recommend 4-6 euploid blastocysts be banked/stockpiled before transferring.

Good luck and G-d bless!

Geoff Sher

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